Neurological System

Li Yanmei
Department of Nuclear Medicine
General Hospital of NXMC
email: amay5059@163.com
cellphone: 13895496683

1 PET/CT SPECT/CT
 Nuclear neurology

1.Cerebral blood flow perfusion tomography

2.Cerebral metabolic imaging

3.Neurotransmitter and neuroreceptor imaging.

2
 Objectives
Master the rationale of cerebral blood flow perfusion
imaging and cerebral glucose metabolic imaging.

Master the clinical applications of cerebral blood flow

perfusion imaging and cerebral glucose metabolic
imaging.

Familiar with the image interpretation of cerebral

blood flow perfusion imaging and cerebral glucose
metabolic imaging.

3
 Introduction
Before the development of computed tomography
(CT) in the 1970s, radionuclide brain scans were
the only noninvasive method for diagnosing
diseases of the brain, including tumors ,strokes,
and vascular anomalies.

4
 In current practice, MRI and CT play preem
inent roles in clinical brain imaging, producin
g superb anatomical images of the central n
ervous system (CNS). but nuclear medicine t
echniques provide unique diagnostic informati
on based on imaging physiology.

5
SPECT and PET can both visualize
alterations in function before
anatomical changes can be
detected.

6
Clinical diagnoses based on abnormalities
of cerebral blood flow(CBF) and glucose
metabolism are now made routinely using
various single-photon and positron
radiopharmaceuticals with both PET and
SPECT instrumentation.

7
Especially in recent years, the study on central
neurotransmitter and functional activities of brai
n receptor in various physiological and pathologic
al conditions from the molecular level in vivo. Th
erefore, nuclear neurology has unique advantages
in clinical diagnosis and treatment of neuro-psyc
hiatric diseases, cerebral physiological and bioch
emical function, mechanism of pathology and cog
nitive function in the human brain and has broad
prospects.
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 Cerebral Anatomy

9
 The brain consists of the two cerebral
hemispheres . Each cerebral hemisphere is
associated with sensory and motor function
for the opposite side of the body.

10
 The cerebral cortex is composed of gray matter
and anatomically divided into lobes, respectively,
the occipital lobe, the frontal lobe, parietal lobe
and the temporal lobe.

【 11】
11
The most posterior segment of the cortex is the
occipital lobe, with the right and left visual
cortices on either side of the fissure. A large,
deep fissure, the lateral sulcus, divides the
frontal and parietal lobes from the temporal
lobe.

12
 The frontal lobe extends from the anterior portion of
the brain to the central sulcus. Extending along the
central gyrus, which is the motor center of the
cortex. The postcentral gyrus, the sensory center of
the cortex, runs along the posterior margin of the
central fissure.

13
 Beneath the gray matter of the cerebral
cortex lies the white matter, composed
of myelinated fibers connecting the
cortex with other parts of the brain and
spinal cord.

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 The basal ganglion
what’s the
composed o
f the basal
ganlion?

15
The basal ganglion (caudate nucleus,
putamen, and globus pallidus ) is the central
gray matter of the cerebrum and lies
between the insula and the thalamus,
separated by the internal capsule of the
cortical white matter.

16
 Cerebral Blood Flow Perfusion
Tomography and the Quantification
of Regional Cerebral Blood Flow

17
 Rationale
1. SPECT cerebral perfusion imaging.
Cerebral perfusion agents share several
common characteristics that they are lipophilic
and have a small molecular size and a neutral
charge. They are permitting rapidly diffusion
cross the normal blood-brain barrier, and then
taken up by brain cells. It is converted to a
water-solubility complex that can not diffuse
back across the BBB and fixed in the brain
cells.

18
 Radiopharmaceuticals
The Tc-99m labeled agents used routinely
for SPECT cerebral perfusion imaging.

1. Tc-99m HMPAO
2. Tc-99m ECD.

19
 The Tc-99m perfusion agents are
relatively fixed in brain cells.
Therefore, delayed imaging shows
what the perfusion pattern looked
like at the time of injection.

