Defining an Acidosis-Based Ischemic Penumbra from pH-Weighted MRI

It has been proposed that the spatial mismatch between deficits on perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI) in MRI can be used to decide regarding thrombolytic treatment in acute stroke. However, uncertainty remains about the meaning and reversibility of the perfusion deficit and even part of the diffusion deficit. Thus, there remains a need for continued development of imaging technology that can better define a potentially salvageable ischemic area at risk of infarction. Amide proton transfer imaging is a novel MRI method that can map tissue pH changes, thus providing the potential to separate the PWI/DWI mismatch into an acidosis-based penumbra and a zone of benign oligemia. In this totally noninvasive method, the pH dependence of the chemical exchange between amide protons in endogenous proteins and peptides and water protons is exploited. Early results in animal models of ischemia show promise to derive an acidosis penumbra. Possible translation to the clinic and hurdles standing in the way of achieving this are discussed.