Microvascular disease not type 2 diabetes is associated with increased cortical porosity: A study of cortical bone microstructure and intracortical vessel characteristics.

Introduction: Fracture risk is elevated in type 2 diabetes (T2D) despite normal or even high bone mineral density (BMD). Microvascular disease (MVD) is a diabetic complication, but also associated with other diseases, for example chronic kidney disease. We hypothesize that increased fracture risk in T2D could be due to increased cortical porosity (Ct.Po) driven by expansion of the vascular network in MVD. The purpose of this study was to investigate associations of T2D and MVD with cortical microstructure and intracortical vessel parameters. Methods: The study group consisted of 75 participants (38 with T2D and 37 without T2D). High-resolution peripheral quantitative CT (HR-pQCT) and dynamic contrast-enhanced MRI (DCE-MRI) of the ultra-distal tibia were performed to assess cortical bone and intracortical vessels (outcomes). MVD was defined as ≥1 manifestation including neuropathy, nephropathy, or retinopathy based on clinical exams in all participants. Adjusted means of outcomes were compared between groups with/without T2D or between participants with/without MVD in both groups using linear regression models adjusting for age, sex, BMI, and T2D as applicable. Results: MVD was found in 21 (55 %) participants with T2D and in 9 (24 %) participants without T2D. In T2D, cortical pore diameter (Ct.Po.Dm) and diameter distribution (Ct.Po.Dm.SD) were significantly higher by 14.6 µm (3.6 %, 95 % confidence interval [CI]: 2.70, 26.5 µm, p = 0.017) and by 8.73 µm (4.8 %, CI: 0.79, 16.7 µm, p = 0.032), respectively. In MVD, but not in T2D, cortical porosity was significantly higher by 2.25 % (relative increase = 12.9 %, CI: 0.53, 3.97 %, p = 0.011) and cortical BMD (Ct.BMD) was significantly lower by -43.6 mg/cm3 (2.6 %, CI: -77.4, -9.81 mg/cm3, p = 0.012). In T2D, vessel volume and vessel diameter were significantly higher by 0.02 mm3 (13.3 %, CI: 0.004, 0.04 mm3, p = 0.017) and 15.4 µm (2.9 %, CI: 0.42, 30.4 µm, p = 0.044), respectively. In MVD, vessel density was significantly higher by 0.11 mm-3 (17.8 %, CI: 0.01, 0.21 mm-3, p = 0.033) and vessel volume and diameter were significantly lower by -0.02 mm3 (13.7 %, CI: -0.04, -0.004 mm3, p = 0.015) and - 14.6 µm (2.8 %, CI: -29.1, -0.11 µm, p = 0.048), respectively. Conclusions: The presence of MVD, rather than T2D, was associated with increased cortical porosity. Increased porosity in MVD was coupled with a larger number of smaller vessels, which could indicate upregulation of neovascularization triggered by ischemia. It is unclear why higher variability and average diameters of pores in T2D were accompanied by larger vessels.

Thigh muscle and fat volumes are associated with knee cartilage abnormalities and bone marrow edema-like lesions: data from the osteoarthritis initiative.

OBJECTIVE: To investigate the associations of thigh muscle and fat volumes with structural abnormalities on MRI related to knee osteoarthritis. MATERIALS AND METHODS: MRI studies of the thighs and knees from 100 individuals were randomly selected from the Osteoarthritis Initiative Cohort. Whole Organ MR Scoring (WORMS) and effusion-synovitis scoring were performed in all knee MRI. Thigh muscles, intermuscular fat, and subcutaneous fat were manually segmented in 15 consecutive MR thigh images. Radiographic Kellgren-Lawrence grades (KLG) were also obtained in all knee radiographs. Independent t-tests were used to investigate the associations between thigh muscle and fat volumes, and sex. Mixed-effects analyses were obtained to investigate the associations between thigh muscle and fat volumes, KLG, WOMAC pain score, cartilage and bone marrow WORMS, as well as effusion-synovitis scores. RESULTS: Women had higher subcutaneous fat volume than men (616.82 vs. 229.13 cm3, p < 0.01) and men had higher muscle volumes than women (p < 0.01). Quadriceps (coef = -2.15, p = 0.01) and vastus medialis (coef = -1.84, p = 0.03) volumes were negatively associated with the WORMS cartilage scores. Intermuscular fat volume (coef = 0.48, p = 0.01) was positively associated with WORMS bone marrow edema-like lesion (BMEL) scores. The quadriceps (coef = -0.99, p < 0.01) and hamstring (coef = -0.59, p = 0.01) volumes were negatively associated with WORMS BMEL scores. No evidence of an association was found between thigh muscle and fat volumes with KLG and effusion-synovitis grading (p > 0.05). CONCLUSION: Increased quadriceps and hamstring volumes were negatively associated with cartilage lesion and BMEL scores while no evidence of an association was found between thigh muscle and fat volumes, and radiographic knee osteoarthritis or effusion-synovitis grading.

