Analysis and correction of biases in cross‐relaxation MRI due to biexponential longitudinal relaxation

PURPOSE: Cross-relaxation imaging (CRI) is a family of quantitative magnetization transfer techniques that utilize images obtained with off-resonance saturation and longitudinal relaxation rate (R1) maps reconstructed by the variable flip angle (VFA) method. It was demonstrated recently that a significant bias in an apparent VFA R1 estimation occurs in macromolecule-rich tissues due to magnetization transfer (MT)-induced biexponential behavior of longitudinal relaxation of water protons. The purpose of this article is to characterize theoretically and experimentally the resulting bias in the CRI maps and propose methods to correct it. THEORY: The modified CRI algorithm is proposed, which corrects for such biases and yields accurate parametric bound pool fraction f, cross-relaxation rate k, and R1 maps. Additionally, an analytical correction procedure is introduced to recalculate previously obtained parameter values. RESULTS: The systematic errors due to unaccounted MT-induced biexponential relaxation can be characterized as an overestimation of R1, f, and k, with a relative bias comparable with the magnitude of f. The phantom and human in vivo experiments demonstrate that both proposed modified CRI and analytical correction approaches significantly improve the accuracy of the CRI method. CONCLUSION: The accuracy of the CRI method can be considerably improved by taking into account the contribution of MT-induced biexponential longitudinal relaxation into variable flip angle R1 measurements.