| This dissertation focuses on instrumentation development for optical monitoring of hemodynamics in rodent brains, which would allow neurophysiologists, conducting pre-clinical research on brain diseases and disorders, to better understand disease onset and progression, and evaluate treatment options.;Three specific challenges in applying optical tools to brain imaging were addressed: (1) the limited robustness of optical imaging in the presence of misfocus, (2) the low sensitivity in imaging brain activity under anaesthesia in chronic, longitudinal studies, and (3) the limited penetration depth of optical microscopy in tissue.;Two methods were proposed to address misfocus-related imaging artefacts, which enable quantitative optical measurements of blood flow to take place across large fields of view and over long imaging time-frames. A system for blood flow monitoring with extended depth of field was developed, showing improved ability to accurately image flow speeds over large areas in the brain. In addition, a novel measure for misfocus was proposed, enabling robust autofocusing in the presence of measurement noise. A miniaturized, skull-mounted multi-modal optical imaging system was designed for imaging brain blood flow and oxygenation changes in freely-behaving animals. This device constituted the first demonstration of wide-field optical imaging of brain blood flow and oxygenation in a chronic setting, suitable for longitudinal studies of brain disease progression and investigating treatment efficacy. Lastly, a novel endoscopy method was proposed to measure flow speeds of scattering fluids through a single, multi-mode optical fiber. This endoscopy method could enable imaging blood flow speeds in deep brain structures using a minimally-invasive probe that is over 2x smaller than conventional micro-endoscopes used today.;Combined, the accomplishments described in this dissertation contributed to making optical measurements of brain hemodynamics applicable to a wider range of imaging assays, and to making optical imaging a more accessible tool for the study of brain vasculature. |
