Posterior capsule edema in adhesive capsulitis: comparison with established non-contrast MRI findings and multivariable analysis.

OBJECTIVES: To evaluate posterior glenohumeral capsule edema compared to other MRI findings in adhesive capsulitis (AC). METHODS: This study was approved by the local Institutional Review Board and it is HIPAA compliant. A retrospective search identified subjects who received fluoroscopically guided intra-articular corticosteroid injections for AC and had an MRI within 6 months prior to injection. The study group was compared with an age-, sex-, and side-matched control group who underwent the same procedures but did not have AC. MRIs were evaluated for edema of posterior capsule, anterior capsule, axillary pouch, coracohumeral ligament (CHL) and rotator interval (RI), thickness of axillary pouch and CHL, thickness of anterior capsule, RI and subcoracoid fat replacement, and teres minor atrophy and edema. Multivariable analysis was performed. RESULTS: A total of 57 subjects with AC and 57 matched controls were studied: mean age 52 ± 7 (range 31-71) years, 37 female and 20 male, 22 right and 35 left. Posterior capsule edema was more common in the AC group vs. control group (66.7 vs 17.5%, p < 0.001). Multivariable analysis showed posterior capsule edema, CHL edema, and axillary pouch (glenoid) thickness (optimum cutoff = 4 mm) were significant independent predictors of AC. Simplified analysis using these three variables had an area under the curve of 0.860 (95%CI: 0.792-0.928). With all three variables present, the sensitivity and specificity for AC were 32% and 98%, respectively. CONCLUSIONS: Posterior joint capsule edema may be helpful to confirm AC. Posterior capsule edema, CHL edema, and axillary pouch (glenoid) thickness produce a strong model for distinguishing AC from controls. CLINICAL RELEVANCE STATEMENT: Edema involving the posterior shoulder joint capsule is an imaging marker of capsulitis and is useful in differentiating patients with adhesive capsulitis from those without in conjunction with other proven MRI findings. KEY POINTS: • Posterior capsule edema has a sensitivity of 66.7% and a specificity of 82.5% for the detection of adhesive capsulitis. • Posterior capsule edema, coracohumeral ligament (CHL) edema, and axillary pouch (glenoid) thickness were significant independent predictors of adhesive capsulitis, and combining these variables together produces a very strong model for distinguishing cases from controls (AUC = 0.860). • Optimal cutoff values for CHL, axillary pouch (humeral), axillary pouch (glenoid), and axillary pouch (total) thickness were 2.5, 2.6, 4, and 6.3 mm, respectively.

Decreased rotator cuff muscle cross-sectional areas in subjects with adhesive capsulitis: a study comparing male and female subjects.

OBJECTIVE: To compare rotator cuff (RC) muscle cross-sectional areas (CSA) in subjects with adhesive capsulitis (AC) to age- and sex-matched controls. MATERIALS AND METHODS: We retrospectively analyzed 97 shoulder MRIs or MR arthrography studies, of which 42 were clinically diagnosed with AC (27 female, 15 male) and 55 were age- and sex-matched controls (38 female, 17 male). All AC subjects underwent imaging ≥ 6 months after symptom onset. All imaging was examined to exclude RC full-thickness tears and prior surgery. A standardized T1 sagittal MR image was segmented in each subject to obtain the CSA of subscapularis (SSC), supraspinatus (SSP), and infraspinatus (ISP) muscles. Differences in CSAs between AC and control subjects were analyzed by sex (females and males separately) and all subjects combined. RESULTS: AC females had significantly decreased SSC (P = 0.002) and total (P = 0.006) CSAs compared to controls. Male AC subjects showed decreased SSC (P = 0.044), SSP (P = 0.001), and total (P = 0.005) CSAs. Across all subjects, male and female, the AC cohort had significantly decreased SSC (P = 0.019) and total (P = 0.029) CSAs compared to controls. CONCLUSION: Decreased RC muscle CSAs were present in AC subjects with ≥ 6 months of symptom duration, with decreased SSC and total CSAs in male and female subjects, and decreased SSP CSA in males.

Cross-sectional areas of rotator cuff muscles in males without tears on shoulder MRI.

