PhD Oral Exam - Ali Rezaei, Physics

When studying for a doctoral degree (PhD), candidates submit a thesis that provides a critical review of the current state of knowledge of the thesis subject as well as the student’s own contributions to the subject. The distinguishing criterion of doctoral graduate research is a significant and original contribution to knowledge.

Once accepted, the candidate presents the thesis orally. This oral exam is open to the public.

Abstract

Coronary artery disease (CAD) and cardiovascular risk factors are associated with cognitive decline and dementia, yet the cerebral tissue and physiological alterations underlying these relationships remain poorly understood. In particular, white matter (WM) microstructural abnormalities may precede visible lesions, while changes in cerebral pulsatility, perfusion, and oxygen metabolism in gray matter (GM) may contribute to making the brain vulnerable to ischemic episodes. This thesis comprises three studies using quantitative MRI to characterize WM microstructure and GM vascular and metabolic health in relation to CAD and cardiovascular risk burden, with particular attention to watershed regions at arterial borders.

The first study compared cognitively unimpaired individuals including 46 with CAD and 40 healthy controls using myelin- and iron-sensitive MRI measurements. Individuals with CAD exhibited lower magnetization transfer saturation and longitudinal relaxation rates, alongside higher magnetic susceptibility, predominantly in normal-appearing WM (NAWM) watershed regions. These findings were consistent with reduced myelin and possible iron accumulation, and the MRI alterations were associated with poorer cognition.

Building on these findings, the second study examined 43 individuals with CAD to determine whether NAWM alterations varied with CAD severity and revascularization history. Higher SYNTAX scores were associated with lower myelin-sensitive measurements, particularly in anterior and middle cerebral arterial territories. Compared with percutaneous coronary intervention, coronary artery bypass grafting was associated with more widespread reductions in myelin-sensitive measures and higher magnetic susceptibility in watershed regions.

The third study investigated 127 cognitively intact older adults, combining resting-state functional MRI, arterial spin labeling, and susceptibility mapping to assess cerebral pulsatility index, blood flow, oxygen extraction fraction, and consumption. Higher Framingham Risk Scores were associated with greater pulsatility and lower cerebral blood flow and oxygen consumption. Elevated pulsatility was associated with reduced perfusion and oxygen consumption, while positive associations with oxygen extraction were specific to watershed GM. Mediation analyses suggested that pulsatility partly accounted for risk-related differences in perfusion and oxygen consumption, particularly in watershed regions.

Together, these studies identify complementary microstructural and physiological correlates of cardiovascular disease and risk, highlighting watershed regions as vulnerable regions and the potential value of multimodal qMRI for detecting cerebral alterations before cognitive impairment occurrence.