Non-Contrast-Enhanced MRI for Brain Perfusion Mapping of Lewy Body Dementia - Project Abstract Cognitive impairment is a significant non-motor symptom of Parkinson's disease (PD). At least 75% of PD patients surviving for more than 10 years will develop Parkinson’s disease dementia (PDD) and the incidence rate of dementia in PD is 4-6 times of the general population. PDD and dementia with Lewy bodies (DLB), jointly known as Lewy body dementia (LBD), are both caused by abnormal deposits of proteins in the brain called Lewy bodies, and account for 4-10% of all dementia patients. Cerebral blood flow (CBF) is considered an important biomarker for neurodegeneration. There remains an urgent unmet need to establish reliable and practical neuroimaging biomarkers related to cognitive functions to describe both the spatial and temporal progression of LBD. Arterial spin labeling (ASL) is a completely noninvasive method for measuring CBF and is ideal for frequent non-invasive longitudinal monitoring. ASL methods typically apply spatially selective inversion modules to supply arteries distant from imaging volumes, which is known to render underestimation of CBF due to transit time delay, especially among elderly subjects. Velocity-selective arterial spin labeling (VSASL) was proposed to remove the time-delay artifact. Our group has implemented the first velocity-selective inversion (VSI) based VSASL with 3D segmented GRASE acquisition and demonstrated its higher sensitivity to perfusion signal over conventional ASL methods. Furthermore, our preliminary data showed that VSASL with 3D single-shot stack-of-spiral-based turbo FLASH acquisition delivered better perfusion image quality with fewer artifacts than using segmented GRASE, and high temporal resolution potentially allowing adequate retrospective motion correction. The overarching goal is to test the hypothesis that the VSASL-based CBF pattern is a reliable biomarker for LBD that predicts long-term cognitive impairment and dementia outcomes: Aim 1, we will conduct further technical developments for 3D VSASL with accelerated acquisitions and improved immunity to head motion; Aim 2, we will assess VSASL’s between- session reproducibility and its reliability to detect regional changes in CBF related to movement tasks and the dopaminergic medication; Aim 3, we will investigate VSASL’s sensitivity to early cognitive impairment in patients leading to LBD through both cross-sectional and longitudinal comparisons. These studies are to ensure the optimized VSASL MRI technique with high reproducibility, reliability, and sensitivity to detect early changes in brain perfusion that are correlated with cognitive impairment and dementia in patients leading to LBD.
