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FDG PET/CT in Dementia Imaging SAIMA MUZAHIR; MD ERLANGER HEALTH TENNESSEE INTERVENTIONAL AND IMAGING ASSOCIATES Introduction Dementia characterized by progressively deteriorating dysfunction of various intellectual domains: Memory Language Executive function Magnitude of Problem Estimated 35.6 million people with Alzheimer’s disease (AD) and other dementias worldwide in 20091. With rapid aging societies around the world, the number of people with dementia is projected to reach 66 million by 2030 2 The global economic cost of dementia in 2010 was estimated at U.S. $ 604 billion. Ferri CP et al. World Alzheimer report 2009. Wortmann M. Dementia: a global health priority- Alzheimers Res Ther 2012. Types Of Dementia Alzheimer’s disease (50-60%) Frontotemporal dementia (15-25%) Lewy Body dementia (LBD) (15-25%) Vascular dementia (VAD) Chronic traumatic encephalopathy (CTE) Parkinson’s disease dementia (PDD) Dementia Diagnosis The diagnosis of a primary neurodegenerative disorder is commonly made by excluding secondary causes. The workup of patients with cognitive impairment involves: anatomic imaging (computed tomography [CT] and magnetic resonance [MR] imaging) performed concurrently with biochemical and laboratory investigations to exclude dementia due to structural, vascular, metabolic, inflammatory, hormonal, or toxic causes. Dementia Diagnosis Challenges Distinguishing between different neurodegenerative disorders on the basis of clinical assessment alone may be difficult. Diagnosis is particularly challenging in the early stages of disease, especially in patients with higher levels of education who may experience significant decline in cognitive function before being recognized as having cognitive impairment on standardized neuropsychologic tests. Co-morbid conditions (depression, use of certain medications). Clinicians require a high degree of certainty before making a diagnosis of Alzheimer’s disease or some other neurodegenerative disorder, since the impact on patients and their families can be devastating. Accurate diagnosis is important because emerging therapeutic regimens vary depending on the cause of the dementia. Diagnostic Accuracies Of Different Imaging Modalities And CSF Markers in AD AJR 2014 Alzheimer’s Disease Clinical diagnosis Clinical criteria for AD are conserved to be the basis of the diagnosis. The cognitive changes in AD tend to follow a characteristic pattern, beginning with memory impairment and spreading to language, praxis and visuospatial deficit. Sporadic or genetic factors. Histopathologic analysis is the standard of reference for the diagnosis of Alzheimer’s disease. The presence of intraneuronal deposits of abnormally phosphorylated t protein (neurofibrillary tangles) and extracellular b-amyloid (senile plaques) are seen in Alzheimer disease. Alzheimer’s disease However clinical diagnosis, even when combined with any of the neurophysiological tests available, is neither sensitive nor specific to be considered as a reference standard in diagnosing dementia. A Need For Imaging Biomarker FDG PET is a biomarker for NEURONAL DEGENERATION in dementia. Studies have shown that appropriate use of FDG PET for evaluating patients with dementia can add valuable information to the clinical workup of without adding to the overall costs of evaluation and management. Molecular Imaging FDG PET/CT F-18 FDG PET ( 2-[fluorine-18]fluoro-2-deoxy-d-glucose) is a highly useful imaging modality for the diagnosis of neurodegenerative disorders. FDG is an analog of glucose, the main energy substrate of the brain. After uptake and phosphorylation by hexokinase, FDG becomes trapped in neurons, allowing imaging and measurement of the cerebral metabolic rate for glucose. This is closely related to neuronal and synaptic function in numerous human resting and functional activation studies. Characteristic patterns of altered metabolism seen at FDG PET can markedly improve the clinical diagnosis for specific types of dementia such as FTD, Alzheimer disease, and DLB, each of which has characteristic metabolic signatures, although there is some overlap. Recognition of the common patterns of altered cortical metabolism seen in these various entities is crucial for identifying the cause of cognitive impairment. With use of proper technique, and with the increasing availability of computer-assisted diagnostic (CAD) statistical mapping tools, the neuroimager can play a key role in the workup of patients with cognitive impairment. Imaging Findings in AD MRI Early: “Normal” or medial temporal atrophy Late: Generalized atrophy FDG PET Early: Hypometabolism in the temporal/parietal regions Late: Generalized hypometabolism (with sparing of primary sensorimotor cortex) Amyloid PET All stages: Generalized cortical amyloid deposition Amyloid binding may also occur with normal aging Glucose use Patterns in Brain Glucose use in the cerebral hemispheres is usually symmetric. With normal aging, the largest FDG uptake decrease has been observed bilaterally in the: SUPERIOR MEDIAL FRONTAL ANTERIOR AND MIDDLE CINGULATED CORTEX BILATERAL PARIETAL CORTICES SUPERIOR AND INFERIOR PARIETAL CORTEX Brown et al. Radiographics 2014 3 D SSP surface map Z Score map Normal Brain 46-year-old woman who underwent FDG PET/ CT study of brain and whose findings were normal. A and B, Three-dimensional stereotactic surface projection images of FDG metabolism (A) and FDG hypometabolism (B) of brain show normal brain metabolism and no evidence of significant hypometabolism (> 1 SD) for age-matched population. Age-matched z score was compared with normal database (Cortex ID software, GE Healthcare). A =anterior, P = posterior. Normal Elderly Brain Healthy elderly male subject, 78 years of age, Mini-Mental State Examination score 30. A, A slight enlargement of the right inferior horn of the lateral ventricle is seen on the T1-weighted MR image. B, The regional glucose metabolism is not reduced on the FDG-PET images. Note that the posterior cingulate glucose metabolism is much larger than that in other regions. C, PiB-PET shows nonspecific accumulation in the white matter but no PiB accumulation in the gray matter. The amyloid deposit is negative. Alzheimer’s disease Early Alzheimer’s disease A patient with early Alzheimer’s disease, 77 years of age, Mini-Mental State Examination score 25. A, Minimal atrophy was seen in the right hippocampus. B, FDG-PET shows reduced glucose metabolism in the bilateral parietotemporal association cortices and poster cingulate gyri and precuneus. C, PiB accumulations are demonstrated in the cerebral cortice except for the occipital and medial temporal regions. Medial parietal and frontal accumulations of PiB are high, indicative of positive amyloid deposit. 