20
 After intravenous injection, relative
uptake of agent by brain cells is
positively related to regional
cerebral blood flow(rCBF). With
image reconstruction, we can obtain
cross-sectional images, coronal-
sectional and sagittal-sectional
images which show the radioactivity
distribution in brain, cerebellum,
basal ganglia and brain stem.

21
With ROI technology and certain
physiological mathematical models,
regional cerebral blood flow in parts
and cerebral mean blood flow can be
calculated.

22
 Rationale
2. PET cerebral perfusion imaging.
5min after intravenous injection of the d
rug(13NH3.H2O), with 2 or 3-dimensional
acquisition modes for PET cerebral blood
flow perfusion imaging, high quality image
s of above mentioned three different sec
tions and related quantitative parameters
can be obtained by processing raw data.

23
 Stress test of cerebral blood flow perfusion imaging

As the brain blood supply system has a certain reserve

capacity, the conventional cerebral blood flow
tomography can not show the abnormality commonly
when the cerebral blood flow reserve is only
decreased. Stress test of SPECT or PET cerebral
perfusion tomography can reflect the changes in
cerebral blood flow and metabolism, it could provide
the positive rate of ischemic encephalopathy, in
particularly the positive rate of a potential ischemic
encephalopathy lesions.

24
There are several stress test methods commonly used:

drug intervention test

exercise stress test
CO2 inhalation test.

This stress test is mainly used to evaluate the reserve

of cerebral circulation and it has great value on the
early diagnosis of ischemic cerebrovascular disease.

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 Methodology

Functional brain imaging requires strict

adherence to a standard protocol.
The radiopharmaceutical should always be
injected under the same environmental
circumstances (e. g, room lighting,
background noise, patient position ).

26
 Standardization is important for
proper interpretation. Otherwise,
functional differences in metabolism
and thus perfusion may be seen.

27
 For example, occipital parasagittal
visual center activation depends on
whether the eyes are open or
closed.

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 Image Interpretation

29
Normal distribution
SPECT cerebral perfusion
radiopharmaceuticals are distributed
throughout the gray matter of the brain ,
and uptake reflects the distribution of
rCBF.

30
 Normal distribution

Relatively high uptake is in the gray matter

of brain and cerebellum, basal ganglion,
thalamus and brain stem on the cerebral
perfusion images. The radioactivity is
distributed in symmetry and uniform.

31
Uptake is highest in the cerebellum,
followed by the temporal, parietal,
frontal lobes and the basal ganglia,
which have slightly lower cortical uptake
(75% to 85% of the cerebellar uptake )
.

32
Uptake in white matter is considerably
less because of the lower CBF.

As a result, white matter is not seen

on SPECT imaging because it fades
into the background.

33
The appearance of a central cold
area seen on cross-sectional SPECT
images is caused by not only the
ventricular cavities, but also white
matter.

34
 PET imaging of cerebral blood
perfusion is similar to the findings of
SPECT, but more clearly.

35
 Normal distribution of F-18 FDG. C, Cerebellum; Ca, caudate; F, fron
tal lobe; O, occipital lobe; P, parietal lobe; PA, putamen, T, temporal
lobe; Th, thalamus. The cortex appears bilaterally symmetry increas
ed radionuclide concentration. Any significant asymmetry suggests a
bnormal perfusion to that side.
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37
 Clinical Applications

38
Clinical Applications
1.Diagnosis of transient ischemic attack(TIA).

2.Diagnosis of cerebral infarction(CI).

3.Diagnosis and differential diagnosis of

Alzheimer’s disease(AD).

4.Localization of epileptic foci.

5.Differential diagnosis of recurrent brain tumor from

necrosis after radiotherapy or surgery.

6.Functional study of brain.

7.Other clinical applications.

39
1.Transient ischemic attack(TIA)

TIA is caused by temporary shortage of bl

ood supply to brain from carotid artery or
vertebrobasilar artery system. There are
no obvious clinical symptoms when the pati
ent comes to see a doctor. The results of
neurological examination and conventional C
T or MR are usually negative.

40
rCBF tomography can show ischemic changes in
nearly 50% of the patients’ brain, and the lesion
of TIA appears as decreased uptake or defect of
various degrees. The rate of positive result is
higher than by CT or MR.

