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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
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
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
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)
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
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
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
Dosimetria nella terapia del tumore tiroideo con radioiodio: studio comparativo della biocinetica fra il
primo ed il secondo trattamento. P. Moresco, Pietra Ligure (SV)
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
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.
TB74
120% TB74 120%
TB53 TB53
100% 100%
TB37 TB37
80% 80% TB23
TB23
HC_RC
HC_RC
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
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.
C. Chiesa
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.
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:
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
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
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.
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.
1
Normal Tissue Complication probability
0.8
0.6
0.4
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.
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).
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
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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
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.
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).
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.
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
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.
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.
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.
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
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
10 10
RM absorbed dose (Gy)
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
1
Normal Tissue Complication probability
0.8
0.6
0.4
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%).
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.
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.
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.
provisional 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
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.
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
ND=4,563*(Nbkg)1/2+2,706
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.
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
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.
Radioembolizzazione di lesioni epatiche con sfere SIR® caricate con 90Y: confronto tra dosimetria da
SPECT con 99mTc-MAA e PET con 90Y
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.
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
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).
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.
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
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
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.
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.
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
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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.
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).
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MEDICINA LA FISICA MEDICA
RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
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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.
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
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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
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.
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.
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
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.
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%).
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.
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%.
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.
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
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)
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 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
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.
Analyzing the ratio between measured and theoretical SUV results in a similar logarithmic pattern for all the
phantoms and for all the physicians:
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
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)
Where the error is measured as the standard deviation of the distribution of the values for each 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
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.
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)
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.
(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.
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
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.
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
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.
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.
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).
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.
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).
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.
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TOPIC ESC
MEDICINA LA FISICA MEDICA
RADIOTERAPIA IMAGING NIR RADIOLOGIA FORMAZIONE NELLE STRUTTURE RADIOPROTEZIONE
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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
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
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
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]
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.
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.
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
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:
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
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
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.
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
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
(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,
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.
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
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.
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)
[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)
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.
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 volC 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
Implementation and verify of attenuation map for motion–induced misalignament in PET-CT brain
registration .
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.