Orientation-independent magnetization transfer imaging of brain white matter

White matter in the brain has a highly anisotropic structure, leading to orientation-dependent MRI contrasts, such as those observed in quantitative magnetization transfer (MT). These orientation-dependent contrasts can complicate the quantification of tissue parameters, posing significant challenges for correction methods. A common physical mechanism underlying this orientation dependence is residual dipolar coupling (RDC), which plays a critical role in the anisotropy observed in MRI spin relaxation. A novel technique, macromolecular proton fraction mapping based on spin-lock (MPF-SL), was recently proposed to achieve orientation-independent MT measurements by minimizing RDC effects during data acquisition. This study aimed to validate the orientation independence of MPF-SL in vivo in brain white matter. Experiments were conducted on 20 healthy volunteers, with data collected at two different head orientations. MRI exams were repeated one week apart. MPF-SL measurements showed negligible differences (<2%) between head orientations, while conventional quantitative MT imaging exhibited statistically significant variation (p < 0.05). Both methods demonstrated good repeatability, with intraclass correlation coefficients (ICC) > 0.75, bias < 0.05%, and limits of agreement < 0.5%. These findings confirm that MPF-SL effectively addresses orientation-dependent limitations in MT measurements of white matter, offering a reliable approach for future clinical and research applications.