AUTHOR=Motta Melissa , Ramadan Amanda , Hillis Argye E. , Gottesman Rebecca F. , Leigh Richard TITLE=Diffusion–Perfusion Mismatch: An Opportunity for Improvement in Cortical Function JOURNAL=Frontiers in Neurology VOLUME=Volume 5 - 2014 YEAR=2015 URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2014.00280 DOI=10.3389/fneur.2014.00280 ISSN=1664-2295 ABSTRACT=Objective: There has been controversy over whether diffusion-perfusion mismatch provides a biomarker for the ischemic penumbra. Regions of the diffusion-perfusion mismatch that do not progress to infarct in the absence of reperfusion are considered to represent “benign oligemia.” However, at least in some cases (particularly large vessel stenosis), some of this hypoperfused tissue may remain dysfunctional for a prolonged period without progressing to infarct and may recover function if eventually reperfused. We hypothesized that patients with persistent diffusion-perfusion mismatch using a hypoperfusion threshold of 4-5.9 seconds delay on time-to-peak maps at least sometimes have persistent cognitive deficits relative to those who show some reperfusion. Methods: We tested this hypothesis in 38 patients with acute ischemic stroke who had simple cognitive tests and MRI with diffusion and perfusion imaging within 24 hours of onset and again within 10 days, most of whom had large vessel stenosis. Results: When we evaluated all patients or only patients who did not have infarct growth, persistent hypoperfusion was associated with a lack of cognitive improvement compared with those who had reperfused (p<0.001). Initial volume of hypoperfusion did not correlate with the later infarct volume (progression to infarct), but change in volume of hypoperfusion correlated with change in cognitive performance (p=0.0001). Multivariable regression showed that the change in volume of hypoperfused tissue of 4-5.9 sec delay (p=0.002), and change in volume of ischemic tissue on DWI (p=0.02) were independently associated with change in cognitive function. Conclusion: Our results provide additional evevidence that non-infarcted tissue with a TTP delay of 4-5.9 sec may be associated with persistent deficits, even if it does not always result in imminent progression to infarct. This tissue may represent the occasional opportunity to intervene to improve function even days after onset.