Osteoporosis is a common age-related disease characterized by reduced bone density and increased fracture-risk. Microstructural quality of trabecular bone (Tb), commonly found at axial skeletal sites and at the end of long bones, is an important determinant of bone-strength and fracture-risk. High-resolution emerging CT scanners enable in vivo measurement of Tb microstructures at peripheral sites. However, resolution-dependence of microstructural measures and wide resolution-discrepancies among various CT scanners together with rapid upgrades in technology warrant data harmonization in CT-based cross-sectional and longitudinal bone studies. This paper presents a deep learning-based method for high-resolution reconstruction of Tb microstructures from low-resolution CT scans using GAN-CIRCLE. A network was developed and evaluated using post-registered ankle CT scans of nineteen volunteers on both low-and highresolution CT scanners. 9,000 matching pairs of low-and high-resolution patches of size 64×64 were randomly harvested from ten volunteers for training and validation. Another 5,000 matching pairs of patches from nine other volunteers were used for evaluation. Quantitative comparison shows that predicted high-resolution scans have significantly improved structural similarity index (p < 0.01) with true high-resolution scans as compared to the same metric for low-resolution data. Different Tb microstructural measures such as thickness, spacing, and network area density are also computed from low-and predicted high-resolution images, and compared with the values derived from true high-resolution scans. Thickness and network area measures from predicted

Osteoporosis, characterized by reduced bone mineral density and micro-architectural degeneration, significantly enhances fracture-risk. There are several viable methods for trabecular bone micro-imaging, which widely vary in terms of technology, reconstruction principle, spatial resolution, and acquisition time. We have performed an excised cadaveric bone specimen study to evaluate different CT-imaging modalities for trabecular bone microstructural analysis. Excised cadaveric bone specimens from the distal radius were scanned using micro-CT and four in vivo CT imaging modalities: HR-pQCT, dental CBCT, wholebody MDCT, and extremity CBCT. A new algorithm was developed to optimize soft thresholding parameters for individual in vivo CT modalities for computing quantitative bone volume fraction maps. Finally, agreement of trabecular bone micro-structural measures, derived from different in vivo CT imaging, with reference measures from micro-CT imaging was examined. Observed values of most trabecular measures, including trabecular bone volume, network area, transverse and plate-rod micro-structure, thickness, and spacing, for in vivo CT modalities were higher than their micro-CT-based reference values. In general, HR-pQCT-based trabecular bone measures were closer to their reference values as compared to other in vivo CT modalities. Despite large differences in observed values of measures among modalities, high linear correlation (r Î [0.94 0.99]) was found between micro-CT and in vivo CT-derived measures of trabecular bone volume, transverse and plate micro-structural volume, and network area. All HR-pQCT-derived trabecular measures, except the erosion index, showed high correlation (r Î [0.91 0.99]). The plate-width measure showed a higher correlation (r Î [0.72 0.91]) among in vivo and micro-CT modalities than its counterpart binary plate-rod characterization-based measure erosion index (r Î [0.65 0.81]). Although a strong correlation was observed between micro-structural measures from in vivo and micro-CT imaging, large shifts in their values for in vivo modalities warrant proper scanner calibration prior to adopting in multi-site and longitudinal studies.

