Muscle Fat Infiltration Research Articles

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

BackgroundAdverse 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.MethodsThere 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).ResultsMuscle 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.

Psoriasis Is Associated With Myosteatosis but Not Sarcopenia: A Case-Control Study.

Background: The link between psoriasis and body fat (or obesity) has been well established. However, there are no reports detailing the possible relationship between psoriasis and fat infiltration in skeletal muscle, also known as myosteatosis. A recent study reported the possible association between psoriasis, arthritis, and sarcopenia (the loss of skeletal muscle mass or function). The present study aimed to explore the possible associations of chronic plaque psoriasis with myosteatosis and sarcopenia.Methods: We conducted a case-control study. In-patients with chronic plaque psoriasis were retrospectively recruited. Healthy controls were prospectively and continuously recruited. Unenhanced cross-sectional chest computed tomography images at the 12th thoracic vertebral level were analyzed using Mimics software. Skeletal muscle area (SMA), skeletal muscle radiodensity (SMD), and intermuscular adiposity tissue (IMAT) were measured. The skeletal muscle index (SMI) was calculated as SMA/height2. The percentage of IMAT (IMAT%) was calculated as IMAT/SMA × 100%. Myosteatosis was defined by SMD or IMAT%, whereas sarcopenia was defined by SMI. Propensity score matching was performed to adjust for the main confounders. Logistic regression models were used to evaluate the associations of psoriasis with myosteatosis and sarcopenia.Results: We included 155 psoriasis patients and 512 healthy controls. After propensity score matching, we retained 310 controls. The prevalence of sarcopenia was not significantly different between the psoriasis and control groups (men: 9.8% vs. 14.4%, p = 0.244; women: 7.0% vs. 11.7%, p = 0.548). Psoriasis patients were more prone to SMD-defined myosteatosis (men: 39.3% vs. 20.8%; women: 46.5% vs. 16.0%; both p < 0.001) and IMAT%-defined myosteatosis (men: 21.4% vs. 12.5%, p = 0.034; women: 46.5 vs. 28.7%, p = 0.042) than the control group. After adjustment for potential confounders, psoriasis was not significantly associated with sarcopenia (odds ratio [OR] 0.51, 95% confidence interval [CI] 0.25–1.19, p = 0.136). However, psoriasis was associated with SMD-defined myosteatosis (OR 3.16, 95% CI 1.86–5.37, p < 0.001) and IMAT%-defined myosteatosis (OR 1.76, 95% CI 1.04–3.00; p = 0.037).Conclusions: Chronic plaque psoriasis is independently associated with myosteatosis but not sarcopenia. Since fat and muscle are considered endocrine organs and can drive the inflammatory process, further studies detailing the interaction between psoriasis, fat, and skeletal muscle are warranted.

The Quantity and Quality of Lumbar Muscles and Lumbopelvic Parameters in Patients With Degenerative Spondylolisthesis.

IntroductionLumbar degenerative spondylolisthesis (DS) is one of the most common causes of low back pain. The lumbar muscles, such as the psoas major (PM), erector spinae (ES), and multifidus (MF) muscles, play an important role in the stability and functional movement of the lumbar spine. The quantities and qualities of these muscles may be related to the occurrence of DS and lumbopelvic parameters, such as lumbar lordosis (LL) and sacral slope (SS). However,the influence of lumbar muscles on DS and lumbopelvic alignment is not well understood.MethodsPatients with L4 DS (DS group, n=25) and without DS (non-DS group, n=25) were included. Using sagittal reconstructed CT images of patients who visited our hospital for reasons other than low back disorders, LL, upper lumbar lordosis ([ULL] L1-L4), lower lumbar lordosis ([LLL] L4-S1), and SS were examined. To evaluate the quantity and quality of lumbar muscles, the gross cross-sectional area (GCSA), functional cross-sectional area (FCSA), and fat infiltration (FI) of the PM, ES, and MF muscles were measured by CT images. The lumbopelvic parameters, FCSA, GCSA, and FI of lumbar muscles were compared between the two groups. Then, each lumbar muscle parameter was analyzed for correlation with DS and lumbopelvic parameters.ResultsDS patients displayed significantly greater ULL and lower FI of the PM and ES muscles than non-DS patients (p=0.0078, 0.031, and 0.010, respectively). The FI of the ES muscle was significantly correlated with the presence of DS (p=0.010). The FCSA of the ES and MF muscles and the GCSA of the MF muscle showed a significant correlation with LL and SS in the non-DS group (p<0.05), but not in the DS group..ConclusionULL was greater in L4 DS patients, possibly related to the better quality of the ES muscle. All DS patients showed mild (grade I) spondylolisthesis, suggesting the possibility that lumbar muscle quality is better in patients with mild DS than in those without DS. The ES and MF muscles may play an important role in maintaining the lumbar lordotic angle in non-DS patients but not in DS patients.

