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Despite advancements in medical care, hip fractures impose a significant burden on individuals and healthcare systems. This paper focuses on the prediction of hip fracture risk in older and middle-aged adults, where falls and compromised bone quality are predominant factors. We propose a novel staged model that combines advanced imaging and clinical data to improve predictive performance. By using CNNs to extract features from hip DXA images, along with clinical variables, shape measurements, and texture features, our method provides a comprehensive framework for assessing fracture risk. A staged machine learning-based model was developed using two ensemble models: Ensemble 1 (clinical variables only) and Ensemble 2 (clinical variables and DXA imaging features). This staged approach used uncertainty quantification from Ensemble 1 to decide if DXA features are necessary for further prediction. Ensemble 2 exhibited the highest performance, achieving an AUC of 0.9541, an accuracy of 0.9195, a sensitivity of 0.8078, and a specificity of 0.9427. The staged model also performed well, with an AUC of 0.8486, an accuracy of 0.8611, a sensitivity of 0.5578, and a specificity of 0.9249, outperforming Ensemble 1, which had an AUC of 0.5549, an accuracy of 0.7239, a sensitivity of 0.1956, and a specificity of 0.8343. Furthermore, the staged model suggested that 54.49% of patients did not require DXA scanning. It effectively balanced accuracy and specificity, offering a robust solution when DXA data acquisition is not always feasible. Statistical tests confirmed significant differences between the models, highlighting the advantages of the advanced modeling strategies. Our staged approach could identify individuals at risk with a high accuracy but reduce the unnecessary DXA scanning. It has great promise to guide interventions to prevent hip fractures with reduced cost and radiation., Comment: 29 pages, 5 figures, 6 tables

Aims. The purpose of this study is to create a multi-stage machine learning model to predict cardiac resynchronization therapy (CRT) response for heart failure (HF) patients. This model exploits uncertainty quantification to recommend additional collection of single-photon emission computed tomography myocardial perfusion imaging (SPECT MPI) variables if baseline clinical variables and features from electrocardiogram (ECG) are not sufficient. Methods. 218 patients who underwent rest-gated SPECT MPI were enrolled in this study. CRT response was defined as an increase in left ventricular ejection fraction (LVEF) > 5% at a 6+-1 month follow-up. A multi-stage ML model was created by combining two ensemble models: Ensemble 1 was trained with clinical variables and ECG; Ensemble 2 included Ensemble 1 plus SPECT MPI features. Uncertainty quantification from Ensemble 1 allowed for multi-stage decision-making to determine if the acquisition of SPECT data for a patient is necessary. The performance of the multi-stage model was compared with that of Ensemble models 1 and 2. Results. The response rate for CRT was 55.5% (n = 121) with overall male gender 61.0% (n = 133), an average age of 62.0+-11.8, and LVEF of 27.7+-11.0. The multi-stage model performed similarly to Ensemble 2 (which utilized the additional SPECT data) with AUC of 0.75 vs. 0.77, accuracy of 0.71 vs. 0.69, sensitivity of 0.70 vs. 0.72, and specificity 0.72 vs. 0.65, respectively. However, the multi-stage model only required SPECT MPI data for 52.7% of the patients across all folds. Conclusions. By using rule-based logic stemming from uncertainty quantification, the multi-stage model was able to reduce the need for additional SPECT MPI data acquisition without sacrificing performance., Comment: 30 pages,6 figures. arXiv admin note: text overlap with arXiv:2305.02475

Hip fracture risk assessment is an important but challenging task. Quantitative CT-based patient specific finite element analysis (FEA) computes the force (fracture load) to break the proximal femur in a particular loading condition. It provides different structural information about the proximal femur that can influence a subject overall fracture risk. To obtain a more robust measure of fracture risk, we used principal component analysis (PCA) to develop a global FEA computed fracture risk index that incorporates the FEA-computed yield and ultimate failure loads and energies to failure in four loading conditions (single-limb stance and impact from a fall onto the posterior, posterolateral, and lateral aspects of the greater trochanter) of 110 hip fracture subjects and 235 age and sex matched control subjects from the AGES-Reykjavik study. We found that the first PC (PC1) of the FE parameters was the only significant predictor of hip fracture. Using a logistic regression model, we determined if prediction performance for hip fracture using PC1 differed from that using FE parameters combined by stratified random resampling with respect to hip fracture status. The results showed that the average of the area under the receive operating characteristic curve (AUC) using PC1 was always higher than that using all FE parameters combined in the male subjects. The AUC of PC1 and AUC of the FE parameters combined were not significantly different than that in the female subjects or in all subjects, Comment: 27 pages, 4 figures

