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.
