Metformin mitigates adipogenesis of fibro-adipogenic progenitors after rotator cuff tears via activating mTOR/ULK1-mediated autophagy.

Muscular fatty infiltration is a common issue after rotator cuff tears (RCTs), which impair shoulder function. Females suffer a higher prevalence and a more severe degree of muscular fatty infiltration after RCT when compared with males, with the underlying mechanisms remaining unclear. Fibro-adipogenic progenitors (FAPs) are the primary source of muscular fatty infiltration following RCT. Our findings disclose that gender-specific disparities in muscular fatty infiltration are linked to mTOR/ULK1-mediated autophagy of FAPs. Decreased autophagic activity contributes to adipogenic differentiation in female FAPs after RCT. Furthermore, metformin could enhance mTOR/ULK1-mediated autophagic processes of FAPs, thereby alleviating fatty infiltration and improving shoulder functionality after RCT. Together, our study reveals that gender differences in muscular fatty infiltration arise from distinct autophagic activities. Metformin could be a promising noninvasive intervention to ameliorate muscular fatty infiltration of RCT.NEW & NOTEWORTHY The current study demonstrated that gender-specific disparities in muscular fatty infiltration are attributed to mTOR/ULK1-mediated autophagy of FAPs. Decreased autophagic activity contributes to adipogenic differentiation in female FAPs after RCT. Moreover, metformin could enhance mTOR/ULK1-mediated autophagic processes of FAPs, thereby alleviating fatty infiltration and improving shoulder functionality after RCT. Therefore, metformin could be a promising noninvasive intervention to ameliorate muscular fatty infiltration of RCT.

Fatty infiltration of gastrocnemius-soleus muscle complex: Considerations for myosteatosis rehabilitation.

Although previous studies have reported fatty infiltration of the gastrocnemius-soleus complex, little is known about the volumetric distribution and patterns of fatty infiltration. The purpose of this anatomical study was to document and quantify the frequency, distribution, and pattern of fatty infiltration of the gastrocnemius-soleus complex. One hundred formalin-embalmed specimens (mean age 78.1 ± 12.3 years; 48F/52M) were serially dissected to document the frequency, distribution, and pattern of fatty infiltration in the medial and lateral heads of gastrocnemius and soleus muscles. Fatty infiltration was found in 23% of specimens, 13 unilaterally (8F/5M) and 10 (5M/5F) bilaterally. The fatty infiltration process was observed to begin medially from the medial aspect of the medial head of gastrocnemius and medial margin of soleus and then progressed laterally throughout the medial head of gastrocnemius and the marginal, anterior, and posterior soleus. The lateral head of gastrocnemius remained primarily muscular in all specimens. Microscopically, the pattern of infiltration was demonstrated as intramuscular with intact aponeuroses, and septa. The remaining endo-, peri-, and epimysium preserved the overall contour of the gastrocnemius-soleus complex, even in cases of significant fatty replacement. Since the external contour of the calf is preserved, the presence of fatty infiltration may be underdiagnosed in the clinic without imaging. Myosteatosis is associated with gait and balance challenges in the elderly, which can impact quality of life and result in increased risk of falling. The findings of the study have implications in the rehabilitation management of elderly patients with sarcopenia and myosteatosis.

The validity of ultrasound and shear wave elastography to assess the quality of the rotator cuff.

OBJECTIVES: US with shear wave elastography (SWE) could reduce the burden and costs of the diagnostic process for patients with rotator cuff disorders. The aim of this study is to investigate the validity of US and SWE in preoperative assessment of fatty infiltration (FI) and muscle atrophy of the supraspinatus (SSP) and infraspinatus (ISP) muscles. METHODS: Patients with a rotator cuff disorder and a recent shoulder CT or MRI scan were eligible to participate. Goutallier and Warner stages of the SSP and ISP muscle were measured on the scan, for assessment of FI and muscle atrophy, respectively. These findings were compared with shear wave velocities (SWVs) assessed on US. Visual assessment of FI on US was compared with the Goutallier stage. To quantify the amount of muscle atrophy, the occupation ratio between SSP fossa and muscle was measured on MRI and US. RESULTS: Seventy-eight shoulders were included in the analysis. The correlation found between the occupation ratio on US and Warner and Goutallier stage and ratio on MRI ranged between r = - 0.550 to 0.589. The Goutallier stage of ISP and SSP muscle assessed on US showed a fair correlation with the Goutallier stage on a scan of r = 0.574 and r = 0.582, respectively. There was a poor correlation between the SWVs and scan results (r = - 0.116 to 0.07). CONCLUSION: SWE is not a valid method to measure the amount of FI or muscle atrophy in the SSP muscle. Therefore, SWE is not a suitable alternative for MRI in standard preoperative diagnostics in rotator cuff pathologies. CLINICAL RELEVANCE STATEMENT: Shear wave elastography should not be used in the diagnostics of rotator cuff pathologies. KEY POINTS: • There is a fair correlation between the Goutallier stage of the supraspinatus and infraspinatus muscle assessed on MRI and CT and visual assessment of fatty infiltration achieved on US. • Shear wave elastography is not a valid tool for the determination of the amount of fatty infiltration or muscle atrophy. • Shear wave elastography should not be used as a cheaper and less burdensome alternative for diagnostics in rotator cuff pathologies.

