Thesis (Ph. D.)--University of Rochester. Department of Physics and Astronomy, 2021.
Quantifying the presence of magnetic susceptibility sources throughout the brain makes it possible to better understand the pathomechanisms of disease processes. Magnetic susceptibility sources introduce inhomogeneities into an external magnetic field that influence the biological signals that can be detected with magnetic resonance imaging (MRI). Cerebral small vessel disease (CSVD) is a common neurodegenerative disease impacting over 95% of adults over the age of 65 that is diagnosed using MRI. Human Immunodeficiency Virus Type I (HIV) is a disease that is accompanied by diffuse chronic inflammation in the central nervous system and accelerated signs of CSVD, even with effective viral suppression by combination antiretroviral therapy (cART). By enrolling a cohort of HIV-infected (HIV+) individuals and healthy age-matched controls with similar cardiovascular risk, we use advanced multi-modality MRI to explore the underlying mechanisms of HIV-associated CSVD (Chap. 3). We use quantitative susceptibility mapping (QSM) and Monte Carlo simulations of pathological brain iron deposition to derive a novel MRI biomarker that is more sensitive to changes in brain tissue susceptibility than other standard analyses (Chap. 5). We also show that QSM has relationships with cardiovascular health, white matter hyperintensities (WMHs), and platelet-monocyte complexes (PMCs), which may reflect microglial dysfunction in HIV infection (Chaps. 4 and 6). We also correct for susceptibility-induced distortions in diffusion MRI, functional MRI, and arterial spin labeling (ASL) to examine brain connectivity network disruptions (Chap. 7), declines in cognition (Chap. 8), and changes to white matter microstructure (Chap. 9) and vascular health (Chap. 10) in the presence of HIV and CSVD. The role of magnetic susceptibility in the aging brain is crucial for the understanding of brain mechanisms and may play an important role in the eventual clinical translation to more effectively prevent and treat cerebrovascular disease.
