P-31 magnetic resonance spectroscopy in skeletal muscle: Experts' consensus recommendations

Skeletal muscle phosphorus-31 31P MRS is the oldest MRS methodology to be applied to in vivo metabolic research. The technical requirements of 31P MRS in skeletal muscle depend on the research question, and to assess those questions requires understanding both the relevant muscle physiology, and how 31P 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 31P 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 1H MRS measurements) can help in the physiological/metabolic interpretation of 31P 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

Reproducibility of human cardiac phosphorus magnetic resonance spectroscopy (31P-MRS) at 7T

Purpose: We test the reproducibility of human cardiac phosphorus magnetic resonance spectroscopy (31P-MRS) at ultra-high field strength (7T) for the first time. The primary motivation of this work was to assess the reproducibility of a ‘rapid’ 6½ minute 31P threedimensional chemical shift imaging (3D-CSI) sequence which, if sufficiently reproducible, would allow the study of stress-response processes. We compare this to an established 28 minute protocol, designed to record high quality spectra in a clinically-feasible scan time. Finally, we use this opportunity to compare the effect of per-subject B0 shimming on data quality and reproducibility in the 6 ½ min protocol. Methods: 10 healthy subjects were scanned on two occasions: one to test the 28 minute 3DCSI protocol, and one to test the 6½ minute protocol. Spectra were fitted using the OXSA Matlab toolbox. The phosphocreatine to adenosine triphosphate concentration ratio (“PCr/ATP”) from each scan was analysed for intra- and inter-subject variability. The impact of different strategies for voxel selection was assessed. Results: There were no significant differences between repeated measurements in the same subject. For the 28 min protocol, PCr/ATP in the midseptal voxel across all scans was 1.91 ± 0.36 (mean ± inter-subject SD). For the 6½ min protocol, PCr/ATP in the midseptal voxel was 1.76 ± 0.40. The coefficients of reproducibility (CR) were 0.49 (28 min) and 0.67 (6½ min). Per-subject B0-shimming improved the fitted PCr/ATP precision (for 6½ min scans), but had negligible effect on the coefficients of reproducibility (0.67 vs 0.66). Conclusions: Both 7T protocols show improved reproducibility compared to a previous 3T study by Tyler et al. Our results will enable informed power calculations and protocol selection for future clinical research studies.We thank Professor D. J. Tyler for providing the raw data from his 3 T reproducibility study (ref 15). Funded by a Sir Henry Dale Fellowship from the Wellcome Trust and the Royal Society to CTR [098436/Z/12/B]. JE receives a DPhil studentship from the Medical Research Council (UK). The support of the Slovak Grant Agency VEGA (grant #2/0001/17) and APVV (grant #15- 0029) is also acknowledged

Validation of the Official Slovak Version of the Unified Dyskinesia Rating Scale (UDysRS)

After successful clinimetric testing of the Unified Dyskinesia Rating Scale (UDysRS), a program for translation and validation of non-English versions of the UDysRS was initiated. The aim of this study was to validate and confirm the factor structure of the Slovak translation of the UDysRS. We examined 251 patients with Parkinson’s disease and dyskinesia using the Slovak version of the UDysRS. The average age of our sample was 65.2 ± 9.2 years and average disease duration was 10.9 ± 5.0 years. Slovak data were compared using confirmatory factor analysis with the Spanish data. To be designated as the official Slovak UDysRS translation, the comparative fit index (CFI) had to be ≥0.90 relative to the Spanish language version. Exploratory factor analysis was performed to explore the underlying factor structure without the constraint of a prespecified factor structure. For all four parts of the Slovak UDysRS, the CFI, in comparison with the Spanish language factor structure, was ≥0.98. Isolated differences in the factor structure of the Slovak UDysRS were identified by exploratory factor analysis compared with the Spanish version. The Slovak version of the UDysRS was designated as an official non-English translation and can be downloaded from the website of the International Parkinson and Movement Disorder Society

Aerobic-Strength Exercise Improves Metabolism and Clinical State in Parkinson’s Disease Patients

Regular exercise ameliorates motor symptoms in Parkinson’s disease (PD). Here, we aimed to provide evidence that exercise brings additional benefits to the whole-body metabolism and skeletal muscle molecular and functional characteristics, which might help to explain exercise-induced improvements in the clinical state. 3-months supervised endurance/strength training was performed in early/mid-stage PD patients and age/gender-matched individuals (n = 11/11). The effects of exercise on resting energy expenditure (REE), glucose metabolism, adiposity, and muscle energy metabolism (31P-MRS) were evaluated and compared to non-exercising PD patients. Two muscle biopsies were taken to determine intervention-induced changes in fiber type, mitochondrial content, and expression of genes related to muscle energy metabolism, as well as proliferative and regenerative capacity. Exercise improved the clinical disability score (MDS-UPDRS), bradykinesia, balance, walking speed, REE, and glucose metabolism and increased muscle expression of energy sensors (AMPK). However, the exercise-induced increase in muscle mass/strength, mitochondrial content, type II fiber size, and postexercise phosphocreatine (PCr) recovery (31P-MRS) were found only in controls. Nevertheless, MDS-UPDRS was associated with muscle AMPK and mechano-growth factor (MGF) expression. Improvements in fasting glycemia were positively associated with muscle function and the expression of Sirt1 and Cox7a1, and the parameters of fitness/strength were positively associated with the expression of MyHC2, MyHC7, and MGF. Moreover, reduced bradykinesia was associated with better muscle metabolism (maximal oxidative capacity and postexercise PCr recovery; 31P-MRS). Exercise training improved the clinical state in early/mid-stage Parkinson’s disease patients, including motor functions and whole-body metabolism. Although the adaptive response to exercise in PD was different from that of controls, exercise-induced improvements in the PD clinical state were associated with specific adaptive changes in muscle functional, metabolic, and molecular characteristics.Clinical Trial Registrationwww.ClinicalTrials.gov, identifier NCT02253732