Sensitivity and Source of Amine-Proton Exchange and Amide-Proton Transfer Magnetic Resonance Imaging in Cerebral Ischemia

Purpose Amide‐proton transfer (APT) and amine–water proton exchange (APEX) MRI can be viable to map pH‐decreasing ischemic regions. However, their exact contributions are unclear. Methods We measured APEX‐ and APT‐weighted magnetization transfer ratio asymmetry (denoted as APEXw and APTw), apparent diffusion coefficient, T2, and T1 images and localized proton spectra in rats with permanent middle cerebral artery occlusion at 9.4 T. Phantoms and theoretical studies were also performed. Results Within 1‐h postocclusion, APEXw and APTw maps showed hyperintensity (3.1% of M0) and hypointensity (−1.8%), respectively, in regions with decreased apparent diffusion coefficient. Ischemia increased lactate and gamma aminobutyric acid concentrations, but decreased glutamate and taurine concentrations. Over time, the APEXw contrast decreased with glutamate, taurine, and creatine, whereas the APTw contrast and lactate level were similar. Phantom and theoretical studies suggest that the source of APEXw signal is mainly from proteins at normal pH, whereas at decreased pH, gamma aminobutyric acid and glutamate contributions increase, inducing the positive APEXw contrast in ischemic regions. The APTw contrast is sensitive to lactate concentration and pH, but contaminated from contributions of the faster APEX processes. Conclusion Positive APEXw contrast is more sensitive to ischemia than negative APTw contrast. They may provide complementary tissue metabolic information. Magn Reson Med 71:118–132, 2014. © 2013 Wiley Periodicals, Inc.