MRI profile and response to endovascular reperfusion after stroke (DEFUSE 2): a prospective cohort study

Abstract

Background: Whether endovascular stroke treatment improves clinical outcomes is unclear because of the paucity of data from randomised placebo-controlled trials. We aimed to establish whether MRI can be used to identify patients who are most likely to benefit from endovascular reperfusion.

Methods: In this prospective cohort study we consecutively enrolled patients scheduled to have endovascular treatment within 12 h of onset of stroke at eight centres in the USA and one in Austria. Aided by an automated image analysis computer program, investigators interpreted a baseline MRI scan taken before treatment to establish whether the patient had an MRI profile (target mismatch) that suggested salvageable tissue was present. Reperfusion was assessed on an early follow-up MRI scan (within 12 h of the revascularisation procedure) and defined as a more than 50% reduction in the volume of the lesion from baseline on perfusion-weighted MRI. The primary outcome was favourable clinical response, defined as an improvement of 8 or more on the National Institutes of Health Stroke Scale between baseline and day 30 or a score of 0-1 at day 30. The secondary clinical endpoint was good functional outcome, defined as a modified Rankin scale score of 2 or less at day 90. Analyses were adjusted for imbalances in baseline predictors of outcome. Investigators assessing outcomes were masked to baseline data.

Findings: 138 patients were enrolled. 110 patients had catheter angiography and of these 104 had an MRI profile and 99 could be assessed for reperfusion. 46 of 78 (59%) patients with target mismatch and 12 of 21 (57%) patients without target mismatch had reperfusion after endovascular treatment. The adjusted odds ratio (OR) for favourable clinical response associated with reperfusion was 8·8 (95% CI 2·7-29·0) in the target mismatch group and 0·2 (0·0-1·6) in the no target mismatch group (p=0·003 for difference between ORs). Reperfusion was associated with increased good functional outcome at 90 days (OR 4·0, 95% CI 1·3-12·2) in the target mismatch group, but not in the no target mismatch group (1·9, 0·2-18·7).

Interpretation: Target mismatch patients who had early reperfusion after endovascular stroke treatment had more favourable clinical outcomes. No association between reperfusion and favourable outcomes was present in patients without target mismatch. Our data suggest that a randomised controlled trial of endovascular treatment for patients with the target mismatch profile is warranted.

Funding: National Institute for Neurological Disorders and Stroke.

Figure 1. Examples of RAPID output

An example of the output of the automated MR image processing software (RAPID) for a patient with the Target Mismatch Profile (above); in this patient the volume of irreversibly injured ischemic tissue is estimated on the DWI map to be 10 ccm which is considerably smaller than the volume of critically hypoperfused tissue (estimated to be 51 ccm on the PWI map) yielding a mismatch ratio of 4·9. The example below demonstrates the No Mismatch profile; the estimated volume of irreversibly injured tissue (56 ccm) is approximately the same as the volume of critically hypoperfused tissue (53 ccm) yielding a mismatch ratio of 0·9.

Figure 2. Disposition of patients

The Total Cohort consists of 138 patients who were considered for endovascular therapy and consented to participation in the study. All 138 patients underwent a baseline MRI. Following the baseline MRI examination the decision was made not to proceed with the endovascular procedure in twenty-eight patients. Among the remaining 110 patients who underwent catheter angiography (Endovascular Cohort), the local investigator deemed the baseline PWI to be of sufficient quality for assessment of Target Mismatch in 104 patients (MRI profile cohort). In 5 of these 104 patients reperfusion could not be assessed (see ** below) and these 5 cases were excluded from the primary clinical analysis which required an assessment of reperfusion status to calculate the odds ratio of favorable clinical response in patients with reperfusion compared to patients without reperfusion. Thirteen of the 99 patients who were included in the primary clinical analyses did not have a 5-day follow-up MRI and were excluded from the radiographic outcome analysis which compared infarct growth between patients with and without reperfusion. *Reasons that patients did not undergo an endovascular procedure are absence of large vessel occlusion on MR angiography (n=8); large DWI lesion (n= 12); clinical improvement (n= 4); and other (n=4). Of the 28 patients who did not undergo an endovascular procedure, 24 had the No Target Mismatch profile. **In five patients who underwent catheter angiography, reperfusion could not be assessed because these patients did not have a vessel occlusion on cerebral angiography and they had a small (<10 ml) perfusion lesion at baseline.

Figure 3. Functional outcome (modified Rankin Scale) at 90 days for patients with and without Target Mismatch

Scores on the modified Rankin Scale are categorized as good outcome with no or minimal disability (mRS 0–2, green bars), disabled and dependent on others for activities of daily living (mRS 3–4, yellow bars), and bedridden or dead (mRS 5–6, red bars). p=0·04 for the comparison of good functional outcome (mRS 0–2 at 90 days) between patients with and without reperfusion in the Target Mismatch group (Panel A). There is no significant difference in good outcome between patients with and without reperfusion in the No Target Mismatch cohort (Panel B).