Quantitative optical imaging platform for studying neurovascular hemodynamics during ischemic stroke

Sullender, Colin Tan
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The measurement of cerebral hemodynamics is vital for the study of physiological and pathophysiological conditions in the brain. Preclinical research examining the mechanisms, outcomes, and efficacies of interventions during ischemic stroke require quantitative imaging technologies. This dissertation presents the development of an optical imaging platform capable of chronic in vivo monitoring of cortical hemodynamics during ischemic stroke and the subsequent recovery. The system combines two different imaging techniques, laser speckle contrast imaging (LSCI) and oxygen-dependent quenching of phosphorescence, to measure cerebral blood flow (CBF) and dissolved oxygen tension (pO2) within cortical vasculature. Phosphorescence signal localization is achieved through the use of a spatial light modulator to selectively pattern excitation light in order to overcome the traditional limitations of the imaging modality. The spatial light modulator is also utilized to perform artery-targeted photothrombosis for the induction of highly-localized, reproducible infarcts as an extension of the photothrombotic model of ischemic stroke. The LSCI hardware implements the multi-exposure speckle imaging (MESI) technique for robust estimates of CBF that facilitate day-to-day and between-subject comparisons. The integration of an awake imaging system eliminates the confounding effects of anesthesia upon cerebral hemodynamics. The capabilities of the complete optical imaging platform are demonstrated by monitoring the acute hemodynamic response during targeted photothrombosis and the chronic recovery of the resulting ischemic infarct