Bone Marrow Adiposity Alterations in Type 2 Diabetes Are Sex-Specific and Associated with Serum Lipid Levels.

Type 2 diabetes (T2D) has negative effects on skeletal health. A proposed mechanism of diabetic bone disease connects hyperlipidemia to increased bone marrow adiposity and decreased bone quality. Previous research on Type 1 diabetes reported positive associations between serum lipid levels and marrow adiposity, but no data exist for T2D. In addition, marrow adiposity is sex-dependent in healthy populations, but sex has not been addressed adequately in previous reports of marrow adiposity in T2D. The purpose of this study was to quantify associations of marrow adiposity and composition with T2D status, serum lipid levels, and sex. T2D patients and normoglycemic controls (n = 39/37) were included. Single-voxel magnetic resonance spectroscopy (MRS) was performed at the spine and tibia. Quantitative MRS outcomes of marrow adiposity and composition were calculated. Linear regression models were used to compare MRS outcomes among groups and to evaluate associations of MRS outcomes with serum lipid levels. All analyses were performed on sex-stratified subgroups. Total, unsaturated, and saturated fat content at the spine were lower in T2D participants compared to controls in age-adjusted models; these differences were significant in men but not in women. In our study cohort, total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were lower in T2D participants compared to controls. Adjustment for LDL, HDL, and statin use attenuated the association of T2D status with unsaturated fat but not saturated fat in men. Further analysis confirmed significant associations between serum lipid levels and MRS outcomes. Specifically, we found a positive association between LDL cholesterol and total marrow fat in the male T2D group and a negative association between HDL and total marrow fat in the female T2D group. In conclusion, our results suggest that marrow adiposity and composition are associated with lipid levels as well as T2D status, and these relationships are sex-specific. © 2023 American Society for Bone and Mineral Research (ASBMR).

Comparative Study of Raw Ultrasound Data Representations in Deep Learning to Classify Hepatic Steatosis.

Adiposity accumulation in the liver is an early-stage indicator of non-alcoholic fatty liver disease. Analysis of ultrasound (US) backscatter echoes from liver parenchyma with deep learning (DL) may offer an affordable alternative for hepatic steatosis staging. The aim of this work was to compare DL classification scores for liver steatosis using different data representations constructed from raw US data. Steatosis in N = 31 patients with confirmed or suspected non-alcoholic fatty liver disease was stratified based on fat-fraction cutoff values using magnetic resonance imaging as a reference standard. US radiofrequency (RF) frames (raw data) and clinical B-mode images were acquired. Intermediate image formation stages were modeled from RF data. Power spectrum representations and phase representations were also calculated. Co-registered patches were used to independently train 1-, 2- and 3-D convolutional neural networks (CNNs), and classifications scores were compared with cross-validation. There were 67,800 patches available for 2-D/3-D classification and 1,830,600 patches for 1-D classification. The results were also compared with radiologist B-mode annotations and quantitative ultrasound (QUS) metrics. Patch classification scores (area under the receiver operating characteristic curve [AUROC]) revealed significant reductions along successive stages of the image formation process (p < 0.001). Patient AUROCs were 0.994 for RF data and 0.938 for clinical B-mode images. For all image formation stages, 2-D CNNs revealed higher patch and patient AUROCs than 1-D CNNs. CNNs trained with power spectrum representations converged faster than those trained with RF data. Phase information, which is usually discarded in the image formation process, provided a patient AUROC of 0.988. DL models trained with RF and power spectrum data (AUROC = 0.998) provided higher scores than conventional QUS metrics and multiparametric combinations thereof (AUROC = 0.986). Radiologist annotations indicated lower hepatic steatosis classification accuracies (Acc = 0.914) with respect to magnetic resonance imaging proton density fat fraction that DL models (Acc = 0.989). Access to raw ultrasound data combined with artificial intelligence techniques may offer superior opportunities for quantitative tissue diagnostics than conventional sonographic images.

