Prevalence of and Impact on the Outcome of Myosteatosis in Patients with Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

BACKGROUND: Limited data exist on the prevalence of myosteatosis (i.e., excess accumulation of fat in skeletal muscles) in hepatocellular carcinoma (HCC) patients, and no systematic review or meta-analysis has been conducted in this context. METHODS: We searched for articles published from inception until November 2023 to assess the prevalence of myosteatosis in patients with HCC. RESULTS: Ten studies with 3316 patients focusing on myosteatosis and HCC were included. The overall prevalence of myosteatosis in HCC patients was 50% [95% Confidence Interval (CI): 35-65%]. Using the body mass index-based criteria (two studies), the prevalence was 34%, while gender-based criteria (eight studies) yielded 54% (p = 0.31). In Asian studies (n = 8), the prevalence was 45%, compared to 69% in non-Asian countries (two studies) (p = 0.02). For viral-associated HCC (eight studies), the prevalence was 49%, rising to 65% in non-alcoholic fatty liver disease-associated cases (three studies) and 86% in alcoholic liver disease-associated cases (three studies) (p < 0.01). The prevalence of myosteatosis was higher in Child-Pugh class C (3 studies, 91%) than in A (7 studies, 73%) or B (6 studies, 50%) (p = 0.02), but with no difference between Barcelona Clinic Liver Cancer stage A (3 studies, 66%), B (4 studies, 44%) and C (3 studies, 62%) (p = 0.80). Patients with myosteatosis had a significantly higher mortality (six studies) (Relative Risk: 1.35 (95%CI: 1.13-1.62, p < 0.01). CONCLUSION: The prevalence of myosteatosis is high in HCC patients and is associated with more severe liver disease and higher mortality rates.

Daily blood flow restriction does not preserve muscle mass and strength during 2 weeks of bed rest.

We measured the impact of blood flow restriction on muscle protein synthesis rates, muscle mass and strength during 2 weeks of strict bed rest. Twelve healthy, male adults (age: 24 ± 3 years, body mass index: 23.7 ± 3.1 kg/m2 ) were subjected to 14 days of strict bed rest with unilateral blood flow restriction performed three times daily in three 5 min cycles (200 mmHg). Participants consumed deuterium oxide and we collected blood and saliva samples throughout 2 weeks of bed rest. Before and immediately after bed rest, lean body mass (dual-energy X-ray absorptiometry scan) and thigh muscle volume (magnetic resonance imaging scan) were assessed in both the blood flow restricted (BFR) and control (CON) leg. Muscle biopsies were collected and unilateral muscle strength (one-repetition maximum; 1RM) was assessed for both legs before and after the bed rest period. Bed rest resulted in 1.8 ± 1.0 kg lean body mass loss (P < 0.001). Thigh muscle volume declined from 7.1 ± 1.1 to 6.7 ± 1.0 L in CON and from 7.0 ± 1.1 to 6.7 ± 1.0 L in BFR (P < 0.001), with no differences between treatments (P = 0.497). In addition, 1RM leg extension strength decreased from 60.2 ± 10.6 to 54.8 ± 10.9 kg in CON and from 59.2 ± 12.1 to 52.9 ± 12.0 kg in BFR (P = 0.014), with no differences between treatments (P = 0.594). Muscle protein synthesis rates during bed rest did not differ between the BFR and CON leg (1.11 ± 0.12 vs. 1.08 ± 0.13%/day, respectively; P = 0.302). Two weeks of bed rest substantially reduces skeletal muscle mass and strength. Blood flow restriction during bed rest does not modulate daily muscle protein synthesis rates and does not preserve muscle mass or strength. KEY POINTS: Bed rest, often necessary for recovery from illness or injury, leads to the loss of muscle mass and strength. It has been postulated that blood flow restriction may attenuate the loss of muscle mass and strength during bed rest. We investigated the effect of blood flow restriction on muscle protein synthesis rates, muscle mass and strength during 2 weeks of strict bed rest. Blood flow restriction applied during bed rest does not modulate daily muscle protein synthesis rates and does not preserve muscle mass or strength. Blood flow restriction is not effective in preventing muscle atrophy during a prolonged period of bed rest.

Mitochondrial-derived microprotein MOTS-c attenuates immobilization-induced skeletal muscle atrophy by suppressing lipid infiltration.

