Sei sulla pagina 1di 122

TORINO 16 -19 Novembre 2013

MEDICINA NUCLEARE RELAZIONI A INVITO • RELAZIONI LIBERE • POSTER

RELAZIONI A INVITO
Procedure avanzate per imaging PET. R. Matheoud, Novara

Diversi punti di vista: imaging SPECT per dosimetria a livello di voxel. M. Pacilio, Roma

Le nuove frontiere: dosimetria nelle terapie con alfa emettitori. C. Chiesa, Milano

Le nuove frontiere: la pianificazione di erapie combinate. M. Cremonesi, Milano

Dosimetria previsionale: carcinoma tiroideo (alte dosi) e SIRT.


A. Baroli, Busto Arsizio (VA) - M. Cremonesi, Milano - M. Maccauro, Milano - M. Salvatori, Roma

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
TORINO 16 -19 Novembre 2013

MEDICINA NUCLEARE RELAZIONI A INVITO • RELAZIONI LIBERE • POSTER

RELAZIONI LIBERE
Un rivelatore basato su un innovativo collimatore a fori paralleli per applicazioni in medicina nucleare.
M. Longo, Roma

Procedura per la validazione di una nuova matematica della posizione per gamma camere a scintillazione
con piccolo FoV. C. Marchioni Roma

Valutazione di una mini gamma camera per ottimizzazione dell’imaging intraoperatorio del linfonodo
sentinella nel melanoma. L. Riccardi, Padova

Ottimizzazione dell’algoritmo di ricostruzione iterativo in un sistema ibrido SPECT/CT di ultima


generazione. L. Gallo, Castelfranco Veneto (TV)
Influenza del numero di iterazioni e della frequenza di taglio del filtro nella valutazione dei parametri di
funzionalità miocardica per un algoritmo di ricostruzione iterativa con recupero della risoluzione spaziale.
I. Martinelli, Milano

Un modello generale per la dosimetria interna in volumi ellissoidali per emettitori alfa, beta e gamma.
D. Lizio, Novara

Dosimetria del midollo rosso, delle lesioni e correlazione dose-tossicità nella terapia del carcinoma
tiroideo metastatico con attività massimizzate di 131I. Marcata riduzione della dose assorbita dalle lesioni
dopo ripetuti trattamenti. L. Bianchi, Busto Arsizio (VA)

Confronto dosimetrico e analisi del follow-up clinico nel trattamento personalizzato dell’ipertiroidismo.
M. Cacciatori, Como

Risultati clinici a lungo termine della terapia con radioiodio basata sulla dose assorbita e su uno studio
dosimetrico pretrattamento personalizzato nelle autonomie tiroidee. C. Canzi, Milano

Radioimmunoterapia metabolica con anticorpi umani: dosimetria previsionale con 124I ed effettiva con 131I.
C. Bianchi, Milano

Valore del suspension level per la sensibilità delle sonde intraoperatorie nella ricerca del linfonodo
sentinella in pazienti con melanoma. S. Valzano, Novara

Radioembolizzazione di lesioni epatiche con microsfere caricate con 90Y: confronto tra dosimetria da
SPECT con 99mTc-MAA e PET con 90Y. F. Guerriero, Milano
Un metodo basato sui grafi per la segmentazione di volumi target biologici. A. Stefano, Palermo/Cefalù (PA)
Confronto e validazione di due algoritmi innovativi per la segmentazione semi-automatica di immagini
PET. M. Pacilio, Roma
Effetto del disallineamento delle immagini PET e CT sulla quantificazione dell’uptake di 18F-fluoride
nell’osso. D. D’Ambrosio, Pavia

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
TORINO 16 -19 Novembre 2013

MEDICINA NUCLEARE RELAZIONI A INVITO • RELAZIONI LIBERE • POSTER

POSTER
Impatto degli algoritmi iterativi nella definizione delle lesioni e nella qua tificazione nel sis ema PET/CT
Discovery-710. E. Lorenzini, Massa-Carrara

Correzioni di uniformità dell’ampiezza degli impulsi per una piccola gamma camera a cristallo continuo:
LaBr3:Ce(5%). T. Insero, Roma
Valutazione degli algoritmi di ricostruzione iterativi con recupero della risoluzione per la riduzione della
dose nei pazienti sottoposti a imaging di perfusione miocardica: uno studio multicentrico.
C. Scabbio, Milano

Valutazione di lesioni polmonari con tecnica ad inspirio forzato su tomografo PET/CT a 4 anelli: evidenze
da uno studio pre-clinico e clinico. S. Ren Kaiser, Brescia
Confronto fra metodi innovativi per la produzione di 99Mo allo scopo di realizzare generatori 99Mo/99mTc.
M. Gambaccini, Ferrara

Gioie e dolori in sei anni di gestione di un ciclotrone da 11 MeV per uso biomedico. M. C. Bagnara, Genova

Implementazione di un database differenziato per età di pazienti normali per l’analisi con SPM di studi
F-FDG PET neurologici cerebrali. R. Stoico, Legnano (MI)
18

Studio della dipendenza del Contrast Recovery Coefficent (CRC) in funzione dell’energia nelle immagini di
bremsstrahlung del fantoccio NEMA IEC standard riempito con Y-90 e acquisito con SPECT-CT.
F. Bonutti, Udine

Rivelabilità dei recettori della somatostatina con SPECT: confronto di due algoritmi di ricostruzione
iterativi. F. Voltini, Milano
Valutazione di un algoritmo di ricostruzione iterativo con recupero della risoluzione per SPECT-CT
miocardica di perfusione. L. Gallo, Castelfranco Veneto (TV)

Utilizzo di un algoritmo di ricostruzione iterativo evoluto in una gamma camera cardiologica


convenzionale. R. Soavi, Bologna

Valutazione del calcolo del SUV di un tomografo PET-CT e correlazione con i parametri misurati nei
controlli di qualità. M. Sireus, Cagliari

Accuratezza delle correzioni per attenuazione scatter nell’imaging miocardico SPECT/CT. C. Ghetti, Parma

Software di analisi dei logfiles p odotti dal ciclotrone della General Electric© MINItrace©. A. Loi, Cagliari

Valutazione clinica dell’algoritmo di ricostruzione iterativo 3D-OSEM per l’imaging SPECT miocardico.
C. Ghetti, Parma

Ottimizzazione e personalizzazione del radiofarmaco in medicina nucleare: l’esperienza di Trento.


R. Visentin, Trento

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
TORINO 16 -19 Novembre 2013

MEDICINA NUCLEARE RELAZIONI A INVITO • RELAZIONI LIBERE • POSTER


POSTER

Dosimetria al midollo rosso nella terapia con radioiodio del carcinoma differenziato della tiroide
metastatico: confronto in pazienti pluritrattati. E. Richetta, Torino
Influenza del metodo di calcolo dei fattori S a livello di voxel su distribuzioni di dose 3D in
radioterapia metabolica. M. Pacilio, Roma

Dosimetria al midollo rosso per pazienti affetti da carcinoma differenziato della tiroide: confronto dei
risultati pre-terapia e in corso di trattamento. A. Miranti, Torino

Dosimetria SIRT a livello di voxel come strumento di lavoro: verso un nuovo standard? D. Viscomi, Roma

Impatto dell’approccio dosimetrico a livello voxel nei trattamenti di radioembolizzazione di HCC con
microsfere di 90Y. A. Giostra, Torino
VoxelMed: sistema di calcolo di voxel dosimetry per terapia radiometabolica. V. Ferri, Reggio Emilia

Esperienze di pianificazione del trattamento di radioembolizzazione di lesioni epatiche. A. Terulla, Cuneo


Valutazione della dose in procedure PET-TC con 18F-FDG per sospetta vasculite dei grandi vasi.
L. Ferri, Genova
Dosimetria previsionale al midollo rosso con I-131 e I-124 nel carcinoma differenziato della tiroide: è
un valore affidabile? G. Rossi, Macerata

Dose efficace nel trattamento del morbo di Basedow. C. Canzi, Milano


Dosimetria pre-trattamento nella terapia con 131I dell’ipertiroidismo: confronto tra metodi di valutazione
della massa ed algoritmi di calcolo della dose. E. Richetta, Torino
177
Lu-SPECT/TC: imaging quantitativo e validazione di un software commerciale per studi di dosimetria.
L. D’Ambrosio, Napoli

Valutazione dell’attività residua in pazienti sottoposti a terapia tiroidea con 131I. M. Cacciatori, Como
Metodo semplificato per l’individualizzazione dell’attività terapeutica nella radioablazione del
residuo tiroideo, analisi di 4 anni di esperienza. S. Fattori, Macerata

Valutazioni statistiche di intensità di rateo di esposizione in pazienti sottoposti a terapia radiometabolica


con I-131 per tumori differenziati della tiroide: l’esperienza del Policlinico di Messina. I. Ielo, Messina
Dosimetria renale nella terapia recettoriale con radiopeptidi 177Lu e 90Y: influenza dei tempi
di acquisizione, del metodo di integrazione della curva attività tempo e dei fattori di rischio.
F. Guerriero, Milano

Dosimetria nella terapia del tumore tiroideo con radioiodio: studio comparativo della biocinetica fra il
primo ed il secondo trattamento. P. Moresco, Pietra Ligure (SV)

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
TORINO 16 -19 Novembre 2013

MEDICINA NUCLEARE RELAZIONI A INVITO • RELAZIONI LIBERE • POSTER


POSTER

Studi di scattering basati su metodo Monte Carlo allo scopo di implementare correzioni
paziente-specifiche per dosimetria 3D in radioterapia metabolica: risultati preliminari con
fantocci. D. Becci, Roma
Una tecnica innovativa di chirurgia radioguidata per la resezione completa dei tumori. R. Faccini, Roma
Definizione dei volumi di trattamento radioterapico nei tumori testa-collo tramite PET.
O. Ferrando, La Spezia
Implementazione e verifica del metodo di ricostruzione della mappa di attenuazione dopo movimento
durante scansioni PET-TC Brain. L. Ferri, Genova

La SPECT/CT potrebbe essere uno strumento utile nella valutazione dei volumi tiroidei nella malattia
di Basedow-Graves? O. Ferrando, La Spezia

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Procedure avanzate per imaging PET
R. Matheoud, S.Valzano, M.Brambilla
Medical Physics Department A.O. U. Maggiore della Carità, Novara

Introduction. Accurate quantification in PET requires correction for a number of physical factors, such as photon
attenuation, Compton scattering and random coincidences and for the limited spatial resolution.
The limited spatial resolution is usually coupled to image noise so that any improvements in resolution are
accompanied by increased noise. This limited resolution results in quantitative bias when imaging small objects.
The principal partial volume effect in emission tomography corresponds to spill-over of counts between different
image regions due to the point-spread function (PSF) of the system. In general the PSF in PET images depends on
the position of the source in the field of view of the scanner.
Nowadays, iterative reconstruction algorithm in PET imaging has been enriched with the inclusion of the detector
PSF and some commercial products are now available.
In this work the iterative reconstruction algorithm TrueX, which incorporates the recover of PSF of the system, was
characterized and compared to the traditional OSEM3D that is present on a Biograph HiRez pico-3D PET/CT
system (Siemens Medical Solutions).
Materials and methods. Measurements were performed on the NEMA IEC Body Phantom Set™ (Data Spectrum
Corporation, Hillsborough, NC) that contains 6 coplanar spheres, with internal diameters (ID) of: 10, 13, 17, 22, 28
and 37 mm. A supplemental set of two micro hollow spheres of ID 6.5, 8.1 mm (Data Spectrum Corporation) and 1
sphere of 57.4 mm was positioned at the bottom of the phantom. The background of the IEC phantom was filled
with 3 kBq/ml activity concentration of 18F-FDG. A standard protocol was designed to generate nine different
target-to-backgroud ratios (TB) (2.5:1, 4:1, 8:1, 16:1, 25:1, 35:1, 47:1, 55:1 and 70:1) realized in nine separate
sessions that were acquired with four different emission scan durations (ESD) of 2, 3, 4 and 5 min to provide
independent replicates of the experiments.
The entire set of acquisitions (4x9 datasets) was reconstructed over a 256x256 matrix with a pixel size of 2.6 mm
and a 2mm slice thickness with two different iterative reconstruction algorithms: the AW-OSEM3D (3 iterations
and 8 subsets and a Gaussian smoothing filter of 4, 6 and 8mm) and the TrueX (3 iterations and 8 subsets and a
Gaussian smoothing filter of 4mm). These images have been used to analyze the image quality in terms of hot
sphere contrast recovery coefficient (HC_RC) and maximum SUV (SUVmax) of the spheres.
The 5’ acquisition data (9 datasets) were reconstructed over a 128x128 matrix with 5.25 mm pixel size and 2 mm
slice thickness with two different iterative reconstruction algorithms: the AW-OSEM3D and the TrueX both with
3 iterations and 8 subsets and a Gaussian smoothing filter of 4mm. These images have been used to derive an
adaptive thresholding algorythm (ATA) for both the reconstruction algorithms used. Thresholds (TH) were
determined as a percentage of the maximum intensity in the largest cross sectional area of the spheres and were
entirely based on the apparent activity concentration in the images.
The relationship between the best TH and the variables A, TB and FWHM, all linearly related to TH, was
established using multiple linear regression methods for each combination of ESD, using the model:
TH = B0 +B1 x sphere A (mm2) + B2 x (1-1/TBR)+ B3 x FWHM (mm) + E
where B0, B1, B2 and B3 are the regression coefficients that need to be estimated and E is the error term.
Results. HC_RC values are reported in Figure 1 and 2 for TrueX and Osem3D, respectively.

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Truex OSEM-3D

TB74
120% TB74 120%
TB53 TB53
100% 100%
TB37 TB37
80% 80% TB23
TB23

HC_RC
HC_RC

60% TB16 60% TB16

TB8 40% TB8


40%
TB3 TB3
20% 20%
TB2 TB2
0% 0%
0 10 20 30 40 0 10 20 30 40

Diam eter, m m Diameter, mm

SUVmax values are reported in Figure 3 and 4 for TrueX and Osem3D, respectively.
TRUEX OSEM 3D

50 40
74 74
45 35
SUVmax

SUVmax

40 53,3 53,3
37 30 37
35
30 23,3 25 23,3
25 16,4 20 16,4
20 7,5 15 7,5
15 3,2
3,2 10
10
1,5 5 1,5
5
0 0
0 10 20 30 40 50 60 70 0 10 20 30 40 50 60 70
Diameter, mm Diameter, mm

The regression equations that best summarize the results obtained in a multiple regression model with TH as the
predicted variable for OSEM3D and TrueX are:
Osem3D: TH = 82.1 – 49.9*(1-1/TB) + 0.927*FWHM r2 = 0.92
TrueX: TH = 70.6 – 37.8*(1-1/TB) + 0.0017*A r2 = 0.60
Discussion and conclusions.
The results obtained in the present work show that, at least for the settings used of a non-TOF PET system, the
resolution recovery reconstruction algorithm in quantitative PET imaging need to be accurately validated before its
introduction in clinical routine.
Moreover, the application of an adaptive thresholding method on PET images reconstructed with the resolution
recovery algorithm leads to important volume misestimations.

References:
[1] K. Erlandsson et al, A review of partial volume correction techniques for emission tomography and their
applications in neurology, cardiology and oncology, Physics in Medicine and Biology (2012) 57, R119-R159
[2] V. Y. Panin, Fully 3-D PET Reconstruction With System Matrix Derived From Point Source Measurements,
IEEE Transaction on Medical Imaging (2006) 25, 907-921

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
SPECT imaging for voxel dosimetry
M. Pacilio1, D. Becci2.
(1) Azienda Ospedaliera San Camillo Forlanini, Rome (2) Scuola di Specializzazione in Fisica Medica, Rome
The tailoring of the radionuclide therapy treatment is needed to deliver therapeutic dose to tumor while avoiding
critical organ toxicity, improving the treatment efficacy. Direct measurement of absorbed dose in radionuclide
therapy is not feasible, so the absorbed dose is usually estimated from activity quantification obtained with non-
invasive imaging. Pretreatment tracer imaging allows to predict the absorbed dose during therapy (i.e., treatment
planning). Most clinical studies performed in radionuclide therapy have not shown a strong correlation between
tumor dose and response. This is possibly due to inaccuracies in dose estimation or because typically only mean
tumor dose was used. In radionuclide therapy, the absorbed dose non-uniformity across a target volume can be (and
usually is) greater than other radiation therapy modalities, owning to the non-uniformities in the activity deposition.
The non-uniformity of the absorbed dose distribution affects significantly the cell survival fraction in tumor and
normal tissue, so mean tumor dose cannot provide sufficient information.
Voxel dosimetry (or 3D dosimetry) consists into dosimetric calculations allowing to obtain 3D distribution of the
absorbed dose (i.e., the absorbed dose at the voxel level) using morphologic and functional (PET or SPECT)
imaging [1]. Several calculation techniques are available, such as direct Monte Carlo simulations, convolution of
voxel S values or dose point kernel, employing tomographic images of cumulated activity derived from PET or
SPECT biokinetic studies [2-10]. All methodologies can be deemed equivalent, at least for anatomic regions
characterized by nearly-uniform density tissue [11], whereas direct Monte Carlo (MC) simulation is generally
considered the gold standard, since it can account for inhomogeneity of absorbing media.
The main sources of uncertainty in voxel dosimetry derive from cumulated activity quantifications, which
constitute the input data for dosimetric calculations. The activity quantification at the voxel level requires dedicated
acquisition procedures, optimized to guarantee adequate accuracy. Remarkably, SPECT-CT images find
application for many of the main therapeutic applications, but this is not the case for PET-CT. This is mainly due
to the possibilities of mimic therapy with the same radiocompound, when the radionuclide is also a -emitter, or
with the same therapeutic molecule labeled with a -emitting radionuclide having similar chemical behavior.
Moreover, besides the less widespread availability of +-emitters, their T1/2,phys results very often too short for
performing biokinetic study with an adequate temporal window. So, the greater availability of options makes
SPECT -imaging more valuable for dosimetric studies [12].
Biokinetic studies for voxel dosimetry require co-registration of several functional images acquired at different
time, and biokinetic description at the voxel level, so data collecting and processing is still really challenging,
mainly due to the long acquisition time required for SPECT-CT studies, and to the need of several time points for
adequate sampling. In some cases a serial SPECT-CT study can present too many difficulties to guarantee an
adequate level of accuracy. The biokinetic description at the level of the overall volume of interest, together with a
spatial distribution of activity described by a unique SPECT study, results very often more feasible [1,13-17]. This
is the easiest option for taking into account the biokinetics at the voxel level, even though it implies a loss of
accuracy which sometimes is difficult to predict.
Several additional factors contribute to dosimetric uncertainty, mainly due to degradation and quality loss of the
SPECT images. It is worth mentioning that SPECT imaging and reconstruction techniques for quantification in
radionuclide therapy are not necessarily the same as those designed to optimize diagnostic imaging quality.
Quantitative SPECT (QSPECT) requires modeling and compensations of image degrading factors, so QSPECT
imaging methods, which incorporate compensation for non-uniform attenuation, scatter, and collimator–detector
response (CDR), have been developed and evaluated for voxel dosimetry by several groups [18-22]. QSPECT has
been demonstrated to provide improved quantification of total organ activity and mean absorbed dose: for instance,
a simulation study modeling 111In Zevalin [21], the error in mean organ activity estimates with advanced QSPECT
methods was found to be less than 5.5% for most organs. Recently, the MIRD Committee published the Pamphlet
No. 23 with the aim to provide an overview <<..intended as an introduction to an upcoming series of MIRD

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
pamphlets with detailed radionuclide-specific recommendations intended to provide best-practice SPECT
quantification–based guidance for radionuclide dosimetry>> [23]. The acquisition protocols should be optimized
according to the involved radionuclide (i.e., position, number and widths of the energy windows) and expected
tomographic spatial resolution of the imaging system. Iterative algorithms for image reconstruction are strongly
advisable for QSPECT. For attenuation corrections, CT-based attenuation maps are preferred as they have lower
noise, better spatial resolution, and better contrast and are generally faster and easier to acquire. Hybrid SPECT-CT
(or PET-CT) systems allow accurate images co-registration, guaranteeing adequate attenuation correction. But
several additional features of image reconstruction should be optimized, e.g. for the OSEM algorithm, number of
iterations and subsets, postreconstruction low-pass filtering, corrections for the scatter component, as well as a
proper modeling of the collimator-detector response. Last but not least, partial volume effects should be also
assessed, trying to delineate accurately the tumor volume [24] and performing recovery corrections which account
for the anatomic shape of the objects (considering the whole objects with a uniform uptake). Voxel-by-voxel
correction strategies to recover the true activity distribution have been widely investigated for PET imaging [25-
26], but for SPECT imaging there are currently no well-validated methods.
The importance of using optimal reconstruction and regularization parameters was widely evidenced in the
literature, but it is still being studied, also for understanding if parameters should be different at each time point, or
a single set of parameters for all time points could produce results with adequate accuracy [27].

References:
[1] W. E. Bolch et al, MIRD Pamphlet No. 17: the dosimetry of nonuniform activity distributions – radionuclide S
values at the voxel level, J Nucl Med (1999) 40, 11S-36S.
[2] J. M. Franquiz et al, Beta voxel S values for internal emitter dosimetry, Med Phys (2003) 30, 1030-1032
[3] A. Dieudonné et al, Clinical Feasibility of Fast 3-Dimensional Dosimetry of the Liver for Treatment Planning
of Hepatocellular Carcinoma with 90Y-Microspheres, J Nucl Med (2011) 52, 1930–1937.
[4] M. E. Ferrari et al, 3D dosimetry in patients with early breast cancer undergoing Intraoperative Avidination for
Radionuclide Therapy (IART) combined with external beam radiation therapy, Eur J Nucl Med Mol Imaging
(2012) 39, 1702-1711.
[5] M. Pacilio et al, Differences among Monte Carlo codes in the calculations of voxel S values for radionuclide
targeted therapy and analysis of their impact on absorbed dose evaluations, Med Phys (2009) 36, 1543-1552.
[6] F. Botta et al, Calculation of electron and isotopes dose point kernels with FLUKA Monte Carlo code for
dosimetry in nuclear medicine therapy, Med Phys (2011) 38, 3944-3954.
[7] E. Amato et al, An analytical method for computing voxel S factors for electrons and photons, Med Phys (2012)
39, 6808-6817.
[8] N. Lanconelli et al., A free database of radionuclide voxel S values for the dosimetry of nonuniform activity
distributions, Phys Med Biol (2012) 57, 517-533.
[9] A. Prideaux et al, Three-dimensional radiobiologic dosimetry: application of radiobiologic modeling to patient-
specific 3-dimensional imaging-based internal dosimetry, J Nucl Med (2007) 48, 1008-1016.
[10] S. Marcatili et al, Development and validation of RAYDOSE: a Geant4-based application for molecular
radiotherapy, Phys Med Biol (2013) 58, 2491–2508.
[11] A. Dieudonné et al, Fine-resolution voxel S values for constructing absorbed dose distributions at variable
voxel size, J Nucl Med (2010) 51, 1600-1607.
[12] S. Fanti, M. Farsad and L. Mansi Eds. Atlas of SPECT-CT. (2011) Springer-Verlag Berlin Heidelberg.
[13] G. Sgouros et al, Patient-specific, 3-dimensional dosimetry in non-Hodgkin’s lymphoma patients treated with
131I-anti-B1 antibody: assessment of tumor dose-response. J Nucl Med (2003) 44, 260–268.

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
[14] M. Garkavij et al, 177Lu [DOTA0, Tyr3] octreotate therapy in patients with disseminated neuroendocrine
tumors: analysis of dosimetry with impact on future therapeutic strategy, Cancer (2010) 116, 1084–1092.
[15] K.F. Koral et al, Update on hybrid conjugate-view SPECT tumor dosimetry and response in 131I-tositumomab
therapy of previously untreated lymphoma patients, J Nucl Med (2003) 44, 457–464.
[16] K. Assié et al, Comparison between 2D and 3D dosimetry protocols in 90Y-ibritumomab tiuxetan
radioimmunotherapy of patients with non-Hodgkin’s lymphom, Cancer Biother Radiopharm (2008) 23, 53–64.
[17] J. Grimes et al, JADA: a graphical user interface for comprehensive internal dose assessment in nuclear
medicine, Med Phys (2013) 40, 072501.
[18] M. Ljungberg et al, A 3-dimensional absorbed dose calculation method based on quantitative SPECT for
radionuclide therapy: evaluation for 131I using Monte Carlo simulation, J Nucl Med (2002) 43, 1101–1109.
[19] M. Ljungberg et al, 3D absorbed dose calculations based on SPECT: evaluation for 111-In/90-Y therapy using
Monte Carlo simulations, Cancer Biother Radiopharm (2003) 18, 99–107.
[20] Y.K. Dewaraja et al, Accurate dosimetry in 131I radionuclide therapy using patient-specific, 3-dimensional
methods for SPECT reconstruction and absorbed dose calculation, J Nucl Med (2005 ) 46, 840–849.
[21] B. He et al, A Monte Carlo and physical phantom evaluation of quantitative In-111 SPECT, Phys Med Biol
(2005) 50, 4169–4185.
[22] B. He and E.C. Frey, Comparison of conventional, model-based quantitative planar, and quantitative SPECT
image processing methods for organ activity estimation using In-111 agents, Phys Med Biol (2006 ), 51 3967–
3981.
[23] Y.K. Dewaraja et al, MIRD Pamphlet No. 23: Quantitative SPECT for patient-specific 3-dimensional
dosimetry in internal radionuclide therapy, J Nucl Med (2012) 53, 1310–1325.
[24] M. Pacilio et al, An innovative iterative thresholding algorithm for tumour segmentation and volumetric
quantification on SPECT images: Monte Carlo-based methodology and validation, Med Phys (2011) 38, 3050-
3061.
[25] X. Geets et al, A gradient-based method for segmenting FDG-PET images: methodology and validation, Eur J
Nucl Med Mol Imaging (2007) 34, 1427-1438.
[26] N. Bouisson et al, Incorporation of wavelet-based denoising in iterative deconvolution for partial volume
correction in whole-body PET imaging, Eur J Nucl Med Mol Imaging (2009) 36, 1064-1075.
[27] L. Cheng et al, Improved dose–volume histogram estimates for radiopharmaceutical therapy by optimizing
quantitative SPECT reconstruction parameters, Phys Med Biol (2013) 58, 3631-3647.

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Dosimetry of alpha particle emitters for targeted radionuclide therapy

C. Chiesa

Fondazione IRCCS Istituto Nazionale Tumori, Milano, Italy

Foreword

This work is the summary of the MIRD Pamphlet No. 22 [1] with the addition of personal considerations and
informations kindly provided by members of the EANM Dosimetry Committee. We address interest readers to the
original document which is the richest review of available literature about this topic.
The clinical interest toward α-particle emitters in nuclear medicine therapy, derives from the fact that with these
nuclides it is possible to sterilize individual tumor cells solely from self-irradiation, while this is generally not
possible with β-particle emitters, mantaining at the same time an acceptable toxicity profile.

Radiobiology of alpha & beta particles: LET, range, dose rate, oxigen effect

The symple physical basis of the difference between alpha and betas rays is the ratio between their masses, which
is about 8000 to 1. This huge difference, toghether with the electric charge larger only a factor of 2 and the
emission energy higher only a factor of 10, imply that alphas travels with non relativistic speed (about 1/20 of the
light speed), while betas are relativistic with speed practically equal to the light speed. The slower alphas exhange
therefore much higher momentum with the electrons in the medium their are crossing, with a resulting much higher
Linear Energy Transfer (LET), measured in keV/micron. LET of alphas of 5.9 MeV and 8.4 MeV are 80
keV/micron and 61 keV/microsn respectively, while betas of 100 and 500 keV have LET of 0.2 - 0.5 keV/micron.
This much higher LET of an apha particle results in much higher ionization density along its track and much
shorter range than beta particles. Both these features have extremely important implications in radionuclide therapy
and dosimetry.
The ionization density has a marked influence on the shape of the survival curve as a function of the dose.
Low LET radiations (photons and electrons) exhibit 3 to 9 ionization over a 3 nanometer distance. The alpha
particle range is so short that few cell diameters, typically 5, are crossed by each particle. Beta rays cross a hundred
of cells, so their efficacy has a collective character (figure 2). With beta projectiles, linear quadratic cellular
survival curves were obtained, meaning that type B damage (dual Single Strand Break of the DNA in one site,
following two independent hits) do have an important relative contribution. On the contrary, high LET alpha
particles with more than 10 ionizations per nanometer showed purely linear survival curves, without shoulder. This
is a clear indication that the damage mechanism is mainly the Double Strand Break (DSB) due to a single hit.
It is clear in cases of combinations of radiopharmaceuticals and cells where the absence of the quadratic
was demonstrated, a simple linear model could be applied, without considering the dose rate effects, i.e. the
neglecting Biologically Effective Dose concept.
From these experiments we understand that the concentration of ionizations along the alpha track is so high
that a single hit to DNA is capable to kill a cell. This is an advantage if the track does cross the DNA structure, but
it is a waste of dose if it does not. Figure 3 represent this concept. It is clear that in the case of beta rays, the
concept of mean dose is meaningful, evn if averaged on a macroscopic volume which can be as small as a voxel
accessible in vivo with human scanner (some millimiter side). Mean dose can be meaninless with alphas, or, better,
scarcely predictive of the biological effect, since the same amount of energy deposited by a projectile shooted from
the cellular membrane, from the cytoplasma or from inside the nucleus could give completely different biological
effects.

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Planning combined treatments of external beam radiation therapy and molecular radiotherapy.

Marta Cremonesi, Mahila Ferrari, Francesca Botta, Francesco Guerriero

Fisica Sanitaria, Istituto Europeo di oncologia, Milano

Introduction
The use of combined treatments is mostly applied in cancer therapy. Different techniques such as surgery,
chemotherapy, radiation therapies can have a synergic effect to eradicate or reduce tumoral lesions. The more
recent literature offers interesting examples of studies combining different radiation therapy modalities such as
external beam radiation therapy (EBRT) and Molecular RadioTherapy (MRT) with radiopharmaceuticals. The aim
of this strategy is to increase the efficacy of the treatment by a higher irradiation of the target in the respect of
threshold limits to different critical tissues. A further advantage is the possibility to combine a local effect (from
EBRT) to the effect of a systemic therapy (MRT), potentially able to irradiate lesions not yet documented due to
resolution limits.
Several authors have described the theoretical approach for a combined EBRT and MRT that includes
radiobiological considerations about the normal organ tolerability and tumor control. To date, the clinical studies
are not yet optimized, being based on empirical approaches and aiming to assess feasibility and toxicity. They are
of concern though as they offer relevant information for future perspectives. Considerations for a combined
treatment may also apply to patients coming to MRT after other treatment options including EBRT, or vice versa.
The present work offers an overview of the rationale guiding the combination of EBRT and MRT and summarizes
the main results of some interesting clinical trials.

Methods
The implementation of combined therapies has to rely on the accuracy of each among several steps. The image co-
registration, required to correlate the information from the two modalities, should be as accurate as possible in
order to avoid any error propagation to the combined result.
Dose estimation in EBRT has a very high accuracy as compared with MRT, where many factors contribute to the
final quality of the datum, and where all the possible efforts should be put in action to improve the final result.
When performing MRT image-based dosimetry, for example, nuclear medicine images should be properly
reconstructed and corrected for scatter, attenuation, response of the system in order to gain accuracy. Moreover, the
low spatial resolution of nuclear medicine images represents an intrinsic limit, smoothing the activity distribution
and consequently the calculated absorbed dose distribution. So, proper correction for partial volume effect has also
to be implemented. With images of sufficient accuracy, 3D dosimetry methods are recommended, based on
convolution methods or direct Monte Carlo simulations to calculate the absorbed dose at voxel level.
Once an acceptable accuracy of MRT dosimetry can be assumed, the problem raises to convert the MRT
information into EBRT information or vice versa, due to the very different characterists of the two modalities, first
of all different dose rates. MRT delivers the dose with a continuous slowing down dose rate, as a result of activity
distribution and biological and physical decay, whilst EBRT delivers the dose almost instantaneously with multiple
fractions. Consequently, different biological effects are expected to occur for a same absorbed dose delivered with
one or another modality.
In several studies the linear quadratic model has been proposed to combine the absorbed doses from these two
techniques through the Biological Effective Dose (BED) concept. BED is a parameter which adequately takes into
account not only the amount of dose delivered, but also the time dependency of the delivery in relation to the tissue
response to the radiation injury. Thus, under the hypothesis of the linear quadratic model, a same biological effect
is expected to occur for a same BED delivered with one or another modality. The principal equations are here
summarized:

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
ln(SF) = -αBED (1)

DEBRT / n
for EBRT: BED = DEBRT 1 + (2)
α /β

G(∞) ⋅ DMRT
for MRT: BED= DMRT 1 + (3)
α /β

where SF is the fraction of cells surviving after irradiation; α/β relates the intrinsic radio-sensitivity α to the
potential sparing capacity (β); DEBRT is the absorbed dose delivered with EBRT in n fractions (dose per fraction:
DEBRT/n), and DMRT is the absorbed dose delivered with MRT. G(∞) is the Lea-Catcheside factor that accounts for a
protracted radiation where repair of subletal DNA damage can occur during irradiation. G(∞) is a function of the
repair constant µ. For MRT with monoexponential ( ) dose rate, equation (3) simplifies as:

DMRT ⋅ λ
BED= DMRT 1 + (4)
(µ + λ) ⋅ α / β

The radiobiolgical parameters included in eq. 1-4 are specific for tissues and the effects. Typically, / ranges are
7-20 Gy and 0.5-6 Gy for acutely and late responding tissues, respectively. Typical α/ values assumed are 10 Gy
for tumors and 3 Gy for normal organs. The repair constant µ can be e.g. 0.46 h-1 (T rep =1.5 h) for normal tissues
and 1.3 h-1 (T rep= 0.54 h) for tumors.
In case of dose heterogeneity, the Equivalent Uniform Biological Effective Dose (EUBED) has been defined for
tumors and organs with parallel structure to represent the biological dose which would result from a uniform dose
and that would produce the same number of surviving cells. It can be calculated to assess the possible
radiobiological effect, according to the following equation:

EUBED = (5)

where P( ) represents the probability density function of BED ( ), and exp(-α ) is the expression of the
fraction of surviving cells SF.
In some cases of MRT the Equivalent Uniform Dose (EUD) can be a useful parameter to be extrapolated from:
λ
EUBEDMRT = EUDMRT (1 + EUDMRT ) (6)
(µ + λ) ⋅ α / β
This mirrors equation 4 but accounts for heterogeneity. Similarly, EUD for EBRT can be derived as the solution of
the following equation:

EUDEBRT
EUBEDEBRT = EUDEBRT (1 + (7)
n ⋅ α /β

Examples where the LQ model is applied

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
The methods described above propose a useful guide to integrate different modalities but still remain models that
have to be validated by clinical trials. To date, they are applied in rare cases, to show a theoretical advantage from a
combined approach or when a rationale is preferred to empiricism to build a clinical protocol. Here follow the most
representative examples taken from the literature.
In the paper by Bodey et al, some cases are described showing the advantage from a therapy combination as
compared to a single modality of treatment. For different patients who underwent MRT, hypothetical EBRT
treatment planning was also prepared obtaining dose and BED distribution maps for each therapy and for their
combination. The absorbed doses from MRT were converted into corresponding doses for the EBRT schedule
using the LQ model. The Dose Volume Histograms (DVH) of the EBRT alone or the combination strategy were
compared for the tumor and the organ at risk. E.g. for a patient affected by retroperitoneal neuroblastoma and
treated with 131I- MIBG (33 GBq), the EBRT treatment planning delivering a dose of 60 Gy to the isocenter was
considered. For the combined therapy, the EBRT contribution was scaled in order to deliver a same minimum dose
to the clinical target volume (CTV) as with EBRT alone. In this patient the organ at risk was the left kidney, and
the analysis of the DVHs (figure 1) highlighted the advantage of the combined solution for both the kidney and the
CTV. The mean dose ratio between kidney and CTV was 0.40 vs. 0.16 for the EBRT alone vs. the combination.
Another study by Hobbs et al. applies the equations of the linear quadratic model in search of therapy optimization
in a patient with osteogenic sarcoma enrolled in a protocol of high-dose 153Sm-EDTPM. Although the patient did
not receive the treatment, the case was studied for subsequent Intensity modulated radiation therapy (IMRT)
designed in order to deliver a dose of 30 Gy to 90% of the tumor (2 Gy/fraction) while minimizing the dose to the
spinal cord. The paper emphasizes the importance of dosimetry accuracy. Tumor is drawn on CT. SPECT images
are corrected for attenuation, scatter, collimator detector response, partial volume effect and coregistered with CT
to be input of the 3DRD software for dosimetry evaluations with Monte Carlo simulations. BED maps for MRT are
converted into absorbed dose maps of EBRT and the relative contribution of EBRT established by a factor such
that the highest voxel total absorbed dose in the spinal cord involved preserved the constraint of 50 Gy. With the
administered activity of 16.7 GBq, the average absorbed doses from MRT normalized to EBRT were 22.6 Gy to
the tumor and 3.9 Gy to the spinal cord, while for EBRT alone they were 54.6 Gy and 18.6 Gy, respectively. The
evaluations revealed the superiority of the combined treatment, with an average value of 71.5 Gy to the tumor and
20.6 Gy to the spinal cord.
A new procedure called IART® (Intraoperative Avidination for Radionuclide Therapy) was recently used in
patients with early breast cancer undergoing conservative surgery. The purpose of this therapy is to irradiate the
residual mammary gland immediately after surgery in order to give an anticipated boost to the tumor bed. It
consists of the administration of 3.7 GBq of 90Y-biotin to be combined to a shortened course of EBRT. The study
by Ferrari et al. (14 patients) performed a voxel dosimetry analysis to investigate the dose heterogeneity of IART.
Its impact on therapy outcome was assessed using the linear quadratic model, evaluating the biologically effective
dose (BED) distribution. Dose-volume and BED-volume histograms were generated to derive EUBED and EUD
values for IART. The following radiobiological parameters were used: α/ =10, µ=0.5 h-1, α=0.3 Gy-1. The median
BED and EUBED values were 21.8 (15.9–29.3) Gy and 22.8 (17.3–31.8) Gy, respectively. The median EUD was
20.4 (16.5–29.4) Gy, with EUD/mean absorbed dose ratio >0.9, indicative of acceptable uniformity in the target.
The effects of IART were compared with those of EBRT, extrapolating the number of EBRT fractions that would
cover the same EUBED produced by IART. The median value was 9.5 (7.2 - 13.3) fractions, corresponding to
about 2 weeks of EBRT at 2 Gy/fraction. These evaluations allowed to tailor the subsequent number of EBRT
fractions needed to complete the treatment and deliver the prescribed radiation dose (e.g. about 70 Gy BED). Over
35 patients treated only 1 relapsed at 5 years post treatment, but larger series should be considered to derive
conclusions about the equivalence of IART+EBRT vs. standard EBRT.

