The tri-exponential model is an accurate tool to monitor muscle tissue disease activity devoid of bias introduced by fat infiltration.

Quantitative NMRI and (31)P NMRS indices are reported in the forearms of 24 patients with Duchenne muscular dystrophy (DMD) (6-18 years, 14 non-ambulant) amenable to exon 53 skipping therapy and in 12 age-matched male controls (CONT). Examinations carried out at 3 T comprised multi-slice 17-echo measurements of muscle water T2 and heterogeneity, three-point Dixon imaging of fat fraction in flexor and extensor muscles (FLEX, EXT), and non-localised spectroscopy of phosphate metabolites. We studied four imaging indices, eight metabolic ratios combining ATP, phosphocreatine, phosphomonoesters and phosphodiesters, the cytosolic inorganic phosphate (Pia ) and an alkaline (Pib) pool present in dystrophic muscle, and average pH. All indices differed between DMD and CONT, except for muscle water T2 . Measurements were outside the 95th percentile of age-matched CONT values in over 65% of cases for percentage fat signal (%F), and in 78-100% of cases for all spectroscopic indices. T2 was elevated in one-third of FLEX measurements, whereas %pixels > 39 ms and T2 heterogeneity were abnormal in one-half of the examinations. The FLEX muscles had higher fat infiltration and T2 than EXT muscle groups. All indices, except pH, correlated with patient age, although the correlation was negative for T2 . However, in non-ambulant patients, the correlation with years since loss of ambulation was stronger than the correlation with age, and the slope of evolution per year was steeper after loss of ambulation. All indices except Pi/gATP differed between ambulant and non-ambulant patients; however, T2 and %pixels > 39 ms were highest in ambulant patients, possibly owing to the greater extent of inflammatory processes earlier in the disease. All other indices were worse in non-ambulant subjects. Quantitative measurements obtained from patients at different disease stages covered a broad range of abnormalities that evolved with the disease, and metabolic indices were up to 10-fold above normal from the onset, thus establishing a variety of potential markers for future therapy.

Adult late-onset Pompe disease is most often a slowly progressive limb-girdle and spine extensor muscle dystrophy, due to defective lysosomal acid maltase. With the exception of the few patients who present with a dramatically accelerated clinical course, standard diagnostic imaging fail to detect and evaluate disease progression between two successive visits. In muscle dystrophy of very rapid evolution, like the Duchenne disease, quantitative NMR imaging has successfully demonstrated its capacity to objectivate both disease activity and degenerative changes progression over short follow-up periods. The purpose of this retrospective monocentric open-label study was to investigate whether quantitative NMR imaging can monitor disease progression in adult Pompe patients despite its very slow nature. Quantitative imaging of Pompe patients succeeded in demonstrating that muscle fatty infiltration increased on average by 0.9 %/year, with the hamstring and adductor muscles showing the fastest degradation. Muscle water T2 mapping revealed that 32 % of all muscles had abnormally high T2 in at least one of two successive examinations. When muscle water T2 was abnormal, fatty degenerative changes were further increased by 0.61 %/year. Enzyme replacement therapy resulted in 0.68 %/year slowdown of the muscle fatty infiltration, in both muscles with normal and high T2s.Electronic supplementary materialThe online version of this article (doi:10.1007/s10545-015-9825-9) contains supplementary material, which is available to authorized users.

