Toward In Vivo MRI of the Tissue Proton Exchange Rate in Humans

Quantification of proton exchange rate (k(ex)) is a challenge in MR studies. Current techniques either have low resolutions or are dependent on the estimation of parameters that are not measurable. The Omega plot method, on the other hand, provides a direct way for determining k(ex) independent of the agent concentration. However, it cannot be used for in vivo studies without some modification due to the contributions from the water signal. In vivo tissue proton exchange rate (k(ex)) MRI, based on the direct saturation (DS) removed Omega plot, quantifies the weighted average of k(ex) of the endogenous tissue metabolites. This technique has been successfully employed for imaging the variation in the k(ex) of ex vivo phantoms, as well as in vivo human brains in healthy subjects, and stroke or multiple sclerosis (MS) patients. In this paper, we present a brief review of the methods used for k(ex) imaging with a focus on the development of in vivo k(ex) MRI technique based on the DS-removed Omega plot. We then review the recent clinical studies utilizing this technique for better characterizing brain lesions. We also outline technical challenges for the presented technique and discuss its prospects for detecting tissue microenvironmental changes under oxidative stress.