Hepatocellular carcinoma in patients with non-alcoholic fatty liver disease is associated with heterogeneous pattern of fat infiltration in skeletal muscles.

OBJECTIVES: To evaluate the association between fat infiltration in skeletal muscles (myosteatosis) and hepatocellular carcinoma (HCC) in patients with non-alcoholic fatty liver disease (NAFLD). METHODS: In a cross-sectional cohort of 72 histologically proven NAFLD patients (n = 38 with non-alcoholic steatohepatitis; NASH), among which 20 had HCC diagnosed on biopsy, we used proton density fat fraction (PDFF) at MRI to evaluate myosteatosis in skeletal muscles (mean fat fraction and first order radiomic-based pattern) at the third lumbar level, namely in erector spinae (ES), quadratus lumborum (QL), psoas, oblique, and rectus muscles. RESULTS: PDFFES was 70% higher in patients with HCC when compared to those without HCC (9.6 ± 5.5% versus 5.7 ± 3.0%, respectively, p < 0.001). In multivariate logistic regression, PDFFES was a significant predictor of the presence of HCC (AUC = 0.72, 95% CI 0.57-0.86, p = 0.002) independently from age, sex, visceral fat area, and liver fibrosis stage (all p < 0.05). The relationship between PDFFES and HCC was exacerbated in patients with NASH (AUC = 0.79, 95% CI 0.63-0.86, p = 0.006). In patients with NASH, radiomics features of heterogeneity such as energy and entropy in any of the paraspinal muscles (i.e., ES, QL, or psoas) were independent predictors of HCC. EnergyES identified patients with HCC (n = 13) in the NASH population with AUC = 0.92 (95% CI 0.82-1.00, p < 0.001). CONCLUSION: In patients with NAFLD, and more specifically in those with NASH, the degree and heterogeneity of myosteatosis is independently associated with HCC irrespective of liver fibrosis stage. CLINICAL RELEVANCE STATEMENT: Our data suggest that myosteatosis could be used as a biomarker of HCC in the ever-expanding NAFLD population and pave the way for further investigation in longitudinal studies. KEY POINTS: • HCC in patients with non-alcoholic fatty liver disease, and more specifically in those with non-alcoholic steatohepatitis, is independently associated with severe fatty infiltration (myosteatosis) of paravertebral skeletal muscles. • Association between myosteatosis and HCC is independent from liver fibrosis stage. • Histogram-based radiomics features of myosteatosis predicts the risk of HCC in patients with non-alcoholic steatohepatitis.

Inter-software and inter-threshold reliability of quantitative paraspinal muscle segmentation.

PURPOSE: Changes in the cross-sectional area (CSA) and functional cross-sectional area (FCSA) of the lumbar multifidus (MF) and erector spinae muscles (ES) are factors that can contribute to low back pain. For the assessment of muscle CSA and composition there are various software and threshold methods used for tissue segmentation in quantitative analysis. However, there is currently no gold standard for software as well as muscle segmentation. This study aims to analyze the measurement error between different image processing software and different threshold methods for muscle segmentation. METHODS: Magnetic resonance images (MRI) of 60 patients were evaluated. Muscle CSA and FCSA measurements were acquired from axial T2-weighted MRI of the MF and ES at L4/L5 and L5/S1. CSA, FCSA, and FCSA/CSA ratio were measured independently by two observers. The MRI images were measured using two different software programs (ImageJ and Amira) and with two threshold methods (Circle/Overlap method) for each software to evaluate FCSA and FCSA/CSA ratio. RESULTS: Inter-software comparisons revealed high inter-rater reliability. However, poor inter-rater reliability were obtained with different threshold methods. CSA, FCSA, and FCSA/CSA showed excellent inter-software agreement of 0.75-0.99 regardless of the threshold segmentation method. The inter-rater reliability between the two observers ranged between 0.75 and 0.99. Comparison of the two segmentation methods revealed agreement between 0.19 and 0.84. FCSA and FCSA/CSA measured via the Overlap method were significantly higher than those measured via the Circle method (P < 0.01). CONCLUSION: The present study showed a high degree of reliability with very good agreement between the two software programs. However, study results based on different threshold methods should not be directly compared.

Association of MRI findings with paraspinal muscles fat infiltration at lower lumbar levels in patients with chronic low back pain: a multicenter prospective study.