COLLAGEN RELATED MUSCLE DISEASES: EP.56 Collagen VI-related neuropathy

Pathogenic variants in the collagen 6 (COL6A1-3) genes cause Bethlem myopathy, Ullrich congenital muscular dystrophy or intermediate phenotypes. Typical clinical characteristics for these disorders include contractures and skin changes. Recently, more patients have been diagnosed with collagen VI-related diseases due to Next Generation Sequencing technology, and the clinical spectrum has equally expanded. We present a new phenotype of collagen VI-related disease with predominantly axonal neuropathy. Five patients from three unrelated families with childhood onset neuromuscular disease were clinically re-evaluated in adulthood. Three of the patients had an initial diagnosis of spinal muscular atrophy in their childhood and two were previously diagnosed with unspecific myopathy. Upon re-evaluation of the diagnoses, we re-examined previous muscle biopsies, repeated neurophysiological examinations and performed MRI of the thighs as well as Next Generation Sequencing with gene panels for neuromuscular disorders. All five patients were shown to be compound heterozygous for the same two variants in the COL6A3 gene (c.7447A>G and c.8567+2dupT). On clinical examination they all had proximal paresis and Achilles tendon contractures. Four patients demonstrated weakness for finger extension and were developing finger flexor contractures. Pes cavus was present in four patients. Electromyography in childhood and adulthood showed a predominantly neurogenic pattern in both proximal and distal muscles in all patients. Muscle biopsies were previously done in three patients and displayed mixed neurogenic and myopathic findings. MRI showed typical collagen VI-related peripheral fat infiltration in the thigh muscles of all patients. The currently investigated patients expand the clinical spectrum of collagen VI-related disease. Patients with both axonal neuropathy and contractures may have a collagen VI-related disorder.

MRI assessment of epaxial myosteatosis in dogs with intervertebral disc extrusions and associations with patient factors and outcome.

Fat infiltration of skeletal muscle (myosteatosis) is a characteristic of reduced muscle quality. Objectives of this retrospective, observer agreement, methods comparison, cross-sectional study were to compare epaxial myosteatosis of dogs with surgically confirmed intervertebral disc extrusion (IVDE) using a visual semi-quantitative method and quantitative 2-point Dixon fat-water chemical-shift separation MRI method. Thoracolumbar MRI studies of 86 dogs were reviewed. Assessed locations were the site of extrusion and the adjacent intervertebral disc space immediately cranial. A visual fat score (VFS) was assigned to fat infiltration of the epaxial muscles. Quantitative assessment of fat infiltration was determined by calculating a muscle-fat fraction (MFF). There was moderate agreement between the two reviewers for VFS assessment (weighted Kappa 0.60, 95%CI 0.53-0.66) with moderate to strong correlation between scoring methods (P≤.001). Both VFS (P=.023, P=.02) and MFF (P=.041, P=.043) were significantly correlated with neurologic grade at presentation for the erector spinae muscle group at both sites. Higher VFS in the multifidus muscle increased the odds of a successful outcome when assessed at the extrusion site (odds ratio and 95%CI 4.3 (1.02-78.7), P=.0461). In summary, the visual and Dixon method of epaxial muscle-fat assessment are feasible in dogs with IVDE with moderate to strong correlation. Increased VFS of myosteatosis in the multifidus muscle at the extrusion site significantly increased the odds of a successful outcome. Further studies are indicated to assess the utility of myosteatosis as an MRI imaging biomarker in the preoperative imaging assessment of dogs with IVDE.

