The Central Nervous System

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 ( Ethylene Cysteine Diethylester): 99m

 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 (d,I-N-isopropyl-p-iodoamphetamine hydrochloride): 123

 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 nonspecific 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 99m

acquiring image time

Tc-HMPAO

1~1.5h

Tc-ECD

30min~1h

I-IMP

20min and 2h

99m

123

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 3.2 3.3 3.4 3.5 3.6

Epilepsy : the Detection of a Seizure focus: Acute CNS Ischemia / Infarction: Transient Ischemic Attacks: Brain death Cerebral hemorrhage Preoperative temporary balloon occlusion of the internal carotid artery 3.7 Dementia: Alzheimer’s Dementia, Parkinson’s Disease, Multiinfarct 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.