Endovascular thrombectomy for ischemic stroke 6 to 16 hours after a patient was last known to be well plus standard medical therapy resulted in better functional outcomes than standard medical therapy alone among patients with proximal middle-cerebral-artery or internal-carotid-artery occlusion and a region of tissue that was ischemic but not yet infarcted. (Funded by the National Institute of Neurological Disorders and Stroke; DEFUSE 3 ClinicalTrials.gov number, NCT02586415 .).

For stroke patients treated 3 to 6 hours after onset, baseline MRI findings can identify subgroups that are likely to benefit from reperfusion therapies and can potentially identify subgroups that are unlikely to benefit or may be harmed.

Background It is uncertain if endovascular stroke therapy leads to improved clinical outcomes due to a paucity of data from randomized placebo-controlled trials. The aim of this study was to determine if MRI can be used to identify patients who are most likely to benefit from endovascular reperfusion. Methods Consecutive patients, scheduled to undergo endovascular therapy within 12 hours of stroke onset, were enrolled in a multi-center prospective cohort study. Aided by an automated image analysis software program, investigators interpreted the baseline MRI. They determined, prior to endovascular treatment, if the patient had an MRI profile (Target Mismatch) that suggested salvageable tissue was present. Reperfusion was assessed on an early follow-up MRI and defined as a >50% reduction in the volume of the baseline perfusion lesion. A favorable clinical response was defined as a ≥8 point improvement on the NIH Stroke Scale (NIHSS) between baseline and day 30 or an NIHSS score of 0–1 at 30 days. Findings Following endovascular therapy reperfusion occurred in 46 of 78 (59%) Target Mismatch patients and in 12 of 21 (57%) No Target Mismatch patients. The adjusted odds ratio for favorable clinical response associated with reperfusion was 8·5 (95% CI 2·6 – 28) in the Target Mismatch group and 0·2 (95% CI 0·0 – 1·6) in the No Target Mismatch group (p=0·003 for difference between odds ratios). Reperfusion was associated with an increased odds of good functional outcome at 90 days (OR is 5.2, 95% CI 1.4–19) and attenuation of infarct growth at 5 days (30 ml of median growth with reperfusion vs. 73 ml without reperfusion, p=0·01) in the Target Mismatch group but not in patients without Target Mismatch. Interpretation Target Mismatch patients who achieved early reperfusion following endovascular stroke therapy had more favorable clinical outcomes and less infarct growth. No association between reperfusion and favorable outcomes was present in patients without Target Mismatch. These data support a randomized controlled trial of endovascular treatment in patients with the Target Mismatch profile.

Diffusion-perfusion mismatch can be used to identify acute stroke patients that could benefit from reperfusion therapies. Early assessment of the mismatch facilitates necessary diagnosis and treatment decisions in acute stroke. We developed the RApid processing of PerfusIon and Diffusion (RAPID) for unsupervised, fully automated processing of perfusion and diffusion data for the purpose of expedited routine clinical assessment. The RAPID system computes quantitative perfusion maps (cerebral blood volume, CBV; cerebral blood flow, CBF; mean transit time, MTT; and the time until the residue function reaches its peak, T max ) using deconvolution of tissue and arterial signals. Diffusion-weighted imaging/perfusionweighted imaging (DWI/PWI) mismatch is automatically determined using infarct core segmentation of ADC maps and perfusion deficits segmented from T max maps. The performance of RAPID was evaluated on 63 acute stroke cases, in which diffusion and perfusion lesion volumes were outlined by both a human reader and the RAPID system. The correlation of outlined lesion volumes obtained from both methods was r 2 ¼ 0.99 for DWI and r 2 ¼ 0.96 for PWI. For mismatch identification, RAPID showed 100% sensitivity and 91% specificity. The mismatch information is made available on the hospital's PACS within 5-7 min. Results indicate that the automated system is sufficiently accurate and fast enough to be used for routine care as well as in clinical trials.

Background and Purpose-We sought to assess whether the volume of the ischemic penumbra can be estimated more accurately by altering the threshold selected for defining perfusion-weighting imaging (PWI) lesions. Methods-DEFUSE is a multicenter study in which consecutive acute stroke patients were treated with intravenous tissue-type plasminogen activator 3 to 6 hours after stroke onset. Magnetic resonance imaging scans were obtained before, 3 to 6 hours after, and 30 days after treatment. Baseline and posttreatment PWI volumes were defined according to increasing Tmax delay thresholds (Ͼ2, Ͼ4, Ͼ6, and Ͼ8 seconds). Penumbra salvage was defined as the difference between the baseline PWI lesion and the final infarct volume (30-day fluid-attenuated inversion recovery sequence). We hypothesized that the optimal PWI threshold would provide the strongest correlations between penumbra salvage volumes and various clinical and imaging-based outcomes. Results-Thirty-three patients met the inclusion criteria. The correlation between infarct growth and penumbra salvage volume was significantly better for PWI lesions defined by Tmax Ͼ6 seconds versus Tmax Ͼ2 seconds, as was the difference in median penumbra salvage volume in patients with a favorable versus an unfavorable clinical response. Among patients who did not experience early reperfusion, the Tmax Ͼ4 seconds threshold provided a more accurate prediction of final infarct volume than the Ͼ2 seconds threshold. Conclusions-Defining PWI lesions based on a stricter Tmax threshold than the standard Ͼ2 seconds delay appears to provide more a reliable estimate of the volume of the ischemic penumbra in stroke patients imaged between 3 and 6 hours after symptom onset. A threshold between 4 and 6 seconds appears optimal for early identification of critically hypoperfused tissue.