Accuracy and uncertainty of asymmetric magnetization transfer ratio quantification for amide proton transfer (APT) imaging at 3T: A Monte Carlo study

Amide proton transfer (APT) imaging offers a novel and powerful MRI contrast mechanism for quantitative molecular imaging based on the principle of chemical exchange saturation transfer (CEST). Asymmetric magnetization transfer ratio (MTR_asym) quantification is crucial for Z-spectrum analysis of APT imaging, but is still challenging, particularly at clinical field strength. This paper studies the accuracy and uncertainty in the quantification of MTR_asym for APT imaging at 3T, by using high-order polynomial fitting of Z-spectrum through Monte Carlo simulation. Results show that polynomial fitting is a biased estimator that consistently underestimates MTR_asym. For a fixed polynomial order, the accuracy of MTR_asym is almost constant with regard to signal-to-noise ratio (SNR) while the uncertainty decreases exponentially with SNR. The higher order polynomial fitting increases both the accuracy and the uncertainty of MTR_asym. For different APT signal intensity levels, the relative accuracy and the absolute uncertainty keep constant for a fixed polynomial order. These results indicate the limitations and pitfalls of polynomial fitting for MTR_asym quantification so better quantification technique for MTR_asym estimation is warranted.