2006 Cns
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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 ( 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: 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 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 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.
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 ( 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: 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 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 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.