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
The impact of the radiobiological parameters remains an open issue of the model, but the update of values that
become available from specific studies can be easily included. For instance, in IART, the α/ value of 4.6 Gy
derived from the more recent literature should replace the α/ of 10 Gy considered. As a consequence, there is the
need of one more fraction (2 Gy) of EBRT after IART to compensate a lower D2Gy/fr value derived.

Feasibility studies
Besides the previous examples, the literature offers several clinical trials that are of great interest despite they are
not optimized on a theoretical basis but rely on empirical background. They are essentially studies of feasibility
and/or tolerability, or retrospective studies, using standard or empirical protocols for EBRT and MRT. A limited
number of patients is typically involved. MRT is provided with fixed activities (one fits all), or activities per body
surface area, so that absorbed doses are not personalized. Dosimetry evaluations for MRT are not always
performed, and radiobiological models are not considered/applied. Nevertheless, these studies represent a rich
source of information for future tailored planning on a patient specific basis. The examples that follow show the
wide range of applications emerging, and the potential of the combined treatment strategy, opening the way to
prospective optimized studies.
153
Sm-EDTM, bone metastases - A prospective clinical trial described by Baczyk et al. compared the analgetic
effectiveness and toxicity of monotherapy with 153Sm-EDTM isotope to combined therapy of 153Sm-EDTM
followed by EBRT. 88 patients affected by metastatic prostate cancer were included, having at least 3 bone
metastases. The administered activity of 153Sm-EDTM was 37 MBq/kg and different EBRT schedules were applied
3 to 14 days after (8 Gy x 1 fraction; 4 Gy x 5 fractions; 3 Gy x 10 fractions). The impact of different EBRT
absorbed doses and dosimetry from 153Sm-EDTM were not considered. The results indicated that combined therapy
did not intensify the toxicity and was more effective than isotope therapy alone.

PRRT, meningiomas - In a study by Kreissl et al. the feasibility and tolerability of a combination of peptide
receptor radionuclide therapy (PRRT) with EBRT has been assessed in 10 patients affected by irresectable
meningioma. Patients were administered with 7.4±0.3 GBq of 177Lu-DOTATATE
/DOTATOC. Two to 9 days after MRT, EBRT with IMRT technique was performed, with a schedule decided
individually based on clinical considerations with the aim to avoid possible toxicity. Median absorbed dose (D95)
among patients was 53 Gy ranging 40 to 60 Gy with 1.8-2 Gy/fraction, and a limit of 54 Gy was set to the optic
organs. In four patients the EBRT dose to the target was empirically reduced because of concerns to the optical
nerve due to summation of doses. Absorbed doses were simply summed without considering DVH or the BED
formalism (LQ model). The study however showed the feasibility and tolerability of PRRT+EBRT.
131
I-MIBG, pheochromocytomas and non head and neck paragangliomas - The role of EBRT in the management of
patients with malignant pheochromocytoma or non head and neck paraganglioma is controversial. Fishbein et al.
have described sequential 131I-MIBG (2 mCi/kg per two treatments) and EBRT in 5 patients affectet by these
tumors. The 131I-MIBG scan was used to assist the EBRT planning. The dose limiting toxicity for 131I-MIBG is
hematologic, while IMRT was used to spare the peritumoral normal tissues (bone marrow, bowel). Two to 6
Gy/fraction schemes were applied, for a total EBRT absorbed dose ranging 30 to 54 Gy. Areas irradiated with
EBRT showed durable objective response, whereas out-of-field systemic progression required other treatment. The
results showed that EBRT can be highly effective in local management of malignant paraganglioma and can be
used with 131I-MIBG due to nonoverlapping toxicities with excellent control of locally bulky tumors.

Radioimmunotherapy, follicular lymphoma - The strategy of combining EBRT with Radioimmuno-therapy (RIT)
with 90Y-ibritumomab tiuxetan (90Y-IT) was applied by Burdick et al. in patients with relapsed or refractory bulky
(>5 cm) follicular lymphoma, in the attempt to improve therapeutic response. In a group of 11 patients, a reduced

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
regimen of 24 Gy given in 8 fractions (vs. a standard of 40 Gy delivered in 2 Gy/fraction) was planned to reduce
the time interval with 90Y-IT. As a result, with α/ =10 for lymphoma, the BED was 31.2 Gy as compared to the
standard 48 Gy. 90Y-IT (0.3, 0.4 mCi/kg) was administered after recovery of blood counts and the biodistribution
analysis with 111In-IT. However, no dosimetry evaluations were performed/shown for the RIT. The
complete/overall response rate of 64% and with no relapsed lesions within EBRT field, confirmed the efficacy of
EBRT to pre-treat bulky sites before 90Y-IT. EBRT followed by 90Y-IT did not showed the relapse of bulky
disease, reaching 100% of local control, with a median progression free survival of 18 months. It was concluded
that the combined treatment may improve clinical outcomes and extend survival.

Radioimmunotherapy, brain metastases - RIT with 131I-L19SIP (4.1 GBq/m2) in addition to whole brain
radiotherapy (30 Gy in 10 fractions) has been proposed by Poli et al in 6 patients affected by multiple brain
metastases from solid cancer. Patient eligibility was decided based on a previsional dosimetry evaluation with 124I-
L19SIP, to guarantee absorbed doses to the red marrow within 2 Gy. RIT showed a wide variability of the absorbed
doses to brain lesions (median 0.38; range:0.10-1.37 Gy/GBq) as well as to extracranial lesions (median 1.41;
range: 0.15-5.38 Gy/GBq), leading to 2.4 (0.7-8.1) Gy and 7.3 (1.1-35.8) Gy, respectively. The study could assess
the tolerability of the treatment, laying the foundations for future optimization of the combining therapy that might
compensate the variability of the RIT absorbed doses.

Radioembolization, liver lesions - The safety of the radioembolization (RE) of liver lesions with 90Y microspheres
has been retrospectively studied by Lam et al. in patients who came at RE after previous EBRT. 31 patients were
considered, with the DVH analysis for the EBRT planning. RE was administered with empirical methods according
to the manufacturer protocols. No DVH for RE were considered/shown. The mean absorbed doses to the non
tumoral liver was 4.4 (0-23) Gy for EBRT and for RE the mean dose to the liver was 58 (27-149) Gy. Patients who
experienced hepato-toxicity of grade II or higher (39% of cases) received also higher EBRT absorbed doses to the
liver, with a trend also of higher cumulative absorbed doses. Two patients, who had fatal RE induced liver disease
(REILD), received the highest absorbed doses for EBRT (21,23 Gy) and RE (92, 149 Gy). A multivariate analysis
indicated the mean EBRT doses as the only independent predictor of toxicity, with the fraction of liver exposed to
at least 30 Gy (V30) being the strongest predictor of toxicity, with a threshold for hepatotoxicity at a volume of
∼10% and a threshold for fatal REILD at a volume of ∼30%. Exact thresholds for safe RE after EBRT were not
established. It is concluded that the dose-response relationship for hepatotoxicity after RE remains unclear, owing
to the uncertainty of the RE dose distribution in comparison with EBRT. It is deduced that the liver tolerates a
much higher mean dose from RE in comparison with RT, likely because of the inhomogeneity of microsphere
distribution. However, it has to be said that besides the simple mean absorbed doses, the analysis of the dose
distribution in RE and considerations from radiobiological models are lacking in the study. These could have lead
to relevant information and possibly to different conclusions.

Conclusions
Treatments combining EBRT and radiopharmaceutical therapy are a promising option that can be applied in many
different scenarios, and may be more advantageous than a single radiation modality, with improved conformality of
the target and reduced irradiation of critical tissues. In fact, different therapies have usually different organs at risk,
so the properties of each therapy can be fully exploited. The implementation of special EBRT techniques (such as
IMRT) can be designed to complement the typical inhomogeneous dose distribution of MRT, potentially increasing
the efficacy of the combined result. To date, clinical trials are based on empirical approaches but allow to derive
crucial information. A wide variety of possible applications have already been proposed in the literature, including
combinations of EBRT with MRT. This scenario envisages future development of prospective clinical studies
towards optimization.

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Dosimetry in Therapy of Metastatic Differentiated Thyroid Cancer (MDTC) Administering High 131I
Activity: the experience of Busto Arsizio Hospital (Italy)
A. Baroli*, L.Bianchi^, L. Pedrazzini*, A. Pepe^, G.Lomuscio*, E.Di Mauro*.
Dept Oncology - Nuclear Medicine Unit*, Azienda Ospedaliera “Ospedale di Circolo di Busto Arsizio” - p.le
G.Solaro 3, 21052 Busto Arsizio (Va) - Italy
Health Physics Unit^, Azienda Ospedaliera “Ospedale di Circolo di Busto Arsizio” - p.le G.Solaro 3, 21052 Busto
Arsizio (Va) - Italy

Background
Despite the low aggressiveness of metastatic differentiated thyroid cancer (MTDC) and the fact that its treatment
with radioiodine is well consolidated, still some percentage of patients are lost, or become refractory along the
sequence of treatments. High activity treatments seem to improve the outcome compared to multiple treatments
with lower activities.
Radioiodine-avid metastases should be treated with RAIT when objective benefit is demonstrated (decrease in the
size of the lesions, decreasing Thyroglobulin - Tg). The selection of RAIT activity to administer can be made
empirically (100-200 mCi 131I) or estimated by lesional dosimetry or dosimetry to limit wholebody retention to 80
mCi at 48 hours and 200 cGy to the red bone marrow.
In the near future Empiric radioactive iodine therapy (100-200 mCi 131I) might be considered only in patients with
elevated Tg levels after T4 withdrawal of 10 ng/mL or higher, or a level of 5 ng/mL or higher after rh TSH
stimulation or rising serum Tg levels in whom imaging has failed to reveal a potential tumor source. If the post
therapy scan is negative, no further RAIT therapy should be administered.
Physicians understood that empiric guidelines were imprecise and did not fully reflect the underlying anatomy,
physiology, and dosimetry. A method has been developed to calculate complication probability factors for non-
uniformly irradiated normal organs using dose volume histograms and complication probabilities for uniform
partial organ irradiation. The complication probability is then obtained from known complication probabilities for
uniform partial organ irradiation.
Purpose of the Study:
To understand the role of Dosimetry in the optimization of Radio Active Iodine Treatments (RAIT) in order to both
comply the 2 Gy red marrow (RM) absorbed dose constraint and kill lesions (absorbed dose threshold = 80 Gy).
To evaluate the impact of 131I high activity therapy treatments of metastatic differentiated thyroid cancer (MTDC)
in terms of feasibility, tolerance, efficacy, and the role that dosimetry can play.
However, careful hazard assessment is mandatory in order to establish the risk benefit ratio.
Methods:
17 patients underwent treatment with 131I in euthyroidism regimen after rhTSH stimulation. Activity ranged from
6.2 GBq to 24.1 GBq. 8 of them had multiple treatments, for a total of 27 treatments. Red marrow (RM), blood
(BL) and metastases peri-treatment dosimetry was performed according to the Italian multicentric protocol (daily
blood samples, whole body counting and planar static scintigram up to 96 h, with point source dead time correction
and triple energy window scatter correction). In 12 cases, prospective red marrow dosimetry was performed too,
under identical rhTSH stimulation conditions, with the purpose of evaluating the possibility of complying the 2 Gy
RM dose constraint. The dose to 45 lesions was evaluated. In 2 cases, lesion prospective dosimetry was performed
too. Post treatment seriated hemochrome assay allowed to evaluate the severity of myelotoxic effects.

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Results:
The treatments were generally well tolerated, also at the highest doses. Only transient toxicity was observed, with a
complete restoration within 3-6 months. Mean absorbed dose was 1.48 Gy for RM (range 0.36 - 6.67 Gy, 1.91 Gy
for BL (range 0.43 - 8.71 Gy), 153 Gy for metastases (range 1.1 - 778 Gy). In 20 cases on a total of 23 of repeated
treatments on the same metastases, a dose reduction per unit of administered activity was observed in the following
treatment. In 9 cases RM dose showed <50% discrepancies between prospective and peri-treatment dosimetry
evaluations (mean difference 37%, range -28% +284%).
In particular the following chart of Normal Tissue Complication Probability (NTCP) shows what the hazards based
on absorbed dose for PLT or WBC toxicity > G2.
The abscissa of each point is the median of the red marrow/blood absorbed dose in the dose bin considered, i.e. [0 -
1.5] Gy, [1.5 – 2.5] Gy, [2.5-5.0] Gy for red marrow, while [0 – 2.0] Gy, [2.0 -3.0] Gy, [3.0 – 6.0] Gy for blood

1
Normal Tissue Complication probability

0.8

0.6

0.4

0.2 Red marrow


Red Marrow
Blood
Blood
0

0 1 2 3 4 5 6 7 8 9
Absorbed dose [Gy]

Conclusions:
The results obtained confirm that high activity RAIT is well-tolerated, even at RM absorbed dose beyond the value
of 1.7 Gy (or 2.2 Gy BL absorbed dose) which we consider the limit for severe toxicity, without in patients treated,
persistent haematological side effects or worsening quality of life.
Since after the first treatment lesions become progressively less iodine-avid, our study suggests that a “first big
shoot” is desirable instead of lower activity repeated treatments.
The workload is high, especially for the medical physicist, when compared with no-dosimetry treatments, but
surely advisable to improve the value of the treatments.

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Bibliography
Lee JJ et al Ann Nucl Med 2008 22: 727-734
Individualized dosimetry of in the management of metastatic thyroid cancer.
C Chiesa, et all. - Q. J. Med Mol Imaging 2009 53: 546 - 561.
Revised American Thyroid Association Management Guidelines for Patients with Thyroid Nodules
and Differentiated Thyroid Cancer.
David S. Cooper, M.D.1 (Chair)* et all. THYROID Volume 19, Number 11, 2009
Use of normal Tissue Complication probability models in the clinic
L B. Marks et all. - Int. J. Radiation Oncology Biol. Phys., Vol. 76, No. 3, Supplement, pp. S10–S19, 2010

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Un rivelatore basato su un innovativo collimatore a fori paralleli per applicazioni in medicina nucleare.

A new detector based on a novel parallel hole collimator for nuclear medicine applications.
M. Longo1, M. N. Cinti2,3, S. Lo Meo4, N. Villani1, R. Pellegrini2,3, R. Pani2,3
(1) Post Graduate School of Medical Physics, Sapienza University of Rome, Rome Italy
(2) Dept. of Molecular Medicine, “Sapienza” University, Rome, Italy
(3) INFN, Section of Rome I, Rome Italy
(4) Enea, Bologne, Italy

Purpose: The main limitations of radioisotope molecular imaging are the ring geometry and the object-to-detector
distance, which impairs spatial resolution, efficiency and image quality. The best information in image detection
can be obtained by performing image acquisition through the use of small gamma cameras placed in close
proximity to the object. A new detector based on a novel parallel hole collimator with variable slanted angles is
proposed in the following.
Methods and materials: This device is based on a gamma camera with high spatial resolution, achieved with a
planar scintillation crystal of NaI:Tl, coupled with an array of position sensitive photomultipliers. The device is
able to acquire planar images by a static detector placed in close proximity to the object of interest. These images
are used to perform a 3D reconstruction of the entire object through the use of the Shift and Add (SAA) method. It
is a mathematical method to line up each image based on its shifting amount to generate reconstruction slices at
specified depths. The shift amount is calculated according to the geometric parameters of the acquisition. In order
to verify the effectiveness of the technique, Monte Carlo simulations are implemented. The simulated phantom is a
cylinder with a diameter of 7.5 cm and a height of 10 cm with two spheres, representing the hot spots, which have a
diameter of 5 mm and 10 mm respectively. The cylinder dimensions are compatible with a typical human breast.
Results: The results show that the technique works properly in terms of coronal and sagittal spatial resolution,
about 3-5 mm, allowing the identification of the depth to which lesions are placed inside the object. A sub-optimal
response in terms of spatial resolution in z, about 8-9 mm, could be solved by eliminating reconstruction
projections at small angles, even if this implies a reduction of contrast and signal to noise ratio (SNR).
Conclusion: The discussed device works in the proximity of the patient to detect objects placed at a distances
ranged from 0 to 8 cm, thus allowing planar resolutions 5 times higher than that obtainable with a traditional SPET.
Compared with the traditional tomographic reconstruction, the SAA produces comparable spatial resolutions, while
preserving the image counts for SNR calculation.
References:
[1] Y. Chen, J. Y Lo and J. T. Dobbins III., Two dimensional Shift-And-Add Algorithm for Digital Breast
Tomosynthesis Reconstruction, Med. Phys. (2006), 33 (6).

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Procedura per la validazione di una nuova matematica della posizione per gamma
camere a scintillazione con piccolo FoV.

Procedure to validate new position arithmetic for small-FoV scintillation gamma


cameras.
C. Marchioni1,2, M. Bettiol1,2, R. Pellegrini2,3, M.N. Cinti2,3, P. Bennati2,3, G. De Vincentis4, R.
Pani2,3
(1) Post Graduate School of Medical Physics, Sapienza University of Rome, Rome, Italy
(2) INFN, Section of Roma 1, Rome, Italy
(3) Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy
(4) Department of Radiological, Oncological and Pathological Sciences, Sapienza University
of Rome, Rome, Italy

Purpose: Position arithmetic based on centroid algorithm with fixed weights (Anger logic)
limits the potentiality of small FoV (less than 10 cm) high-resolution gamma cameras with
continuous crystals. Previously we proposed a new centroid algorithm based on floating
weights, correlated to the scintillation event position [1]. In this work we implemented a
numerical method with the aim to validate this algorithm.
Methods and materials: In the procedure, the model of interaction is simply statistical and it
keeps out energy transfer through matter: the numerical method simulates a charge
distribution, according to the Scrimger-Baker distribution [2], sampled by 8x8 anode matrix.
This simulation is iterated in order to reproduce an interaction of a photon beam in a
scintillation crystal. The position linearity (L) and intrinsic spatial resolution (iSR) responses
were evaluated, simulating a crystal surface scanning, as a function of crystal thick,
considering a 48x48 mm2 detector surface. We compared simulated results with experimental
ones coming from three scintillation gamma cameras, based on LaBr3:Ce(5%) continuous
crystal coupled to Hamamatsu H8500 MA-PMT. A 64 independent channels electronic
readout was utilized to read the 64 outputs coming from the 8x8 anodic plane of MA-PMT.
Results: The new algorithm reduces the light distribution spread, improving as a consequence
L and iSR. In the thinnest crystal (4 mm), iSR improvement is about 40% on the overall
crystal surface. In the thickest one (10 mm), iSR improvement relates only to the crystal
sides, without chancing iSR in the middle of FoV. The improvement in spatial linearity
produces a FOV enhancement of 40% and 50% for the thinnest and thickest crystal
respectively. The new position arithmetic works properly producing a strong image
performance improvement. Experimental data trend agrees with the simulated one.
Conclusion: The new algorithm allows of revisiting the use of small FoV planar camera,
making possible to achieve gamma cameras with small detection area and high imaging
performances. The numerical method is a fast predictive method to know image parameters of
planar gamma cameras.
References:
[1] R. Pani et al., New position arithmetic for scintillation camera based on floating weight
system, NSS MIC IEEE CR (2011) 3395-3398
[2] J. W. Scrimger et al., Investigation of Light Distribution from Scintillations in a Gamma
Camera Crystal, Phys. Med. Biol. (1967) 12,101-103

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Valutazione  di  una  mini  gamma  camera  per  ottimizzazione  dell’imaging  intraoperatorio  del  
linfonodo  sentinella  nel  melanoma  
 
Assessment  of  a  mini  gamma  camera  for  optimisation  of  melanoma  sentinel  node  
intraoperative  imaging    
 
L.  Riccardi1,  M.  Bignotto1,  R.  Sanco2,  R.  Zandonà1  and  M.  Paiusco1  
 
(1)  Medical  Physics  Department,  Veneto  Institute  of  Oncology  IOV-­‐IRCCS,  Padova,  Italy  
(2)  Radiotherapy  and  Nuclear  Medicine  Unit,  Veneto  Institute  of  Oncology,  IOV  IRCCS,  35128  Padua,  Italy    
 
Purpose:  as  general  recommendation  for  sentinel  node  (SN)  melanoma  biopsy,  a  minimum  administered  10  
MBq  activity  has  been  suggested1  at  the  time  of  surgery.  Since  the  uptake  of  radiotracer  by  SNs  can  be  less  
than  1%,  values  lower  than  100  kBq  are  expected.  Moreover,  a  widely  accepted  criterion  of  effectiveness  is  
to  remove  any  lymph  node  (LN)  more  radioactive  than  10%  of  the  hottest  SN.  Intraoperative  imaging  
detectors  thus  operate  in  a  field  of  low  activities,  typically  tens-­‐hundreds  of  kilobequerels.  The  aim  of  this  
work  is  to  experimentally  evaluate  a  mini  gamma  camera  (Sentinella  102,  Oncovision)  in  a  realistic  range  of  
activities  and  optimise  its  use  for  melanoma  SN  biopsies.  
 
Materials  and  methods:  a  8.0  mm  in  diameter  hollow  sphere  filled  with  known  activity  of  99mTc  was  used  to  
simulate  a  standard  SN.  The  efficiency  of  the  portable  gamma  camera  was  expressed  as  counts  per  minute  
(cpm)  per  unit  of  activity  (kBq).  The  counts  were  determined  from  a  circular  region  of  interest  (ROI).  This  
ROI-­‐referred  sensitivity  was  indicated  as  SROI.  For  various  collimator-­‐to-­‐surface  distances  (CSD),  
measurements  were  performed  with  the  radioactive  sphere  placed  at  different  depths  in  a  water  phantom.  
The  variation  of  SROI  within  the    field  of  view  (FOV)  was  also  evaluated.  The  ability  of  the  gamma  camera  to  
resolve  a  couple  of  sources  with  different  activities  and  distances    was  tested  with  a  specifically  designed  
solid  water  modular  phantom.  Finally,  the  effect  of  poor  counting  statistics  on  perception  of  observers  was  
investigated.  The  results  of  this  test  were  used  to  figure  out  a  threshold  of  detectability,  which  was  used  in  
combination  with  the  measured  SROI  values  to  identify  a  set  of  minimal  settings.    
 
Results:  the  efficiency  of  the  mini  gamma  camera  is  largely  dependent  on  geometrical  conditions.  In  dual  
source  imaging  two  LNs  are  efficiently  resolved,  but  the  weaker  one  is  undersized.  The  inter-­‐operators  
variability  can  be  relevant,  but  it  is  steadily  included  within  20%  when  ROI  counts  overcome  a  threshold  of  
about  50.  Based  both  on  this  threshold  and  measured  SROI  values,  the  recommended  10  MBq  value  results  
plenty  appropriate  for  imaging  SNs.  
 
Conclusions:   the   portable   gamma   camera   revealed   to   be   suitable   to   image   sources   in   a   range   of   low  
activities,  typically  tens-­‐hundreds  of  kilobequerels.    
 
[1]  H.  Chakera.  et  al.,  “EANM-­‐EORTC  general  recommendations  for  sentinel  node  diagnostics  in  melanoma,”  Eur.  J.  
Nucl.  Med.  Mol.  Imaging  (2009)  36,    1713-­‐1742    
 
 

ELENCO
 
TOPIC ESC
 
  MEDICINA LA FISICA MEDICA
RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
  RICERCA NUCLEARE
SANITARIE
 
Ottimizzazione dell’algoritmo di ricostruzione iterativo in un sistema ibrido SPECT/CT di ultima
generazione

Optimization of the iterative reconstruction algorithm in a last-generation SPECT/CT hybrid system


Alice Ferretti1, Lara Gallo1, Enrico Bolla1, Marcello Gava2, Elena Bellan2

(1) O. “San Giacomo Apostolo”, ULSS 8, Castelfranco Veneto (TV)


(2) O. “Maria della Misericordia”, ULSS 18, Rovigo

Purpose
To investigate the performances of the iterative reconstruction algorithm in a last-generation hybrid Single Photon
Emission Computed Tomography/Computed Tomography (SPECT/CT) system.

Methods and materials


The SPECT/CT system (GE Discovery NM/CT 670) was equipped with a two-head SPECT system and a 16-slices
CT scanner. Two cylindrical phantoms of similar sizes were used in the present study. The first one (internal
diameter 20.2 cm and height 20.0 cm) was equipped with 3 capillary tubes (internal diameter 1mm, activity 40
MBq 99mTc each), one central and two peripheral, at a distance of 7.5cm from the centre, along perpendicular
directions. Initially the phantom background was empty to evaluate the tomographic spatial resolution without
scattering, and then it was filled with water.
The second phantom (a Jaszczak type cylindrical phantom, internal diameter 21.6 cm and height 18.6 cm) was
equipped with 6 hollow spheres (internal diameters from 31.3 to 9.8 mm, concentration of 99mTc of 70.4 kBq/ml
each). The background was filled with a solution of water and 99mTc, with a radioactivity concentration of 8.8
kBq/ml, in order to produce an intrinsic contrast spheres-to-background of 8:1.
The acquisition protocol consisted of an initial low-dose CT scan, followed by a SPECT acquisition, including 120
views of 45 sec each, for a whole arc of 360° (180° each head).
The iterative OSEM algorithm used in reconstruction was evaluated testing different settings.
The tomographic spatial resolution (central and transverse), computed as the full-with at half-maximum (FWHM)
of the line sources, was evaluated changing the number of iterations and the post-reconstruction filter.
The CT-based attenuation correction (AC) and the scatter correction (SC) were evaluated in terms of axial flatness
and noise (coefficient of variation CV= σ/PVmean) of the images, in the uniform part of the Jaszczak phantom.
Moreover, the partial volume effect (PVE) was investigated calculating the recovery coefficients (RC) of the small
hot spheres as a function of the number of iterations and the post-reconstruction filter:
PVmean, sphere PV mean,bkg
RC 
C sphere Cbkg
where PVmean,sphere and PVmean,bkg are respectively the mean pixel-value in each sphere and in the
background, while Csphere and Cbkg are the real activity concentrations present in spheres and background.

Results
The tomographic spatial resolution acquired with and without scatter appeared equivalent, with the exception of the
transverse tangential one, which appeared reduced in the acquisition with scatter. The tomographic resolution
improved when the critical frequency of the filter increased, while it appeared unchanged when the number of
iterations was increased (figure 1).

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Figure 1 - Spatial resolution with scatter (phantom filled Figure 2 – Image noise as a function of the four different
with water). settings of the reconstruction algorithm.

Both uniformity and noise improved by decreasing the number of iterations and the critical frequency of the post-
reconstruction filter (figure 2). No-AC images underestimated the central counts of about 70% (vs. 2.1% in AC
images).
As shown in figure 3, the RC increased significantly with the diameter of the spheres (22% for the 9.8 mm sphere
vs. 100% for the 31.3 mm sphere), while slightly with the critical frequency (22.4% with f = 0.48 vs. 26.5% with f
= 0.80, for the smallest sphere) and with the number of iterations (22.4% with 2 iterations vs. 24.1% with 3
iterations, for the smallest sphere). Only the smallest sphere detectability appeared critical.

Figure 3 – PVE recovery coefficients as a function of the spheres internal diameters, for five different settings of the
reconstruction algorithm.

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Discussion

SPECT images are intrinsically affected by some inaccuracies: photon attenuation, photon scatter, limited spatial
resolution [1]. The use of iterative reconstruction algorithms, including CT-based attenuation correction, is now the
state-of-the-art and generally their use is recommended to have highly accurate SPECT studies [1-2].
We investigated the impact of the reconstruction process on the final image quality, in particular varying: a) the
whole number of iterations (product of iterations by subsets) used and b) the post-processing filter used to reduce
the noise. Decreasing the number of subsets and increasing the post-reconstruction filter, the noise variance
decreased, increasing the hot spheres detectability (figures 2-3). Conversely, they produced a worsening in spatial
resolution, causing broaden edges of the hot spheres (figure 1). The CT-based AC and the SC are essential for
quantification in SPECT (i.e. for radiometabolic therapies) [2]. In the present study they appeared efficient,
improving the spatial resolution with scatter (figure 2b), the noise (figure 3) and reducing the PVE (figure 3).

Conclusion

The SPECT/CT reconstruction settings appeared decisive to obtain accurate emissive images. In particular the best
compromise between spatial resolution and image noise should be investigated, as the reconstruction parameters
affected inversely these two characteristics.

References:

[1] Ritt P, Vija H, Hornegger J, Kuwert T. Absolute quantification in SPECT. Eur J Nucl Med Mol Imaging. 2011;
38 (Suppl.1): S69–S77

[2] Zeintl J, Vija AH, Yahil A, Hornegger J, Kuwert T. Quantitative Accuracy of Clinical 99mTc SPECT/CT
Using Ordered-Subset Expectation Maximization with 3-Dimensional Resolution Recovery, Attenuation, and
Scatter Correction. J Nucl Med. 2010; 51: 921–928

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Influenza del numero di iterazioni e della frequenza di taglio del filtro nella valutazione dei parametri di
funzionalità miocardica per un algoritmo di ricostruzione iterativa con recupero della risoluzione spaziale.

Influence of iterations and filter cut-off frequency in evaluating MPI functional parameters for an iterative
reconstruction algorithm with resolution recovery.
M. Lecchi(1), I. Martinelli (1), C. Scabbio(1), L. Tagliabue(1), A. Strinchini(1), G. Lucignani(1)
(1)Department of Health Sciences, University of Milan and Nuclear Medicine Unit, San Paolo Hospital, Milan,
Italy

Purpose: In recent myocardial perfusion imaging (MPI) studies, iterative reconstruction algorithms with resolution
recovery (IR-RR) have shown better performance in term of image quality and patient dose than the standard filter
back projection (FBP). The study purpose was to analyze, in patients undergoing gated MPI, the influence of IR-
RR reconstruction parameters (number of iterations and filter cut-off frequency) in evaluating ejection fraction
(EF), end-systolic volume (ESV) and end-diastolic volume (EDV).
Methods and materials: A group of 30 consecutive patients with reversible perfusion defects undergoing
rest/stress 99mTc-tetrofosmin gated SPECT was retrospectively studied. Non-gated projections were reconstructed
using Astonish (Philips) algorithm with 4 iterations, 8 subset and a cut-off frequency of 1.0. For gated projections,
five sets of SPECT images were reconstructed with: 1) FBP (0.45 c.f., order 5); 2) IR-RR, 4it. 8sub. 0.8c.f. (setting
present in literature); 3) IR-RR, 3it. 8sub. 2c.f. (default setting); 4) IR-RR, 3it. 8sub. 1c.f.; 5) IR-RR, 4it. 8sub. 2c.f.
Using Autoquant software (ver. 7.0) EF, ESV and EDV were estimated for each image set, rest and stress scans
independently considered. IR-RR results respect to FBP ones were analyzed according to the method of Bland and
Altman (mean diff [+1.96sd, -1.96sd]). The hypothesis of zero bias was examined by a paired t-test. A p-value <
0.01 was considered significant.
Results: For IR-RR, the EDV and ESV values rose by increasing iteration number and/or cut-off frequency, while
FE ones decreased, for both rest and stress scans. EDV values were significant different from FBP ones for all sets
of IR-RR reconstructions: for the default setting, bias = -2.8[2.6; -8.2] and -3,5[3.4; -10.4] for rest and stress scans,
respectively. For ESV and FE, the hypothesis of zero bias were not rejected only for the default IR-RR setting,
while for the other image sets the differences resulted significant: biasmax (ESV)= -7.1[-0.6; -13.7] and biasmax
(EF)= +3.2[8.8; -2.4] for IR-RR setting present in literature.
Conclusion: MPI functional parameters strongly depended on IR-RR iteration number and filter cut-off frequency
chosen. It is important to verify and standardize the IR-RR reconstruction parameters for the clinical protocol used
and for each new protocol implemented for reducing patient dose. A revision of normal limits of MPI functional
parameters could be also required.

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Un modello generale per la dosimetria interna in volumi ellissoidali per emettitori alfa, beta e gamma.

A general model for internal dosimetry in ellipsoidal volumes for alpha, beta and gamma emitters.
D. Lizio1, E. Amato2, A. Italiano3, S. Baldari2.
(1) Medical Physics Department, University Hospital “Maggiore della Carità”, Novara, Italy.
(2) Section of Radiological Sciences, Department of Biomedical Sciences and of Morphologic and
Functional Imaging, University of Messina, Italy.
(3) Gruppo Collegato di Messina, Istituto Nazionale di Fisica Nucleare, Italy.

Introduction:
Metabolic radiotherapy is a widely used technique for the treatment of many diseases. It exploits the
correlations between the metabolic properties of the organ or tissue to be treated and a particular
radionuclide. Exploiting the tropism of the radionuclide considered, it is possible to accumulate a radioactive
source in the organ under examination.
The estimate of the dose is essential in assessing the risk / benefit in the applications of radiation in medicine
and may become a sufficient condition for the non-utilization of the therapy in question.
The traditional procedure for the evaluation of the dose absorbed after administration of a
radiopharmaceutical is described by the formalism MIRD (Medical Internal Radiation Dose Commitee). The
method consists in evaluating the dose to a target organ by two components: the sources embedded in the
target tissue and those in the adjacent tissues. The dose absorbed by a target k, Dk, in the presence of a single
source h, is expressed as follows:
D (rk ← rh ) = Ah S (rk ← rh )
~
(1)
where rk is the region where the target organ, rh indicate the region (point, line, area or volume) of the body
~
source, Ah is the activity accumulated in the source organ and S is the average dose absorbed by the target
per unit cumulated activity in the source. The definition of S is as follows:
∑ ∆ φ (ri i k ← rh )
S (rk ← rh ) = i
(2)
mk
with Σi ∆i = Σi ni Ei: energy emitted per transition; φ i: fraction of energy absorbed by the target of type i (rk)
emitted by the body source (rh) and mk is the mass of the target organ.
When the target dimensions are much greater than the range of the electron emitted by the source, supposed
uniformly distributed within the target volume, the absorbed fraction tends to unity. When, instead, this
condition is not fulfilled, as in small target volumes such as in ovarian carcinoma or multiple autonomous
thyroid nodules (ATN), the absorbed fraction lowers significantly and its dependence on target dimension
and α orβ − energy can not be neglected. A similar discourse we can take with regard to the absorbed fraction
of gamma rays by searching for a dependency with the size of the volumes considered.

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
We developed and analytical model to calculate radiation absorbed doses in ellipsoidal volumes uniformly
uptaking a generic alpha, beta, and/or gamma emitting radionuclide. Our model is based on simulative data
obtained through Monte Carlo simulations in GEANT4 of monoenergetic and uniform distributions of
emissions of each radiation type.
Methods and Materials:
Validation:
in order to validate GEANT4 for medical physics applications, different simulations were conducted. Geant4
implements different physics models for electron interaction, based either on theories, or on experimental
data and parametrisations [1] [2]. In order to validate our code we carried out two different simulations: 1) a
collimated beam of monoenergetic electrons (E = 0.3-1 MeV) on semi-infinite aluminium and water targets;
2) uniformly distributed sources of monoenergetic electrons and sources of 90Y and 131I radionuclides in
water spheres. The aim of the first simulation was to determine the energy deposition and particle ranges as a
function of cuts in range [1] and multiple scattering step limitation [3]. The aim of the second simulation was
to compare the absorbed fractions for electrons in water spheres obtained by our Monte Carlo with the
reference data[4].
Concerning photons, a complete discussion about the validation of Geant4 at the energies relevant for our
study, also for medical applications, can be found in the works by Amako et al [5] and Carrier et al [9].
In order to directly check the validity of our evaluations for absorbed fractions, we compared the absorbed
fractions for gamma emitters characterized by four energies (80, 140, 364 and 662 keV) homogeneously
distributed in unit-density tissue with the results presented by Stabin [8]. In order to improve the
comparison accuracy, the same tissue composition used in the cited work was adopted [10].
The absorbed fractions for alpha particles in spheres have been reported by Bardies and Myers(1990)[11] for
spheres labelled on the surface and by the MIRD Committee (Goddu et al 1997)[12] for spherical cellular
models, for a variety of cell dimensions and electron and alpha-particle energies and radionuclide emission
spectra. In order to benchmark our methods, monoenergetic alphas were distributed on the spherical surfaces
for direct comparison with Bardies and Myers (1990), while a benchmark for uniform volume distributions
has been obtained taking as a reference the cellular S values S(C←C) from Goddu et al (1997), i.e. the S
value calculated when considering the whole cell C as source and target.
Simulation:
we developed a Monte Carlo simulation in Geant4 to calculate the absorbed fractions for electrons
emitted by 199Au, 177Lu, 131I, 153Sm, 186Re and 90Y, characterized by average energies ranging from 86 keV
and 949 keV.
We studied the absorbed fractions for photons, characterized by energies ranging from 10 keV to 1000
keV, which can be emitted by gamma radionuclides uniformly distributed in ellipsoidal volumes of
various ellipticity of soft tissue.
Moreover we calculated the absorbed fractions of monoenergetic alpha particles of seven energies: 0.1,
0.2, 0.5, 1, 2, 5 and 10 MeV.
Eight different geometries were simulated for each volume: the sphere, three oblate and prolate
ellipsoidal, and one scalene ellipsoidal shape.
In the most general case, for alpha, beta and gamma emitting radionuclide the average dose to the
target volume is given by:

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
~
A
D = Dα + Dβ + Dγ = Edep ,
m
dm(E)
Edep = ∑ nα , i Eα ,iφα , i +∫ Eφ (E)dE + ∑ ne,i Ee,iφe,i + ∑ nγ ,i Eγ ,iφγ ,i (3)
i dE i i
Where Edep is the average energy deposition per disintegration, while nα, ne, and nγ are the monoenergetic
alpha, electron (Auger conversion) and photon (X or γ) emission probabilities, respectively, of energies Eα,
Ee and Eγ.
φα, φε and φγ are the alpha, electron and photon absorbed fractions, obtained from equation 4:
−1
 ρ 
φ ( ρ ) = 1 + 0s  (4)
 ρ 
and from our previous model [13-15], where ρ0 and s are two parameters. In equation 4 the “generalized
radius” is defined as:
V
ρ =3 ,
S
where V is the target volume and S its surface. For ellipsoidal shapes they can be calculated from:
 (ab )d + (bc )d + (ac )d
1/ d
4 
V = πabc and S ≅ 4 

3  3 
where d = ln3/ln2 ≈ 8/5. The approximated formula for S gives a relative error below 1.2% [3]. For a
spherical volume, ρ coincides whit the radius.
In equation (3) the integral represents the contribution due to the continuous beta spectrum. This generalized
model accounts for all the possible decay modes of the radionuclide considered.