The fatty degeneration of the lumbar erector spinae muscles affects dynamic spinal compensation ability during gait in adult spinal deformity

This study aimed to investigate whether fat infiltration in lumbar paravertebral muscles assessed by magnetic resonance imaging (MRI) could be related to dynamic sagittal spino-pelvic balance during gait in adult spinal deformity (ASD). This is a retrospective analysis of 28 patients with ASD. The fat infiltration rate of lumbar erector spinae muscles, multifidus muscles and psoas major muscles was measured by T2 weighted axial MRI at L1-2 and L4-5. Dynamic sagittal spinal and pelvic angles during gait were evaluated using 3D motion analysis. The correlation between fat infiltration rate of those muscles with variations in dynamic kinematic variables while walking and static radiological parameters was analyzed. Spinal kyphosis and pelvic anteversion significantly increased during gait. Fat infiltration rate of erector spinae muscles at L1-2 was positively correlated with thoracic kyphosis (r = 0.392, p = 0.039) and pelvic tilt (r = 0.415, p = 0.028). Increase of spinal kyphosis during walking was positively correlated with fat infiltration rate of erector spinae muscles both at L1-2 (r = 0.394, p = 0.038) and L4-5 (r = 0.428, p = 0.023). Qualitative evaluation of lumbar erector spinae muscles assessed by fat infiltration rate has the potential to reflect dynamic spino-pelvic balance during gait.

MRI-Determined Psoas Muscle Fat Infiltration Correlates with Severity of Weight Loss during Cancer Cachexia.

Simple SummaryDuring cancer cachexia, patients experience profound weight loss due to metabolic dysfunction, resulting in muscle composition alterations. The proton density fat fraction (PDFF) using magnetic resonance imaging (MRI) is an established biomarker to assess changes of muscle composition. We evaluated the suitability of MRI-determined psoas and erector spinae muscle PDFF and fat volume as biomarkers for monitoring cachexia development in an oncological cohort of 58 patients and assessed the regional variation in muscle parameters over time. Our results indicate that psoas muscle PDFF and fat volume could serve as MRI-determined biomarkers for early risk stratification and disease monitoring regarding progression and severity of weight loss in cancer cachexia.Purpose: To evaluate the suitability of psoas and erector spinae muscle proton density fat fraction (PDFF) and fat volume as biomarkers for monitoring cachexia severity in an oncological cohort, and to evaluate regional variances in muscle parameters over time. Methods: In this prospective study, 58 oncological patients were examined by a 3 T MRI receiving between one and five scans. Muscle volume and PDFF were measured, segmentation masks were divided into proximal, middle and distal muscle section. Results: A regional variation of fat distribution in erector spinae muscle at baseline was found (p < 0.01). During follow-ups significant relative change of muscle parameters was observed. Relative maximum change of erector spinae muscle showed a significant regional variation. Correlation testing with age as a covariate revealed significant correlations for baseline psoas fat volume (r = −0.55, p < 0.01) and baseline psoas PDFF (r = −0.52, p = 0.02) with maximum BMI change during the course of the disease. Conclusion: In erector spinae muscles, a regional variation of fat distribution at baseline and relative maximum change of muscle parameters was observed. Our results indicate that psoas muscle PDFF and fat volume could serve as MRI-determined biomarkers for early risk stratification and disease monitoring regarding progression and severity of weight loss in cancer cachexia.

