RAPID automated patient selection for reperfusion therapy: a pooled analysis of the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) and the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution (DEFUSE) Study

Abstract

Background and purpose: The aim of this study was to determine if automated MRI analysis software (RAPID) can be used to identify patients with stroke in whom reperfusion is associated with an increased chance of good outcome.

Methods: Baseline diffusion- and perfusion-weighted MRI scans from the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution study (DEFUSE; n=74) and the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET; n=100) were reprocessed with RAPID. Based on RAPID-generated diffusion-weighted imaging and perfusion-weighted imaging lesion volumes, patients were categorized according to 3 prespecified MRI profiles that were hypothesized to predict benefit (Target Mismatch), harm (Malignant), and no effect (No Mismatch) from reperfusion. Favorable clinical response was defined as a National Institutes of Health Stroke Scale score of 0 to 1 or a ≥ 8-point improvement on the National Institutes of Health Stroke Scale score at Day 90.

Results: In Target Mismatch patients, reperfusion was strongly associated with a favorable clinical response (OR, 5.6; 95% CI, 2.1 to 15.3) and attenuation of infarct growth (10 ± 23 mL with reperfusion versus 40 ± 44 mL without reperfusion; P<0.001). In Malignant profile patients, reperfusion was not associated with a favorable clinical response (OR, 0.74; 95% CI, 0.1 to 5.8) or attenuation of infarct growth (85 ± 74 mL with reperfusion versus 95 ± 79 mL without reperfusion; P=0.7). Reperfusion was also not associated with a favorable clinical response (OR, 1.05; 95% CI, 0.1 to 9.4) or attenuation of lesion growth (10 ± 15 mL with reperfusion versus 17 ± 30 mL without reperfusion; P=0.9) in No Mismatch patients.

Conclusions: MRI profiles that are associated with a differential response to reperfusion can be identified with RAPID. This supports the use of automated image analysis software such as RAPID for patient selection in acute stroke trials.

Figure 1. Relationships between reperfusion and favorable clinical response in patients with the Target Mismatch, the Malignant and the No Mismatch profiles

FCR indicates favorable clinical response, defined as a National Institutes of Health Stroke Scale score of 0–1 at day 90 or an improvement of ≥8 points on the NIHSS score between baseline and day 90. The forest plots demonstrate that reperfusion is associated with favorable clinical response in Target Mismatch patients (top), but not in patients with the Malignant (middle) and No Mismatch (bottom) profiles.

Figure 2. Modified Rankin Scale at 90 days in Target Mismatch patients

The distribution of scores on the Modified Rankin Scale assessed at 90 days is shown for patients with a Target Mismatch. The statistical comparison of the outcomes was performed with the Mann-Whitney U test using all seven categories of the modified Rankin Scale (mRS). The outcomes of Target Mismatch patients with early reperfusion were more favorable compared to Target Mismatch patients without early reperfusion (p<0.001).