Results:
Validation:
Concerning the first set of simulations for electrons, the results show that the percent differences are below
3%, as reported by data refences. Moreover we compared the range in continuous slowing-down
approximation (CSDA) calculated in our simulation with the data from NIST for aluminium and water
revealing a full match.
For photons, the comparison between the absorbed fractions evaluated by means of our code and the data
presented in Stabin and Konijnenberg [4] reveals a full agreement between the data.
The comparison between the alpha absorbed fractions evaluated whit our code and the values presented in
Bardies and Myers(1990) and Goddu et al (1997) reveals an agreement between the two data sets within an
deviation = ± 16% for surface distributions and within -1/+12% for volume distributions. These
discrepancies can be explained taking into account the fact that both reference data [11-12] were calculated
by means of deterministic approaches, while the present work reports the results of a Monte Carlo-based
calculation method.

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Simulation:
we found that the absorbed fraction for all radiations is a function of the “generalized radius” introduced, and
such dependence can be analytically described by radiation-specific parametric functions.
These functions, introduced in an electronic spreadsheet, allow to calculate the dose to a generic ellipsoidal
volume, from any radiation emission spectrum, that can contain multiple alpha emissions, or electrons
(monoenergetic or continuous beta spectra) and X-ray or gamma photons.
Discussion and Conclusion:The agreement between our data and the references can be regarded as a further
validation of our method. These results allow us to calculate the dose in ellipsoids from alpha emitters and
allows, together with the previous works dealing with photons and electrons, a comprehensive treatment of
absorbed fractions from alpha-emitting radionuclides and their daughters uniformly distributed in ellipsoidal
volumes of any ellipticity and volume, in the whole range of practical interest for internal dosimetry in
nuclear medicine therapeutic applications, as well as in radiological protection estimations of doses from an
internal contamination.
References:
[1] Agostinelli S et al 2003 GEANT4 – a simulation toolkit Nucl. Instr. Meth. A 506 250.
[2] Allison J et al 2006 Geant4 developments and applications IEEE Trans. Nucl. Sci. 53 270-8.
[3] Urban L 2006 A model for multiple scattering in Geant4 CERN-OPEN-2006–077.
[4] Siegel J A and Stabin M G 1994 Absorbed fractions for electrons and beta particles in spheres of various
sizes J Nucl Med 35 152-6. [8] Stabin M G and Konijnenberg M W 2000 Re-evaluation of absorbed fractions
for photons and electrons in spheres of various sizes J. Nucl. Med. 41 149-160.
[5] Amako K et al 2006 Geant4 and its validation Nucl. Phys. B - Proc. Suppl. 150 44-9.
[6] Carrier J F et al 2004 Validation of Geant4, an object-oriented Monte Carlo toolkit, for simulations in
medical physics Med. Phys. 31 484-92.
[7] Ellett W H and Humes R M 1971 Aborbed fractions for small volumes containing photon-emitting
radioactivity – MIRD Pamphlet no. 8 J. Nucl. Med. S 5 25-32.
[8] Bardies M and Myers M J 1990 A simplified approach to alpha dosimetry for small spheres labelled on
the surface Phys. Med. Biol. 35 1551–61
[9] Goddu S M et al 1997 MIRD Cellular S Values: Self-Absorbed Dose Per Unit Cumulated Activity for
Selected Radionuclides and Monoenergetic Electrons and Alpha Particles Emitters Incorporated Into
Different Cell Compartments (Reston, VA: Society of Nuclear Medicine)
[10]E. Amato, D. Lizio, and S. Baldari (2011). Absorbed fractions for electrons in ellipsoidal
volumes. Physics in Medicine and Biology, 357-365, 56;
[11]E. Amato, D. Lizio, S. Baldari (2009). Absorbed fractions for photons in ellipsoidal volumes.
Physics in Medicine and Biology, N479- N487, 54;
[12]E. Amato, D. Lizio, S. Baldari (2009). Absorbed fractions in ellipsoidal volumes for -
radionuclides employed in internal radiotherapy. Physics in Medicine and Biology, 4171- 4180, 54.

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Red Marrow, Lesion Dosimetry and Dose-Toxicity correlation during maximized 131I Activity Therapy of
Metastatic Differentiated Thyroid Cancer. Marked reduction of lesion absorbed dose after repeated
radioiodine treatments
L.Bianchi 1, A.Baroli1, G.Lomuscio1, L.Pedrazzini1, A.Pepe1, L.Pozzi2, C.Chiesa3

(1) A.O. Ospedale di Circolo di Busto Arsizio , Busto Arsizio (VA)


(2) A.O. Ospedale di Circolo di Varese , Varese (VA)
(3) Fondazione IRCCS Istituto Nazionale Tumori Milano (MI)

Purpose: the purpose of the present study was to evaluate red marrow, lesion dosimetry and clinical outcome in
131
I high activity therapy treatments of metastatic differentiated thyroid cancer (MTDC). Many aspects of the
activity were evaluated, such as feasibility, tolerance and efficacy.

Methods
17 MDTC patients underwent 27 treatments with 131I, with activity ranging from 6.2 GBq to 24.1 GBq (Mean
Activity 12.9 GBq). 8 of them had multiple treatments. 16 treatments were performed following thyroid hormone
withdrawal (hypothyroidism regimen); the assumption of levothyroxine was suspended at least 4 weeks before
treatment, and a diet low in iodine was followed at least for 3 weeks before treatment. 11 treatments were
conducted after stimulation with recombinant human TSH (rh-TSH) (euthyroidism regimen); 0.9 mg of Thyrogen
were administered 48 and 24 h before administering 131I therapeutic activity.
In order to perform red marrow and blood peri-therapy dosimetry, daily blood samples and total body counts
beyond 96 hours with external probe were collected according to the Standard Operating Procedures of the
European Association of Nuclear Medicine. Lesion dosimetry was based on 4 daily planar scintigrams, the first one
at 24 after administration and the last one beyond 96 h. Dead time, scatter and attenuation correction, and
instrumentation calibration were performed according to the guidelines of Italian Association of Physicists in
Medicine (AIFM) and Italian Association of Nuclear Medicine (AIMN).
In 12 cases prospective dosimetry was performed too, with the purpose of evaluating the possibility of both
maximizing the therapeutic activity and complying the 2 Gy red marrow dose constraint. In the other 15 treatments
the activity to be administered was determined following the traditional empiric method, based on clinical
considerations performed by the physician.
45 lesions were dosimetrically evaluated, and in 2 cases prospective dosimetry was performed too.
The severity of myelotoxic effects was monitored during the follow up, basing on blood withdrawals at 15 days, 1
month, 3 months, 6 months and then every 6 months.

Results
Treatments were generally well tolerated, also at the highest red marrow absorbed doses. Only transient
haematological toxicity was observed in 9 treatments, with a complete spontaneous restoration within 3 months,
even after red marrow absorbed dose larger than 2 Gy and repeated administrations. Red marrow absorbed doses
ranged from 0.49 to 6.67 Gy (mean 1.44 Gy), blood absorbed dose from 0.63 to 8.71 Gy (mean 1.89 Gy), lesions
absorbed doses from 1.1 Gy to 778 Gy.

Dose-activity correlation: the unexpected result is a good blood or red marrow dose-activity correlation only for the
hormone withdrawal regimen. The best correlation is in the case of blood absorbed dose

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
rhTSH vs hypothyroidism: medians of the distributions of absorbed dose per unit activity obtained with peri-
treatment dosimetry are not statistically different for the two regimen considered, but the dispersion of values is
more remarkable after rh-TSH stimulation

Red Marrow absorbed dose per unit activity Blood absorbed dose per unit activity
0.5 0.5

0.4 0.4
Gy/GBq

Gy/GBq

0.3 0.3

0.2 0.2

0.1 0.1

0.0 0.0
al

al
n

n
io

io
aw

aw
at

at
dr

dr
ul

ul
ith

ith
im

im
w

w
st

st
on

on
SH

SH
m

m
-T

-T
or

or
rh

rh
H

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Toxicity: Mann-Whitney test between patients with and without hematological toxicity. The differences of
median of RM or BL absorbed doses are highly significant

10 10
RM absorbed dose (Gy)

BL absorbed dose (Gy)


p = 0.0007 p = 0.0005
8 8

6 6

4 4

2 2

0 0
4

4
3

3
G

G
G

G
<

or

<

or
ty

ty
3

3
ci

ci
G

G
xi

xi
C

C
to

to
B

B
W

W
C

C
B

B
or

or
W

W
T

T
or

or
PL

PL
T

T
PL

PL

ROC analysis in terms of red marrow and blood absorbed doses determined peri-therapeutically as markers for
toxicity. The group of patients with marked toxicity (PLT or WBC, G3 or G4) was considered as true positive. The
extremely high value of AUC means that the absorbed dose is an excellent marker to predict hematological toxicity

Hematological toxicity vs RM absorbed dose

Area under ROC curve 0,98


Std. Error 0,02
95% confidence interval 0,93 to 1,02

Hematological toxicity vs BL absorbed dose

Area under ROC curve 0,99


Std. Error 0,02
95% confidence interval 0,96 to 1,02

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
The Lyman Normal Tissue Complication Probability (NTCP) curve was calculated for PLT or WBC toxicity > G2.
The abscissa of each point is the median of the red marrow/blood absorbed dose in the dose bin considered, i.e. [0 -
1.5] Gy, [1.5 2.5] Gy, [2.5-5.0] Gy for red marrow, while [0 2.0] Gy, [2.0 -3.0] Gy, [3.0 6.0] Gy for blood
NTCP curve, applied for the first time for radioiodine therapy, fully confirm the Benua s criterion.

1
Normal Tissue Complication probability

0.8

0.6

0.4

0.2 Red marrow


Red Marrow
Blood
Blood
0

0 1 2 3 4 5 6 7 8 9
Absorbed dose [Gy]

Previsional dosimetry: mismatch between red marrow prospective ad peritherapeutic dosimetry ranged from -28%
to + 40%, in agreement with other published data, with a single outlier (+254%).

Treatment ID Therapeutic Previsional Therapy Previsional Difference


Activity activity RM RM therapy vs
(GBq) (MBq) Gy/GBq Gy/GBq previsional (%)

Patients treated under hypothyroidism regimen

4_1 17,0 110 0,082 0,059 40


7 10,0 30 0,065 0,090 -28
8_1 13,3 110 0,055 0,049 11
8_2 14,4 110 0,055 0,048 16
9 14,8 93 0,066 0,066 1

Patients treated under euthyroidism regimen (rh-TSH stimulation)

3_1 20,5 30 0,084 0,092 -9


3_2 22,1 120 0,082 0,092 -10
6_1 10,9 60 0,313 0,081 284
6_3 11,2 70 0,181 0,089 105
10_1 14,9 110 0,215 0,154 39
11_1 15,1 30 0,062 0,067 -7
15 10,0 100 0,051 0,051 1

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Lesion dosimetry: in 18 lesions on a total of 20 studied during repeated treatments on two patients, an absorbed
dose reduction of 83% (median) was observed, while two lesions in the first patient had a median increase of
585%.
Treat RM M1 M2 M3 M4 M5 M6 M7 M8 M9
ID A (MBq) (Gy) (Gy) (Gy) (Gy) (Gy) (Gy) (Gy) (Gy) (Gy) (Gy)
1_1 9,62 1,19 331 - - - - - - - -
1_2 12,05 0,7 10 - - - - - - - -
3_1 20,5 1,72 69 20 - - - - - - -
8_1 13,32 0,73 48 - - - - - - - -
14 6,22 0,28 59 - - - - - - - -
9 14,8 0,98 16 - - - - - - - -
4_2 12,95 0,49 1 - - - - - - - -
16 9,25 0,6 12 - - - - - - - -
12 24,05 3,19 49 - - - - - - - -
6_1 10,92 3,42 127 477 82 415 127 247 778 152 316
6_2 17,76 6,67 49 161 624 239 774 168 125 - 169
6_3 11,2 2,03 4,1 19,9 - - 4,3 - 4 78,3 11
10_1 14,9 0,8 224 265 40 26 403 12 - - -
10_2 12,21 2,92 21 2 35 7 73 1 - - -

Conclusions
Pery-therapy blood or red marrow dosimetry demonstrated a realiable predictive power of possible undesirable
myelodepresion after one month. Prospective blood or red marrow dosimetry has the potential being a similarly
powerful predictive tool, but further investigation of the pre- peri-therapy mismatch are advisable.
Despite this possible mismatch, in our experience high activity treatments were well-tolerated, also when red
marrow and blood absorbed dose were much higher than2 Gy. No medical action was required for haematological
recovery. Contrarily to the case of remnant ablation, blood or red marrow absorbe dose per unit activity do not
show a systematic reduction in the euthyroidism subgroup. This is a consequence of presence of extended
metastatic involvement.
Since lesions became progressively less iodine-avid in case of repeated treatments, the "first big-shot" strategy
with the highest safe activity seems to be advisable to fully exploit the potential of radioiodine therapy of
metastatic differentiated thyroid cancer.

References:
1) Lassmann M, Hänscheid H, Chiesa C, Hindorf C, Flux G, Luster M EANM Dosimetry Committee series on
standard operational procedures for pre-therapeutic dosimetry - I. blood and bone marrow dosimetry in
differentiated thyroid cancer therapy. Eur J Nucl Med Mol Imaging. 2008;35:1402-1412
2) Lassman M, Chiesa C, Flux G, Bardies M EANM Dosimetry Committee guidance document: good practice of
clinical dosimetry reporting. Eur J Nucl Med Mol Imaging. 2011;38:192-200.

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
3) Chiesa C, Indovina L, Traino C et al. DOSIMETRIA DURANTE TERAPIA DI CARCINOMA
DIFFERENZIATO DELLA TIROIDE METASTATICO - PROTOCOLLO DOSIMETRICO
www.fisicamedica.it/aifm/periodico/2006/2006_4_Fisica_in_Medicina.pdf
4) Benua RS, Cicale NR, Sonenberg M, Rawson RW The relation of radioiodine dosimetry to results and
complications in the treatment of metastatic thyroid cancer. Am J Roentgenol.1962;87: 171-182
5) Maxon HR, Thomas SR, Hertzberg VS, Kereiakes JG, Chen IW, Sperling MI, Saenger EL Relation between
effective radiation dose and outcome of radioiodine therapy for thyroid cancer. N Engl J Med. 1983; 309:937-941.
6) Leeper RD The effect of 131I therapy on survival of patients with metastatic papillary or folliculary thyroid
carcinoma. J Clin Endocrinol Metab. 1973; 36: 1143-1152

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Dosimetric comparison and follow-up analysis for clinical evaluation in hyperthyroidism customized
treatment
M. Cacciatori1, R. Posterli2, P. Urso1, G. Frigerio1, V. Conti1, A. Corso2, A. Ostinelli1
(1) Department of Medical Physics, Sant’Anna Hospital, Como, Italy
(2) Department of Nuclear Medicine, Sant’Anna Hospital, Como, Italy
Aim: The treatment of choice in most of hyperthyroidism cases is actually the radioiodine therapy. The critical
issue is the administered activity, that on one hand should be adequate to pathology remission and on the other as
low as possible for radioprotection reasons. Personalized radioiodine treatment in hyperthyroidism aims to restore
euthyroidism or to achieve ipothyroidism, focusing on the dose optimization. An accurate assessment of the
pathological volume and a dosimetry procedure implementation prior to therapy is binding by European and
national directives. The correct dose identification, however requires the accurate determination of some critical
parameters, as the thyroid mass, the maximum radioiodine uptake (Umax) and the radio-tracer effective half-life
(T1/2eff).
This work presents a comparison between two different approaches in the activity evaluation: the most accurate
one employs Umax and T1/2eff calculated using pre-treatment measures, while the other considers Umax as the 24-
hours uptake (U24)and the T1/2eff the standard fixed value of 5.5 days. The effectiveness of the most accurate and
personalized therapeutic approach was studied by analyzing the clinical response in patients treated at Sant'Anna
Hospital in Como.
Methods and materials: This study involves a total of 155 patients, affected by Graves’ diseases (43.9%) and
toxic nodular goitre (56.1%). The investigated sample was constituted by 79.4% females and 20.6% males, with an
average age of 59.8 years. The AIMN (Associazione Italiana di Medicina Nuclere e Imaging Molecolare) and
AIFM (Associazione Italiana in Fisica Medica) protocol was applied for extensive routine thyroid activity
evaluation to deliver the prescribed dose to the target. This protocol take into account the gland size and its
reduction during treatment, the iodine uptake, and the iodine turnover.
In the pre-treatment phase, a 131I sodium-iodide track activity (about 0.2 MBq) was administered, in order to
identify Umax and T1/2eff by uptake data fitting through a bi-exponential curve. Activity measurement were
performed at 2, 24, 96 hours from the administration points, with an additional point at 6 hours for Graves' disease.
The functional thyroid mass was evaluated by processing tomographic 99mTc-pertecnetate SPECT or SPECT/CT
images through a specific 3–D reconstruction software developed in MatLab 7.1. The used semi-automatic SPECT
segmentation procedure employs threshold values depending on object size and image contrast.
The treatment procedure was based on the intravenous administration of a single amount of 131I, its quick
absorption into the bloodstream and its gradual uptake by the thyroid gland.
The post-treatment follow-up was carried out by periodical hormones checks. The statistical analysis pertained to
the healing dependence on thyroid masses, administered activities, doses, Umax and T1/2eff and the kind of pathology,
also considering age and gender of patients.
Results: The standard activity resulted to be significantly different from the personalized one (∆A%mean=
22.3±31.2 %, p<0.001), with high variability among patients (-58.3÷110.7 %). The average value of the radioiodine
effective half-life is equal to 140.4 h (5.8 days) (∆T1/2eff%mean = 0.1±29.1%, range = -31.0÷172.2 h) and the
average difference between the calculated Umax value and the U24 was 6.9±5.6% (range =-26.5÷4.3%).
The analysis also highlights the large inter-subjects variability, since underlined by the ranges of personalized
radioiodine kinetic parameters and functional thyroid volume, as T1/2eff varies between 49 and 191 h, Umax between
9 and 82 % and thyroid masses between 5 and 108 g.
The success of the customized approach, evaluated by the study of the individual clinical outcomes, was tested by
the frequency of treatment success at the end of a follow-up period of at least 8 months. Data showed all uninodular
and multinodular toxic goitres cleared up in a single treatment, that was also sufficient for Graves’ disease for

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
94.2% of patients, evolving in hypothyroidism (72.1%) or in stable euthyroidism (27.9%). Not remitted patients,
characterized by higher pathological mass, cleared up with a second treatment.

Conclusions: The study shows that accuracy in activity customization provided an effective tool for
hyperthyroidism treatment, as suggested by the follow-up on treated patients, reporting low frequencies of Graves'
disease re-treatments and the total remission of nodular goitre. However, administered activities, not exceeding the
600 MBq limit imposed by Italian legislation for outpatient treatments, often entailed insufficient doses for larger
thyroid masses in Graves’ disease patients, determining the necessity of a second treatment.
Moreover, activities calculated by the personalized approach largely differ from the ones achieved by less rigorous
one, obtaining a more effective dose optimization, that is a critical aspect if considering the large inter-subjects
variability. It is reasonable to affirm that the less accurate technique fails to take into account the individual patient
characteristics, such as uptake, retention, whole body clearance and radiation dose reminder of the body.
The measurement of radioiodine uptake before radioiodine therapy is therefore recommended to prevent
inappropriate administration to a patient.
The significant differences among patients radioiodine turnover and thyroid masses seem to emphasize the
importance that the personalized patient dosimetry plays in contemporary nuclear medicine therapy.

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Risultati   clinici   a   lungo   termine   della   terapia   con   radioiodio   basata   sulla   dose   assorbita   e   su   uno  
studio  dosimetrico  pretrattamento  personalizzato  nelle  autonomie  tiroidee  
 
Long  term  clinical  outcome  of  radioiodine  therapy  based  on  tissue  absorbed  dose  and  pretreatment  
individualized  dosimetric  study  in  thyroid  autonomy  
C.Canzi,  M.Castellani,  V.Longari,  F.Zito,  F.Voltini,  R.Benti  
Fondazione  IRCCS  Ca’  Granda  –  Ospedale  Maggiore  Policlinico,  Milano  
 

After  a  long  lasting  debate  about  the  therapy  goal  in  functional  autonomies,  nowadays  many  authors  agree  
about   the   opportunity   to   point   to   a   stable   euthyroid   status   after,   possibly,   a   single   radioiodine  
administration.   Clinical   outcome   of   radioiodine   treatment   of   hyperthyroidism   was   often   related   to   the  
therapeutic   131I   activity   administered   to   the   patient   rather   than   to   the   dose   released   to   the   therapy   target  
and  only  recently  the  concept  of  dose-­‐effect  correlation  has  been  considered.    
Purpose   of   this   work   was   to   verify   if   an   approach   based   on   a   pretreatment   dosimetric   study   allows   to  
release  a  dose  (Gy)  effective  to  obtain  a  stable  euthyroid  status  avoiding  both  hyperthyroidism  persistence  
and  onset  of  hypothyroidism.      
Materials   and   methods:   261   hyperthyroid   patients   (91   and   170   with   uni   and   multi   focal   autonomies    
respectively)  underwent  a  pretreament  dosimetric  study  based  on  the  administration  of    111  MBq  of  123I,  on  
multiple  uptake  measurements  with  a  gammacamera  and  on  the  MIRD  formula  to  determine  the  therapeutic  
131I  activity  to  release  a  dose  of  about  200  Gy  to  the  therapy  target.  The  same  study  was  repeated  after  the  

administration   of   calculated   131I   therapeutic   activity   to   evaluate   the   really   released   dose.   None   of   the  
patients  had  previous  radiometabolic  treatment.  Antithyroid  drugs,  if  administered,  were  withdrawn  at  least  
20  days  before  both  dosimetry  and  therapy.  Each  patient  clinical  outcome  was  monitored  with  biochemical  
analysis   (TSH,   FT3   and   FT4)   1,   3,   6   and   12   months   after   therapy   and   then   once   a   year.   Median   follow   up   was  
48  months  (range  1-­‐120  months).    
Results:   Mean   therapeutic   131I   administered   activity   was   394±195   MBq   (range   66-­‐600   MBq).   The   dose  
really   released   was   160±64   Gy   to   the   therapy   target   and   111±76   Gy   to   secondary   nodules   in   multifocal  
autonomies.  Clinical  outcomes  at  follow-­‐up  times  are  here  reported:  
 
Follow-­‐up  times  (months)  
1   3   6   12   24   36   48   60   72  
84   96   108   120    
Eu   30%   70%   81%   86%   87%   89%   85%   84%   78%   81%   81%   77%          77%  
Hypo   0%   2%   2%   5%   6%   8%   10%   11%   17%   17%   19%   23%      23%  
Hyper  70%   28%   17%   9%   6%   3%   5%   5%   5%   2%   0%   0%   0%  
 
Conclusions:   The   therapeutic   approach   based   on   a   pretreatment   dosimetric   study   allowed   to  
obtain   very   good   and   stable   clinical   results.   The   released   doses   resulted   lower   than   the   values  
suggested   by   Italian   guidelines.   The   range   of   administered   131I   activity   was   quite   wide   due   to  
patient  specific  tailoring  of  the  treatment.    
 
 

ELENCO
 
TOPIC ESC
 
  MEDICINA LA FISICA MEDICA
RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
  RICERCA NUCLEARE
SANITARIE
 
Radioimmunotherapy with human antibody: 124I provisional and 131I effective dosimetry
C. Bianchi1, G.L. Poli2, G. Virotta2, R. Moretti2.
(1) Scuola di Specializzazione in Fisica Medica, Milano (2) A.O. Papa Giovanni XXIII, Bergamo

Purpose: The A.O. Papa Giovanni XXIII enrolled 6 patients in the clinical trial EudraCT no 2009-013002-13,
which investigated the radioimmunotherapy (RIT) with 131I-labeled L19SIP (Small Immuno Protein format
antibody) in addition to whole brain radiotherapy in patients with multiple brain metastases from solid cancer. The
RIT was preceded by a diagnostic phase with administration of about 185MBq 124I-L19SIP. Patients exhibiting
favourable tumor-targeting (brain lesion/normal brain activity concentration ratio > 4 at 24 hours post injection)
and with a provisional dose to the bone red marrow less than 2 Gy, were then treated with 4107 MBq/m2 of 131I-
L19SIP. The provisional and the effective dose to lesions (intra and extracranial) and to healthy organs (including
the red marrow) were evaluated.
Methods and materials: The dose to the bone red marrow was calculated using the method based on the MIRD
formalism, described in the EANM guidelines [1]. It was assessed by measuring activities in blood samples (HPGe
detector, properly calibrated) and whole body (LaBr scintillator) at 0.5, 4, 24, 48, 72 and 96 hours after
administration. Lesions and healthy organs doses were estimated from imaging data acquired with a PET scanner in
the diagnostic phase and with a gammacamera in the therapeutic phase. During the diagnostic phase patients
underwent a series of PET/CT assessments conducted usually at 1, 4, 24, 48 and 96 hours after administration; total
body scans were acquired with 4 minutes per bed position, whereas brain scans were registered using one single
bed position for 20 minutes. During the therapeutic phase brain SPECT and WB acquisition were performed at 48,
72 and 96 hours after administration. To obtain activity values quantitatively correct, both devices were properly
calibrated for each configuration used. The PET scanner was calibrated for 124I: using the IEC Body Phantom,
recovery coefficients were determined as a function of the sphere volume for different S:B ratios [2]. The
gammacamera was calibrated for 131I: for the SPECT calibration was followed the PET method, for the WB the
guidelines [3]. The dose to lesions was determined using the S factor of the MIRD model for a sphere. The dose to
healthy organs was evaluated with the software OLINDA/EXM.
Results: The average dose to the red marrow from the diagnostic and therapeutic phase was 0.201 Gy/GBq (range
0.074-0.149 Gy/GBq) and 0.210 Gy/GBq (range 0.082-0.173 Gy/GBq), respectively (table 1). The difference
between the provisional 124I dose and the effective 131I dose is not statistically significant (p-value 0.3399). The
average calculated dose to the bone red marrow for administration of up to7.4 GBq was therefore always below the
2 Gy threshold of the inclusion criteria. In the patients follow up, a temporary reduction of the red blood cells,
white blood cells and platelet concentration was observed: it returns to normal value within 30-40 days. All brain
lesions for which a dosimetric evaluation was possible had an elevated activity concentration ratio between lesions
and healthy brain, always higher than the eligibility threshold. The provisional dose to the lesions was very
variable, ranging between 0.7-8.1 Gy and 1.1-35.8 Gy for brain and extracranial lesions, respectively. This dose
was slightly lower than the effective dose evaluated from 131I imaging (range 1.3-10.5 Gy and 5.3-69.0 Gy for brain
and extracranial lesions, respectively). However, lesion doses are on average higher than those for healthy organs.
Also the effective healthy organs dose was slightly higher than the provisional dose, but the interpatient difference
between the provisional and effective dose was analysed using a paired t test and it was found not to be statistically
significant for the most of healthy organs. The healthy organs dose is represented in figure 1. The difference
between provisional and effective average dose to thyroid reflects a poor compliance of some patients to thyroid
blocking therapy in the diagnostic phase of the study.
Conclusion: The method used for red marrow dose estimation provided comparable provisional and post-therapy
results. The difference between the provisional and the effective dose to lesions and healthy organs is probably due
to few imaging data acquired in the therapeutic phase and the several corrections applied to these images.
ImmunoPET with 124I-labeled L19SIP offers significant advantages over conventional 131I imaging, particularly
with respect to the accuracy of dosimetric results so that this methodology could be favored for future use.

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Furthermore, the study indicates that antibody uptake can be highly variable even in different lesions of the same
patient and that immunoPET procedures may guide product development with armed antibodies.
Reference
[1] Hindorf C, Glatting C, Chiesa C, Linden O, Flux G, EANM dosimetry committee guidelines for bone marrow
and whole body dosimetry, Eur J Nucl Med Mol Imaging (2010)
[2] Jentzen W, Weise R, Kupferschlager J et al, Iodine-124 PET dosimetry in differentiated thyroid cancer:
recovery coefficients in 2D and 3D modes for PET/CT systems, Eur J Nucl Med Mol Imaging (2008); 35(3):611-23
[3] Chiesa C, Indovina L, Traino C, Sarti G, Savi A, Amato E, De Agostini A, Pedroli G, Dosimetria durante
terapia di carciroma differenziato della tiroide metastatico, http://www.fisicamedica.org/
Red marrow dose
Patient [Gy/GBq]
provisional effective
1 0.184 0.174
2 0.234 0.242
3 0.175 0.170
4 0.256 0.309
5 0.187 0.190
6 0.168 0.177
Table 1 Provisional and effective red marrow dose obtained for each patient.

provisional dosimetry

2.5 effective dosimetry

2.0
[Gy/GBq]

1.5
Dose

1.0

0.5

0.0
Total Body
Red Marrow
LLI Wall
Brain

ULI Wall
Gallbladder Wall

Stomach Wall

Heart Wall

Muscle

Skin

Spleen

Thyroid

Urinary Blad. Wall


Small Intestine

Effective Dose
Liver
Adrenals

Breasts

Kidneys

Lungs

Ovaries

Pancreas

Testes

Thymus

Uterus
Osteogenic Cells

Figure 1 Average provisional and effective healthy organs dose. The thyroid dose is influenced by the thyroid
blocking therapy.

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
SUSPENSION LEVEL FOR THE SENSITIVITY OF INTRA-OPERATIVE GAMMA PROBES USED
FOR SENTINEL LYMPH NODE DETECTION IN MELANOMA PATIENTS.

VALORE DEL SUSPENSION LEVEL PER LA SENSIBILITA’ DELLE SONDE INTRA OPERATORIE
NELLA RICERCA DEL LINFONODI SENTINELLA IN PAZIENTI CON MELANOMA.

Serena Valzano1, Roberta Matheoud1, Roberto Giorgione2, Gian Mauro Sacchetti3, Enrico Colombo2,
Pamela Farinelli2, Marco Brambilla1

1
Medical Physics Department, University Hospital - Novara
2
Dermatology Department, University Hospital - Novara
3
Nuclear Medicine Department, University Hospital - Novara

Intra-operative probes are now an important technology in the management of cancer, since they enable surgeons to
localise small tumours or lymph nodes to be removed in a surgical procedure. The most established type of intra-
operative probe is the non-imaging gamma probe and the most common application is the detection of the sentinel
lymph node (SLN).
Scintillation gamma probes may be quantitatively characterized by several performance parameters, such as spatial
and energy resolution, but one of the most relevant is probe sensitivity (or efficiency) that is the detected count rate
per unit activity. Unfortunately, the protocols for the measurements of sensitivity do not establish minimum
performance levels or minimum acceptance criteria for quality control tests. The purpose of this study was to
determine the suspension levels for the sensitivity of an intra-operative scintillation gamma probe in the detection
of the SLN in melanoma patients, based on experimental measurements performed both in vivo and in vitro.
During a period of 12 months 38 consecutive patients (16 women and 22 men) with melanoma were enrolled. All
the patients underwent a lymphatic scintigraphy after intradermic administration of 14 MBq of 99mTechnetium-
nanocolloid and after 4 hours the surgical procedure was started. The images were obtained using a dual head
gamma camera, with low energy and high-resolution collimators. Scintigraphy was used to determine the draining
lymph node basin to distinguish SLN from non-SLN, to determine the number of SLN and to mark their location
on the skin.
The number of count rate was measured using the gamma probe (LVR15, Nucleomed) simulate three different
sensitivity values: the optimal probe sensitivity (OPT) of 6.9+0.7 cps/kBq, the low probe sensitivity (LOW) of
2.5+0.3 cps/kBq and a very low probe sensitivity (VLOW) of 1.4+0.2 cps/kBq. For assessment of sensitivity
performance of the probe in different operation settings, a fixed source of an aged 57Co pen was used that simulate
the level of activity uptake in the target. The source was usually positioned in air at the centre and in contact with
probe’s sensitive area, and corresponding counts were acquired.
The three gamma probes were used in three moment of surgical procedure: before skin incision (PRE), after a small
incision when SLN was identified (INVIVO) and when the SLN was removed (EXVIVO). For an ex vivo
background, the instrument table of the scrub nurse was used. The measures of PRE, INVIVO and EXVIVO for
SLN and for background were repeated in each patient with those levels of probe sensitivity.
The surgical procedure was simulated in the laboratory using Bowie chabazites, a kind of natural zeolites that are
hydrated crystalline aluminosilicates with absorpitive proprieties; the average density was reported to be 1.73 g/cm3
with irregular shapes and volumes were in the range 0.2-1.5 mm3. The methodology followed to use zeolites as
radioactive sources of different shapes, dimensions and activity concentrations for lesion simulation in Nuclear

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Medicine imaging. Source were allowed to decay after preparation in order to provide a range of count-rate similar
to SLN, and were placed in a cylindrical phantom and immersed in water at depths ranging from 0 to 10 cm from
the surface where the collimated probe was positioned.
According to the Curries equation, the mean number of net count-rate (ND) corresponding to the minimum
detection activity that achieves to detect the lymph node is:

ND=4,563*(Nbkg)1/2+2,706

defining Nbkg the background count-rate:


Overall, 43 SLNs, classified according to the principal characteristics of the primary tumor (38) and lymphatic
drainage (5) were removed with a mean source to detector distance of 46+24 mm (min 12 and max 92 mm), as
measuring during the lateral acquisition of scintigraphy. The volume of the excised SLNs averaged 0.48 cm3 and
no statistically significant correlation was found between SLN probe count rates and SLN depth or volumes.
As expected, the mean value of the count rate detected in the three moment of the surgical procedure reflected the
correspondent sensitivity of the probe (Table 1).

Table 1 Count rate characteristics of the SLN during the surgical procedure

Count rate before incision Count rate intraoperative (cps) Count rate ex-vivo after incision
(cps) (cps)
OPTPRE 232 OPTINVIVO 641 OPTEXVIVO 766
LOWPRE 103 LOWINVIVO 332 LOWEXVIVO 372
VLOWPRE 67 VLOWINVIVO 158 VLOWEXVIVO 158
Background 13.1 Background 0,2

All the SLN have been detected with OPT probe. Having set a ND to 20 cps/kBq, four (9%) SLN could not have
been identified with LOW probe and nine (17%) SLN with VLOW probe. These results are showed in Figure 1.

Figure 1 Number of SLN detected with three probes

The phantom simulation showed results in agreement with the clinical ones (see Table 2): with an activity level of
1 MBq into the target, the count-rate measured were always above the trigger level of 20 cps, irrespective of the
probe sensitivity and of the distance from the source to the probe. With activity level of 0.1 MBq in the target, the

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
count rate decreased under 20 cps already at a depth of 2-4 cm when the sensitivity probe was under of 2.5
cps/kBq.

Table 2 Count rate characteristics of simulated SLN using the zeolites

Activity (MBq) Depth in water Count rate OPT Count rate LOW Count rate
(mm) (cps) (cps) VLOW (cps)
0 134 100 73
2 45 35 25
4 27 21 17
0.1
6 14 13 10
8 8 7 6
10 6 5 4
0 563 199 126
2 195 92 65
4 87 44 32
0.5
6 48 29 20
8 29 20 14
10 20 13 8
0 1816 1109 667
2 692 429 292
4 398 254 188
1
6 176 136 98
8 87 68 50
10 55 44 32

The definition of suspension level will help the medical physics expert in the management of a particular medical
device with respect to the system performance and safety. According to the results of this study, intraoperative
gamma probes used in the research of SLN melanoma patients having an absolute equal or lower than 2.5 cps/kBq
should be suspended of medical use and the performance must be investigated.
The evaluation of gamma probe systems is important and should be performed at acceptance tests and during
quality control programs. The definition of an appropriate suspension level for intraoperative gamma probe
sensitivity of 2.5 cps/kBq has been proposed in the present study, based on experimental measured performed in
the clinical scenario of detection SLN in melanoma patients.

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
90
Y SIR®-spheres Radioembolization (RE) of liver lesions: comparing dosimetry with 99mTc-MAA
SPECT and 90Y PET

Radioembolizzazione di lesioni epatiche con sfere SIR® caricate con 90Y: confronto tra dosimetria da
SPECT con 99mTc-MAA e PET con 90Y

F. Guerriero1, M. E. Ferrari1, F. Botta1, G. Pedroli1, C. Grana2, G. Bonomo3, F. Orsi3, G. Paganelli2, and M.


Cremonesi1
1
Medical Physics Department, European Institute of Oncology , Milan 20141, Italy
2
Nuclear Medicine Department, European Institute of Oncology , Milan 20141, Italy
3
Interventional Radiology Unit, European Institute of Oncology , Milan 20141, Italy

Aim In RE of liver lesions the activity is often administered based on empirical criteria. The reliability of
pre-treatment dosimetry is under debate, although several cases of toxicity in BSA-based treatments have
been reported. In our center 99mTc MacroAggregated Albumin(MAA) SPECT is acquired for previsional
dosimetry, and the injected activity is established with the constraint of ~40 Gy of normal liver equivalent
uniform dose (EUD). Our aim was to compare the dosimetric outcomes derived from therapy simulation
(SPECT) and post therapy images (90Y-PET) in the non tumoral liver treated (NT) and in liver lesions (T).

Methods 12 patients with 17 liver lesions underwent 99mTc-MAA SPECT and after 1-2 weeks were injected
with 90Y SIR-spheres. NT and T volumes were determined by contrast enhanced CT. The day after SIRT
patients underwent 90Y PET-CT. Voxel dosimetry was performed (MIRD 17 publication). Dose-volume
histograms were derived, and the mean absorbed dose (D), the EUD and the equivalent uniform biological
effective dose (EUBED) calculated for NT and T (α=0.017 and 0.3 Gy-1, α/β=2.5 and 10 Gy-2, Trepair= 2.5 and
1.5 h, for NT and T, respectively). D from the partition MIRD model was also compared.

Results Median T volume was 41cc [9-523], NT+T volume 593cc [262-994]. Whole liver volume was
1287cc [913-1798]. The injected activity was 1.7 GBq [0.8-2.9]. For NT according to SPECT, median D
was 131 Gy [53-187], EUD 69 Gy [48-102], EUBED 143 Gy [82-260]. For T median D was 356 Gy [140-
458], EUD 165 Gy [63-334], EUBED 229 Gy [72-588]. Discrepancy between voxel dosimetry and partition
model (as regards D) was within 10%, nonetheless dose non-uniformity was high, being EUD/D 0.6±0.2. A
good correlation was found for D vs. EUD (r2=0.95), as well as for EUD vs. EUBED (r2=0.99).

Considering PET vs. SPECT, the DPET over DSPECT ratio was 1.05 (0.80-1.33) for NT, i.e. SPECT was a good
predictor. For T the ratio was 0.75 (0.40-2.09), and no linear correlation was found between SPECT and PET
dosimetric parameters (e.g. for EUD, r2=0.4). However a monotonous trend in tumor DSPECT vs. DPET
(ρspearman=0.8) was found. Similar results were derived for EUD and EUBED. None of patients experienced
early (4-12 mo) liver toxicity.