41
Stress test can be applied to further improve
the sensitivity of examination, and is helpful
for the examination for chronic focus in low-
flow state in patients without obvious clinical
symptoms. rCBF tomography is of important
value for early diagnosis of TIA and prevention
of the occurrence of cerebral infarction.

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Signs and symptoms of a stroke can
be caused by transient hypoperfusion
or ischemia. Rather than progressing
to a completed stroke, the event
resolves completely within 24h.

43
Approximately 60% of patients who
have had transient ischemic attacks
(TIAs) later have a completed
stroke. More than 80% of CT
studies are normal in patients with a
TIA.

44
SPECT perfusion studies may be abnormal
in up to 60% of patients during the first
24h, 40% by day 2, and decreasing over
1 week. The defects seen may predict
the area of eventual stroke. The rate of
positive result is higher than by CT or
MR.

45
2.Diagnosis of cerebral infarction(CI)

rCBF tomography can be used in the early

stage of infarction, the lesion shows
localized or largescale decreased uptake
or defect.

46
Small lacunar infarction might not
often be revealed on SPECT images
because of the limitation of the
instrument, but CT or MR images
could show the apparent structural
change of the lesion and so that they
have higher positive detection rate.

47
 However, rCBF tomography can show
crossed cerebellar diaschisis which is
difficult to be found by CT or MR.
The signs show decreased uptake in
the contralateral cerebellum of the
lesion;

48
 Small number of cases may show the
phenomena of luxury perfusion, which
means if collateral circulation is rich,
several days after the incidence, there
will be abnormal increased uptake area
around pathological changes area in
rCBF tomography.

49
 Acute cerebral infarction
Decreased rCBF can be seen immediately after
the acute cerebrovascular event. During the
first 8h after infarction, only 20% of CT
scans are positive, whereas 90% of SPECT
scans are abnormal.

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 The need for a rapid and accurate
method to differentiate stroke
subtypes is becoming increasingly
important as more specific therapies
become available.

51
 Classifying stroke patients based on
clinical information and anatomical
imaging has significant limitations.
Imaging during the subacute phase
of a stroke should be interpreted
cautiously.

52
Defects seen on SPECT are often
larger than those seen on CT.
suggesting an area of ischemic
brain tissue surrounding the
infarction at risk for infarction.

53
 This CBF is seen 1 to 10 days after
stroke onset. Decreased cerebellar
perfusion contralateral to the cortical
infarct (crossed cerebellar
diaschisis ) is often noted during the
acute and subacute phases of stroke
and is thought to result from
metabolic inhibition from direct
neuroconnections.

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Cerebrovascular reserve
SPECT has the potential for
detecting low flow states and for
evaluating cerebrovascular reserve.

55
 Specially performed SPECT studies
and drug interventions may be able
to identify patients who might
benefit from intervention, such as
carotid endarterectomy, temporal-
middle cerebral artery bypass
procedures, or IV thrombolytic
therapy.

56
 Subarachnoid hemorrhage
One half of intracranial
hemorrhages occur secondary to
SAH, with a mortality rate
approaching 50%. The cause is
rupture of an intracranial aneurysm.

57
 The acute
hemorrhage
results in stroke
symptoms, and an
abnormal rCBF
pattern is seen
with SPECT.

58
 Delayed symptoms and signs may
occur secondary to major vessel
spasm, which often are not evident
on CT, and can guide therapy.

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3.Differential diagnosis of dementia

The diagnosis of dementia implies

loss of mental faculties sufficient to
interfere with social and
occupational functioning.

60
 Deficits include memory, language, and
visual-spatial perceptions. Psychiatric
symptoms may occur.

Dementia has a number of possible

causes including Alzheimer disease,
Parkinson disease, Huntington chorea,
Wilson disease and so on.

61
 The clinical diagnosis is often
difficult and delayed, and
anatomical imaging modalities such
as CT and MRI may not reveal
changes such as atrophy until the
end stages of disease.

【 62】
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 SPECT and PET, on the other hand,
have been shown useful in early
diagnosis of Alzheimer disease. In
addition, these functional modalities
show promise for the identification of
subjects early before damage is too
severe for therapy to have any
benefit.

