The Central Nervous

System
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
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:
3.9 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.
 99mTc-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

To perform 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
3.5 Cerebral hemorrhage
3.6 Preoperative temporatry 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.
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.