Conclusion These results support the usefulness of previsional dosimetry to avoid liver toxicity. The
monotonous trend in dose to T calculated with SPECT versus that from PET supports the treatment
according to the previsional dosimetric results.

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
A graph-based method for biological target volume segmentation.
A.Stefano1,2, S.Vitabile3, G. Russo2, M. Ippolito4, D. Sardina5, M.G. Sabini5, F.Gallivanone6, I. Castiglioni6 and
M.C. Gilardi6,7.
(1) DICGIM, University of Palermo, Palermo (2) IBFM CNR - LATO, Cefalù (PA) (3) Di.Bi.MEF, University of
Palermo, Palermo (4) Nuclear Medicine Department, Cannizzaro Hospital, Catania (5) Medical Physics Unit,
Cannizzaro Hospital, Catania (6) IBFM CNR, Segrate (MI) (7) University of Milano-Bicocca, Milano

Purpose: Computerized tomography (CT) is considered to be the gold standard for target tumor delineation and
dose calculation in head and neck cancer (HNC) radiotherapy (RT) treatments. CT imaging is based on the
variation of tissue density and provides high resolution morphological information. Nevertheless, CT imaging may
not show the viable extension of tumors and it does not localize isolated positive lymph nodes. Vice versa, Positron
Emission Tomography (PET) imaging provides molecular-functional information of lesions with a low spatial
resolution. The 18F-fluoro-2-deoxy-D-glucose (FDG), an analogue of glucose, is the radiotracer commonly used in
PET studies. FDG PET is able to characterize lesions that remain equivocal on CT and to detect CT invisible
lesions, offering the opportunity to radically change the patient treatment. In RT, within or without the CT gross
tumor volume (GTV), it is possible to define the PET biological target volume (BTV) and to apply a specific
deliver radiation strategy to these regions. BTV delineation is challenging because of the low spatial resolution and
high noise level in PET images. In addition, BTV varies substantially depending on the algorithm used. Visual
delineation is widely-used, but it is strongly operator-dependent.
The aim of this work is the development of a robust, fast, accurate, and scanner independent segmentation method
of the BTV. The method has been tested on phantom images in order to assess the accuracy respect to region
growing (RG) standard approach. To assess the applicability in a clinical environment, a pilot patient study was
also considered.
Materials and Methods: The NEMA IEC body phantom including six spheres of different diameters (10,13,17,22,
and 37mm) was used to estimate the BTV segmentation accuracy. Spheres and background were filled with FDG
with a ratio between measured sphere radioactivity concentration and measured background radioactivity
concentration (S/B) that ranged from 1.5 to 11 for 7 experiments at 2 different matrix sizes (256x256 voxels of
2.73x2.73x3.27 mm3 voxel size and 512x512 voxels of 1.36x1.36x3.75 mm3 voxel size).
The patient study was selected to evaluate clinical applicability of the PET segmentation algorithm: a 80 years old
male with HNC fasted for 12 hours before PET exam and was intravenous injected with FDG. PET/CT scan began
60 minutes after the injection and was performed in diagnostic position with the patient on a flat carbon bed similar
to the RT treatment couch. A thermoplastic mask was used for the immobilization of the head.
In phantom studies, the sphere sizes were known and a manual segmentation was not required. In patient study, the
GTV was manually outlined by the radiation oncologist. The BTV was manually defined by the radiation
oncologist in consensus with the nuclear medicine physician. The semi-automatic BTV segmentation was obtained
using a graph-based approach in which the seeds (foreground and background) were specified by the user inputs.
An undirected graph G can be represented as a pair G = (V,E) with nodes v ∈ V and edges e ∈ E ⊆ VxV. A node vi
is a neighbor of another node vj if they are connected by an edge eij with a weight wij (wij=wji being an undirected
graph). This approach represent an image as a graph in which the voxels are its nodes and the edges are defined by
a cost function which maps a change in image intensity to edge weights. The image is then converted into a lattice
where some pixels are known (nodes with label specified by user input) and some pixels are not known. The
delineation problem is to assign a label to unknown nodes. This is done by trying to find the minimum cost/energy
among all possible scenarios in the graph to provide an optimal segmentation. In our study, the random walks
(RW) method proposed by Grady [1] was used.
The RW problem is to determine the highest probabilities for each pixel to reach the target node and has the same

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
solution as the combinatorial Dirichlet problem: D[x]= (XTLx)/2 where L indicates the graph’s Laplacian matrix
and x the vector of the probabilities that each voxel is included in target region.
The Gaussian weighting function for PET image was defined as: wij = exp(-B(SUVi-SUVj)^2) where SUV is the
Standardized Uptake Value, the widely used PET semi-quantitative parameter. In our experiments, the B weighting
factor was set to 50. Hence the image is converted into a lattice where SUV of each voxel is mapped to wij.
To obtain the BTV delineation, the operator chooses the best slice containing the target lesion in order to identify
the target seed with a single mouse click and RW algorithm partitions the nodes into two disjoint subsets (lesion
and background).

The effectiveness of the proposed method has been evaluated comparing to well-known and commonly used RG
method, calculating the difference between actual sphere sizes and semi-automatic PET segmentations. For each
sphere of the phantoms, the percentage difference (E%) was calculated at different S/B. In a phantom study the
morphological regions must match with metabolic regions. This is not true in patient studies: the patient study was
mainly used to assess the applicability in a clinical environment of the RW algorithm.
At last, the average of the time for delineating BTV in phantom and patient studies was recorded to assess
algorithm performances. RWg and RG algorithms were implemented on the Matlab R2012b simulation
environment, running on a general purpose PC with a 3.00GHz Intel R CoreTM i5-2320 processor, 4 GB memory,
and 64-bit Windows 7 Professional.
Results: Table 1 shows the percentage segmentation accuracy results as 100-E% averaged on different spheres in
each phantom experiment: phantoms (a-e) with a sampling matrix of 256x256 voxels and a S/B of 1.5-2 (a), 2-3
(b), 3-5 (c), 5-6 (d), and 6-7 (e), and phantoms (f-g) with a sampling matrix of 128x128 voxels and a S/B range of
3.5-9 (f), and 9-11 (g).

Table 1. Segmentation accuracy % in NEMA experiments


(a) (b) (c) (d) (e) (f) (g)
RW 92.2±6.6 94.5±3.2 94.5±4.4 95.5±4.1 95.3±2.7 93.4±6.6 94.5±1.4
RG 82.8 87.7±15 83.8±7.4 87.7±16 91.9±3.8 87.1±12 90.3±1.4

The E% range of RW algorithm between segmented and real sizes was found to be from 0.5% up to 16.8% without
any restriction in diameter and in S/B. The range reduced from 0.5% up to 5.4% for the spheres with a diameter
>1.7cm. The minimum error was obtained in the sphere with a diameter of 3.7 cm and with a S/B of 5 (c). For the
spheres with a diameter <1.7cm, the range was found to be from 4.5% up to 16.8%. The maximum error was
obtained in the smaller sphere with a S/B of 3.5 (g). RW algorithm failed in the smaller sphere segmentation at
very low S/B ((a) and (b)) where the percentage segmentation accuracy was obtained by considering the five
spheres with a diameter > 1 cm. The average of the time for 1 slice segmentation was around 0.1 seconds in
128x128 images and around 0.2 seconds in 256x256 images.
The E% range of PET delineation using RG algorithm was found to be from 9.3% up to 36.3% for the sphere < 17
mm diameter and from 0.7% up to 20.4% for the sphere > 17 mm diameter, respectively. RG algorithm failed to
delineate spheres with a diameter of 1 cm. In the experiment with a S/B<2 (a) only the sphere with a diameter of
3.7 cm was segmented. The average of the time for 1 slice delineation was around 0.11 seconds in both 128x128
and 256x256 images.
In the clinical case, BTV radically changed the treatment volume because uptake was found outside the GTV in a
involved lymph node not CT visible. The volume (13 slices) was segmented in around 1.4 seconds.

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Conclusion: The aim of this work was to validate a FDG-PET image segmentation algorithm based on RW and to
assess its applicability in a clinical environment. The RW algorithm segments PET images from SUV and it is very
fast if compared against the time needed for a manual segmentation.
In the NEMA IEC body phantom experiments, the accuracy of RW segmentation was higher than RG
segmentation. This was evident for the spheres with a diameter of 1 cm, despite a drop in the RW accuracy for the
smaller spheres at low S/B. This was compatible with the severe errors in the volume estimation produced by
partial volume effect (PVE), one of the most important physical factors that impacts the quality and the quantitative
accuracy in PET images [2]. Several corrective techniques have been developed and a PVE correction method
could be included in the algorithm, such as that described in [3]. Increasing the target size, RW time performance
and accuracy remain steady, while RG accuracy increases and time performance decreases. Moreover, RW method
provided resolution independent results considering the two set of images tested. In the clinical case, FDG-PET has
been proved to modify size, location, and shape of RT treatment planning, leading to the opportunity to prevent
potential disease progression. In many cases, such as the one presented in the paper, qualitative interpretation and
manual contouring are sufficient to obtain fundamental information for patient care, including invisible metastases
using traditional radiologic techniques. However, the implementation of automatic algorithms to estimate BTV for
RT treatment is mandatory and the RW meets the requirements in a clinical environment.
References:
[1] L. Grady, Random walks for image segmentation, Ieee Transactions on Pattern Analysis and Machine
Intelligence (2006) 28,1768-83
[2] M. Soret, S.L. Bacharach, I. Buvat: Partial-volume effect in PET tumor imaging. Journal of Nuclear Medicine
(2007) 48, 932-945
[3] F. Gallivanone, A. Stefano, E. Grosso, C. Canevari, L. Gianolli, C. Messa, M.C. Gilardi, I. Castiglioni: PVE
Correction in PET-CT Whole-Body Oncological Studies From PVE-Affected Images. Ieee Transactions on
Nuclear Science (2011) 58, 736-747

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Confronto e validazione di due algoritmi innovativi per la segmentazione semi-
automatica di immagini PET

COMPARISON AND VALIDATION IN CLINICAL SETTINGS OF TWO INNOVATIVE SEMI-


AUTOMATIC ALGORITHMS FOR VOLUME DELINEATION ON PET IMAGES

Basile C1, Caselli F2, Ciaschini A2, Botta F3, Cremonesi M3, Paganelli G3, Pacilio M1

1
San Camillo-Forlanini Hospital , Rome, Italy
2
Tor Vergata University, Rome, Italy
3
Istituto Europeo di Oncologia, Milan, Italy

AIM - Various methods are proposed for PET-based delineation: adaptive thresholding, region growing,
Markov random field models, artificial neural networks, and many others, but performance in clinical
settings remains the most challenging issue. Two methods for segmentation on PET images have been
implemented: the recovering iterative thresholding method (RIThM), proposed by Pacilio et al for SPECT
images (Med Phys 2011), and a denoising-deblurring pre-processing method with subsequent
segmentation (DDS). In this work, validation results on clinical images are presented.
MATERIALS AND METHODS - The RIThM is an iterative adaptive thresholding-based method, using
threshold-volume calibrations of the PET scanner at different source-to-background ratios, with further
inclusion of recovery coefficients for improving the segmentation accuracy. The DDS method is based on
the work of Boussion et al (Eur J Nucl Med Mol Imaging 2009): deconvolution was performed by the
Lucy-Richardson algorithm, incorporating a Wavelet-based denoising at each iteration (in order to
eliminate the noise observed in classical deconvolution methods), and subsequent segmentation
performed by marker-controlled watershed transform. Both of these methods were coded using
MATLAB (R2009b). The performance of the methods was analyzed with clinical PET images of 22
patients, for which the PET volumes of interest (VOIs, secondary spleens, lymph nodes, and bladders
internal volume) were expected to correspond with those on the CT images, used as reference. The
agreement between CT and PET VOIs was statistically analyzed, by linear regression fit and Bland-
Altman plots with ±95% confidence interval (CI).
RESULTS - For RIThM, a good correlation (R2=0.955, slope=1.018) was obtained (22 cases), as
confirmed also by the Bland-Altman plot: differences within the ±95% CI (except for one case), with a
mean difference (bias line) close to zero. For DSS, preliminary results (8 cases) seem to show a good
performance (R2=0.974).
CONCLUSION - The results confirm the robustness and accuracy of RIThM method. A wider variety of
cases is under analysis to confirm these results and further investigate the potential of the two methods. In
addition, the appropriate combination of deconvolution and denoising of DSS seems really promising
also for reducing partial volume effects at the voxel level in PET images.

 
ELENCO
 
TOPIC ESC
 
  MEDICINA LA FISICA MEDICA
RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
  RICERCA NUCLEARE
SANITARIE
 
Impact of PET and CT images misalignment on 18F-Fluoride bone uptake quantification
D. D’Ambrosio1, I. Carne1, P. Montagna2, E.G. Spinapolice2, C. Fuccio2, E. Brugola2, G. Trifirò2, D. Fantinato1
(1) Medical Physics Unit, Salvatore Maugeri Foundation, Pavia (2) Nuclear Medicine Unit, Salvatore Maugeri
Foundation, Pavia

Introduction: Accurate attenuation correction (AC) is an important issue for quantitative analysis of PET
radiopharmaceutical distribution. In integrated PET/CT scanners, AC is typically performed using CT image. The
accuracy of AC depends both on the accuracy of PET and CT images co-registration and on the accuracy of the
scaling method applied to create a μ-map at 511 keV [1]. As PET and CT studies are performed at different
acquisition times, a potential mis-registration between the emission and transmission data can be found in
evaluating PET/CT images. Thus, such spatial misalignment, due to patient motion and patient breath can lead to
artifacts in reconstructed PET image. Such effect has been widely discussed in literature, as concerning radiotracer
uptake quantitation in soft tissue. The accuracy of CT-based attenuation correction in PET/CT bone imaging has
been recently investigated by Abella et al. as concerning the scaling method used to get a μ-map at 511 keV [2].
The purpose of this study is to evaluate the impact of PET and CT data misalignment in quantifying bone uptake
when a specific bone radiopharmaceutical, such as 18F-Fluoride, is used.
Materials and methods: The NEMA/IEC IQ Body (IQ) Phantom was filled with an homogeneous solution
containing about 90 MBq of 18F and water. In order to simulate the attenuation of bone tissue, a cylindrical
polyethylene insert (diameter equal to 51 mm), typically used to mimic lung tissue, was filled with a mixture of
plastic grains and dust. In order to obtain a typical clinical radiopharmaceutical distribution, the IQ phantom was
filled to get a bone-to-background activity concentration ratio equal to 20. PET/CT images of IQ phantom were
acquired using the Discovery VCT 690 PET/CT tomograph (GE Healthcare). Three CT acquisitions were
performed at 100 kVp, 120 kVp and 140 kVp. In order to model PET and CT misalignment in radial direction,
manual shifts equal to 2 mm, 5 mm, 10 mm and 15 mm between PET and CT data were applied by using ACQC
software (GE Healthcare). Therefore, PET images were reconstructed by using 3D-OSEM iterative algorithm (3
iterations, 16 subsets) with time of flight and point spread function information. As different CT images were used
for attenuation correction, fifteen PET images were reconstructed. PET images corrected using CT data
reconstructed without applying any manual shift were used as reference images (PETREF(V), where V is equal to
100 kVp, 120 kVp or 140 kVp). PET and CT image registration was checked using a dedicated PET/CT alignment
phantom as a part of quality assurance program. In order to evaluate the effect of different misaligned attenuation
map on radiotracer bone uptake, PET images corrected using shifted CT images (PETSHIFT(V), where shift is equal
to 2 mm, 5 mm, 10 mm and 15 mm and V is equal to 100 kVp, 120 kVp and 140 kVp) were compared with
PETREF(V) images. More precisely, PETSHIFT(V) and PETREF(V) images were analysed by drawing volumes of
interest (VOIs) over bony and background regions. VOIs were drawn large enough to avoid bias due to partial
volume effect in measuring radiotracer concentration. Maximum and mean uptake values of bone structures were
measured and percentage differences were estimated for each PETSHIFT(V) image in respect to the related
PETREF(V). Mean bone-to-background ratio were also calculated over VOIs drawn across PETSHIFT(V) and
PETREF(V) images.
Results: For PET/CT misalignment equal to 2 mm, no percentage differences were found between PETREF(V) and
PETSHIFT(V) in terms of mean uptake, for each value of V. Thus, the effect of a 2 mm-shift was null and
independent on kVp used in CT acquisitions. Misalignment equal to 5 mm, 10 mm and 15 mm produced an
underestimation in terms of mean uptake percentage difference up to 0.5%, 3.0% and 5.9%, respectively. Also in
this case, such differences were not dependent on kVp used for CT image acquisition. The analysis of maximum
uptake value performed for each PET/CT misalignment has shown no significant percentage difference with
respect to PETREF(V), regardless of the kVp used during CT acquisition. The mismatch between PET and CT

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
images yielded a bone-to-background ratio bias up to 0.5%, 2.4% and 4.5% for shifts equal to 5 mm, 10 mm and 15
mm, respectively. No bone-to-background ratio bias was measured for PET/CT misalignment equal to 2 mm.

Discussion and conclusion: 18F-Fluoride PET/CT imaging is increasingly used for bone studies. Images are often
qualitatively evaluated. However, quantitative comparisons between different 18F-Fluoride PET images are
sometimes needed (i.e. in follow-up studies). In this case, an accurate co-registration between the emission and
transmission data becomes more important as a PET/CT mismatch can cause artefacts in reconstructed PET data.
Initial results of this work show that PET/CT misalignment up to 2 mm doesn’t affect quantification of 18F-Fluoride
uptake of bony structures. Increasing the misalignment between PET and CT images, the error in quantification of
bone radiotracer uptake increases. In this study, a bone-to-background ratio equal to 20 was chosen in order to
reproduce a typical clinical radiotracer distribution. The impact of an inaccurate co-registration of PET and CT
images on quantification of radiotracer uptake in bony structures will be further investigated in order to evaluate
different clinical situation, i.e. different bone-to-background ratio and different bony region dimension in order to
better model bone metastases size.

References:
[1] P.E. Kinahan, Attenuation correction for a combined 3D PET/CT scanner, Med. Phys. (1998) 25 (10), 2046-53
[2] M. Abella, Accuracy of CT-based attenuation correction in PET/CT bone imaging, Phys. Med. Biol. (2012) 57,
2477-2490

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Impatto degli algoritmi iterativi nella definizione delle lesioni e nella quantificazione nel sistema
PET/CT Discovery-710.

Effect of 3D iterative reconstruction algorithm in lesion definition and in quantification in the


Discovery-710 CT/PET system
E. Lorenzini (1), S. Luxardo (1), G. Marcozzi (1), P. Bianchi (2), P. Bertolaccini (2), A. Tofani (1).
(1) U. O. Fisica Sanitaria Azienda USL1 di Massa e Carrara, (2) U. O. Medicina Nucleare Azienda USL1 di
Massa e Carrara

Purpose: In the aim of finding a path towards quantification in a diagnostic and radiotherapic use of positron
emission tomography, we investigated the impact of choosing different 3D iterative reconstruction
algorithms at disposal in the new hybrid PET/CT system manufactured by GE Medical Systems both terms
of definition of lesion volumes and contrast.
Methods and materials: The PET tomograph part of Discovery 710 is provided with a block of LYSO
detector and a computing system implementing the state-of-art reconstruction algorithms which include both
time-of-flight information and detector response.
Time of flight is a technique that localizes the decay site based on the arrival time of the photons at the
detector. Considering the timing resolution in the clinical range of the tomograph (555ps – 565ps), the
uncertainty in spatial localization is still 16-17cm. Anyway, adding timing information to each correction
step within the iterative loop (normalization, randoms, deadtime, scatter, attenuation), the algorithm VUE
Point FX has a strong impact on scatter reduction, improving image quality in terms of greater contrast and
activity delineation.
The detector response depends on different parameters such as detector geometry, detector sampling width,
and parallax effect, which cause a different point response depending on the position of the source in the
acquisition field of view (FOV). The Sharp IR algorithms takes into account for this variation by
incorporating measurements of the detector response to a point source placed all over the FOV in the
reconstruction process [1].
By means of the image quality phantom described in the NEMA NU-2-2007 procedures, and by considering
two kind of reconstruction protocols, one (A) optimized to get the best resolution results (post filter 2mm, 18
subsets, 5 iterations, 60 Mc), the other (B) studied in order to have “diagnostic” images in clinical situation
(post filter 5mm, 16 subsets, 3 iterations, 30 Mc), we compared the reconstructed hot contrast for the spheres
of 10, 13, 17 and 22 mm diameter in terms of recovery coefficients (defined as the ratio of observed
concentration in the final image to the real activity concentration) for different types of algorithms: HD (fully
3D iterative reconstruction), FX, HDSIR (HD+SharpIR) and FXSIR (FX+SharpIR), and for various
lesion/background activity ratios (4:1, 8:1). Furthermore, we investigated which kind of threshold could be
the most accurate in order to get the correct lesion definition in terms of 3D ROI volume.
Results: With protocol A, we found that TOF significantly improves contrast more than what can be
achieved with HDSIR only, in particular for small lesion, which can be detected anyway.
In volume definition, using SharpIR and the small Gaussian filter the fixed threshold of 40% is not more
suitable, and it has to be lowered to 34%. Anyway, when using 40% threshold the error in estimating
volume could be high with no TOF and in very small lesions, but it has a limited impact on contouring (max
2.5 mm radius HD).
With protocol B (the one routinely used in our hospital) the recovery coefficient is 50% less than in A in the
smallest sphere lesion, so reconstruction parameters have an impact on contrast especially at high
frequencies. The difference among the various algorithms are almost the same: again FXSIR gives the best
result. In volume definition the most accurate threshold seems to be 45% (43% with SIR 46% NOSIR)
instead of 40% (this mainly because of the smoothing caused by the gaussian filter), but the smallest lesion is
well definable only with FXSIR algorithm.

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Figura 1: recovery coefficient vs sphere dimension using VuePoint FX and sharp IR for the two
reconstruction protocols.

Figura 2: recovery coefficient vs sphere dimension in clinical conditions using the reconstruction
algorithms at disposal.

Conclusion: The efficiency of the new iterative reconstruction algorithms was found to be very high for both
activity and volume quantification especially for small lesions in clinical conditions. This makes it possible
to lower the injected activity, keeping constant image quality and reconstruction time.

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Correzioni di uniformità dell’ampiezza degli impulsi per una piccola gamma camera a cristallo
continuo:LaBr3:Ce(5%).

Uniformity corrections of Pulse height for small gamma cameras based on LaBr3:Ce (5%) continuous
crystal.
T. Insero1, M.N. Cinti2,3, R. Pellegrini2,3, Christian Borrazzo4, A.Fabbri5,6, G. De Vincentis7 and R. Pani2,3.  

(1) Medical Physics Post Graduate School, Sapienza University of Rome, Rome, Italy
(2) INFN, Section of Rome I, Rome, Italy
(3) Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy
(4) Department of Physics, University of Rome ”Roma 3”, Rome, Italy
(5) Department of Physics, University of Rome ”Roma 3”, Rome, Italy
(6) INFN, Section of Roma Tre, Italy, Rome, Italy
(7)Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Rome, Italy

Purpose: diagnostic imaging needs of high accuracy in image quality in order to provide functional and anatomical
information of biological tissues. Recently the scientific research have investigated on the imaging capability of
LaBr3:Ce(5%) scintillation crystal, in continuous configuration, obtaining important results as 1 mm of intrinsic
spatial resolution and about 7% at 122 keV in energy resolution. An important requirement for these detectors is
the response uniformity on the overall FoV. In the proposed detector, the procedure to uniform the overall response
of detector is made difficult by the non uniformity in anodes gain of the position sensitive photomultiplier. So in
this work a method to correct this factor is proposed.
Methods and materials:the studied small FoV gamma camera is based on a continuous crystal (48x48 mm)
coupled to a Multi anode PMT Hamamatsu H8500C-100. The 64 outputs, coming from the 8x8 anodic array, are
read by a 64 channels dedicated electronics readout. To analyze the local response of detector, a scanning of the
detector surface with a 2 mm collimated Co57 source was made, irradiating the crystal in correspondence of each
anode, obtaining a map of the detector response in term of spatial and energy resolution and point spread function
of the scintillation light. The method utilized to uniform the response implies different steps, first of all the
application of the Hamamatsu matrix of the anodic gain, in order to obtain a first level of correction of the pulse
height distribution. The effect of the gain correction on the light point spread function, and as a consequence on the
spatial information, was evaluated applying separately opportune matrices of corrections.
Results:the matrices of corrections allowed to obtain, in terms of pulse height distribution, a response uniformity
of about 3%, and an improving of energy windowing up to 30%. Furthermore an improvement of spatial linearity
and resolution on the overall scintillation crystal was obtained (47%). On the contrary all correction procedures
reduces the energy resolution from 7% to 17%.
Conclusion:the performances obtained, permits to operate with a large window in energy, and to obtain very good
responses in term of position linearity and spatial resolution practically in overall detector area.

ELENCO
 
TOPIC ESC
 
  MEDICINA LA FISICA MEDICA
RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
  RICERCA NUCLEARE
SANITARIE
 
Valutazione degli algoritmi di ricostruzione iterativi con recupero della risoluzione per la riduzione della
dose nei pazienti sottoposti a imaging di perfusione miocardica: uno studio multicentrico.

Evaluation of the iterative reconstruction algorithms with resolution recovery for reducing patient dose in
MPI: a multicenter study.

C. Scabbio(1), O. Zoccarato(2), E. De Ponti(3), M. Brambilla(4), R. Matheoud(4), S. Morzenti(3), S. Garancini(5),


M. Menzaghi(5), M. Lecchi(1)
(1) Department of Health Sciences, University of Milan and Nuclear Medicine Unit, San Paolo Hospital, Milan,
Italy
(2) Unit of Nuclear Medicine, S. Maugeri Foundation, IRCCS, Scientific Institute of Veruno (NO), Italy
(3) Medical Physics Department, San Gerardo Hospital, Monza, Italy
(4) Unit of Medical Physics, University Hospital ‘Maggiore della Carità’, Novara, Italy
(5) Unit of Nuclear Medicine, Ospedale di Circolo, Varese, Italy

Purpose: Recent studies have highlighted the ability of the new iterative reconstruction algorithms with resolution
recovery (IR) to halve the patient dose in SPECT MPI, with the same diagnostic accuracy as the standard
procedure. The CILDA (Cardiac Imaging Low Dose Algorithms) project aims to establish the lower limit of
radioactivity that can be administered to patients in SPECT MPI, independently of the IR used while preserving
diagnostic accuracy.
Methods and materials: In four different nuclear-medicine centers, an anthropomorphic phantom was used to
simulate clinical STRESS scans. Two sets (with and without a cold transmural defect, TD) of five separate scans
were acquired with total counts of 6(standard in vivo counting statistics), 4(75% of standard counts), 3(50%),
1.5(25%) and 0.8 Mcounts(12.5%).
Three sets of SPECT images were reconstructed with: 1)FBP, 2)OSEM and 3)the new IR available in the different
centers: Evolution for cardiac (GE), Astonish (Philips), Flash 3D (Siemens) and Wide beam reconstruction, WBR
(UltraSPECT). In the case 3), the IR dataset included no correction(NC), correction for attenuation(AC), for
scatter(SC) or for both(ACSC).
All image sets have been centrally analyzed to evaluate:
A)TD contrast in LV wall (%)
B)LV wall thickness (FWHM of the medial sections)
C)Contrast between LV wall and inner chamber (%)
D)Noise (CV% on liver signal).
The maximum (DMAX) and minimum (DMIN) differences between IR results and FBP and OSEM ones were finally
evaluated.
Results: For the first 3 physical parameters considered, D MIN were positive for all counting-statistics and for all IR
dataset considered:
A) OSEM: DMAX=15.2% (IR-SC, 1.5Mc), DMIN=1.3% (IR-AC, 0.8Mc);
FBP: DMAX=16.2% (IR-SC, 3Mc), DMIN=3% (IR-AC, 0.8Mc);
B) OSEM: DMAX=5mm (IR-SC, 3Mc), DMIN=1.1mm (IR-AC, 6Mc);
FBP: DMAX=6.2mm (IR-SC, 0.8Mc), DMIN=2mm (IR-AC, 1.5Mc);
C) OSEM: DMAX=33% (IR-SC, 0.8Mc), DMIN=14.8% (IR-AC, 1.5Mc);
FBP: DMAX=32.8% (IR-SC, 0.8Mc), DMIN=11.2% (IR-AC, 1.5Mc).
IR dataset showed lower noise than FBP and OSEM for all counting-statistics:
D) OSEM: DMAX=-7.5% (IR-ACSC, 1.5Mc), DMIN=-0.2% (IR-SC, 6Mc);
FBP: DMAX=-9.7% (IR-ACSC, 1.5Mc), DMIN=-1.9% (IR-SC, 6Mc).

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Conclusion: The IR algorithms provide better results for all counting-statistics. The AC and SC should be included
in the reconstruction process: AC alone must be applied carefully, while SC shows better results in contrast and
resolution.

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Valutazione   di   lesioni   polmonari   con   tecnica   ad   inspirio   forzato   su   tomografo   PET/CT   a   4   anelli:  
evidenze  da  uno  studio  pre-­‐clinico  e  clinico.  
 
Deep   Inspiration   Breath-­‐Hold   technique   on   a   4-­‐rings   PET/CT   scanner   in   evaluating   lung   lesions:  
evidences  from  a  phantom  and  clinical  study.  
 
Stefano   Ren   Kaiser1,   Federico   Caobelli2,   Erinda   Puta2,   Valentina   Massetti2,   Michela   Andreoli2,   Angelica  
Mostarda2,  Alberto  Soffientini2,  Claudio  Pizzocaro2,  Ugo  Paolo  Guerra2,  M.  Galelli1.  
 
(1)  Medical  Physics  Department,  Fondazione  Poliambulanza  –  Istituto  Ospedaliero,  Brescia,  Italy  
(2)  Nuclear  Medicine  Department,  Fondazione  Poliambulanza  –  Istituto  Ospedaliero,  Brescia,  Italy  
 
Purpose:  Capability  of  a  4-­‐rings  PET/CT  scanner  in  detection  of  small  size  objects  is  evaluated  in  simulated  
Deep   Inspiration   Breath   Hold   (DIBH)   acquisition   in   order   to   investigate   the   clinical   feasibility   of   DIBH  
PET/CT  scan  technique  for  lung  lesion  detection.  
A   clinical   study   is   then   performed   to   compare   pulmonary   diseases   detection   between   DIBH   and   Free  
Breathing  (FB)  PET/CT  scans.  
Methods   and   materials:   A   pre-­‐clinical   study   is   performed   in   a   torso   phantom,   which   embeds   six   hollow  
solid   spheres   of   different   volume   (0.53   cm3–24.65   cm3),   to   evaluate   the   shortest   simulated   DIBH   acquisition  
time   in   function   of   the   minimum   detectable   lesion   that   Biograph   mCT   TOF   PET/CT   scanner   (Siemens  
Medical  Solution  AG)  can  detect.  PET/CT  scans  of  the  phantom  are  performed  by  changing  acquisition  time  
(5   s–90   s)   and   sphere-­‐to-­‐background   (S/B)   activity   ratio   values   (3:1–17.2:1).   Activity   densities   and   contrast  
values   of   sphere   objects   are   studied   in   function   of   sphere   volume,   acquisition   time   and   S/B   activity   ratio  
value.  
In  the  clinical  study,  25  patients  with  pulmonary  lesions  undergo  a  standard  whole  body  [18F]FDG  PET/CT  
scan  in  free  breathing  followed  by  a  20  s  single  thorax  acquisition  PET/CT  in  DIBH  acquisition.  Lung  lesion  
displacement  between  PET  and  CT  images  and  lesion  maximum  standardized  uptake  value  (SUVmax)  both  in  
FB  and  DIBH  PET/CT  acquisitions  are  recorded.  
Results:  Concerning  phantom  study,  in  the  middle  S/B  ratio  range,  with  a  5–15  s  acquisition  the  1.10  cm3  
sphere  contrast  is  constant  with  S/B  value,  while  it  significantly  increases  as  activity  increases  when  a  20–30  
s  acquisition  is  performed.  Therefore,  to  perform  a  20–30  s  acquisition  means  to  improve  the  detectability  of  
1.10  cm3  sphere  also  with  a  lower  S/B  ratio  value;  on  the  contrary,  a  5–15  s  acquisition  does  not  give  any  
significant  contribute  to  the  detectability  of  this  lesion  nor  to  the  smaller  one.  
Regarding  clinical  study,  overall  27  lesions  are  studied.  In  19/27  lesions  a  misalignment  between  PET  and  
CT   images   in   FB   acquisition   can   be   found.   PET/CT   scans   in   DIBH   studies   show   a   significant   reduction   of  
misalignment  and  an  increase  of  SUVmax  compared  to  FB.  
Conclusion:  Phantom  study  indicates  that  a  20  s  acquisition  time  should  provide  an  accurate  evaluation  of  
small   sphere   shaped   lesions.   The   single   20   s   acquisition   of   DIBH   PET/CT   is   a   feasible   technique   for   lung  
lesion   detection   in   the   clinical   setting   and   requires   only   a   minor   increase   in   examination   time   without  
particular  patient  training.  
 
 
 

ELENCO
 
TOPIC ESC
 
  MEDICINA LA FISICA MEDICA
RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
  RICERCA NUCLEARE
SANITARIE
 
Comparison of innovative 99Mo production routes aimed at the realization of 99Mo/99mTc generators.

Confronto fra metodi innovativi per la produzione di 99Mo allo scopo di realizzare generatori 99Mo/99mTc.

G. Pupillo1, M. Gambaccini1, A.Taibi1, J. Esposito2.


(1) University of Ferrara and INFN Ferrara (2) INFN, Legnaro (PD)

Purpose: The recent crisis of 99Mo production by nuclear reactors caused an unexpected worldwide 99mTc
shortening, forcing the international scientific community to find alternative production routes for these vital
nuclides. One of the possibilities is to replace the current reactor-based method with the accelerator-based one. The
aim of this work is the comparison between the innovative production routes based on the 96Zr(α,n)99Mo and
100
Mo(p,x)99mTc, 99Mo reactions. Since the 96Zr(α,n)99Mo reaction was evaluated only once [1], a new
measurement of this cross section was performed and will be also presented.
Methods and materials: The nuclear reaction 96Zr(α,n)99Mo was evaluated using the well known stacked foil
technique at the facility ARRONAX [2], by using the 67 MeV α-beam with a current of about 200 nA. Considering
that 96Zr is 2.8% of natural Zr targets, in order to produce an adequate 99Mo activity the irradiation time was about
4 hours. The nuclear reactions on enriched Mo-100 targets were already evaluated in the last 40 years in different
experimental campaigns. In case of a direct 99mTc production is important the evaluation of other Tc nuclides co-
produced in the target, since a chemical purification is not able to separate isotopes of the same element [3].
Results: The cross section measurements of the reaction 96Zr(α,n)99Mo reported refer to a 100% enriched 96Zr
target. The results obtained in the different irradiations show excellent agreement and indicate that the ideal energy
range for 99Mo production is 13-25 MeV. The values were compare with literature [1], finding good agreement in
the trend of the cross section but an higher peak value. In case of the reaction 100Mo(p,x)99Mo, the ideal energy
window is above 20 MeV, while for a direct 99mTc production the proton energy has to be lower than 25 MeV, in
order to reduce as much as possible the production of other Tc-nuclides.
Conclusion: Innovative production routes of 99Mo and 99mTc are studied, in particular the comparison between the
alpha-induced reaction 96Zr(α,n)99Mo and the proton-induced reactions on Mo-100 targets. In case of using an α-
beam on natural Zr targets the production yield of Mo-99 is low (since 96Zr is only the 2.8% on natural Zr) but no
other radioactive Mo-isotopes are produced and neither Tc nuclides. For these reasons the 96Zr(α,n)99Mo reaction is
an interesting alternative production route, providing high specific activity 99mTc, aimed at the realization of
99
Mo/99mTc generators. In the case of 99Mo production via proton beams, the specific activity is low in comparison
with standard generators but the final 99mTc purity is the same of standard generators. On the contrary, the
production yield in case of a direct 99mTc production is interesting, but particular attention has to be paid to the
production of contaminants Tc-nuclides that will be also present in the final product. For these reasons, it is
necessary to perform short irradiations (about 3 hours) using a proton beam in the energy window 23-9 MeV.
References:
[1] D.P. Chowdhury, Sujiit Pal, S.K. Saha, S. Gangadharan, Nucl Instrum Meth B, 103 (1995) 261-266
[2] F. Haddad, L. Ferrer, A. Guertin, T. Carlier, N. Michel, J. Barbet, J.F. Chatal, Eur J Nucl Med Mol Imaging, 35
(2008) 1377-1387
[3] Celler A, Hou X, Bnard F and Ruth T 2011 Theoretical modeling of yields for proton-induced
reactions on natuaral and enriched molybdenum targets Phys. Med. Biol. 56 5469-84

ELENCO
 
TOPIC ESC
 
  MEDICINA LA FISICA MEDICA
RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
  RICERCA NUCLEARE
SANITARIE
 
Gioie e dolori in sei anni di gestione di un ciclotrone da 11 MeV per uso biomedico
Our six years experience in managing an 11 MeV medical cyclotron: delights & sorrows

M.C.Bagnara1, M.Andrei2, R.Bampi1, M.Bevegni1, G. De Pascalis1, C.Ghersi3, F.Levrero1, E.M.L.Vaccara1,


C.Vite4, A.Pilot1.
(1) U.O. Fisica Medica e Sanitaria, IRCCS Azienda Ospedaliera Universitaria San Martino – IST Istituto Nazionale
per la Ricerca sul Cancro, Genova
(2) Modulo Fisica Sanitaria, ASL3 Genovese, Genova
(3) U.O. Medicina Nucleare IRCCS Azienda Ospedaliera Universitaria San Martino – IST Istituto Nazionale per la
Ricerca sul Cancro, Genova
(4) Dipartimento di Diagnostica per Immagini, CDI Centro Diagnostico Italiano, Milano

Purpose: Nowadays, some Medical Physics units include in their activities the management of medical cyclotrons,
used to produce radionuclides for positron emission tomography (PET) imaging.
This is the case of our working team, where medical physicists hold all the cyclotron activities, including
production, while all the other radiopharmacy activities are performed by the Nuclear Medicine unit.
The aim of this study is a retrospective analysis of our optimization process, regarding cyclotron only.
Methods and materials: A self-shielded medical cyclotron (11 MeV Siemens Elipse RD) has been installed in
2007 in our hospital; up to now exclusively engaged in the production of 18F- for FDG (Fluorodeoxyglucose) and
NaF (Sodium Fluoride), currently we are starting up the production of 11C-CO2 for Choline.
In all these years we had to deal with some problems affecting cyclotron downtime or the yield of delivered 18F;
therefore, in a continuous reviewing process, many topics have been implemented or improved and our principal
actions has been:
- Optimize working procedures and running parameters
- Review some plant issues (i.e. conditioning, to improve cooling system)
- Install switching valves (to allow dual beam production and delivery)
- Modify the delivery system: tubing materials and layout (to improve delivery and facilitate inspection and lines
replacement)
- Add chromatographic filters to lines (to prevent clogging with silver and junk)
- Modify the 18F target body position on target changers (to improve target cooling)
The 18F supplied to the chemistry module (Siemens Explora FDG4) and the final FDG production have been
monitored in these years for more than 1600 runs, together with other indicators, such as ion source performances,
running parameters, delivery time, downtime, maintenances.
Results: The impact of each improvement was identified. The connection between FDG production, maintenances
and other aspects leads to appreciate the improvements and to identify possible additional aspects to refine the total
yield of the system. Our current downtime is around 10%.
Conclusion: The optimization process in the management of medical cyclotrons definitely requires a
multidisciplinary approach, including physics, engineering and radiochemistry issues.
In our experience, the detailed knowledge and the continuous monitoring of each single step improves the process
of radionuclides production, delivery and radiopharmaceutical synthesis.

