| Summary: | Magnetic resonance spectroscopy (MRS) is a noninvasive technique for measuring metabolite concentration. It can be used for preclinical small animal brain studies using rodents to provide information about neurodegenerative diseases and metabolic disorders. However, data acquisition from small volumes in a limited scan time is technically challenging due to its inherently low sensitivity. To mitigate this problem, this study investigated the feasibility of a low-rank denoising method in enhancing the quality of single voxel multinuclei (<sup>31</sup>P and <sup>1</sup>H) MRS data at 9.4 T. Performance was evaluated using in vivo MRS data from a normal mouse brain (<sup>31</sup>P and <sup>1</sup>H) and stroke mouse model (<sup>1</sup>H) by comparison with signal-to-noise ratios (SNRs), Cramer-Rao lower bounds (CRLBs), and metabolite concentrations of a linear combination of model analysis results. In <sup>31</sup>P MRS data, low-rank denoising resulted in improved SNRs and reduced metabolite quantification uncertainty compared with the original data. In <sup>1</sup>H MRS data, the method also improved the SNRs, CRLBs, but it performed better for <sup>31</sup>P MRS data with relatively simpler patterns compared to the <sup>1</sup>H MRS data. Therefore, we suggest that the low-rank denoising method can improve spectra SNR and metabolite quantification uncertainty in single-voxel in vivo <sup>31</sup>P and <sup>1</sup>H MRS data, and it might be more effective for <sup>31</sup>P MRS data. The main contribution of this study is that we demonstrated the effectiveness of the low-rank denoising method on small-volume single-voxel MRS data. We anticipate that our results will be useful for the precise quantification of low-concentration metabolites, further reducing data acquisition voxel size, and scan time in preclinical MRS studies.
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