Mitochondrial open reading frame of the 12S ribosomal RNA type-c (MOTS-c), a mitochondrial microprotein, has been described as a novel regulator of glucose and lipid metabolism. In addition to its role as a metabolic regulator, MOTS-c prevents skeletal muscle atrophy in high fat-fed mice. Here, we examined the preventive effect of MOTS-c on skeletal muscle mass, using an immobilization-induced muscle atrophy model, and explored its underlying mechanisms. Male C57BL/6J mice (10 wk old) were randomly assigned to one of the three experimental groups: nonimmobilization control group (sterilized water injection), immobilization control group (sterilized water injection), and immobilization and MOTS-c-treated group (15 mg/kg/day MOTS-c injection). We used casting tape for the immobilization experiment. After 8 days of the experimental period, skeletal muscle samples were collected and used for Western blotting, RNA sequencing, and lipid and collagen assays. Immobilization reduced ∼15% of muscle mass, whereas MOTS-c treatment attenuated muscle loss, with only a 5% reduction. MOTS-c treatment also normalized phospho-AKT, phospho-FOXO1, and phospho-FOXO3a expression levels and reduced circulating inflammatory cytokines, such as interleukin-1b (IL-1ß), interleukin-6 (IL-6), chemokine C-X-C motif ligand 1 (CXCL1), and monocyte chemoattractant protein 1 (MCP-1), in immobilized mice. Unbiased RNA sequencing and its downstream analyses demonstrated that MOTS-c modified adipogenesis-modulating gene expression within the peroxisome proliferator-activated receptor (PPAR) pathway. Supporting this observation, muscle fatty acid levels were lower in the MOTS-c-treated group than in the casted control mice. These results suggest that MOTS-c treatment inhibits skeletal muscle lipid infiltration by regulating adipogenesis-related genes and prevents immobilization-induced muscle atrophy.NEW & NOTEWORTHY MOTS-c, a mitochondrial microprotein, attenuates immobilization-induced skeletal muscle atrophy. MOTS-c treatment improves systemic inflammation and skeletal muscle AKT/FOXOs signaling pathways. Furthermore, unbiased RNA sequencing and subsequent assays revealed that MOTS-c prevents lipid infiltration in skeletal muscle. Since lipid accumulation is one of the common pathologies among other skeletal muscle atrophies induced by aging, obesity, cancer cachexia, and denervation, MOTS-c treatment could be effective in other muscle atrophy models as well.

Association between severity of the cervical foraminal stenosis and paraspinal muscle parameters in patients undergoing anterior cervical discectomy and fusion.

OBJECTIVE: The cervical multifidus and rotatores muscles are innervated by the posterior rami of the spinal nerves of the corresponding level, and it has been hypothesized that cervical foraminal stenosis (CFS) affecting the spinal nerves results in changes in these muscles. The purpose of this study was to evaluate the relationship between the severity of CFS and fat infiltration (FI) of the multifidus and rotatores muscles. METHODS: Patients who received preoperative cervical MRI, underwent anterior cervical decompression and fusion between 2015 and 2018, and met inclusion and exclusion criteria were included. Multifidus and rotatores muscles were segmented bilaterally from C3 to C7, and the percent FI was measured using custom-written MATLAB software. The severity of the CFS was assessed by the Kim classification. Multivariable linear mixed models were conducted and adjusted for age, sex, BMI, and repeated measures. RESULTS: In total, 149 patients were included. Linear mixed modeling results showed that a more severe CFS at C3-4 was correlated with a greater FI of the multifidus and rotatores muscles at C4 (estimate 0.034, 95% CI 0.003-0.064; p = 0.031), a more severe CFS at C4-5 was correlated with a greater FI of the multifidus and rotatores muscles at C5 (estimate 0.037, 95% CI 0.015-0.057; p < 0.001), a more severe CFS at C5-6 was correlated with a greater FI of the multifidus and rotatores muscles at C6 (estimate 0.041, 95% CI 0.019-0.062; p < 0.001) and C7 (estimate 0.035, 95% CI 0.012-0.058; p = 0.003), and a more severe CFS at C6-7 was correlated with a greater FI of the multifidus and rotatores muscles at C7 (estimate 0.049, 95% CI 0.027-0.071; p < 0.001). CONCLUSIONS: These results demonstrated level- and side-specific correlations between the FI of the multifidus and rotatores muscles and severity of CFS. Given the segmental innervation of the multifidus and rotatores muscles, the authors hypothesize that the observed increased FI could be reflective of changes due to muscle denervation from CFS.

Percentiles for paraspinal muscle parameters at the L3 vertebra level in patients undergoing lumbar computed tomography scanning.

