MRI Biomarkers in Acute Ischemic Stroke: A Conceptual Framework and Historical Analysis

Over the past 2 decades, advanced multimodal imaging has offered much promise for stroke investigators and clinicians, particularly those interested in using imaging to optimize and extend the time window for acute ischemic stroke therapies. Multimodal imaging has many potential applications in the acute stroke setting, such as the following: (1) to confirm the diagnosis of acute cerebral ischemia and exclude contraindications to treatment (eg, acute blood because of hemorrhagic transformation [HT]; (2) to select patients likely to benefit or not benefit from therapies (eg, by characterizing the extent of core irreversibly injured tissue, salvageable penumbra, or markers of high risk for HT); and (3) to serve as a surrogate or auxiliary outcome measure to test putative treatments.However, the promise of advanced multimodal imaging as a selection modality to optimize efficacy and safety of new treatments for stroke and also as a surrogate end point to test interventions has yet to be fully realized. Both of these applications use neuroimaging as a biomarker. A critical analysis of both the successes and missteps of studies performed to date, including translation of animal models to human studies, can provide valuable lessons that can be applied to the design of future studies. Applying current definitions and criteria for biomarkers to stroke neuroimaging research helps provide a conceptual framework for this analysis.The National Institutes of Health Biomarkers Definitions Working Group defines a biomarker as a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention.1 Biomarkers (Table 1 shows types, definitions, and examples) can be used as a diagnostic tool, a prognostic tool, a predictive tool (for predicting response to an intervention), or a substitute for a clinical outcome to measure the response to an intervention (surrogate end …