【 63】
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 Although PET has higher sensitivity an
d higher resolution than SPECT, the o
verall patterns seen in dementia are si
milar for both rCGM and rCBF.

【 64】
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 Alzheimer’s disease: Alzheimer
disease (AD) is the most prevalent
cause of dementia.

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 Brain biopsy is the only definitive
method of diagnosis but is rarely
used.

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 Alzheimer’s diseases has characteristic
pathological findings. Abnormal tangles
of never fibers and degenerative
neuronal lobes bilaterally. The patient’s
degree of dysfunction is related to the
number of these abnormal cortical
structures.

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The classic scintigraphic pattern for
Alzheimer’s disease on SPECT
perfusion imaging is bilateral
posterior temporal and parietal
hypoperfusion.

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 Alzheimer disease. SPECT images reveal decreased perfusion to the
temporal parietal cortex.

【 69】
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 Bilateral posterior temporal and parietal hypometabolism and h
ypoperfusion.

【 70】
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Other dementias: Other causes of
dementia have characteristic
patterns as well. Pick’s disease is
characterized by frontal lobe
hypoperfusion.

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 Pick’s disease

Pick disease is rare. It classically shows frontal hypoperfusion with a sh

arp anterior-to-posterior cutoff.

【 72】
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Huntington’s chorea
The symptoms of the hereditary disorder
Huntington’s chorea, also called
Huntington’s disease, develop insidiously
and usually are manifested between ages
35 and 50 years, inevitably progressing to
uncontrollable choreiform movements and
dementia. Basal ganglia atrophy, especially
the caudate nuclei.

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 The caudate and putamen are deficient in
the inhibitory neurotransmitter GABA (gam
ma-aminobutyric acid) and in glutamic acid
decarboxylase.

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 Both PET and SPECT imaging can
show decreased uptake in the
caudate nucleus, which often
precedes the atrophy seen on CT, in
patients with moderate to severe
Huntington’s chorea.

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 Multiinfarct dementia
The scintigraphic pattern of multiinfar
ct dementia shows multiple asymmetric
al perfusion defects, often involving th
e primary cortex and deep structures.

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 Multiinfarct dementia

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4.Localization of epileptic foci
Many patients with partial complex
seizures unresponsive to anticonvulsant
drug therapy may be helped by temporal
lobectomy.

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Excision of well-localized foci can
lead to elimination of seizures or
significantly improved
pharmacological control in 80% of
surgical patients. Only a few
undergo surgery, however, partly
because of the difficulty of
adequate seizure focus localization.

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 F-18 FDG PET and SPECT
perfusion agents can localize
epileptic foci.

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 Seizure foci are seen as areas of
hyperperfusion in the ictal phase and
hypoperfusion in the interictal phase,
usually in the temporal lobes.

ictal phase interictal phase

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 5. Differential diagnosis of recurrent b
rain tumor from necrosis after radiother
apy or surgery.
rCBF tomography can not provide decisi
ve information in the diagnosis of brain t
umors, but it has some value on distinguis
hing radiation or surgery necrosis from t
umor recurrence.

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 Tumor recurrence appears increased rCB
F. 99mTc-MIBI imaging can be used to d
emonstrate the activity and malignant gr
ade of tumors. If regional uptake on 99
mTc-MIBI images abnormally increased
it supports more possibility of tumor rec
urrence. In this regard, nuclear medicine
imaging is superior to CT and MR.

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 6.Functional study of brain.
CBF reflects the functional activities o
f human brain to some extent, so that th
e combined applications of Rcbf tomograp
h with a variety of physiological stimulati
on test can study the changing of relatio
nship between the reaction to physiologic
al stimulation and the anatomical structur
e in the human brain.

85
 The stimulation of visual, auditory and lan
guage can cause increased brain blood flow
in occipital visual center, the temporal aud
itory center and frontal language center o
r mental activity area, which could be obs
erved on Rcbf imaging. It shows the incre
ased uptake on the contralateral precentra
l and post-central gyrus motor and sensor
y dominant central on the quantitative ima
ges analysis of right upper limb and right l
ower limb weight-bearing freely exercise.

