David G. Sherman Lecture: Improving Stroke Diagnosis and Treatment—A Journey Toward the End of Time

In the 2024 David G. Sherman Lecture, Steven J. Warach, illustrating with examples from his research, walks through the history of magnetic resonance imaging in acute stroke from the 1990s and early 2000s with the introduction, validation, and application of diffusion-weighted imaging, penumbral imaging (the diffusion-perfusion mismatch), and other imaging markers of the acute stroke pathology into routine clinical practice and stroke trials. The adaptation of diffusion-weighted imaging for clinical scanners in the acute hospital setting began a revolution in ischemic stroke diagnosis as the presence, location, and size of ischemic lesions could now be visualized at the earliest times after stroke onset when computed tomography and conventional magnetic resonance imaging still appeared normal. In combination with perfusion magnetic resonance imaging, diffusion-weighted imaging made imaging of the ischemic penumbra a practical reality for routine clinical use and feasible for integration as a selection tool into clinical trials. It was apparent from the initial use of diffusion-perfusion imaging in acute stroke that many patients had persistence of penumbra as late as 24 hours after stroke onset although the probability of penumbra decreased over time. The therapeutic time window for ischemic stroke selected by clinical and temporal criteria reflected the decreased proportion of patients with the therapeutic target over time rather than the absence of the penumbral target in all patients at later times. This work provided the empirical and conceptual framework for the shift toward selection and evaluation of patients for acute stroke therapies based on direct observation of the target pathology and away from the exclusive dependence on clinical and temporal surrogates to infer the presence of stroke therapeutic targets, a shift that has expanded the indications for acute reperfusion therapies over the last 10 years.