Voxel-wise Optimization of Pseudo Voigt Profile (VOPVP) for Z-spectra fitting in chemical exchange saturation transfer (CEST) MRI

Lihong Zhang, Yingcheng Zhao, Yanrong Chen, Chongxue Bie, Yuhua Liang, Xiaowei He, Xiaolei Song


Background: Chemical exchange saturation transfer (CEST) MRI is a promising approach for detecting biochemical alterations in cancers and neurological diseases, but the quantification can be challenging. Among numerous quantification methods, Lorentzian difference (LD) is relatively simple and widely used, which employs Lorentzian line-shape as a reference to describe the direct saturation (DS) of water and takes account of difference against experimental CEST spectra data. However, LD often overestimates CEST and nuclear overhauser enhancement (NOE) effects. Specifically, for fast-exchanging CEST species require higher saturation power (B1_sat) or in the presence of strong magnetization transfer (MT) contrast, Z-spectrum appears more like a Gaussian line-shape rather than a Lorentzian line-shape.
Methods: To improve the conventional LD analysis, the present study developed and validated a novel fitting algorithm through a linear combination of Gaussian and Lorentzian function as the reference spectra, namely, Voxel-wise Optimization of Pseudo Voigt Profile (VOPVP). The experimental Z-spectra were pre-fitted with Gaussian and Lorentzian method independently, in order to determine Lorentzian proportionality coefficient (a). To further compensate for the line-shape changes under different B1_sat’s, a B1-dependent adjustment was applied to the experimental Z-spectra (Z_exp) according to the prior knowledge learned from 5-pool Bloch equation-based simulations at a range of B1_sat’s. Then, the obtained Z-spectra (Z_B1adj) was fitted by the previously defined VOPVP function. Considering the asymmetric component of MT, the positive- and negative-side of Z-spectra were fitted separately, while the middle part (−0.6 to 0.6 ppm, consisted primarily of DS) was fitted using Lorentzian function. Finally, the difference between Z_VOPVP and Z_exp was defined as the CEST and NOE contrast. To validate our VOPVP method, an extensive simulation of CEST Z-spectra was performed using 5-pool model and 6-pool model with greater MT component.
Results: In comparison with LD approach, VOPVP exhibited lower sum of squares due to error (SSE) and higher goodness of fit (R-square) for the experimental Z-spectra at all B1_sat. Moreover, the results indicated that VOPVP fitting improved the overestimated contributions from amide proton transfer (APT) and NOE through LD at all B1_sat. Despite that the relationship for B1-dependent adjustment was pre-determined using a single 5-pool model, the VOPVP fittings obtained accurate quantification for multiple 6-pool models with a range of T1w’s and T2w’s. The robustness of VOPVP fitting was also proved by simulations using 3T parameters. Furthermore, we assessed VOPVP in vivo in a glioblastoma-bearing mouse. Compared to LD maps, VOPVP quantification maps displayed higher contrast-to-noise ratio between tumor and normal contralateral tissue for APT, glutamate and nuclear overhauser effect (NOE), when B1_sat >1 µT.
Conclusions: As an improvement of LD method, VOPVP fitting can serve as a simple, robust and more accurate approach for quantifying CEST and NOE contrast.