MR imaging of oxygen extraction and neurovascular coupling.

S ince the approval of tissue-type plasminogen activator (tPA) for the treatment of acute ischemic stroke by the Food and Drug Administration, 1 the search for means to identify patients who may benefit from this treatment beyond the approved therapeutic window has been actively pursued. One of the most successful examples is the European Cooperative Acute Stroke Study III (ECASS III) trial, 2,3 which demonstrated that efficacy of tPA treatment could be extended from the original 3 hours to 4.5 hours from onset. In addition, with an accumulating arsenal of mechanical clot retrieval devices, promising to achieve more effective reperfusion than intravenous -tPA, 4–6 it is likely that the therapeutic windows for these retrieval devices will differ from that of intravenous-tPA. Different collateral flow patterns, comorbidities, and intrinsic tissue vulnerabilities among individual patients further complicate the use of a fixed therapeutic time-window for all patients and different treatments. Therefore, insights into brain tissue viability at the time of presentation may aid in the management of acute stroke. Toward this end, imaging approaches have been actively sought to provide a potential signature for tissue viability. 7 Specifically, the diffusion/perfusion mismatch (DPM) concept has been widely advocated as a potential approach to depict the presence or absence of ischemic penumbra. 8–10 The underlying hypothesis is that lesions defined by abnormal diffusion most likely reflect irreversible injury, whereas regions defined by abnormal perfusion represent critically hypoperfused tissue. The region of DPM with normal diffusion but abnormal perfusion is, in theory, the region at risk of evolving to infarc-tion if reperfusion-promoting therapies are not administered. Although the overall hypothesis of DPM is straightforward and diffusion weighted images (DWI) and perfusion-weighted images (PWI) are readily available, the means by which DWI and PWI lesions are defined vary widely, leading to, potentially , inconsistent results among groups with the use of DPM to predict outcomes. For example, the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution 2 (DEFUSE-2) investigators 11 proposed a set of criteria for defining DPM, termed target DPM, based on observations of DWI lesion growth and clinical outcome in patients undergoing intra-arterial therapy for acute hemispheric stroke. However, the observations of the acute reversal of DWI lesions and the failure of all diffusion lesions to evolve to infarction suggest that the presumption that all DWI-defined lesions truly reflect the irreversibly damaged ischemic core may be invalid. Similarly, it has been difficult to …