BACKGROUND: Computed tomography (CT) is the gold standard for analyzing muscle parameters. PURPOSE: To clarify sex-specific paraspinal muscle area (PMA), paraspinal muscle index (PMI), and muscle fat infiltration (MFI) percentiles. MATERIAL AND METHODS: This was a cross-sectional study of 760 individuals (45% men; age range = 20-92 years; mean age = 53.4 ± 21.1 years) with a body mass index (BMI) in the range of 16.4-38.1 kg/m2. CT scans were retrospectively used to establish PMA, PMI, and MFI at L3 level using a deep-learning (DL) tool. Sex-specific distributions for these parameters were assessed based on associations between age/BMI and individual muscle parameters, after which age- and BMI-specific percentile estimates were determined. The 5th percentile was regarded as the cutoff for PMA/PMI, and the 95th percentile was regarded as the cutoff for MFI. RESULTS: Sex-specific PMA, PMI, and MFI cutoffs in the paraspinal muscles group were 52.9 cm2, 15.0 cm2/m2, and 33.3%, respectively, in men, and 33.2 cm2, 9.5 cm2/m2, and 41.2% in women. Age was moderately negatively correlated with PMA and was strongly negatively correlated with PMI, but age was strongly positively correlated with MFI. BMI was moderately positively correlated with PMA/PMI in men and strongly positively correlated in women; BMI was weakly positively correlated with MFI, thus enabling the establishment of age- and BMI-specific cutoff percentiles. CONCLUSION: Sex-specific PMA, PMI, and MFI percentiles and age- and BMI-specific cutoff values for these parameters were successfully established for an outpatient population.

Fat infiltration in the thigh muscles is associated with symptomatic spinal stenosis and reduced physical functioning in adults with achondroplasia.

BACKGROUND: Symptomatic spinal stenosis is a prevalent complication in adults with achondroplasia. Increased muscle fat infiltration (MFI) and reduced thigh muscle volumes have also been reported, but the pathophysiology is poorly understood. We explored whether the increased MFI and reduced thigh muscle volumes were associated with the presence of symptomatic spinal stenosis and physical functioning. METHODS: MFI and thigh muscle volumes were assessed by MRI in 40 adults with achondroplasia, and compared to 80 average-statured controls, matched for BMI, gender, and age. In achondroplasia participants, the six-minute walk-test (6MWT), the 30-s sit-to-stand test (30sSTS), and a questionnaire (the IPAQ) assessed physical functioning. RESULTS: Symptomatic spinal stenosis was present in 25 of the participants (the stenosis group), while 15 did not have stenosis (the non-stenosis group). In the stenosis group, 84% (21/25) had undergone at least one spinal decompression surgery. The stenosis group had significantly higher MFI than the non-stenosis group, with an age-, gender and BMI-adjusted difference in total MFI of 3.3 percentage points (pp) (95% confidence interval [CI] 0.04 to 6.3 pp; p = 0.03). Compared to matched controls, the mean age-adjusted difference was 3.3 pp (95% CI 1.7 to 4.9 pp; p < 0.01). The non-stenosis group had MFI similar to controls (age-adjusted difference - 0.9 pp, 95% CI - 3.4 to 1.8 pp; p = 0.51). MFI was strongly correlated with the 6MWT (r = - 0.81, - 0.83, and - 0.86; all p-values < 0.01), and moderately correlated with the 30sSTS (r = - 0.56, - 0.57, and - 0.59; all p-values < 0.01). There were no significant differences in muscle volumes or physical activity level between the stenosis group and the non-stenosis group. CONCLUSION: Increased MFI in the thigh muscles was associated with the presence of symptomatic spinal stenosis, reduced functional walking capacity, and reduced lower limb muscle strength. The causality between spinal stenosis, accumulation of thigh MFI, and surgical outcomes need further study. We have demonstrated that MRI might serve as an objective muscle biomarker in future achondroplasia studies, in addition to functional outcome measures. The method could potentially aid in optimizing the timing of spinal decompression surgery and in planning of post-surgery rehabilitation.

Adverse muscle composition is a significant risk factor for all-cause mortality in NAFLD.

