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.

Purpose: 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. Methods: Multiparametric MRI, including T1, T2, diffusion and Z‐spectrum, were performed in rats after middle cerebral artery occlusion. We analyzed the conventional Z‐spectrum IΔωI0 and the apparent exchange spectrum RexΔω, being the difference between the relaxation‐scaled inverse Z‐spectrum and the intrinsic spinlock relaxation rate R1·cos2θ·I0IΔω-R1ρΔω. The ischemia‐induced change was calculated as the spectral difference between the diffusion lesion and the contralateral normal area. Results: 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. Conclusion: Our study shows that after the relaxation‐effect correction, the APT effect is the dominant contributing factor to pH‐weighted MTRasym following acute stroke. [ABSTRACT FROM AUTHOR]