Refined Ischemic Penumbra Imaging with Tissue pH and Diffusion Kurtosis Magnetic Resonance Imaging

Imaging has played a vital role in our mechanistic understanding of acute ischemia and the management of acute stroke patients. The most recent DAWN and DEFUSE-3 trials showed that endovascular therapy could be extended to a selected group of late-presenting stroke patients with the aid of imaging. Although perfusion and diffusion MRI have been commonly used in stroke imaging, the approximation of their mismatch as the penumbra is oversimplified, particularly in the era of endovascular therapy. Briefly, the hypoperfusion lesion includes the benign oligemia that does not proceed to infarction. Also, with prompt and effective reperfusion therapy, a portion of the diffusion lesion is potentially reversible. Therefore, advanced imaging that provides improved ischemic tissue characterization may enable new experimental stroke therapeutics and eventually further individualize stroke treatment upon translation to the clinical setting. Specifically, pH imaging captures tissue of altered metabolic state that demarcates the hypoperfused lesion into ischemic penumbra and benign oligemia, which remains promising to define the ischemic penumbra's outer boundary. On the other hand, diffusion kurtosis imaging (DKI) differentiates the most severely damaged and irreversibly injured diffusion lesion from the portion of diffusion lesion that is potentially reversible, refining the inner boundary of the penumbra. Altogether, the development of advanced imaging has the potential to not only transform the experimental stroke research but also aid clinical translation and patient management.