Background & Aims: Adverse muscle composition (MC) (i.e., low muscle volume and high muscle fat) has previously been linked to poor functional performance and comorbidities in non-alcoholic fatty liver disease (NAFLD). In this study we aimed to investigate associations of all-cause mortality with liver fat, NAFLD, and MC in the UK Biobank imaging study. Methods: Magnetic resonance images of 40,174 participants were analyzed for liver proton density fat fraction (PDFF), thigh fat-free muscle volume (FFMV) z-score, and muscle fat infiltration (MFI) using the AMRA® Researcher. Participants with NAFLD were sex-, age-, and BMI-matched to participants without NAFLD with low alcohol consumption. Adverse MC was identified using previously published cut-offs. All-cause mortality was investigated using Cox regression. Models within NAFLD were crude and subsequently adjusted for sex, age, BMI (M1), hand grip strength, physical activity, smoking, alcohol (M2), and previous cancer, coronary heart disease, type 2 diabetes (M3). Results: A total of 5,069 participants had NAFLD. During a mean (±SD) follow-up of 3.9 (±1.4) years, 150 out of the 10,138 participants (53% men, age 64.4 [±7.6] years, BMI 29.7 [±4.4] kg/m2) died. In the matched dataset, neither NAFLD nor liver PDFF were associated with all-cause mortality, while all MC variables achieved significance. Within NAFLD, adverse MC, MFI and FFMV z-score were significantly associated with all-cause mortality and remained so in M1 and M2 (crude hazard ratios [HRs] 2.84, 95% CI 1.70-4.75, p <0.001; 1.15, 95% CI 1.07-1.24, p <0.001; 0.70, 95% CI 0.55-0.88, p <0.001). In M3, the relationship was attenuated for adverse MC and FFMV z-score (adjusted HRs 1.72, 95% CI 1.00-2.98, p = 0.051; 0.77, 95% CI 0.58-1.02, p = 0.069) but remained significant for MFI (adjusted HR 1.13, 95% CI 1.01-1.26, p = 0.026). Conclusions: Neither NAFLD nor liver PDFF was predictive of all-cause mortality. Adverse MC was a strong predictor of all-cause mortality in individuals with NAFLD. Impact and implications: Individuals with fatty liver disease and poor muscle health more often suffer from poor functional performance and comorbidities. This study shows that they are also at a higher risk of dying. The study results indicate that measuring muscle health (the patient's muscle volume and how much fat they have in their muscles) could help in the early detection of high-risk patients and enable targeted preventative care.

Muscle fat infiltration in chronic kidney disease: a marker related to muscle quality, muscle strength and sarcopenia.

Muscle fat infiltration (MFI) also known as myosteatosis refers to any deposit of lipids found in the skeletal muscle. MFI is preferably assessed by image-based methods like computed tomography (CT), magnetic resonance image (MRI) and ultrasound, normally from muscle groups located in the legs, arms and in the trunk. MFI is understood as a marker of muscle quality, where a muscle with higher fat deposition has lower contraction power and capacity to produce force per unit of muscle mass. This concept supports the hypothesis that a decrease in muscle strength is not always explained by a decrease in muscle mass, but also by other factors, including lipid deposition in the muscle. In the general population, MFI is associated with older age, physical inactivity and with insulin resistance and inflammation. In chronic kidney disease (CKD), MFI has been associated with a decrease in muscle strength and impaired muscle quality as well as with metabolic abnormalities, cardiovascular disease and increased mortality. Interventions aimed at reducing MFI in CKD are incipient, but it seems that guided exercise can ameliorate muscle quality in patients on hemodialysis. The aim of this narrative review about MFI in CKD is to draw attention to a still not often addressed complication in CKD. We conclude that more studies are warranted to investigate mechanisms and factors promoting MFI in CKD. Thus, clinical trials aimed at understanding the type, frequency and intensity of exercise that can diminish MFI and improve the clinical condition of the patients are needed.

Morphological Changes of Deep Extensor Neck Muscles in Relation to the Maximum Level of Cord Compression and Canal Compromise in Patients With Degenerative Cervical Myelopathy.

STUDY DESIGN: Cross-sectional study. OBJECTIVES: To examine the relationship between morphological changes of the deep extensor neck muscles in patients with degenerative cervical myelopathy (DCM) and the level of maximum spinal cord compression (MSCC) and canal compromise (MCC). A secondary objective was to examine the relationship between muscle morphological changes with neck pain and functional scores related to neck pain and interference. METHODS: A total of 171 patients with DCM were included. Total cross-sectional area (CSA), functional CSA (fat free area, FCSA), ratio of FCSA/CSA (fatty infiltration) and asymmetry of the multifidus (MF) and semispinalis cervicis (SCer) together, and cervical muscle as a group (eg, MF, SCer, semispinalis capitis, splenius capitis) were obtained from T2-weighted axial MR images at mid-disc, at the level of maximum cord compression and the level below. The relationship between the muscle parameters of interest, MSCC, MCC and functional scores including the Neck Disability Index (NDI) was assessed using multivariate linear regression models, adjusting for age, body mass index and sex. RESULTS: Greater MF + Scer fatty infiltration was associated with greater MCC (P = .032) and MSCC (P = .049) at the same level. Greater asymmetry in MF + SCer CSA was also associated with greater MCC (P = .006). Similarly, greater asymmetry in FCSA and FCSA/CSA of the entire extensor muscle was associated with greater MCC (P = .011, P = .013). There was a negative association between asymmetry in FCSA MF + SCer, FCSA/CSA MF + SCer and FCSA/CSA group muscles with NDI score at the level below. CONCLUSION: Greater MCC is associated with increased fatty infiltration and greater asymmetry of the deep cervical muscles in patients with DCM. A negative association between muscle asymmetry and NDI scores was also observed which has implications for clinical prediction around axial neck pain.