OBJECTIVE: In chronic low back pain (CLBP), the relationship between spinal pathologies and paraspinal muscles fat infiltration remains unclear. This study aims to evaluate the relationship between MRI findings and paraspinal muscles morphology and fat infiltration in CLBP patients by quantitative MRI. METHODS: All the CLBP patients were enrolled from July 2021 to December 2022 in four medical institutions. The cross-sectional area (CSA) and proton density fat fraction (PDFF) of the multifidus (MF) and erector spinae (ES) muscles at the central level of the L4/5 and L5/S1 intervertebral discs were measured. MRI findings included degenerative lumbar spondylolisthesis (DLS), intervertebral disc degeneration (IVDD), facet arthrosis, disc bulge or herniation, and disease duration. The relationship between MRI findings and the paraspinal muscles PDFF and CSA in CLBP patients was analyzed. RESULTS: A total of 493 CLBP patients were included in the study (198 females, 295 males), with an average age of 45.68 ± 12.91 years. Our research indicates that the number of MRI findings are correlated with the paraspinal muscles PDFF at the L4/5 level, but is not significant. Moreover, the grading of IVDD is the primary factor influencing the paraspinal muscles PDFF at the L4-S1 level (BES at L4/5=1.845, P < 0.05); DLS was a significant factor affecting the PDFF of MF at the L4/5 level (B = 4.774, P < 0.05). After including age, gender, and Body Mass Index (BMI) as control variables in the multivariable regression analysis, age has a significant positive impact on the paraspinal muscles PDFF at the L4-S1 level, with the largest AUC for ES PDFF at the L4/5 level (AUC = 0.646, cut-off value = 47.5), while males have lower PDFF compared to females. BMI has a positive impact on the ES PDFF only at the L4/5 level (AUC = 0.559, cut-off value = 24.535). CONCLUSION: The degree of paraspinal muscles fat infiltration in CLBP patients is related to the cumulative or synergistic effects of multiple factors, especially at the L4/L5 level. Although age and BMI are important factors affecting the degree of paraspinal muscles PDFF in CLBP patients, their diagnostic efficacy is moderate.

Association of physical activity with fatty infiltration of muscles after total hip arthroplasty.

OBJECTIVE: This study aimed to investigate the association between muscle density as an indicator of fatty infiltration of lower extremity muscles and physical activity (PA) after total hip arthroplasty (THA) and identify the patient characteristics with high postoperative PA. METHODS: This study included 62 female patients who underwent THA for unilateral hip osteoarthritis. Muscle density of the gluteus maximus, gluteus medius, iliopsoas, and quadriceps muscles was measured using computed tomography (CT). PA was assessed using University of California, Los Angeles (UCLA) activity scores. CT and UCLA activity score were obtained before and 1 year after THA. The patients were divided into two groups, sufficient (score ≥ 6) and insufficient (score < 6) activity groups, based on their level of PA as determined by their UCLA activity score 1 year after THA. The association of PA with the amount of changes in muscle density was examined with Spearman's rank correlation coefficient. Logistic regression analysis was performed to identify postoperative factors determining PA at 1 year after THA. RESULTS: Spearman's rank correlation coefficient showed a significantly positive association between recovery in PA and an increase in muscle density of the gluteus maximus, gluteus medius, iliopsoas, and quadriceps muscles. Additionally, logistic regression analysis confirmed that postoperative muscle densities of the gluteus maximus and quadriceps muscles were variables determining the PA 1 year after THA. CONCLUSION: The findings of this study indicated that the improvement of fatty infiltration in lower limb muscles, especially in the gluteus maximus and quadriceps, is likely to promote the increase in postoperative PA.

Single slice MR image estimation of 3D supraspinatus intramuscular fatty infiltration in older adults: relevance for clinical practice and research.

OBJECTIVE: (1) To compare older adults stratified by supraspinatus tendon tear status (STT status)-no tear (Intact), partial-thickness (PT) tear, full-thickness (FT) tear-by 3D Dixon fat fraction (3D-FF); 2D fat fraction (2D-FF); and 2D Goutallier grade (2D-GG) at the Y-shaped view, and 1.4 cm and 2.8 cm medial to the Y-shaped view. Stratified by STT status to determine (2) correlation of 3D-FF with 2D-FF and 2D-GG and (3) inter-rater reliability at and medial to the Y-shaped view. MATERIALS AND METHODS: Forty-five volunteers ≥ 60 years recruited prospectively received shoulder MRI. 3D-FF and 2D-FF were measured on 6-point-Dixon MRI by three trainees. Goutallier grade was assessed on T1-weighted MRI by three fellowship-trained diagnostic radiologists. Descriptive, reliability, and correlation analyses were performed. RESULTS: Groups showed no difference in age. The FT group showed higher (p < 0.05) mean 3D-FF (14.09% ± 10.99%), mean 2D-FF (1.4 cm medial to Y-shaped view, 14.91% ± 12.11%; 2.8 cm medial to Y-shaped view, 13.32% ± 9.48%), and mean 2D-GG (Y-shaped view, 1.71 ± 0.78; 1.4 cm medial to Y-shaped view, 1.71 ± 0.69; 2.8 cm medial to Y-shaped view, 1.71 ± 0.72), relative to Intact/PT groups. 3D-FF showed strong correlation with 2D-FF among all groups/all analyses (rho, 0.80-0.98; p < 0.001). 3D-FF showed strong correlation with 2D-GG for all FT group analyses (rho, 0.85-0.91; p < 0.05). 3D-FF showed moderate-to-strong correlation considering all Intact/PT group analyses (rho, 0.51-0.79; p < 0.50). Dixon fat fraction showed excellent reliability for all groups (≥ 0.884, intraclass correlation coefficient). Goutallier grade showed excellent reliability for FT group (0.771, weighted Fleiss's kappa) but poor (0.294) and fair (0.502) for Intact and PT groups, respectively. CONCLUSION: Single slice MR image estimation of 3D supraspinatus intramuscular fatty infiltration has merit for continued use in clinical populations requiring potential rotator-cuff-repair surgery. However, Dixon fat fraction should be prioritized for use in research over Goutallier grade due to superior reliability.

