Regional variation of thigh muscle fat infiltration in patients with neuromuscular diseases compared to healthy controls.

BACKGROUND: Chemical shift encoding-based water-fat magnetic resonance imaging (CSE-MRI) measures a quantitative biomarker: the proton density fat fraction (PDFF). The aim was to assess regional and proximo-distal PDFF variations at the thigh in patients with myotonic dystrophy type 2 (DM2), limb-girdle muscular dystrophy type 2A (LGMD2A), and late-onset Pompe disease (LOPD) as compared to healthy controls. METHODS: Seven patients (n=2 DM2, n=2 LGMD2A, n=3 LOPD) and 20 controls were recruited. A 3D-spoiled gradient echo sequence was used to scan the thigh musculature. Muscles were manually segmented to generate mean muscle PDFF. RESULTS: In all three disease entities, there was an increase in muscle fat replacement compared to healthy controls. However, within each disease group, there were patients with a shorter time since symptom onset that only showed mild PDFF elevation (range, 10% to 20%) compared to controls (P≤0.05), whereas patients with a longer period since symptom onset showed a more severe grade of fat replacement with a range of 50% to 70% (P<0.01). Increased PDFF of around 5% was observed for vastus medialis, semimembranosus and gracilis muscles in advanced compared to early DM2. LGMD2A_1 showed an early disease stage with predominantly mild PDFF elevations over all muscles and levels (10.9%±7.1%) compared to controls. The quadriceps, gracilis and biceps femoris muscles showed the highest difference between LGMD2A_1 with 5 years since symptom onset (average PDFF 11.1%±6.9%) compared to LGMD2A_2 with 32 years since symptom onset (average PDFF 66.3%±6.3%). For LOPD patients, overall PDFF elevations were observed in all major hip flexors and extensors (range, 25.8% to 30.8%) compared to controls (range, 1.7% to 2.3%, P<0.05). Proximal-to-distal PDFF highly varied within and between diseases and within controls. The intra-reader reliability was high (reproducibility coefficient ≤2.19%). CONCLUSIONS: By quantitatively measuring muscle fat infiltration at the thigh, we identified candidate muscles for disease monitoring due to their gradual PDFF elevation with longer disease duration. Regional variation between proximal, central, and distal muscle PDFF was high and is important to consider when performing longitudinal MRI follow-ups in the clinical setting or in longitudinal studies.

Association of Thigh Muscle Strength with Texture Features Based on Proton Density Fat Fraction Maps Derived from Chemical Shift Encoding-Based Water-Fat MRI.

PURPOSE: Based on conventional and quantitative magnetic resonance imaging (MRI), texture analysis (TA) has shown encouraging results as a biomarker for tissue structure. Chemical shift encoding-based water-fat MRI (CSE-MRI)-derived proton density fat fraction (PDFF) of thigh muscles has been associated with musculoskeletal, metabolic, and neuromuscular disorders and was demonstrated to predict muscle strength. The purpose of this study was to investigate PDFF-based TA of thigh muscles as a predictor of thigh muscle strength in comparison to mean PDFF. METHODS: 30 healthy subjects (age = 30 ± 6 years; 15 females) underwent CSE-MRI of the lumbar spine at 3T, using a six-echo 3D spoiled gradient echo sequence. Quadriceps (EXT) and ischiocrural (FLEX) muscles were segmented to extract mean PDFF and texture features. Muscle flexion and extension strength were measured with an isokinetic dynamometer. RESULTS: Of the eleven extracted texture features, Variance(global) showed the highest significant correlation with extension strength (p < 0.001, R2adj = 0.712), and Correlation showed the highest significant correlation with flexion strength (p = 0.016, R2adj = 0.658). Multivariate linear regression models identified Variance(global) and sex, but not PDFF, as significant predictors of extension strength (R2adj = 0.709; p < 0.001), while mean PDFF, sex, and BMI, but none of the texture features, were identified as significant predictors of flexion strength (R2adj = 0.674; p < 0.001). CONCLUSIONS: Prediction of quadriceps muscle strength can be improved beyond mean PDFF by means of TA, indicating the capability to quantify muscular fat infiltration patterns.

Texture Features of Proton Density Fat Fraction Maps from Chemical Shift Encoding-Based MRI Predict Paraspinal Muscle Strength.

