We will design, and construct a combined near infrared (NIR) and magnetic resonance (MR) imaging system for studying brain oxygenation, and apply it to the study of brain hypoxia/ischemia. Normal function of brain, as well as pathologies such as stroke, birth asphyxia, tumors, hydrocephalus and epilepsy all induce changes in oxygenation. Imaging methods which provide high spatial and temporal information concerning brain oxygenation would be of significant use. This NIR/MR imager will provide spatially resolved data on cerebral oxygen utilization, extraction, blood volume and blood saturation. The main goal is to show that, by using structural information from the MRI, one can constrain the reconstruction of NIR data to obtain true NIR images. We can then co-register these oxygenation images with any MR imaging modality including diffusion, perfusion and BOLD (blood oxygen level dependent imaging). NIR provides accurate information on hemoglobin content and saturation but, without the developments which we propose, NIR data are difficult to reconstruct into an image. We will verify NIRS reconstruction algorithms for a range of study diameters. Then we will construct appropriate NMR hardware compatible with the NIBS imaging system and combine the two to create the hybrid imaging modality. We will test this on phantoms and on animal models. After developing the system, we have two hypothesis driven aims designed to show the potential of the imager, as well as to provide unique data on hypoxia/ischemia. We will test the hypothesis that the hippocampus has a high oxygen extraction during normoxia, and reduced capacity to increase extraction during hypoxia. This difference in extraction may be one of the mechanisms of increased hypoxia sensitivity in the hippocampus. We also hypothesize that the brain has a reduced extraction, and cerebral blood flow during reperfusion after hypothermic ischemia. Such a pattern of oxygenation has been implicated in neurological impairment after cardiopulmonary bypass. On the other hand, this is the period of increased oxidative damage post-ischemia, and so reduced oxygenation during reperfusion may be beneficial under some situations. We will assess brain tissue oxygenation and blood flow (using MR perfusion imaging) during ischemia/reperfusion during normoxia and hypothermia. This grant will produce a novel imaging modality which can non-invasively monitor cerebral oxygenation, structure, and blood flow.
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