Stroke onset time using sodium MRI in rat focal cerebral ischemia

Background and Purpose - Thrombolytic therapy with intravenous tPA must be administered within 3 hours after stroke onset. However, stroke onset time cannot be established in 20% to 45% of potential patients. We propose that the rate of increase of the brain concentration of sodium ([Na+](br)) after stroke, monitored using sodium MRI in a rat model of cortical ischemia, is linear in each individual animal, can locate the ischemic region, and can be used to estimate onset time. Methods - After induction of focal cortical ischemia in rats under isoflurane anesthesia, [Na+](br) time course maps were acquired continuously on a 3 T whole body scanner from 2 to 7 hours after occlusion followed by T2-weighted proton images. Microtubule-associated protein-2 immunostained brain sections were used to verify the location of the infarct. Results - The ischemic region identified with microtubule-associated protein-2 corresponded to the region of maximum [Na+](br) increase (P < 0.001; n = 5), and all of the animals demonstrated high linearity. [Na+](br) increased at a mean rate of 25 +/- 4.7%/ h in ischemic tissue (P < 0.013) but not in normal cortex (1.0 +/- 1.1%/ h; P = 0.42). The mean onset time error was 1 +/- 4 minutes (n = 4). Conclusions - These results of sodium MRI show that the region of maximum [Na+](br) increase corresponds to the ischemic region. Although [Na+](br) increases at a different rate in each animal, the increase is linear, and, therefore, onset time can be estimated. These findings suggest that this method can be used as a ticking clock to estimate time elapsed after vascular occlusion.