Peripheral Quantitative Computed Tomography Derived Muscle Density Is Associated With Physical Performance in Older Adults

PurposeThe assessment of body composition is an integral part in diagnosing sarcopenia. The purpose of this study was to determine the relationships between peripheral quantitative computed tomography (pQCT)-derived measures of body composition and measures of physical performance in older adults. MethodsMuscle density, muscle area, and fat area of 168 patients aged 65 years and older (76.3±6.5) were measured with pQCT at the distal forearm additionally to clinical assessment consisting of medical history, physical examination and physical assessment including hand grip strength, gait speed and chair rise tests. Regression analyses assessed associations between patients’ physical performance and pQCT derived data. ResultsAmong the three pQCT parameters, especially muscle density was significantly correlated with all of the three measures of physical performance even after adjusting for sex, age, BMI, vitamin D serum level and the level of physical activity. The same analysis for muscle area achieved significance level only for handgrip strength but not for gait speed nor for chair rise time. Fat area was significantly correlated only with gait speed after adjusting for sex and age. The association of muscle density with physical performance held up in an additional subanalysis stratified by body mass index. ConclusionMuscle density, a proxy for muscle fat infiltration, seems to be better than muscle area or fat area at assessing muscle quality and physical performance in older adults. This association seems to be independent of the body mass index.

Multi-muscle deep learning segmentation to automate the quantification of muscle fat infiltration in cervical spine conditions

Muscle fat infiltration (MFI) has been widely reported across cervical spine disorders. The quantification of MFI requires time-consuming and rater-dependent manual segmentation techniques. A convolutional neural network (CNN) model was trained to segment seven cervical spine muscle groups (left and right muscles segmented separately, 14 muscles total) from Dixon MRI scans (n = 17, 17 scans < 2 weeks post motor vehicle collision (MVC), and 17 scans 12 months post MVC). The CNN MFI measures demonstrated high test reliability and accuracy in an independent testing dataset (n = 18, 9 scans < 2 weeks post MVC, and 9 scans 12 months post MVC). Using the CNN in 84 participants with scans < 2 weeks post MVC (61 females, 23 males, age = 34.2 ± 10.7 years) differences in MFI between the muscle groups and relationships between MFI and sex, age, and body mass index (BMI) were explored. Averaging across all muscles, females had significantly higher MFI than males (p = 0.026). The deep cervical muscles demonstrated significantly greater MFI than the more superficial muscles (p < 0.001), and only MFI within the deep cervical muscles was moderately correlated to age (r > 0.300, p ≤ 0.001). CNN’s allow for the accurate and rapid, quantitative assessment of the composition of the architecturally complex muscles traversing the cervical spine. Acknowledging the wider reports of MFI in cervical spine disorders and the time required to manually segment the individual muscles, this CNN may have diagnostic, prognostic, and predictive value in disorders of the cervical spine.

A Leptin Receptor Antagonist Attenuates Adipose Tissue Browning and Muscle Wasting in Infantile Nephropathic Cystinosis-Associated Cachexia.

Mice lacking the functional cystinosin gene (Ctns−/−), a model of infantile nephropathic cystinosis (INC), exhibit the cachexia phenotype with adipose tissue browning and muscle wasting. Elevated leptin signaling is an important cause of chronic kidney disease-associated cachexia. The pegylated leptin receptor antagonist (PLA) binds to but does not activate the leptin receptor. We tested the efficacy of this PLA in Ctns−/− mice. We treated 12-month-old Ctns−/− mice and control mice with PLA (7 mg/kg/day, IP) or saline as a vehicle for 28 days. PLA normalized food intake and weight gain, increased fat and lean mass, decreased metabolic rate and improved muscle function. It also attenuated perturbations of energy homeostasis in adipose tissue and muscle in Ctns−/− mice. PLA attenuated adipose tissue browning in Ctns−/− mice. PLA increased gastrocnemius weight and fiber size as well as attenuated muscle fat infiltration in Ctns−/− mice. This was accompanied by correcting the increased expression of muscle wasting signaling while promoting the decreased expression of myogenesis in gastrocnemius of Ctns−/− mice. PLA attenuated aberrant expressed muscle genes that have been associated with muscle atrophy, increased energy expenditure and lipolysis in Ctns−/− mice. Leptin antagonism may represent a viable therapeutic strategy for adipose tissue browning and muscle wasting in INC.

