Quantitative magnetization transfer MRI unbiased by on-resonance saturation and dipolar order contributions

Purpose To demonstrate the bias in quantitative MT (qMT) measures introduced by the presence of dipolar order and on-resonance saturation (ONRS) effects using magnetization transfer (MT) spoiled gradient-recalled (SPGR) acquisitions, and propose changes to the acquisition and analysis strategies to remove these biases.Methods The proposed framework consists of SPGR sequences prepared with simultaneous dual-offset frequency-saturation pulses to cancel out dipolar order and associated relaxation (T-1D) effects in Z-spectrum acquisitions, and a matched quantitative MT (qMT) mathematical model that includes ONRS effects of readout pulses. Variable flip angle and MT data were fitted jointly to simultaneously estimate qMT parameters (macromolecular proton fraction [MPF], T-2,T-f, T-2,T-b, R, and free pool T-1). This framework is compared with standard qMT and investigated in terms of reproducibility, and then further developed to follow a joint single-point qMT methodology for combined estimation of MPF and T-1.Results Bland-Altman analyses demonstrated a systematic underestimation of MPF (-2.5% and -1.3%, on average, in white and gray matter, respectively) and overestimation of T-1 (47.1 ms and 38.6 ms, on average, in white and gray matter, respectively) if both ONRS and dipolar order effects are ignored. Reproducibility of the proposed framework is excellent (?MPF = -0.03% and ?T-1 = -19.0 ms). The single-point methodology yielded consistent MPF and T-1 values with respective maximum relative average bias of -0.15% and -3.5 ms found in white matter.Conclusion The influence of acquisition strategy and matched mathematical model with regard to ONRS and dipolar order effects in qMT-SPGR frameworks has been investigated. The proposed framework holds promise for improved accuracy with reproducibility.