Texture analysis (TA) has shown promise as a surrogate marker for tissue structure, based on conventional and quantitative MRI sequences. Chemical-shift-encoding-based MRI (CSE-MRI)-derived proton density fat fraction (PDFF) of paraspinal muscles has been associated with various medical conditions including lumbar back pain (LBP) and neuromuscular diseases (NMD). Its application has been shown to improve the prediction of paraspinal muscle strength beyond muscle volume. Since mean PDFF values do not fully reflect muscle tissue structure, the purpose of our study was to investigate PDFF-based TA of paraspinal muscles as a predictor of muscle strength, as compared to mean PDFF. We performed 3T-MRI of the lumbar spine in 26 healthy subjects (age = 30 ± 6 years; 15 females) using a six-echo 3D spoiled gradient echo sequence for chemical-shift-encoding-based water-fat separation. Erector spinae (ES) and psoas (PS) muscles were segmented bilaterally from level L2-L5 to extract mean PDFF and texture features. Muscle flexion and extension strength was measured with an isokinetic dynamometer. Out of the eleven texture features extracted for each muscle, Kurtosis(global) of ES showed the highest significant correlation (r = 0.59, p = 0.001) with extension strength and Variance(global) of PS showed the highest significant correlation (r = 0.63, p = 0.001) with flexion strength. Using multivariate linear regression models, Kurtosis(global) of ES and BMI were identified as significant predictors of extension strength (R2adj = 0.42; p < 0.001), and Variance(global) and Skewness(global) of PS were identified as significant predictors of flexion strength (R2adj = 0.59; p = 0.001), while mean PDFF was not identified as a significant predictor. TA of CSE-MRI-based PDFF maps improves the prediction of paraspinal muscle strength beyond mean PDFF, potentially reflecting the ability to quantify the pattern of muscular fat infiltration. In the future, this may help to improve the pathophysiological understanding, diagnosis, monitoring and treatment evaluation of diseases with paraspinal muscle involvement, e.g., NMD and LBP.

Association of quadriceps muscle, gluteal muscle, and femoral bone marrow composition using chemical shift encoding-based water-fat MRI: a preliminary study in healthy young volunteers.

BACKGROUND: We investigated the composition of the gluteal (gluteus maximus, medius, and minimus) and quadriceps (rectus femoris, vastus lateralis, medialis, and intermedius) muscle groups and its associations with femoral bone marrow using chemical shift encoding-based water-fat magnetic resonance imaging (CSE-MRI) to improve our understanding of muscle-bone interaction. METHODS: Thirty healthy volunteers (15 males, aged 30.5 ± 4.9 years [mean ± standard deviation]; 15 females, aged 29.9 ± 7.1 years) were recruited. A six-echo three-dimensional spoiled gradient-echo sequence was used for 3-T CSE-MRI at the thigh and hip region. The proton density fat fraction (PDFF) of the gluteal and quadriceps muscle groups as well as of the femoral head, neck, and greater trochanter bone marrow were extracted and averaged over both sides. RESULTS: PDFF values of all analysed bone marrow compartments were significantly higher in men than in women (p ≤ 0.047). PDFF values of the analysed muscles showed no significant difference between men and women (p ≥ 0.707). After adjusting for age and body mass index, moderate significant correlations of PDFF values were observed between the gluteal and quadriceps muscle groups (r = 0.670) and between femoral subregions (from r = 0.613 to r = 0.655). Regarding muscle-bone interactions, only the PDFF of the quadriceps muscle and greater trochanter bone marrow showed a significant correlation (r = 0.375). CONCLUSIONS: The composition of the muscle and bone marrow compartments at the thigh and hip region in young, healthy subjects seems to be quite distinct, without evidence for a strong muscle-bone interaction.

Association of thigh and paraspinal muscle composition in young adults using chemical shift encoding-based water-fat MRI.

BACKGROUND: Paraspinal and thigh muscles comprise the major muscle groups of the body. We investigated the composition of the psoas, erector spinae, quadriceps femoris and hamstring muscle groups and their association to each other using chemical shift encoding-based water-fat magnetic resonance imaging (MRI) in adult volunteers. Our aim was to elucidate fat distribution patterns within these muscle groups. METHODS: Thirty volunteers [15 males, age: 30.5±4.9 years, body mass index (BMI): 27.6±2.8 kg/m2 and 15 females, age: 29.9±7.0 years, BMI: 25.8±1.4 kg/m2] were recruited for this study. A six-echo 3D spoiled gradient echo sequence was used for chemical shift encoding-based water-fat separation at the lumbar spine and bilateral thigh. Proton density fat fraction (PDFF), cross-sectional area (CSA) and contractile mass index (CMI) of the psoas, erector spinae, quadriceps femoris and hamstring muscle groups were determined bilaterally and averaged over both sides. RESULTS: CSA and CMI values calculated for the erector spinae, psoas, quadriceps and hamstring muscle groups showed significant differences between men and women (P<0.05). With regard to PDFF measurement only the erector spinae showed significant differences between men and women (9.5%±2.4% vs. 11.7%±2.8%, P=0.015). The CMI of the psoas muscle as well as the erector spinae muscle showed significant correlations with the quadriceps muscle (r=0.691, P<0.0001 and r=0.761, P<0.0001) and the hamstring group (r=0.588, P=0.001 and r=0.603, P<0.0001). CONCLUSIONS: CMI values of the erector spinae and psoas muscles were associated with those of the quadriceps femoris and hamstring musculature. These findings suggest a concordant spatial fat accumulation within the analyzed muscles in young adults and warrants further investigations in ageing and diseased muscle.

