Opportunistic hip fracture risk prediction in Men from X-ray: Findings from the Osteoporosis in Men (MrOS) Study

Osteoporosis is a common disease that increases fracture risk. Hip fractures, especially in elderly people, lead to increased morbidity, decreased quality of life and increased mortality. Being a silent disease before fracture, osteoporosis often remains undiagnosed and untreated. Areal bone mineral density (aBMD) assessed by dual-energy X-ray absorptiometry (DXA) is the gold-standard method for osteoporosis diagnosis and hence also for future fracture prediction (prognostic). However, the required special equipment is not broadly available everywhere, in particular not to patients in developing countries. We propose a deep learning classification model (FORM) that can directly predict hip fracture risk from either plain radiographs (X-ray) or 2D projection images of computed tomography (CT) data. Our method is fully automated and therefore well suited for opportunistic screening settings, identifying high risk patients in a broader population without additional screening. FORM was trained and evaluated on X-rays and CT projections from the Osteoporosis in Men (MrOS) study. 3108 X-rays (89 incident hip fractures) or 2150 CTs (80 incident hip fractures) with a 80/20 split were used. We show that FORM can correctly predict the 10-year hip fracture risk with a validation AUC of 81.44 +- 3.11% / 81.04 +- 5.54% (mean +- STD) including additional information like age, BMI, fall history and health background across a 5-fold cross validation on the X-ray and CT cohort, respectively. Our approach significantly (p < 0.01) outperforms previous methods like Cox Proportional-Hazards Model and \frax with 70.19 +- 6.58 and 74.72 +- 7.21 respectively on the X-ray cohort. Our model outperform on both cohorts hip aBMD based predictions. We are confident that FORM can contribute on improving osteoporosis diagnosis at an early stage.Comment: Accepted at MICCAI 2022 Workshop (PRIME

Binary Local Fractal Dimension: a Precise Structure Parameter for 3D High Resolution Computed Tomography Images of the Human Spongiosa

We present the Binary Local Fractal Dimension (LFD) to analyze osteoporosis induced fracture risk with clinical 3D high resolution quantitative computed tomographic (HRCT) images of human vertebrae. We test if LFD parameters provide precise additional information besides bone mineral density (BMD) and standard descriptors of bone quality, for example bone surface ratio (BS/BV). We define a weighted LFD (wLFD) using the ¯R2 of the H¨older exponents. We compare the LFD with standard methods (distance transform, direct secant method and run-length method) on 5 vertebrae × 8 volumes of interest and 5 repeated scans. The wLFD contains the highest direct and BMD-independent precision (R2 = 0.985 and R2 = 0.949), followed by BS/BV (R2 = 0.977 and R2 = 0.920) including low correlation with BMD (wLFD: R2 = 0.704, BS/BV: R2 = 0.814). LFD improves the translation from reference μCT- to clinical HRCT-resolution. In conclusion, LFD provides a strong diagnostic tool to characterize bone quality to predict osteoporosis induced fracture risk.Sociedad Argentina de Informática e Investigación Operativ

Binary Local Fractal Dimension: a Precise Structure Parameter for 3D High Resolution Computed Tomography Images of the Human Spongiosa

We present the Binary Local Fractal Dimension (LFD) to analyze osteoporosis induced fracture risk with clinical 3D high resolution quantitative computed tomographic (HRCT) images of human vertebrae. We test if LFD parameters provide precise additional information besides bone mineral density (BMD) and standard descriptors of bone quality, for example bone surface ratio (BS/BV). We define a weighted LFD (wLFD) using the ¯R2 of the H¨older exponents. We compare the LFD with standard methods (distance transform, direct secant method and run-length method) on 5 vertebrae × 8 volumes of interest and 5 repeated scans. The wLFD contains the highest direct and BMD-independent precision (R2 = 0.985 and R2 = 0.949), followed by BS/BV (R2 = 0.977 and R2 = 0.920) including low correlation with BMD (wLFD: R2 = 0.704, BS/BV: R2 = 0.814). LFD improves the translation from reference μCT- to clinical HRCT-resolution. In conclusion, LFD provides a strong diagnostic tool to characterize bone quality to predict osteoporosis induced fracture risk.Sociedad Argentina de Informática e Investigación Operativ

Binary Local Fractal Dimension: a Precise Structure Parameter for 3D High Resolution Computed Tomography Images of the Human Spongiosa

We present the Binary Local Fractal Dimension (LFD) to analyze osteoporosis induced fracture risk with clinical 3D high resolution quantitative computed tomographic (HRCT) images of human vertebrae. We test if LFD parameters provide precise additional information besides bone mineral density (BMD) and standard descriptors of bone quality, for example bone surface ratio (BS/BV). We define a weighted LFD (wLFD) using the ¯R2 of the H¨older exponents. We compare the LFD with standard methods (distance transform, direct secant method and run-length method) on 5 vertebrae × 8 volumes of interest and 5 repeated scans. The wLFD contains the highest direct and BMD-independent precision (R2 = 0.985 and R2 = 0.949), followed by BS/BV (R2 = 0.977 and R2 = 0.920) including low correlation with BMD (wLFD: R2 = 0.704, BS/BV: R2 = 0.814). LFD improves the translation from reference μCT- to clinical HRCT-resolution. In conclusion, LFD provides a strong diagnostic tool to characterize bone quality to predict osteoporosis induced fracture risk.Sociedad Argentina de Informática e Investigación Operativ

Correction: Large cortical bone pores in the tibia are associated with proximal femur strength

[This corrects the article DOI: 10.1371/journal.pone.0215405.

