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.

Amide proton transfer (APT) MRI is promising to serve as a surrogate metabolic imaging biomarker of acute stroke. Although the magnetization transfer ratio asymmetry (MTR_asym ) 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 MTR_asym 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 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.

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 ΔR_ex 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 MTR_asym .

Our study shows that after the relaxation-effect correction, the APT effect is the dominant contributing factor to pH-weighted MTR_asym following acute stroke.