Zhu, Wei2025-04-212025-04-212023-01https://hdl.handle.net/11299/271374University of Minnesota Ph.D. dissertation. January 2023. Major: Biophysical Sciences and Medical Physics. Advisor: Wei Chen. 1 computer file (PDF); xv, 159 pages.Probing brain functions at laminar and columnar level provides opportunities in understanding local and remote neural circuits that are critical for cognition and behaviors. High field functional magnetic resonance imaging (fMRI) based on blood oxygenation level dependent contrast (BOLD) is one such tool capable of non-invasively mapping functional columns and/or layer responses at working or resting state. However, several challenges exist even for mapping at the ultrahigh field. These challenges include but not limited to 1) unwanted mapping specificity towards draining veins commonly seen in T2* weighted BOLD, 2) sensitivity drop due to the increased spatial resolution, 3) debatable spatial alignment between vasculature and functional columns, 4) a growing need for an improved post-processing procedure tailored to mesoscopic mapping regime, and 5) tortuous BOLD origins entangled with the complex neurovascular coupling. In this thesis, we provide effective solutions to each challenge in specific applications, aiming to advance the current fMRI technology to facilitate cutting edge brain research. We also demonstrate the feasibility of using high-resolution rs-fMRI to map the brain connectome at the laminar level in mice with an inherited genetic lysosomal disorder named mucopolysaccharidosis type I (MPS I).enfMRI preprocessing pipelinefunctional magnetic resonance imagingimage denoisinglaminar brain connectomemagnetic resonance angiogramtwo photon microscopyThesis or Dissertation