86
 7. Other clinical applications
Radioactivity uptake can increase
or decrease when the migraine
attacks.

87
 Psychiatric diseases
Cerebral blood flow in patients with
schizophrenia shows a step change from
front to back. The most serious damage is
in the frontal lobe, the left side is more
severe than the right. It commonly shows
significantly decreased uptake in left
lower basal ganglia and left temporal lobe.

88
 Patients with severe mental
depression have decreased uptake in
frontal lobe and the front of
parietal lobe.

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At present, functional scintigraphy may be of
most value in identifying patients with psychiatric
symptoms in whom underlying organic disease is
suspected.
The role of PET in the investigation of
neurological disorders.

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 Cerebral Metabolic Imaging
Fluorine-18 FDG:Glucose Metabolism

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 A new era in NM brain imaging emerged with the development
of Positron emission tomography (PET) and PET/CT

92
The potential of PET is that virtually any
compound of biological interest (e. g. protein,
sugar, fat, receptors, enzymes) can
theoretically be labeled with radioactive
oxygen, nitrogen, or carbon and used as a
radiotracer.

93 11
C-choline 18
F-FDG 11
C-MET
PET led the way by imaging physiological
and biochemical processes in the brain,
including cerebral blood flow (CBF),
glucose metabolism, and oxygen
utilization, which had both important
research and clinical impact.

94
The brain is an obligate user. F-18 FDG is a
glucose analog, allowing accurate assessment of
regional cerebral glucose metabolism(rCGM).In
addition to reflecting regional cerebral blood
flow(rCBF).

F-18 FDG is the only positron

radiopharmaceutical used routinely on a clinical
basis at present .

95
Mechanism of uptake
F-18 FDG is able to cross the blood –brain barrier
using glucose transporter system and enters the neuron.
Then it is phosphorylated by hexokinase to
deoxyglucose-6-phospate. Unlike glucose-6-phosphate,
FDG is not metabolized further and cannot diffuse from
the brain; it is metabolically trapped intracellularly.

96
 Pharmacokinetics
Approximately 4% of the administered
dose is localized to the brain.By 35
minutes after injection, 95% of peak
uptake is achieved. Urinary excretion is
rapid, with10% to 40% of the injected
dose cleared in 2 hours.

97
Dosimetry
The dose of F-18 FDG is typically 5-10mCi.
F-18 FDG should be injected in a quiet, dimly
lit room with the patient remaining still and
undisturbed during the uptake period.
Imaging begins 30 to 60 minutes after
injection. A scan time of 15 to 30 minutes is
typical. To correct for attenuation, a
transmission scan using an external source is
also acquired.

98
Methodology

Patients should fast for 4 to 6 hours before

injected, and should avoid strenuous exercise
for a few days before the test.
Because exercise and insulin will shunt FDG
to the muscles and reduce brain uptake.

99
 Normal and abnormal distribution
Relative uptake of F-18 FDG is directly
related to regional glucose consumption.
Uptake in gray matter is three to four times
that in white matter. Increased focal or
regional uptake relative to normal brain occurs
with increased metabolism, as seen with
malignant tumors and ictal seizure foci.
Decreased uptake is seen in areas of reduced
regional glucose metabolism.

100
 NORMAL
IMAGING OF
18F-FDG

101
 Clinical applications

1. Epilepsy
2. Dementia
3. Movement disorders
4. Cerebrovascular disease
5. Tumor.
6. Cerebral activation studies.

102
 1. Epilepsy

Epilepsy is a group of neurological disorders

characterized by recurrent seizures. Between
10% to 20% of these new cases are medically
intractable and suitable for surgical treatment if
a localized seizure focus can be proved in their
brain. Non-invasive localization of foci can be
obtained in some patients with radionuclide
imaging and these approaches play a substantial
role in clinical management of epilepsy.

103
 Epilepsy
In general, during an epileptic seizure, cerebral
metabolism and blood flow are markedly
increased. In the interictal phase, cerebral
metabolism and blood flow are markedly
decreased. usually in the temporal lobes.

104
 ictal phase interictal phase

105
 With high-resolution PET images,
accurate localization of seizure foci
can be achieve to aid in determining
the appropriate surgical intervention.