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Normal subjects database, differentiated by age, of 18 F-FDG brain PET for SPM analysis.
R. Stoico, P. Baruzzi, G. Gianduia, L. Maffioli.
A.O. Ospedale Civile Legnano, Legnano, Italy.
Introduction
In Nuclear Medicine the visual diagnosis of brain studies shows some problems in particular in the detection
and localization of hypo-metabolic areas with confidence. In this case the introduction of semi-quantitative
approach has become more and more important.
The quantitative evaluation of hypo-metabolic areas was usually performed by the use of manually drawn
not-reproducible region of interest (ROI). Moreover the use of fixed geometry ROI (circles) can introduce
biases, as anatomical structure of the brain may not be described best by this kind of geometry [1-4].
The introduction of different types of voxel-by-voxel-based techniques for clinical evaluation has eliminated
many limitations in data-analysis.
Structural Parametric Mapping (SPM) software is now most widely used in clinical evaluation of brain
studies. It was based on the comparison of two group of patients (pathologic subjects vs. normal controls), so
it is very important to create a database of normal controls to perform the analysis.
The creation and increase of database of normal 18 F-FDG brain studies often represents critical point for
general medium hospital. It was due to 18 F-FDG brain studies not as numerous as whole body studies.
Therefore, the aim of this study was to create and increase the healthy-subjects “controls group” by using
high resolution (HR) head and neck and whole body PET/CT scans of non-neurological patients.
In order to reduce bias related to age, normal controls were divided in age classes.
Materials and methods
133 18 F-FDG PET studies were performed. 34 patients underwent 18 F-FDG brain PET/CT: 9 without (Group
A) and 25 with brain disorders (Group B). 30 non-neurological patients underwent 18 F-FDG HR head and
neck PET/CT (Group C); the remaining 69 patients underwent 18 F-FDG whole body PET/CT (Group D).
4MBq/kg were administered to patients undergone whole body studies, while a dose range of 90-150 MBq
was considered in head and neck and brain studies.All the patients were invited to relax in the waiting-
administration room before the examination.
Pet Imaging
The examinations were performed on Philips Gemini TF PET-CT system. A low-dose CT was performed
(120 kV, 100 mAs for normotype patients). 2 x 2 mm2 pixel size and 2 mm slice thickness were used in PET
acquisition, in order to obtain a better resolution. Image reconstruction was performed with a iterative
algorithm ASTONISH.
SPM processing
The acquired images were processed according structural parametric mapping (SPM) procedure. SPM
software (ver. 8, http.//www.fil.ion.ucl.ac.uk/spm/) run on MathLab (ver. R2012a – 7.14.0.739). All the
images were extracted by processing workstation in DICOM format. The original dataset of Group C and
Group D was cropped to get the healthy brain volume. The DICOM file was converted in SPM header and
image files. The image file was spatially re-aligned with PET template included in SPM. The spatial re-
alignment was manually made. Then a normalization by the use of 4th degree B-spline interpolation and 8
mm-smooth of the image file were made on each image.
Normal Patients Database
In order to group the normal patients about gender, age or pathology, an Access (Microsoft Office ver. 2007)
database was created. The “controls group” was organized in 5 age classes: younger than 40 y, 40-50 y, 50-
60 y, 60-70 y and older than 70 y. The classification by age was performed both for normal and pathologic
patients. In SPM the normal patients group was created by using subjects of Group A, Group C and Group
D.
Statistical analysis
Intra-group SPM statistical analysis was performed for healthy subjects to test the homogeneity of the group.
The intra-group analysis was performed only for patients older than 70 years because most statistically
significant for cases’ number. Inter-group SPM analysis was done between pathologic patients and normal
ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
controls group. A two sample T-test analysis (p<0.001) was used in intra and inter-group analysis. SPM
results of inter-group analysis was matched with NM visual reports previously written by two blinded
experienced NM physicians.
Results
Intra-group SPM analysis of healthy patients older than 70 years (38 patients) showed statistically significant
differences in 16 cases. Therefore, these patients were excluded from normal database. Inter-group SPM
analysis of pathologic patients (15 cases) detected hypo-metabolic areas in any patient and was concordant in
all cases with NM visual reports.
Discussion
Our analysis showed that SPM software can be a valid tool to support the visual assessment of nuclear
medicine physicians. This result was in agreement with clinical validation of SPM performed by Signorini et
al [5]. In that study, the authors stated that it is possible to assess regional metabolic brain abnormalities with
SPM that is a fast procedure as required by clinical needs.
However, in our study an increase in the number of normal controls was requested in order to have a better
statistical significance. For this reason, whole body and HR head and neck PET/CT scans can be considered
useful studies to increase normal database.
The limits of our study were a limitation of the analysis to patients older than 70 years age and the number of
subjects in the same class.
This study introduced in clinical routine more attention about the inclusion of the brain in all whole body
acquisitions, especially in younger patients (< 50 years). This approach was in agreement with dosimetric
evaluation. Low-dose CT acquisitions were performed to all patients and in particular radiological
parameters were always modified in agreement with anatomical features and age of the patients.
Conclusion
Our study showed that: 1) a “normal database” can be increased by adding HR head and neck and whole
body PET/CT scans of non-neurological healthy subjects, without any technical problem; 2) SPM software,
with an “extended” normal database, represents a robust tool to support NM physicians visual analysis, in
particular for borderline cases; 3) the age differentiation is necessary, in order to obtain a meaningful
analysis of hypo-metabolic areas.
References
[1] Zeki S., Watson J.D.G., Lueck C.J., et al. 1991 A direct demonstration of functional specialization in
human visual cortex. J. Neurosci. 11(3):641-649.
[2] Friston K. J., Frith C.D., Liddle P.F. and Frackowiak R. S. J. 1993 Functional connectivity: The principal
component analysis of large (PET) dataset. J. Cereb. Blood Flow Metab. 13:5-14.
[3] Paulesu E., Frith C.D. and Frackowiak R. S. J. 1993 The neural correlates of the verbal component of
working memory. Nature 362:342-344.
[4] Perani D., Cappa S. F., Bettinardi V., Bressi S., Gorno-Tempini M., Matarrese M. and Fazio F. 1995
Different neural systems for the recognition of animals and man-made tools. Neuroreport 6(12):1637-41.
[5] Signorini M, Paulesu E, Friston K, Perani D, Colleluori A., Lucignani G, Grassi F, Bettinardi V,
Frackowiak R. S. J. and Fazio F. 1999 Rapid assessment of regional cerebral metabolic abnormalities in
single subjects with quantitative and nonquantitative [18F]FDG PET: A clinical validation of statistical
parametric mapping. NeuroImage 9: 63-80.

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Studio della dipendenza del Contrast Recovery Coefficent (CRC) in funzione dell’energia nelle
immagini di bremsstrahlung del fantoccio NEMA IEC standard riempito con Y-90 e acquisito con
SPECT-CT.

Energy dependence of Contrast Recovery Coefficient (CRC) of Y-90 bremsstrahlung images of NEMA
IEC phantom acquired with a SPECT-CT system
F. Bonutti1, A. Cecotti2, E.D. Schiava1, G. Magro3,4, L. Bastianutti2, D. Primossi2, D. Stanic2, M. Rossi2,
O.Geatti2, R. Padovani1.
(1) A.O.U. S. Maria della Misericordia, Medical Physics Dept., Udine - (2) A.O.U. S. Maria della
Misericordia, Nuclear Medicine Dept., Udine - (3) CNAO National Center for Oncological Hadrontherapy,
Pavia - (4) University of Pavia

Purpose: to analyze the energy dependence of the CRC on SPECT-CT bremsstrahlung images of the
NEMA-IEC phantom filled with Y-90.
Methods and materials: the optimization of SPECT-CT bremsstrahlung images on patients treated with Y-
90 microspheres is affected by the energy dependence of sensitivity, spatial resolution and contrast, [1]. We
already studied the spatial resolution, finding the best central energy at 140-150 keV. Here, we focused on
the CRC energy dependence. The NEMA-IEC phantom (PET/IEC-Body/P) filled with Y-90 was acquired
with a SPECT-CT system (Symbia, Siemens). The 6 spheres were prepared with an initial activity of 3.47
MBq/ml; the background compartment with 0.45 MBq/ml (R=7.8). One acquisition was made with a 64x64
matrix using 5 simultaneously energy windows centered on 110, 130, 149, 169 and 190 keV, and a second
acquisition using 4 simultaneous windows centered at 100, 150, 200 and 250 keV. Images were
reconstructed for each window with the OSEM Flash3D algorithm, 4 iteration., 6 subset. For each dataset, on
the central section of the spheres, 6 ROIs were drawn around the circumferences identified by CT, in order to
calculate the average number of counts. The latter quantity, for the background compartment, was calculated
inside a ROI drawn on the phantom boundary contour excluding the spheres contours. The CRCs were
evaluated for each window energy and sphere radius. Data coming from the 2 different acquisitions were
merged and weight-interpolated to figure out a global CRC behavior.
Results : between 100 and 200 keV larger spheres (I-II) show a slightly better CR around 150 keV, while for
the others (II-VI) CR is almost constant. CRC falls down at 250 keV, with a loss, compared with 150 keV,
which equals -31% (I sphere), -25% (II), -22% (III), -3% (IV).
Conclusion: we found a contrast loss for energies higher than 200 keV, mainly due to the increasing fraction
of bremsstrahlung photons passing through the collimator’s septa. Considering also what we found about the
spatial resolution, a good choice for the acquisition window is from 100 to 200 keV (HE collimators). In the
clinical routine we are currently using such energy window, divided into 5 equal-sized subwindows to
increase the attenuation correction accuracy.
References: [1] Elschot, M. et al., Quantitative Evaluation of Scintillation Camera Imaging Characteristics
of Isotopes Used in Liver Radioembolization, PLoS ONE 6(11): e26174. doi:10.1371/journal.pone.0026174.

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Somatostatin receptors’ detectability with SPECT acquisition :
comparison of two iterative reconstruction algorithms
F.Voltini, C.Canzi, F. Zito, G. Marotta, L.Florimonte, M. Schiavini and R. Benti

Nuclear Medicine Department, IRCCS Fondazione Ca’ Granda Ospedale Maggiore, Milan, Italy.
Aim
The choice of algorithm used for SPECT images reconstruction may be crucial for lesion detectability.
The aim of this work was to evaluate the performance in somatostatin receptors’ lesions detectability of two
iterative algorithms commercially available.
Material and Methods
γ-camera was used for data acquisition. SPECT patient examination was simulated using Alderson phantom
containing lungs, heart, liver and 8 spherical inserts reproduced tumoral foci: 2-thorax, 4-external wall of
111
liver, 2-abdomen. Mediastinum and abdomen were filled with In water solution with 0.59 kBq/ml, and
liver with 5.2 kBq/ml. Five lesions (1÷2ml) were filled with 74 kBq/ml and the smallest (0.5ml) with 444
kBq/ml . SPECT phantom acquisitions were performed by circular-orbits (CO) and body-contour (BC).
The iterative algorithm are: Osem-2D and FLH-3DTM. The reconstruction parameters were 20sub-sets
combined respectively with 5, 10, 15, 20,30 iterations (IT) and Gauss postfiltering.
The images were evaluated by two observers which detected the lesions and assigned to each of them a score
on 5 points scale, to grade the detectability from 1 (doubt) to 5 (very good). Fixed the orbits to analyze
differences between Osem-2D and Flash-3DTM with the same iterations, a paired t-test (PT1) was assessed
between correspondent scores of each lesion. The differences between studies OC and BC were examined
with paired t-test (PT2) between correspondent scores of each lesion for the sets of images reconstructed,
with the same algorithm and number IT. The mean value of scores assigned to each detected lesion, were
summarize as figure of merit (MSC) calculated as mean of the scores of each lesions detected for each set of
images reconstructed.
Images show the position of some lesions placed on: external wall of liver (EXLV), abdomen (ABD) and
thorax (TH).

EXLV
ABD
TH

ABD

ABD

ABD

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Results
The observers detected 6 foci of 8 for all sets of images for both the algorithms and both orbits. Two of three
lesions of 0.5 ml, adherent to the liver, were not recognized, while one close to the liver but not adherent was
identified. The test PT1 was significative (P<0.05) for all the sets of images considered while PT2 was
significative only for images reconstructed with 20IT and 30IT.
The lesions with volumes between 1÷2ml were always detected. The ranges of MSC values for images
reconstructed with different number of iterations with Osem-2D were for OC: 4÷4,2 for BC: 3,7÷3,8 while
for Flash-3DTM were for OC: 4,7÷4,8 and for BC: 4,0÷4,5. The highest values of MSC both for OC (4.2)
were reached for Osem-2D with 20IT while for Flash-3DTM with 10IT OC (4.8).

The tables show the results for the two observers.

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Conclusions

Flash-3D show better lesion detectability than OSEM-2D. SPECT examination with circular orbit and
Flash-3D are preferable for somatostatin receptors’ detectability, optimization of iterations is mandatory to
achieve the best image quality.
Further increase of iterations for both algorithms and particularly for Flash-3DTM and BC creates important
artefacts.

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Valutazione di un algoritmo di ricostruzione iterativo con recupero della risoluzione per SPECT-CT
miocardica di perfusione.

Evaluation of an iterative reconstruction algorithm with resolution recovery for SPECT-CT myocardial
perfusion imaging.
L. Gallo1, E. Bolla1, A. Ferretti1. E. Milan1
(1) O. “San Giacomo Apostolo” ULSS 8, Castelfranco Veneto (TV)
Purpose
Last generation iterative reconstruction algorithms for SPECT Myocardial Perfusion Imaging (MPI) can
incorporate a 3D modeling of collimator-detector response function, in order to correct for noise and resolution
degradation and they can implement correction for scatter and CT-based attenuation. These algorithms are at the
base of the feasibility of half-time or half-dose SPECT MPI [1]. The aim of this study was to evaluate a
commercial iterative algorithm with resolution recovery compared to standard methods. Evaluation regards image
quality and percentage contrast in presence of a known perfusion defect, by varying acquisition counts.
Methods and materials
A chest phantom with a cardiac insert was used. Into the left ventricle (LV) wall a small cold insert was placed to
simulate a perfusion defect of diameter 2 cm on middle portion, antero-lateral segment. LV wall was filled with a
solution of 99mTc of about 150 kBq/ml. Activity concentration was chosen to approach average clinical counts in a
ROI centered on heart. Inner cavity and space between LV and lungs were filled with water. Some water bags were
placed around phantom simulating breasts. The SPECT/CT system (GE Discovery NM/CT 670) was equipped with
a two-head SPECT system and a 16-slices CT scanner. Multiple acquisitions were made in L-mode, LEHR
collimators, gated, 90° orbit, 60 views, 64x64 matrix and time per view varying from 35 to 10 sec. Reference time
per view was 25 sec; activity concentration values for different time duration was normalized to this reference time.
A low dose CT scan was performed for attenuation correction. Data were reconstructed with Filtered Back
Projection (FBP) and with Iterative Reconstruction (IR). IR was performed with and without Attenuation and
Scatter Corrections (ACSC and NC), also with and without Resolution Recovery (RR). The reconstruction package
with Resolution Recovery used was the Myovation with Evolution for Cardiac (GE). ROIs were placed in short-
axis slices on perfusion defect, on inner cavity and on LV wall; ROIs were drown to respect real dimensions of
each phantom insert. Defect percentage contrast (Cdef%), inner cavity percentage contrast (Ccav%) and wall signal-
to-noise ratio (SNRwall) were calculated. Cdef(cav)% was calculated as
Cdef%= (PVm,wall – PVm,def(cav))/PVm,wall *100
were PVm,wall PVm,def(cav) are mean pixel values of the ROIs placed on LV wall and on cold defect (cold cavity),
respectively. Image quality was graded visually, from poor to excellent, by an expert nuclear medicine physician.

Results
Image quality.
Images corrected for attenuation and scatter appeared with a very uniform radioactivity distribution inside LV wall.
No differences were found in image quality scores for IRACSCRR series by decreasing counts until 37% of
average clinical counts.
Percentage contrast for small perfusion defect (cold insert).
How could be expected, the smallest Cdef% values was found for FBP series, from 40% down to 28% as the
acquisition time decreases. Evolution for Cardiac doesn’t affect FBP because it’s added to Iterative Reconstruction
package.
For IR series, Cdef% versus activity concentration resulted quite constant when RR is applied. Cdef% worse in IR
without RR series when the total counts decreased below 50% (figure 1). Resolution Recovery improved
percentage contrast. The highest value of Cdef% was obtained for IRNCRR series (59%).

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
About SNRwall we don’t found significant differences among reconstructed series. Mean values of SNRwall ranging
from 9 for FBP to 11.5 for IRNCRR.

Defect percentage contrast - IR series Defect percentage contrast - IR series


70.0 70.0

60.0 60.0

50.0 50.0
Cdef %

Cdef %
40.0 40.0
IRACSCRR
30.0 30.0 IRNCRR
IRACRR
20.0 20.0 IRNC
IRACSC
10.0 10.0
0% 20% 40% 60% 80% 100% 120% 140% 0% 20% 40% 60% 80% 100% 120% 140%
Normalized activity concentration (%) Normalized activity concentration (%)

A) B)
Figure 1. Percentage contrast for small cold insert versus normalized activity concentration for IR series. A)
corrected series B) non corrected series.

Percentage contrast for inner cavity.


In general, highest values of percentage contrast was found for inner cold cavity compared with Cdef%, because
cavity is much greater than cold defect, so mean pixel value in ROI was less affect by partial volume effect. The
highest value of Ccav% was found for IRACSCRR series (82%). (figure 2).

Cavity percentage contrast - IR series Cavity percentage contrast - IR series


90.0 90.0

80.0 80.0

70.0 70.0
Ccav%
Ccav%

60.0 60.0
IRACSCRR
50.0 50.0 IRNCRR
IRACRR
40.0 40.0 IRNC
IRACSC
30.0 30.0
0% 20% 40% 60% 80% 100% 120% 140% 0% 20% 40% 60% 80% 100% 120% 140%
Normalized activity concentration (%) Normalized activity concentration (%)

A) B)
Figure 2. Percentage contrast for inner cold cavity versus normalized activity concentration for IR series. A)
corrected series B) non corrected series.

Discussion
Data shown in figure 1 seem to contrast with data shown in figure 2 where corrected series give higher percent
contrast values than non-corrected series. A possible interpretation may be the fact that attenuation correction lead
to a counts distribution increase on LV radioactive wall and maybe a higher count spill-over on the small cold
insert region. Further investigations are needed to take into account for possible correlations with insert position
and dimension and with attenuation material distribution.
Resolution Recovery package effectively improve image quality and contrast that resulted quite constant until
activity reduction fell below 50%.

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Conclusion
IR improved percentage contrast compared to FBP. For time or dose reduction, the Resolution Recovery package
for SPECT/CT MPI permits to maintain both acceptable image quality and defect detectability, until count statistic
approach 40% of average clinical counts.

References

[1] I. Ali, Half-Time SPECT myocardial Perfusion Imaging with Attenuation Correction, J Nucl Med (2009) 50,
554-562.
[2] T. Belhocine, Half-time resolution recovery package for SPECT-CT MPI: A pilot study, J Nucl Med (2007) 48
(suppl), 234P.

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Utilizzo di un algoritmo di ricostruzione iterativo evoluto in una gamma camera cardiologica convenzionale.

An advanced iterative reconstruction method in a conventional cardiac gamma camera.


L. Pagan1, R. Soavi1.
(1) UO Fisica Sanitaria - Maggiore Hospital, AUSL Bologna

Purpose: the recent installation in our hospital of the system CARDIO MD III (Philips Healthcare), dedicated
cardiac gamma camera with conventional detectors (NaI (Tl)), but current hardware and software of the latest
generation, has given rise to a technical assessment that allows for opportunities to optimize the diagnostic
workflow, dose savings and reduced acquisition times.
Methods and materials: Gamma Cardio acceptance tests were performed according to the NEMA
recommendations. SPECT images reconstruction was carried out with both traditional algorithm (Filtered Back
Projection - FBP) and advanced iterative algorithm (Astonish Philips), following the manufacturer's
recommendations with regard to the number of iterations and subsets.
Results: the structural characteristics of the camera, especially the small size of the crystal and the technology of
the photomultipliers, led to a 35% increase in average sensitivity than other systems general purpose (GP-SPECT)
in the department (mean values: GP-SPECT = (71±4) cps/MBq, CARDIO MD = (96±4) cps/MBq).
The tomographic reconstruction of the images performed with iterative algorithm showed an average gain in spatial
resolution nearly two times compared with FBP reconstruction (average values: FWHM (FBP) = (9.7 ± 0.4) mm
FWHM (iterative) = (5.5 ± 0.6) mm). The sensitivity and image quality improvement allow the department to
manage and "personalize" patient exams in terms of suitable selection of acquisition time and administered activity.
In fact, decreasing the time or the activity, or a combination of both, the system is able to produce images of
diagnostic quality comparable with that of the other systems. Otherwise, for standard time and administered
activity, gamma Cardio MD provides better quality images.
These technical features in clinical practice resulting in a shorter acquisition time (up to 50% of the standard time),
with consequent reduction of costs and increase in productivity of the department, as well as a reduction of the
patient dose that can exceed 40%.
References:
[1] H. Hines et al., National Electrical Manufactures Association Recommendations for Implementing SPECT
Instrumentation Quality Control, J Nucl Med. (2000) 41, 383-389
[2] P. Knoll et al., Comparison of advanced iterative reconstruction methods for SPECT/TC, Z. Med. Phys. (2012)
22, 58-69
[3] O. Zoccarato, Innovative reconstruction algorithms in cardiac SPECT scintigraphy, Q J Nucl Med Mol Imaging
(2012) 56, 230-246

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
SUV evaluation in PET-CT tomograph and correlation with Quality Control measured parameters

M. Sireus1, A. Loi2, V. Fanti1, R. Marzeddu2, S. Aste2, F. Portesani2, M. Carta2, S. Serci2, P.G. Serra2, N. Pisu3, F.
Pesella3, F. Santagata3, P.F. Chapelle3, G. Melis3
(1) Università degli Studi di Cagliari – Dipartimento di Fisica
(2) Alliance Medical – Centro PET c/o Azienda Ospedaliera Brotzu – Cagliari,
(3) S.C. Medicina Nucleare Azienda Ospedaliera Brotzu - Cagliari

INTRODUCTION
Parameters measured in PET-CT scanners quality controls provide, according to NEMA-2001 protocol, values of
technical efficiency of our equipment without showing a direct correlation with its clinical use.
The SUV (Standardized Uptake Value) [1] is the only measurable parameter which plays a role in clinical ambit. It
is a semiquantitative value that allows to estimate the uptake of the radiopharmaceutical in different tissues of the
human body [2].
The SUV is defined as:

(1)

There are many factors that can affect the good measurement of SUV:
• the effect of partial volume;
• the spill-over effect;
• the shape and size of the ROI [3];
• the methods of image reconstruction and parameters of the used tomograph [4];
• the size of the patient [5].
The reproducibility of the result is then not very high. A proposal to reduce, at least, the influence of the partial
volume and spill-over effects is to correct the value obtained by the formula:

(2)

Where RC stands for Recovery Coefficient.


In our study we wonder how the evaluation of SUV can depend directly on the technical characteristics of the
machines, how the physicians are aware of the potentials and the limitations of the method and the technology in
their possession and if they are able to go behind the simple “numerical” results in the interpretation of the images.

METHODS AND MATERIALS


Once calibrated the PET-CT Discovery ST® scanner with the Well Counter, we proceed with our study. The idea
is to create a clinical situation, filling the four smaller spheres of IEC phantom [6] (10 mm, 13 mm, 17 mm, 22
mm) of a solution of and red dye so as to simulate hot zones. The two spheres of larger diameter (28 mm, 37
mm) are filled with physiological solution and blue dye so as to identify cold zones. The rest of the phantom is
injected with a concentration lower than that of the hot spheres. Table 1 shows the test conditions:
Acquisition number Acivity of the Total activity of the Theoretical SUV in

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
bachground (kBq) sphere (kBq) each sphere
1 (t= 0) 39552 860 21,7
2 (t= 82 min) 55714 588 10,7
3 (t= 150 min) 59275 333 5,7
Table 1- Activity and timing of SUV measures and its theoretical value.

The reports obtained and identified by fancy names (Goofy®- acquisition 1, Mickey Mouse®- acquisition 2,
Donald Duck®- acquisition 3) have been proposed for their analysis in the form of real patients to the nuclear
physicians in the PET center.

RESULTS
All physicians have shown the presence of the hot and cold lesions and the lung insert, bringing the following
values of the sizes of the lesions:

Graph 1- Dimensions of the lesions evaluated by the physicians for Goofy.

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Graph 2- Dimensions of the lesions evaluated by the physicians for Mickey Mouse.

Graph 3- Dimensions of the lesions evaluated by the physicians for Donald Duck.

The results obtained by the physicians are slightly different, depending on the used methods, and corrected when
we consider like error the limit related to the intrinsic spatial resolution of the instrument. If, in fact, we take into

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
account that the lesions aren’t at the center of the FOV (Field Of View), the spatial resolution will not be equal to
the maximum value given by the instrument (5 mm), but it will have already undergone a degradation.
As instead regards the measure of the SUV, the results obtained are presented in the graphs 4, 5, 6:

Graph 4- SUV values measured for Goofy compared to the true value.

Graph 5- SUV values measured for Mickey Mouse compared to the true value.

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Graph 6- SUV values measured for Donald Duck compared to the true value.

Analyzing the ratio between measured and theoretical SUV results in a similar logarithmic pattern for all the
phantoms and for all the physicians:

Graph 7- Values of relative Goofy’s SUV compared to true value.

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Graph 8- Values of relative Mickey Mouse’s SUV compared to true value.

Graph 9- Values of relative Donald Duck’s SUV compared to true value.

From our study it’s evident that the values of SUV, referring to the sphere of 10 mm, are far away from the real
value for all phantoms and for all physicians. The measured values are close to the real ones as the size of the
lesion increases: this occurs regardless of the used activity and of the physician who inspect the report. The error on
the evaluation of SUV is, on average, of 60% for the smallest sphere, with a tendency to decrease already from the
sphere of 13 mm (30%) up to the sphere of 17 mm (10%) and 22 mm (5%). This result is expected based on the
quality of image: the effects of partial volume and spill-over contribute to an incorrect assessment of the parameter,
especially for smaller lesions.
If we consider the activity normally injected to a patient of 70 Kg (370 MBq) and a concentration of activity equal
to that of the sphere of 1 cm of Donald Duck patient, we obtain a SUV theoretical

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
value of 6.4. This parameter, if measured by one of our physicians, is reduced by about half, leading to an
assessment of uncertain lesion or, at worst, cold lesion. For these values of activities, however, we get the NECR
(Noise Equivalent Count Rate) peak value of the tomograph: this corresponds to the maximum efficiency reached
by our instrument. Although the used scanner reflects the technical characteristic specified by the manufacturer,
then, the instrumental limits at the base of its functioning contribute heavily to an incorrect assessment of the SUV.
As regards the clinical evaluation of the lesions, we have obtained the same results for Goofy and Mickey Mouse:
Sphere 1 Sphere 2 Sphere 3 Sphere 4 Sphere 5 Sphere 6
Physician 1 hot hot hot hot cold cold
Physician 2 hot hot hot hot cold cold
Physician 3 hot hot hot hot cold cold
Physician 4 hot hot hot hot cold cold
Table 2- Lesion’s clinical evaluation by physicians for Goofy and Mickey Mouse.

For Donald Duck, instead, the results are:


Sphere 1 Sphere 2 Sphere 3 Sphere 4 Sphere 5 Sphere 6
Physician 1 uncertain hot hot hot cold cold
Physician 2 uncertain hot hot hot cold cold
Physician 3 cold uncertain hot hot cold cold
Physician 4 uncertain uncertain hot hot cold cold
Table 3- Lesion’s clinical evaluation by physicians for Donald Duck.

This differences are linked to the lower activity of the hot spheres that results in lower value of the SUV. More in
this case, the physicians have pointed the need to know the patient’s medical history to give a correct evaluation, as
it is, however, in a real case. Another aid to diagnosis is the exact anatomical location of the lesion: from here it is
easier to distinguish between a hot or cold lesion and an uncertain area affected by a phlogistic process that
corresponds to high absorption of activity. The SUV is, therefore, more inadequate where it would be necessary a
greater accuracy and reliability, that is, in the case of very small lesions.
Starting from the relation (2), we can calculate the RCs related to our measures as:

(3)

By averaging the values for each sphere, we obtain:


AVERAGE RCs (%) ERROR
Sphere 1 31,7 12,8
Sphere 2 66,1 13,3
Sphere 3 81,4 6,8
Sphere 4 87,3 5,9
Table 4- Average percentage RCs and their error.

Where the error is measured as the standard deviation of the distribution of the values for each sphere.

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Graph 10- Average percentage RC values for every sphere .

The average values of RCs and their errors decrease as the size of the sphere increases: this is correct since the
partial volume and spill-over effects are smaller just for the larger spheres and their SUV values need less
correction.
CONCLUSIONS
The reliability of the SUV as a semiquantitative parameter to measure the uptake in different tissues and, then, to
quantify the distinction between regular and hyperactive metabolism in an organism, isn’t very high. In light of the
obtained results, the SUV is a precise but inaccurate measurement. This problem is more evident where it would be
necessary to have a quantitative as well as qualitative evaluation, that is, for smaller lesions. Precisely for them the
measured SUV becomes highly unreliable and may be underestimated, as occurred in our study, even 50-60% for
lesions twice the spatial resolution of the scanner.
The first hoped goal is that the scientific community and the manufacturers conduct a research to ensure that the
measurement provided by the scanners is as reliable as possible, by changing, for example, the algorithm for
SUV’s computing.
Some limits, as shown, can be overcome with the use of RCs. Other possible way is, for example, the
normalization of the SUV’s measured values compared to those obtained for the healthy liver tissue, as advised by
the physicians that work in the center. The results obtained, in fact, have them stimulated to a greater insight into
the operations of the machine at their disposal.

REFERENCES
[1] JOSEPH A. THIE– Understanding the Standardized Uptake Value, Its Methods and Implication for Usage-
JNM, 2004
[2] HUANG SC- Anatomy of SUV. Standardized uptake value- Nucl Med Biol, 2000
[3] MARINKE WESTERTERP et al. – Quantification of FDG PET studies using standardized uptake values in
multi-centre trials: effects of image reconstruction, resolution and ROI definition parameters- EJNMM, 2007
[4] HEIKO SCHÖDER et al.– Clinical Implication of Different Image Reconstruction Parameters for Interpretation
of Whole-Body PET Studies in Cancer Patients– JNM, 2004
[5] CHUN K. KIM et al.– Standardized Uptake Values of FDG: Body Surface Area Correction is Preferable to
Body Weight Correction- JNM 1994
ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
[6] KIM GREER et al.- NEMA IEC Body Phantom Set User’s Manual– Data Spectrum Corporation, 2006.

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Accuracy of attenuation and scatter corrections in SPECT-CT Myocardial Imaging

C. Ghetti(1), F. Palleri(1), C. Cidda(2), G. Serreli(1), G.Baldari (2), L. Ruffini(2)


1
Servizio di Fisica Sanitaria, Azienda Ospedaliero-Universitaria, Parma, Italy
2
Servizio di Medicina Nucleare, Azienda Ospedaliero-Universitaria, Parma, Italy

Myocardial studies with integrated SPECT/TC systems can be corrected not only for scatter but also for
attenuation. In this work the accuracy of these corrections has been evaluated with a dedicated phantom.
We used a SPECT-PET/CT thorax phantom (Data Spectrum) to mimic a clinical condition of attenuation and
scatter. The phantom is provided with two cylinders that were filled with the same radioactive solution: one
positioned inside and the other outside the phantom. The phantom was scanned with Siemens Symbia T6 SPECT-
CT using the clinical acquisition protocol for myocardial studies. The radionuclides used for this investigation
were Tc-99m (396 MBq/l) and I-123 (162 MBq/l), that are commonly used in our Department to study myocardial
perfusion and cardiac autonomic innervation. In order to perform scatter correction the clinical protocols employ a
two-window and a three-window method for Tc-99m and I-123 respectively. Images were reconstructed using
Siemens Flash 3D, an OSEM-3D algorithm, which provides corrections of nuclear data for attenuation using CT
µ-maps and applies an addictive correction for scatter. We have performed three different reconstructions: without
corrections, applying the attenuation correction only and applying both the corrections for attenuation and scatter.
On the transverse images the percentage difference of the mean counts between the inner cylinder and the outer
were evaluated. Since in both cylinders the radioactive concentration is the same and the only difference is the
attenuation and scatter due to the water surrounding the inner cylinder, this percentage should be ideally zero.
Furthermore, reconstructions were performed using different combinations of iterations and subsets to evaluate
their effect on image corrections.
Without corrections, with attenuation correction only and with both attenuation and scatter corrections applied, the
percentage differences were respectively -77%,-27%,-10% for Tc-99m and -75%,-21%,-8% for I-123 with 8
iterations and 4 subsets (Fig.2). Increasing the number of iterations and subsets (8i/8s, 16i/8s, 16i/16s, 24i/16s) the
corrections were more accurate with percentage
differences ranging from –10% to –1% (24i/16s) for Tc-99m and from –8% to –1.6% (16i/16s) for I-123.
Myocardial images result slightly under-corrected for attenuation and scatter using the standard settings.
However, good results can be obtained increasing the number of iterations/subsets.

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Software di analisi dei logfiles prodotti dal ciclotrone della General Electric© MINItrace©
A. Loi1, R. Marzeddu1, S.Aste1, M. Carta1, F.Portesani1, S. Serci1
(1) Alliance Medical srl, Cagliari
Lo sviluppo della tecnica e dell’ingegneria degli acceleratori nel campo della ricerca della fisica delle particelle ha
portato anche allo sviluppo e commercializzazione di ciclotroni con prestazioni, dimensioni e costi tali da poter
essere installati all’interno di strutture ospedaliere. Questo ha consentito la diffusione della metodica diagnostica
PET (Positron Emission Tomography) nei servizi di medicina nucleare. La PET si basa sull’utilizzo di traccianti
marcati con radioisotopi + a breve emivita (18F, 11C, 13N, 15O), alcuni dei quali devono necessariamente
prodotti in loco attraverso il ciclotrone.
A partire dal febbraio del 2007 presso il Centro PET della Struttura Complessa di Medicina Nucleare dell’Azienda
Ospedaliera “Brotzu” (A.O.B.) di Cagliari è in funzione un ciclotrone MINItrace della General Electric (GE). Tale
sistema è utilizzato per produzione di 18F e 11C con i quali, data la contemporanea presenza dei laboratori per la
sintesi e controllo di qualità, vengono sintetizzati i radiofarmaci 18F-FDG e 11C-colina utilizzati presso i servizi di
diagnostica PET delle strutture di Medicina Nucleare della A.O.B e dell’ospedale oncologico “A. Businco”.
I tecnici addetti alla gestione del ciclotrone hanno anche il compito di valutarne il funzionamento. Per ottimizzare il
controllo e il monitoraggio del sistema è stato sviluppato un software che consente di elaborare graficamente e
numericamente i dati di ciascun irraggiamento e di memorizzarli. La possibilità di effettuare delle analisi sulla
evoluzione temporale dei parametri consente di caratterizzare particolari stati del sistema: in particolare si possono
studiare le eventuali relazioni tra anomalie o guasti e l’andamento di determinati parametri al fine di poter
prevedere il verificarsi di un determinato guasto.
Il sistema MINItrace è composto da un ciclotrone auto-schermato da 9,6 MeV per protoni e dall’insieme dei sotto-
sistemi necessari al suo funzionamento quali l’unità di controllo generale, i sistemi da vuoto e di raffreddamento e
il generatore di radiofrequenza. Il ciclotrone in senso stretto consiste in un camera di accelerazione cilindrica per
ioni H- a sviluppo verticale (del diametro di circa 90 cm e altezza 20 cm) posta tra le espansioni polari di un
elettromagnete tipo Azimuthally Varying Fiernd (AVF). Il campo magnetico medio all’interno della camera è pari
a circa 1.6 T mentre il grado di vuoto raggiunge 9x10-8 mbar. All’interno della camera sono disposti due elettrodi
(dees) alimentati con un segnale ad alta frequenza di modulo 35 kV e frequenza 101 MHz. La combinazione del
segnale di radiofrequenza e del campo magnetico fanno si che gli ioni H- si muovano in un’orbita a spirale di
raggio crescente, aumentando la loro energia cinetica ad ogni orbita di circa 25 keV. Una volta raggiunta la parte
più esterna della camera, gli ioni H- vengono tramutati in protoni per effetto del passaggio attraverso un sottile
foglio di grafite (stripping) e deflessi verso uno dei bersagli (target) disposti sul fianco esterno della camera.
L’interazione dei protoni ad alta energia (9,6 MeV) con il mezzo (liquido o gassoso) di riempimento del target
genera i radioisotopi β+ utilizzati per la marcatura dei radiofarmaci PET.
Nel sistema MINItrace la camera di accelerazione e i target sono inseriti all’interno di un involucro di cemento
borato che limita notevolmente l’emissione di fotoni gamma, particelle alfa e neutroni assicurando un rateo
inferiore a 10 uSv/h ad 1 m, con 50 uA di corrente sul target 18F(1). Le dimensioni ridotte e l’autoschermatura
consentono l’inserimento del sistema in locali di dimensioni contenute. Il funzionamento del sistema di
accelerazione richiede inoltre una serie di servizi accessori quali sicurezze, monitoraggio ambientale e circuito di
raffreddamento e ventilazione appositi il cui buon funzionamento è necessario per garantire l’operatività del
ciclotrone.
L’operatore del ciclotrone ha il compito di seguire il funzionamento del ciclotrone durante la fase di irraggiamento.
Attraverso la consolle di gestione del ciclotrone chiamata Master System (MS) è possibile monitorare in tempo
reale l’andamento di un set di parametri di funzionamento del sistema tra cui corrente e le tensione della sorgente di
ioni, corrente del magnete, frequenza del segnale RF, tensione delle dees, correnti del foil di estrazione, dei
collimatori e dei target, pressione della camera. Per quanto l’operatore possa seguire con attenzione le variazioni
dei suddetti parametri è difficoltoso valutare il loro evolversi durante l’intero irraggiamento a meno di evidenti
ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
anomalie. Per ogni bombardamento viene generato un file di testo (logfile) in cui sono memorizzati la sequenza dei
valori dei parametri di irraggiamento, aggiornati ogni 2 secondi circa, pertanto attraverso una analisi a posteriori
dei logfiles l’operatore ha la possibilità di fare una valutazione più approfondita dell’andamento dei parametri di
irraggiamento e individuare anomalie, segnali di malfunzionamento o indicativi dell’usura di sottosistema.
Sebbene i logfiles possano essere visualizzati direttamente sulla consolle MS non viene fornito uno strumento di
analisi grafica e statistica dedicato. L’operatore ha solo la possibilità di scorrere la sequenza di valori cercando
eventuali irregolarità e di dare un giudizio di massima sull’andamento dell’irraggiamento. Al fine di rendere più
efficace ed oggettivo il controllo e la valutazione del funzionamento del sistema è stato sviluppato un software
dedicato all’analisi statistica e grafica dei dati contenuti nei logfiles con lo scopo di verificare il corretto
funzionamento del sistema o individuare eventuali anomalie e segnali di usura..
Il software è stato sviluppato in ambiente Microsoft Excel e consiste in un foglio di calcolo, utilizzato per la
gestione dei dati e dei grafici, e dall’insieme dei sottoprogrammi (macro) sviluppati per automatizzare le operazioni
di importazione del file, di elaborazione, di calcolo, di gestione dei grafici e di archiviazione. Le macro sono scritte
nel linguaggio VBA (Visual Basic for Applications) ovvero una implementazione del Visual Basic integrata in
Excel che consente di sfruttare le proprietà tipiche di un linguaggio di programmazione ad alto livello per creare
interfacce grafiche personalizzate e gestire attraverso il codice tutti gli oggetti di Excel. L’utilizzo del VBA ha
consentito di automatizzare le procedure di analisi e archiviazione dei dati e di facilitare la gestione dei grafici.
Attraverso l’importazione dei logfiles, l’operatore ha la possibilità di generare un report di irraggiamento
contenente i valori statistici più rappresentativi per ciascuno dei parametri acquisiti durante il bombardamento ed
elaborare grafici e report relativi all’andamento dei parametri in un determinato intervallo temporale, evidenziando
eventuali derive anomale. La valutazione viene basata sull’osservazione dei valori statistici dei parametri di
controllo ovvero sul loro confronto con dei valori di riferimento (ottenuti da bombardamenti con il sistema in
buone condizioni) e sul loro andamento nel tempo. In particolare l’analisi di determinati trend temporali può essere
associato a dei guasti o degradazioni specifiche consentendo di prevenire la richiesta di manutenzione.
Il software sin qui sviluppato viene utilizzato per il controllo giornaliero del funzionamento del sistema
consentendo di correggere gli eventuali errori o anomalie, apportare migliorie e individuare nuove funzionalità.
Inoltre è stato utilizzato per analizzare l’andamento temporale della tensione e della corrente della sorgente di ioni
in coincidenza dei guasti occorsi nell’ultimo anno. Sono stati evidenziati il ripetersi di due diversi trend evolutivi
precedenti al blocco del dispositivo e riconducibili a due diverse modalità di guasto.