Correction to: Associations of thigh muscle fat infiltration with isometric strength measurements based on chemical shift encoding-based water-fat magnetic resonance imaging.

After publication of this article [1], it is noticed it contained some errors in the Methods section.

Associations of thigh muscle fat infiltration with isometric strength measurements based on chemical shift encoding-based water-fat magnetic resonance imaging.

BACKGROUND: Assessment of the thigh muscle fat composition using magnetic resonance imaging (MRI) can provide surrogate markers in subjects suffering from various musculoskeletal disorders including knee osteoarthritis or neuromuscular diseases. However, little is known about the relationship with muscle strength. Therefore, we investigated the associations of thigh muscle fat with isometric strength measurements. METHODS: Twenty healthy subjects (10 females; median age 27 years, range 22-41 years) underwent chemical shift encoding-based water-fat MRI, followed by bilateral extraction of the proton density fat fraction (PDFF) and calculation of relative cross-sectional area (relCSA) of quadriceps and ischiocrural muscles. Relative maximum voluntary isometric contraction (relMVIC) in knee extension and flexion was measured with a rotational dynamometer. Correlations between PDFF, relCSA, and relMVIC were evaluated, and multivariate regression was applied to identify significant predictors of muscle strength. RESULTS: Significant correlations between the PDFF and relMVIC were observed for quadriceps and ischiocrural muscles bilaterally (p = 0.001 to 0.049). PDFF, but not relCSA, was a statistically significant (p = 0.001 to 0.049) predictor of relMVIC in multivariate regression models, except for left-sided relMVIC in extension. In this case, PDFF (p = 0.005) and relCSA (p = 0.015) of quadriceps muscles significantly contributed to the statistical model with R2adj = 0.548. CONCLUSION: Chemical shift encoding-based water-fat MRI could detect changes in muscle composition by quantifying muscular fat that correlates well with both extensor and flexor relMVIC of the thigh. Our results help to initiate early, individualised treatments to maintain or improve muscle function in subjects who do not or not yet show pathological fatty muscle infiltration.

Paraspinal Muscle DTI Metrics Predict Muscle Strength.

BACKGROUND: The paraspinal muscles play an important role in the onset and progression of lower back pain. It would be of clinical interest to identify imaging biomarkers of the paraspinal musculature that are related to muscle function and strength. Diffusion tensor imaging (DTI) enables the microstructural examination of muscle tissue and its pathological changes. PURPOSE: To investigate associations of DTI parameters of the lumbar paraspinal muscles with isometric strength measurements in healthy volunteers. STUDY TYPE: Prospective. SUBJECTS: Twenty-one healthy subjects (12 male, 9 female; age = 30.1 ± 5.6 years; body mass index [BMI] = 27.5 ± 2.6 kg/m2 ) were recruited. FIELD STRENGTH/SEQUENCE: 3 T/single-shot echo planar imaging (ss-EPI) DTI in 24 directions; six-echo 3D spoiled gradient echo sequence for chemical shift encoding-based water-fat separation. ASSESSMENT: Paraspinal muscles at the lumbar spine were examined. Erector spinae muscles were segmented bilaterally; cross-sectional area (CSA), proton density fat fraction (PDFF), and DTI parameters were calculated. Muscle flexion and extension maximum isometric torque values [Nm] at the back were measured with an isokinetic dynamometer and the ratio of extension to flexion strength (E/F) calculated. STATISTICAL TESTS: Pearson correlation coefficients; multivariate regression models. RESULTS: Significant positive correlations were found between the ratio of extension to flexion (E/F) strength and mean diffusivity (MD) (P = 0.019), RD (P = 0.02) and the eigenvalues (λ1: P = 0.026, λ2: P = 0.033, λ3: P = 0.014). In multivariate regression models λ3 of the erector spinae muscle λ3 and gender remained statistically significant predictors of E/F (R2adj = 0.42, P = 0.003). DATA CONCLUSION: DTI allowed the identification of muscle microstructure differences related to back muscle function that were not reflected by CSA and PDFF. DTI may potentially track subtle changes of back muscle tissue composition. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:816-823.