Overexpression of PRDM16 Improves Muscle Function after Rotator Cuff Tears.

INTRODUCTION: Muscle atrophy, fibrosis and fatty infiltration (FI) are commonly seen in rotator cuff tears (RCT), which are critical factors that directly determine the clinical outcomes for patients with this injury. Therefore, improving muscle quality after RCT is crucial in improving the clinical outcome of tendon repair. In recent years, it has been discovered that adults have functional beige/brown adipose tissue (BAT) which can secrete batokines to promote muscle growth. PRDM16, a PR-domain containing protein, was discovered with the ability to determine the brown fat cell fate and stimulate its development. Thus, the goal of this study is to discover the role of PRDM16 in improving muscle function after massive tendon tears using a transgenic mouse model with an elevated level of PRDM16 expression. METHODS: Transgenic aP2 driven PRDM16 overexpression mice and C57BL/6J mice underwent unilateral supraspinatus (SS) tendon transection and suprascapular nerve transection (TTDN) as described previously (N=8 in each group). DigiGait was performed to evaluate forelimb function at 6 weeks post the TTDN injury. Bilateral SS muscles, interscapular brown fat, epididymal white fat, and inguinal beige fat were harvested for analysis. The expression of PRDM16 in adipose tissue was detected by Western Blot. Masson's trichome staining was conducted to evaluate the muscle fibrosis and Oil Red O staining was used to determine the fat infiltration. Muscle fiber type was determined by MHC expression via immunostaining. All data was presented in the form of mean±SD. T-test and two-way ANOVA analysis was performed to determine a statistically significant difference between groups. Significance was considered when P<0.05. RESULTS: Western blot data showed an increased expression of PRDM16 protein in both white and brown fat in PRDM16-overexpression mice compared to wild-type (WT) mice. Even though PRDM16 overexpression had no effect on increasing muscle weight, it significantly improved the forelimbs function with longer brake, stance and stride time, larger stride length and paw area in mice after RCT. Additionally, PRDM16 overexpression mice showed no difference in amount of fibrosis when compared to WT mice, however, they had significantly reduced area of fatty infiltration. These mice also exhibited abundant MHC-IIx fiber percentage in supraspinatus muscle after TTDN. CONCLUSION: Overexpression of PRDM16 significantly improved muscle function and reduced fatty infiltration after rotator cuff tears. Promoting BAT activity is beneficial in improving rotator cuff muscle quality and shoulder function after RCT.

Medial scapular body (MSB) Goutallier classification: MRI-based reliability and validity of evaluation of the Goutallier classification for grading fatty infiltration of the rotator cuff.

BACKGROUND: The degree of atrophy and fatty infiltration of rotator cuff muscle belly is a key predictor for cuff repairability. Traditionally, Goutallier grading of fatty infiltration is assessed at sagittal scapular Y-view. Massive rotator cuff tears are associated with tendon retraction and medial retraction of cuff musculature, resulting in medialization of the muscle bulk. Thus, standard Y-view can misrepresent the region of interest and may misguide clinicians when assessing repairability. It is hypothesized that by assessing the muscle belly with multiple medial sagittal magnetic resonance imaging (MRI) sections at the medial scapular body, the Medial Scapular Body-Goutallier Classification (MSB-GC) will improve reliability and repeatability, giving a more representative approximation to the degree of fatty infiltration, as compared with the original Y-view. METHODS: Fatty infiltration of the rotator cuff muscles were classified based on the Goutallier grade (0-4) at 3 defined sections: section 1, original Y-view; section 2, level of suprascapular notch; and section 3, 3 cm medial to the suprascapular notch on MRI scans. Six subspecialist fellowship-trained shoulder surgeons and 3 musculoskeletal radiologists independently evaluated deidentified MRI scans of included patients. RESULTS: Of 80 scans, 78% (n = 62) were massive cuff tears involving the supraspinatus, infraspinatus, and subscapularis tendons. Interobserver reliability (consistency between observers) for Goutallier grade was excellent for all 3 predefined sections (range: 0.87-0.95). Intraobserver reliability (repeatability) for Goutallier grade was excellent for all 3 sections and 4 rotator cuff muscles (range: 0.83-0.97). There was a moderate to strong positive correlation of Goutallier grades between sections 1 and 3 and between sections 2 and 3 and these were statistically significant (P < .001). There was a reduction in the severity of fatty infiltration on the Goutallier classification from sections 1 to 3 across all muscles: 42.5% of both supraspinatus and infraspinatus were downgraded by 1, 20% of supraspinatus and 3.8% of infraspinatus were downgraded by 2, and 2.5% of supraspinatus were downgraded by 3. CONCLUSION: This study found that applying the Goutallier classification to more medial MRI sections (MSB-GC) resulted in assignment of lower grades for all rotator cuff muscles. Additionally, this method demonstrated excellent test-retest reliability and repeatability. Inclusion of a more medial view or whole scapula on MRI, especially in advanced levels of tear retraction, could be more reliable and representative for assessment of the degree of fatty infiltration within the muscle bulk that could help predict tear repairability and therefore improve clinical decision making, which should be studied further in clinical studies.