Il software oggetto di questa tesi è stato sviluppato per ottimizzare e migliorare le procedura di acquisizione,
gestione e analisi dei dati contenuti nei logfiles. La possibilità di archiviare una elevata quantità di dati e di poterle
incrociare tra loro lo rende uno strumento utile e potente nell’analisi dei malfunzionamenti e della loro
caratterizzazione. I risultati ottenuti dall’analisi dei dati relativi ai più recenti guasti occorsi alla sorgente di ioni
hanno consentito di caratterizzare l’evoluzione dei parametri prima del blocco e quindi di stabilire delle
connessioni tra guasto e specifiche evoluzioni dei parametri operativi. L’estensione di questi studi agli altri
sottosistemi del ciclotrone potrebbe consentire di caratterizzare altre tipologie di guasti suggerendo con anticipo la
necessità di una manutenzione. La scoperta di tali associazioni aprirebbe alla possibilità di individuare con anticipo
il verificarsi di un certo guasto e alla possibilità di pianificare le necessarie manutenzioni. In alcuni casi, si avrebbe
il grande vantaggio di poter ridurre o eliminare i giorni di fermo macchina, limitando i disagi legati alla
sospensione del servizio diagnostico PET.

Riferimenti:
[1] R. Marzeddu, Sviluppo di un software di controllo e analisi del funzionamento del ciclotrone GE MINItrace™,
Tesi di specializzazione in Fisica Medica (2013)

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Clinical evaluation of 3D-OSEM iterative reconstruction for SPECT myocardial imaging.

C.Ghetti1, F.Palleri1, G.Serreli1, C.Cidda2, G.Baldari2, L.Ruffini2, F.Zavoli2


1
Servizio di Fisica Sanitaria, Azienda Ospedaliero-Universitaria, Parma, Italy
2
Dipartimento di Diagnostica per Immagini, Azienda Ospedaliero-Universitaria, Parma, Italy

The clinical impact of a 3-D OSEM (ordered-subsets expectation-maximization) algorithm in myocardial SPECT
imaging has been investigated. Image quality and interpretation of myocardial functionality of iterative
reconstructions (IR) have been compared to standard Filtered back-projection (FBP). In addition, the effect of
increasing the number of iterations has been evaluated.
Myocardial SPECT studies of 30 patients (15 males and 15 females with age ranging from 40 to 80 year) randomly
selected, have been retrospectively analyzed.
All patients had a 2 day stress-rest protocol with Tc-99m MIBI (740 MBq injected for each scan). SPECT was
performed using Siemens Symbia T6 SPECT-CT with a 90° detectors configuration, non circular orbit, high
resolution collimators, 32 views, 64x64 matrix, 25 s/view. Images were processed with FBP and with an innovative
3D-OSEM algorithm, Flash 3D (Siemens). This software incorporates a 3D parallel hole collimation model. Three
iterative reconstructions have been performed using different combinations of iterations and subsets : 8i/4s(default
settings), 16i/8s and 24i/16s for a total of 120 reconstructions (4 for patient), each containing stress and rest
datasets.
Three expert Nuclear Medicine Physicians of our Department, blinded to clinical data, evaluated all reconstructions
by giving a subjective rating to image quality from 1 (enought) to 3 (excellent). They also made a diagnosis on
myocardial perfusion abnormalities, negative or positive according to the presence of a reversible or irreversible
perfusion defect.
All physicians gave the best scores to images processed with FBP. Iterative reconstructions performed with 8i/4s
demonstrated similar results while increasing the number of iterations scores got worse.
Physicians gave interpretations on IR8i/4s, IR16i/8s, IR24i/16s different from FBP in the following percentage of
cases: 10%, 7%, 10% (phys 1), 7%, 10%, 20% (phys 2), 10, 27%, and 43 % (phys 3).
FBP reconstructions demonstrated a superior subjective quality; 3D OSEM iterative reconstructions with default
settings gave performances similar to FBP while iterative reconstructions with an increased number of iterations
got worse assessments probably because they appear less familiar.
In about 80% of discrepancies the diagnosis made on IR lead to false positive diagnosis. As a consequence, the use
of a 3D Osem algorithm for myocardial perfusion images may result misleading.

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Optimization and personalization of radiopharmaceuticals in Nuclear Medicine: the experience of Trento

R. Visentin1, S. Agostini2, F. Chierichetti2, A. Valentini1

(1) Medical Physics Service – A.P.S.S. of Trento – Trento, (2) Nuclear Medicine Department - S. Chiara Hospital
of Trento– A.P.S.S.di Trento

Purpose: We describe planning, structural and organizational changes introduced in the Nuclear Medicine
Department of S.Chiara Hospital in Trento, to fulfill the requirements introduced by NBP-MN, in compliance with
the ALARA principle and the radioprotection (RP) standards. This to improve the diagnostic quality and efficacy,
to avoid unnecessary patient exposure to radiation, in compliance with safety standards.

Methods and materials: legislative alignment has resulted in:


- planning and restructuring of our radiopharmacy. The areas are compartmentalized
(preparations/control/extemporaneous preparations) and classified according to GMP standards and RP
directions;
- acquisition of devices for the manufacturing of radiopharmaceuticals (RF) (shielded hot cells and isolator in
Class A-GMP) and for quality controls (QC) (activimeters, radiochromatograph, etc.);
- implementation and customization of a software integrated with our RIS, which allows traceability of the
whole process, from the materials acquisition to the single customized administration;
- redefinition of the QC program;
- revision of the procedures for the management of radioactive material from the acceptance to the waste
disposal;
- equipment of laboratory to perform QC, including chemical waste management;
- definition and implementation of RF specifications and QC procedures before the administration to the patient
of a custom task;
- training in RF specific aspects to all the personnel involved in production, QC tests and release of final
products;
- implementation of algorithms for customizing the administered activity to the type of examination and RF,
taking into account age, medical condition, sex and body surface area of patients. The efficacy of our
algorithms in terms of diagnostic efficacy in vivo with phantoms is evaluating;
- application of qualification and validation principles were performed for all critical instrumentations.
Results: radioactive products are manufactured in a controlled (environmental and radioactive) areas. All steps
take place in self-contained and dedicated facilities to radiopharmaceuticals. A program for QC is active. A
qualification of critical instrumentations is followed.
Conclusion: adjustment according to regulatory procedures of the premises for manufacturing RF has provided a
structural and functional reorganization involving ambient, work, personnel and procedures. The optimization and
the global quality improved.
Bibliografia
[1] NBP- MN: Norme di Buona Preparazione dei Radiofarmaci in Medicina Nucleare, FUI XII ed.
[2] I Supplemento della XI Edizione della Farmacopea Italiana pag. 1533-1541 Norme di Buona preparazione
dei Radiofarmaci in Medicina Nucleare
[3] Linee Guida per l'applicazione delle norme di buona preparazione dei radiofarmaci in medicina nucleare
Suppl. Ord. alla G.U. della Repubblica Italiana, n. 274 del 23/11/2010 - Serie generale
[4] GMP - Good manufacturing practice
[5] Decreto Legislativo del Governo 17 marzo 1995 n° 230 modificato dal D.Lgs. 26 maggio 2000, n. 187, dal
D.Lgs. 26 maggio 2000, n. 241 dal D.Lgs. 9 maggio 2001, n. 257 dal D.Lgs. 26 marzo 2001, n.151 e dalla
Legge 1 marzo 2002, n. 39 "Attuazione delle direttive 89/618/Euratom, 90/641/Euratom, 92/3/Euratom e
96/29/Euratom in materia di radiazioni ionizzanti."

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
[6] D.Lgs n. 187 del 26 maggio 2000, n. 187. Attuazione della Direttiva 97/43 EURATOM, in materia di
protezione sanitaria delle persone contro i pericoli delle radiazioni ionizzanti connesse ad esposizioni
mediche. Suppl. Ord. alla G.U. n. 157 del 7/7/2000
[7] Documenti AIMN
[8] DPR 14 gennaio 1997. Approvazione dell’atto di indirizzo e coordinamento alle regioni e alle province
autonome in materia di requisiti strutturali, tecnologici e organizzativi per l’esercizio delle attività sanitarie
da parte delle strutture pubbliche e private. Suppl. Ord. n. 42 G.U. 20/2/1997
[9] D.M. 19 novembre 2003. Attività di preparazione del radiofarmaco. G.U. n. 15 del 20/1/2004
[10] ICRP Publication 75.Ann. ICRP 27 (1), 1997 General Principles for Radiation Protection of Workers
[11] Norma UNI 10491 – nov 1995. “Criteri per la costruzione di installazioni adibite alla manipolazione di
sorgenti radioattive non sigillate”.

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Dosimetria al midollo rosso nella terapia con radioiodio del carcinoma differenziato della tiroide
metastatico: confronto in pazienti pluritrattati

Red marrow dosimetry in radioiodine therapy of metastatic differentiated thyroid carcinoma: comparison
in patients with repeated treatments

E. Richetta1, A. Giostra1, A. Miranti1, E. Gino1, F. Maimone1, F. Dutto2, M. Ariano2, N. Migliore2, R.E. Pellerito2,
M. Stasi2.
(1) Medical Physics Department, A.O. Ordine Mauriziano, Torino
(2) Nuclear Medicine Department, A.O. Ordine Mauriziano, Torino

Purpose: Administered activity of 131I in metastatic differentiated thyroid carcinoma is often limited by
haematological toxicity related to dose delivered to red marrow. In our institution the Italian Multicentrical AIFM
Protocol [1,2] are routinely applied for pre-treatment and in therapy red marrow and blood dose evaluations since
2009. The comparison in patients with repeated treatments allows to evaluate repeatability and uncertainty, in order
to perform safe activity’s escalation.
Methods and materials: Pre-treatment dosimetry is performed one week before therapy by administering an oral
trace activity (mean 23.6, 11.4 - 74 MBq). Blood samples and AP-PA whole body (WB) measurements are
performed at 2, 24, 48, 96 h. For in therapy dosimetry, detectors placed on patient’s beds provided WB AP counts
(every 2 h, 0 -72h) while blood samples were acquired at 2, 24, 48, 72h after therapeutic administration (mean
6920, 1857 - 9210 MBq). Doses were collected in a homemade database: patients with more than 2 dosimetry were
extracted. 17 patients underwent overall 60 dosimetry (26 pre-treatment, 34 in therapy). Dose per unit of activity
(Gy/MBq) to red marrow and to blood were calculated: for each patient relative variation among pre-treatment
values as well as in therapy results were evaluated. Patient’s relative variations as function of time were analyzed.
Results: Dose per unit of activity showed to be variable in time and it isn’t possible to find a constant value during
the clinical history of patients. The mean(±1STD) of pre-treatments variations are (-22.0 ± 23.9 %) for dose to
blood and (-18.3 ± 29.6 and -19.4 ± 28.1 %) for red marrow (AIFM and Traino methods). In therapy variations
showed to be smaller (blood: 8.0 ± 28.1 %, red marrow: AIFM 5.7 ± 25.9 %, Traino 5.8 ± 26.3 %). Also pre-
treatment versus in therapy mean shift is significant (blood: 13.3 ± 26.9 %, red marrow AIFM 8.7 ± 24.3 %, red
marrow Traino 9.3 ± 24.3 %). Dose (Gy/MBq) decreases over time in 65 % of cases: red marrow mean value
(±1St.Dev.) -24.2 ± 21 % and increase in 35 % (+33.3 ± 33 %).
Conclusion: High doses variation in time suggests to repeat pre and in therapy dosimetry every new radioiodine
treatment. Correlation with hormonal parameters must be further investigated.
References:
[1] AIFM “Dosimetria durante terapia di carcinoma differenziato della tiroide metastatico: protocollo
dosimetrico”
[2] EAMN Dosimetry Committee guidelines for bone marrow and whole-body dosimetry

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Influenza del metodo di calcolo dei fattori S a livello di voxel su distribuzioni di dose 3D in radioterapia
metabolica.

Impact of the method for calculating voxel S-values on 3D dose distributions in radionuclide
therapy

Pacilio M1, Cremonesi M2, Amato E3, Botta F2, Cornejo Díaz N4, Torres Aroche LA5, Coca Perez MA5,
Vergara Gil A4, Basile C1, Lanconelli N6
1
San Camillo Forlanini Hospital, Rome, Italy, 2European Institute of Oncology, Milan, Italy, 3University
of Messina, Messina, Italy, 4Centre for Radiological Protection and Hygiene, Havana, Cuba, 5Centre for
Clinical Research, Havana, Cuba, 6University “Alma Mater Studiorum”, Bologna, Italy.

AIM-Voxel dosimetry by MIRD formalism requires extensive calculations of voxel S-values (VSVs), due to
different geometries, reconstruction matrices and zoom factors. Alternatively to Monte Carlo (MC) simulations,
VSVs can be calculated by Dose Point Kernel (DPK) convolution, and analytical models (AMs). 3D-dosimetry can
be also performed with Local Energy Deposition (LED), or a rescaled LED method recently proposed. The aim of
this study is to investigate the influence of calculation methods on the 3D-dosimetry.
MATERIALS & METHODS-VSVs were calculated for soft tissue by DPK convolution using published data for
water (Cross, AECL–Report 1992; Furhang et al, Med Phys 1996), and by analytically modelling the deposited
energy as a function of the distance (Amato et al, Med Phys 2012). Dosimetry was also performed with LED, or
with a novel method (NM) proposed by Traino et al (Med Phys 2013), based on rescaled OLINDA/EXM self-
irradiation S-factors for the sphere model. Soft tissue spheroidal clusters with uniform activity distributions and
various masses were simulated by the software CALDOSE (Pacilio et al, Med Phys 2009). Moreover, 10
treatments with 90Y derivatives (voxel size: 4.42 mm) were considered for comparisons in clinical settings. An
IDL-based software (Torres Aroche et al, ALASBIMN Journal 2011) was used for 3D-dosimetry, and VSVs from
the website www.medphys.it were assumed as reference. Comparisons were performed for: 1) doses associated to
95%, or 50% of the volume (D95%, or D50%) in cumulative DVHs, and 2) dose profiles. For clinical cases,
volumes of interest (VOIs) were defined by isocount levels of 10%, 30% and 50% of the maximum count.
RESULTS-For system models, the DPK method evidenced D95%, and D50% differences in the range (-1.5%/0%),
for 131I, 188Re, and 90Y (always negative). Differences for the AM ranged between -3.4% and 4.4%. Clinical
dosimetry yielded D95% and D50% differences down to -1.7% for DPK, -3.5% for AM, between -3.0% and 2.7%
for NM and up to 2.7% for LED. Differences of dose profiles with reference data (for doses>10Gy) were
systematic for DPK (about -1.7%) and AM (-3.5%), or between -20% to 10% for LED and NM. LED and NM
dose profiles were identical in some cases, or rescaled by a constant value in others.
CONCLUSION-Dosimetric estimates was scarcely affected by using either the DPK or the AM method. For 90Y
treatments, LED and NM yielded very similar results, with higher differences with respect to reference data.

ELENCO
 
TOPIC ESC
 
  MEDICINA LA FISICA MEDICA
RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
  RICERCA NUCLEARE
SANITARIE
 
Red Marrow Dosimetry in Radioiodine Treatment of Differentiated Thyroid Carcinoma (DTC): Pre-
Treatment Versus In-Therapy Results

Dosimetria al midollo rosso per pazienti affetti da carcinoma differenziato della tiroide: confronto dei
risultati pre-terapia e in corso di trattamento
A. Miranti1, A. Giostra1, E. Richetta1, E. Gino1, C. Tessarin1; C. Ferrettini 2; M. Ariano2; C. Agrusa2; A.
Codegone2; R.E. Pellerito2; M. Stasi1
(1) Medical Physics Department, AO Mauriziano Hospital of Turin, Italy
(2) Nuclear Medicine Department, AO Mauriziano Hospital of Turin, Italy
Introduction: Differentiated Thyroid Carcinoma (DTC) is a relatively rare malignancy with about 30% of patients
who present recurrences and about 15% who develop distant metastases; 50% of them die within 5 years because
of metastatic disease. DTC is well managed by using surgery followed by metabolic radiotherapy with radioiodine
(I-131), the latter one being the preferred therapeutic option in case of unresectable metastases.
Despite the long experience in I-131 metabolic radiotherapy of thyroid tumors, the main approach to I-131 therapy
still consists in the administration of fixed activities to patients; dosimetric methods for the estimation of the
therapeutic activity to be administered are based either on the calculation of the dose delivered to lesions or on the
estimation of radiation dose absorbed by healthy organs and tissues, in order to avoid toxicity to Organs At Risk
(OARs) while escalating the administered activity. Red marrow (RM) is, for most of the patients, the main OAR
influencing the Maximum Administrable Activity (MAA), with a maximum tolerable dose generally assumed
equal to 2 Gy. Lung is also OAR in case of diffuse lung metastases, and MAA is estimated by means of a pre-
treatment (PT) dosimetric study.
The aim of this work is to study the predictive power of PT dosimetry compared to in-therapy (IT) dosimetry, in
order to establish the amount of uncertainty which needs to be considered when choosing MAA on the basis of PT
dosimetric results. On this purpose, we compared PT dose estimation to RM to the dose actually absorbed IT.
Methods and materials: AO Mauriziano Hospital of Turin applied, in 2008, to the dosimetric protocol of the
Internal Dosimetry group of AIFM [1]. Materials and methods used to evaluate RM dose have been borrowed by
the protocol and adapted to the routine of our center, where RM dosimetry is routinely performed both in a PT
diagnostic phase and during treatment, with about two patients per week who undergo dosimetric studies.
Nuclear Medicine physicians select for dosimetry those patients who has a persistent disease, already treated by
using I-131, and those patients who have metastases, in order to evaluate the possibility of administering higher I-
131 activities avoiding OAR toxicities due to high I-131 uptake or high residence time. Patients have to suspend
assumption of thyroid hormone pharmaceuticals and iodine through diet 4 weeks prior to PT dosimetry, i.e. 5
weeks prior to IT dosimetry. Among these patients, for the present study we selected only those patients who
performed both PT and IT dosimetries, at a distance of 7±1 days, following the procedures described hereinafter.
RM dosimetry requires whole body (WB) measurements, in order to estimate the cross dose received by RM from
the rest of the body, and blood I-131 concentration data, which is descriptive of the dose self-absorbed by RM.
For PT dosimetry, each patient orally receives a diagnostic activity (15 MBq) of [131I]-iodide. Blood samples are
withdrawn at 2, 24, 48, 62 and 96 or 165 hours after activity administration, measured with a NaI well counter,
converted to activity by applying a calibration curve and corrected by physical decay to the time of withdrawal.
WB counts are collected at 2, 24, 48, 62 and 96 hours after activity administration with a NaI counter placed at a
distance of 3 m from patient’s body, both in Antero/Posterior and in Postero/Anterior directions. The final WB
measurement is the geometrical mean of the two projections.
During therapy, WB measurements are performed by using a system of Geiger counter hanging on the ceiling on
patients’ beds, at a distance from the WB of 2.50 m, every 2 hours, from 8 AM to 10 PM. The WB retention
function was assumed to be a bi-exponential curve, while cumulated activity in blood per ml was estimated by
fitting data using a mono-exponential function.

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
We used two different formulas to evaluate RM and blood dose. Both of them rely on the same acquired data, but
differ in the approach to patient specific S-value definition: AIFM formula linearly scale S-values to patient-
specific RM mass, while EANM formula calculates absorbed dose to blood linearly scaling S-factors.
Uncertainties of absorbed dose calculation by internally retained radionuclides are difficult to estimate, therefore
uncertainty in the order of magnitude of 10-20%, reported by Stabin, are considered to be appropriate and must be
associated to the presented data.
PT and IT dosimetries have been normalized to the administered activity and then the relative percentage dose
difference (%DD) and the absolute percentage dose difference (%DDAbs) were calculated. This analysis has been
performed also for the single dose contributions of blood (BDC) and WB (WBDC).
Correlation analysis with %DD and age at the time of the diagnosis (patients’ grouped by 20-50, 51-65, >65 years),
WB weight (≤80 kg, >80 kg), patients’ sex, presence and site of metastases was performed with an ANOVA
(ANalysis Of VAriance) method.
Results: In the period September 2008-March 2013, 284 dosimetries have been performed on more than 200
patients. Among this dataset, for the present work 47 patients have been selected for analysis, for a total amount of
53 PT and 53 IT dosimetries, on the basis of the selection criteria previously reported.
Selected patients are mostly female (55%), with a mean(±SD) age of 56±15 years, range (20÷84), mostly affected
by papillary cancer (51%), followed by follicular cancer (32%) and poorly differentiated cancer (17%). Only a
small group of patients was not affected by metastatic disease (8 patients), while focal lung metastases were found
in 16 patients, diffuse lung metastases in 9 patients, single bone metastases in 5 patients, multiple bone metastases
in 3 patients and lymph-node metastases in 8 patients.
Analyzed patients received a median[25-75 percentile] activity of 16[15.7-16.7] MBq, during PT dosimetry, and
7424[7223-7448] MBq, during IT dosimetry. Appling EAMN method a median[25-75 percentile] PT and IT RM
dose of 8.2[6.8-11]·10-5 Gy/MBq and 8.8[7.5-11]·10-5 Gy/MBq respectively were obtained; with AIFM method a
median[25-75 percentile] PT and IT RM dose of 6.6[5.1-7.8]·10-5 Gy/MBq and 6.6[5.5-8]·10-5 Gy/MBq were
found.
Wilcoxon t-test between the whole population of PT vs IT normalized RM doses showed a statistically significant
difference between the two groups. The same results were obtained for the single BDC and WBDC as well.
The median[25-75 percentile] %DDAbs between PT and IT dosimetric results is 14.7[7.1-29.4]% for EANM method
and 12.1[6.9-22.9]% for AIFM method. BDC is, on average, 16% higher, while WBDC is 7% lower, during IT
compared to PT dosimetry for all of the calculation methods.
Correlation analysis showed a statistically significant (p<0.05) %DDAbs between male and female patients with
EANM formula, while, when using AIFM formula, patients with focal lung metastases have a statistically
significant lower (p<0.05) %DDAbs from those affected by multiple bone metastases and by multiple metastases.
Discussions: Wilcoxon t-test highlighted the statistically significant difference between PT and IT kinetics. The
slope of the lines interpolating IT vs PT total normalized doses and BDC was always > 1.1, while for WBDC it is
about 0.9, confirming that total doses and BDC are higher during therapy, while WB cumulated activity is lower.
As a consequence, %DD between PT and IT dosimetries are, on average, positive. This result may be explained by
a stunning effect, since WB uptake is reduced during IT compared to PT dosimetry, and in the meanwhile activity
is released in the blood, causing a higher blood retained activity and an overall RM higher radiation dose. For the
others, differences in serum TSH levels between the fourth (PT dosimetry) and the fifth (IT dosimetry) week may
explain observed dose discrepancy. High R2 values for total dose (>0.7) and WBDC (R2>0.8) show the potential
correlation between the two kinetics, while data on BDC are more dispersed, as confirmed by lower R2 values
(<0.7).
Observed %DD are, on average, in the order of magnitude of the uncertainties of the dosimetric method, therefore
they may be related to the intrinsic limitations of the applied dosimetric methodology.
The study of correlation aimed to investigate whether there are patients for whom PT dosimetry is less predictive in
the evaluation of the MAA. Unfortunately, this study gave only small indications: correlation of %DD with sex
may be explained by the discrepancy between the standard male model used for S-factors modeling and the men
ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
who underwent dosimetries; the significantly different %DD between those patients affected by lung metastases
compared to patients with bone or multiple metastases, for whom %DD is higher, was observed only for AIFM
formula, where WBDC is higher. This result is probably related to patients’ compliance. Correlation study may be
improved, and different results may be observed, by the enlargement of patients’ dataset and the different
stratification of patients into more and different classes.
Dosimetric approach determining individual MAA may reduce toxicity in patients for whom fixed activities are not
safe while improving effectiveness of the therapy, although the latter purpose still need to be validly demonstrated
by clinical data. As well, it is not clear whether PT dosimetry is capable to cause stunning effect, reducing I-131
therapeutic activity uptake.
Dose assessment in nuclear medicine is affected by large evaluation errors and requires long times and great
compliance by both patients and hospital’s staff. Nevertheless, internal dosimetry procedures and our scientific
knowledge regarding dosimetric approach to therapy may be improved by the implementation of widely accepted
dosimetric protocols.

References:
[1] Chiesa C. et al., Dosimetria durante terapia del carcinoma differenziato della tiroide metastatico. Protocollo
Dosimetrico. 2008

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Dosimetria SIRT a livello di voxel come strumento di lavoro: verso un nuovo standard?

SIRT voxel dosimetry as working tool: towards a new standard?


S.Giancola1,  D.Viscomi2,  M.Pacilio3,  S.D’Onofrio1,  L.D’Addio1,  W.Pavan1,  S.Lauretti1  
 
(1)  Medical  Physics  Unit  -­‐  “S.  Maria  Goretti”  Hospital  -­‐  Latina,  Italy  
(2)  Medical  Physics  School  -­‐  “La  Sapienza”  University  -­‐  Rome,  Italy  
(3)  Medical  Physics  Unit  -­‐  “S.  Camillo-­‐Forlanini”  Hospital  -­‐  Rome,  Italy  
 
Purpose:   SIRT   is   a   targeted   treatment   for   inoperable   liver   tumors   delivering   millions   of   tiny   radioactive  
beads   directly   to   the   lesions.   In   spite   of   its   increasing   favour,   the   most   employed   methods   for   dose   and  
activity   evaluation   lack   in   accuracy   when   dealing   with   heterogeneous   biodistribution   and   volumetric  
structuring.   Instead,   a   voxel   dosimetry   approach   provides   a   more   reliable   3D   dose   evaluation   and  
consequently   a   wider   spectrum   of     therapeutic   opportunities   (e.g.   dose   escalation,   more   selective   lesion  
treatments,  organ  at  risk  sparing  and  radiobiological  modelling).    
Methods   and   materials:   a   PC   based   code   was   implemented   in   a   MatLab©   environment,   backing   the  
operative   work   flow.   SIRT   was   simulated   by   an   angiographic   procedure   infusing   into   liver   Tc99m   labelled  
MAA  as  a  surrogate  for  Y90-­‐spheres.  CT  and  SPECT  acquisitions  allowed  for  microspheres  distribution  as  well  
as   hepatic   vasculature   and   possible   shunts   evaluation.   CT   scans   provided   adequate   texture   for   ROIs  
contouring   at   proper   geometrical   resolving   power.   Then,   the   code   matched   CT   and   SPECT   images   so   to  
obtain   an   overall   consistent   spatial   reference   frame.   On   the   grounded   assumption,   within   certain  
constraints,  of  a  suitable  superposition  between  Y90-­‐spheres  and  Tc99m  labelled  MAA  distributions,  given  also  
the  simplified  Y90-­‐spheres  biokinetic  which  involves  only  physical  decay,  dose  calculations  were  performed  
by  voxel  convolution  of  Y90-­‐S  values  kernel  with  co-­‐registered  SPECT  image  arrays.    
Results:  the  code  computed  dose  distributions  at  CT  anatomic  level  (achieving  a  satisfactory  patient-­‐specific  
dosimetry),   the   activity   to   be   administered   to   deliver   a   prescribed   dose   to   a   target   ROI,   and   the   resulting  
dose  values  in  any  other  given  ROI.  Graphic  visualization  of  isodose  levels,  dose-­‐volume  histograms  and  3D  
dose  representations  were  also  gained.    
Conclusion:   this   computational   procedure   improves   by   far   the   accuracy   in   the   evaluation   of   3D   dose  
distributions  with  reasonable  processing  time.  Considering  how  physical  dose  distributes  at  voxel  level  and  
the   usual   prescription   of   the   target   dose   in   terms   of   mean   dose,   it   was   not   unexpected   to   often   detect   a  
considerable   difference   in   the   planned   activity   to   be   delivered   when   compared   with   current   calculation  
methods.   As   a   consequence   of   this   approach,   the   assessment   of   biological   dose   distributions   and   normal  
liver   tolerance   values   becomes   a   key   issue,   especially   as   far   as   criteria   for   liver   residual   functionality   are  
concerned.  
 
 
 

ELENCO
 
TOPIC ESC
 
  MEDICINA LA FISICA MEDICA
RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
  RICERCA NUCLEARE
SANITARIE
 
Impatto dell’approccio dosimetrico a livello voxel nei trattamenti di radioembolizzazione di HCC con
microsfere di 90Y
A. Giostra1, E. Gino1, E. Richetta1, A. Miranti1, A. Di Dia 2, M. Stasi1
(1)Medical Physics Department, Mauriziano Umberto I Hospital, Torino
(2)Medical Physics Department, Institute for Cancer Treatment and Research, Candiolo (Torino)

Scopo. La Radioterapia Interna Selettiva (SIRT) con microsfere di ittrio-90 ( 90Y) è sempre più diffusa come terapia
dei tumori epatici non resecabili. Nonostante l’approccio dosimetrico sia sempre più utilizzato, ad oggi non sono
chiare le correlazioni tra dose e risposta per il tumore e per la parte sana del fegato; per tale ragione la scelta
dell’attività da somministrare nella maggior parte dei casi ricade sui valori proposti dalle case produttrici delle
microsfere. Questi metodi, detti empirici, si basano sulle caratteristiche morfologiche del paziente (peso e altezza) e
sulla percentuale di tumore rispetto al fegato, mentre non considerano la distribuzione spaziale dell’ 90Y nel fegato.
Presso l’A.O. Mauriziano di Torino dal 2008 a oggi sono stati effettuati 37 trattamenti di radioembolizzazione con
Y90 Sir-Spheres per un totale di 29 pazienti.
Al fine di personalizzare l’attività somministrata e ottimizzare la distribuzione di dose, i trattamenti sono stati
preceduti da uno studio dosimetrico a livello voxel.

Materiali e Metodi.
I dati riportati si riferiscono ad un set di 17 pazienti affetti da carcinoma epatico. Per ciascuno di essi il trattamento
di radioembolizzazione è stato preceduto da uno studio angiografico della vascolarizzazione epatica, dall’iniezione
di 99mTc-MAA, dall’acquisizione di immagini planari total-body e tomografiche. Le immagini SPECT sono state
utilizzate per verificare l’overlap tra il volume di massima concentrazione di radioattivo e il volume target
identificato dal radiologo su immagini TC acquisite precedentemente.
Le distribuzioni di attività di 99Tc sono state usate come input di un programma in MatLab che permette di calcolare
a livello voxel la distribuzione di dose nei volumi interessati: il tumore e il fegato sano. Tutti i pazienti sono stati
trattati selettivamente a livello del lobo interessato dal tumore e per tale ragione il calcolo delle dosi al fegato sano
si riferisce al volume del lobo trattato. Il programma, oltre a fornire il valore di dose per attività somministrata per i
volumi di interesse, mostra i DVH per valori di attività somministrata definiti dall’utente. Sotto l’ipotesi che i
macroaggregati e le microsfere si distribuiscano nello stesso modo è stata calcolata la dose rilasciata agli organi per
valori di attività somministrate pari a quelle suggerite dai due metodi empirici (Metodo della BSA e Metodo delle
Attività Fisse).

Risultati.
Sul set di pazienti analizzati il valori medi di attività suggeriti dai metodi empirici, risultano 1.9±0.3 GBq per il
metodo della BSA e 2.4±0.5 GBq per il metodo delle attività fisse. Le ricostruzioni SPECT ottenute a seguito della
somministrazione di 99mTc-MAA sono state utilizzate per stimare la distribuzione di dose a livello voxel.
I valori di dose per attività somministrata (Gy/GBq) ottenuti dal software sono riassunti in Tabella 1.

Dose minima (Gy/GBq) Dose media (Gy/GBq) Dose massima (Gy/GBq)

Lesione 60 ± 70 150 ± 140 600 ± 300

Parte sana del lobo trattato 5±4 20 ± 13 80 ± 90

Tabella.1. Valori medi di dose minima, media e massima per attività somministrata (Gy/GBq) per il tumore e la
parte sana del lobo trattato (x± ).

I valori di dose media al target e alla parte sana del lodo trattato sono stati calcolati nell’ipotesi di attività
somministrate pari a quelle suggerite dai metodi empirici e confrontati con i valori di riferimento: D lobo<40Gy e
Dlesione>120Gy al fine di ottimizzare la dose al paziente. I risultati sono riassunti in Tabella.2.

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Dose per Asomm=ABSA (Gy) Dose se Asomm=AA-FISSE (Gy)

Lesione 260 ± 230 330 ± 250

Parte sana del lobo trattato 41 ± 25 50 ± 30

Tabella.2. Valori di dose alla lesione e alla parte sana del lobo trattato per valori di attività somministrata pari a
quella fornita dai due metodi empirici (x± ).

Le attività effettivamente somministrate ai pazienti sono state in media di 1.6±0.2 GBq [range 1,2-1,8 GBq] .
Le immagini di bremsstrahlung ottenute il giorno dopo il trattamento hanno evidenziato per tutti i pazienti un buon
accordo tra le distribuzioni di attività di 99mTc-MAA e 90Y-Sir-Spheres. Sono stati pertanto calcolati i valori di dose
rilasciati nei volumi di interesse (Tabella3).

Dose minima (Gy) Dose media (Gy) Dose massima (Gy)

Lesione 120 ± 140 250 ± 260 700 ± 500

Parte sana del lobo trattato 11 ± 7 40 ± 30 160 ± 170

Tabella.3. Valori di dose minima, media e massima rilasciata al tumore e alla parte sana del lobo trattato (x± )

Conclusioni: Sei dei ventinove pazienti trattati presso il nostro centro hanno mostrato una risposta completa al
trattamento e per due di loro è stata resa possibile la resezione del tumore. I risultati ottenuti dai calcoli di dose a
livello voxel hanno talvolta comportato una revisione dei valori di attività somministrabile al paziente rispetto ai
valori suggeriti dai metodi empirici. Studi ulteriori risultano necessari per standardizzare il metodo e migliorare le
attuali conoscenze sulla correlazione dose e risposta nei trattamenti di radioembolizzazione per i tumori del fegato.

