Wednesday, September 18, 2024
9/18/2024
PROJECT SUMMARY Alzheimer’s disease (AD) affects 6 million Americans and is projected to increase to 14 million by the year 2050, with no effective treatment strategies. It is becoming increasingly recognized that AD is multifactorial in nature; the most common mixed dementia pathology is AD amyloid and tau depositions in concert with cerebrovascular disease. However, the exact role of vascular disease in relation to tissue pathology and AD pathogenesis is still uncertain. Magnetic resonance imaging (MRI) is frequently used to observe structural brain changes in AD, but also has the capacity to functionally assess cerebrovascular disease, including cerebral blood flow, pulsatility, perfusion, and white matter lesions of vascular origin. Using 4D flow MRI and pseudo-continuous arterial spin labeling (pCASL), our research group has shown that alterations in cerebrovascular flow and perfusion exist in AD cohorts. We plan to further our vascular imaging territory by utilizing MRI to derive aortic pulse wave velocity (PWV) measures to indirectly asses aortic stiffness, an independent predictor for systemic cardiovascular disease. However, these acquisitions (1) typically require breath-holds to reduce respiratory motion artifacts, which may not be possible in some aging or AD individuals and (2) require high temporal resolution to accurately resolve flow waveforms. Aim 1 is designed to address this by developing a novel, accelerated, free-breathing MR methodology to measure aortic PWV, providing a metric for global cardiovascular health. Specifically, we will employ a radial simultaneous multi-slice (SMS) phase contrast sequence with through-plane encoding and constrained reconstruction to greatly improve resolution capabilities. Aim 2 will validate obtained aortic PWV measurements (from Aim 1) against gold-standard pressure wire measurements with in-vitro testing in 3D printed aortic models and test repeatability of such measures in healthy volunteers. In collaboration with other members at the UW, our research group has implemented methods to probe microvascular pulsatility using displacement encoding stimulated echo (DENSE) sequences as well as measure cerebrovascular PWV using highly- constrained 4D flow reconstructions. Aim 3 seeks to combine cranial 4D flow, pCASL, DENSE, structural brain imaging, and methods from Aim 1, to simultaneously assess multiscale vascular health and structural changes in a group of AD-confirmed and healthy age- and sex-matched controls. This would be the first study to bring together these advanced quantitative MR imaging techniques, providing new insights into vascular disease amongst those with and without AD as well as knowledge of how vascular disease relates to structural changes. Completion of the proposed project and training plan will expand the academic scope of the applicant and foster his goals of becoming an independent investigator focused on translational imaging research.
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