Objective: To explore the value of nuclear magnetic resonance (NMR) and functional assessments for follow-up of ambulatory and nonambulatory patients with Duchenne muscular dystrophy (DMD).Methods: Twenty-five 53-skippable patients with DMD were included in this study; 15 were nonambulatory at baseline. All patients underwent clinical and functional assessments every 6 months using the Motor Function Measure (MFM), hand grip and key pinch strength, MoviPlate, and NMR spectroscopy and imaging studies.Results: Upper limb distal strength decreased in nonambulatory patients over the period of 1 year; ambulatory patients showed improvement during the same period. The same applied for several NMRS indices, such as phosphocreatine/adenosine triphosphate, which decreased in older patients but increased in younger ambulatory patients. Fat infiltration in the upper limbs increased linearly with age. Almost all NMR and functional assessment results correlated. Conclusions:Our results underscore complementarity of functional and NMR assessments in patients with DMD. Sensitivity to change of various indices may differ according to disease stage. MFM 5 Motor Function Measure; NMR 5 nuclear magnetic resonance; NMRI 5 nuclear magnetic resonance imaging; NMRS 5 nuclear magnetic resonance spectroscopy; PCr 5 phosphocreatine; Pi 5 inorganic phosphate; Pia 5 cytosolic inorganic phosphate; Pib 5 anomalous alkaline pool present in dystrophic muscle; PDE 5 phosphodiester; PME 5 phosphomonoester; TR 5 repetition time.

Muscle mass is particularly relevant to follow during aging, owing to its link with physical performance and autonomy. The objectives of this work were to assess muscle volume (MV) and intramuscular fat (IMF) for all the muscles of the thigh in a large population of young and elderly healthy individuals using magnetic resonance imaging (MRI) to test the effect of gender and age on MV and IMF and to determine the best representative slice for the estimation of MV and IMF. The study enrolled 105 healthy young (range 20-30 years) and older (range 70-80 years) subjects. MRI scans were acquired along the femur length using a three-dimension three-point Dixon proton density-weighted gradient echo sequence. MV and IMF were estimated from all the slices. The effects of age and gender on MV and IMF were assessed. Predictive equations for MV and IMF were established using a single slice at various femur levels for each muscle in order to reduce the analysis process. MV was decreased with aging in both genders, particularly in the quadriceps femoris. IMF was largely increased with aging in men and, to a lesser extent, in women. Percentages of MV decrease and IMF increase with aging varied according to the muscle. Predictive equations to predict MV and IMF from single slices are provided and were validated. This study is the first one to provide muscle volume and intramuscular fat infiltration in all the muscles of the thigh in a large population of young and elderly healthy subjects.

This work has demonstrated the excellent reliability of manual segmentation to assess cross-sectional areas and therefore the volume of individual QF muscles using MRI. It may serve as a basis for a future segmentation consensus of the QF muscles.

Skeletal muscle inflammation/necrosis and fat infiltration are strong indicators of disease activity and progression in many neuromuscular disorders. They can be assessed by muscle T2 relaxometry and water-fat separation techniques, respectively. In the present work, we exploited differences between water and fat T1 and T2 relaxivities by applying a bi-component extended phase graph (EPG) fitting approach to simultaneously quantify the muscle water T2 and fat fraction from standard multi-slice multi-echo (MSME) acquisitions in the presence of stimulated echoes. Experimental decay curves were adjusted to the theoretical model using either an iterative non-negative least-squares (NNLS) procedure or a pattern recognition approach. Twenty-two patients (age, 49 ± 18 years) were selected to cover a large range of muscle fat infiltration. Four cases of chronic or subchronic juvenile dermatomyositis (age, 8 ± 3 years) were investigated before and 3 months following steroid treatment. For control, five healthy volunteers (age, 25 ± 2 years) were recruited. All subjects underwent the MSME sequence and EPG fitting procedure. The EPG fitting algorithm allowed a precise estimation of water T2 and fat fraction in diseased muscle, even in the presence of large B1(+) inhomogeneities. In the whole cohort of patients, there was no overall correlation between water T2 values obtained with the proposed method and the fat fraction estimated inside muscle tissues (R(2) = 0.02). In the patients with dermatomyositis, there was a significant decrease in water T2 (-4.09 ± 3.7 ms) consequent to steroid treatment. The pattern recognition approach resulted in a 20-fold decrease in processing time relative to the iterative NNLS procedure. The fat fraction derived from the EPG fitting approach correlated well with the fat fraction derived from a standard three-point Dixon method (≈1.5% bias). The bi-component EPG fitting analysis is a precise tool to monitor muscle tissue disease activity and is able to handle bias introduced by fat infiltration and B1(+) inhomogeneities.

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