Alteration of skeletal muscle energy metabolism assessed by 31P MRS in clinical routine, part 2: Clinical application

Background: In this second part of a two-part paper, we intend to demonstrate the impact of the previously proposed advanced quality control pipeline. To understand its benefit and challenge the proposed methodology in a real scenario, we chose to compare the outcome when applying it to the analysis of two patient populations with a significant but highly different types of fatigue: COVID19 and multiple sclerosis (MS). Experimental: 31P-MRS was performed on a 3T clinical MRI, in 19 COVID19 patients, 38 MS patients, and 40 matched healthy controls. Dynamic acquisitions using an MR-compatible ergometer ran over a rest(40s), exercise(2min), and a recovery phase(6min). Long and short TR acquisitions were also made at rest for T1 correction. The advanced data quality control pipeline presented in part 1 is applied to the selected patient cohorts to investigate its impact on clinical outcomes. We first used power and sample size analysis to estimate objectively the impact of adding QCS. Then, comparisons between patients and healthy control groups using validated QCS were performed using unpaired T-tests or Mann-Whitney tests (p<0.05).Results: The application of the QCS resulted in increased statistical power, changed the values of several outcome measures, and reduced variability (SD). A significant difference was found between the T1PCr and T1Pi of MS patients and healthy controls. Furthermore, the use of a fixed correction factor led to systematically higher estimated concentrations of PCr and Pi than when using individually corrected factors. We observed significant differences between the two patient populations and healthy controls for resting [PCr] -- MS only, [Pi], [ADP], [H2PO4-] and pH -- COVID19 only, and post-exercise [PCr],[Pi] and [H2PO4-] - MS only. The dynamic indicators $\tau$PCr, $\tau$Pi, ViPCr and Vmax were reduced for COVID19 and MS patients compared to controls. Conclusion: Our results show that QCS in dynamic 31P-MRS studies results in smaller data variability and therefore impacts study sample size and power. Although QCS resulted in discarded data and therefore reduced the acceptable data and subject numbers, this rigorous and unbiased approach allowed for proper assessment of muscle metabolites and metabolism in patient populations. The outcomes include an increased metabolite T1, which directly affect the T1 correction factor applied to the amplitudes of the metabolite, and a prolonged $\tau$PCr indicating reduced muscle oxidative capacity for patients with MS and COVID19.