Defining pseudoparalysis and pseudoparesis: a consensus study.

BACKGROUND: The purpose of this study was to establish consensus statements via a modified Delphi process on the definition of shoulder pseudoparalysis and pseudoparesis. METHODS: A consensus process on the definition of a diagnosis of pseudoparalysis utilizing a modified Delphi technique was conducted, and 26 shoulder/sports surgeons from 11 countries, selected based on their level of expertise in the field, participated in these consensus statements. Consensus was defined as achieving 80%-89% agreement, whereas strong consensus was defined as 90%-99% agreement, and unanimous consensus was indicated by 100% agreement with a proposed statement. RESULTS: Three statements regarding the diagnosis of pseudoparalysis reached strong (>89%) consensus: passive range of motion should be unaffected, the passive range of abduction should not be considered, and diagnosis should be excluded if lidocaine injection produces a substantial improvement in range of motion. Additionally, consensus (>79%) was reached that the active range of external rotation should not be considered for diagnosis, pain as a cause of restricted motion must be excluded, and that distinctions between restricted active flexion and external rotation should be made by range of motion rather than tear characteristics. No consensus could be reached on statements regarding the size, number of tendons or chronicity of cuff tears. Nor was there agreement on the active range of flexion permitted or on the difference between pseudoparalysis and pseudoparesis. CONCLUSION: A modified Delphi process was utilized to establish consensus on the definition of shoulder pseudoparalysis and pseudoparesis. Unfortunately, almost half of the statements did not reach consensus, and agreement could not be reached across all domains for a unifying definition for the diagnosis of pseudoparalysis in the setting of rotator cuff tears. Furthermore, it was not agreed how or whether pseudoparalysis should be differentiated from pseudoparesis. Based on the lack of a consensus for these terms, studies should report explicitly how these terms are defined when they are used.

Parathyroid hormone promotes induction of beige adipocytes and reversibly ameliorates muscle quality and atrophy following chronic rotator cuff tear in a rat model.

BACKGROUND: Fatty infiltration (FI) and muscle atrophy (MA) in the rotator cuff muscles following rotator cuff tears (RCT) persist postrepair, increasing the risk of re-tears. Brown adipocyte-like "beige adipocytes" are expected to have a therapeutic effect on intramuscular FI and MA due to their lipolytic activity and the muscle regenerative effects of their secreted factors. However, whether parathyroid hormone (PTH) ameliorates the already advanced FI and MA remains unknown. Therefore, this study aimed to clarify whether PTH promotes the expression of beige adipocytes and ameliorates advanced FI and MA following chronic RCT in rats. METHODS: Supraspinatus muscles were harvested from rats with chronic RCT after 4 or 8 weeks of PTH treatment and compared to those in the control group or to those at the start of treatment. FI was assessed by Oil Red O staining, and the staining area was evaluated as a percentage of the muscle cross-sectional area. MA was evaluated by measuring muscle wet weight and cross-sectional area of muscle fiber. Beige adipocyte expression was evaluated by immunostaining for uncoupling protein 1 (UCP1). Fibro-adipogenic progenitors (FAPs) were separated from muscle-injured mice. We assessed whether PTH could diminish fat droplet accumulation by promoting the differentiation of FAPs into beige adipocytes. RESULTS: After 4 weeks, PTH reduced the area fraction of FI in the rat supraspinatus muscle following chronic RCT compared with that at the beginning of treatment (P = .028). In addition, PTH increased wet muscle mass (P < .001), and muscle fiber cross-sectional area (P = .018) compared with measurements at the start of treatment. PTH administration promoted the expression of UCP1, a beige adipocyte marker, in the supraspinatus muscle (P = .019). PTH increased gene expression of beige adipocyte-related markers and suppressed fat droplet accumulation even after adipogenic differentiation of FAPs (P = .004) but did not reduce fat droplets that had already accumulated in in vitro experiments. CONCLUSIONS: PTH facilitated beige adipocyte expression and reversibly ameliorated muscle quality and atrophy following chronic RCT by hindering fat droplet accumulation and facilitating muscle regeneration. Therefore, PTH may be a medical treatment for FI and MA following RCT, leading to expanded rotator cuff repair indications.

