Investigating the origin of pH-sensitive magnetization transfer ratio asymmetry MRI contrast during the acute stroke: Correction of T1 change reveals the dominant amide proton transfer MRI signal.

Abstract

Amide proton transfer (APT) MRI is promising to serve as a surrogate metabolic imaging biomarker of acute stroke. Although the magnetization transfer ratio asymmetry (MTRasym ) has been used commonly, the origin of pH-weighted MRI effect remains an area of investigation, including contributions from APT, semisolid MT contrast asymmetry, and nuclear Overhauser enhancement effects. Our study aimed to determine the origin of pH-weighted MTRasym contrast following acute stroke. Multiparametric MRI, including T1 , T2 , diffusion and Z-spectrum, were performed in rats after middle cerebral artery occlusion. We analyzed the conventional Z-spectrum and the apparent exchange spectrum , being the difference between the relaxation-scaled inverse Z-spectrum and the intrinsic spinlock relaxation rate . The ischemia-induced change was calculated as the spectral difference between the diffusion lesion and the contralateral normal area. The conventional Z-spectrum signal change at -3.5 ppm dominates that at +3.5 ppm (-1.16 ± 0.39% vs. 0.76 ± 0.26%, P < .01) following acute stroke. In comparison, the magnitude of ΔRex change at 3.5 ppm becomes significantly larger than that at -3.5 ppm (-2.80 ± 0.40% vs. -0.94 ± 0.80%, P < .001), with their SNR being 7.0 and 1.2, respectively. We extended the magnetization transfer and relaxation normalized APT concept to the apparent exchange-dependent relaxation image, documenting an enhanced pH contrast between the ischemic lesion and the intact tissue, over that of MTRasym . Our study shows that after the relaxation-effect correction, the APT effect is the dominant contributing factor to pH-weighted MTRasym following acute stroke.