Chronic monitoring of cortical hemodynamics after ischemic stroke using funcional optical imaging techniques
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The roles of the vascular architecture and blood flow in response to neurovascular diseases are important in predicting physiological outcomes. Observing these parameters chronically with optical imaging techniques provides insight into the neurovascular recovery process. We develop and deploy optical imaging systems for monitoring the progression of vascular structure, perfusion, and functional blood response after ischemic stroke in a chronic rodent model to observe vascular dynamics of the cortex under normal and diseased pathologies. Specifically, we monitor the progression of the vascular structure and cerebral blood flow (CBF) over a chronic period in the rodent cortex after photo-thrombotic occlusion. Multi-Exposure Speckle Imaging (MESI) provides surface measurements of microvascular flow dynamics while Two-Photon Fluorescence Microscopy offers direct visualization of the microvascular structure. We observe the occurrence of vascular reorientation in the sub-surface microvascular structure over a 35 day post-occlusion period. We also correlate MESI flow estimates in the parenchyma with sub-surface microvascular volume fractions from two-photon microscopy to assess how vascular density influences the surface-integrated MESI measurements. Next, we develop and validate a MESI technique for measuring absolute changes of the functional blood flow response to forepaw stimulation in rodents, termed FA MESI. The optimal camera exposures for capturing the CBF response to forepaw stimulation are extracted from a training set of animal data and the feasibility of the technique is demonstrated in a testing animal set by comparing functional response results between new and existing techniques. We then deploy this system in a chronic study monitoring the progression of hemodynamic parameters after ischemic stroke within the functionally responding area of the cortex. The progression of the regional CBF perfusion and absolute changes in the magnitude of the functional blood flow response are monitored chronically after photo-thrombotic occlusion. We compare the differences between absolute and relative measurements of the functional blood flow responses, and validate FA MESI by comparing baseline measurements to 15-exposure MESI over the sampled flow distributions. We demonstrate the differences measured between the functional outcomes and the regional CBF perfusion over a three week post-occlusion time period.