OBJECTIVE: To establish reference values of rotator cuff (RC) cross sectional area (CSA) in males. MATERIALS AND METHODS: We retrospectively analyzed shoulder MRIs from 500 patients aged 13-78 years, grouped as follows (N=100 in each): <20, 20-30, 30-40, 40-50, >50 years. All examinations were reviewed to exclude prior surgery, tears, or significant RC pathology. We segmented a standardized T1 sagittal MR image in each case to obtain CSA of supraspinatus (SUP), infraspinatus/teres minor (INF), and subscapularis (SUB) muscles. Across age groups, we recorded individual and total muscle CSA. We also performed ratios between individual muscle CSA and total CSA to examine total muscle mass contribution over age groups. We tested for differences between age groups controlled for BMI. RESULTS: CSAs for SUP, INF, SUB, and total RC CSA were lower in subjects >50 years compared to all other groups (P<0.003 for all comparisons), persisting after controlling for BMI (P<0.03). Relative contribution of SUP CSA to total RC CSA was stable across age groups (P>0.32). INF CSA relative to total RC CSA increased with age, whereas SUB decreased (P<0.005). Subjects >50 years showed lower SUP (-15%), INF (-6%), and SUB (-21%) CSA, when compared to mean CSAs of all subjects <50 years. Total RC CSA significantly correlated with age (r=-0.34, P<0.001), persisting after controlling for BMI (r=-0.42, P<0.001). CONCLUSION: RC muscles in male subjects with no tears on MRI show decreasing CSA with age, independent of BMI.

Proteomic Analysis of Hepatic Fibrosis in Human Immunodeficiency Virus-Associated Nonalcoholic Fatty Liver Disease Demonstrates Up-regulation of Immune Response and Tissue Repair Pathways.

BACKGROUND: Human immunodeficiency virus (HIV)-associated nonalcoholic fatty liver disease (NAFLD) is characterized by a high prevalence of hepatic fibrosis as a strong clinical predictor of all-cause and liver-specific mortality risk. METHODS: We leveraged data from an earlier clinical trial to define the circulating proteomic signature of hepatic fibrosis in HIV-associated NAFLD. A total of 183 plasma proteins within 2 high-multiplex panels were quantified at baseline and at 12 months (Olink Cardiovascular III; Immuno-Oncology). RESULTS: Twenty proteins were up-regulated at baseline among participants with fibrosis stages 2-3 versus 0-1. Proteins most differentially expressed included matrix metalloproteinase 2 (P < .001), insulin-like growth factor-binding protein 7 (P = .001), and collagen α1(I) chain (P = .001). Proteins were enriched within pathways including response to tumor necrosis factor and aminopeptidase activity. Key proteins correlated directly with visceral adiposity and glucose intolerance and inversely with CD4+ T-cell count. Within the placebo-treated arm, 11 proteins differentially increased among individuals with hepatic fibrosis progression over a 12-month period (P < .05). CONCLUSIONS: Among individuals with HIV-associated NAFLD, hepatic fibrosis was associated with a distinct proteomic signature involving up-regulation of tissue repair and immune response pathways. These findings enhance our understanding of potential mechanisms and biomarkers of hepatic fibrosis in HIV.

Randomized Placebo-Controlled Trial to Evaluate Effects of Eplerenone on Myocardial Perfusion and Function Among Persons With Human Immunodeficiency Virus (HIV)-Results From the MIRACLE HIV Study.