The role of IL-1 in adipose browning and muscle wasting in CKD-associated cachexia

Cytokines such as IL-6, TNF-α and IL-1β trigger inflammatory cascades which may play a role in the pathogenesis of chronic kidney disease (CKD)-associated cachexia. CKD was induced by 5/6 nephrectomy in mice. We studied energy homeostasis in Il1β−/−/CKD, Il6−/−/CKD and Tnfα−/−/CKD mice and compared with wild type (WT)/CKD controls. Parameters of cachexia phenotype were completely normalized in Il1β−/−/CKD mice but were only partially rescued in Il6−/−/CKD and Tnfα−/−/CKD mice. We tested the effects of anakinra, an IL-1 receptor antagonist, on CKD-associated cachexia. WT/CKD mice were treated with anakinra (2.5 mg/kg/day, IP) or saline for 6 weeks and compared with WT/Sham controls. Anakinra normalized food intake and weight gain, fat and lean mass content, metabolic rate and muscle function, and also attenuated molecular perturbations of energy homeostasis in adipose tissue and muscle in WT/CKD mice. Anakinra decreased serum and muscle expression of IL-6, TNF-α and IL-1β in WT/CKD mice. Anakinra attenuated browning of white adipose tissue in WT/CKD mice. Moreover, anakinra normalized gastrocnemius weight and fiber size as well as attenuated muscle fat infiltration in WT/CKD mice. This was accompanied by correcting the increased muscle wasting signaling pathways while promoting the decreased myogenesis process in gastrocnemius of WT/CKD mice. We performed qPCR analysis for the top 20 differentially expressed muscle genes previously identified via RNAseq analysis in WT/CKD mice versus controls. Importantly, 17 differentially expressed muscle genes were attenuated in anakinra treated WT/CKD mice. In conclusion, IL-1 receptor antagonism may represent a novel targeted treatment for adipose tissue browning and muscle wasting in CKD.

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°.

Cardiac and skeletal muscle predictors of impaired cardiorespiratory fitness post-anthracycline chemotherapy for breast cancer

This study aimed to characterize peak exercise cardiac function and thigh muscle fatty infiltration and their relationships with VO2peak among anthracycline-treated breast cancer survivors (BCS). BCS who received anthracycline chemotherapy ~ 1 year earlier (n = 16) and matched controls (matched-CON, n = 16) were enrolled. Resting and peak exercise cardiac function, myocardial T1 mapping (marker of fibrosis), and thigh muscle fat infiltration were assessed by magnetic resonance imaging, and VO2peak by cycle test. Compared to matched-CON, BCS had lower peak SV (64 ± 9 vs 57 ± 10 mL/m2, p = 0.038), GLS (− 30.4 ± 2.2 vs − 28.0 ± 2.5%, p = 0.008), and arteriovenous oxygen difference (16.4 ± 3.6 vs 15.2 ± 3.9 mL/100 mL, p = 0.054). Mediation analysis showed: (1) greater myocardial T1 time (fibrosis) is inversely related to cardiac output and end-systolic volume exercise reserve; (2) greater thigh muscle fatty infiltration is inversely related to arteriovenous oxygen difference; both of which negatively influence VO2peak. Peak SV (R2 = 65%) and thigh muscle fat fraction (R2 = 68%) were similarly strong independent predictors of VO2peak in BCS and matched-CON combined. Post-anthracyclines, myocardial fibrosis is associated with impaired cardiac reserve, and thigh muscle fatty infiltration is associated with impaired oxygen extraction, which both contribute to VO2peak.

Targeting interleukin-1 for reversing fat browning and muscle wasting in infantile nephropathic cystinosis.

