hybrid diffusion imaging (hydi) of white matter

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Bryan J. Neth1, Akiva Mintz1, Kiran Sai1, H. Donald Gage1,. Carol Shively1, Thomas ..... Veterans Hospital, Madison, WI, USA; 2Wisconsin Alzheimer's. Institute ...
Poster Presentations: Sunday, July 24, 2016

was calculated for nine regions typically associated with tau deposition in PSP (midbrain, caudate, putamen, pallidum, supplementary motor area, superior frontal lobe, pre and post central cortex, and thalamus). Results: The PSP subjects showed evidence for subtle elevated tau-PET uptake compared to CN subjects across all regions. Uptake was particularly evident in midbrain, pallidum, supplementary motor area and precentral cortex (Figure). The degree of tau-PET uptake in PSP was lower than AD across all regions except midbrain, pallidum and thalamus. Subtle regional differences were observed between the different clinical variants of PSP. Uptake was generally the highest in those with Richardson’s syndrome across all regions, except for precentral cortex and supplementary motor area which showed highest uptake in PPAOS. PAGF predominantly involved basal ganglia and post-surgical PSP showed subtle uptake in midbrain and thalamus. Conclusions: PET imaging using AV-1451 can detect a signal across the different clinical variants of PSP, although the degree of uptake is far less than that observed in AD. This ligand may be sensitive enough to detect regional differences across the clinical variants of PSP.

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DUAL-TRACER ACETOACETATE AND GLUCOSE METABOLISM ARE ASSOCIATED WITH NEUROPATHOLOGIC AMYLOID BURDEN AND ALZHEIMER’S BIOMARKERS IN THE CSF

Bryan J. Neth1, Akiva Mintz1, Kiran Sai1, H. Donald Gage1, Carol Shively1, Thomas C. Register1, Matthew J. Jorgensen1, Rachel N. Andrews1, Hannah M. Atkins1, Beth Uberseder1, J. Mark Cline1, Stephen Cunnane2, Christian-Alexandre Castellano2, C. Dirk Keene3, Thomas J. Montine3, Joseph Maldjian4, Ben Wagner4, Timothy M. Hughes1, Suzanne Craft1, 1Wake Forest School of Medicine, Winston-Salem, NC, USA; 2Universite de Sherbrooke, Sherbrooke, QC, Canada; 3University of Washington School of Medicine, Seattle, WA, USA; 4University of Texas Southwestern Medical Center, Dallas, TX, USA. Contact e-mail: bneth@ wakehealth.edu Background: Glucose hypometabolism as visualized by FDG

PET is a well-established feature of Alzheimer’s disease

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(AD) that is evident years prior to the onset of clinical symptoms. Glucose is one of several metabolic fuels that the brain can utilize. To date, we know very little about how other cerebral energy sources are impacted by the disease and relate to disease pathology. We now have the opportunity to study both glucose and ketone body (acetoacetate or AcAc) metabolism in the same imaging session and can study several metabolic fuels and their interaction with AD pathology. Methods: Nine non-human primate (vervet) subjects were imaged with a novel dual-tracer, 11C-Acetoacetate/18F-Fluorodeoxyglucose PET imaging technique and 3T structural MRI used for anatomic co-registration of PET images. The same vervets had CSF sampled for Ab1-42, Ab1-40, total and phosphorylated Tau prior to necropsy. Additionally, Ab42 and Ab40 quantification in the temporal and parietal lobes were performed using a guanidine extraction method. Global, bilateral hippocampal, and AD regional composite (medial temporal, cingulate, and parietal) glucose and acetoacetate metabolic uptake were calculated and associated with AD neuropathology measures using Spearman correlation. Results: FDG and AcAc uptake were not significantly correlated either globally or in the AD-associated regions. Global FDG uptake was modestly correlated with CSF levels of Ab1-42 (R¼0.63, p¼0.07) and total Tau (R¼0.75, p¼0.05), while Global AcAc uptake was negatively correlated with parietal Ab40 burden (R¼-0.83, p 20 but psychometric performance within normal limits. All subjects received HYDI in a Siemens Prisma scanner using a multi-band accelerated EPI diffusion sequence. The HYDI protocol consisted of 5 diffusionweighted b-value shells, and was used for parametric diffusion model fitting (NODDI), non-parametric q-space analysis, and DTI. Maps of diffusion metrics were non-linearly transformed to standard MNI space using FSL FNIRT. Four WM ROIs were defined in standard MNI space by intersecting subjects’ mean WM skeleton with the WM atlas from John Hopkins University (JHU) ICBM-DT-813 (Fig. 1). ANCOVA analysis was used to test significance of diffusion metrics between SCD and CN groups covarying for age (significance at p