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Development of an home-made software for voxel dosimetry (VoxelMed) in radiopeptide therapy.
Comparison with the commercial software STRATOS ® by Philips.
V.Ferri1, E.Grassi1, F.Fioroni1,E.Mezzenga1, M.A.Sarti1, T. Paulus3, A.Froio2, A.Filice2, A.Versari2, M.Iori1
(1) Medical Physics Dept. (2) Nuclear Medicine Dept., IRCCS - S. Maria Nuova Hospital, Viale Risorgimento 80,
I-42123 Reggio Emilia, Italy (3) Philips Technologie GmbH Innovative Technologies, Pauwelsstr. 17, 52074
Aachen, Germany
Purpose
Targeted radionuclide therapy is a rapidly growing modality. While commercial treatment planning systems (TPS)
are entering the market, many medical centres use systems developed in-house for dosimetry at voxel level.
We developed a prototype for voxel-based radiopeptide therapy (VoxelMed), based on CERR (Computational
Environment for Radiotherapy Research, www.cerr.info) environment. The module is able to calculate and
visualize in 3D the absorbed dose distributions for some radioactive tracers. Time-activity curve (TAC) integrals
are calculated at the voxel level and dose distributions are computable for the tumours and critical organs.
Furthermore, a quantitative comparison was performed between the two fully 3D voxel-based software: our code
VoxelMed and Stratos® (Philips Research, Aachen, Germany).
The aim of the present work is to test the module VoxelMed by comparison of the results obtained with Stratos
when processing the same image sets.
Methods
VoxelMed was designed on CERR, which is a platform originally created for developing and sharing research
results in radiation therapy treatment planning [1, 2]. CERR was written in the widely used Matlab language.
VoxelMed is a module which tools are provided for every step in dose calculation process from loading the images
to dose estimation. The specific S-values were simulated by the Department of Physics, Medical Imaging
Department, University of Bologna (www.medphys.it) [3] for a homogeneous medium corresponding to a soft
tissue (density 1g/ml).
In number of decays (ND) calculation, STRATOS by default applies the trapezoidal rule plus a physical half-time
mono-exponential tail after the last time point, while VoxelMed applies the trapezoidal method up to the last time
point plus an effective half-life as a mono-exponential tail after the latter. For a proper comparison with STRATOS,
in this work VoxelMed was also designed to apply both effective and physical half-life after the last time point.
Both Stratos and VoxelMed software include tools for segmentation, image co-registration, 3D visualization, fusion
display, dose matrices, and DVH.
The validation of both software was performed through various radioactive phantoms. One of them was filled with
different volume (98,26.5,19,11.5,5.6,2.57,1.15 ml) spherical inserts in order to perform partial volume effect
(PVE) analysis. Phantom were acquired with two standard clinical SPECT-CT protocol for brain and body,
respectively. A cohort of 10 patients was then studied after a therapeutic administration of 177Lu-labeled peptides
with renal protection (mean administered activity per cycle was 5.7 ± 1.2 Gbq). All patients underwent a series of
SPECT-CT scans of the abdomen (at 1, 4, 24, 44, 72h p.i.).
Time-activity curve integrals and dose distribution at voxel level were calculated for kidneys, the main critical
organs. The percentage discrepancy of the two software was evaluated for activity, number of decays per unit
activity (ND/A), and absorbed dose (D/A). Dose-volume histogram (DVH) was evaluated in phantoms and
patients. For non homogeneity evaluation, the analysis of the coefficients of variation for ND/A and D/A was also
performed. Statistical analysis was performed through non-parametric Wilcoxon test (significance level of 0.05)
designed to evaluate the difference between two samples (ND/A and D/A absolute values) with a limited number of
data.
The voxel-based results for D/A estimation are also compared to the standard OLINDA/EXM organ level approach.
Results
In absence of partial volume effect the absorbed doses in phantoms computed with VoxelMed and STRATOS are
within 5% of each other. PVE is completely absent only in volumes larger than 98 ml, making the correction for
ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
PVE mandatory when studying small volumes like lesions; the differences that emerged were related to volume
delineation and misalignment.
Results suggest an important variability in ND/A and D/A estimation in patient, but they are positively comparable.
The ND/A and D/A in kidneys in the cohort of patients show a mean difference of nearly 10% between the two
voxel-based methods. The same trend emerges by comparison of the two voxel methods with OLINDA/EXM
results. Volume contouring and images alignment, both of which are more critical in clinical cases, are the most
likely reasons for differences. Results for CAT evaluation at voxel level in case of two methods (physical half-time
vs effective half time) are slightly different, but the statistical tests performed on data provided no significant
difference between them.
An added value of dosimetry at voxel level is the non homogeneity dose estimate in regions of interest, which may
be evaluated through coefficients of variation and DVH. The coefficients of variation for ND/A and D/A have an
important inter-patient variability and strongly depend on the adopted method for time-activity curve integrals
evaluation.
Conclusions
This study demonstrates that a fully 3D voxel dosimetry with multiple SPECT acquisition is feasible, and that it
allows better insight of absorbed dose distribution with respect to mean dose approach. The module presented in
this work provides a versatile set of tools for each step in dose calculation process. It can be used to efficiently
perform patient specific internal dose assessment in different situations (radio-pharmaceuticals, acquisition
protocol, CAT integral calculation).
When comparing different dosimetric methods, it is not possible to overlook a few aspects, such as the integral
calculation technique, as well as getting ready images for dosimetry computation. All the methodologies should be
compared in detail, as indicated from the EANM guideline "Good dosimetry reporting" [4].
A voxel-based method can be successfully realized in clinical practice in presence of a fully 3D protocol. A
comparison with the commercial software STRATOS was carried out. Extensive knowledge of the internal
dosimetry software calculation methods is strongly recommended prior to their implementation in the clinical
routine.
References:
1. Deasy JO, Blanco AI, Clark VH. CERR: A Computational Environment for Radiotherapy Research.
Med Phys (2003);30:979e985.
2. E Spezi, P Downes, R Jarvis, Radu E, Staffurth J, Patient-specific three-dimensional concomitant dose
from cone beam computed tomography exposure in image-guided radiotherapy Int J Radiation Oncol
Biol Phys (2012), Vol. 83, No. 1, pp. 419E426
3. Lanconelli N, Pacilio M, Lo Meo S, Botta F, Di Dia A, Torres Aroche LA, Coca Perez MA, Cremonesi
M. A free database of radionuclide voxel S values for the dosimetry of non uniform activity
distributions. Physics in Medicine and Biology (2012); Vol. 57, 517-533
4. Lassmann M, Chiesa C, Flux G, Bardiès M EANM Dosimetry Committee guidance document: good
practice of clinical dosimetry reporting. Eur J Nucl Med Mol Imaging (2011) 38:192–200.

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Esperienze di pianificazione del trattamento di radioembolizzazione di lesioni epatiche.
Treatment planning in radioembolization of hepatocarcinoma with glass Y90 spheres

Alessandra Terulla1, Eleonora Lanzi1, Alberto Biggi2, Maurizio Grosso3, Patrizia Carucci4, and Stéphane Chauvie1
1
Medical Physics, 2Nuclear Medicine and 3Radiology Units of Santa Croce e Carle Hospital, Cuneo 4Radiology
Units of Molinette Hospital, Torino

Purpose: The aim of this work was to report the treatment planning strategy in radioembolization of
hepatocarcinoma (HCC) with glass Y90 spheres.
Methods: Patient work-up for HCC radioembolization consists of a super-selective angiography with 99mTc-MAA
injection in different hepatic artery followed by SPECT-CT. Prescription dose is 120 Gy to the target lobe, 100 Gy
in case of cirrhosis (range 80-150 Gy). Absorbed dose is calculated on a voxel base using MIRD formalism for
self-irradiation only and assuming an identical MAA and sphere distribution. Mean dose to the whole liver, to the
treated lobe and to the target lesions is calculated from the dose matrix. Target lesion is defined as the volume of
distribution of 70% or 95% of MAA, eventually adjusted on CT border to avoid PVE effects. Brehmstrahlung
imaging was acquired after the sphere administration to all patients. H* was calculated at 1 m distance for all
patients.
Results: 25 patients with Child A, 2 with Child B and 1 metastatic HCC were treated.
9 patients were excluded: 3 patients because of large liver volume involved; 2 because of worsening in health
conditions; 4 because of extrahepatic activity: 1 in the small intestine and 3 in the lung (lung shunt ranging 23-28
%, dose to the lungs > 30 Gy). Lung shunt for the treated patients was 4.7±5.9% (range 0-25 %, dose to the lungs <
30 Gy). Mean injected activity was 2.6±1.2 GBq (range 1-6 GBq). Mean dose to the treated lobe was 98.4±30.5 Gy
(range 50-140 Gy). H* at 30 cm was 0.21±0.19 mSv/GBq (on a complete decay).
Conclusions: dose calculation to the target lesion is easily achievable in a medical physics unit. Besides dose is
prescripted to the treatment lobe, dose has to be reported in the whole liver, the treated lobe and in to the target
lesion to possibly correlate with the liver toxicity (Chiesa et al, QJNMMI 2012) and to the treatment response.  

ELENCO
 
TOPIC ESC
 
  MEDICINA LA FISICA MEDICA
RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
  RICERCA NUCLEARE
SANITARIE
 
Valutazione della dose in procedure PET-TC con 18F-FDG per sospetta vasculite dei grandi vasi.

Estimation of radiation dose in PET/CT scanning for diagnosing large vessel vasulities.
L. Ferri1, M. Bevegni1. S. Fiordoro 2 , G.Taccini 1
(1) Medical Physics (2) Nuclear Medicine, A.O.U IRCCS San Martino IST, Genoa, Italy.

Purpose: 18F FDG PET CT is used above all when there is a suspicion of large vessel vasculities (LVV). The aim
of this study is to obtain the magnitude of the effective dose and the dose to specific organs from PET and CT.
Methods and materials: We retrospectively reviewed patients investigated with total body 18F FDG PET CT since
June 2008.
PET CT imaging was performed on a hybrid system (Siemens Biograph™16 TruePoint™). The scan was extended
from the skull base to the proximal segment of the lower limb and was obtained 45 min after intravenous
administration of 18F FDG (5.5 MBq/Kg). CT scan parameters were 95 mAs (quality reference mA with Care Dose
system for beam-intensity modulation) and 120 kV.
For each patient dose coefficients recommended by International Commission on Radiological Protection 80 [1]
were applied to 18F-FDG activity administrated to estimate the mean doses to bladder wall, brain, LLI wall, heart
and kidneys for the PET scan. For each CT scan, software provides: eff mAs, DLP and CTDI vol. CTDIair was
previously measured while nCTDIair was calculated for each CT scan. We have valued scan length and average
mAs for five regions: brain, neck, chest, abdomen and pelvis. The effective doses for both pediatric and adults
patients were calculated according to DLP and weighting factors recommended in Galanski M et al.[2]
Results: We have obtained mean effective dose for several groups of not-oncologic patients differing by age. Both
PET and CT significantly contribute to the effective dose from PET/CT imaging.
Conclusion: Having knowledge of the magnitude of the effective dose and the dose to specific organs
from PET and CT, and considering the role of CT in the context of PET/CT we provide a practical insight
necessary to reduce the radiation dose to the patient without compromising the quality of the patient's care.
References:
[1]International Commission of Radiation Protection. Radiation Dose to Patients from Radiopharmaceuticals. ICRP
Publication 80. Pergamon Press, London, UK(1997)
[2]Galanski M, Nagel HD, Stamm G Pediatric CT Exposure Practice in the Federal Republic of Germany,
Medizinische Hochschule Hannover (2006).

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Dosimetria  previsionale  al  midollo  rosso  con  I-­‐131  e  I-­‐124  nel  carcinoma  differenziato  della  tiroide:  
è  un  valore  affidabile?  

Previsional  red  marrow  dosimetry  in  differentiated  thyroid  cancer  with  I-­‐131  and  I-­‐124:  is  a  reliable  
value?  

G.Rossi1,  M.  Camarda1,  P.  D’Avenia1,  E.  Di  Nicola1,  L.  Montani1,  C.  Bartolozzi1,  A.  M.  Dente1,  N.  Gasparrini1,  S.  
Fattori1.  
(1)  Servizio  di  Fisica  Medica,  Ospedale  di  Macerata,  Macerata  

Purpose:  for  patients  affected  by  with  differentiated  thyroid  cancer  (DTC)  we  always  consider  a  dosimetric  
limit  of  2  Gy/treatment  for  the  red  marrow  protection.  
Aim  of  this  work  was  to  evaluate  confidence  between  previsional  and  post  therapy  red  marrow  dosimetry  in  
order  to  guarantee  patients  safety.  
Methods  and  Materials:  we  studied  7  patients  (pts)  affected  by  DTC  at  multiple  treatment  phase,  enrolled  
for  subsequent  radioiodine  therapy.  
For   5/7   pts   we   administered   a   trace   activity   of   I131   (74   MBq)   and   for   2/7   we   administered   a   trace   activity   of  
I124   (74   MBq).Then   we   collected     6   blood   samples   the   week   before   therapy   and   6   blood   samples   during  
therapy  after  administration  of  I131  (range  5550-­‐9213  MBq).  We  analyzed  10  whole  body  counts  before  and  
during  therapy,  considering  the  ant-­‐post  geometric  mean.  We  calculated  the  residence  times  for  blood  and  
remainder   of   the   body.   By   the   use   of   OLINDA/EXM   we   had   the   values   of   dose/administered   activity  
(mSv/MBq),  allow  for  proportionality  between  blood  and  red  marrow.  
Results:  we  found  that  for  6/7  the  red  marrow  behaviour  is  different  from  pre  and  post  administration  of  
radioiodine  therapy.  The  cumulated  activity  were  always  higher  during  therapy  till  the  50th  hours  and  then  
are  superimposable  with  the  previsional  ones.  In  one  patient  we  found  that  previsional  value  are  higher  than  
post  therapy  evaluation,  both  for  red  marrow  and  for  whole  body.  
The  variability  range  of  the  residence  times  between  pre-­‐and  post-­‐therapy  dosimetry  was  38%-­‐84%.  
Regarding  to  whole  body  analysis,  we  found  that  the  residence  times  are  superimposable  for  4/7  patients.  
For   1/4   we   found   a   oscillating   behaviour   of   the   cumulated   activity   but   resulting   in   an   overlapping   of   the  
residence  times  pre  and  post  therapy.  
For  2/7,  we  found  a  higher  value  during  therapy,  probably  due  to  the  presence  of  diffuse  bone  metastases.  
For  1/7  we  found  a  lower  value  during  therapy.    
No  patients  received  a  dose  to  the  red  marrow  higher  than  the  accepted  limit  of  2  Gy.  
Conclusions:   the   different   behaviour   of   red   marrow   residence   times   point   out   the   need   to   validate   the  
absorbed  dose  during  therapy.  Our  work  will  carry  on  with  the  analysis  of  the  follow  up  of  the  patients,  with  
particular  focus  on  their  red  marrow  safety.    
Moreover,   it   is   important   to   consider   localization   and   uptake   values   of   bone   metastases   in   order   to   try   to  
hypothesize  the  behaviour  during  therapy  and  any  eventual  variation  in  the  prediction.  

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Dose  efficace  nel  trattamento  del  morbo  di  Basedow  
 
131I  dose  effective  in  Basedow  disease  treatment  

C.Canzi,  V.Longari,  M.Castellani,  F.Zito,  F.Voltini,  R.Benti  


Fondazione  IRCCS  Cà  Granda  Ospedale  Maggiore  Policlinico,  Milano  
 
 
Basedow  hyperthyroidism  has  an  autoimmune  origin  and  for  this  reason  the  radioiodine  therapy  should  aim  
at  a  complete  ablation  of  the  gland  to  avoid  relapse  of  the  disease.  Aim  of  this  work  is  to  find  a  dose  value  
effective  in  giving  rise  to  hypothyroidism  within  1  year  from  the  radioiodine  treatment  in  Basedow  patients.  
Materials   &   Methods:   For   70   Basedow   patients   at   their   first   radioiodine   treatment   (11   M,   median   age   53y  
(range  25-­‐88y),  17  with  subclinical  hyperthyroidism  and  53  with  overt  hyperthyroidism)  the  dose  released  
after  oral  administration  of  a  131I  therapeutic  activity  (median  414  MBq,    range  148-­‐625  MBq)  was  calculated  
by   means   of   6   uptake   measurents   at   2,   4,   24,   48,   96   and   168   hours   and   the   use   of   the   MIRD   formula.   Uptake  
measurements  were  performed  with  a  gammacamera  equipped  with  a  high  energy  collimator.  Therapeutic  
activities  were  determined  by  means  of  patient  specific  pre-­‐treatment  dosimetric  studies.  Antithyroid  drugs,  
if   administered,   were   withdrawn   at   least   7   days   before   both   dosimetric   and   therapeutic   administration.  
Clinical  outcome  of  each  patient  was  monitored  with  biochemical  analysis  (TSH,  FT3  and  FT4)  1,  3,  6  and  12  
months   after   therapy.   Results:   All   the   patients   (12)   that   received   less   than   200   Gy   remained   hyperthyroid  
after   1   year   of   follow-­‐up;   in   the   dose   interval   between   200   and   250   Gy,   5   patients   remained   hyperthyroid  
and  5  became  hypothyroid;  for  doses  higher  than  250  Gy  (up  to  463  Gy  with  a  median  value  of  334Gy)  all  
patients  (53)  became  hypothyroid  within  12  months  (48  of  which  even  in  6  months).  Doses  were  increased  
during  time  on  the  basis  of  the  clinical  results  of  the  previously  performed  therapies.  Out  of  the  17  patients  
who   were   still   hyperthyroid   after   12   months   from   the   first   therapy,   8   were   submitted   to   a   second  
administration,   1   was   submitted   to   surgery,   3   stayed   in   a   wait   and   watch   condition   and   5   were   missed   at  
follow  up.  Conclusions:  The  results  of  the  present  work  suggest  that  the  target  dose  for  Basedow  disease  to  
reach   a   hypothyroid   status   within   1   year   from   131I   therapy   should   be   250-­‐300   Gy   as   also   reported   by   the  
recently   published   European   guidelines   for   therapy   of   benign   thyroid   disease   (ref.1).   In   fact,   the   clinical  
outcome   after   the   release   of   doses   between   200   and   250   Gy   resulted   patient   dependent   and   for   doses   ≤   200  
Gy  hyperthyroidism  persisted  in  all  patients.  
 
Ref.1:  “EANM  Procedure  Guidelines  for  therapy  of  benign  thyroid  disease”  Eur  J  Nucl  Med  Mol  Imaging  2010;  
37:2218-­‐2228.  
 
 

ELENCO
 
TOPIC ESC
 
  MEDICINA LA FISICA MEDICA
RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
  RICERCA NUCLEARE
SANITARIE
 
 
131
Pre-treatment dosimetry in I therapy of hyperthyroidism: comparison of mass evaluation methods and
dose algorithms calculation

Dosimetria pre-trattamento nella terapia con 131I dell’ipertiroidismo: confronto tra metodi di valutazione
della massa ed algoritmi di calcolo della dose

E. Richetta1, A. Giostra1, I. Trabucco2, A. Guida3, G. Santopolo2, G. Brusasco2, R.E. Pellerito2, M. Stasi1

(1) Medical Physics Department, A.O. Ordine Mauriziano, Turin, Italy


(2) Nuclear Medicine Department, A.O. Ordine Mauriziano, Turin, Italy
(3) University of Turin, C.d.L. Tecniche di Radiologia Medica per Immagini e Radioterapia

Purpose: The Italian Guidelines for 131I treatment of hyperthyroidisms strongly suggests dose evaluation to
determine optimal administered activity in order to achieve long-term euthyroidism. Correct dose calculation is
greatly conditioned by a proper mass measure. Aim of this work was to compare different mass calculation’s
methods obtained from ultrasound and scintigraphic images. The mass uncertainty was related to different dose
algorithms to evaluate variations in the optimal activity to be administered.
Methods and materials: To 27 patients (18 Plummer and 9 Basedow disease) an oral trace activity of 131I (5 MBq)
was administered to evaluate uptake (2, 28, 96 h p.a.) on planar images (Mediso TH45). The mass (mus) was
measured on ultrasound images (ellipsoidal model) and on scintigraphy using different algorithms (Dottorini,
Goodwin, Fazekas, Allen) provided by the gamma camera dedicated tool. Mass differences were evaluated and the
formula that fits the best ultrasound results was chosen to calculate scintigraphic mass (msc.). From these values
(mus and msc) doses were calculated with the gamma camera provided formulas (Marinelli, Banjok, Traino) and
with RAI Extimator Tool. Personalized activity to deliver 200 Gy (Plummer) and 300 Gy (Basedow) was
calculated and compared with those actually administered.
Results: Using scintigraphic images, mass calculation varied significantly from ultrasound results (total patients:
mean variation -10 ± 53 %, Plummer patients: mean -7 ± 69 %, Basedow patients mean: -12 ± 37 %) . Dottorini’s
formula fits the best in Plummer patients (-7 ± 23 %), instead Fazekas methods was chosen for Basedow (1 ± 4 %).
Compared with the calculated values, the administered activity showed to be insufficient for 63 % of patients
(mean: -60 % when calculated with mus and – 68 % with msc) and too high for 36 % (mean with mus + 35 % and
with msc + 32 %). Mean activity’s variation calculated with different methods, was 10 ± 21 %. Marinelli formula
provided in all cases higher values (mean: + 32 %). Traino formula was chosen as standard method for the
operative protocol.
Conclusion: A personalized dosimetry can significantly influence the treatment and an accurate activity calculation
can protect patients from diseases caused by under and overestimation.

ELENCO
 
TOPIC ESC
 
  MEDICINA LA FISICA MEDICA
RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
  RICERCA NUCLEARE
SANITARIE
 
177
Lu-SPECT/TC: imaging quantitativo e validazione di un software commerciale per
studi di dosimetria

Quantitative 177Lu-SPECT/CT imaging and validation of a commercial dosimetry


software

L.D'Ambrosio1,2, L.Aloj1, D.Madesani3, A.Morisco1, M.Aurilio1, A.Prisco1, F.Di Gennaro1,


S.Lastoria1
(1) SC Medicina Nucleare, Istituto Nazionale Tumori Fondazione "G. Pascale" IRCCS,
Napoli; (2) UOSD Fisica Sanitaria, Istituto Nazionale Tumori, Fondazione "G. Pascale"
IRCCS, Napoli; (3) GE Healthcare, Milano

Purpose: 3D dosimetry is an appealing yet complex application of SPECT/CT in patients


undergoing radionuclide therapy. In this study we have developed a quantitative imaging
protocol and we have validated commercially available dosimetry software (Dosimetry
Toolkit Package, GE Healthcare) in patients undergoing 177Lu-DOTATATE therapy.
Methods and materials: Dosimetry toolkit uses multi SPECT/CT and/or WB planar datasets
for quantifying changes in radiopharmaceutical uptake over time to determine residence
times. This software includes tools for performing reconstruction of SPECT/CT data,
registration of all scans to a common reference, segmentation of the different organs, creating
time activity curves, curve fitting and calculation of residence times. All acquisitions were
performed using a hybrid dual-head SPECT-CT camera (Discovery 670, GE Healthcare)
equipped with medium energy collimator using a triple-energy window. SPECT images were
reconstructed using an iterative reconstruction algorithm with attenuation, scatter and
collimator depth-dependent three-dimensional resolution recovery correction. Camera
sensitivity was determined utilizing a point source. Accuracy of activity quantification was
performed on a large homogeneous source with addition of attenuating/scattering medium. A
NEMA/IEC body phantom was utilized to measure the recovery coefficient that the software
does not take into account. The residence times for organs at risk were calculated in six
patients. OLINDA-EXM software was used to calculate absorbed doses.
Results: 177Lu-sensitivity factor was 13 counts/MBq*s. The measured activity was consistent
with the decay-corrected calibrated activity for large volumes (>100 cc). The recovery
coefficient varied from 0.71 (26.5 ml) to 0.16 (2.5 ml) in the absence of background activity
and from 0.58 to 0.13 with a source to background activity ratio of 20:1. The activity
concentrations measured in the spheres were dependent on the reconstruction parameters. The
mean absorbed doses observed were 0.69 Gy/GBq for liver, 0.76 Gy/GBq for spleen, 0.55
Gy/GBq for kidneys and 0.08 Gy/GBq for lungs.
Conclusion: Quantitative SPECT with 177Lu has high accuracy both in our phantom and in
clinical practice. Dosimetry toolkit simplifies the procedure for quantifying absorbed dose
reduces the processing time and improves accuracy of results compared to manual methods.  

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Evaluation of the residual activity in patients exposed to 131I thyroid therapy.
M.Cacciatori, A.Ostinelli, V.Conti, M.Duchini, P.Urso, C.Berlusconi, G.Frigerio.
A.O. Sant’Anna, Como

Purpose: 131I-iodide therapy is currently the most common treatment for hyperthyroidisms and thyroid carcinomas.
In these cases, relevant radioiodine activities are often administrated to patients, causing significant residual intakes
during the post treatment period. Such an issue is of critical concern in the radiation protection field. For this
reason, radionuclide therapy practice (Annex I, Part II, paragraph 6 of Decreto Legislativo 187/00) requires
verification of compliance with the safety standards relating to hospitalization of patients undergoing such
treatments. The most direct approach to this problem consists in the determination of the patient residual activity at
the time of hospital discharge.
A systematic study was thus performed to achieve a method to assess the agreement with the dose constraint
requirements, for the case of patient discharge from nuclear medicine clinics or hospital protected rooms.
Methods and materials: A mathematical model based on in vivo radiometric external measurements (H*(10) rates)
was implemented in order to evaluate the radioiodine amount in patients, A, starting from the radiation field
measurement and the following physical properties of 131I:
• Γ constant = 56.1 mSv h-1 GBq-1 m2,
• linear coefficient of absorption in water µa = 0.0324 cm-1,
• linear attenuation coefficient in water µ = 0.111 cm-1.
The basic relationship can be expressed by the mathematical formula:
& * (10) D 2
H
A=
Γ
where, the residual activity can be calculated by the H*(10) rate and the source-detector distance D. This approach
required a careful analysis of the uncertainties affecting the data, the theoretical assumptions underlying the
physical events and the need to introduce appropriate correction factors. First of all, the distance d between the
detector and the patient body surface is not the effective distance deff of the point source representing the extended
radioisotope distribution within the patient.
To quantify this variable two H*(10) rates (R1 and R2) were measured at known prefixed distances from the patient
(d1 and d2), by placing the detector in line to the sternum.
Applying the distance inverse square law and extrapolating the experimental values, the effective distance is
obtained by adding ∆d to d1 and d2, where:
∆d = (d1 - d2 C) / (C - 1)
and C = (R2 / R1)½. In this way, the correction factor is given by: Fd = deff / d, for 1 m normalized distance
At the same time, the attenuation of photon radiation due to the patient body tissues must be considered. The
radiation interaction with the tissue ∆d is accounted by the formula:
Rx = Ro e-µ ∆d = Ro FT
with FT = average transmission factor.
It must be emphasized that the ∆d value is the same obtained from the calculation of the effective distance.
So, the mathematical relationship for estimating the patient residual activity becomes:
& * (10) d 2
H
A = Fd 1/FT
2

Γ
where Fd and FT are the correction factors accounting for the effective distance and for the patient interaction
respectively. Prior to the clinical start-up, a plastic scintillator detector (ATOMTEX AT1123) was characterized in

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
terms of both absolute dose reading and response linearity versus radiation field intensity: H*(10) rate
measurements were performed by 131I point sources of different intensities and in different geometrical conditions
(see Figure 1).
Results: The study sample consisted of 70 patients affected by Graves’ disease (55%), uninodular (19%) and
multinodular (26%) toxic goiter, who underwent hyperthyroidism radioiodine therapy. According to preset
standard criteria and to specific detector-patient distances (1÷4 m), the acquisitions were taken at three different
times: after the radioiodine administration, at the discharge (3÷4 hours later) and at the follow-up date (six days
later). A validation test was conducted 20 - 30 minutes after administration of known activities of radioiodine,
before the patient had made urination (i.e. with the whole activity inside his body). This test confirmed the method
reliability, as the mean difference between administered and measured activities was -0.8%, with R2 = 0.9822 and a
4.1% standard deviation. This outcome is clearly shown by Figure 2. Moreover, the analysis assessed that the
residual activity percentage was, on the average, 82.8% ± 11.3% of the initial value at 3-4 hours after the
radioiodine administration. This percentage decreased to 28.8% ± 11.6% about six days later.
Potential experimental errors affecting these results
80
can be attributed to the following sources of
uncertainty:
experimental data ( Sv/h)

60
1) saturation effect of the instrument with a loss of
y = 0.9065x + 1.7139 efficiency at higher count rates, 2) inaccuracy in
R2 = 0.9937 determining the exact distance between the source
40 (patient) and the measurement point (a substantial
Figure 1 improvement can be introduced by the use of a laser
meter), 3) variability in the radioiodine distribution
20 (concentration in body and thyroid) in relation to the
bisector type and extent of the specific disease, 4) inaccuracy
in the identification of the time intervals between
0
0 20 40 60 80
administration and measure, 5) radiation background
teorical data (mSv/h)
change during measurements due to radioactive
patients transit, 6) differences in the patient posture
1000
that can modify the successive estimates of the
effective depth.
measured activity [MBq]

Another interesting remark coming from the


800 statistical analysis concerns the effective depth ∆d
y = 1.0524x - 27.884
of the radioiodine distribution: while after
R2 = 0.9822
600 administration its average value is estimated to be
5.1 ± 2.9 mm, 4 hours away it decreases to 2.8 ±
2.7 mm and 6 days after to 1.2 ± 2.6 mm. By
400 Figure 2 applying the Student's t test, highly significant
differences are evidenced (P = 0.0004), that can be
200 interpreted as the consequence of the progressive
uptake of the iodine by the thyroid gland.
administered activity [MBq]
Conclusion: The preliminary verification of the
0
instrument response is fundamental to validate the
0 200 400 600 800 1000
procedure for assessing the residual activity in
131
patients undergoing I radionuclide therapy and to determine the reliability of the experimental data. The
subsequent clinical testing soon after iodine administration ensures the reliability of the whole approach. Therefore
it can be stated that this method provides an effective tool for performing the assessment of patient residual activity
at discharge time and to verify the fulfillment of the standards of practice. In fact, simple and single external
ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
measures can lead to errors up to 36% in the residual activity evaluation. On the contrary, the application of the
proposed method significantly reduces the margin of error within an approximate range of ± 8%. Patient residual
activities assessed in the present study resulted to be non negligible, suggesting the need of attention towards
bystander. Moreover, the method can be applied under normal operating conditions and can be customized both for
carcinoma treatments and for radioisotopes other than 131I.
Bibliography:
• ICRP Publication 94: Release of Nuclear Medicine Patients after Therapy with Unsealed Sources, June 2004
• NRPB-W60: Optimization of Monitoring for Internal Exposure (OMINEX), august 2004
• IAEA safety Reports Series no. 63: Release of Patients After Radionuclide Therapy, 2009
• NCRP Report No. 155 - Management of Radionuclide Therapy Patients (2006)
• IAEA Safety Reports Series No. 16 - Calibration of radiation protection monitoring instruments - Vienna,
2000

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
METODO SEMPLIFICATO PER L’INDIDUALIZZAZIONE DELLA ATTIVITÀ TERAPEUTICA
NELLA RADIOABLAZIONE DEL RESIDUO TIROIDEO, ANALISI DI 4 ANNI DI ESPERIENZA
S. Fattori, M. Camarda, P. D'Avenia, E. Di Nicola, L. Montani, G. Rossi
Servizio di Fisica Medica, Area Vasta 3 Macerata, ASUR Marche

Scopo
Quando si pianifica un trattamento con radioiodio per l’ablazione del residuo tiroideo dopo l’asportazione
chirurgica della tiroide in caso di carcinoma, è importante una valutazione fisico-dosimetrica per la definizione
dell’attività ottimale da somministrare. I residui tiroidei da ablare hanno dimensioni e captazioni differenti da
paziente a paziente, è perciò importante cercare di attuare una personalizzazione del trattamento. Con questo lavoro
si intende valutare 4 anni di esperienza nell’applicazione di una procedura pratica e veloce per la valutazione
dosimetrica pre-trattamento che impiega personale e attrezzature per il minor tempo possibile, quindi con un
impatto moderato sull’economia generale del sistema, sia per quanto riguarda il Servizio di Fisica Medica che di
Medicina Nucleare.
Materiali e metodi
Al giorno 1 si somministra al paziente un’attività traccia di circa 7.4 MBq di iodio 131 liquido. Alla quarta ora si
effettua una misura dell’attività ritenuta a livello del collo mediante sonda per captazione dedicata (NaICl). A 24
ore si effettua una seconda misura con sonda dedicata ed una scintigrafia del collo con collimatore pin-hole e si si
esegue un’ecografia del collo del paziente per l’individuazione dei residui di tessuto tiroideo ed eventuali linfonodi
associati. Si confrontano ecografia ed immagine scintigrafica per l’individuazione dei residui captanti il radioiodio
e per la definizione delle dimensioni dei singoli residui tramite sonda ecografica.
Si ipotizza un’emivita del radioiodio nel residuo di 2.5 gg. Con i dati raccolti di captazione a 24h, volume ed
emivita, e utilizzando i fattori S per lo I131 (MIRD), si stima l’attività da somministrare per dare al residuo una
dose di 300 Gy. L’attività di I131 così calcolata viene somministrata al paziente al giorno 2.
Si è analizzato il periodo temporale tra aprile 2009 e aprile 2013. Sono stati esclusi dalla statistica tutti i pazienti
che hanno eseguito il primo trattamento presso altri centri ed i pazienti metastatici.
Risultati
Il valore medio di uptake pre-terapia è 2.4 % (range 0.1-63). L’attività media somministrata è stata di 1754 MBq
(range 557-3710, dev. st. 644). In 814/863 pazienti si è avuta una completa ablazione (94%). In 49 (6%) pazienti è
stato necessario ripetere il trattamento.
Conclusioni
Il metodo utilizzato consente di ricoverare il paziente solo il giorno prima della somministrazione dell’attività
terapeutica, cosa che in ogni caso deve essere fatta per consentire l’esecuzione dei normali esami e visite di routine.
Le approssimazioni apportate dal metodo proposto rispetto ad una procedura più rigorosa che prevedrebbe anche
l’esecuzione di scintigrafie, TC e la definizione dell’emivita specifica, non hanno inficiato il risultato in termini di
risposta alla terapia. L’applicazione del metodo più rigoroso è comunque auspicabile quando è possibile inserirlo
all’interno della programmazione del reparto poiché consente una migliore razionalizzazione e minimizzazione
della dose al paziente. La procedura semplificata garantisce comunque una discreta individualizzazione del
trattamento con un tempo-uomo and tempo-macchina minimo consentendo, oltre che una riduzione della dose al
paziente,e quindi alla popolazione, anche un risparmio in termini economici.

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Statistical evaluations of measured exposure rates in patients undergoing radioiodine therapy with I-131 for
differentiated thyroid cancer: Messina Polyclinic experience

Valutazioni statistiche di intensità di rateo di esposizione in pazienti sottoposti a Terapia Radiometabolica


con I-131 per tumori differenziati della tiroide: l’esperienza del Policlinico di Messina

I. Ielo(1), A. Brogna(1), F. Midili(1), C. Siragusa(1), A. Cristaudo(1), A. Giacobbe(1), A. Campennì (2),


S.Baldari(2), V. Mongelli(1)

(1) A.O.U. Policlinico “G. Martino di Messina”- U.O.C. di Fisica Sanitaria

(2) A.O.U. Policlinico “G. Martino di Messina”- U.O.C. di Medicina Nucleare

Background:
In radiotherapy treatment with iodine-131 for activity administered over 600 MBq (16 mCi), the legislation
(D.lgs.187/00 All.1 part. II 6-7) requires hospitalization of the patient in hospital stay protected (leaded room –
metabolic department). Patient discharge is possible when activity level becomes below that limit, consequently
exposure rate measurements around the patient are essential.
Hospitalization time depends on the administered dose and radioisotope biological half-life. Although the iodine
metabolism is known, it’s not easy to predict the time at which the activity retention falls below 600 MBq, as the
effectiveness of the processes of elimination is affected by a variety of factors (renal function, gastric absorption,
age, etc..), different from individual to individual.
Nevertheless, on the basis of a simple statistical analysis of exposure rate measurements at 1 m data, the
hospitalization time could be predicted, allowing a more accurate planning of a therapeutic department.

Purpose:
The purpose of this work is to obtain information on the probabilistic nature of the hospitalization time in relation
to the dose administered , in order to optimize the planning of the treatments.

Method and materials:


The examined sample consists of patients affected by differential thyroid cancer underwent to total thyroidectomy
and, some months later, to radioiodine therapy (RIT) by different ablative activity of I-131.
A period of about six months of Department of Nuclear Medicine of the Messina Policlinic activity has been
evaluated. During this period 58 treatments with an availability of 2-4 beds were carried out.
The dose administered to the sample varies from a minimum of 2220 MBq (60 mCi ) to a maximum of 3700 MBq
(100 mCi ) . It has been made the hypothesis that in this interval the clearance activity of the iodine is independent
from the value of the administered dose has been made.
Before patient’s discharge, exposure rate measurements (µSv/h) were performed at 1 m around the patient, in
different body areas (thyroid and bladder) and at different times: 4h, 24h and 48h after administration.

To discharge the patient, the exposure rate measurement must be lower than 30 µSv/h that corresponds to 600 MBq
of activity retention.
The measurements have been performed using a Victoreen Fluke Medical Biomedical ionization chamber. The
trends obtained on different patients at different distances show that , at a distance of 1 m, the perturbation induced

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
by the distribution of the radioisotope in the body does not exceed 15 % , and, at the same time, that such distance
ensures a satisfactory level of instrument sensitivity. So, probabilistic nature indications about patients
hospitalization time were carried out through the study of the activity retention estimation by exposure rate
measurements on patients.

Results:

Table 1 and Table 2 show the values of measured exposure rate for thyroid and bladder at a distance of 1 m around
the patient and for the whole sample analyzed. The data were measured 48 hours after dose administration,
respectively, equal to 3700 MBq and 2220 MBq, and before examining the possibility of patient discharge.
Subsequently, cumulative distribution was evaluated.
The sample analyzed with the administered dose is equal to 3700 MBq in 39 patients. Out of these ones, 30 patients
(corresponding to 77% of the sample) show exposure rate lower than 30 µSv /h and so they may be discharged
after 48 hours of hospitalization while the remaining 23% must necessarily stay in the hospital unless nuclear
doctor justifies the discharge after the evaluation of patient lifestyle under defined behavioural boundaries.
The situation is different in the group of 17 patients submitted to a dose of 2220 MBq. In this case, 100% of
patients show after 48 h an exposure rate lower than 30 µSv / h and a residual activity lower than the limit required
by the legislation (600MBq) for the hospitalization.

Obtained data have been reported in a “exposure rate – 1m” distribution histogram as shown in Fig.1 and Fig.2.
Table 3 shows the probability that the dose decreases to a value less than or equal to 600 MBq after a specified
time of hospitalization. These values were obtained by exposure rate measurements taken at different times: 4h,
24h and 48h after administration.

Conclusion:

Thanks to achieved results, hospitalization planning significantly improved.


To plan the treatments on the basis of the values of Tab.3, it is necessary only to set the minimum value of
discharge probability, which represents the level of uncertainty associated with the success of discharge
programming. For example, given 75% as the minimum value of probability on which the planning is based, since
for a dose of 3700 MBq (100 mCi) after 2 days hospitalization we have the 77% probability of discharging the
patient, it would be possible to forecast between Monday and Friday two consecutive admissions to two days of
hospitalization.
On the basis of these estimation, it is already possible to improve the planning of department therapeutic activity.
Treatment planning in the Messina Polyclinic’s Nuclear Medicine Department has long been made on the basis of
these assessments, ensuring a consistent number of treatments.

