The Central Nervous

System

XIE XIN LI
Department of Nuclear Medicine,
First Affiliated Hospital,
Zhengzhou University
The Central Nervous System
 Between 50’s and 70’s conventional
brain scintigraphy has had an
important role in diagnosing brain
disease, e.g. brain tumor,
cerebrovascular disease,
inflammation, trauma, and so on.
The Central Nervous System
 Since the middle of 70’s, CT has had a vital
impact on the study of the central nervous
system, and has become unrivaled in the
assessment of size and shape of the
cerebral ventricles.
 It’s sensitivity and specificity in the
detection of space-occupying disease has
led to a dramatic reduction of the
conventional brain scintigraphy.
The Central Nervous System
 Did the nuclear medicine disappear in the
field of CNS examination?

NO
The Central Nervous System
 In 80’s, along with the appearing of new
radiopharmacerticals, PET and SPECT, nuclear
medicine examination has been successfully
applied to the measurement of

– global or regional cerebral blood flow,

– global or regional cerebral metabolism of
glucose,
– and the distribution, density and the affinity
ability of neuroreceptors.
The Central Nervous System

 BRAIN IMAGING
– Cerebral perfusion imaging
– Cerebral metabolism imaging
– CSF(cerebrospinal fluid) IMAGING:
• Assessment of flow patterns of the
cerebrospinal fluid.
• In assessing surgical shunt relief.
• In detecting CSF leakage.
The Central Nervous System
 BRAIN IMAGING:
– Conventional brain scintigraphy.
• The radiopharmaceutical can’t cross the intact
blood brain barrier. SPECT
– Functional brain scintigraphy.
• The radiopharmaceutical can cross the intact
blood brain barrier.
1. Brain perfusion scintigraphy SPECT
2. Brain metabolism scintigraphy PET
3. Brain neuroreceptor scintigraphy PET
 BRAIN PERFUSSION
SCINTIGRAPHY

 The radiopharmaceuticals can cross

the intact blood brain barrier.
 The distribution of the
radiopharmaceuticals in the brain is
proportional to regional cerebral blood
flow (rCBF).
1. RADIOPHARMACEUTICALS

 99mTc-HMPAO,
 99mTc-ECD,
 123I-IMP
1. RADIOPHARMACEUTICALS

1.1 99mTc- HMPAO

(Hexamethylpropylenamine oxime )
 HMPAO is a lipophilic compound which is chemically
unstable in-vitro (it undergoes oxidation).
 Due to rapid decomposition of the compound in vitro to
a hydrophilic compound which will not cross the blood
brain barrier, the agent must be used within 30
minutes of its preparation.
 The distribution of the tracer is proportional to the
regional cerebral blood flow, the ratio of gray to
white matter activity is about 2.5:1.
1. RADIOPHARMACEUTICALS

1.2 Tc-ECD
99m

( Ethylene Cysteine Diethylester):

 The retention mechanism is related to rapid ester
hydrolysis with conversion of the parent 1,1-isomer to a
charged hydrophilic compound that no longer has the
capability of diffusing back across the blood brain
barrier.
 Unlike HMPAO, the compound is stable in-vitro. The
agent is good for 6 hours after reconstitution, as
compared to less than 30 minutes for 99mTc-HMPAO.
1. RADIOPHARMACEUTICALS

1.3 I-IMP
123

(d,I-N-isopropyl-p-iodoamphetamine
hydrochloride):

 IMP is lipophilic- it dissolves in the lipid membrane of

the capillary vessels of the brain and rapidly passes
through the blood-brain barrier by passive diffusion.
 Retention in the brain is controlled by binding to non-
specific amphetamine binding sites on the brain
cells.
1. RADIOPHARMACEUTICALS

 About 6 to 9% of the injected dose

localizes to the brain. Peak brain activity is
reached within 20 minutes.
 The remainder of the tracer predominantly
localizes to the lungs (33%), liver (45%),
and kidneys.
 Some delayed cerebral uptake occurs due
to slow pulmonary release.
 Imaging must be done promptly as IMP
metabolites will washout and redistribute
over time.
1. RADIOPHARMACEUTICALS

 The optimal imaging time is about 20

minutes when the CNS levels of IMP reach a
transient peak and cortical IMP uptake is
approximately proportional to regional
cerebral blood flow.
 Images obtained greater than 1 hour after
injection show a loss of definition between
cortex and white matter due to washout
from the cortex and cerebellum which
gradually fills in the white matter tracts.
 This latter distribution pattern more likely
reflects amine binding sites.
 1. RADIOPHARMACEUTICALS

