Imaging Core

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Project Summary: Yale ADRC Imaging Core The Yale Alzheimer Disease Research Center has the overall goal to advance understanding and treatment of Alzheimer’s disease (AD). This effort requires integration of a wide array of core functions, including Clinical, Neuropathology, and Neuroimaging. Human imaging studies allow for the development of imaging biomarkers of AD, characterization of the temporal sequence of AD pathology, and lead to better assignment of patients to clinical research studies and clinical trials. Imaging is a major strength at Yale, as exemplified by the breadth and depth offered by the Yale PET Center and the Yale Magnetic Resonance Research Center (MRRC). In the PET Center, an example of recent significant work is the introduction of PET synaptic imaging with the SV2A tracer 11C-UCB-J. In MRI, the Yale MRRC has generated numerous novel methods to characterize an individual’s functional connectome and relate the functional organization to behavior and clinical variables Overall, these two Centers develop cutting edge imaging technologies and apply these techniques to answer important clinical questions. By creating this Yale ADRC Imaging Core (YAIC), we leverage the vast experience of Yale’s imaging strengths to provide state-of-the-art acquisition and analysis of imaging data and to focus on the development of novel approaches to AD. The YAIC will provide a common infrastructure for acquisition, processing, and analysis of multimodal imaging data, to support and train AD investigators and develop the next generation of imaging tools. The current and future methods will be applied to ongoing imaging studies to acquire a rich, multi-faceted and multi-modality dataset in human subjects. In addition, the translational component of this program examines the utility of nonhuman primates (NHPs) as a model for human AD. The Imaging Core will perform the following specific aims: Aim 1: To develop and optimize PET image and data analysis strategies to facilitate within- and between-subject comparisons. Multi-tracer within- subject correlations are important, involving amyloid, tau, synaptic density, and glucose metabolism. Aim 2: To enhance our MR-based functional connectome modeling to better functionally phenotype patients and link brain to behavior. This approach provides a functional profile for each individual while localizing the networks and revealing the network organizing principles supporting these functions. Aim 3: To develop and enrich multi- modality analyses between PET and fMRI for within- and between-subject studies. The combination of fMRI- based connectivity with the regional patterns of neurodegeneration measurable with PET provides an ideal opportunity for understanding the pathways of disease progression. Aim 4: To extend the methodologies developed for human analysis to NHP data. Ongoing studies in aged NHPs are being performed, providing the opportunity to compare in vivo PET and MR imaging with post-mortem measures provided by the Neuropathology Core.