Studies have also found that after

surgical excision of the seizure foci,
there is usually significant improvement
in the function of remaining brain.

106
 Imaging with PET utilizing receptor
techniques may provide further
insight in the investigation of
patients with seizures.

107
2. Dementia
Dementia is usually defined as a chronic,
cognitive impairment. Clinical symptoms may
vary, and the functional decline can occur
rapidly over months or slowly over years.

108
 Patients with AD have decreased whole-
brain glucose metabolism with the
bilateral parietal and temporal lobes
particularly affected. This biparietal
hypometabolism has been referred to as
the ‘typical’ pattern of AD.

109
 3. Movement disorders
Uptake measured in the basal ganglia allows
Parkinson’s disease to be distinguished from
other movement disorders.

In the normal person, the the basal ganglia appears

bilaterally symmetry and uniform, but in the PD
patients, showing decreased activity.

110
4. Cerebrocascular diseases

Patients with cerebrovascular disease are usuall

y studied by MRI or CT after the onset of symp
toms. CT and MRI, although crucial for different
iating ischemia from hemorrhage, are insufficient
for the complete assessment.

111
 Cerebrocascular diseases

PET imaging has been of great benefit in further

understanding the pathophysiology of cerebrovasc
ular disorders, allowing for the detection of infa
rct earlier and with higher sensitivity than anato
mical imaging with either MRI or CT.

112
 Furthermore, PET imaging has been
useful in evaluating the extent of the
functional damage since area not
immediately affected by the infarct may
also show hypometabolism or decreased
blood flow.

113
 PET can help determine which
patients are at risk for stroke,
indicate which are most likely to
benefit from intervention, and even
predict stroke recovery.

114
5. Brain tumors
For the long time the diagnosis of b
rain tumors has been relying on CT and
MRI. These imaging modalities may ha
ve partial answers and must be comple
mented by functional imaging.

115
 Brain tumors
PET can play an important role in the
study and management of brain tumors
, including the preoperative grading of
tumors, determination of prognosis, an
d differentiation of recurrent tumor fr
om radiation necrosis.

116
 Brain tumors

The mechanisms of tracers’ uptake and rete

ntion are markedly different in neoplastic tis
sue which may be related to the rate of gro
wth and cell type of the tumor.

117
 Brain tumors

18F-FDG is the most important tracer fo

r oncological studies. Relatively simple sy
nthesis and long half-life have made it qu
ite popular in neuro-oncology.

118
 F-18 FDG uptake is related to metabolic acti
vity and therefore to tumor grade. Because o
f this, PET can help direct biopsy to the most
aggressive region of a tumor.

119
 High-grade primary brain tumors are
hypermetabolic, as seen with F-18
FDG, whereas low-grade tumors are
hypometabolic. FDG can more
accurately predict the degree of
malignancy of a tumor than CT or MRI.

120
Unlike CT or MRI, PET can distinguish
radiation necrosis from tumor
recurrence. Area of radiation necrosis
are hypometabolic while tumor
recurrence appears hypermetabolic.

121
 PET has also been used to determine
tumor response to radiation and
chemotherapy and eventual patient
survival.

122
 The patients whose tumor have
decreased glucose metabolism after
radiation therapy tend to have a
better prognosis than those who do
not show such a response.

123
 6.Cerebral activation studies

One of the most exciting use of PET

is for cerebral activation studies.

124
The results from such studies may
help define specific areas of the
brain that are responsible for
various aspects of thought, speech,
sensation, motor function, emotion,
and other complicated functions.

125
126
 Questions
1.What are the characteristics of Pick’s disease, AD, m
ultiinfarct dementia and Hunting disease in cerebral bloo
d flow perfusion imaging?
2. What’s the feature of the TC-99m perfusion cerebr
al blood flow radiopharmaceticals?
3.What are the cerebral blood flow perfusion imaging ra
tionale and clinical application?
4. What are the cerebral glucose metabolic imaging rati
onale and clinical application?
5. What are the seizure characteristics in brain metabo
lism and cerebral blood flow perfusion imaging?

127