Mo-fi-disc scoring system: Towards understanding the radiological tools to better delineate the disease process and enhancing our solutions for low back pain in artificial intelligence era.

BACKGROUND: 'Mo-fi-disc' is a new scoring system that quantifies degeneration of the lumbar spine and predicts the intensity of low back pain (LBP). However, its association with LBP-related disability is unknown. In the present study, we aimed to analyze whether 'Mo-fi-disc' scoring system could predict LBP-related disability and distinguish patients with LBP from asymptomatic subjects, while the spine medicine marching towards the era of artificial intelligence (AI). METHODS: This is a cross-sectional analysis of a prospectively collected database. We included age-, gender-, and BMI-matched 132 subjects (patients: 66, asymptomatic subjects: 66). Modic changes (Mo), fatty infiltration in the paraspinal muscles (fi), and intervertebral disc degeneration (disc) were evaluated using 'Mo-fi-disc' scoring system on lumbar spine magnetic resonance imaging. Pain and disability were evaluated with visual analogue scale (VAS) and Oswestry disability index (ODI), respectively. RESULTS: A Mo-fi-disc score of 5.5 was the most appropriate cut-off value. Mo-fi-disc scoring system had an OR of 1.79 in distinguishing patients with LBP from asymptomatic subjects. One point increment in VAS and ODI had ORs of 1.82 and 1.13 for predicting higher Mo-fi-disc scores. CONCLUSION: 'Mo-fi-disc' scoring system is a useful tool depicting intensity of LBP and LBP-related disability. The cut off value of Mo-fi-disc score is 5.5 to distinguish patients with LBP from asymptomatic subjects. This scoring system, with progressive improvement of its faults, could help clinicians to select appropriate patients for conservative and surgical management in the very near future, in AI-based spine medicine. IRB APPROVAL NO: ATADEK 2019-12/4.

Subscapularis impairment on magnetic resonance imaging is correlated with functional limitations in neonatal brachial plexus palsy.

PURPOSE: The relationship between functional shoulder deficits in children with neonatal brachial plexus palsy (NBPP) and magnetic resonance imaging (MRI) shoulder abnormalities was evaluated. METHODS: Shoulder function was assessed in 16 children (mean age: 5.8 years; range: 3-12 years) with NBPP based on shoulder rotator muscle strength, as measured using an isokinetic dynamometer and the modified Mallet score. The thickness and fatty infiltration of the subscapularis and infraspinatus muscles, and the morphology of the glenoid on MRI, were also determined. RESULTS: The highest subscapularis fatty infiltration subgroup of NBPP patients promoted the highest alteration muscle thickness and modified Mallet score. CONCLUSIONS: In NBPP children, subscapularis impairments play a major role in the functional limitations. This study of pediatric NBPP patients highlighted the value of adding an examination of the muscles to routine MRI assessment of bone parameters in the shoulders of NBPP children. TRIAL REGISTRATION: NCT03440658.

Fatty infiltration of the erector spinae at the upper lumbar spine could be a landmark for low back pain.

PURPOSE: Intervertebral disc degeneration (IVDD), Modic changes, and fatty infiltration in the paraspinal muscles are possible causes of low back pain (LBP). Multifidus has been the most commonly blamed paraspinal muscle in the etiology of LBP. However, it contributes to 20% of the extensor moment on the lumbar spine. In the present study, we aimed to identify whether patients with LBP and asymptomatic subjects differed in terms of intervertebral discs, end-plates, and fatty infiltration in their paraspinal muscles. METHODS: Consecutive women and men, who visited the spine outpatient clinics with chronic LBP and had lumbar spine MRI for their LBP without leg pain were included. Asymptomatic subjects without LBP/leg pain for the last year were recruited. Modic changes, IVDD, and fatty infiltration in the paraspinal muscles were evaluated on lumbar spine magnetic resonance imagings of the patients with LBP and age-, gender- and BMI-matched asymptomatic controls. RESULTS: Low back pain was closely associated with fatty infiltration in the paraspinal muscles at all lumbar levels whereas it had association with severe IVDD and Modic changes at lower lumbar levels. Multifidus at the lower lumbar levels was the fattiest paraspinal muscle in both asymptomatic subjects and patients with LBP. Patients with LBP had severe fatty infiltration in the erector spinae at the upper lumbar levels. CONCLUSION: Severe IVDD and Modic changes were more common at lower lumbar levels in patients with LBP. Both asymptomatic subjects and those with LBP had fatty multifidus at lower lumbar levels, whereas those with LBP had fatty infiltration in the erector spinae at upper lumbar levels. We suggest that fatty infiltration could have started in the multifidus. The erector spinae had greater contribution to the lumbar extension compared to the multifidus. Thus, LBP could develop when the quality of the erector spinae at the upper lumbar levels impairs due to fatty infiltration.

Caveolin-1 is involved in fatty infiltration and bone-tendon healing of rotator cuff tear.

