Osteoporosis is an age-related bone disease causing increased bone loss and enhanced bone fragility and fracture-risk. Osteoporotic imaging plays important roles in quantitative assessment of bone quality, strength, and fracture-risk, and plays important roles in evaluating disease severity and treatment planning. High-resolution CT imaging on dedicated scanners is used for finite element (FE) analysis (FEA) of trabecular bone (Tb) microstructure. However, Tb micro FEA on clinical CT imaging is challenging and yet to be established due to difficulties with binary segmentation of Tb at relatively low-resolution. Here, we present a CT-based material density adjusted nonlinear FEA method for computing Tb shear modulus, while avoiding explicit segmentation of Tb micro-network. FE meshes were constructed over upright cylindrical VOIs derived from CT scans after alignment of tibia axes with the image axes. Image voxels were modelled as cubical mesh elements, and their mechanical properties were derived from their CT-derived ash-density. Tibiofemoral direction was used to define shear loading directions. The method was optimized and evaluated using clinical CT and micro-CT scans of cadaveric ankle specimens (n = 10). FEA stress propagation along Tb microstructures and nominal leakages over marrow space was confirmed. CT-derived shear modulus values were highly reproducible (ICC = 0.98) and high linear correlation (r ≥ 0.83) was observed with micro-CT-derived reference values. Nonlinear FEA using clinical CT imaging will broaden the scope of micro-mechanical analysis of Tb network at relatively low in vivo resolution alleviating the need for binary segmentation of Tb, while accounting for microdistribution of bone minerals.
Osteoporosis is an age-related disease associated with reduced bone density and increased fracture-risk. It is known that bone microstructural quality is a significant determinant of trabecular bone strength and fracture-risk. Emerging CT technology allows high-resolution in vivo imaging at peripheral sites enabling assessment of bone microstructure at low radiation. Resolution dependence of bone microstructural measures together with varying technologies and rapid upgrades in CT scanners warrants data-harmonization in multi-site as well as longitudinal studies. This paper presents an unsupervised deep learning method for high-resolution reconstruction of bone microstructure from low-resolution CT scans using GAN-CIRCLE. The unsupervised training alleviates the need of registered low- and high-resolution images, which is often unavailable. Low- and high-resolution ankle CT scans of twenty volunteers were used for training, validation, and evaluation. Ten thousand unregistered low- and high-resolution patches of size 64×64 were randomly harvested from CT scans of ten volunteers for training and validation. Five thousand matched pairs of low- and highresolution patches were generated for evaluation after registering CT scan pairs from other ten volunteers. 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 derived from low-resolution data. Also, trabecular bone microstructural measures such as thickness and network area measures computed from predicted high-resolution CT images showed higher (CCC = [0.90, 0.84]) agreement with the reference measures from true high-resolution scans compared to the same measures derived from low-resolution images (CCC = [0.66, 0.83]).
Osteoporosis is a common age-related disease associated with increased bone loss causing reduced bone strength and enhanced fracture-risk. Finite element (FE) modelling is used to estimate bone strength from high-resolution threedimensional (3-D) imaging modalities including micro-CT, MRI, and HR-pQCT. Emerging technologies of multi-row detector CT (MDCT) imaging offer spatial image resolution comparable to human trabecular thickness. However, at the current MDCT resolution regime, FE modelling based on segmented trabecular bone (Tb) microstructure suffers from noise and other imaging artifacts. In this paper, we present a bone mineral density (BMD)-adjusted FE modeling method of Tb microstructure from MDCT imaging without requiring Tb segmentation. The method spatially varies mechanical stiffness based on local ash-density estimated from MDCT-derived calcium hydroxyapatite (CHA) density and, thus, models the hypothesis that stress-flow is primarily absorbed by Tb microstructure as compared to marrow space under mechanical compression. Specifically, an MDCT-based linear FE analysis method was developed using a voxel-mesh and the above model of space-varying stiffness, and the performance of the method was examined. For FE analysis, an axial cylindrical image core of 8mm diameter from 4-6% of distal tibia was extracted after aligning the tibial bone axis with the coordinate z-axis of the image space. Intra-class correlation coefficient (ICC) of 0.98 was observed in a repeat MDCT scan reproducibility experiment using cadaveric distal tibia specimens (n = 10). Also, high linear correlation (r = 0.87) was found between von Mises stress values and MDCT based CHA at individual voxels supporting the central hypothesis of our method.
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 images showed higher agreement with true high-resolution CT (CCC = [0.95, 0.91]) derived values than the same measures from low-resolution images (CCC = [0.72, 0.88]).