Paraspinal Muscle in Chronic Low Back Pain: Comparison Between Standard Parameters and Chemical Shift Encoding-Based Water-Fat MRI.

BACKGROUND: Paraspinal musculature (PSM) is increasingly recognized as a contributor to low back pain (LBP), but with conventional MRI sequences, assessment is limited. Chemical shift encoding-based water-fat MRI (CSE-MRI) enables the measurement of PSM fat fraction (FF), which may assist investigations of chronic LBP. PURPOSE: To investigate associations between PSM parameters from conventional MRI and CSE-MRI and between PSM parameters and pain. STUDY TYPE: Prospective, cross-sectional. POPULATION: Eighty-four adults with chronic LBP (44.6 ± 13.4 years; 48 males). FIELD STRENGTH/SEQUENCE: 3-T, T1-weighted fast spin-echo and iterative decomposition of water and fat with echo asymmetry and least squares estimation sequences. ASSESSMENT: T1-weighted images for Goutallier classification (GC), muscle volume, lumbar indentation value, and muscle-fat index, CSE-MRI for FF extraction (L1/2-L5/S1). Pain was self-reported using a visual analogue scale (VAS). Intra- and/or interreader agreement was assessed for MRI-derived parameters. STATISTICAL TESTS: Mixed-effects and linear regression models to 1) assess relationships between PSM parameters (entire cohort and subgroup with GC grades 0 and 1; statistical significance α = 0.0025) and 2) evaluate associations of PSM parameters with pain (α = 0.05). Intraclass correlation coefficients (ICCs) for intra- and/or interreader agreement. RESULTS: The FF showed excellent intra- and interreader agreement (ICC range: 0.97-0.99) and was significantly associated with GC at all spinal levels. Subgroup analysis suggested that early/subtle changes in PSM are detectable with FF but not with GC, given the absence of significant associations between FF and GC (P-value range: 0.036 at L5/S1 to 0.784 at L2/L3). Averaged over all spinal levels, FF and GC were significantly associated with VAS scores. DATA CONCLUSION: In the absence of FF, GC may be the best surrogate for PSM quality. Given the ability of CSE-MRI to detect muscle alterations at early stages of PSM degeneration, this technique may have potential for further investigations of the role of PSM in chronic LBP. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.

Diagnostic Performance of 9 Quantitative Ultrasound Parameters for Detection and Classification of Hepatic Steatosis in Nonalcoholic Fatty Liver Disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease worldwide. Quantitative ultrasound (QUS) parameters based on radiofrequency raw data show promise in quantifying liver fat. PURPOSE: The aim of this study was to evaluate the diagnostic performance of 9 QUS parameters compared with magnetic resonance imaging (MRI)-estimated proton density fat fraction (PDFF) in detecting and staging hepatic steatosis in patients with or suspected of NAFLD. MATERIALS AND METHODS: In this Health Insurance Portability and Accountability Act-compliant institutional review board-approved prospective study, 31 participants with or suspected of NAFLD, without other underlying chronic liver diseases (13 men, 18 women; average age, 52 years [range, 26-90 years]), were examined. The following parameters were obtained: acoustic attenuation coefficient (AC); hepatorenal index (HRI); Nakagami parameter; shear wave elastography measures such as shear wave elasticity, viscosity, and dispersion; and spectroscopy-derived parameters including spectral intercept (SI), spectral slope (SS), and midband fit (MBF). The diagnostic ability (area under the receiver operating characteristic curves and accuracy) of QUS parameters was assessed against different MRI-PDFF cutoffs (the reference standard): 6.4%, 17.4%, and 22.1%. Linearity with MRI-PDFF was evaluated with Spearman correlation coefficients (p). RESULTS: The AC, SI, Nakagami, SS, HRI, and MBF strongly correlated with MRI-PDFF (P = 0.89, 0.89, 0.88, -0.87, 0.81, and 0.71, respectively [P < 0.01]), with highest area under the receiver operating characteristic curves (ranging from 0.85 to 1) for identifying hepatic steatosis using 6.4%, 17.4%, and 22.1% MRI-PDFF cutoffs. In contrast, shear wave elasticity, shear wave viscosity, and shear wave dispersion did not strongly correlate to MRI-PDFF (P = 0.45, 0.38, and 0.07, respectively) and had poor diagnostic performance. CONCLUSION: The AC, Nakagami, SI, SS, MBF, and HRI best correlate with MRI-PDFF and show high diagnostic performance for detecting and classifying hepatic steatosis in our study population. SUMMARY STATEMENT: Quantitative ultrasound is an accurate alternative to MRI-based techniques for evaluating hepatic steatosis in patients with or at risk of NAFLD. KEY FINDINGS: Our preliminary results show that specific quantitative ultrasound parameters accurately detect different degrees of hepatic steatosis in NAFLD.

