1. Neurological Nuclear Medicine
Department of Nuclear Medicine
Renji Hospital

2. Brain Blood Circulation

3. Blood Brain Barrier, BBB
内皮细胞间为紧密连接，无胞饮作用。只能通过主动扩散。

4. Not penetrate through BBB
Brain Imaging Agents
Not penetrate through BBB
99mTcO4-
99mTc-GH
201Tl
99mTc-DTPA

5. Brain Imaging Agents (Cont.)
Penetrate through BBB
Perfusion
99mTc-ECD
99mTc-HMPAO
123I-IMP
Metabolic
18F-FDG
Receptor and Transporter
11C-NMSP
99mTc-TRODAT-1

6. Requirements for penetrating through BBB
Small molecule
None electronically charged
Lipophilic

7. Brain Perfusion Imaging
The injected tracer is freely diffusible from the blood pool into the brain.
There is complete extraction of the tracer by the brain.
Once taken up by the brain, the tracer is “trapped”, or that efflux from the brain is accounted for.
Following the initial tracer uptake, there is no subsequent redistribution.

8. Normal perfusion image

9. Tomographic perfusion image of the brain

10. Tomographic perfusion image of the brain

11. Tomographic perfusion image of the brain

12. Tomographic perfusion image of the brain

13. Abnormal Patterns Focal decreased uptake Focal increased uptake
Crossed cerebellar diaschisis
Enlargement of white matter or midline shift
Structure disorder
Abnormal distribution of the tracer
cerebral atrophy
Dissymmetric distribution

14. Visual Analysis

15. Semi-quantitative Analysis

16. Clinical Indications of Brain Perfusion Imaging
Cerebral ischemia
Dementia
Seizures
Alzheimer diseases
psychiatric diseases
Brain death
Parkinson's Disease

17. Clinical Applications of Brain Perfusion Imaging

18. Cerebral Vascular Diseases
Acute CNS Ischemia/Infarction
Transient Ischemic Attacks(TIA)

19. Acute CNS Ischemia/Infarction
A focal or regional area of hypo- or absent perfusion on SPECT images.
Larger defects area on SPECT than those noted on CT. The defects represent a combination of a central zone of infarction surrounded by a penumbra zone of ischemia but potentially  viable tissue.

20. Acute CNS Ischemia/Infarction(Cont.)
Confirm the presence of cerebral infarction, monitor the effects of acute thrombolytic  therapy, and to predict stroke outcome .
Higher sensitive than CT in the early (first 24 hours) detection of  acute ischemia, sensitivity 88-95% vs % for CT, MRI has a sensitivity of about 80% for the detection of acute  infarction .

21. Subacute Phase Infarction
Size of the infarct may be grossly underestimated due to luxury perfusion
Luxury perfusion :uncoupling of flow and metabolism following an infarct. Apparently increased or normal tracer uptake despite the absence of metabolism in the involved area possibly related to either local breakdown in the blood-brain barrier or hyperemia from local tissue acidosis

22. Crossed Cerebellar Diaschisis
Crossed cerebellar diaschisis (CCD): decreased cerebellar perfusion contralateral to the cortical infarct during the acute and subacute phases of middle cerebral artery territory strokes.
Mechanism: loss of axons interconnecting the infarcted cortical regions with other brain structures
intact vascular reserve: activity increase in these areas following the administration of diamox due to the increased perfusion to these areas.

23. Crossed Cerebellar Diaschisis

24. Transient Ischemic Attacks
It occurs in 10 to 20% of stroke patients. One third of these patients suffer a stroke within 5 years without treatment.

25. Transient Ischemic Attacks(Cont.)
Single or multiple cerebral blood perfusion defect or abscent
Early detecting ischemia region with SPECT compared to CT or MRI.
Sensitivity is about 55-60% with SPECT, the sensitivity declines with time.
SPECT CBF stress test with Diamox has been shown to increase the likelihood of detection of residual blood flow changes after TIA.