Osteoporosis is a common age-related disease characterized by reduced bone mineral density (BMD), micro-structural deterioration, and enhanced fracture-risk. Although, BMD is clinically used to define osteoporosis, there are compelling evidences that bone micro-structural properties are strong determinants of bone strength and fracture-risk. Reliable measures of effective trabecular bone (Tb) micro-structural features are of paramount clinical significance. Tb consists of transverse and longitudinal micro-structures, and there is a hypothesis that transverse trabeculae improve bone strength by arresting buckling of longitudinal trabeculae. In this paper, we present an emerging clinical CT-based new method for characterizing transverse and longitudinal trabeculae, validate the method, and examine its application in human studies. Specifically, we examine repeat CT scan reproducibility, and evaluate the relationships of these measures with gender and body size using human CT data from the Iowa Bone Development Study (IBDS) (n = 99; 49 female). Based on a cadaveric ankle study (n = 12), both transverse and longitudinal Tb measures are found reproducible (ICC < 0.94). It was observed in the IBDS human data that males have significantly higher trabecular bone measures than females for both inner (p < 0.05) and outer (p < 0.01) regions of interest (ROIs). For weight, Spearman correlations ranged 0.43-0.48 for inner ROI measures and 0.50-0.52 for outer ROI measures for females versus 0.30-0.34 and 0.23-0.25 for males. Correlation with height was lower (0.36-0.39), but still mostly significant for females. No association of trabecular measures with height was found for males.
Osteoporosis, associated with reduced bone mineral density and structural degeneration, greatly increases the risk of fragility fracture. A major challenge of volumetric bone imaging of the hip is the selection of regions of interest (ROIs) for computation of regional bone measurements. Here, we develop an MRI-based active shape model (ASM) of the human proximal femur used to automatically generate ROIs. Major challenges in developing the ASM of a complex three-dimensional (3-D) shape lie in determining a large number of anatomically consistent landmarks for a set of training shapes. In this paper, we develop a new method of generating the proximal femur ASM, where two types of landmarks, namely fiducial and secondary landmarks, are used. The method of computing the MRI-based proximal femur ASM consists of—(1) segmentation of the proximal femur bone volume, (2) smoothing the bone surface, (3) drawing fiducial landmark lines on training shapes, (4) drawing secondary landmarks on a reference shape, (5) landmark mesh generation on the reference shape using both fiducial and secondary landmarks, (6) generation of secondary landmarks on other training shapes using the correspondence of fiducial landmarks and an elastic deformation of the landmark mesh, (7) computation of the active shape model. An MRI-based shape model of the human proximalfemur has been developed using hip MR scans of 45 post-menopausal women. The results of secondary landmark generation were visually satisfactory and no topology violation or notable geometric distortion artifacts were observed. Performance of the method was examined in terms of shape representation errors in a leave-one-out test. The mean and standard deviation of leave-one-out shape representation errors were 2.27 and 0.61 voxels respectively. The experimental results suggest that the framework of fiducial and secondary landmark allows reliable computation statistical shape models for complex 3-D anatomic structures.
KEYWORDS: Bone, Image segmentation, In vivo imaging, Modeling, 3D image reconstruction, 3D image processing, Biological research, 3D modeling, Algorithm development, Finite element methods, Reconstruction algorithms
Osteoporosis is associated with increased fracture risk. Recent advancement in the area of in vivo imaging allows segmentation of trabecular bone (TB) microstructures, which is a known key determinant of bone strength and fracture risk. An accurate biomechanical modelling of TB micro-architecture provides a comprehensive summary measure of bone strength and fracture risk. In this paper, a new direct TB biomechanical modelling method using nonlinear manifold-based volumetric reconstruction of trabecular network is presented. It is accomplished in two sequential modules. The first module reconstructs a nonlinear manifold-based volumetric representation of TB networks from three-dimensional digital images. Specifically, it starts with the fuzzy digital segmentation of a TB network, and computes its surface and curve skeletons. An individual trabecula is identified as a topological segment in the curve skeleton. Using geometric analysis, smoothing and optimization techniques, the algorithm generates smooth, curved, and continuous representations of individual trabeculae glued at their junctions. Also, the method generates a geometrically consistent TB volume at junctions. In the second module, a direct computational biomechanical stress-strain analysis is applied on the reconstructed TB volume to predict mechanical measures. The accuracy of the method was examined using micro-CT imaging of cadaveric distal tibia specimens (N = 12). A high linear correlation (r = 0.95) between TB volume computed using the new manifold-modelling algorithm and that directly derived from the voxel-based micro-CT images was observed. Young’s modulus (YM) was computed using direct mechanical analysis on the TB manifold-model over a cubical volume of interest (VOI), and its correlation with the YM, computed using micro-CT based conventional finite-element analysis over the same VOI, was examined. A moderate linear correlation (r = 0.77) was observed between the two YM measures. This preliminary results show the accuracy of the new nonlinear manifold modelling algorithm for TB, and demonstrate the feasibility of a new direct mechanical strain-strain analysis on a nonlinear manifold model of a highly complex biological structure.
Osteoporosis is associated with an increased risk of low-trauma fractures. Segmentation of trabecular bone (TB) is essential to assess TB microstructure, which is a key determinant of bone strength and fracture risk. Here, we present a new method for TB segmentation for in vivo CT imaging. The method uses Hessian matrix-guided anisotropic diffusion to improve local separability of trabecular structures, followed by a new multi-scale morphological reconstruction algorithm for TB segmentation. High sensitivity (0.93), specificity (0.93), and accuracy (0.92) were observed for the new method based on regional manual thresholding on in vivo CT images. Mechanical tests have shown that TB segmentation using the new method improved the ability of derived TB spacing measure for predicting actual bone strength (R2=0.83).
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