Quantification ofin vivopH-weighted amide proton transfer (APT) MRI in acute ischemic stroke

Abstract

Amide proton transfer (APT) imaging is a specific form of chemical exchange saturation transfer (CEST) MRI that probes the pH-dependent amide proton exchange.The endogenous APT MRI is sensitive to tissue acidosis, which may complement the commonly used perfusion and diffusion scans for characterizing heterogeneous ischemic tissue damage. Whereas the saturation transfer asymmetry analysis (MTR asym ) may reasonably compensate for direct RF saturation, in vivo MTR asym is however, susceptible to an intrinsically asymmetric shift (MTR' asym ). Specifically, the reference scan for the endogenous APT MRI is 7 ppm upfield from that of the label scan, and subjects to concomitant RF irradiation effects, including nuclear overhauser effect (NOE)-mediated saturation transfer and semisolid macromolecular magnetization transfer. As such, the commonly used asymmetry analysis could not fully compensate for such slightly asymmetric concomitant RF irradiation effects, and MTR asym has to be delineated in order to properly characterize the pH-weighted APT MRI contrast. Given that there is very little change in relaxation time immediately after ischemia and the concomitant RF irradiation effects only minimally depends on pH, the APT contrast can be obtained as the difference of MTR asym between the normal and ischemic regions. Thereby, the endogenous amide proton concentration and exchange rate can be solved using a dual 2-pool model, and the in vivo MTR' asym can be calculated by subtracting the solved APT contrast from asymmetry analysis (i.e., MTR' asym =MTR asym -APTR). In addition, MTR' asym can be quantified using the classical 2-pool exchange model. In sum, our study delineated the conventional in vivo pH-sensitive MTR asym contrast so that pHspecific contrast can be obtained for imaging ischemic tissue acidosis. SUMMARYAmide proton transfer (APT) imaging is pH sensitive, and has been shown promising to complement perfusion and diffusion MRI for stratifying heterogeneous ischemic tissue injury. Whereas conventional asymmetry analysis (MTR asym ) reasonably compensates for the direct RF saturation effect, it is susceptible to an intrinsically asymmetric shift (MTR' asym ). To improve tissue acidosis mapping, we delineated pHsensitive APT effect from confounding factors using an animal model of stroke. We quantified concentration and exchange rate for both APT and nuclear overhauser effects (NOE). Our study elucidated conventional pH-weighted MTR asym contrast so that more specific pH-sensitive images can be obtained for characterizing ischemic acidosis.