Background Ctns −/− mice, a mouse model of infantile nephropathic cystinosis, exhibit hypermetabolism with adipose tissue browning and profound muscle wasting. Inflammatory cytokines such as interleukin (IL)‐1 trigger inflammatory cascades and may be an important cause for cachexia. We employed genetic and pharmacological approaches to investigate the effects of IL‐1 blockade in Ctns −/− mice.MethodsWe generated Ctns −/− Il1β −/− mice, and we treated Ctns −/− and wild‐type control mice with IL‐1 receptor antagonist, anakinra (2.5 mg/kg/day, IP) or saline as vehicle for 6 weeks. In each of these mouse lines, we characterized the cachexia phenotype consisting of anorexia, loss of weight, fat mass and lean mass, elevation of metabolic rate, and reduced in vivo muscle function (rotarod activity and grip strength). We quantitated energy homeostasis by measuring the protein content of uncoupling proteins (UCPs) and adenosine triphosphate in adipose tissue and skeletal muscle. We measured skeletal muscle fiber area and intramuscular fatty infiltration. We also studied expression of molecules regulating adipose tissue browning and muscle mass metabolism. Finally, we evaluated the impact of anakinra on the muscle transcriptome in Ctns −/− mice.ResultsSkeletal muscle expression of IL‐1β was significantly elevated in Ctns −/− mice relative to wild‐type control mice. Cachexia was completely normalized in Ctns −/− Il1β −/− mice relative to Ctns −/− mice. We showed that anakinra attenuated the cachexia phenotype in Ctns −/− mice. Anakinra normalized UCPs and adenosine triphosphate content of adipose tissue and muscle in Ctns −/− mice. Anakinra attenuated aberrant expression of beige adipose cell biomarkers (UCP‐1, CD137, Tmem26, and Tbx1) and molecules implicated in adipocyte tissue browning (Cox2/Pgf2α, Tlr2, Myd88, and Traf6) in inguinal white adipose tissue in Ctns −/− mice. Moreover, anakinra normalized gastrocnemius weight and fiber size and attenuated muscle fat infiltration in Ctns −/− mice. This was accompanied by correction of the increased muscle wasting signalling pathways (increased protein content of ERK1/2, JNK, p38 MAPK, and nuclear factor‐κB p65 and mRNA expression of Atrogin‐1 and Myostatin) and the decreased myogenesis process (decreased mRNA expression of MyoD and Myogenin) in the gastrocnemius muscle of Ctns −/− mice. Previously, we identified the top 20 differentially expressed skeletal muscle genes in Ctns −/− mice by RNAseq. Aberrant expression of these 20 genes have been implicated in muscle wasting, increased energy expenditure, and lipolysis. We showed that anakinra attenuated 12 of those top 20 differentially expressed muscle genes in Ctns −/− mice.ConclusionsAnakinra may provide a targeted novel therapy for patients with infantile nephropathic cystinosis.

Fatty infiltration in cervical flexors and extensors in patients with degenerative cervical myelopathy using a multi-muscle segmentation model.

In patients with degenerative cervical myelopathy (DCM) that have spinal cord compression and sensorimotor deficits, surgical decompression is often performed. However, there is heterogeneity in clinical presentation and post-surgical functional recovery. Primary: a) to assess differences in muscle fat infiltration (MFI) in patients with DCM versus controls, b) to assess association between MFI and clinical disability. Secondary: to assess association between MFI pre-surgery and post-surgical functional recovery. Cross-sectional case control study. Eighteen patients with DCM (58.6 ± 14.2 years, 10 M/8F) and 25 controls (52.6 ± 11.8 years, 13M/12 F) underwent 3D Dixon fat-water imaging. A convolutional neural network (CNN) was used to segment cervical muscles (MFSS- multifidus and semispinalis cervicis, LC- longus capitis/colli) and quantify MFI. Modified Japanese Orthopedic Association (mJOA) and Nurick were collected. Patients with DCM had significantly higher MFI in MFSS (20.63 ± 5.43 vs 17.04 ± 5.24, p = 0.043) and LC (18.74 ± 6.7 vs 13.66 ± 4.91, p = 0.021) than controls. Patients with increased MFI in LC and MFSS had higher disability (LC: Nurick (Spearman's ρ = 0.436, p = 0.003) and mJOA (ρ = -0.399, p = 0.008)). Increased MFI in LC pre-surgery was associated with post-surgical improvement in Nurick (ρ = -0.664, p = 0.026) and mJOA (ρ = -0.603, p = 0.049). In DCM, increased muscle adiposity is significantly associated with sensorimotor deficits, clinical disability, and functional recovery after surgery. Accurate and time efficient evaluation of fat infiltration in cervical muscles may be conducted through implementation of CNN models.

