In this acute intervention study, we investigated the potential benefit of ketone supplementation in humans by studying cardiac phosphocreatine to adenosine-triphosphate ratios (PCr/ATP) and... Show moreIn this acute intervention study, we investigated the potential benefit of ketone supplementation in humans by studying cardiac phosphocreatine to adenosine-triphosphate ratios (PCr/ATP) and skeletal muscle PCr recovery using phosphorus magnetic resonance spectroscopy (P-31-MRS) before and after ingestion of a ketone ester drink. We recruited 28 healthy individuals: 12 aged 23-70 years for cardiac P-31-MRS, and 16 aged 60-75 years for skeletal muscle P-31-MRS. Baseline and post-intervention resting cardiac and dynamic skeletal muscle P-31-MRS scans were performed in one visit, where 25 g of the ketone monoester, deltaG(R), was administered after the baseline scan. Administration was timed so that post-intervention P-31-MRS would take place 30 min after deltaG(R) ingestion. The deltaG(R) ketone drink was well-tolerated by all participants. In participants who provided blood samples, post-intervention blood glucose, lactate and non-esterified fatty acid concentrations decreased significantly (-28.8%, p MUCH LESS-THAN 0.001; -28.2%, p = 0.02; and -49.1%, p MUCH LESS-THAN 0.001, respectively), while levels of the ketone body D-beta-hydroxybutyrate significantly increased from mean (standard deviation) 0.7 (0.3) to 4.0 (1.1) mmol/L after 30 min (p MUCH LESS-THAN 0.001). There were no significant changes in cardiac PCr/ATP or skeletal muscle metabolic parameters between baseline and post-intervention. Acute ketone supplementation caused mild ketosis in blood, with drops in glucose, lactate, and free fatty acids; however, such changes were not associated with changes in P-31-MRS measures in the heart or in skeletal muscle. Future work may focus on the effect of longer-term ketone supplementation on tissue energetics in groups with compromised mitochondrial function. Show less
The article of Lopez et al describes the use of a multi-parametric MR approach to study muscle T-2 relaxation times and P-31-MRS indices of energetics and sarcolemma integrity in a mouse model of... Show moreThe article of Lopez et al describes the use of a multi-parametric MR approach to study muscle T-2 relaxation times and P-31-MRS indices of energetics and sarcolemma integrity in a mouse model of DMD, the mdx mouse. Muscular dystrophies have a multi-factorial disease cascade, and there are several MR methods used to assess these. Aspects that reflect disease progression are outlined on the left, while features that are more related to disease activity are outlined on the right. Show less
Quantitative MRI and MRS of muscle are increasingly being used to measure individual pathophysiological processes in Becker muscular dystrophy (BMD). In particular, muscle fat fraction was shown to... Show moreQuantitative MRI and MRS of muscle are increasingly being used to measure individual pathophysiological processes in Becker muscular dystrophy (BMD). In particular, muscle fat fraction was shown to be highly associated with functional tests in BMD. However, the muscle strength per unit of contractile cross-sectional area is lower in patients with BMD compared with healthy controls. This suggests that the quality of the non-fat-replaced (NFR) muscle tissue is lower than in healthy controls. Consequently, a measure that reflects changes in muscle tissue itself is needed. Here, we explore the potential of waterT(2)relaxation times, diffusion parameters and phosphorus metabolic indices as early disease markers in patients with BMD. For this purpose, we examined these measures in fat-replaced (FR) and NFR lower leg muscles in patients with BMD and compared these values with those in healthy controls. Quantitative proton MRI (three-point Dixon, multi-spin-echo and diffusion-weighted spin-echo echo planar imaging) and 2D chemical shift imaging(31)P MRS data were acquired in 24 patients with BMD (age 18.8-66.2 years) and 13 healthy controls (age 21.3-63.6 years). Muscle fat fractions, phosphorus metabolic indices, and averages and standard deviations (SDs) of the waterT(2)relaxation times and diffusion tensor imaging (DTI) parameters were assessed in six individual leg muscles. Phosphodiester levels were increased in the NFR and FR tibialis anterior, FR peroneus and FR gastrocnemius lateralis muscles. No clear pattern was visible for the other metabolic indices. IncreasedT(2)SD was found in the majority of FR muscles compared with NFR and healthy control muscles. No differences in average waterT(2)relaxation times or DTI indices were found between groups. Overall, our results indicate that primarily muscles that are further along in the disease process showed increases inT(2)heterogeneity and changes in some metabolic indices. No clear differences were found for the DTI indices between groups. Show less
Meyerspeer, M.; Boesch, C.; Cameron, D.; Dezortova, M.; Forbes, S.C.; Heerschap, A.; ... ; Experts Working Grp P MR 2020
Skeletal muscle phosphorus-31 P-31 MRS is the oldest MRS methodology to be applied to in vivo metabolic research. The technical requirements of P-31 MRS in skeletal muscle depend on the research... Show moreSkeletal muscle phosphorus-31 P-31 MRS is the oldest MRS methodology to be applied to in vivo metabolic research. The technical requirements of P-31 MRS in skeletal muscle depend on the research question, and to assess those questions requires understanding both the relevant muscle physiology, and how P-31 MRS methods can probe it. Here we consider basic signal-acquisition parameters related to radio frequency excitation, TR, TE, spectral resolution, shim and localisation. We make specific recommendations for studies of resting and exercising muscle, including magnetisation transfer, and for data processing. We summarise the metabolic information that can be quantitatively assessed with P-31 MRS, either measured directly or derived by calculations that depend on particular metabolic models, and we give advice on potential problems of interpretation. We give expected values and tolerable ranges for some measured quantities, and minimum requirements for reporting acquisition parameters and experimental results in publications. Reliable examination depends on a reproducible setup, standardised preconditioning of the subject, and careful control of potential difficulties, and we summarise some important considerations and potential confounders. Our recommendations include the quantification and standardisation of contraction intensity, and how best to account for heterogeneous muscle recruitment. We highlight some pitfalls in the assessment of mitochondrial function by analysis of phosphocreatine (PCr) recovery kinetics. Finally, we outline how complementary techniques (near-infrared spectroscopy, arterial spin labelling, BOLD and various other MRI and H-1 MRS measurements) can help in the physiological/metabolic interpretation of P-31 MRS studies by providing information about blood flow and oxygen delivery/utilisation. Our recommendations will assist in achieving the fullest possible reliable picture of muscle physiology and pathophysiology. Show less
