Tissue sodium concentration (TSC), as measured by sodium imaging, will be correlated with diffusion (apparent diffusion coefficient, ADC) and perfusion (relative cerebral blood volume, rCBV; tissue transit time, TTT; arrival time, TA) from proton MRI over the first 12 hours of embolic stroke in a non-human primate model. These quantitative MR imaging parameters will be correlated with histological markers of tissue status including TTC, H&E and TUNEL staining. The goal is to establish if TSC an be used as a measure of tissue viability in assessment of acute stroke. Early intervention with thrombolysis enhances the clinical outcome if the tissue is still viable. As reperfusion of infarcted tissue increases the risk of adverse hemorrhage, the FDA approves a limited window of acceptable risk-benefit ratio of 3 hours from the onset of neurological symptoms in a non-hemorrhagic stroke. A rapid method for assessment of tissue viability in this setting would aid in tailoring clinical management to the pathophysiology of each patient. The central hypothesis is that there is a critical increase in TSC due to loss of sodium ion homeostasis in a region of restricted diffusion (reduced ADC) that indicates a significant loss of tissue viability in stroke. An acute embolic stroke model in a non-human primate is used to determine if a critical threshold of TSC defines tissue viability during the natural progression of stroke thereby predicting recovery following reperfusion after thrombolysis with recombinant tissue plasminogen activator (rt-PA) This animal model is required to establish the magnitude and rate of change of TSC in a well-controlled setting that can be applied in the clinical setting. Other proton MRI parameters used clinically in stroke are water diffusion and perfusion. The same comprehensive, yet efficient MRI protocol as I have used in MRI examinations of both acute and sub-acute stroke patients, allows TSC, ADC and blood pool perfusion parameters or rCBV, TTT and TA to be correlated in this acute stroke model and compared to histological parameters of necrosis and apoptosis. The novel twisted projection imaging acquisition produces high quality, high-resolution sodium images while echo-planar imaging is used for diffusion and perfusion imaging. A dual-frequency, dual-quadrature, 23NA/1H RF coil ensures co-registration of images and maps in minimum time without moving the subject. This well-controlled animal model examines if there is a critical TSC threshold that accurately predicts tissue viability as part of this comprehensive MR imaging protocol being used for clinical management of acute stroke.
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