Redefining Ischemic Core, Penumbra, and Target Mismatch on Perfusion Imaging in Acute Anterior Distal Medium Vessel...

Recent trials of endovascular thrombectomy (EVT) for acute distal medium vessel occlusions (DMVOs) were negative but also used inconsistent imaging-based inclusion criteria, whereas many successful large vessel occlusion (LVO) EVT trials used empirically validated perfusion imaging-based target mismatch (TMM) criteria: an ischemic penumbra (time-to-maximum [Tmax] >6 s) to core (relative cerebral blood flow [rCBF] <30%) mismatch ratio ≥1.8 and mismatch volume ≥15 mL. We aimed to determine optimal corresponding definitions in DMVOs to improve patient selection for EVT.

We retrospectively analyzed patients with acute anterior DMVOs from prospectively collected databases at 4 comprehensive stroke centers. To assess core, we evaluated how well pretreatment rCBF <20%, <30%, <34%, and <38% volumes correlated with magnetic resonance imaging-based posttreatment follow-up infarct volumes in successfully recanalized patients. To evaluate penumbra, we assessed how well pretreatment Tmax >4 s, >6 s, >8 s, and >10 s volumes correlated with follow-up infarct volumes in unrecanalized patients. Then, we evaluated whether these improved parameters for core and penumbra better quantified LVO TMM and identified an optimal DMVO TMM definition.

In 122 core (recanalized) patients, rCBF <38% most strongly correlated with follow-up infarct volumes (concordance correlation coefficient 0.30 [95% CI, 0.15-0.48]), outperforming rCBF <30% (concordance correlation coefficient 0.21 [0.10-0.35]) (P<0.001). In 70 penumbra (unrecanalized) patients, Tmax >8 s most strongly correlated with follow-up infarct volumes (concordance correlation coefficient 0.49 [0.25-0.77]), outperforming Tmax >6 s (concordance correlation coefficient 0.39 [0.17-0.68]) (P<0.001). In 180 patients undergoing EVT with Tmax >6 s to rCBF <30% mismatch ratio ≥1.8 and mismatch volume ≥15 mL, recomputing mismatch ratio and mismatch volume using Tmax >8 s and rCBF <38% separated those with favorable outcomes (P = 0.007), and Tmax >8 s to rCBF <38% mismatch ratio ≥2.2 and mismatch volume ≥10 mL maximally separated them (P<0.001, absolute risk reduction 26%).

In acute anterior DMVOs, rCBF <38% and Tmax >8 s best correspond to ischemic core and penumbra, respectively; more favorably quantify LVO TMM; and reveal optimal TMM criteria. These results should be prospectively investigated as inclusion criteria for EVT in this population and suggest recent negative DMVO EVT trials may have been confounded by suboptimal patient selection.