BACKGROUND: Caveolin-1 has been predicted, based on RNA transcriptome sequencing, as a key gene in rotator cuff tear (RCT) and it is related to fatty infiltration. This study aims to elucidate the upstream and downstream mechanism of Caveolin-1 in fatty infiltration and bone-tendon healing after RCT in rat models. METHODS: Differentially expressed genes related to RCT were screened, followed by functional enrichment analysis and protein-protein interaction analysis. GATA6 was overexpressed and Caveolin-1 was knocked down in tendon stem cells (TSCs) to evaluate their effects on the adipogenic differentiation of TSCs. In addition, a RCT rat model was constructed and injected with lentivirus carrying oe-GATA6, oe-Caveolin-1 alone or in combination to assess their roles in fatty infiltration and bone-tendon healing. RESULTS AND CONCLUSION: Caveolin-1 was identified as a key gene involved in the RCT process. In vitro results demonstrated that Caveolin-1 knockdown inhibited adipogenic differentiation of TSCs by activating the cAMP/PKA pathway. GATA6 inhibited the transcription of Caveolin-1 and inhibited its expression, thus suppressing the adipogenic differentiation of TSCs. In vivo data confirmed that GATA6 overexpression activated the cAMP/PKA pathway by downregulating Caveolin-1 and consequently repressed fatty infiltration, promoted bone-tendon healing, improved biomechanical properties and reduced the rupture risk of injured tendon in rats after RCT. Overall, this study provides novel insights into the mechanistic action of Caveolin-1 in the fatty infiltration and bone-tendon healing after RCT.

The relationship between clinical examination measures and ultrasound measures of fascia thickness surrounding trunk muscles or lumbar multifidus fatty infiltrations: An exploratory study.

Patients with chronic low back pain (CLBP) exhibit remodelling of the lumbar soft tissues such as muscle fatty infiltrations (MFI) and fibrosis of the lumbar multifidus (LuM) muscles, thickness changes of the thoracolumbar fascia (TLF) and perimuscular connective tissues (PMCT) surrounding the abdominal lateral wall muscles. Rehabilitative ultrasound imaging (RUSI) parameters such as thickness and echogenicity are sensitive to this remodelling. This experimental laboratory study aimed to explore whether these RUSI parameters (LuM echogenicity and fascia thicknesses), hereafter called dependent variables (DV) were linked to independent variables (IV) such as (1) other RUSI parameters (trunk muscle thickness and activation) and (2) physical and psychological measures. RUSI measures, as well as a clinical examination comprising physical tests and psychological questionnaires, were collected from 70 participants with LBP. The following RUSI dependent variables (RUSI-DV), measures of passive tissues were performed bilaterally: (1) LuM echogenicity (MFI/fibrosis) at three vertebral levels (L3/L4, L4/L5 and L5/S1); (2) TLF posterior layer thickness, and (3) PMCT thickness of the fasciae between subcutaneous tissue thickness (STT) and external oblique (PMCTSTT/EO ), between external and internal oblique (PMCTEO/IO ), between IO and transversus abdominis (PMCTIO/TrA ) and between TrA and intra-abdominal content (PMCTTrA/IA ). RUSI measures of trunk muscle's function (thickness and activation), also called measures of active muscle tissues, were considered as independent variables (RUSI-IV), along with physical tests related to lumbar stability (n = 6), motor control deficits (n = 7), trunk muscle endurance (n = 4), physical performance (n = 4), lumbar posture (n = 2), and range of motion (ROM) tests (n = 6). Psychosocial measures included pain catastrophizing, fear-avoidance beliefs, psychological distress, illness perceptions and concepts related to adherence to a home-based exercise programme (physical activity level, self-efficacy, social support, outcome expectations). Six multivariate regression models (forward stepwise selection) were generated, using RUSI-DV measures as dependent variables and RUSI-IV/physical/psychosocial measures as independent variables (predictors). The six multivariate models included three to five predictors, explaining 63% of total LuM echogenicity variance, between 41% and 46% of trunk superficial fasciae variance (TLF, PMCTSTT/EO ) and between 28% and 37% of deeper abdominal wall fasciae variance (PMCTEO/IO , PMCTIO/TrA and PMCTTrA/IA ). These variables were from RUSI-IV (LuM thickness at rest, activation of IO and TrA), body composition (percent fat) and clinical physical examination (lumbar and pelvis flexion ROM, aberrant movements, passive and active straight-leg raise, loaded-reach test) from the biological domain, as well as from the lifestyle (physical activity level during sports), psychological (psychological distress-cognitive subscale, fear-avoidance beliefs during physical activities, self-efficacy to exercise) and social (family support to exercise) domains. Biological, psychological, social and lifestyle factors each accounted for substantial variance in RUSI-passive parameters. These findings are in keeping with a conceptual link between tissue remodelling and factors such as local and systemic inflammation. Possible explanations are discussed, in keeping with the hypothesis-generating nature of this study (exploratory). However, to impact clinical practice, further research is needed to determine if the most plausible predictors of trunk fasciae thickness and LuM fatty infiltrations have an effect on these parameters.