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Tab1 and Tab 2. Measured exposure rate for
thyroid and bladder at a distance of 1 m for
3700 and 2220 MBq administrered dose

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Fig.1 Exposure rate distribution - 3700 MBq

Figura 2 Exposure rate distribution - 2220 MBq

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Tab.3 Estimation of probability dose reduction to <600 MBq vs administered dose

References:
[1] D.Lgs 187 /00 – Attuazione della direttiva 97/43/Euratom in materia di protezione sanitaria delle persone contro i
pericoli delle radiazioni ionizzanti connesse ad esposizioni mediche.

[2] Protezione dalle radiazioni 97 – Protezioni dalle radiazioni conseguenti a terapie con I-131, 2000 Direzione generale
ambiente

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Kidney dosimetry in 177Lu and 90Y Peptide Receptor Radionuclide Therapy (PRRT): influence of
image timing, time-activity integration method, and risk factors

Dosimetria renale nella terapia recettoriale con radiopeptidi 177Lu e 90Y: influenza dei tempi di
acquisizione, del metodo di integrazione della curva attività tempo e dei fattori di rischio

F. Guerriero1-2, M. E. Ferrari1, F. Botta1, F. Fioroni3, E. Grassi3, A. Versari4, A. Sarnelli5,


M. Pacilio6, E. Amato7, L. Strigari8, L. Bodei9, G. Paganelli9, M. Iori3, G. Pedroli1 and M. Cremonesi1
1
Medical Physics Department, European Institute of Oncology , Milan 20141, Italy
2
School of Medical Physics, University of Milan, Milan 20122, Italy
3
Medical Physics Department, Santa Maria Nuova Hospital, Reggio Emilia 42100, Italy
4
Nuclear Medicine Department, Santa Maria Nuova Hospital, Reggio Emilia 42100, Italy
5
Medical Physics Department, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei tumori,
Meldola 47014, Italy
6
Department of Medical Physics, Azienda Ospedaliera S. Camillo Forlanini, Rome 00151, Italy
7
Section of Radiological Sciences, Department of Biomedical Sciences and of Morphologic and Functional
Imaging, University of Messina, Messina 98125, Italy
8
Laboratory of Medical Physics and Expert Systems, National Cancer Institute Regina Elena, Rome 00144,
Italy
9
Nuclear Medicine Department, European Institute of Oncology , Milan 20141, Italy

Purposes Kidney dosimetry in 177Lu- and 90Y- PRRT requires whole-body/SPECT scans to extrapolate the
peptide kinetics. In clinical studies 3 to 6 time points are gathered to balance between a time- consuming
procedure and sufficient information. The optimal compromise is to be established. We investigated the most
adequate timing for imaging and time-activity interpolating curve, as well as the influence of risk factors for
kidney toxicity and of the peptide (DOTATOC/DOTATATE).
Methods After therapeutic administration of 177Lu-DOTATATE (28 pts) and 177Lu-DOTATOC (30 pts),
patients underwent SPECT scans at 2 and 6 hour, 1, 2, and 3 days. Kidney time-activity data were
interpolated by i) trapezoids with physical decay from the last point on, ii) trapezoids with exponential decay
traversing the last two data points, iii) a mono-exponential fitting, iv) a bi-exponential fitting, and v) a mono-
exponential fitting with all data sets (for each radiopeptide) sharing the same decay constant (λ). For each
patient, the best curve was evaluated both by F-test and visually by trained physicists. i), ii), iii), and iv) were
also conducted skipping either the 6h or the 3d datum. Kidney absorbed dose (D) and Biologically Effective
Dose (BED) were calculated in the hypothesis that either 177Lu or 90Y could be chosen as therapeutic nuclide.
The influence on D of the peptide used and of the risk factors was investigated by means of the t-test.
Results Regarding the analytical methods (iii, iv, v), for 177Lu marked variations were found as compared to
the best D estimates (ratios 1.0±0.25), minor (< 10%) as regards the so called relative effectiveness factor
RE=BED/D. For 90Y, D and BED estimates from the three methods were in good agreement. i) and ii) gave
the highest discrepancies, as high as 20%-50%. Risk factors (hypertension, diabetes) caused a rather
significant 20% increase in dose (p<0.10), with DOTATATE effecting an increase of 25% as compared to
DOTATOC (p<0.05).
Conclusion Four data points seem essential to derive the kinetics. If data are not gathered up to two effective
half lives (∼100 h for 177Lu, ∼60-70 h for 90Y), the dose calculation is strongly influenced by the interpolating
method, and should be carefully chosen. The 6 h acquisition could be spared if the aforesaid conditions are
fulfilled. Method v) is inadequate for 177Lu-therapy, but could be used in 90Y-therapy. Risk factors as well as
DOTATATE peptide cause a 20-25 % increase each in D.  

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Dosimetry in Radioiodine Therapy of Thyroid Cancer: A Case Report of Biokinetics Comparison between
First and Second Treatment.
P. Moresco(1), L. Di Ciolo(2), L. Bertolazzi(2)
(1) S.C. Fisica Sanitaria, Ospedale S. Corona di Pietra Ligure ASL2 Savonese; (2) S.C. Medicina Nucleare,
Ospedale S. Corona di Pietra Ligure ASL2 Savonese

Aim of this work has been to compare the iodine retention curves in blood and in the whole body in a young female
patient affected by differentiated thyroid carcinoma (DTC), before and after four months since radioiodine
treatment (administered activity 3145 MBq, serum TG=4.4, TSH 43, FT3=0.96, FT4<0.3 ng/ml), preliminary to a
second treatment, in order to verify if the pre-therapeutic dosimetry data can be used as a reference also for
successive treatments and to determine the activity to be administered in a single cycle delivering a blood absorbed
dose equivalent to several treatments.
Methods and materials: Whole body probe measurements and whole blood collections (2 ml samples) were
conducted 2, 6, 24, 96 and 120 hours after 131I (10MBq) administration to obtain time-activity curves, on the
patient after complete thyroid hormone withdrawal. The values obtained in the first probe count, nominally 2h after
administration with no interim excretion was used to normalize all successive measurements (activity at 2 h =
100%).
Post-therapy dosimetry (serum TG=0.88, FT3/FT4 withdrawal) highlights a reduction in blood retention after 24
hours of 35%, which corresponds to a reduction in blood equivalent dose (0.057 Gy/GBq vs. 0.087 Gy/GBq).
Conclusion: In patients with advanced differentiated thyroid carcinoma (DTC), therapy with the highest safe 131I
activity is desirable to maximize tumor radiation dose and yet to avoid severe myelotoxicity.
The European Association of Nuclear Medicine (EANM) published a standard operational procedure (SOP) for
pre-therapeutic dosimetry in DTC patients incorporating the safety threshold of 2 Gy absorbed dose to the blood as
a surrogate for the red marrow.
In our Centre usually patients are given a standard fixed activity reflecting the physician’s estimation of the
patient’s tumor burden or type, age group, etc.
We perform individualized pre-therapeutic dosimetry, according to EANM SOP, only in selected patients
belonging to critical groups by age (20-40 years, long life expectancy; above 70 years, modified renal iodine
clearance) or by lymphnodal positivity.
Patients return for a second treatment in 10% of the cases. A limited number of them has undergone up to six
treatments with a cumulated activity up to 25 GBq.
The result of this study shows that dosimetry is necessary before each one of several treatments and it confirms the
higher effectiveness of a single high dose treatment reducing the cumulated administered activity compared with
the repeated, limited dose schedules.

References:
[1] M. Lassmann et al., EANM Dosimetry Committee series on standard operational procedures for pre-
therapeutic dosimetry I: blood and bone marrow dosimetry in differentiated thyroid cancer therapy, Eur J Nucl Med
Mol Imaging (2008) 35: 1405-1412
[2] C. Hindorf et al., EANM Dosimetry Committee guidelines for bone marrow and whole-body dosimetry, Eur J
Nucl Med Mol Imaging (2010)
[3] F. A. Verburg et al., The absorbed dose to the blood is a better predictor of ablation success than the
administered 131I activity in thyrpid cancer patients, Eur J Nucl Med Mol Imaging (2011) 38: 673-680
[4] V.Hartung-Knemeyer et. al., Pre-therapeutic blood dosimetry in patients with differentiated thyroid carcinoma
using 134-iodine: predicted blood doses correlate with changes in blood cell counts after radioiodine therapy and
depend on modes of TSH stimulation and number of preceding radioiodine therapies, Ann Nucl Med (2012)
26:723-729

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Studi di scattering basati su metodo Monte Carlo allo scopo di implementare correzioni paziente-specifiche
per dosimetria 3D in radioterapia metabolica: risultati preliminari con fantocci

Monte Carlo based scattering studies aiming to patient-specific corrections for 3D dosimetry in radionuclide
therapy: preliminary results with phantoms

Becci D1, Pacilio M2, Torres Aroche LA3, Coca Perez MA3, Cremonesi M4, Botta F4, Basile C2, Ventroni
G5, Pani R6
1
Post Graduate School of Medical Physics, Sapienza University of Rome, Italy, 2Medical Physics Department, San
Camillo Forlanini Hospital, Rome, Italy, 3Medical Physics Department, Centre for Clinical Research, Havana,
Cuba, 4Medical Physics Department, European Institute of Oncology, Milan, Italy, 5Nuclear Medicine Department,
San Camillo Forlanini Hospital, Rome, Italy, 6Molecular Medicine Department, Sapienza University of Rome,
Italy.

AIM-Scatter correction is crucial for improving accuracy in 3D dosimetry for radionuclide therapy. Multiple-
energy windows techniques are generally used in clinical imaging without any patient-specific optimization of
window width (WW) or scatter multipliers (SM). Our investigation aims to develop Monte Carlo (MC)-based
procedures for patient-specific scatter corrections in clinical settings. Preliminarily, a study with Jaszczak and
Zubal phantoms was performed, and the results are here reported.
MATERIALS & METHODS-The SIMIND code was used for MC simulations, basing on Jaszczak phantom
experimental acquisitions the benchmarking with the GE Infinia Hawkeye 4 SPECT/CT system, in terms of:
mean counts in ROI positioned on background and hot objects (1 cylindrical and 5 spherical objects), and counts
profiles on both projections and tomographic image, for 99mTc imaging. All reconstructions (experimental and
simulated studies) were performed with the GE Xeleris 2 workstation, with OSEM (2 iterations, 10 subsets).
For attenuation correction, Chang's first order was applied for Jaszczak, and non-uniform attenuation map
was created for Zubal phantom. So far, the Zubal phantom torso was simulated with the following 99mTc
activity concentrations ratios: liver and spleen, 50; lungs, 15; other organs, 1. The gold-standard (GS)
images were the MC scatter-free simulations of both phantoms for MC studies, or the "empty-tank" acquisition of
the Jaszczak phantom, for experimental studies. The three-energy (with both trapezoidal, or triangular
approximations, TEW and rTEW, respectively), and dual-energy window (with a 10% wide scatter window
centered @120 keV, DEW) methods were optimized in terms of WW or SM, by counts profiles comparisons and
normalized-mean-square-error (NMSE) between the GS and tested tomographic images.
RESULTS-The best methods (among those examined up to now) were the following. For Jaszczak phantom: with
DEW, SM=2.2 (NMSE=1.2%); with TEW, SM=1.1 and WW=4% (NMSE=0.2%); these values were also verified
experimentally. For Zubal phantom: with DEW, SM=0.44, (NMSE=1.04%); with rTEW, SM=0.33 and WW=4%
(NMSE=1.1%). So, the standard GE protocol (DEW with SM=1.1) would not result adequate for accurate 3D
dosimetry.
CONCLUSION- For the tested methods, the optimized values for SM differ notably between Jaszczak and Zubal
phantom, confirming that scatter corrections specialized for patient and anatomical district are strongly advisable
for 3D dosimetry.

ELENCO
 
TOPIC ESC
 
  MEDICINA LA FISICA MEDICA
RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
  RICERCA NUCLEARE
SANITARIE
 
A Novel Radioguided Surgery Technique Exploiting β - decays

E. Solfaroli(a), G. Baroni(b), F. Bellini(c,d), F. Collamati(c,d), M. Cremonesi(e), E. De Lucia(j), P. Ferroli(f), S.


Fiore(g), C. M. Grana(e), M. Marafini(h,d), I. Mattei(i,j), S. Morganti(d), G. Paganelli(e), V. Patera(k,d),L.
Piersanti(k,j), A. Russomando(a), M. Schiariti(f), A. Sarti(k,d), A. Sciubba(k,d), C. Voena(d), R. Faccini(c,d)

(a) Center for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia, Roma, Italy;
(b) Dip. Bioingegneria, Politecnico di Milano, Italy;
(c) Dip. Fisica, Univ. Di Roma 'La Sapienza', Roma, Italy;
(d) INFN sezione di Roma, Roma, Italy;
(e) Istituto Europeo di Oncologia, Milano, Italy;
(f) Fondazione Istituto Neurologico Carlo Besta, Milano, Italy;
(g) ENEA UTTMAT-IRR, Casaccia R.C., Roma, Italy;
(h) Museo Storico della Fisica e Centro Studi e Ricerche `E. Fermi', Roma, Italy;
(i) Dipartimento di Fisica, Universit\`a Roma Tre, Roma, Italy;
(j) Laboratori Nazionali di Frascati dell'INFN, Frascati, Italy;
(k) Dip. Scienze di Base Applicate all'Ingegneria, Univ. Di Roma 'La Sapienza', Roma, Italy.

The radio-guided surgery (RGS), which was first developed some 60 years ago, is a surgical technique that enables
the surgeon to perform complete lesion resections, minimizing the amount of healthy tissue removed [1]. The basic
idea is to administer to the patient, before surgery, a radio-labelled tracer that is preferentially taken up by the
tumor and to exploit, during surgery, a specific probe system[2] to detect the emission released by the targeted
tumor cells in real time. After the mass removal, the surgeon explores the lesion with the radiation detection probe
and looks for tumor remnants, difficult to identify by the naked eye. Hence, the impact of RGS on the surgical
management of cancer patients includes providing vital and real-time information to the surgeon regarding the
location and extent of disease, as well as the assessment of surgical resection margins.

Some current clinical applications of RGS are: radio-immuno-guided surgery (RIGS) for colon cancer, complete
sentinel-node mapping for malignant melanoma and breast cancer, and detection of parathyroid adenoma and bone
tumors (such as osteoid osteoma).

In general, established methods make use of a γ radiation detection probe but other radiation detection devices,
exploiting β+ decaying tracers, are under development (e.g. Ref. [3]). The β+ decays emit positrons that can be
detected directly, although, interacting with the electrons in the body, they annihilate and produce γs.

A limit to the applicability of the RGS to other tumours comes from the high penetration power of the γ radiation.
It can traverse large amounts of tissue, so it is not desirable in surgical environment since an eventual uptake of the
tracer in nearby healthy tissue would represent a non-negligible background, sometimes preventing the
applicability of the technique. This is for instance the case for brain tumors for which RGS is not applied due to the
large uptake of radio-tracers from the healthy brain when β+ emitting tracers, like $^{18F-FDG, are administered.

This paper present an alternative tecnique based on b- radiation detction that may extend the applicability of the
radio-guided surgery. The main advantage of such approach is that b- radiation penetrates only a few millimetres,

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
not considering bremsstrahlung emission, which yields long range γ radiation in less than 0.1% of the cases, and
therefore the RGS exploiting β- emitters suffers from a lower background rate.
A β- probe, detecting electrons and operating with low radiation background, provides a clearer delineation of
margins of radioactive tissue , requires a smaller radio-pharmaceutical activity to detect residuals and allows the
technique to be applied also to cases with a large uptake of nearby healthy organs. The lower administered dose,
together with the short range of electrons, also implies an almost negligible exposure for the medical team and
therefore a larger number of RGSs per year for the surgeon. Finally a β- probe, detecting electrons and operating
with low radiation background, provides a clearer delineation of margins of radioactive tissue and it is a more
compact, simple and economic tool, an essential feature for application in surgery as the access to the lesion is
limited.

In order to develop a radio-guided technique exploiting β- decays and to quantify the impact of this innovation in
the field, our research activity has evolved in two directions: the identification of a clinical case for testing and the
development of a specific intra-operative probe device.

The clinical case.


To identify a first clinical case to test this technique, a β- emitting tracer taken up preferentially by a tumor of
interest is needed. We note that patients affected by meningioma can be treated with the Peptide Receptor
Radionuclide Therapy (PRRT) (e.g. Ref. [4]) which involves systemic administration of synthetic somatostatin
analogues, such as DOTATOC, radio-labelled with suitable β- emitting radionuclide, like 90Y. The PRRT has been
developed over the past two decades and its therapeutic efficacy and safety have already been demonstrated in
many clinical trials. Therefore the 90Y labelled DOTATOC is identified as a good candidate for a radio-guided
removal of meningioma.
In perspective, a similar tracer is to be searched for glioma (each tumor of interest requires its own tracer) that
represent an even more interesting disease.

The β - detecting probe.


As far as the probe design is concerned, the choice of the materials and the readout electronics is driven by the need
to maximize the sensitivity to electrons, while minimizing the sensitivity to photons. P-terphenyl was adopted after
a detailed study [5] due to its high light yield and low density, with consequent scarce sensitivity to photons.

A first prototype of the β- probe was developed: the core is a cylindrical scintillator (diameter 2.1 mm, height 1.7
mm) of poli-crystalline P-terphenyl, shielded from the external light by a thin PVC layer. A 2.8 mm thick ring of
PVC wraps the scintillator and shields it against radiation coming from the sides. The device is encapsulated inside
a thin aluminium body for easy handling and to preserve it from mechanical stress and external light. The probe
prototype was tested in laboratory, using the 90Y β- radionuclide in physiological saline.
The short half life (64 h) makes possible to study a wide range of activity from 22 to 5 kBq/ml: DICOM images
obtained with a Positron Emission Tomography with 68Ga-DOTATOC for patients affected by meningioma were
used to estimate that administering a typical diagnostic activity of 3 MBq/kg of 68Ga-DOTATOC to a patient, the
tumor activity is about 20 kBq/ml. We therefore explore activity at most as high as the diagnostic one.

We tested the response of the first prototype to four phantoms simulating cancerous residuals with different
topologies: the 0.1 ml volume phantom (called "RESIDUAL") has dimensions compatible with residuals well
identified with nuclear magnetic resonance imaging technique and it represents a good reference for further clinical
tests; other three cylindrical phantoms have same area of the circular face (13 mm2) but different heights (1, 2, 3

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
mm, called "H1", "H2, "H3" respectively), to check the effect of the phantom depth in the probe response and in
distinguishing the residual edge.

Tuning the electronic threshold of our device to have a background rate of 0.2 cps, we measured for each phantom
rates ranging from 2.3 cps (for the H1 sample) to 18 cps (for the RESIDUAL sample). We also verified that in all
the cases moving the probe away from the phantoms results in a decrease in rate, reaching half of the central value
when the centre of the probe is 0.5 mm far from the volume edge.

Estimation of the β - RGS performance under real conditions for a meningioma.

To translate the observed rates into actual sensitivity to tumor residuals, the impact of the background from the
noise coming from uptake in healthy tissues is needed. Given the detection efficiencies estimated in the laboratory
tests and the above-mentioned DICOM images of the uptake of 68Ga-DOTATOC, we have implemented a
simulation with the FLUKA program [6] to estimate such background, mostly coming from the dura mater close to
the lesion, that reveals an activity a factor ten smaller than the tumor.
The simulation allows therefore to conclude that the healthy dura mater yields in the probe a signal of 3 cps, if the
tumor takes 22kBq/ml and 0.7 cps if it takes 5 kBq/ml.

From the signal and background rates, taking into account the Poisson fluctuations of the actual counts in a given
time interval, we could compute the false positive and the false negative rates. By requiring both the false positive
and the false negative rates to be below 1% we could estimate the minimal time that the probe needs to be on the
sample of interest. From these calculations we conclude that at 22kBq/ml all the samples are visible within 2s,
while 5kBq/ml would require to wait at least 10s. Further development is therefore ongoing on the probe to be able
to reduce such intervals in order to allow the system to work with 5kBq/ml.

Finally, To evaluate the amount of radiation absorbed by the surgeons themselves we simulated a set-up similar to
the common situation of an operating room. Both activities of neoplastic cells and normal tissue were taken into
account, according to the ratios obtained from the aforementioned studies on PET images.
The equivalent dose to the surgeon's hands computed for RGS with 90Y emitting tracer is expected to be smaller
than µSv/hour. This value is to be compared with the corresponding value for established RGS with 99mTc as radio-
label tracer, which is 24 µSv/hour. Similarly, the whole body of the surgeon takes 0.13 µSv/hour with the β- RGS
here proposed, to be compared with approximately 6 µSv/hour delivered by the 99mTc RGS.

[1] see, for instance, Mariani G, Giuliano A E, Strauss H W Edts, "Radioguided Surgery: A Comprehensive Team
Approach" Springer (2006)

[2] see, for instance, Hoffman E J, Tornai M P, Janecek M, Patt B E and Iwanczyk J S, "Intraoperative probes and
imaging probes", Eur J Nucl Med (1999) 26:913 or

Povoski S P et al. "A comprehensive overview of radioguided surgery using gamma detection probe technology",
World Journal of Surgical Oncology (2009) 7:11

[3] Bogalhas,F. et al. ”Development of a positron probe for localization and excision of brain tumours during
surgery.” Phys. Med. Biol. 54 443-4453 (2009)

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
[4] Bartolomei M, Bodei L, De Cicco C, Grana C M, Cremonesi M, Botteri E, Baio S M, Aric\'o D, Sansovini M
and Paganelli G "Peptide receptor radionuclide therapy with (90)Y-DOTATOC in recurrent meningioma" Eur J
Nucl Med Mol Imaging (2009) 36:1407-1416

[5] M. Angelone et al., “Properties of para-terphenyl as detector for α, β, and γ radiation”, arXiv:1305.0442,
submitted to T.N.S.

[6] Ferrari,A. Sala,P.R. Fasso,A. and Ranft,J. ”FLUKA: a multi particle transport code.” Tech. Rep. CERN-2005-
10, INFN/TC05/11, SLAC-R-773 (2005)

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Gross tumour volume definition using PET for of head and neck cancer
O. Ferrando1, F. Foppiano1, M. Piergentili1, A. Chimenz1, T. Scolaro2, A. Ciarmiello3, C. Gaeta3
(1) S.C. Fisica Sanitaria (2) S.C. Radioterapia (3) S.C. Medicina Nucleare, ASL5 Spezzino, La Spezia

Purpose: For radiation therapy applications target volume contouring using positron emission tomography (PET)
is an important tool to delineate tumour boundary. Gross tumour volume (GTV) contours for radiotherapy are
typically based on computed tomographic data. Clinical studies, however, indicate that PET has higher sensitivity
than CT in detecting and staging neoplastic lesions, therefore, imaging with FDG (fluore-2-deoxyglucose) PET in
conjunction with CT can improve the accuracy of the target definition. In this study we investigate the possibility
to define tumour volumes using PET imaging in head and neck cancer. GTV contouring on PET images was
performed using an adaptive thresholding method based on standardized uptake value (SUV). The GTV contours
obtained with PET images were compared to GTV contours defined on CT images in order to assess discrepancies
and validate the segmentation method based on adaptive thresholds.
Materials and Methods: In January 2013 a GE DISCOVERY TM 710 PET/CT scanner was installed in our
institution. Up to now we have selected and analysed a set of 15 patients with histological diagnosis of head and
neck cancer who undergo conformal-3D radiotherapy. For these patients FDG-PET images were acquired and
PET-Based tumour volumes were determined with an automatic image segmentation tool (PETVCAR Ge
Healthcare) that defines the best threshold for volume contouring as a percentage of the maximum standardized
uptake value (SUV). SUV is a measurement of the uptake in a tumour normalized at a certain distribution volume
and it is calculated as follows [1]:
Act voi kBq/ mL
SUV =
Act admin MBq/ BW Kg 
where Act is the activity concentration measured in the volume of interest, Act is the administered activity
voi admin
corrected for the physical decay of 18F and BW is the body weight.
Different elements influence the accuracy of the standard uptake values in PET studies such as: variations in PET
tomograph calibrations, cross-calibration of PET camera and the dose calibrator used to measure patient FDG
activities, patient preparation and acquisition protocol, image reconstruction data. These elements can have 30%
-50% effects on the measured SUV value [2]. For these reasons a set of quality control must be carried out before
starting PET image evaluation based on SUV calculations. Daily quality controls (energy shifts, coincidences,
singles, deadtime, timing) are needed to check detector failure or electronic drift. Cross calibration of PET camera
and dose calibrator have to be performed at the aim to minimize the differences in activity measurement between
the two systems. Image reconstruction parameters, scan time and patient preparation can influence SUV values and
therefore it is important to select an appropriate protocol for image acquisition and reconstruction.
SUV calculations and thresholds depend also on the segmentation tools used for volume contouring. Threfore
these tools must be validated before being used for radiotherapy target volume definition. A validation method is
based on anthropomorphic phantom studies containing spheres of different volumes and activity concentrations as
described in the follows. To define the accuracy of the concentration activity determined with the segmentation tool
and the relationship between thresholds and volume, we performed a study using a cylindrical phantom (NEMA
IEC image quality phantom) with 9 spheres of different volumes ranging from 0.1 mL to 100 mL. Each sphere was
filled with a concentration of 18F similar to those observed in clinical cases (about 10 kBq/mL). Different
background/sphere ratios (RatioB/S) were used, ranging from 70 to 2. PET scans of the phantom were performed for
3 minutes with Time of Fligth (TOF) acquisition. Images were reconstructed using 3D-OSEM including a filter of
4mm and Point Spread Function algorithm (PSF). In the reconstructions 18 subsets and 3 iterations were used.
Thresholds were calculated as a percentage of the maximum concentration activity inside the sphere.
As shown in Figure 1 the relation between volume and threshold is linear for volumes up to 2.5 mL while for
lower dimensions the partial volume effects cause an increase in threshold values with an exponential beahviour.

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Figure 1. Measured thresholds versus sphere volumes for different RatioB/S

The data for volumes up to 2.5 mL were fitted with a linear regression model to define the following relation:

{C 1  2} spherevol
Threshold =C 1 1 C 2 1⋅sphere volC 2 2⋅
Ratio B / S  Ratio B /S 
C1, and C2 are the coefficients defined by the regression. The PSF algorithm determines spatial resolution of the
imaging system. The use of this algorithm produces some smoothing that can result in an underestimation of
activity concentrations and overestimation of the object size. To compensate for the decrease in measured activity a
recovery coefficient (RC) , defined as the ratio between the observed concentration in the final image and the real
activity concentration, was calculated for each sphere. The Recovery Coefficient can be calculated using the
following formula:
C sphere
 −1
C bkg
RC =
a sphere
 −1
abkg

where Csphere is the measured concentration in the sphere and Cbkg is the measured concentration in the background,
asphere is the true concentration in the sphere and a bkg is the true concentration in the background. The thresholds
values measured on the phantom were corrected by the recovery coefficients for each sphere volumes. Patients
underwent PET/CT scan approximately 60 minutes after administration of about 250 MBq of 18F-FDG. CT images
were acquired at 130 kV and variable mA using the automatic current modulation. PET images were acquired for
3 minutes at each bed position, reconstructed with CT-based attenuation correction and OSEM algorithms. An
individualized thermoplastic mask with external markers imobilized the head and the neck of the patient and served

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
as reference for isocenter localization and patient positioning during the RT treatment. Axial CT images were
acquired and reconstructed with thickness of 2.5 mm thickness (for treatment plan calculations) and with 3.75 mm
thickness for PET fusion. The images were transferred from the PET/CT database to the PET/CT workstation for
SUV analysis. SUV analysis was perfomerd with the same segmentation tool used for the phantom threshold
definition. For each patient SUV max for the tumour lesions and SUV mean for background were reported.
Contouring of the PET images was performed using the thresholding method, the threshold values were adapted to
the Ratio(B/S) and the lesion volumes were evaluated to define the GTV_PET. The delineation of the CT-Based
tumour volume (GTV_CT) was accomplished contouring the primary lesion and lynph nodes on the axial CT images
using the treatment planning contouring tools. The volume of the lesions was calculated and compared with the
volumes defined with PET countouring.
For data analysis and comparison of GTV_CT and GTV_PET we take into consideration the following parameters:
the SUVmax, the threshold defined as a percentage of SUVmax, the GTV defined on the PET only, the GTV
defined on th CT only, the ratio of GTV_PET/GTV_CT and the discrepancy between GTV_PET and GTV_CT .
The threshold range spreads from 27% to 54%, the mean threshold for primary tumour results 30% while for
lymph nodes is 36%. The threshold values increase for smaller volumes. The value of SUV max varies from 3 to
30 mg/mL. Volumes defined with PET were generally larger then volumes defined with CT and discrepancies
between the two modalities have a maximum and mean values of respectively 10% and 3% . PET volumes are
probably greater than CT volumes since in the adaptive thresholding method the values of SUVmax for small
lesions is affected by partial volume effects and result smaller then the true value, therefore the calculated
thresholds as a percentage of the maximum SUV are inadequate.
Conclusions: The aim of this work was the comparison of the tumour volumes defined with the standard
segmentation methods based on CT images with the volumes obtained by segmentation method PET based. We
have analysed the discreapancies bewteen both modalities. To investigate the accuracy of PET derived volumes we
have accomplished a phantom study and analysed a set of clinical cases with head and neck patology. Phantom
data analysis shows that threshold volume curves are dependent on lesion size, source to background ratio, image
reconstruction and smoothing filter. The same dependence was observed on patient data. A mathematical relation
between these parameters can be defined for lesions with volume > 2.5 mL and applied to patient contours to
define the optimal thresholds for lesion volume definition. For smaller lesions, volumes derived from thresholding
methods are strongly sensitive to partial volume effects. A small change in threshold contour can generate a
significant increase in the lesion volume, therefore PET volume definition for lesion with dimensions < 2.5 mL can
be inadequate. From our study we consider that, even if the adaptive thresholding method applied to PET imaging
can be a promising tool to delineate tumour volumes, further investigations must be accomplished before this
thecnique being applied routinary to Radiotherapy target delineation. In particular it should be important, in the
clinical cases where it is feasible, to obtain an histological validation of the lesion volumes defined with PET.
Moreover since the method is system specific, the whole chain from PET scanner to automatic contouring tools and
treatment planning system have to be submitted to a stringent quality control procedure.
References:
[1] R. Boellaard and all, FDG PET and PET/CT: EANM procedure guidelines for tumour PET imaging: version 1,
Eur J Nucl Med Mol Imaging (2010) 37:181-200
[2] R. Boellaard, Standard for PET Image Acquisition and Quantitative Data Analysis, J Nucl Med (2009) 50:11S-
20S

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
Implementazione e verifica del metodo di ricostruzione della mappa di attenuazione dopo movimento
durante scansioni PET-TC Brain.

Implementation and verify of attenuation map for motion–induced misalignament in PET-CT brain
registration .

L. Ferri 1, M.Bevegni 1 , G.Siclari 2 , S.Morbelli 2 , G.Taccini 1


(1) Medical Phisics, (2) Nuclear Medicine, A.O.U. IRCCS San Martino IST, Genoa, Italy.
Purpose: The aim is to provide and verify a procedure to correct misregistration artefact due to the motion of the
patient during the PET scan or between Computed Tomography (CT) and Positron Emission Tomography (PET)
acquisitions.
Methods and materials: CT is used for the attenuation correction of PET to enhance the efficiency of data
acquisition process and to improve the quality of the reconstructed PET data in the brain. Patient motion during the
PET scan and between the PET and CT acquisitions can produce significant artifacts on the fused images as it
cause confusion about the correct position of the origin of the detected photon. Misalignment produces an
erroneous CT attenuation map that can project the bone and water attenuation parameters onto the brain, thereby
under- or over-estimating the attenuation.
PET CT imaging is performed on a hybrid system (Siemens Biograph™16 TruePoint™), PET acquisition in list
mode allows several frames acquisition. Radioactive phantom is used to simulate patient movements. Reasonably
is assumed that patients could move not immediately at the beginning but during PET acquisition, thus radioactive
phantom source is moved after 150 seconds. Reconstruction is performed on the first 2 minuts frame to define the
correct attenuation map. Remaining frame is reconstracted using that correct attenuation map.
Results: We obtain 2 different PET/TC which don’t show misalignement artefact. Physicians could choose the
clinically more relevant reconstruction.
Conclusion: This is only the first step. To be clinically interesting PET/CT images should present enough
detection, next step will be all PET acquisition data reprocessing.
References:
[1] Ay M., Sarkar S Sources of Error and Artifact in CTAC in PET/CT. Iran J Nucl Med 2007, Vol 15 No 2.

ELENCO
 
TOPIC ESC
 
  MEDICINA LA FISICA MEDICA
RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
  RICERCA NUCLEARE
SANITARIE
 
SPECT/CT can be an useful tool to define thyroid volume in Graves’ disease?
O. Ferrando1, F. Foppiano1, L. Mondini1, M. Piergentili1, A. Chimenz1, A. Ciarmiello2, M. Meniconi2
(1) S.C. Fisica Sanitaria (2) S.C. Medicina Nucleare, ASL5 Spezzino, La Spezia

Purpose: For radioiodine therapy in patients with Graves' disease individual dosage are frequently applied. In
these therapies the activity given to patients is proportional to radioiodine uptake an thyroid volume which
therefore has to be defined accurately [1]. Measurement of the thyroid volume are usually made with
ultrasonography or scintigraphy. Ultrasonography is probably the most frequently used modality for thyroid
estimation in the routine clinical setting; volume evaluation is generally made with an ellipsoid model using the
measurement of the dimensions along the three axes of the thyroid lobes. Because of its superficial location, the
thyroid gland is suited fo high-frequency sonography (7-13 MHz transducer) which allows the detection of
clinically non-palpable nodules of 2-3mm size with a more accurate morphological definition of the lesion. It is
also used to determine the size and number of thyroid nodules, to assess the volume of thyroid tissue in cases of
thyromegaly and to differentiate thyroid masses form adjacent non-thyroid volumes.
Scintigraphy is used to produce functional images of the thyroid gland, however the accuracy of planar
scintigraphy in thyroid definition volume is not well established due to translation of a three dimensional volume in
a planar surface. SPECT enables improved accuracy over planar imaging since the volume of interest is calculated
from three-dimensional data. Introduction of hybrid SPECT/CT systems can represents a further improvement in
volume definition since the functional information derived from SPECT are associated with morphological data of
CT images. Aim of this study is to investigate the possible advantages in evaluating thyroid volume with
SPECT/CT systems.
Materials and Methods: In March 2013 an hybrid SPECT/CT Simens Symbia T2 was installed in our institution
and up to now we collected a court of 10 patients classified as hyperthyroid patients for thyroid volume evaluation.
The patients underwent an ultrasonography exam, a planar scintigraphy and a SPECT/CT acquisition. Planar
scintigraphies were acquired on a dual-head gamma camera (Siemens ECAM dual-head) equipped with a pinhole
collimator. Thomografic scintigraphies were acquired with the hybrid system Symbia which includes a dual head
gamma camera integrated with a 2 slices – CT. Thyroid volumes were determined in the three modalities and
compared.
Planar scintigraphy
Planar scintigraphies were done 30 min after intravenous administration of 37 MBq Technetium-99m
pertechnetate. The acquisition was made with a pinhole collimator mounted on one head of the gamma camera
positioned at 90 degrees. The acquisition parameters were: anterior view, 256x256 matrix, zoom factor 1.6, pixel
size 0.9 mm, acquisition time 165 sec. Images were reconstructed using Filtred Back Projection.
On the images an isocontour of 45% of the maximum pixel count was created, the optimal threshold level had
been established by phantom studies with volumes ranging to 10 and 50 mL. The two lobes of the gland were
approximated with two elliposoids which axes are the longest cranio-caudal axis, the medial lateral axis and the
posterior-anterior axis. The thyroid volume evaluation is based on the measurement of long (A) and lateral (B) axes
from the isocontour of the scintigraphic image. The thickness of the lobes (C) is empirically assumed to be equal to
the minor lateral axis of the corrisponding lobe. The volume of each lobe is calculated using the ellipsoid formula:

V =/6⋅A⋅B⋅C
SPECT/CT
After the planar scintigraphy exams, the patients underwent a SPECT/CT. The SPECT exams were made with a
dual head gamma camera equipped with a low energy general purpose parallel hole collimator. The acquisition
parameters were: 128x128 matrix, zoom factor 1, 64 views in step and shoot mode over 360 degrees, total
scanning time of 320 sec. Images were reconstructed using iterative algorithms including attenuation, scatter and
decay corrections.

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE
The CT acquisitions were made with the following parameters: 130 kV, automatic current modulation, 5 mm slice.
The image reconstruction was made with iterative algorithms. The CT acquisitions were used to perform scatter
and attenuation corrections. For the segmentation of the thyroid gland on the SPECT image, a threshold of 45% of
the maximum pixel value was considered. On the CT image the thyroid gland was contoured manually on each
slice by an experienced nuclear physician and the lobe volume was evaluated using the volume definition tools
aivalable on the post-processing workstation.
Ultrasonography
Ultrasonography exams were accomplished with a real-time ultrasound scanner with a 7.5 MHz liner transducer.
The thyroid lobes were scanned with the patient in the supine position and the neck sligthly overextended. The
volume of each lobe was calculated with the standard formula of an ellipsoid.
Results: Comparison of volume thyroid determined from ultrasonography and planar scintigraphy shows a linear
correlation between the two set of data (R2 = 0.84) but planar scintigraphy in most cases overestimates the thyroid
volume (39%). Planar scintigraphy provides two dimensional imaging, the lack of third dimension (depth)
inevitably lead to inaccurate volume estimations. For these reasons we consider that planar scintigraphy is not
adequate for therapeutic dosage calculations. SPECT with attenuation correction and scatter correction provide
more accurate volume estimations. The comparison between thyroid volumes determined with SPECT/CT and
ultrasonography shows a good correlation (R2 = 0.97) with smaller relative volume differences than planar
scintigraphy (10%). Also CT and ultrasonography show good linear correlation with R2 = 0.95.
Conclusions: Comparison of three different modalities (planar scintigraphy, ultrasonography and SPECT/CT) of
acquiring and evaluate thyroid volume shows that planar scintigraphy is inaccurate while SPECT/CT and
ultrasonography are almost equivalent but we observed that the result of the ultrasonography exams can be largely
operator-dependent respect to CT exams. Moreover the use of CT can be particulary indicate in case of thyroids
with large dimensions and retrosternal goiter since it provides a better definition of the total volume than
ultrasonography.
References:
[1] Linee guida SIE-AINM-AIFM per il Trattamento Radiometabolico dell'Ipertiroidismo, AINM, SIE, AIFM
2004

ELENCO TOPIC ESC

MEDICINA LA FISICA MEDICA


RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
RICERCA NUCLEARE
SANITARIE