Abstract
Objective: To compare how at-risk tissue and core infarction were defined in two major trials that tested the use of MRI in selecting acute stroke patients for endovascular recanalization therapy.Methods: MRIs from 12 patients evaluated for possible endovascular therapy were processed using the methods published from two major trials, MR RESCUE and DEFUSE 2. Specifically, volumes of at-risk tissue and core infarction were generated from each patient’s MRI. MRIs were then classified as whether or not they met criteria for salvageable tissue: “penumbral pattern” for MR RESCUE and/or “target profile” for DEFUSE 2 as defined by each trial.Results: Volumes of at-risk tissue measured by the two definitions were correlated (p = 0.017) while the volumes of core infarct were not (p = 0.059). The volume of at-risk tissue was consistently larger when defined by the penumbral pattern than the target profile while the volume of core infarct was consistently larger when defined by the target profile than the penumbral pattern. When these volumes were used to classify the MRI scans, 9 out of 12 patients (75%) were classified as having a penumbral pattern, while only 4 out of 12 patients (33%) were classified as having a target profile. Of the 9 patients classified as penumbral pattern, 5 (55%) were classified differently by the target profile.Interpretation: Our analysis found that the MR RESCUE trial defined salvageable tissue in a way that made it more likely for patients be labeled as favorable for treatment. For the cohort of patients examined in this study, had they been enrolled in both trials, most of the patients identified as having salvageable tissue by the MR RESCUE trial would not have been considered to have salvageable tissue in the DEFUSE 2 trial. Caution should be taken in concluding that MRI selection for endovascular therapy is not effective as imaging selection criteria were substantially different between the two trials.
Highlights
In the stroke literature, the term “penumbra” was originally introduced to describe brain tissue that is electrically dysfunctional due to inadequate blood flow [1]
The volume of at-risk tissue was consistently larger when defined by the penumbral pattern than the target profile while the volume of core infarct was consistently larger when defined by the target profile than the penumbral pattern
Interpretation: Our analysis found that the MR RESCUE trial defined salvageable tissue in a way that made it more likely for patients be labeled as favorable for treatment
Summary
The term “penumbra” was originally introduced to describe brain tissue that is electrically dysfunctional due to inadequate blood flow [1]. The term was subsequently adopted by the MRI literature to reflect “at-risk” tissue estimated by diffusion–perfusion mismatch (DPMM). The mismatch hypothesis was recently tested in two large multicenter NIH-funded clinical trials, DEFUSE 2 [4] and MR RESCUE [5]. In both trials, tissue represented by MRI voxels was classified as at-risk or not at-risk based on diffusion and perfusion values.
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