26. Transient Ischemic Attacks

27. DEMENTIA

28. Alzheimer's Dementia
Dementia affects 10% of people over the age of 60 years and Alzheimer's accounts for roughly 50% of these cases. Alzheimer's disease (AD) has a prevalence of 0.3% in patients aged years, but increases to nearly 11% in year olds . The mental degeneration associated with Alzheimer's is insidious and progressive memory loss is the most important symptom.

29. Alzheimer's Dementia(cont.)
Very early stage: normal CBF perfusion
Early stage: unilateral or bilateral temporoparietal perfusion defect
Moderate to severe stage:bilateral temporoparietal perfusion defect
Advanced stage: bilateral temporoparietal and frontal lobe perfusion defect

30. Alzheimer’s Dementia (SPECT)

31. Alzheimer's Dementia(Cont.)
A correlation has been described between the severity of these defects, and the severity of the patient's dementia .
The cerebellum, primary visual areas, and primary sensorimotor areas along the central sulcus remain relatively intact.
SPECT perfusion imaging has a sensitivity of 63%, a specificity of 82%, a positive predictive value of 81%, a negative predictive value of 65%, and an accuracy of 71% for the diagnosis of Alzheimer's .

32. Multi-infarct Dementia
Multi-infarct dementia (MID) is characterized clinically by multiple cerebral infarcts that occur sporadically and produce a step-wise deterioration in intellectual function. MID is the second most common cause of dementia in the elderly.

33. Multi-infarct Dementia (Cont.)
multiple, bilateral, and randomly distributed cortical perfusion defects that follow vascular territories. The basal ganglia, motor, and sensory cortices may also be involved (spared in Alzheimer's).

34. Pick's Disease (Frontal lobe dementia)
A rare frontal dementia
Symptoms usually include the gradual onset of confusion with respect to place and time, anomia, slowness of comprehension, loss of tact, and changes in personality and behavior.
SPECT images demonstrate bilateral, diffuse decreased frontal lobe perfusion extending to the cingulate gyrus.

35. Epilepsy
Epilepsy is one of the most prevalent neurological disorders.Seizures can be classified as either partial (focal) or generalized. Partial seizures originate in a given area of the brain and can be divided into simple (with no impairment of consciousness) and complex (with impairment of consciousness).
About 10-20% of patients with partial complex seizures have inadequate control on medical treatment.Patients unresponsive to anti-convulsant therapy may be surgical candidates which can render the patient seizure free.

36. Epilepsy (Cont.)
Scalp EEG 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. The role of brain SPECT is to localize the seizure focus.

37. Epilepsy (Cont.)
Ictal Imaging: hyperperfusion at the seizure focus in 80 to 100% of patients. Crossed cerebellar hyperperfusion can also be identified in 75% of patients. Ipsilateral or diffuse cerebellar hyperperfusion may also be seen. Ipsilateral basal ganglia hyperperfusion is also common.
Ictal SPECT: sensitivities 81 to 93%. The positive predictive value for localizing a unilateral seizure focus can be as high as 97% (when the tracer was injected immediately after the seizure).

38. Epilepsy (Cont.)
Inter-ictal Imaging: Inter-ictal (seizure free) SPECT studies will demonstrate an area of diminished tracer activity (hypoperfusion) at the seizure focus in up to 50% of patients.
Inter-ictal PET FDG studies demonstrate a focal area of hypometabolism in 60 to 70% of patients with normal MRI's. The area of hypometabolism is often much larger than the actual area of structural abnormality.

39. Epilepsy (Cont.)
The sensitivity for localization of the ictus site using inter-ictal SPECT scanning ranges from 40 to 66%, which is less sensitive than post-ictal (70%) or ictal (80-90%) SPECT, and inter-ictal PET FDG (70%) imaging.