Skeletal Myosteatosis is Associated with Systemic Inflammation and a Loss of Muscle Bioenergetics in Stable COPD.

Background: Common features among patients with more advanced chronic obstructive pulmonary disease (COPD) are systemic inflammation and a loss of both muscle mass and normal muscle composition. In the present study, we investigated COPD subjects to better understand how thigh muscle fat infiltration (MFI) and energy metabolism relate to each other and to clinical features of COPD with emphasis on systemic inflammation. Methods: Thirty-two Caucasians with stable COPD were investigated using questionnaires, lung function tests, blood analysis and magnetic resonance imaging (MRI) for analysis of body- and thigh muscle composition. Bioenergetics in the resting thigh muscle, expressed as the PCr/Pi ratio, were analysed using 31phosphorus magnetic resonance spectroscopy (31P-MRS). Results: Based on the combination of the MFI adjusted for sex (MFIa) and the thigh fat-tissue free muscle volume, expressed as the deviation from the expected muscle volume of a matched virtual control group (FFMVvcg), all COPD subjects displayed abnormally composed thigh muscles. Clinical features of increased COPD severity, including a decrease of blood oxygenation (r = -0.44, p < 0.05) and FEV1/FVC ratio, reflecting airway obstruction (r = -0.53, p < 0.01) and an increase of COPD symptoms (r = 0.37, p < 0.05) and breathing frequency at rest (r = 0.41, p < 0.05), were all associated with a raise of the PCr/Pi ratio in the thigh muscle. Increased MFIa of the thigh muscle correlated positively with markers of systemic inflammation (white blood cell count, r = 0.41, p < 0.05; fibrinogen, r = 0.44, p < 0.05), and negatively with weekly physical activity (r = -0.40, p < 0.05) and the PCr/Pi ratio in the resting thigh muscle (r = -0.41, p < 0.05). Conclusion: The present study implies a link between systemic inflammation, excessive MFI and a loss of bioenergetics in subjects with stable COPD.

Improving the measurement of intrinsic foot muscle morphology and composition from high-field (7T) magnetic resonance imaging.

Magnetic resonance imaging (MRI) can be used to quantify intrinsic foot muscle morphology and composition. Due to the high spatial resolution required to adequately capture the architecturally complex anatomy, manual segmentation is time consuming and not clinically feasible. The aim of this study was to evaluate if a reduced number of MRI slices can be used to accurately estimate intrinsic foot muscle volume and composition. A three-dimensional 2-point Dixon sequence of the whole foot was acquired at 7-Tesla for thirteen asymptomatic individuals and twenty individuals with plantar heel pain. Slice intervals of 2, 3, 5, 10, 15 and 30 were used to calculate alternative muscle volume and composition, and were compared to reference values calculated from every available slice. Agreement between methods was assessed by calculating mean differences and 95% limits of agreement, and inspection of Bland -Altman plots. In both groups, slice intervals of 2, 3 and 5 provided excellent precision for all muscles (measurement error < 1%). Larger slice intervals of 10, 15 and 30 provided excellent precision for some muscles, but for other muscles (e.g. small forefoot muscles), error was up to 7.3%. Bland-Altman plots showed no systematic measurement bias. This study provides a quantitative basis for selecting a reduced number of slices to measure intrinsic foot muscle volume and composition from MRI. A slice interval of 10 may provide a balance between efficiency (36 mins vs. 6 h) and accuracy (error < 2.4%) across all intrinsic foot muscles in asymptomatic individuals and those with plantar heel pain.

Towards defining muscular regions of interest from axial magnetic resonance imaging with anatomical cross-reference: a scoping review of lateral hip musculature.

BACKGROUND: Measures of hip muscle morphology and composition (e.g., muscle size and fatty infiltration) are possible with magnetic resonance imaging (MRI). Standardised protocols or guidelines do not exist for evaluation of hip muscle characteristics, hindering reliable and valid inter-study analysis. This scoping review aimed to collate and synthesise MRI methods for measuring lateral hip muscle size and fatty infiltration to inform the future development of standardised protocols. METHODS: Five electronic databases (Medline, CINAHL, Embase, SportsDISCUS and AMED) were searched. Healthy or musculoskeletal pain populations that used MRI to assess lateral hip muscle size and fatty infiltration were included. Lateral hip muscles of interest included tensor fascia late (TFL), gluteus maximus, gluteus medius, and gluteus minimus. Data on MRI parameters, axial slice location, muscle size and fatty infiltrate measures were collected and analysed. Cross referencing for anatomical locations were made between MRI axial slice and E-12 anatomical plastinate sections. RESULTS: From 2684 identified publications, 78 studies contributed data on volume (n = 31), cross sectional area (CSA) (n = 24), and fatty infiltration (n = 40). Heterogeneity was observed for MRI parameters and anatomical boundaries scrutinizing hip muscle size and fatty infiltration. Seven single level axial slices were identified that provided consistent CSA measurement, including three for both gluteus maximus and TFL, and four for both gluteus medius and minimus. For assessment of fatty infiltration, six axial slice locations were identified including two for TFL, and four for each of the gluteal muscles. CONCLUSIONS: Several consistent anatomical levels were identified for single axial MR slice to facilitate muscle size and fatty infiltration muscle measures at the hip, providing the basis for reliable and accurate data synthesis and improvements in the validity of future between studies analyses. This work establishes the platform for standardised methods for the MRI assessment of lateral hip musculature and will aid in the examination of musculoskeletal conditions around the hip joint. Further studies into whole muscle measures are required to further optimise methodological parameters for hip muscle assessment.

