Defining the ischemic penumbra using magnetic resonance oxygen metabolic index.

BACKGROUND AND PURPOSE: Penumbral biomarkers promise to individualize treatment windows in acute ischemic stroke. We used a novel magnetic resonance imaging approach that measures oxygen metabolic index (OMI), a parameter closely related to positron emission tomography-derived cerebral metabolic rate of oxygen utilization (CMRO2), to derive a pair of ischemic thresholds: (1) an irreversible-injury threshold that differentiates ischemic core from penumbra and (2) a reversible-injury threshold that differentiates penumbra from tissue not-at-risk for infarction. METHODS: Forty patients with acute ischemic stroke underwent magnetic resonance imaging at 3 time points after stroke onset: <4.5 hours (for OMI threshold derivation), 6 hours (to determine reperfusion status), and 1 month (for infarct probability determination). A dynamic susceptibility contrast method measured cerebral blood flow, and an asymmetrical spin echo sequence measured oxygen extraction fraction, to derive OMI (OMI=cerebral blood flow×oxygen extraction fraction). Putative ischemic threshold pairs were iteratively tested using a computation-intensive method to derive infarct probabilities in 3 tissue groups defined by the thresholds (core, penumbra, and not-at-risk tissue). An optimal threshold pair was chosen based on its ability to predict infarction in the core, reperfusion-dependent survival in the penumbra, and survival in not-at-risk tissue. The predictive abilities of the thresholds were then tested within the same cohort using a 10-fold cross-validation method. RESULTS: The optimal OMI ischemic thresholds were found to be 0.28 and 0.42 of normal values in the contralateral hemisphere. Using the 10-fold cross-validation method, median infarct probabilities were 90.6% for core, 89.7% for nonreperfused penumbra, 9.95% for reperfused penumbra, and 6.28% for not-at-risk tissue. CONCLUSIONS: OMI thresholds, derived using voxel-based, reperfusion-dependent infarct probabilities, delineated the ischemic penumbra with high predictive ability. These thresholds will require confirmation in an independent patient sample.

Preexisting statin use is associated with greater reperfusion in hyperacute ischemic stroke.

BACKGROUND AND PURPOSE: Statin pretreatment has been associated with improved outcomes in patients with ischemic stroke. Although several mechanisms have been examined in animal models, few have been examined in patients. We hypothesized that patients using statins before stroke onset may have greater reperfusion than patients not using statins. METHODS: Acute ischemic stroke patients underwent 2 MR scans: within 4.5 (tp1) and at 6 hours (tp2) after stroke onset. Regions of reperfusion were defined by prolonged mean transit time (MTT) at tp1, which normalized at tp2. Four MTT thresholds were assessed to ensure that results were not spuriously based on an arbitrary threshold. Baseline characteristics, relative reperfusion, and change in NIHSS between tp1 and 1-month follow-up (ΔNIHSS) were compared between patients who were using statins at stroke onset and those who were not. RESULTS: Thirty-one stroke patients were prospectively enrolled; 12 were using statins and 19 were not. Baseline characteristics did not differ between the 2 groups except the statin group had greater coronary artery disease (P=0.03). Patients using statins showed significantly greater reperfusion compared to untreated patients across all MTT thresholds. For MTT of 4 seconds, median relative reperfusion was 50% (interquartile range, 30%-56%) in the preexisting statin group versus 13% (interquartile range, 5%-36%) in the untreated group (P=0.014). The statin group had greater ΔNIHSS (8.8±4.0 points) compared to the untreated group (4.4±5.7 points; P=0.028). CONCLUSIONS: Statin use before ischemic stroke onset was associated with greater early reperfusion and NIHSS improvement. Further studies in larger populations are required to confirm our preliminary findings.

Early changes of tissue perfusion after tissue plasminogen activator in hyperacute ischemic stroke.

BACKGROUND AND PURPOSE: it is hypothesized that tissue plasminogen activator rescues brain tissue by improving perfusion. In this study, we aimed to examine acute regional perfusion changes and how they influence infarction and clinical outcome. METHODS: three sequential MR scans were performed in 15 tissue plasminogen activator-treated patients within 3.5 (tp1), at 6 hours (tp2), and at 1 month (tp3) after stroke onset. "Hypoperfusion" was defined if mean transit time prolongation was more than a threshold (4 thresholds: 3, 4, 5, and 6 seconds). Four regions of interest were classified: (1) "reperfusion"-hypoperfused at tp1, normal at tp2; (2) "nonreperfusion"-hypoperfused at tp1 and tp2; (3) "normal perfusion"-normal at tp1 and tp2; and (4) "new hypoperfusion"-normal at tp1 and hypoperfused at tp2. Risk of infarction was calculated within each region of interest. Associations between tissue perfusion changes and clinical variables were evaluated using stepwise multiple linear regressions. Moreover, the association between National Institutes of Health Stroke Scale changes and perfusion alterations was assessed using linear mixed effect models. RESULTS: regardless of the mean transit time threshold chosen, the risk of infarction in nonreperfused regions (40% to 68%, thresholds 3 to 6 seconds) was higher than reperfused regions (9% to 30%, P<0.05), and it was higher in new hypoperfusion regions (9% to 33%) than normal perfusion regions (3% to 4%, P<0.05). Volume of new hypoperfusion was significantly associated with onset-to-treatment time and initial hypoperfused volume. Overall relative reperfusion was significantly associated with National Institutes of Health Stroke Scale improvement. CONCLUSIONS: early tissue perfusion changes influenced final tissue fate. The development of new hypoperfusion may result from delay in tissue plasminogen activator and a large initial lesion.