Velocity-Selective Arterial Spin Labeling based Perfusion Mapping for Alzheimer's disease

Johns Hopkins University, Baltimore MD

Investigators

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Abstract

Project Abstract Alzheimer's Disease (AD) is the leading cause of dementia in elderly population. Imaging biomarkers have been established on PET with respective tracers for mapping accumulation of amyloid and tau, as well as neurodegeneration. Furthermore, considerable overlap between cerebrovascular disease (CVD) and AD suggest additive or synergistic effects of both pathologies on cognitive decline. Vascular dysfunction has also been recognized as an important biomarker for better understanding and characterizing this multifactorial disease. Reliable mapping of neurodegeneration and vascular dysfunction could play critical roles in many clinical applications. Cerebral blood flow (CBF) is a fundamental hemodynamic parameter that characterizes brain perfusion as both a surrogate of neuro function and a marker for small vessel disease. Arterial spin labeling (ASL) perfusion MRI offers the great advantages of not requiring an exogenous contrast agent and being free of ionizing radiation. Obtaining both structural MRI and perfusion MRI in a single visit to the clinic is highly desirable for scanning the elderly subjects. Interpretation of CBF maps derived from spatially selective ASL methods need to be cautious about the artificial perfusion deficit due to the slow flow often incurred in the older subjects. Despite many efforts in this field, there remains to be an unmet and urgent need to establish a standardized, reliable, and validated ASL-based CBF mapping protocol for multi-site across-vendor neuroimaging studies for AD. Velocity-selective ASL (VSASL) derived CBF maps are ideally suited for characterization of both neurodegeneration and vascular dysfunction among the elderly population, without suffering the limitations presented by the slow flow. We have implemented the first velocity-selective inversion (VSI) based VSASL with 3D acquisition on adult brains and demonstrated its higher sensitivity to perfusion signal over conventional ASL methods. The proposed work capitalizes on the high perfusion sensitivity of VSI- ASL recognized by the first guideline paper for VSASL, as well as accelerated acquisition and reconstruction strategy, and represents its first AD application. The purpose of this study is to further optimize 3D VSI-ASL with accelerated acquisition and reconstruction, and then ensure its multi-vendor compatibility (Aim 1); to evaluate its reproducibility and validity between sessions, vendors, and modalities (Aim 2); to characterize VSI-ASL derived CBF values of various brain regions in cognitively normal (CN) subjects, and patients with MCI and AD through both cross-sectional and longitudinal comparisons (Aim 3). we will have demonstrated the optimized 3D VSI-ASL technique with high reproducibility, validity, and sensitivity to detect changes in brain perfusion and neurodegeneration, which can be readily utilized as a more practical and cost-effective imaging biomarker of neurodegeneration and vascular dysfunction for multi-center and multi-vendor clinical studies of AD and ADRD.