A Novel Mri-Method Allows a Rapid and Robust Assessment of Muscle Quantity and Quality in Hemodialysis Patients.

BackgroundSarcopenia is a prevalent condition in patients on maintenance hemodialysis and associates with mortality. Research using magnetic resonance imaging (MRI) has demonstrated the importance of a proper body size-adjustment in the assessment of muscle mass, and that a muscle composition assessment including measurements of both muscle volume and fat infiltration improves the prediction of comorbidity and survival related to sarcopenia. Such combined muscle composition assessment has not previously been performed in hemodialysis patients.MethodsEleven hemodialysis patients were scanned using whole-body fat and water separated MRI and followed regarding survival and comorbidity for five years. Muscle composition was assessed using AMRA® Researcher. Using data from 9615 UK Biobank participants, sex and BMI-matched muscle volume z-scores and sex-adjusted muscle fat infiltration values were calculated for each patient. These measurements were then used for the calculation of a combined muscle score. Resulting three muscle measurements were associated with survival and comorbidity index.ResultsSix patients exhibited low muscle volume (muscle volume z-score <25th percentile (population wide)), and six patients presented with high muscle fat infiltration (>75th percentile (population wide)). During a 68-months follow-up, five patients died, four were transplanted and two remained on hemodialysis treatment. The combined muscle score was significantly associated with comorbidity index (p<0.05) and was highly predictive of survival (AUROC 0.97).ConclusionsThe combined assessment including both body size-adjusted muscle volume and muscle fat infiltration can be used to analyze muscle composition in hemodialysis patients. MRI based muscle composition assessment reflected comorbidity and predicted survival in hemodialysis patients.

Changes in Cross-sectional Areas of Posterior Extensor Muscles in Thoracic Spine: A 10-year Longitudinal MRI Study

This study aimed to examine changes in the cross-sectional areas (CSAs) of posterior extensor muscles in the thoracic spine over 10 years and identify related factors. The subjects of this study were 85 volunteers (mean age: 44.8 ± 11.5) and the average follow-up period was about 10 years. The CSAs of the transversospinalis muscles, erector spinae muscles, and total CSAs of the extensor muscles from T1/2 to T11/12 were measured on MRI. The extent of muscle fat infiltration was assessed by the signal intensity (luminance) of the extensor muscles’ total cross section compared to a section of pure muscle. Associations of age, sex, body mass index, lifestyle, back pain, neck pain, neck stiffness, and intervertebral disc degeneration with the 10-year CSAs changes and muscle fat infiltration were examined by Poisson regression analysis. The mean CSAs of all index muscles increased significantly. Exercise habit was associated with increased CSAs of the erector spinae muscles and the total area of the extensor muscles. The cross-section mean luminance increased significantly from baseline, indicating a significant increase of fat infiltration in the posterior extensor muscles. Progression of disc degeneration was negatively associated with the increase of fat infiltration in the total extensor muscles.

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.