Imaging of cerebral microvascular pulsatility in cerebral small vessel disease

PROJECT SUMMARY/ABSTRACT Cerebral small vessel disease (cSVD) is a major public health challenge, responsible for approximately 30% of strokes and at least 40% of dementia cases. cSVD is a major vascular pathology in Alzheimer’s disease (AD) and vascular cognitive impairment manifesting as cerebral amyloid angiopathy (CAA) in leptomeningeal

surface and penetrating arteries and arterioles (LPAs) of the cortex and as arteriosclerosis in lenticulostriate arteries (LSAs) in the subcortex, respectively. Based on routine neuroimaging methods, we are unable to directly visualize these vital cerebral small vessels (CSVs), however, we observe their downstream effects on

clinical MRI as cSVD, which manifests as parenchymal vascular brain injuries such as lacunes and other small infarcts, white matter hyperintensities, cerebral microbleeds, and enlarged perivascular spaces (PVSs). In the absence of a routine neuroimaging technique to directly visualize the CSVs, there is a need to better

understand the functional status of these blood vessels to broaden our understanding of these disorders with the promise of early prevention and treatment of cognitive impairment. The proposed research will help to fill this scientific gap by studying arterial pulsatility, an established index of vascular dysfunction. Increased arterial

pulsatility of CSVs induces higher vessel wall shear stress and the possibility of endothelial dysfunction and damage, leakage of the blood brain barrier, and reduced tissue cerebral blood flow (CBF). Increased pulsatility (or reduced vessel wall pulsations) of CSVs could also be associated with a reduction in cerebrospinal fluid-

interstitial fluid (CSF-ISF) exchange resulting in the deposition of toxic waste product in PVSs, which would eventually result in WMH and/or enlargement of PVSs. Therefore, cerebral microvascular pulsatility may play an important role in the pathophysiology of cSVD. Recently, submillimeter resolution 7T MRI has demonstrated

the capability of directly characterizing the hemodynamics and pulsatility of deep cerebral perforating arteries. However, the widespread use of 7T MRI remains limited due to its high cost, limited availability, and inherent technical challenges. To facilitate broader applicability in both clinical and research settings, this research

project proposes to develop two advanced MRI techniques to directly assess cerebral microvascular pulsatility on widely assessable 3T MRI and evaluate cerebral microvascular pulsatility in cSVD by investigating its relationship with the global burden of cSVD as an MRI biomarker of brain parenchymal injury. The successful

completion of this project will yield two complementary MRI imaging tools for the direct assessment of cerebral microvascular pulsatility on widely available 3T MRI, which will further our knowledge of how cerebral micro- vessel dysfunction may contribute to cSVD and provide a clinically relevant and useful novel diagnostic

technology for understanding cSVD.