40. Epilepsy
Ictal
Inter-ictal

41. Brain Death
Lack of intracranial arterial flow: the carotid arteries are visualized in the neck, but there is an abrupt cut-off of activity at the skull base
Sagittal/Venous sinuses are not visualized on subsequent static images
The "hot nose" sign: due to increased flow in the external carotid circulation.
SPECT imaging in patients with brain death demonstrates no cerebral or cerebellar accumulation of the radiotracer

42. Brain Death (dynamic)
Normal perfusion
Brain Death

43. Brain Death (30 Min)
Normal perfusion
Brain Death

44. CNS Trauma
SPECT is more sensitive than CT or MRI in detecting post traumatic CNS abnormalities both in the acute and remote stages. In the setting of acute trauma, small, non-focal frontal or occipital defects are associated with a favorable prognosis. Large or multifocal defects involving the parietal or temporal lobes, the cerebellum, or the brainstem are associated with an unfavorable prognosis.

45. Psychiatric Disorders

46. Psychiatric Disorders
Schizophrenia
hypofrontality on both PET FDG and SPECT perfusion images (i.e., relative decreased frontal perfusion/metabolism).
Improved cortical activity in this region is seen following effective therapy

47. Drug abuse
Cocaine abuser: multiple small perfusion defect in brain cortex
Chronic alcoholics:reversible decreasing frontal lobe flow that reverts to normal with abstinence

48. Stress Test
Various stress methods which help to detect mild or latent abnormality.

49. Stress Methods

50. Diamox Stress test Inhibit carbonic anhydrase
Diamox (Acetazolamide, ACZ)
Inhibit carbonic anhydrase
CO2 concentration increase
Brain vascular dilation

51. Diamox Stress test Procedures
Get baseline image
Diamox 15-20mg/kg iv before tracer injection.
Stress image

54. Clinical Applications of Diamox Stress Test
Silent brain ischemia detection
Cerebrovascular reserve assessment
Cerebrovascular reaction in CCD
Prognosis prediction of cerebrovascular disease

55. 18F-FDG Brain Imaging

56. Tumor Cell Vascular Molecular Mechanism Glycogen Glycolysis 18FDG-1-P
Hexokinase K1
18FDG-6-
phospho-
glucono-lactone K3
18FDG
18FDG
18FDG-6P
HMP
shunt K4 K2
Glucose-6-
phosphatase
18F-fru-6-P
Glucose
transporter
protein
Glycolysis

57. Alzheimer’s Dementia (FDG PET)

59. Parkinson's Disease
Parkinson's is a progressive neurodegenerative disorder resulting from the progressive death of dopaminergic neurons in the nigrostriatal pathway.
Symptoms consist of rigidity, bradykinesia, difficulty in initiating and stopping movement, and a resting tremor

60. Parkinson's Disease(Cont.)
perfusion pattern in these patients is non-specific and demonstrates either normal or mild global cortical deficits. A pattern of bilateral posterior parietal/temporal defects indistinguishable from Alzheimer's may be observed in patients with Parkinson's disease with dementia.

61. Dopamine D2 receptor imaging

62. Research in Neurology: 18F-FP-CIT

63. Research in Neurology: 18F-FP-CIT

64. Brain Tumors
PET can play a role in grading of tumors, predictive of prognosis, differentiation of recurrent tumor from radiation necrosis.
Most high-grade neolpasm are hypermetabolism, low-grade tumors are hypometabolism.
Radiation necrosis are hypometabolism, recurrence are hypermetabolism.

65. Brain Tumor High Grade recurrence post RT
PET FDG TRANSAXIAL
T-1 POST Gd

66. 患者，女性，14岁。癫痫反复发作10年，近一年发作频繁。MRI平扫及增强见：胶质增生或良性胶质瘤。

67. 患者，男，52岁，顶叶胶质瘤2级术后，MRI示顶叶手术部位高信号，为鉴别复发或瘢痕进行PET检查。PET示左侧顶叶FDG代谢增高灶,手术证实肿瘤复发。

68. 患者，女性，65岁。右额顶胶质瘤术（1级）后并放疗15年。CT示：原肿瘤部位有增强。PET显像见该部位明显FDG摄取，考虑复发。

69. Occupational Lesion in Left Parietal lobe

70. Brain Function Study

72. Hearing

73. Thinking

74. Seeing

75. Remembering

76. Moving