BACKGROUND: Increased renin angiotensin aldosterone system (RAAS) activity may contribute to excess cardiovascular disease in people with HIV (PWH). We investigated how RAAS blockade may improve myocardial perfusion, injury, and function among well-treated PWH. METHODS: Forty PWH, on stable ART, without known heart disease were randomized to eplerenone 50 mg PO BID (n = 20) or identical placebo (n = 20) for 12 months. The primary endpoints were (1) myocardial perfusion assessed by coronary flow reserve (CFR) on cardiac PET or stress myocardial blood flow (sMBF) on cardiac MRI or (2) myocardial inflammation by extracellular mass index (ECMi) on cardiac MRI. RESULTS: Beneficial effects on myocardial perfusion were seen for sMBF by cardiac MRI (mean [SD]: 0.09 [0.56] vs -0.53 [0.68] mL/min/g; P = .03) but not CFR by cardiac PET (0.01 [0.64] vs -0.07 [0.48]; P = .72, eplerenone vs placebo). Eplerenone improved parameters of myocardial function on cardiac MRI including left ventricular end diastolic volume (-13 [28] vs 10 [26] mL; P = .03) and global circumferential strain (GCS; median [interquartile range 25th-75th]: -1.3% [-2.9%-1.0%] vs 2.3% [-0.4%-4.1%]; P = .03), eplerenone versus placebo respectively. On cardiac MRI, improvement in sMBF related to improvement in global circumferential strain (ρ = -0.65, P = .057) among those treated with eplerenone. Selecting for those with impaired myocardial perfusion (CFR <2.5 and/or sMBF <1.8), there was a treatment effect of eplerenone versus placebo to improve CFR (0.28 [0.27] vs -0.05 [0.36]; P = .04). Eplerenone prevented a small increase in troponin (0.00 [-0.13-0.00] vs 0.00 [0.00-0.74] ng/L; P = .03) without effects on ECMi (0.9 [-2.3-4.3] vs -0.7 [-2.2--0.1] g/m2; P = .38). CD4+ T-cell count (127 [-38-286] vs -6 [-168-53] cells/µL; P = .02) increased in the eplerenone- versus placebo-treated groups. CONCLUSIONS: RAAS blockade with eplerenone benefitted key indices and prevented worsening of myocardial perfusion, injury, and function among PWH with subclinical cardiac disease when compared with placebo. CLINICAL TRIALS REGISTRATION: NCT02740179 (https://clinicaltrials.gov/ct2/show/NCT02740179?term=NCT02740179&draw=2&rank=1).

Original research: utilization of a convolutional neural network for automated detection of lytic spinal lesions on body CTs.

OBJECTIVE: To develop, train, and test a convolutional neural network (CNN) for detection of spinal lytic lesions in chest, abdomen, and pelvis CT scans. MATERIALS AND METHODS: Cases of malignant spinal lytic lesions in CT scans were identified. Images were manually segmented for the following classes: (i) lesion, (ii) normal bone, (iii) background. If more than one lesion was on a single slice, all lesions were segmented. Images were stored as 128×128 pixel grayscale, with 10% segregated for testing. The training pipeline of the dataset included histogram equalization and data augmentation. A model was trained on Keras/Tensorflow using an 80/20 training/validation split, based on U-Net architecture. Additional testing of the model was performed on 1106 images of healthy controls. Global sensitivity measured detection of any lesion on a single image. Local sensitivity and positive predictive value (PPV) measured detection of all lesions on an image. Global specificity measured false positive rate in non-pathologic bone. RESULTS: Six hundred images were obtained for model creation. The training set consisted of 540 images, which was augmented to 20,000. The test set consisted of 60 images. Model training was performed in triplicate. Mean Dice scores were 0.61 for lytic lesion, 0.95 for normal bone, and 0.99 for background. Mean global sensitivity was 90.6%, local sensitivity was 74.0%, local PPV was 78.3%, and global specificity was 63.3%. At least one false positive lesion was noted in 28.8-44.9% of control images. CONCLUSION: A task-trained CNN showed good sensitivity in detecting spinal lytic lesions in axial CT images.

Role of renin-angiotensin-aldosterone system activation and other metabolic variables in relation to arterial inflammation in HIV.

BACKGROUND: Arterial inflammation remains increased among persons with HIV (PWH) compared with persons without HIV (PWOH) even when controlling for traditional risk factors. We sought to understand whether increased renin-angiotensin-aldosterone system (RAAS) activation may be related to arterial inflammation in PWH and when compared with PWOH. DESIGN: Twenty PWH and 9 PWOH followed a controlled, standardized low and liberal sodium diet to simulate a RAAS-activated and RAAS-suppressed state, respectively. We measured serum lipoprotein-associated phospholipase A2 (LpPLA2) concentrations following both conditions to assess the physiologic dynamics of aldosterone in relation to arterial inflammation. RESULTS: LpPLA2 levels were significantly higher among PWH versus PWOH during both the RAAS-activated state[5.3(4.2, 6.1) versus 4.0(3.0, 4.8)nmol/L, median(interquartile range),p = .01]) and RAAS-suppressed state[4.4(3.9, 5.3) versus 3.8(3.4, 4.1)nmol/L,p = .01]. Among PWH, but not PWOH, LpPLA2 increased significantly with RAAS activation(p = .03). LpPLA2 levels measured during the RAAS-suppressed state among PWH remained relatively higher than LpPLA2 levels under both conditions among PWOH. Log LpPLA2 was related to log aldosterone during the RAAS-activated state(r = .39,p = .04) among all participants. Log LpPLA2 was correlated with visceral fat(r = .46,p = .04) and log systolic blood pressure(r = .57,p = .009) during a RAAS-activated state when an increase in aldosterone was stimulated in HIV. CONCLUSION: LpPLA2 is increased during a RAAS-activated state among PWH, but not among PWOH. Further, LpPLA2 was increased in both RAAS-activated and suppressed states in PWH compared with PWOH. These data suggest a biological link between increased aldosterone and arterial inflammation in this population. Future studies should test RAAS blockade on arterial inflammation as a targeted treatment approach in HIV.

