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Abstract

The broad, long-term goal of this dissertation is to improve quantitative perfusion magnetic resonance imaging (MRI) for diagnosis, prognosis, and treatment of cerebrovascular disease. Perfusion MRI can assess delivery of blood to a capillary bed in tissue, and quantify flow. The first aim of this work tests the hypothesis that standardized quantitative dynamic susceptibility contrast (DSC) MR perfusion improves prediction of therapeutic outcome of experimental flow augmentation in acute ischemic stroke. Further, results of the study support evaluating flow augmentation as a method of minimizing infarct growth during the critical “door to needle” time for thrombolysis, demonstrating its use in pre-clinical stroke research. The second aim of this work tests the hypothesis that overestimation of perfusion deficit, due to blocked arteries delaying and dispersing contrast agent as it travels through the vascular system, can be reduced by use of a local arterial input function (AIF) DSC in intracranial atherosclerosis. Preliminary data supports the hypothesis that local-AIF DSC can return more accurate perfusion in intracranial atherosclerosis by adjusting for pial collateral supply that standard DSC does not. The third aim of this work tests the hypothesis that intravoxel incoherent motion (IVIM) MR perfusion can be quantified in ml/100g/min by derivation from fundamental diffusion principles to agree with gold standard microspheres and DSC at baseline, post-CO2 inhalation, and during acute ischemic stroke. This study returned a 5-minute 10 b-value IVIM sequence and post-processing algorithm that supports IVIM as a method of getting simultaneous quantitative bolus-independent perfusion, water transport time, and diffusion in cerebrovascular disease. Lastly the fourth aim tests the hypothesis that difference in IVIM exponential behavior can be used to separate tissue compartments with different water motion, specifically, cerebrospinal fluid (CSF) segmentation. Tri-exponential behavior seems a promising direction and quadratic discriminant analysis segmentation demonstrated a quantifiable divide between bi-exponential behavior of CSF-dominated voxels, and tissue-perfusion dominated voxels. This further supports IVIM signal not being predominately CSF contamination and being a potential method of measuring quantitative perfusion, diffusion, blood volume, transit time, and cerebrospinal fluid flow of neurovascular disease without contrast agent.

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