The association of sarcopenia and osteoporosis and their role in falls and fractures (literature review)

The progressive and generalized loss of skeletal muscle mass and strength leads to sarcopenia in elderly people. A new geriatric syndrome has been revealed – osteosarcopenia (osteosarcoporosis), which combines low bone mineral density with reduced muscle mass, strength and functional activity. The review presents data on the peculiarities of manifestation of these syndromes, the mechanisms of which are multifactorial and continue to be investigated. They are associated with genetic factors, lifestyle – lack of physical activity and malnutrition. The pathogenesis of sarcopenia involves mechanisms of chronic inflammation, changes in endocrine function, disturbance of neuromuscular connections and low reparation level. Sarcopenia correlates with low quality of life, disability, and death. The review analyzes the prevalence of sarcopenia which increases with age. However, there are conflicting results in the populations, which may be related to different clinical conditions, patient area, lifestyle and the use of different assessment criteria. The analysis of sarcopenia prevalence in men and women showed ambiguous results related to the studied population, involvement of different age groups of patients, different evaluation methods. Metabolic disorders in muscular and bone tissues were summarized on the basis of the analysis of the cross-influence of regulatory factors and metabolism products of these tissues; a close metabolic and functional association between them was shown. Fat infiltration of atrophied muscles and bone marrow is common in patients with sarcopenia and osteosarcoporosis, which affects muscle and bone tissue. Lipotoxicity and local inflammation stimulate the biosynthesis of pro-inflammatory cytokines. Literature analysis has shown controversial data on the association of sarcopenia and osteosarcopenia with falls and fractures, but based on meta-analysis data, which include an extensive body of information, it should be noted that individuals with sarcopenia and osteosarcopenia are more at risk of falls and fractures and require special special attention. The most common fracture in osteosarcopenia is the hip fracture.

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

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. 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. 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%). 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.

975-P: Adverse Muscle Composition Is Linked to a Higher Risk Type 2 Diabetes Phenotype

Background: The link between type 2 diabetes (T2D) and muscle health is not fully understood. Magnetic resonance imaging allows detection of Adverse muscle composition (MC). Method: Thigh fat-free muscle volume (FFMV, higher better) and muscle fat infiltration (MFI, higher worse) was measured in 38974 UK Biobank participants using AMRA Researcher. Persons with T2D (N=1881) were divided into four MC groups: (1) Normal MC, (2) Only low muscle volume (FFMV z-score the population wide 75th percentile (sex-specific)), (4) Adverse MC (low muscle volume and high muscle fat). Cardiovascular disease (CVD) risk was compared between MC groups using Cox proportional hazard modeling (unadjusted and adjusted for sex, age, BMI, prior CVD; referent: Normal MC). Result: Within T2D, Adverse MC was associated with a >2 fold higher hazard ratio (HR) for incident CVD compared to Normal MC. The association persisted after adjusting for prior CVD (Table 1). T2D with Normal MC was only modestly associated with incident CVD compared to sex, age and BMI matched non-T2D controls (HR 1.26, p=0.20). Conclusion: All MC phenotypes were represented in T2D where Adverse MC most strongly associated with higher CVD incidence, whereas CVD risk was only modestly higher in T2D with normal MC compared to controls. Whether improved MC can lessen outcome risks in T2D needs investigation. Disclosure J. Linge: Employee; Self; AMRA Medical AB, Stock/Shareholder; Self; AMRA Medical AB. M. Petersson: Employee; Self; AMRA Medical AB. N. Sattar: Advisory Panel; Self; Amgen Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk, Pfizer Inc., Sanofi, Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc. O. Dahlqvist leinhard: Employee; Self; AMRA Medical AB, Stock/Shareholder; Self; AMRA Medical AB. Funding Pfizer Inc