Association of paraspinal muscle water-fat MRI-based measurements with isometric strength measurements.

OBJECTIVES: Chemical shift encoding-based water-fat MRI derived proton density fat fraction (PDFF) of the paraspinal muscles has been emerging as a surrogate marker in subjects with sarcopenia, lower back pain, injuries and neuromuscular disorders. The present study investigates the performance of paraspinal muscle PDFF and cross-sectional area (CSA) in predicting isometric muscle strength. METHODS: Twenty-six healthy subjects (57.7% women; age: 30 ± 6 years) underwent 3T axial MRI of the lumbar spine using a six-echo 3D spoiled gradient echo sequence for chemical shift encoding-based water-fat separation. Erector spinae and psoas muscles were segmented bilaterally from L2 level to L5 level to determine CSA and PDFF. Muscle flexion and extension maximum isometric torque values [Nm] at the back were measured with an isokinetic dynamometer. RESULTS: Significant correlations between CSA and muscle strength measurements were observed for erector spinae muscle CSA (r = 0.40; p = 0.044) and psoas muscle CSA (r = 0.61; p = 0.001) with relative flexion strength. Erector spinae muscle PDFF correlated significantly with relative muscle strength (extension: r = -0.51; p = 0.008; flexion: r = -0.54; p = 0.005). Erector spinae muscle PDFF, but not CSA, remained a statistically significant (p < 0.05) predictor of relative extensor strength in multivariate regression models (R2adj = 0.34; p = 0.002). CONCLUSIONS: PDFF measurements improved the prediction of paraspinal muscle strength beyond CSA. Therefore, chemical shift encoding-based water-fat MRI may be used to detect subtle changes in the paraspinal muscle composition. KEY POINTS: • We investigated the association of paraspinal muscle fat fraction based on chemical shift encoding-based water-fat MRI with isometric strength measurements in healthy subjects. • Erector spinae muscle PDFF correlated significantly with relative muscle strength. • PDFF measurements improved prediction of paraspinal muscle strength beyond CSA.

Thigh muscle segmentation of chemical shift encoding-based water-fat magnetic resonance images: The reference database MyoSegmenTUM.

Magnetic resonance imaging (MRI) can non-invasively assess muscle anatomy, exercise effects and pathologies with different underlying causes such as neuromuscular diseases (NMD). Quantitative MRI including fat fraction mapping using chemical shift encoding-based water-fat MRI has emerged for reliable determination of muscle volume and fat composition. The data analysis of water-fat images requires segmentation of the different muscles which has been mainly performed manually in the past and is a very time consuming process, currently limiting the clinical applicability. An automatization of the segmentation process would lead to a more time-efficient analysis. In the present work, the manually segmented thigh magnetic resonance imaging database MyoSegmenTUM is presented. It hosts water-fat MR images of both thighs of 15 healthy subjects and 4 patients with NMD with a voxel size of 3.2x2x4 mm3 with the corresponding segmentation masks for four functional muscle groups: quadriceps femoris, sartorius, gracilis, hamstrings. The database is freely accessible online at https://osf.io/svwa7/?view_only=c2c980c17b3a40fca35d088a3cdd83e2. The database is mainly meant as ground truth which can be used as training and test dataset for automatic muscle segmentation algorithms. The segmentation allows extraction of muscle cross sectional area (CSA) and volume. Proton density fat fraction (PDFF) of the defined muscle groups from the corresponding images and quadriceps muscle strength measurements/neurological muscle strength rating can be used for benchmarking purposes.

Association of Quadriceps Muscle Fat With Isometric Strength Measurements in Healthy Males Using Chemical Shift Encoding-Based Water-Fat Magnetic Resonance Imaging.

Magnetic resonance-based assessment of quadriceps muscle fat has been proposed as surrogate marker in sarcopenia, osteoarthritis, and neuromuscular disorders. We presently investigated the association of quadriceps muscle fat with isometric strength measurements in healthy males using chemical shift encoding-based water-fat magnetic resonance imaging. Intermuscular adipose tissue fraction and intramuscular proton density fat fraction correlated significantly (P < 0.05) with isometric strength (up to r = -0.83 and -0.87, respectively). Reproducibility of intermuscular adipose tissue fraction and intramuscular proton density fat fraction was 1.5% and 5.7%, respectively.