Background and Purpose-Matrix metalloproteinases (MMP) may play a role in blood-brain barrier (BBB) disruption after ischemic stroke. We hypothesized that plasma concentrations of MMP-9 are associated with a marker of BBB disruption in patients evaluated for acute stroke. Methods-Patients underwent MRI on presentation and Ϸ24 hours later. The MRI marker, termed hyperintense acute reperfusion injury marker (HARM), is gadolinium enhancement of cerebrospinal fluid on fluid-attenuated inversion recovery MRI. Plasma MMP-9 and tissue inhibitor of matrix metalloproteinase-1 were measured by enzyme-linked immunosorbent assay. Logistic regression models tested for predictors of HARM on 24-hour follow-up scans separately for MMP-9 and the ratio of MMP-9 to TIMP-1. Results-For the 41 patients enrolled, diagnoses were: acute ischemic cerebrovascular syndrome, 33 (80.6%); intracerebral hemorrhage, 6 (14.6%); stroke mimic, 1 (2.4%); and no stroke, 1 (2.4%). HARM was present in 17 (41.5%) patients. In model 1, HARM was associated with baseline plasma MMP-9 concentration (odds ratio [OR], 1.01; 95% confidence interval [CI], 1.001-1.019; Pϭ0.033). In model 2, HARM was associated with the ratio of MMP-9 to tissue inhibitor of matrix metalloproteinase-1 (OR, 4.94; 95% CI, 1.27-19.14; Pϭ0.021). Conclusions-Baseline MMP-9 was a significant predictor of HARM at 24-hour follow-up, supporting the hypothesis that MMP-9 is associated with BBB disruption. If the association between MMP-9 and BBB disruption is confirmed in future studies, HARM may be a useful imaging marker to evaluate MMP-9 inhibition in ischemic stroke and other populations with BBB disruption. (Stroke. 2010;41:e123-e128.)

Background and Purpose Objective imaging methods to identify optimal candidates for late recanalization therapies are needed. The study goals were 1) to develop MRI and CT multiparametric, voxel-based predictive models of infarct core and penumbra in acute ischemic stroke patients, and 2) to develop patient-level imaging criteria for favorable penumbral pattern based on good clinical outcome in response to successful recanalization. Methods An analysis of imaging and clinical data was performed on two cohorts of patients (one screened with CT, the other with MRI) who underwent successful treatment for large vessel, anterior circulation stroke. Subjects were divided 2:1 into derivation and validation cohorts. Pretreatment imaging parameters independently predicting final tissue infarct and final clinical outcome were identified. Results The MRI and CT models were developed and validated from 34 and 32 patients, employing 943,320 and 1,236,917 voxels respectively. The derivation MRI and two-branch CT models had an overall accuracy of 74% and 80% respectively, and were independently validated with an accuracy of 71% and 79% respectively. The imaging criteria of 1) predicted infarct core ≤ 90 mL and 2) ratio of predicted infarct tissue within the at-risk region ≤ 70% identified patients as having a favorable penumbral pattern with 78–100% accuracy. Conclusions Multiparametric voxel-based MRI and CT models were developed to predict the extent of infarct core and overall penumbral pattern status in patients with acute ischemic stroke who may be candidates for late recanalization therapies. These models provide an alternative approach to mismatch in predicting ultimate tissue fate.