Body composition predictors of mortality in patients undergoing surgery for long bone metastases.

BACKGROUND AND OBJECTIVES: Body composition measurements using computed tomography (CT) may serve as imaging biomarkers of survival in patients with and without cancer. This study assesses whether body composition measurements obtained on abdominal CTs are independently associated with 90-day and 1-year mortality in patients with long-bone metastases undergoing surgery. METHODS: This single institutional retrospective study included 212 patients who had undergone surgery for long-bone metastases and had a CT of the abdomen within 90 days before surgery. Quantification of cross-sectional areas (CSA) and CT attenuation of abdominal subcutaneous adipose tissue, visceral adipose tissue, and paraspinous and abdominal muscles were performed at L4. Multivariate Cox proportional-hazards analyses were performed. RESULTS: Sarcopenia was independently associated with 90-day mortality (hazard ratio [HR] = 1.87; 95% confidence interval [CI] = 1.11-3.16; p = 0.019) and 1-year mortality (HR = 1.50; 95% CI = 1.02-2.19; p = 0.038) in multivariate analysis while controlling for clinical variables such as primary tumors, comorbidities, and chemotherapy. Abdominal fat CSAs and muscle attenuation were not associated with mortality. CONCLUSIONS: The presence of sarcopenia assessed by CT is predictive of 90-day and 1-year mortality in patients undergoing surgery for long-bone metastases. This body composition measurement can be used as novel imaging biomarker supplementing existing prognostic tools to optimize patient selection for surgery and improve shared decision making.

Distal Triceps Tendon Tears: Magnetic Resonance Imaging Patterns Using a Systematic Classification.

OBJECTIVE: This study aimed to evaluate distal triceps tendon tear patterns using a systematic classification based on the tendon's layered structure. METHODS: We retrospectively identified Magnetic resonance imaging (MRI) examinations with triceps tendon tears that underwent reconstructive surgery. Magnetic resonance images were reviewed independently by 2 musculoskeletal radiologists to determine tendon layer involvement and ancillary findings, including tear size, involvement of triceps lateral expansion, and presence of olecranon bursal fluid. Surgical reports were scrutinized for level of anatomic detail and correlation with imaging findings. RESULTS: We identified 69 triceps tendon tears in 68 subjects (61 men, 7 women; mean age, 45 ± 12 years) who underwent surgical reconstruction. On MRI, the superficial layer was always involved with either a partial or full-thickness tear. The most common tear pattern was a combination of superficial layer full-thickness tear with deep layer partial tear (25 of 69 [36%]). Mean tear length was 24 ± 12 mm. We found no cases of isolated deep layer tears. Involvement of triceps lateral expansion and presence of bursal fluid correlated positively with tear severity of superficial and deep layers (P < 0.001). Detailed surgical correlation was limited, with only 9 of 69 (13%) of surgical reports containing information specifically addressing individual tendon layers. CONCLUSIONS: Triceps tendon tears show tear patterns following its layered structure and can be assessed by MRI. Radiologists and surgeons are encouraged to describe tear patterns considering both superficial and deep tendon layers.

Breast adipose tissue attenuation as a novel imaging biomarker for cardiometabolic risk.

BACKGROUND: Certain adipose tissue depots infer higher cardiometabolic risk than body mass index (BMI). PURPOSE: To assess breast adipose tissue (BrAT) attenuation as a novel imaging biomarker for cardiometabolic risk. MATERIAL AND METHODS: We studied 151 women (mean age = 56 ± 1 years) across the weight spectrum. BrAT attenuation, abdominal adipose tissue cross-sectional areas (CSA), and attenuation were quantified using non-contrast computed tomography (CT) scans. Cardiometabolic risk factors were assessed from medical records. RESULTS: BrAT attenuation was lower in obese women compared to lean women. BrAT attenuation was inversely associated with BMI, waist circumference, abdominal fat CSA, fasting glucose, and triglycerides (P ≤ 0.02), and positively associated with abdominal adipose tissue attenuation (P < 0.001). BrAT attenuation had a sensitivity of 90% but a specificity of only 35% in detecting the metabolic syndrome (area under the curve = 0.63). CONCLUSION: BrAT attenuation is associated with cardiometabolic risk markers and could serve as an imaging biomarker for opportunistic risk assessment in patients undergoing CT examination of the chest.

