Dr Hussein Farghaly PSMMC Radionuclide Brain Imaging Lecture 5 Dr Hussein Farghaly PSMMC Master Watermark Image: http://williamcalvin.com/BrainForAllSeasons/img/bonoboLH-humanLH-viaTWD.gif

Dementia: An acquired syndrome characterized by: Short-term memory impairment AND At least one of the following: Aphasia - language impairments Apraxia - motor memory impairments Agnosia - sensory memory impairments Abstract thinking / Exec. function impairments Impairment in social and/or occupational fn Not explainable by another disorder

Causes of Dementia Dementia is a manifestation of many diseases. Only about 10% of dementias, such as those caused by vitamin B12 or thyroid hormone deficiency, are treatable

Causes of Dementia Alzheimer Disease (50-70%) Vascular dementia (15%) Frontotemporal dementia (5-10%) Lewy Body disease (25%) Normal Pressure Hydrocephalus (NPH) Depression Intracranial Mass

Diagnosis of Dementia The clinical diagnosis is often difficult and delayed, and anatomical imaging modalities such as CT and MRI may not reveal changes such as atrophy until the end stages of disease. SPECT and PET, on the other hand, have been shown useful in early diagnosis of Alzheimer disease. In addition, these functional modalities show promise for the identification of subjects early before damage is too severe for therapy to have any benefit. Although PET has higher sensitivity and higher resolution than SPECT, the overall patterns seen in dementia are similar for both rCGM and rCBF. In general, the types of dementia can be characterized as posterior, frontotemporal, or vascular. The posterior dementias include Alzheimer disease, Lewy body disease, and Parkinson dementia. Pick disease is the classic frontotemporal dementia.

Alzheimer’s Disease (AD) Progressive neurodegenerative disorder deterioration in cognition, function, and behavior Most common cause dementia in elderly 4 million in U.S. 30 million worldwide Female to male 3:1 $100 billion per year in U.S.

Pathology and Etiology Initial damage of neurons in temporal lobes and later in neocortex Extracellular beta amyloid plaques and intracellular neurofibrillary tangles (tau protein) Plaque buildup induces inflamation causing injury in hippocampus and cerebral cortex

Clinical Diagnosis Accuracy can exceed 90% Detailed history, physical, mental status examination, and neurologic assessment Rule out hypothyroidism, vitamin B12 deficiency, reversible causes of dementia

Imaging Studies Stuctural: CT and MR recommended for routine evaluation of AD Functional: PET and SPECT demonstrate physiologic changes in brain

MR vs. CT Low specificy and sensitivity MR preferred over CT Assess degree of Medial Temporal Lobe Atrophy Amygdala, Hippocampus, Parahippocampal gyrus Rule out other causes dementia

AD vs. Other Dementias NPH: holoventricular enlargement out of proportion to sulcal enlargement; dementia, apraxia, incontinence Generalized atrophy: sulcal and ventricular findings concordant Vascular dementia: multiple areas of high signal intensity on MR; stepwise decline, smokers, HTN, diabetes

Functional Imaging Modalities SPECT and PET Vascular dementia Frontotemporal dementia Lewy Body depression

SPECT imaging Brain uptake of technetium 99m-based lipid-soluble radionuclide 89% sensitivity and 80% specificity for AD Bilateral posterior perfusion abnormality associated with AD Frontal perfusion deficit associated with frontotemporal dementia Patchy uptake pattern associated with vascular dementia

SPECT imaging

Alzheimer Disease VS. Lewy Body disease AD LB Comparison of posterior dementias on Tc-99m HMPAO. Top row: Alzheimer disease generally begins near the superior convexity and involves the parietal and temporal regions laterally (arrows), sparing the occiput and cerebellum (arrowhead). Bottom row: Lewy body disease involves the medial occipital region (arrows) and usually has more caudal extension than Alzheimer disease. Nuclear Medicine: The Requisites textbook

PET imaging FDG and blood flow Deficits in temporoparietal metabolism seen in patients with AD Sparing of basal ganglia, thalamus, cerebellum, and primary sensorimotor complex Sensitivity 87-96%, 73% specificity

Alzheimer disease (A) Transaxial PET images reveal decreased metabolism to the temporal parietal cortex beginning high in the posterior parietal region with sparring of the basal ganglia, thalamus, and cerebellum. Nuclear Medicine: The Requisites textbook

(B) Tc-99m HMPAO SPECT shows that although Alzheimer disease is classically described as a symmetric process, it may be quite asymmetric, as seen in the left posterior parietal region. Nuclear Medicine: The Requisites textbook

(C) As Alzheimer disease becomes more severe it is more diffuse on this SPECT study. Nuclear Medicine: The Requisites textbook

PET imaging Frontotemporal dementias: decreased uptake in frontal and anterior temporal regions Depression: normal scan Vascular: patchy defects in central white matter Lewy body: deficits in occipital lobes and cerebellum

Frontotemporal Dementia

Frontotemporal dementia sparing posterior parietal regions. A, Frontal hypometabolism on PET can be due to many causes and changes visible long before MRI Nuclear Medicine: The Requisites textbook

AD

MID

FTD

Amyloid PET imaging New tracer for PET Carbon-11 (C-11)-labeled Pittsburgh compound B (PiB), Ab—or amyloid PET [F-18]florbetapir, achieved approval by the U.S. Food and Drug Administration in April 2012 Targets amyloid beta senile plaques and neurofibrillary tangles Long retention times in hippocampus

References Jack CR et al. MR Imaging-Based Volume Measurements of the Hippocampal Formation and Anterior Temporal Lobe: Validation Studies. Neuroradiology. Volume 176. No. 1; pp. 205-209. Lehericy et al. Magnetic Resonance Imaging of Alzheimer’s Disease. Eur Radiol (2007) 17: 347-362. Petrella, et al. Neuroimaging and Early Diagnosis of Alzheimer Disease: A Look to the Future. Radiology 2003; 226: 315-336. Zakzanis, Graham, and Campbell. A Meta-Analysis of Structural and Functional Brain Imaging in Dementia of the Alzheimer’s Type: A Neuroimaging Profile. Neuropsychology Review, Vol. 13, No. 1, March 2003.