Using the simultaneously acquired water signal as internal reference allows not only for compensation of phase and frequency fluctuations but also for signal amplitude restoration, and thus improved metabolite ADC estimation. Combination with 2D simultaneous fitting promises access to the diffusion properties even for low signal-to-noise metabolites. The combination of both techniques increases the specificity and sensitivity of estimated metabolite ADC values in the cohort.

It is shown that inclusion of a measured lineshape into modeling of interrelated MR spectra is beneficial and can be combined also with simultaneous spectral and diffusion modeling.

Purpose To optimize acquisition and fitting conditions for nonfocal disease in terms of voxel size and use of individual coil element data. Increasing the voxel size yields a higher signal‐to‐noise ratio, but leads to larger linewidths and more artifacts. Several ways to improve the spectral quality for large voxels are exploited and the optimal use of individual coil signals investigated. Methods Ten human subjects were measured at 3 T using a 64‐channel receive head coil with a semi‐LASER localization sequence under optimized and deliberately mis‐set field homogeneity. Eight different voxel sizes (8 to 99 cm3) were probed. Spectra were fitted either as weighted sums of the individual coil elements or simultaneously without summation. Eighteen metabolites were included in the fit model that also included the lineshapes from all coil elements as reflected in water reference data. Fitting errors for creatine, myo‐Inositol and glutamate are reported as representative parameters to judge optimal acquisition and evaluation conditions. Results Minimal Cramér‐Rao lower bounds and thus optimal acquisition conditions were found for a voxel size of ~ 70 cm3 for the representative upfield metabolites. Spectral quality in terms of lineshape and artifact appearance was determined to differ substantially between coil elements. Simultaneous fitting of spectra from individual coil elements instead of traditional fitting of a weighted sum spectrum reduced Cramer‐Rao lower bounds by up to 17% for large voxel sizes. Conclusion The optimal voxel size for best precision in determined metabolite content is surprisingly large. Such an acquisition condition is most relevant for detection of low‐concentration metabolites, like NAD+ or phenylalanine, but also for longitudinal studies where very small alterations in metabolite content are targeted. In addition, simultaneous fitting of single channel spectra enforcing lineshape and coil sensitivity information proved to be superior to traditional signal combination with subsequent fitting.

It has recently been reported in this journal that local fat depots produce a sizable frequency‐dependent signal attenuation in magnetic resonance spectroscopy (MRS) of the brain. If of a general nature, this effect would question the use of internal reference signals for quantification of MRS and the quantitative use of MRS as a whole. Here, it was attempted to verify this effect and pinpoint the potential causes by acquiring data with various acquisition settings, including two field strengths, two MR scanners from different vendors, different water suppression sequences, RF coils, localization sequences, echo times, and lipid/metabolite phantoms. With all settings tested, the reported effect could not be reproduced, and it is concluded that water referencing and quantitative MRS per se remain valid tools under common acquisition conditions. Copyright © 2015 John Wiley & Sons, Ltd.