Automated detection and segmentation of sclerotic spinal lesions on body CTs using a deep convolutional neural network.

PURPOSE: To develop a deep convolutional neural network capable of detecting spinal sclerotic metastases on body CTs. MATERIALS AND METHODS: Our study was IRB-approved and HIPAA-compliant. Cases of confirmed sclerotic bone metastases in chest, abdomen, and pelvis CTs were identified. Images were manually segmented for 3 classes: background, normal bone, and sclerotic lesion(s). If multiple lesions were present on a slice, all lesions were segmented. A total of 600 images were obtained, with a 90/10 training/testing split. Images were stored as 128 × 128 pixel grayscale and the training dataset underwent a processing pipeline of histogram equalization and data augmentation. We trained our model from scratch on Keras/TensorFlow using an 80/20 training/validation split and a U-Net architecture (64 batch size, 100 epochs, dropout 0.25, initial learning rate 0.0001, sigmoid activation). We also tested our model's true negative and false positive rate with 1104 non-pathologic images. Global sensitivity measured model detection of any lesion on a single image, local sensitivity and positive predictive value (PPV) measured model detection of each lesion on a given image, and local specificity measured the false positive rate in non-pathologic bone. RESULTS: Dice scores were 0.83 for lesion, 0.96 for non-pathologic bone, and 0.99 for background. Global sensitivity was 95% (57/60), local sensitivity was 92% (89/97), local PPV was 97% (89/92), and local specificity was 87% (958/1104). CONCLUSION: A deep convolutional neural network has the potential to assist in detecting sclerotic spinal metastases.

Growth Hormone Releasing Hormone Reduces Circulating Markers of Immune Activation in Parallel with Effects on Hepatic Immune Pathways in Individuals with HIV-infection and Nonalcoholic Fatty Liver Disease.

BACKGROUND: The growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis modulates critical metabolic pathways; however, little is known regarding effects of augmenting pulsatile GH secretion on immune function in humans. This study used proteomics and gene set enrichment analysis to assess effects of a GH releasing hormone (GHRH) analog, tesamorelin, on circulating immune markers and liver tissue in people with human immunodeficiency virus (HIV) (PWH) and nonalcoholic fatty liver disease (NAFLD). METHODS: 92 biomarkers associated with immunity, chemotaxis, and metabolism were measured in plasma samples from 61 PWH with NAFLD who participated in a double-blind, randomized trial of tesamorelin versus placebo for 12 months. Gene set enrichment analysis was performed on serial liver biopsies targeted to immune pathways. RESULTS: Tesamorelin, compared to placebo, decreased interconnected proteins related to cytotoxic T-cell and monocyte activation. Circulating concentrations of 13 proteins were significantly decreased, and no proteins increased, by tesamorelin. These included 4 chemokines (CCL3, CCL4, CCL13 [MCP4], IL8 [CXCL8]), 2 cytokines (IL-10 and CSF-1), and 4 T-cell associated molecules (CD8A, CRTAM, GZMA, ADGRG1), as well as ARG1, Gal-9, and HGF. Network analysis indicated close interaction among the gene pathways responsible for these proteins, with imputational analyses suggesting down-regulation of a closely related cluster of immune pathways. Targeted transcriptomics using liver tissue confirmed a significant end-organ signal of down-regulated immune activation pathways. CONCLUSIONS: Long-term treatment with a GHRH analog reduced markers of T-cell and monocyte/macrophage activity, suggesting that augmentation of the GH axis may ameliorate immune activation in an HIV population with metabolic dysregulation, systemic and end organ inflammation. Clinical Trials Registration. NCT02196831.