Magnetic resonance quantification of skeletal muscle lipid infiltration in a humanized mouse model of Duchenne muscular dystrophy.

Rodent models of Duchenne muscular dystrophy (DMD) often do not recapitulate the severity of muscle wasting and resultant fibro-fatty infiltration observed in DMD patients. Having recently documented severe muscle wasting and fatty deposition in two preclinical models of muscular dystrophy (Dysferlin-null and mdx mice) through apolipoprotein E (ApoE) gene deletion without and with cholesterol-, triglyceride-rich Western diet supplementation, we sought to determine whether magnetic resonance imaging and spectroscopy (MRI and MRS, respectively) could be used to detect, characterize, and compare lipid deposition in mdx-ApoE knockout with mdx mice in a diet-dependent manner. MRI revealed that both mdx and mdx-ApoE mice exhibited elevated proton relaxation time constants (T2 ) in their lower hindlimbs irrespective of diet, indicating both chronic muscle damage and fatty tissue deposition. The mdx-ApoE mice on a Western diet (mdx-ApoEW ) presented with greatest fatty tissue infiltration in the posterior compartment of the hindlimb compared with other groups, as detected by MRI/MRS. High-resolution magic angle spinning confirmed elevated lipid deposition in the posterior compartments of mdx-ApoEW mice in vivo and ex vivo, respectively. In conclusion, the mdx-ApoEW model recapitulates some of the extreme fatty tissue deposition observed clinically in DMD muscle but typically absent in mdx mice. This preclinical model will help facilitate the development of new imaging modalities directly relevant to the image contrast generated in DMD, and help to refine MR-based biomarkers and their relationship to tissue structure and disease progression.

Comparison of paraspinal muscle composition measurements using IDEAL fat-water and T2-weighted MR images.

PURPOSE: The purpose of this study was to evaluate the agreement between paraspinal muscle composition measurements obtained from fat-water images using % fat-signal fraction (%FSF) in comparison to those obtained from T2-weighted magnetic resonance images (MRI) using a thresholding method. METHODS: A sample of 35 subjects (19 females, 16 males; 40.26 ± 11.3 years old) was selected from a cohort of patients with chronic low back pain (LBP). Axial T2-weighted and IDEAL (Lava-Flex, 2 echo sequence) fat and water MR images were obtained using a 3.0 Tesla GE scanner. Multifidus, erector spinae, and psoas major muscle composition measurements were acquired bilaterally at L4-L5 and L5-S1 using both imaging sequences and related measurement methods. All measurements were obtained by the same rater, with a minimum of 7 days between each method. Intra-class correlation coefficients (ICCs) were calculated to assess intra-rater reliability. Pearson Correlation and Bland-Altman 95% limits of agreement were used to assess the agreement between both measurement methods. RESULTS: The intra-rater reliability was excellent for all measurements with ICCs varying between 0.851 and 0.997. Strong positive correlations indicating a strong relationship between composition measurements were obtained from fat-water and T2-weighted images for bilateral multifidus and erector spinae muscles at both spinal levels and the right psoas major muscle at L4-L5, with correlation coefficient r ranging between 0.67 and 0.92. Bland-Altman plots for bilateral multifidus and erector spinae muscles at both levels revealed excellent agreement between the two methods, however, systematic differences between both methods were evident for psoas major fat measurements. CONCLUSION: Our findings suggest that utilizing fat-water and T2-weighted MR images are comparable for quantifying multifidus and erector spinae muscle composition but not of the psoas major. While this suggests that both methods could be used interchangeably for the multifidus and erector spinae, further evaluation is required to expand and confirm our findings to other spinal levels.

Gender differences in lateral pterygoid muscle in patients with anterior disk displacement.

OBJECTIVE: To use quantitative MRI to assess gender differences in lateral pterygoid muscle (LPM) characteristics in patients with anterior disk displacement (ADD). METHODS: Lateral pterygoid muscle of 51 patients diagnosed with temporomandibular joint disorders (TMD) who underwent T1-weighted Dixon and T1-mapping sequences were retrospectively analyzed. There were 34 female patients (10 with bilateral normal position disk [NP]; 24 with bilateral ADD) and 17 male patients (eight with bilateral NP; nine with bilateral ADD) among them. After controlling for age, differences in fat fraction, T1 value, volume and histogram features related to gender and disk status were tested with 2-way ANCOVA or Quade ANCOVA with Bonferroni correction. RESULTS: Volume of LPM in NP was significantly smaller than that of ADD (p < 0.001). Fat fraction of LPM in females with NP was significantly higher than males with NP (p < 0.05). Females with ADD showed a significantly higher T1 value (p < 0.05), and higher intramuscular heterogeneity than males with ADD. CONCLUSIONS: Lateral pterygoid muscle in female TMD patients presented more fatty infiltration in the NP stage and might present more fibrosis in the ADD stage compared with males. Together, this leads to more serious intramuscular heterogeneity during the pathogenesis of ADD in females.