Imaging of experimental stroke models.

The ischemic penumbra is the target of acute stroke therapy. It can be approximated on diffusion/perfusion MRI as the ischemic region with abnormal perfusion and normal diffusion imaging. Using arterial spin labeling perfusion MRI and diffusion MRI, our group has studied the evolution of the diffusion/perfusion mismatch in rat stroke models. Additionally, we have evaluated the effects of high-flow oxygen on the natural history of penumbral evolution, demonstrating that high-flow oxygen "freezes" the evolution of the mismatch and allows for later beneficial use of intravenous tissue plasminogen activator (tPA). Two neuroprotective drugs, Granulocyte colony stimulating factor and a PSD95 inhibitor both impeded the evolution of the mismatch into infarcted tissue in vivo and by histological analysis. Employing a novel technique of clot imaging, our group was able to demonstrate that the combination of tPA plus Annexin-2 was superior to tPA alone in dissolving an embolus and also in reducing the extent of hypoperfused brain tissue of perfusion imaging. The use of these advanced MRI techniques in animal experiments will help to advance clinical imaging of the ischemic penumbra and hopefully contribute to the extension of the therapeutic time window in stroke patients.