Simultaneous multi-transient linear-combination modeling of MRS data improves uncertainty estimation.

The interest in applying and modeling dynamic MRS has recently grown. 2D modeling yields advantages for the precision of metabolite estimation in interrelated MRS data. However, it is unknown whether including all transients simultaneously in a 2D model without averaging (presuming a stable signal) performs similarly to 1D modeling of the averaged spectrum. Therefore, we systematically investigated the accuracy, precision, and uncertainty estimation of both described model approaches. Monte Carlo simulations of synthetic MRS data were used to compare the accuracy and uncertainty estimation of simultaneous 2D multi-transient LCM with 1D-LCM of the average. 2,500 datasets per condition with different noise representations of a 64-transient MRS experiment at 6 signal-to-noise levels for two separate spin systems (scyllo-inositol and GABA) were analyzed. Additional datasets with different levels of noise correlation were also analyzed. Modeling accuracy was assessed by determining the relative bias of the estimated amplitudes against the ground truth, and modeling precision was determined by standard deviations and Cramér-Rao Lower Bounds (CRLB). Amplitude estimates for 1D- and 2D-LCM agreed well and showed similar level of bias compared to the ground truth. Estimated CRLBs agreed well between both models and with ground truth CRLBs. For correlated noise the estimated CRLBs increased with the correlation strength for the 1D-LCM but remained stable for the 2D-LCM. Our results indicate that the model performance of 2D multi-transient LCM is similar to averaged 1D-LCM. This validation on a simplified scenario serves as necessary basis for further applications of 2D modeling.