Sodium MRI for Studying Ischemic Tissue in Acute Stroke

This thesis presents sodium magnetic resonance as an in vivo means for non-invasively visualizing the changes in cell sodium ion homeostasis that occur in ischemic tissue during acute stroke. Single quantum sodium magnetic resonance imaging (MRI) was used to determine the time course of tissue sodium concentration (TSC) in a non-human primate model of reversible focal brain ischemia. In each animal, TSC increased slowly and linearly as a function of time after the onset of focal brain ischemia. Changes in the TSC accumulation were seen upon reperfusion. The results demonstrate that the increase in TSC in ischemic tissue is readily measurable using sodium MRI at clinical magnetic field strengths (3.0 T) in acceptable imaging times (5 minutes). The results also indicate that sodium MRI could predict the stroke onset time in patients that are unsure when their symptoms began, potentially extending the use of thrombolytic therapy to patients that would otherwise not receive treatment. Many studies have hypothesized that the best means for the in vivo study of the changes in cell sodium ion homeostasis that occur during brain ischemia is to use imaging schemes that isolate the sodium NMR signal from the intracellular compartment. This thesis investigates the contribution of the extracellular sodium pool to the brain's triple quantum (TQ) sodium MR signal in the rat using the thulium shift reagent, TmDOTP5-. Within the SNR of the experiment, there was no evidence of any contribution to the TQ sodium MR signal from the sodium in the extracellular brain, vascular, and muscle spaces in the head. Finally, TQ sodium MR images in the in vivo non-human primate are presented for the first time. Moreover, these images were obtained in clinically acceptable 18 minute data acquisition times. TQ sodium MRI during non-human primate focal brain ischemia identified large changes in the ischemic region as early as 34 minutes after the onset of ischemia. The increase in the TQ sodium MRI signal intensity observed in the ischemic hemisphere is hypothesized to be due to an increase in the intracellular sodium concentration as a result of impaired ion homeostasis during evolving brain ischemia