Use of diffusion- and perfusion-weighted magnetic resonance imaging in drug development for ischemic stroke.
Current Drug Targets, CNS and Neurological Disorders, 2(2), 131-141 (2003).
Diffusion- and perfusion-weighted magnetic resonance imaging (DWI and PWI, respectively) are novel imaging modalities that can detect brain ischemia early in its full extent, can be performed in minutes, can be repeated easily, and allow for follow-up of the ischemic lesion size over time with good spatial and temporal resolution. We have used DWI and PWI in evaluating novel therapeutic approaches for ischemic stroke in numerous studies in the rat and lately in humans. It is now clear that DWI and PWI offer a good combination for safe and reliable evaluation of novel drugs on the size and tissue characteristics of brain ischemia. After inducing focal brain ischemia in the rat, one can first detect the presence and extent of ischemia by DWI and hypoperfusion by PWI, calculate the volume of ischemic brain tissue, and then follow the development of the ischemic lesion over time for several hours during treatment, thus detecting in vivo effects of the novel drug on brain ischemia. Successful reperfusion (either mechanically or as a result of thrombolytic therapy) can also be detected easily. DWI and PWI when performed before starting treatment can also exclude the pretreatment bias, a potential reason for false-positive studies in which proper imaging studies are not employed. Thus we can determine the in vivo efficacy (or lack of efficacy) of new therapeutic regimens (both neuroprotective and thrombolytic) rapidly, safely, and reliably by using a small sample size only, and adapt the same strategy to clinical trials.