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.