Macromolecule modelling for improved metabolite quantification using short echo time brain 1 H MRS at 3 T and 7 T: The PRaMM Model.

Purpose: To improve reliability of metabolite quantification at both, 3 T and 7 T, we propose a novel parametrized macromolecules quantification model (PRaMM) for brain 1 H MRS, in which the ratios of macromolecule peak intensities are used as soft constraints. Methods: Full- and metabolite-nulled spectra were acquired in three different brain regions with different ratios of grey and white matter from six healthy volunteers, at both 3 T and 7 T. Metabolite-nulled spectra were used to identify highly correlated macromolecular signal contributions and estimate the ratios of their intensities. These ratios were then used as soft constraints in the proposed PRaMM model for quantification of full spectra. The PRaMM model was validated by comparison with a single component macromolecule model and a macromolecule subtraction technique. Moreover, the influence of the PRaMM model on the repeatability and reproducibility compared to those other methods was investigated. Results: The developed PRaMM model performed better than the two other approaches in all three investigated brain regions. Several estimates of metabolite concentration and their Cramér-Rao lower bounds were affected by the PRaMM model reproducibility, and repeatability of the achieved concentrations were tested by evaluating the method on a second repeated acquisitions dataset. While the observed effects on both metrics were not significant, the fit quality metrics were improved for the PRaMM method (p≤0.0001). Minimally detectable changes are in the range 0.5 - 1.9 mM and percent coefficients of variations are lower than 10% for almost all the clinically relevant metabolites. Furthermore, potential overparameterization was ruled out. Conclusion: Here, the PRaMM model, a method for an improved quantification of metabolites was developed, and a method to investigate the role of the MM background and its individual components from a clinical perspective is proposed.