Osteoporosis causes fragile bone, and bone microstructural quality is a critical determinant of bone strength and fracture risk. This study pursues technical validation of novel CT-based methods for assessment of peripheral bone microstructure together with a human pilot study examining relationships between bone microstructure and vertebral fractures in smokers. To examine the accuracy and reproducibility of the methods, repeat ultra-high-resolution (UHR) CT and micro-CT scans of cadaveric ankle specimens were acquired. Thirty smokers from the University of Iowa COPDGene cohort were recruited at their 5-year follow-up visits. Chest CT scans, collected under the parent study, were used to assess vertebral fractures. UHR CT scans of distal tibia were acquired for this pilot study to obtain peripheral cortical and trabecular bone (Cb and Tb) measures. UHR CT-derived Tb measures, including volumetric bone mineral density (BMD), network area, transverse trabecular density, and mean plate width, showed high correlation (r > 0.901) with their micro-CT-derived values over small regions of interest (ROIs). Both Cb and Tb measures showed high reproducibility-intra-class correlation (ICC) was greater than 0.99 for all Tb measures except erosion index and greater than 0.97 for all Cb measures. Female sex was associated with lower transverse Tb density (p < 0.1), higher Tb spacing (p < 0.05), and lower cortical thickness (p < 0.001). Participants with vertebral fractures had significantly degenerated values (p < 0.05) for all Tb measures except thickness. There were no statistically significant differences for Cb measures between non-fracture and fracture groups. Vertebral fracture-group differences of Tb measures remained significant after adjustment with chronic obstructive pulmonary disease (COPD) status. Although current smokers at baseline had more fractures-81.8% versus 63.2% for former smokers-the difference was not statistically significant. This pilot cross-sectional human study demonstrates CT-based peripheral bone microstructural differences among smokers with and without vertebral fractures.

Purpose Osteoporosis is a bone disease associated with enhanced bone loss, microstructural degeneration, and fracture‐risk. Finite element (FE) modeling is used to estimate trabecular bone (Tb) modulus from high‐resolution three‐dimensional (3‐D) imaging modalities including micro‐computed tomography (CT), magnetic resonance imaging (MRI), and high‐resolution peripheral quantitative CT (HR‐pQCT). This paper validates an application of voxel‐based continuum finite element analysis (FEA) to predict Tb modulus from clinical CT imaging under a condition similar to in vivo imaging by comparing with measures derived by micro‐CT and experimental approaches. Method Voxel‐based continuum FEA methods for CT imaging were implemented using linear and nonlinear models and applied on distal tibial scans under a condition similar to in vivo imaging. First, tibial axis in a CT scan was aligned with the coordinate z‐axis at 150 μm isotropic voxels. FEA was applied on an upright cylindrical volume of interests (VOI) with its axis coinciding with the tibial bone axis. Voxel volume, edge, and vertex elements and their connectivity were defined as per the isotropic image grid. A calibration phantom was used to calibrate CT numbers in Hounsfield unit to bone mineral density (BMD) values, which was then converted into calcium hydroxyapatite (CHA) density. Mechanical properties at each voxel volume element was defined using its ash‐density defined on CT‐derived CHA density. For FEA, the bottom surface of the cylindrical VOI was fixed and a constant displacement was applied along the z‐direction at each vertex element on the top surface to simulate a physical axial compressive loading condition. Finally, a Poisson's ratio of 0.3 was applied, and Tb modulus (MPa) was computed as the ratio of average von Mises stress (MPa) of volume elements on the top surface and the applied displacement. FEA parameters including mesh element size, substep number, and different tolerance values were optimized. Results CT‐derived Tb modulus values using continuum FEA showed high linear correlation with the micro‐CT‐derived reference values (r ∈ [0.87 0.90]) as well as experimentally measured values (r ∈ [0.80 0.87]). Linear correlation of computed modulus with their reference values using continuum FEA with linear modeling was comparable with that obtained by nonlinear modeling. Nonlinear continuum FEA‐based modulus values (mean of 1087.2 MPa) showed greater difference from their reference values (mean of 1498.9 MPa using micro‐CT‐based FEA) as compared with linear continuum methods. High repeat CT scan reproducibility (intra‐class correlation [ICC] = 0.98) was observed for computed modulus values using both linear and nonlinear continuum FEA. It was observed that high stress regions coincide with Tb microstructure as fuzzily characterized by BMD values. Distributions of von Mises stress over Tb microstructure and marrow regions were significantly different (p < 10–8). Conclusion Voxel‐based continuum FEA offers surrogate measures of Tb modulus fr...

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