Clinical Predictors of Liver Fibrosis Presence and Progression in Human Immunodeficiency Virus-Associated Nonalcoholic Fatty Liver Disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) affects more than one-third of people living with human immunodeficiency virus (HIV). Nonetheless, its natural history is poorly understood, including which patients are most likely to have a progressive disease course. METHODS: We leveraged a randomized trial of the growth hormone-releasing hormone analogue tesamorelin to treat NAFLD in HIV. Sixty-one participants with HIV-associated NAFLD were randomized to tesamorelin or placebo for 12 months with serial biopsies. RESULTS: In all participants with baseline biopsies (n = 58), 43% had hepatic fibrosis. Individuals with fibrosis had higher NAFLD Activity Score (NAS) (mean ± standard deviation [SD], 3.6 ± 2.0 vs 2.0 ± 0.8; P < .0001) and visceral fat content (mean ± SD, 284 ± 91 cm2 vs 212 ± 95 cm2; P = .005), but no difference in hepatic fat or body mass index. Among placebo-treated participants with paired biopsies (n = 24), 38% had hepatic fibrosis progression over 12 months. For each 25 cm2 higher visceral fat at baseline, odds of fibrosis progression increased by 37% (odds ratio, 1.37 [95% confidence interval, 1.03-2.07]). There was no difference in baseline NAS between fibrosis progressors and nonprogressors, though NAS rose over time in the progressor group (mean ± SD, 1.1 ± 0.8 vs -0.5 ± 0.6; P < .0001). CONCLUSIONS: In this longitudinal study of HIV-associated NAFLD, high rates of hepatic fibrosis and progression were observed. Visceral adiposity was identified as a novel predictor of worsening fibrosis. In contrast, baseline histologic characteristics did not relate to fibrosis progression.

Body composition predictors of outcome in patients with COVID-19.

BACKGROUND/OBJECTIVE: Obesity is a strong risk factor for adverse outcomes in patients hospitalized with COVID-19, however, the distribution of fat and the amount of muscle mass are more accurate risk factors than BMI. The objective of this study was to assess body composition measures obtained on opportunistic abdominal CTs as predictors of outcome in patients hospitalized with COVID-19. We hypothesized that elevated visceral and intermuscular adipose tissue would be associated with adverse outcome. SUBJECTS/METHODS: Our retrospective study was IRB-approved and HIPAA-compliant. The study group comprised 124 patients (median age: 68 years, IQR: 56, 77; 59 weeks, 65 months) who were admitted with COVID-19 to a single hospital and who had undergone abdominal CT for clinical purposes. Visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), intermuscular adipose tissue (IMAT), and paraspinal and abdominal muscle cross-sectional areas (CSA) were assessed. Clinical information including prognostic factors, time of admission to the intensive care unit (ICU) and time of death within 28 days were obtained. Multivariate time-to-event competing risk models were fitted to estimate the hazard ratio (HR) for a composite outcome of ICU admission/mortality associated with a one standard deviation increase in each body compositional measure. Each model was adjusted for age, sex, race, BMI, and cardiometabolic comorbidities. RESULTS: There were 50 patients who were admitted to the ICU or deceased over a median time of 1 day [IQR 1, 6] from hospital admission. Higher VAT/SAT ratio (HR of 1.30; 95% CI 1.04-1.62, p = 0.022) and higher IMAT CSA (HR of 1.44; 95% CI 1.10-1.89, p = 0.008) were associated with a reduced time to ICU admission or death in adjusted models. CONCLUSION: VAT/SAT and IMAT are predictors of adverse outcome in patients hospitalized with COVID-19, independent of other established prognostic factors. This suggests that body composition measures may serve as novel biomarkers of outcome in patients with COVID-19.

Effect of recombinant human growth hormone on liver fat content in young adults with nonalcoholic fatty liver disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is highly prevalent in young adults with obesity. Obesity is associated with relative growth hormone (GH) deficiency, and data from animal studies and from humans with pituitary GH deficiency suggest a role for GH deficiency in the pathogenesis of NAFLD. The effects of GH on NAFLD in those with obesity are unknown, however, prompting this pilot study to assess effects of GH administration on measures of NAFLD in young adults. METHODS: Twenty-four men and women aged 18-29 years with BMI ≥ 30 kg/m2 , hepatic fat fraction (HFF) ≥ 5% on proton magnetic resonance spectroscopy (1 H-MRS) and insulin-like growth factor 1 (IGF-1) z-score ≤ 0 were randomized to treatment with recombinant human GH (rhGH) versus no treatment for 24 weeks. The primary endpoint was change in HFF. RESULTS: Compared to no treatment, the effect size of rhGH on absolute HFF over 24 weeks was -3.3% (95% confidence interval: -7.8%, 1.2%; p = .14). At 24 weeks, HFF < 5% was achieved in 5 of 9 individuals receiving rhGH versus 1 of 9 individuals receiving no treatment (p = .04). rhGH did not significantly reduce ALT, AST or GGT. Serum IGF-1 increased as expected with rhGH treatment, and there were no changes in fasting lipids, C-reactive protein, fasting glucose or 2-h glucose following an oral glucose tolerance test. CONCLUSION: Data from this pilot study suggest that rhGH treatment in young adults with obesity and NAFLD may have benefits to reduce liver fat content, although larger studies are needed to confirm this effect.