Abstract P070: Longer Sleep Duration Is Associated With Less Myosteatosis In African Caribbean Adults

Introduction: Skeletal muscle is the largest organ in the human body and vital to maintaining metabolic homeostasis. Increased skeletal muscle fat infiltration (i.e. myosteatosis) is now recognized as a major risk factor for cardio-metabolic diseases, independent of general obesity. Modifications in lifestyle, such as sleep, to reduce myosteatosis would be of great public health importance. However, studies of this relationship often use subjective data and are lacking in minority populations. The aim of this study was to examine the relation between objectively measured sleep duration and myosteatosis at the calf among African Caribbeans. Methods: Data were collected on men (n=393) and women (n=438) from the Tobago Health Study. Sleep duration and physical activity was collected using a SenseWear Pro Armband (BodyMedia, Inc.). Participants were instructed to wear the armband at all times, except in water, for 4-7 days. Measures of muscle density, intermuscular adipose tissue (IMAT), and area were obtained by peripheral QCT scans of the calf (Stratec XCT-2000). Model covariates included age, sex, BMI, diabetes, alcohol intake, smoking, and moderate to vigorous physical activity (MVPA). Linear regression was used to assess the relationship of sleep duration on skeletal muscle. Results: Mean sleep duration was 5.5 hours/day (Min 2.2, Max 11.6). Overall, participants were aged 58.7 years, had a BMI of 30.2 kg/m 2 , spent an average of 42 min/day in MVPA, and 18% were diabetic. In fully adjusted models, longer sleep duration was associated with smaller muscle area, but greater muscle density and less IMAT (all P&lt;0.03). There was no interaction of sleep and sex on muscle density, area and IMAT (p-value=0.5184; 0.2730; 0.0954). Conclusions: In African Caribbean men and women, longer sleep duration was associated with less myosteatosis, as well as, less muscle area at the calf. Further research is warranted to understand this relationship longitudinally in order to determine how it may inform lifestyle guidelines in the Caribbean.

Population-based body\u2013brain mapping links brain morphology with anthropometrics and body composition

Understanding complex body–brain processes and the interplay between adipose tissue and brain health is important for understanding comorbidity between psychiatric and cardiometabolic disorders. We investigated associations between brain structure and anthropometric and body composition measures using brain magnetic resonance imaging (MRI; n = 24,728) and body MRI (n = 4973) of generally healthy participants in the UK Biobank. We derived regional and global measures of brain morphometry using FreeSurfer and tested their association with (i) anthropometric measures, and (ii) adipose and muscle tissue measured from body MRI. We identified several significant associations with small effect sizes. Anthropometric measures showed negative, nonlinear, associations with cerebellar/cortical gray matter, and brain stem structures, and positive associations with ventricular volumes. Subcortical structures exhibited mixed effect directionality, with strongest positive association for accumbens. Adipose tissue measures, including liver fat and muscle fat infiltration, were negatively associated with cortical/cerebellum structures, while total thigh muscle volume was positively associated with brain stem and accumbens. Regional investigations of cortical area, thickness, and volume indicated widespread and largely negative associations with anthropometric and adipose tissue measures, with an opposite pattern for thigh muscle volume. Self-reported diabetes, hypertension, or hypercholesterolemia were associated with brain structure. The findings provide new insight into physiological body–brain associations suggestive of shared mechanisms between cardiometabolic risk factors and brain health. Whereas the causality needs to be determined, the observed patterns of body–brain relationships provide a foundation for understanding the underlying mechanisms linking psychiatric disorders with obesity and cardiovascular disease, with potential for the development of new prevention strategies.