The overarching objective of Core B is to support Projects 1-3 by providing archiving and pipelined analyses of acquired data. This functionality is provided through informatics, image analysis and technology development. Projects 1 and 2 will use the identical experimental protocol (glucose/insulin clamping) to investigate the effects of hyperglycemia and hyperinsulinemia on physiological measures of brain function (PET measures of glycolysis and fMRI functional connectivity and task-related mapping) in normal and diabetic humans. Projects 1-2 will be supported by robust, multi-modal image registration techniques. Project 3 will utilize the same experimental intervention (glucose/insulin clamping plus sleep deprivation) in wild type and APP/PS1 mice. The physiological effects of these interventions in mice will be assessed using invasive techniques (microdialysis) and optical intrinsic signal functional connectivity imaging (fcOIS). Basic imaging support will be predominantly based on extant procedures developed in the Neuroimaging Laboratories (NIL) at Washington University School of Medicine. These techniques have been extensively described in previous publications. To maximize the value of the mouse data, state-of the art techniques will be used to assemble mouse histological sections into 3D volumes and to co-register these volumes with the optical data. Novel methods will be developed with the objective of improving experimental techniques used in all three Projects: ? Extending the Extensible Neuroimaging Archive Toolkit (XNAT) informatics platform, developed for human neuroimaging, to accommodate mouse data ? Improving the accuracy, safety and scientific value of quantitative human PET imaging by validation of the recently developed image-derived arterial input function (IDAIF) estimation technique for use with the recently acquired combined PET-MRI scanner ? Development of "awake" mouse optical intrinsic signal imaging (OIS) ? Validation of mouse OIS functional connectivity mapping against stimulus-evoked sensory responses in multiple domains.

Public Health Relevance

Core B support functions constitute a straightforward but necessary component of the research proposed in Projects 1-3. Future human and mouse studies will be advanced by the development of informatics architectures and of the awake mouse OIS technique. Validation of IDAIF for use on the combined PETMRI scanner is a critical step in the development of simultaneous PET-MRI imaging.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Program Projects (P01)
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National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
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Washington University
Saint Louis
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Lim, Miranda M; Gerstner, Jason R; Holtzman, David M (2014) The sleep-wake cycle and Alzheimer's disease: what do we know? Neurodegener Dis Manag 4:351-62
Bauer, Adam Q; Kraft, Andrew W; Wright, Patrick W et al. (2014) Optical imaging of disrupted functional connectivity following ischemic stroke in mice. Neuroimage 99:388-401