Imaging acute ischemic tissue acidosis with pH-sensitive endogenous amide proton transfer (APT) MRI--correction of tissue relaxation and concomitant RF irradiation effects toward mapping quantitative cerebral tissue pH.

Amide proton transfer (APT) MRI is sensitive to ischemic tissue acidosis and has been increasingly used as a research tool to investigate disrupted tissue metabolism during acute stroke. However, magnetization transfer asymmetry (MTR(asym)) analysis is often used for calculating APT contrast, which only provides pH-weighted images. In addition to pH-dependent APT contrast, in vivo MTR(asym) is subject to a baseline shift (ΔMTR'(asym)) attributable to the slightly asymmetric magnetization transfer (MT) effect. Additionally, APT contrast approximately scales with T(1) relaxation time. Tissue relaxation time may also affect the experimentally obtainable APT contrast via saturation efficiency and RF spillover effects. In this study, we acquired perfusion, diffusion, relaxation and pH-weighted APT MRI data, and spectroscopy (MRS) in an animal model of acute ischemic stroke. We modeled in vivo MTR(asym) as a superposition of pH-dependent APT contrast and a baseline shift ΔMTR'(asym) (i.e., MTR(asym)=APTR(pH)+ΔMTR'(asym)), and quantified tissue pH. We found pH of the contralateral normal tissue to be 7.03±0.05 and the ipsilateral ischemic tissue pH was 6.44±0.24, which correlated with tissue perfusion and diffusion rates. In summary, our study established an endogenous and quantitative pH imaging technique for improved characterization of ischemic tissue acidification and metabolism disruption.