Change in Lumbar Muscle Size and Composition on MRI with Long-Duration Spaceflight.

Prolonged microgravity results in muscle atrophy, especially among the anti-gravity spinal muscles. How individual paravertebral muscle groups change in size and composition with spaceflight needs further exploration. This study investigates lumbar spine musculature changes among six crewmembers on long-duration space missions using non-invasive measurement of muscle changes with magnetic resonance imaging (MRI). Pre- and post-flight lumbar images were analyzed for changes in cross-sectional area, volume, and fat infiltration of the psoas (PS), quadratus lumborum (QL), and paraspinal [erector spinae and multifidus (ES + MF)] muscles using mixed models. Crewmembers used onboard exercise equipment, including a cycle ergometer (CEVIS), treadmill (T2/COLBERT), and the advanced resistive exercise device (ARED). Correlations were used to assess muscle changes related to exercise modality. There was substantial variability in muscle changes across crewmembers but collectively a significant decrease in paraspinal area (- 9.0 ± 4.8%, p = 0.04) and a significant increase in QL fat infiltration (7.3 ± 4.1%, p = 0.05). More CEVIS time may have protected against PS volume loss (p = 0.05) and PS fat infiltration (p < 0.01), and more ARED usage may have protected against ES + MF volume loss (p = 0.05). Crewmembers using modern onboard exercise equipment may be less susceptible to muscle changes. However, variability between crewmembers and muscle size and quality losses suggest additional research is needed to ensure in-flight countermeasures preserve muscle health.

Fatty Liver Index and Skeletal Muscle Density.

Accumulation of fat in the liver and skeletal muscle is associated with obesity and poor health outcomes. Liver steatosis is a characteristic of non-alcoholic fatty liver disease (NAFLD) and myosteatosis, of poor muscle quality in sarcopenia. In this study of 403 men (33-96 years), we investigated associations between the fatty liver index (FLI) and muscle density, as markers of fat accumulation in these organs. We also investigated associations between the FLI and parameters of sarcopenia, including DXA-derived appendicular lean mass (ALM) and handgrip strength by dynamometry. Muscle density was measured using pQCT at the radius and tibia. FLI was calculated from BMI, waist circumference, and levels of triglycerides and gamma-glutamyltransferase. There was a pattern of decreasing muscle density across increasing quartiles of FLI. After adjusting for age and lifestyle, mean radial muscle density in Q4 was 2.1% lower than Q1 (p < 0.001) and mean tibial muscle density was 1.8% lower in Q3 and 3.0% lower in Q4, compared to Q1 (p = 0.022 and < 0.001, respectively). After adjusting for age and sedentary lifestyle, participants in the highest FLI quartile were sixfold more likely to have sarcopenia. In conclusion, our results suggest that fat accumulation in the liver co-exists with fat infiltration into skeletal muscle.

Adverse muscle composition predicts all-cause mortality in the UK Biobank imaging study.

