Towards the complex dependence of MTR_asym on T_1w in amide proton transfer (APT) imaging

Amide proton transfer (APT) imaging is a variation of chemical exchange saturation transfer MRI that has shown promise in diagnosing tumors, ischemic stroke, multiple sclerosis, traumatic brain injury, etc. Specific quantification of the APT effect is crucial for the interpretation of APT contrast in pathologies. Conventionally, magnetization transfer ratio with asymmetric analysis (MTR_asym ) has been used to quantify the APT effect. However, some studies indicate that MTR_asym is contaminated by water longitudinal relaxation time (T_1w ), and thus it is necessary to normalize T_1w in MTR_asym to obtain specific quantification of the APT effect. So far, whether to use MTR_asym or the T_1w -normalized MTR_asym is still under debate in the field. In this paper, the influence of T_1w on the quantification of APT was evaluated through theoretical analysis, numerical simulations, and phantom studies for different experimental conditions. Results indicate that there are two types of T_1w effect (T_1w recovery and T_1w -related saturation), which have inverse influences on the steady-state MTR_asym . In situations with no or weak direct water saturation (DS) effect, there is only the T_1w recovery effect, and MTR_asym linearly depends on T_1w . In contrast, in situations with significant DS effects, the dependence of MTR_asym on T_1w is complex, and is dictated by the competition of these two T_1w effects. Therefore, by choosing appropriate irradiation powers, MTR_asym could be roughly insensitive to T_1w . Moreover, in non-steady-state acquisitions with very short irradiation time, MTR_asym is also roughly insensitive to T_1w . Therefore, for steady-state APT imaging at high fields or with very low irradiation powers, where there are no significant DS effects, it is necessary to normalize T_1w to improve the specificity of MTR_asym . However, in clinical MRI systems (usually low fields or non-steady-state acquisitions), T_1w normalization may not be necessary when appropriate sequence parameters are chosen.