Assessment of anti-inflammatory tumor treatment efficacy by longitudinal monitoring employing sonographic micro morphology in a preclinical mouse model

<p>Abstract</p> <p>Background</p> <p>With the development of increasingly sophisticated three-dimensional volumetric imaging methods, tumor volume can serve as a robust and reproducible measurement of drug efficacy. Since the use of molecularly targeted agents in the clinic will almost certainly involve combinations with other therapeutic modalities, the use of volumetric determination can help to identify a dosing schedule of sequential combinations of cytostatic drugs resulting in long term control of tumor growth with minimal toxicity. The aim of this study is to assess high resolution sonography imaging for the in vivo monitoring of efficacy of Infliximab in pancreatic tumor.</p> <p>Methods</p> <p>In the first experiment, primary orthotopic pancreatic tumor growth was measured with Infliximab treatment. In the second experiment, orthotopic tumors were resected ten days after inoculation of tumor cells and tumor recurrence was measured following Infliximab treatment. Tumor progression was evaluated using 3D high resolution sonography.</p> <p>Results</p> <p>Sonography measurement of tumor volume in vivo showed inhibitory effect of Infliximab on primary tumor growth in both non-resected and resected models. Measurement of the dynamics of tumor growth by sonography revealed that in the primary tumor Infliximab is effective against established tumors while in the resection model, Infliximab is more effective at an early stage following tumor resection. Infliximab treatment is also effective in inhibiting tumor growth growth as a result of tumor cell contamination of the surgical field.</p> <p>Conclusions</p> <p>Clinical application of Infliximab is feasible in both the neoadjuvant and adjuvant setting. Infliximab is also effective in slowing the growth of tumor growth under the peritoneum and may have application in treating peritoneal carcinomatosis. Finally the study demonstrates that high resolution sonography is a sensitive imaging modality for the measurement of pancreatic tumor growth.</p

Effect of Constitution on Mass of Individual Organs and Their Association with Metabolic Rate in Humans—A Detailed View on Allometric Scaling

Resting energy expenditure (REE)-power relationships result from multiple underlying factors including weight and height. In addition, detailed body composition, including fat free mass (FFM) and its components, skeletal muscle mass and internal organs with high metabolic rates (i.e. brain, heart, liver, kidneys), are major determinants of REE. Since the mass of individual organs scales to height as well as to weight (and, thus, to constitution), the variance in these associations may also add to the variance in REE. Here we address body composition (measured by magnetic resonance imaging) and REE (assessed by indirect calorimetry) in a group of 330 healthy volunteers differing with respect to age (17–78 years), sex (61% female) and BMI (15.9–47.8 kg/m2). Using three dimensional data interpolation we found that the inter-individual variance related to scaling of organ mass to height and weight and, thus, the constitution-related variances in either FFM (model 1) or kidneys, muscle, brain and liver (model 2) explained up to 43% of the inter-individual variance in REE. These data are the first evidence that constitution adds to the complexity of REE. Since organs scale differently as weight as well as height the “fit” of organ masses within constitution should be considered as a further trait

FRAX (R): Prediction of Major Osteoporotic Fractures in Women from the General Population: The OPUS Study

Purposes: The aim of this study was to analyse how well FRAXH predicts the risk of major osteoporotic and vertebral fractures over 6 years in postmenopausal women from general population. Patients and methods: The OPUS study was conducted in European women aged above 55 years, recruited in 5 centers from random population samples and followed over 6 years. The population for this study consisted of 1748 women (mean age 74.2 years) with information on incident fractures. 742 (43.1%) had a prevalent fracture; 769 (44%) and 155 (8.9%) of them received an antiosteoporotic treatment before and during the study respectively. We compared FRAXH performance with and without bone mineral density (BMD) using receiver operator characteristic (ROC) c-statistical analysis with ORs and areas under receiver operating characteristics curves (AUCs) and net reclassification improvement (NRI). Results: 85 (4.9%) patients had incident major fractures over 6 years. FRAXH with and without BMD predicted these fractures with an AUC of 0.66 and 0.62 respectively. The AUC were 0.60, 0.66, 0.69 for history of low trauma fracture alone, age and femoral neck (FN) BMD and combination of the 3 clinical risk factors, respectively. FRAXH with and without BMD predicted incident radiographic vertebral fracture (n = 65) with an AUC of 0.67 and 0.65 respectively. NRI analysis showed a significant improvement in risk assignment when BMD is added to FRAXH. Conclusions: This study shows that FRAXH with BMD and to a lesser extent also without FN BMD predict major osteoporotic and vertebral fractures in the general population

Genome-Wide Association Study Using Extreme Truncate Selection Identifies Novel Genes Affecting Bone Mineral Density and Fracture Risk

Osteoporotic fracture is a major cause of morbidity and mortality worldwide. Low bone mineral density (BMD) is a major predisposing factor to fracture and is known to be highly heritable. Site-, gender-, and age-specific genetic effects on BMD are thought to be significant, but have largely not been considered in the design of genome-wide association studies (GWAS) of BMD to date. We report here a GWAS using a novel study design focusing on women of a specific age (postmenopausal women, age 55–85 years), with either extreme high or low hip BMD (age- and gender-adjusted BMD z-scores of +1.5 to +4.0, n = 1055, or −4.0 to −1.5, n = 900), with replication in cohorts of women drawn from the general population (n = 20,898). The study replicates 21 of 26 known BMD–associated genes. Additionally, we report suggestive association of a further six new genetic associations in or around the genes CLCN7, GALNT3, IBSP, LTBP3, RSPO3, and SOX4, with replication in two independent datasets. A novel mouse model with a loss-of-function mutation in GALNT3 is also reported, which has high bone mass, supporting the involvement of this gene in BMD determination. In addition to identifying further genes associated with BMD, this study confirms the efficiency of extreme-truncate selection designs for quantitative trait association studies