Deep learning method for segmentation of rotator cuff muscles on MR images.

OBJECTIVE: To develop and validate a deep convolutional neural network (CNN) method capable of (1) selecting a specific shoulder sagittal MR image (Y-view) and (2) automatically segmenting rotator cuff (RC) muscles on a Y-view. We hypothesized a CNN approach can accurately perform both tasks compared with manual reference standards. MATERIAL AND METHODS: We created 2 models: model A for Y-view selection and model B for muscle segmentation. For model A, we manually selected shoulder sagittal T1 Y-views from 258 cases as ground truth to train a classification CNN (Keras/Tensorflow, Inception v3, 16 batch, 100 epochs, dropout 0.2, learning rate 0.001, RMSprop). A top-3 success rate evaluated model A on 100 internal and 50 external test cases. For model B, we manually segmented subscapularis, supraspinatus, and infraspinatus/teres minor on 1048 sagittal T1 Y-views. After histogram equalization and data augmentation, the model was trained from scratch (U-Net, 8 batch, 50 epochs, dropout 0.25, learning rate 0.0001, softmax). Dice (F1) score determined segmentation accuracy on 105 internal and 50 external test images. RESULTS: Model A showed top-3 accuracy > 98% to select an appropriate Y-view. Model B produced accurate RC muscle segmentations with mean Dice scores > 0.93. Individual muscle Dice scores on internal/external datasets were as follows: subscapularis 0.96/0.93, supraspinatus 0.97/0.96, and infraspinatus/teres minor 0.97/0.95. CONCLUSIONS: Our results show overall accurate Y-view selection and automated RC muscle segmentation using a combination of deep CNN algorithms.

A measuring technique for intra-osseous pressure.

OBJECTIVE: Pulsatile intra-osseous pressures result in bone remodeling, and therefore may affect lesion growth and response to treatment. However, there is no known method used to measure intra-osseous pressures. The purpose of this study is to describe a novel image-guided technique for measuring intra-osseous pressures. MATERIALS AND METHODS: This study was IRB-approved and HIPAA compliant. Written informed consent was obtained. Intra-osseous pressure measurements were performed during a CT-guided bone marrow biopsy in eight patients (6 male, 2 female) with mean age 66 ± 13 years (median 72, range 45-87) and suspected or known bone marrow disease. Bone marrow pressure measurements were obtained connecting the biopsy needle to a dedicated monitor using a standard arterial line setup. Monitor data was collected at 5-s intervals in order to record continuous pressure measurements for 2 min. RESULTS: Pressure measurements were successfully performed in all 8 patients. The mean bone marrow pressures were 36.8 ± 7.2 mmHg (median 37.7, range 24.7-47.4). The peak and trough pressures varied by 11%, and the standard deviation of mean pressure measurement varied by 18%. Our findings for marrow pressure measures most closely approximate the pressure profile of the venous system. CONCLUSION: We describe a novel and minimally invasive technique able to provide functional data of bone marrow. This technique has the potential to provide insights into normal and diseased bone marrow and may be helpful to evaluate features of cystic and vascular tumors that may be amenable to percutaneous treatments.

Kinematic MRI of ischiofemoral impingement.