 On 123I-IMP imaging, areas of ischemia

(i.e. those with low CBF, but remaining
metabolism) appear as defects on early
images which "fill in" over time.
 Infarcted areas demonstrate decreased
activity both on early and delayed
images.
 2 EXAMINATION TECHNIQUE:

2.1 Environmental conditions

 A low light, reduced noise, and minimal
traffic environment should be
maintained for 10 minutes before and
after the tracer is given.
 Caffeine containing products should be
held for 24 hours prior to the exam.
 2 EXAMINATION TECHNIQUE:

2.2 Imaging time ----after the tracer is given

radiopharmaceutical acquiring image time

99m
Tc-HMPAO 1~1.5h
99m
Tc-ECD 30min~1h
123
I-IMP 20min and 2h
2 EXAMINATION TECHNIQUE:

2.3 Normal characteristic:

 The visual cortex of the occipital lobes and
the cerebellum are clearly evident as the
areas of most intense activity.
 Midline structures including the basal
ganglia and thalami should be slightly less
intense, but clearly evident and relatively
symmetric.
3. CLINICAL APPLICATION
3.1 Epilepsy : the Detection of a Seizure focus:
3.2 Acute CNS Ischemia / Infarction:
3.3 Transient Ischemic Attacks:
3.4 Brain death
3.5 Cerebral hemorrhage
3.6 Preoperative temporary balloon occlusion of the internal
carotid artery
3.7 Dementia: Alzheimer’s Dementia, Parkinson’s Disease, Multi-
infarct Dementia, HIV, Pick’s Disease
3.8 Psychiatric Disorders:
Schizophrenia ；
Attention Deficit-Hyperactivity Disorder (ADHD),
Bipolar Disorders,
Unipolar Disorders,
Autistic Disorder.
3. CLINICAL APPLICATION

3.1 Epilepsy : the Detection of a

Seizure focus
 About 20% of patients with partial
complex seizures have inadequate
control on medical treatment. Patients
unresponsive to anti-convulsant
therapy may be surgical candidates.
3. CLINICAL APPLICATION

 Scalp EEG (electroencephalo-graph)

often fails to accurately localize the
seizure focus and although depth EEG
is much more accurate, it is also
extremely invasive and suffers from
regional under sampling.
 CT and MRI have low sensitivity for
seizure foci detection, 17% and 34%
respectively.
3. CLINICAL APPLICATION

 During the ictal phase of a complex partial

seizure, there is typically hyperperfusion of the
mesial or lateral aspects of the affected temporal
lobe.
 99m
Tc-HMPAO injected during the ictal state or
in the immediate post-ictal period (within 30 to
60 seconds) will show a focal area increased
activity (hypermetabolic region) at the seizure
focus in 80 to 100% of patients.
3. CLINICAL APPLICATION

 Following the seizure, there is relatively

rapid progression (generally within 20
minutes) to a hypoperfused state which
persists throughout the inter-ictal phase.
 Inter-ictal SPECT studies will
demonstrate an area of diminished
tracer activity at the seizure focus in up
to 50% of patients.
 3. CLINICAL APPLICATION
3.2 Acute CNS Ischemia / Infarction:
 Cerebral SPECT can be used to
– confirm the presence of cerebral
infarction,
– monitor the effects of acute
thrombolytic therapy,
– and to predict stroke outcome.
 3. CLINICAL APPLICATION

 Cerebral SPECT is more sensitive

than CT in the early (first 24 hours)
detection of acute ischemia
(sensitivity 88-95% vs. 20-63% for
CT, MRI has a sensitivity of about
80% for the detection of acute
infarction).
3. CLINICAL APPLICATION

 The defects noted on SPECT are

also frequently larger than those
noted on CT in about 50% of
patients.
– This is because SPECT defects most
likely represent a combination of a
central zone of infarction which is
surrounded by a zone of ischemia,
but potentially viable tissue.
3. CLINICAL APPLICATION

3.3 Transient Ischemic

Attacks(TIA):
 TIA occur in 10 to 20% of stroke patients. If no
treatment is instituted following a TIA, about one
third of these patients suffer a stroke within 5
years.
 The sensitivity of HMPAO imaging in TIA
declines with time, from about 60% in the initial
24 hours following the event, to less than 40%
by 1 week.
3. CLINICAL APPLICATION
 The acetazolamide challenge test may be
useful in identifying CNS territory at risk
in patients experiencing TIA's.
 It may also be useful as a screening tool
in asymptomatic patients.
– Acetazolamide is a carbonic anhydrase
inhibitor that causes an increase in cerebral
CO2.
• This results in vasodilatation and increased flow
in normal cerebral vessels.
• In an area of reduced blood flow, where there has
already been maximal vasodilatation (and thus
loss of cerebrovascular reserve) there can be no
augmentation of flow.
 3. CLINICAL APPLICATION

