Are mice good models for human neuromuscular disease? Comparing muscle excursions in walking between mice and humans

The mouse is one of the most widely used animal models to study neuromuscular diseases and test new therapeutic strategies. However, findings from successful pre-clinical studies using mouse models frequently fail to translate to humans due to various factors. Differences in muscle function between the two species could be crucial but often have been overlooked. The purpose of this study was to evaluate and compare muscle excursions in walking between mice and humans

Fatigue in neuromuscular disorders: focus on Guillain–Barré syndrome and Pompe disease

Fatigue accounts for an important part of the burden experienced by patients with neuromuscular disorders. Substantial high prevalence rates of fatigue are reported in a wide range of neuromuscular disorders, such as Guillain–Barré syndrome and Pompe disease. Fatigue can be subdivided into experienced fatigue and physiological fatigue. Physiological fatigue in turn can be of central or peripheral origin. Peripheral fatigue is an important contributor to fatigue in neuromuscular disorders, but in reaction to neuromuscular disease fatigue of central origin can be an important protective mechanism to restrict further damage. In most cases, severity of fatigue seems to be related with disease severity, possibly with the exception of fatigue occurring in a monophasic disorder like Guillain–Barré syndrome. Treatment of fatigue in neuromuscular disease starts with symptomatic treatment of the underlying disease. When symptoms of fatigue persist, non-pharmacological interventions, such as exercise and cognitive behavioral therapy, can be initiated

Multi-center evaluation of stability and reproducibility of quantitative MRI measures in healthy calf muscles

The purpose of this study was to evaluate temporal stability, multi-center reproducibility and the influence of covariates on a multimodal MR protocol for quantitative muscle imaging and to facilitate its use as a standardized protocol for evaluation of pathology in skeletal muscle. Quantitative T2, quantitative diffusion and four-point Dixon acquisitions of the calf muscles of both legs were repeated within one hour. Sixty-five healthy volunteers (31 females) were included in one of eight 3-T MR systems. Five traveling subjects were examined in six MR scanners. Average values over all slices of water-T2 relaxation time, proton density fat fraction (PDFF) and diffusion metrics were determined for seven muscles. Temporal stability was tested with repeated measured ANOVA and two-way random intraclass correlation coefficient (ICC). Multi-center reproducibility of traveling volunteers was assessed by a two-way mixed ICC. The factors age, body mass index, gender and muscle were tested for covariance. ICCs of temporal stability were between 0.963 and 0.999 for all parameters. Water-T2 relaxation decreased significantly (P < 10−3) within one hour by ~ 1 ms. Multi-center reproducibility showed ICCs within 0.879–0.917 with the lowest ICC for mean diffusivity. Different muscles showed the highest covariance, explaining 20–40% of variance for observed parameters. Standardized acquisition and processing of quantitative muscle MRI data resulted in high comparability among centers. The imaging protocol exhibited high temporal stability over one hour except for water T2 relaxation times. These results show that data pooling is feasible and enables assembling data from patients with neuromuscular diseases, paving the way towards larger studies of rare muscle disorders

Speed of sound ultrasound: comparison with proton density fat fraction assessed with Dixon MRI for fat content quantification of the lower extremity

OBJECTIVES To compare speed of sound (SoS) ultrasound (US) of the calves with Dixon magnetic resonance imaging (MRI) for fat content quantification. MATERIALS AND METHODS The study was approved by the local ethics committee. Fifty calf muscles of 35 women (age range 22-81 years) prospectively underwent an US and subsequent MRI (Dixon sequence) examination as well as body weight and impedance fat measurements. SoS (in m/s) was calculated positioning a reflector on the opposite side of a conventional US machine probe with the calf in between. Fiducial nitroglycerin markers were placed on the calf at the reflector and US probe end positions for later registration of the US sonification volumetric section. An automatic segmentation algorithm separated MRI adipose tissue, muscle and bone regions. MRI fat fraction of the entire leg slice (total) and intramuscular and adipose tissue fat fraction were calculated and correlation analysis and correlation coefficient comparison were performed. RESULTS Median SoS demonstrated a very strong (r = - 0.83 (95% CI - 0.90; - 0.72); p < 0.001) correlation with MRI total fat fraction, a strong (r = - 0.61 (95% CI - 0.76; - 0.40); p < 0.001) correlation with MRI adipose tissue fat fraction and a moderate (r = - 0.54 (95% CI - 0.71; - 0.31); p < 0.001) correlation with MRI intramuscular fat fraction. Impedance body fat percentage correlated strongly with SoS (r = - 0.72 (95% CI - 0.85; - 0.51); p < 0.001) and MRI total fat fraction (r = 0.61 (95% CI 0.34; 0.78); p < 0.001). For electrical impedance, significantly lower correlations (p = 0.033) were found for MRI total fat fraction compared with SoS. CONCLUSIONS Correlations of SoS with Dixon MRI fat fraction measurements were very strong to moderate. KEY POINTS • Correlations of speed of sound with Dixon MRI fat fraction measurements of the same body location were very strong to moderate. • Speed of sound measurements showed a high repeatability. • Speed of sound provides a sufficient discrimination range for fat fraction estimates