OBJECTIVE: To examine the effect of external hip rotation on ischiofemoral (IF) and quadratus femoris (QF) spaces using real-time kinematic MRI, with the hypothesis that hips with IF and QF space narrowing have distinct motion patterns compared with control hips. MATERIALS AND METHODS: This prospective study was IRB-approved and complied with HIPAA guidelines. We recruited women (≥ 18 years) with and without ischiofemoral impingement to undergo kinematic MRI of the hips. A kinematic imaging protocol using T2-HASTE was performed beginning at maximal internal rotation followed by active external hip rotation. The duration of each acquisition was 30 s, providing 8 images/3 s. IF and QF spaces, and femoral metaphyseal and lesser trochanter centroid coordinates were measured on sequential images. Hips were classified as controls or narrowed based on IF and QF space thresholds and compared statistically throughout motion stages. RESULTS: The cohort comprised 12 women (24 hips; 10 control and 14 narrowed hips) aged 58 ± 10 years. External rotation caused IF space reduction of 59% in narrowed hips versus 41% in control hips. QF space decreased 71% in narrowed hips versus 50% in control hips. IF and QF spaces differed significantly between groups only when external rotation exceeded the neutral position (P < 0.02 for both). The lesser trochanter terminated more posteriorly in narrowed hips compared with controls (P = 0.03). CONCLUSIONS: Kinematic MRI during external hip rotation in women with narrowed and control hips reveals dynamic differences in IF and QF spaces and lesser trochanter terminal position.

Association between muscle mass and insulin sensitivity independent of detrimental adipose depots in young adults with overweight/obesity.

BACKGROUND/OBJECTIVE: Less muscle mass has been associated with greater insulin resistance, but whether the association is independent of deleterious adipose depots in young adults with overweight/obesity who are at high risk for type 2 diabetes (T2DM) but are otherwise metabolically healthy is not known. The objective of this study was to determine whether muscle mass is independently associated with insulin sensitivity (IS) in young adults with overweight/obesity. SUBJECTS/METHODS: Cross-sectional Clinical Research Center study of 132 adults, 21-45yo, BMI ≥ 25 kg/m2 and metabolically healthy without T2DM. Primary independent variable: percent ideal appendicular lean mass (ALM) calculated as measured ALM divided by predicted ALM for age, weight, and height, calculated using validated NHANES data-based equation. Primary dependent variable: IS by Matsuda index. RESULTS: Mean age was 34.3 ± 6.8 years, and mean BMI 35.8 ± 5.8 kg/m2 (mean ± SD). Individuals in the highest % ideal ALM tertile had mean IS 45% higher than the lowest tertile [6.94 ± 0.85 vs 4.80 ± 0.56 (mean ± SEM), p = 0.008] (sex interaction p = 0.003). Men in the highest % ideal ALM tertile had mean IS twice the lowest tertile (5.47 ± 0.68 vs 2.68 ± 0.34, p = 0.001), which remained significant controlling for visceral/subcutaneous and intermuscular adipose tissue, and intramyocellular and intrahepatic lipids (p = 0.03). The association was not significant in women. CONCLUSIONS: Muscle mass is associated with IS independent of detrimental adipose depots in young men with overweight/obesity, at risk for T2DM but currently metabolically healthy. Muscle mass relative to sex, age, weight, and height-specific norms may be used to ascertain individual T2DM risk associated with low muscle mass.

MRI texture analysis in acromegaly and its role in predicting response to somatostatin receptor ligands.

PURPOSE: Given the paucity of reliable predictors of tumor recurrence, progression, or response to somatostatin receptor ligand (SRL) therapy in acromegaly, we attempted to determine whether preoperative MR image texture was predictive of these clinical outcomes. We also determined whether image texture could differentiate somatotroph adenomas from non-functioning pituitary adenomas (NFPAs). METHODS: We performed a retrospective study of patients with acromegaly due to a macroadenoma who underwent transsphenoidal surgery at our institution between 2007 and 2015. Clinical data were extracted from electronic medical records. MRI texture analysis was performed on preoperative non-enhanced T1-weighted images using ImageJ (NIH). Logistic and Cox models were used to determine if image texture parameters predicted outcomes. RESULTS: Eighty-nine patients had texture parameters measured, which were compared to that of NFPAs, while 64 of these patients had follow-up and were included in the remainder of analyses. Minimum pixel intensity, skewness, and kurtosis were significantly different in somatotroph adenomas versus NFPAs (area under the receiver operating characteristic curve, 0.7771, for kurtosis). Furthermore, those with a maximum pixel intensity above the median had an increased odds of IGF-I normalization on SRL therapy (OR 5.96, 95% CI 1.33-26.66), which persisted after adjusting for several potential predictors of response. Image texture did not predict tumor recurrence or progression. CONCLUSION: Our data suggest that MRI texture analysis can distinguish NFPAs from somatotroph macroadenomas with good diagnostic accuracy and can predict normalization of IGF-I with SRL therapy.