Orientation independent quantification of macromolecular proton fraction in tissues with suppression of residual dipolar coupling

Quantitative magnetization transfer (MT) imaging enables non-invasive characterization of the macromolecular environment of tissues. However, recent work has highlighted that the quantification of MT parameters exhibits orientation dependence in ordered tissue structures, potentially confounding its clinical applications. Notably, in tissues with ordered structures, such as articular cartilage and myelin, the residual dipolar coupling (RDC) effect can arise owing to incomplete averaging of dipolar-dipolar interactions of water protons. In this study, we demonstrated the confounding effect of RDC on quantitative MT imaging in ordered tissues can be suppressed by using an emerging technique known as macromolecular proton fraction mapping based on spin-lock (MPF-SL). The off-resonance spin-lock pulse in MPF-SL could be designed to generate a strong effective spin-lock field to suppress RDC without violating the specific absorption rate and hardware limitations in clinical scans. Furthermore, removing the water signal in MPF-SL enabled the application of a strong effective spin-lock field without any confounding signal from direct water saturation. Our findings were experimentally validated using human knee specimens and healthy human cartilage. The results demonstrated that MPF-SL exhibits lower sensitivity to tissue orientation compared with R2, R1rho, and saturation-pulse-based MT imaging. Thus, MPF-SL could serve as a valuable orientation-independent technique for quantifying MPF.