BACKGROUND: Adverse muscle composition (MC) as measured by magnetic resonance imaging has previously been linked to poor function, comorbidity, and increased hospitalization. The aim of this study was to investigate if adverse MC predicts all-cause mortality using data from UK Biobank. METHODS: There were 40 178 participants scanned using a 6 min magnetic resonance imaging protocol. Images were analysed for thigh fat-tissue free muscle volume and muscle fat infiltration (MFI) using AMRA® Researcher (AMRA Medical, Linköping, Sweden). For each participant, a sex, weight, and height invariant muscle volume z-score was calculated. Participants were partitioned into four MC groups: (i) normal MC, (ii) only low muscle volume [<25th percentile for muscle volume z-score (population wide)], (iii) only high MFI [>75th percentile (population wide, sex-specific)], and (iv) adverse MC (low muscle volume z-score and high MFI). Association of MC groups with mortality was investigated using Cox proportional-hazard modelling with normal MC as referent (unadjusted and adjusted for low hand grip strength, sex, age, body mass index, previous diagnosis of disease (cancer, type 2 diabetes and coronary heart disease), lifestyle, and socioeconomic factors (smoking, alcohol consumption, physical activity, and Townsend deprivation index). RESULTS: Muscle composition measurements were complete for 39 804 participants [52% female, mean (SD) age 64.2 (7.6) years and body mass index 26.4 (4.4) kg/m2 ]. Three hundred twenty-eight deaths were recorded during a follow-up period of 2.9 (1.4) years after imaging. At imaging, adverse MC was detected in 10.5% of participants. The risk of death from any cause in adverse MC compared with normal MC was 3.71 (95% confidence interval 2.81-4.91, P < 0.001). Only low muscle volume and only high MFI were independently associated with all-cause mortality [1.58 (1.13-2.21), P = 0.007, and 2.02 (1.51-2.71), P < 0.001, respectively]. Adjustment of low hand grip strength [1.77 (1.28-2.44), P < 0.001] did not attenuate the associations with any of the MC groups. In the fully adjusted model, adverse MC and only high MFI remained significant (P < 0.001 and P = 0.020) while the association with only low muscle volume was attenuated to non-significance (P = 0.560). The predictive performance of adverse MC [1.96 (1.42-2.71), P < 0.001] was comparable with that of previous cancer diagnosis [1.93 (1.47-2.53), P < 0.001] and smoking [1.71 (1.02-2.84), P = 0.040]. Low hand grip strength was borderline non-significant [1.34 (0.96-1.88), P = 0.090]. CONCLUSIONS: Adverse MC was a strong and independent predictor of all-cause mortality. Sarcopenia guidelines can be strengthened by including cut-offs for myosteatosis enabling detection of adverse MC.

Quantitative Muscle MRI and Clinical Findings in Women With Pathogenic Dystrophin Gene Variants.

Objective: To explore fat replacement, muscle strength, and clinical features in women heterozygous for a pathogenic DMD variant, we prospectively examined 53 women, assuming that some of these women-despite of the recessive X-linked inheritance-manifested clinical symptoms. Methods: We performed a cross-sectional observational study using MRI and stationary dynamometry of lower extremities, extracted blood muscle biomarkers, and investigated subjective complaints. Results were compared with 19 healthy women. Results: DMD variant carriers were weaker and had higher fat fractions than controls in all investigated muscle groups (p < 0.02). Fat fractions were 18% in carriers vs. 11% in controls in thighs (p = 0.008), and 15 vs. 11% in calf muscles (p = 0.032). Seventy-two percent had fat fractions deviating from controls by two standard deviations (SDs) in one or more of the 16 investigated muscle groups. On strength testing, 40% of the carriers had results deviating from control muscle strength by two SDs in one or more dynamometry assessments. Forty-three carriers (81%) had either reduced muscle strength (<2 SDs from control mean) and/or elevated muscle fat fraction (>2 SDs from control mean). Thirty of these had subjective symptoms. Blood creatine kinase and myoglobin were elevated in 57% of the carriers. Conclusion: Using quantitative methods, this study shows that both clinically symptomatic and asymptomatic women with pathogenic DMD variants show a high prevalence of muscle affection. Longitudinal studies in female carriers of pathogenic DMD variants are needed to follow the evolution of these changes.

The effect on precision and T1 bias comparing two flip angles when estimating muscle fat infiltration using fat-referenced chemical shift-encoded imaging.

Investigation of the effect on accuracy and precision of different parameter settings is important for quantitative MRI. The purpose of this study was to investigate T1 bias and precision for muscle fat infiltration (MFI) measurements using fat-referenced chemical shift MFI measurements at flip angles of 5° and 10°. The fat-referenced measurements were compared with fat fractions, which is a more commonly used measure of MFI. This retrospective study was performed on data from a clinical intervention study including 40 postmenopausal women. Test and retest images were acquired with a 3-T scanner using four-point 3D spoiled gradient multiecho acquisition. Postprocessing included T2* correction and fat-referenced calibration, where the fat signal was calibrated using adipose tissue as reference. The mean MFI was calculated in six different muscle regions using both the fat-referenced fat signal and the fat fraction, defined as the fat signal divided by the sum of the fat and water signals. Both methods used the same fat and water images as input. The variance of the difference between mean MFI from test and retest was used as the measure of precision. The signal-to-noise ratio (SNR) characteristics were analyzed by measuring the full width at half maximum (FWHM) of the fat signal distribution. There was no difference in the mean MFI at different flip angles for the fat-referenced technique (p = 0.66), while the measured fat fractions were 3.3 percentage points larger for 10° compared with 5° (p < 0.001). No significant difference in the precision was found in any of the muscles analyzed. However, the FWHM of the fat signal distribution was significantly (p = 0.01) lower at 10°. This strenghtens the hypothesis that fat-referenced MFI is insensitive to flip angle-induced T1 bias in CSE-MRI, enabling usage of a higher and more SNR-effective flip angle. The lower FWHM in fat-referenced MFI at 10° indicates that high flip angle acquisition is advantageous even although no significant differences in precision were observed comparing 5° and 10°.