 Toperform the study, a baseline

exam is compared to a SPECT
exam performed 25 minutes after
the I.V. administration of 1 gm of
acetazolamide.
3. CLINICAL APPLICATION
 Areas of limited flow reserve will
have decreased tracer activity
on the challenge exam
compared to the baseline study.
 A decrease of 10 to 20% in
activity on the acetazolamide
exam compared to baseline is
considered abnormal.
3. CLINICAL APPLICATION
3.4 Brain death
SPECT imaging in patients with brain death
demonstrates no cerebral or cerebellar
accumulation of the tracer.Additionally ,
as HMPAO is a perfusion tracer , it can
be used to determine the viability of
internal organs which may be used for
transplants.
3.5 Cerebral hemorrhage
In patients with rupture cerebral aneurysms
,there is a high morbidity and mortality in
those patients that survive insult secondary to
vasospasm (with resultant ischemia) and
recurrent bleeding. HMPAO imaging may aid
in defining those patients with significant
cortical vasospasm.
3.6 Preoperative temporary balloon
occlusion of the internal carotid artery
Brain perfusion scintigraphy has been used to
determine whether a patient can tolerate an
internal carotid artery sacrifice or not.
3.7 Dementia: Alzheimer’s Dementia, Parkinson’s Disease,
Multi-infarct Dementia, HIV, Pick’s Disease
Dementias produce deficits in perfusion , in part reflecting
decreased metabolic needs. In Alzheimer’s one classically
sees bilateral decreased metabolism(PET imaging) and
flow(SPECT imaging) in the temporal and parietal lobes
with sparing of the primary sensorimotor and visual
cortexes. The temporoparietal deficits are noted in about
65% of Alzheimer’s patients and are the most consistently
recognizable sign of Alzheimer’s, particularly when
relatively symmetrical.
 Parkinson’s disease
Generally , the perfusion pattern in these
patients is non-specific and demonstrates
either normal or mild global cortical deficits. A
pattern of bilateral parietal defects
indistinguishable from Alzheimer’s may be
observed in patients with Parkinson’s disease
with dementia.
 Multi-infarct dementia
 HMPAO findings that suggest the diagnosis
include multiple , bilateral , and randomly
distributed cortical perfusion defects that
follow vascular territories . The basal ganglia
may also be involved.
 HIV (AIDS dementia complex )
 Multiple areas(small and large) of decreased
perfusion are identified in the cortical and
subcortical regions, often producing a patchy
distribution of the tracer.Basal ganglia
involvement is also common.
3.8 Psychiatric Disorders:
Schizophrenia ；
A finding consistently suggested on both PET FDG and
SPECT perfusion imaging in patients with schizophrenia has
been that of hypofrontality(i.e.,relative decreased frontal
perfusion /metabolism).
Attention Deficit-Hyperactivity Disorder (ADHD),
SPECT imaging has demonstrated hypoperfusion of the
caudate and central frontal lobes, with relatively
hyperperfused occipital lobes in these children.
Bipolar Disorders,
Frontal or global hypometabolism ,as well as
temporal lobe asymmetries.
Unipolar Disorders,
Global hypometabolism and caudate nucleus
hypometabolism.
Autistic Disorder.
Abnormally decreased rCBF was detected within the
temporal and parietal lobes.
Supplement:brain tumors
 There is generally increased uptake of the tracer in
meningiomas when compared to gliomas(the
exception to this is calcified meningiomas which
demonstrate decreased uptake). Within gliomas
,regional tracer uptake increases in relationship to the
grade of malignancy, with low grade(I and II)lesions
demonstrate uptake less than the grade III
tumors.Grade I and II lesions typically demonstrate
uptake less than the cerebellum. Uptake within IV
tumors tends to be mixed(high and low uptake
zones)due to the presence of necrosis within the
lesion.
CONVENTIONAL BRAIN
SCINTIGRAPHY
 CONVENTIONAL BRAIN SCINTIGRAPHY

 Diseases of the brain cause a

breakdown in the blood brain barrier
which permits the uptake of
conventional brain imaging agents.
 It can be used on
– Brain Death,
– Cerebral Vascular Accident,
– Inflammation and Trauma.