The aim of this paper is to design a deep learning-based model to predict proximal femoral strength using multi-view information fusion. Method: We developed new models using multi-view variational autoencoder (MVAE) for feature representation learning and a product of expert (PoE) model for multi-view information fusion. We applied the proposed models to an in-house Louisiana Osteoporosis Study (LOS) cohort with 931 male subjects, including 345 African Americans and 586 Caucasians. With an analytical solution of the product of Gaussian distribution, we adopted variational inference to train the designed MVAE-PoE model to perform common latent feature extraction. We performed genome-wide association studies (GWAS) to select 256 genetic variants with the lowest p-values for each proximal femoral strength and integrated whole genome sequence (WGS) features and DXA-derived imaging features to predict proximal femoral strength. Results: The best prediction model for fall fracture load was acquired by integrating WGS features and DXA-derived imaging features. The designed models achieved the mean absolute percentage error of 18.04%, 6.84% and 7.95% for predicting proximal femoral fracture loads using linear models of fall loading, nonlinear models of fall loading, and nonlinear models of stance loading, respectively. Compared to existing multi-view information fusion methods, the proposed MVAE-PoE achieved the best performance. Conclusion: The proposed models are capable of predicting proximal femoral strength using WGS features and DXA-derived imaging features. Though this tool is not a substitute for FEA using QCT images, it would make improved assessment of hip fracture risk more widely available while avoiding the increased radiation dosage and clinical costs from QCT., Comment: 16 pages, 3 figures

Purpose: Proximal femur image analyses based on quantitative computed tomography (QCT) provide a method to quantify the bone density and evaluate osteoporosis and risk of fracture. We aim to develop a deep-learning-based method for automatic proximal femur segmentation. Methods and Materials: We developed a 3D image segmentation method based on V-Net, an end-to-end fully convolutional neural network (CNN), to extract the proximal femur QCT images automatically. The proposed V-net methodology adopts a compound loss function, which includes a Dice loss and a L2 regularizer. We performed experiments to evaluate the effectiveness of the proposed segmentation method. In the experiments, a QCT dataset which included 397 QCT subjects was used. For the QCT image of each subject, the ground truth for the proximal femur was delineated by a well-trained scientist. During the experiments for the entire cohort then for male and female subjects separately, 90% of the subjects were used in 10-fold cross-validation for training and internal validation, and to select the optimal parameters of the proposed models; the rest of the subjects were used to evaluate the performance of models. Results: Visual comparison demonstrated high agreement between the model prediction and ground truth contours of the proximal femur portion of the QCT images. In the entire cohort, the proposed model achieved a Dice score of 0.9815, a sensitivity of 0.9852 and a specificity of 0.9992. In addition, an R2 score of 0.9956 (p<0.001) was obtained when comparing the volumes measured by our model prediction with the ground truth. Conclusion: This method shows a great promise for clinical application to QCT and QCT-based finite element analysis of the proximal femur for evaluating osteoporosis and hip fracture risk.

The bisphosphonate study is an international collaboration between the NASA and JAXA space agencies to investigate the potential value of antiresorptive drugs to mitigate the well-established bone changes associated with long-duration spaceflight. Our hypothesis is that an antiresorptive drug in combination with in-flight exercise will ameliorate bone loss and hypercalcuria during long-duration spaceflight. We have completed data analysis for 7 crewmembers treated with alendronate during flight and 3 of 10 controls without treatment. We previously reported the pre/postflight changes in bone density and the pre versus in-flight changes in various biomarkers in crewmembers taking alendronate during flight. The purpose of this report is to compare these results with the 12- month follow-up data. The table below presents these data as a percentage change from baseline either immediately postflight or in-flight (biochemical markers) with a 1-year follow-up.

The bisphosphonate study is a collaborative effort between the NASA and JAXA space agencies to investigate the potential for antiresorptive drugs to mitigate bone changes associated with long-duration spaceflight. Elevated bone resorption is a hallmark of human spaceflight and bed rest (common zero-G analog). We tested whether an antiresorptive drug in combination with in-flight exercise would ameliorate bone loss and hypercalcuria during longduration spaceflight. Measurements include DXA, QCT, pQCT, and urine and blood biomarkers. We have completed analysis of 7 crewmembers treated with alendronate during flight and the immediate postflight (R+<2 week) data collection in 5 of 10 controls without treatment. Both groups used the advanced resistive exercise device (ARED) during their missions. We previously reported the pre/postflight results of crew taking alendronate during flight (Osteoporosis Int. 24:2105-2114, 2013). The purpose of this report is to present the 12-month follow-up data in the treated astronauts and to compare these results with preliminary data from untreated crewmembers exercising with ARED (ARED control) or without ARED (Pre-ARED control). Results: the table presents DXA and QCT BMD expressed as percentage change from preflight in the control astronauts (18 Pre-ARED and the current 5 ARED-1-year data not yet available) and the 7 treated subjects. As shown previously the combination of exercise plus antiresorptive is effective in preventing bone loss during flight. Bone measures for treated subjects, 1 year after return from space remain at or near baseline values. Except in one region, the treated group maintained or gained bone 1 year after flight. Biomarker data are not currently available for either control group and therefore not presented. However, data from other studies with or without ARED show elevated bone resorption and urinary Ca excretion while bisphosphonate treated subjects show decreases during flight. Comparing the two control groups suggests significant but incomplete improvement in maintaining BMD using the newer exercise protocols compared to earlier resistive exercise protocols. Quantitative characterization of this improvement requires additional measurements in the ARED control group that we are currently collecting. In conclusion, these results indicate that an antiresorptive may be an effective adjunct to exercise during long-duration spaceflight.