Adverse muscle composition is linked to poor functional performance and metabolic comorbidities in NAFLD.

BACKGROUND & AIMS: Sarcopenia and frailty are recognised as important factors in later stages of liver disease. However, their role in non-alcoholic fatty liver disease (NAFLD) is not yet fully understood. In this study we investigate the associations of MRI-measured adverse muscle composition (AMC: low muscle volume and high muscle fat) with poor function, sarcopenia, and metabolic comorbidity within NAFLD in the large UK Biobank imaging study. METHODS: A total of 9,545 participants were included. Liver fat, fat-tissue free muscle volume, and muscle fat infiltration were quantified using a rapid MRI protocol and automated image analysis (AMRA® Researcher). For each participant, a personalised muscle volume z-score (sex- and body size-specific) was calculated and combined with muscle fat infiltration for AMC detection. The following outcomes were investigated: functional performance (hand grip strength, walking pace, stair climbing, falls) and metabolic comorbidities (coronary heart disease, type 2 diabetes). Sarcopenia was detected by combining MRI thresholds for low muscle quantity and low hand grip strength according to the European working group definition. RESULTS: The prevalence of sarcopenia in NAFLD (1.6%) was significantly lower (p <0.05) compared with controls without fatty liver (3.4%), whereas the prevalence of poor function and metabolic comorbidity was similar or higher. Of the 1,204 participants with NAFLD, 169 (14%) had AMC and showed 1.7-2.4× higher prevalence of poor function (all p <0.05) as well as 2.1× and 3.3× higher prevalence of type 2 diabetes and coronary heart disease (p <0.001), respectively, compared with those without AMC. CONCLUSIONS: AMC is a prevalent and highly vulnerable NAFLD phenotype displaying poor function and high prevalence of metabolic comorbidity. Sarcopenia guidelines can be strengthened by including cut-offs for muscle fat, enabling AMC detection. LAY SUMMARY: Today, it is hard to predict whether a patient with fatty liver disease will progress to more severe liver disease. This study shows that measuring muscle health (the patient's muscle volume and how much fat they have in their muscles) could help identify the more vulnerable patients and enable early prevention of severe liver disease.

New insights into intrinsic foot muscle morphology and composition using ultra-high-field (7-Tesla) magnetic resonance imaging.

BACKGROUND: The intrinsic muscles of the foot are key contributors to foot function and are important to evaluate in lower limb disorders. Magnetic resonance imaging (MRI), provides a non-invasive option to measure muscle morphology and composition, which are primary determinants of muscle function. Ultra-high-field (7-T) magnetic resonance imaging provides sufficient signal to evaluate the morphology of the intrinsic foot muscles, and, when combined with chemical-shift sequences, measures of muscle composition can be obtained. Here we aim to provide a proof-of-concept method for measuring intrinsic foot muscle morphology and composition with high-field MRI. METHODS: One healthy female (age 39 years, mass 65 kg, height 1.73 m) underwent MRI. A T1-weighted VIBE - radio-frequency spoiled 3D steady state GRE - sequence of the whole foot was acquired on a Siemens 7T MAGNETOM scanner, as well as a 3T MAGNETOM Prisma scanner for comparison. A high-resolution fat/water separation image was also acquired using a 3D 2-point DIXON sequence at 7T. Coronal plane images from 3T and 7T scanners were compared. Using 3D Slicer software, regions of interest were manually contoured for each muscle on 7T images. Muscle volumes and percentage of muscle fat infiltration were calculated (muscle fat infiltration % = Fat/(Fat + Water) x100) for each muscle. RESULTS: Compared to the 3T images, the 7T images provided superior resolution, particularly at the forefoot, to facilitate segmentation of individual muscles. Muscle volumes ranged from 1.5 cm3 and 19.8 cm3, and percentage muscle fat infiltration ranged from 9.2-15.0%. CONCLUSIONS: This proof-of-concept study demonstrates a feasible method of quantifying muscle morphology and composition for individual intrinsic foot muscles using advanced high-field MRI techniques. This method can be used in future studies to better understand intrinsic foot muscle morphology and composition in healthy individuals, as well as those with lower disorders.