Quantitative ultrasound approaches for diagnosis and monitoring hepatic steatosis in nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease is a major global health concern with increasing prevalence, associated with obesity and metabolic syndrome. Recently, quantitative ultrasound-based imaging techniques have dramatically improved the ability of ultrasound to detect and quantify hepatic steatosis. These newer ultrasound techniques possess many inherent advantages similar to conventional ultrasound such as universal availability, real-time capability, and relatively low cost along with quantitative rather than a qualitative assessment of liver fat. In addition, quantitative ultrasound-based imaging techniques are less operator dependent than traditional ultrasound. Here we review several different emerging quantitative ultrasound-based approaches used for detection and quantification of hepatic steatosis in patients at risk for nonalcoholic fatty liver disease. We also briefly summarize other clinically available imaging modalities for evaluating hepatic steatosis such as MRI, CT, and serum analysis.

ACR Ultrasound Liver Reporting and Data System: Multicenter Assessment of Clinical Performance at One Year.

PURPOSE: The aim of this study was to evaluate the clinical performance of the ACR's Ultrasound Liver Reporting and Data System (US LI-RADS™) for detecting hepatocellular carcinoma (HCC) in patients at high risk for HCC. METHODS: In this retrospective, multicenter study, 2,050 patients at high risk for HCC (1,078 men and 972 women; mean age, 57.7 years) at five sites in the United States had undergone screening liver ultrasound from January 2017 to February 2018, and US LI-RADS observation categories and visualization scores were assigned on a clinical basis. Ultrasound reports and patient records were retrospectively reviewed and follow-up imaging studies and/or pathologic reports recorded. Descriptive statistics were generated, and multivariate logistic regression analysis was used to analyze the relationship of clinical and reader-based predictors of limited visualization. Diagnostic performance data were calculated in the subset of patients with confirmatory testing. RESULTS: The most common indications for HCC screening were cirrhosis (n = 1,054 [51.4%]), noncirrhotic hepatitis B virus infection (n = 555 [27.1%]), and noncirrhotic hepatitis C virus infection (n = 234 [11.4%]). US LI-RADS observation categories assigned were US-1 (negative) in 90.4% (n = 1,854), US-2 (subthreshold) in 4.6% (n = 95), and US-3 (positive) in 4.9% (n = 101). Visualization scores were A (no or minimal limitations) in 76.8% (n = 1,575), B (moderate limitations) in 18.9% (n = 388), and C (severe limitations) in 4.2% (n = 87). Confirmatory tests, including multiphase contrast-enhanced CT or MRI (n = 331) or histopathology (n = 18), were available for 349 patients (17.0%). The sensitivity of US LI-RADS in this subset of patients was 82.4%, specificity was 74.2%, positive predictive value was 35.3%, and negative predictive value was 96.1%. CONCLUSIONS: Approximately 90% of US LI-RADS screening examinations were negative, 5% subthreshold, and 5% positive. Visualization scores were diagnostically acceptable in the vast majority (>95%) of examinations. US LI-RADS emphasized sensitivity and negative predictive value, which are key characteristics of a screening test.