57-year-old woman with history of cognitive decline. A. Three-dimensional stereotactic surface projection images of FDG metabolism B. FDG hypometabolism of brain show distinct hypometabolism in posterior cingulate cortex (right greater than left), feature consistent with amnestic mild cognitive impairment. Age-matched z score was compared with normal database (Cortex ID software,GE Healthcare). Combination of MR Imaging and PET Yuan et al performed a meta-analysis and meta-regression on the diagnostic performance data for MR imaging, SPECT, and FDG-PET in subjects with MCI and reported that FDG-PET performed slightly better than SPECT and structural MR imaging in the prediction of conversion to AD in patients with MCI, while a combination of PET and structural MR imaging improved the diagnostic accuracy of dementia. Kawachi et al also compared the diagnostic performance of FDG-PET and voxel-based morphometry (VBM) on MR imaging in the same group of patients with very mild AD and reported an accuracy of 89% for FDG-PET diagnosis and 83% for VBM–MR imaging diagnosis, while the accuracy of combination FDG-PET and VBM-MR imaging diagnosis was 94%. Kawachi T, Ishii K, Sakamoto S, et al. Eur J Nucl Med Mol Imaging 2006. 81-year-old man with history of cognitive decline, over course of few months. Study was requested to evaluate for Alzheimer’s disease (AD) versus frontotemporal dementia. Three-dimensional stereotactic surface projection images of FDG metabolism and FDG hypometabolism. Brain show hypometabolism in bilateral frontal, temporal, and parietal cortexes with sparing of sensory motor and occipital cortex, spatial distribution pattern typically seen in advanced stages of AD. Age-matched z score was compared with normal database Diffuse Lewy Body Disease Most common neurodegenerative disorder in patients over 65 years of age. The classic clinical triad includes (a) fluctuating levels of cognitive arousal (b) visual hallucinations, and (c) spontaneous parkinsonism. In addition, the patient’s clinical condition may worsen following the administration of neuroleptic medications Bilateral parietal and posterior temporal hypometabolism and posterior cingulate gyral hypometabolism similar to that seen in Alzheimer disease. However, there can also be associated involvement of the occipital lobes, which are spared in Alzheimer disease. Imaging with dopamine transporter agents can also help distinguish DLB from Alzheimer disease when clinical and FDG imaging findings are indeterminate. An Alzheimer disease pattern of hypometabolism and a positive dopamine transporter scan indicate that DLB is the most likely diagnosis. Primary visual cortical hypometabolism is highly specific and moderately sensitive for distinguishing DLB from Alzheimer disease. Frontotemporal Dementia Classic FTD is characterized by hypometabolism in the frontal and anterior temporal lobes with involvement of the anterior cingulate gyrus. 75 year old male presenting with confusion, cognitive decline, memory loss, irritability and mood changes. FDG PET Medicare Coverage Dementia and Neurodegenerative Effective 9/15/2004, “An FDG PET scan is considered reasonable and necessary in patients with: a recent diagnosis of dementia, documented cognitive decline of at least 6 months, meet diagnostic criteria for both AD and FTD.” http://www.cms.gov/Regulations-andGuidance/Guidance/Manuals/downloads/ncd 103c1_Part4.pdf FDG PET Medicare Coverage Dementia and Neurodegenerative Diseases Additional prerequisites include: Comprehensive evaluation already completed, including brain CT or MRI Evaluation by “a physician experienced in the diagnosis and assessment of dementia” Evaluation is indeterminate and FDG PET is reasonably expected to clarify the diagnosis between FTD and AD SPECT or PET have not already been obtained in the past 12 months AND significant clinical changes have occurred Quality Control FDG PET and interobserver variability The interpreting radiologist also needs to be aware of the terminology used by our neurology colleagues when reporting brain images. Automated voxel-based statistical analysis has been uniformly used in FDG PET–based research to provide standardized, objective, and quantitative validation of observed metabolic changes in neurodegenerative disorders. Studies have found that the performance of automated systems and expert readers is equivalent with respect to receiver operating curve characteristics for all types of neurodegenerative disorders. Dementia workup: Asking the right questions I want to work up a patient with cognitive symptoms. What imaging modality should I order? What is the clinical suspicion(s)? What is the local access to advanced imaging techniques? Do patient comorbidities suggest a wider DDx? Are there any patient-specific limitations to imaging (foreign body, tolerance of prolonged scan times, body habitus, etc)? The illiterate of the 21st century will not be those who cannot read and write, but those who cannot learn, unlearn, and relearn. Questions??? Questions???