Imaging and Biomarker Core

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Abstract The Imaging and Biomarker (IB) Core will characterize participants in the Clinical Core through neuroimaging and fluid biomarker analysis, in conformity with prevailing standards. A further focus is to rigorously describe topographic phenotypes of the participants and to link this information to cognitive, fluid biomarker, genetic, and neuropathologic data generated by the Center. The Core will also provide an information architecture and consulting expertise to represent the imaging data to ADRC-affiliated studies and investigators. Many UW ADRC-affiliated studies require human subjects who are well-characterized with imaging and fluid biomarkers. MRI imaging will be obtained on all normal cognition, MCI, and mild AD participants in the Clinical and Native Research and Resource (NRRC) Cores. We will characterize our Clinical Core cohort with A|T|N classification, primarily with CSF biomarkers (A, T) and MRI (N) imaging. The IB Core will coordinate PET scans in ADRC affiliate projects or co-enroll affiliate subjects in the Clinical Core to ensure Clinical Core subjects have PET scanning performed. We provide expertise in planning and analyzing PET molecular imaging studies. Affiliated studies are investigating specific candidate mechanisms of AD, as well as whether, and why, different pathological mechanisms inherent in AD have differing patterns of impact over the cerebral cortex. For such studies, the brain space is a point of integration of the other biomarkers of AD. We have organized the IB Core and its interactions with the Clinical and Neuropathology Cores such that topographical heterogeneity, determined from imaging data, is incorporated as a phenotypic characteristic, along with cognitive domain, fluid biomarker, and genetic data. We will measure cortical degeneration, as well as cortical sparing, across a set of brain regions that represent the range and variability of involvement in AD. Another important aspect of cognitive variability is the relationship of the degree of cognitive impairment that results from a given degree of neurodegeneration (cognitive resilience). Thus we will also extract measures of cognitive resilience from cognitive and anatomic data, as another phenotypic dimension. We will provide consulting expertise in informatics/machine learning, image analysis and statistics for the description and analysis of these data. We have also structured the Core to support the same multidisciplinary phenotyping in decedents from the Clinical cohort who come to autopsy. We will perform ex vivo MRI in all, and process structural measures as in the in vivo studies. We will sample tissue from the same regions that we target with imaging in living participants. We will calculate analogous resilience measures. Ex vivo MRI will also enable targeted sampling of MRI-apparent abnormalities at autopsy and mapping neuropathologic data into standard anatomical space.