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STUDY DESIGN: Micro-computed tomography- (micro-CT-) based finite element analysis of cadaveric human lumbar vertebrae virtually implanted with total disc arthroplasty (TDA) implants. OBJECTIVE: (1) Assess the relationship between vertebral porosity and maximum levels of bone-tissue stress following TDA; (2) determine whether the implant's loading mode (axial compression vs. sagittal bending) alters the relationship between vertebral porosity and bone-tissue stress. SUMMARY OF BACKGROUND DATA: Implant subsidence may be related to the bone biomechanics in the underlying vertebral body, which are poorly understood. For example, it remains unclear how the stresses that develop in the supporting bone tissue depend on the implant's loading mode or on typical inter-individual variations in vertebral morphology. METHODS: Data from micro-CT scans from 12 human lumbar vertebrae (8 males, 4 females; 51-89 years of age; bone volume fraction [BV/TV] = 0.060-0.145) were used to construct high-resolution finite element models (37 µm element edge length) comprising disc-vertebra-implant motion segments. Implants were loaded to 800 N of force in axial compression, flexion-, and extension-induced impingement. For comparison, the same net loads were applied via an intact disc without an implant. Linear regression was used to assess the relationship between BV/TV, loading mode, and the specimen-specific change in stress caused by implantation. RESULTS: The increase in maximum bone-tissue stress caused by implantation depended on loading mode (P < 0.001), increasing more in bending-induced impingement than axial compression (for the same applied force). The change in maximum stress was significantly associated with BV/TV (P = 0.002): higher porosity vertebrae experienced a disproportionate increase in stress compared with lower porosity vertebrae. There was a significant interaction between loading mode and BV/TV (P = 0.002), indicating that loading mode altered the relationship between BV/TV and the change in maximum bone-tissue stress. CONCLUSION: Typically-sized TDA implants disproportionately increase the bone-tissue stress in more porous vertebrae; this affect is accentuated when the implant impinges in sagittal bending.Level of Evidence: N/A.

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Calculations of X-ray wave propagation in large objects are needed for modeling diffractive X-ray optics and for optimization-based approaches to image reconstruction for objects that extend beyond the depth of focus. We describe three methods for calculating wave propagation with large arrays on parallel computing systems with distributed memory: (1) a full-array Fresnel multislice approach, (2) a tiling-based short-distance Fresnel multislice approach, and (3) a finite difference approach. We find that the first approach suffers from internode communication delays when the transverse array size becomes large, while the second and third approaches have similar scaling to large array size problems (with the second approach offering about three times the compute speed).

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Clinical use of pharmacogenomic (PGx) knowledge at the bedside is new and complex. Our program has implemented multiple PGx-CDS interventions in different clinical settings and in multiple commercial EHRs. Herein, we discuss lessons learned and propose general technical guidelines related to PGx implementation.

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The mechanisms of age-related vertebral fragility remain unclear, but may be related to the degree of "structural redundancy" of the vertebra; ie, its ability to safely redistribute stress internally after local trabecular failure from an isolated mechanical overload. To better understand this issue, we performed biomechanical testing and nonlinear micro-CT-based finite element analysis on 12 elderly human thoracic ninth vertebral bodies (age 76.9 ± 10.8 years). After experimentally overloading the vertebrae to measure strength, we used nonlinear finite element analysis to estimate the amount of failed tissue and understand the failure mechanisms. We found that the amount of failed tissue per unit bone mass decreased with decreasing bone volume fraction (r(2) = 0.66, p < 0.01). Thus, for the weak vertebrae with low bone volume fraction, overall failure of the vertebra occurred after failure of just a tiny proportion of the bone tissue (<5%). This small proportion of failed tissue had two sources: the existence of fewer vertically oriented load paths to which load could be redistributed from failed trabeculae; and the vulnerability of the trabeculae in these few load paths to undergo bending-type failure mechanisms, which further weaken the bone. Taken together, these characteristics suggest that diminished structural redundancy may be an important aspect of age-related vertebral fragility: vertebrae with low bone volume fraction are highly susceptible to collapse because so few trabeculae are available for load redistribution if the external loads cause any trabeculae to fail.

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High-resolution peripheral quantitative computed tomography (HR-pQCT) is a newly developed in vivo clinical imaging modality. It can assess the 3D microstructure of cortical and trabecular bone at the distal radius and tibia and is suitable as an input for microstructural finite element (microFE) analysis to evaluate bone's mechanical competence. In order for microstructural and image-based microFE analyses to become standard clinical tools, validation with a current gold standard, namely, high-resolution micro-computed tomography (microCT), is required. Microstructural measurements of 19 human cadaveric distal tibiae were performed for the registered HR-pQCT and microCT images, respectively. Next, whole bone stiffness, trabecular bone stiffness, and elastic moduli of cubic subvolumes of trabecular bone in both HR-pQCT and microCT images were determined by microFE analysis. The standard HR-pQCT patient protocol measurements, derived bone volume fraction (BV/TV(d)), trabecular number (Tb.N*), trabecular thickness (Tb.Th), trabecular spacing (Tb.Sp), and cortical thickness (Ct.Th), as well as the voxel-based direct measurements, BV/TV, Tb.N*, Tb.Th*, Tb.Sp*, Ct.Th, bone surface-to-volume ratio (BS/BV), structure model index (SMI), and connectivity density (Conn.D), correlated well with their respective gold standards, and both contributed to microFE-predicted mechanical properties in either single or multiple linear regressions. The mechanical measurements, although overestimated by HR-pQCT, correlated highly with their gold standards. Moreover, elastic moduli of cubic subvolumes of trabecular bone predicted whole bone or trabecular bone stiffness in distal tibia. We conclude that microstructural measurements and mechanical parameters of distal tibia can be efficiently derived from HR-pQCT images and provide additional information regarding bone fragility.

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UNLABELLED: The biomechanical role of the vertebral cortical shell remains poorly understood. Using high-resolution finite element modeling of a cohort of elderly vertebrae, we found that the biomechanical role of the shell can be substantial and that the load sharing between the cortical and trabecular bone is complex. As a result, a more integrative measure of the trabecular and cortical bone should improve noninvasive assessment of fracture risk and treatments. INTRODUCTION: A fundamental but poorly understood issue in the assessment of both osteoporotic vertebral fracture risk and effects of treatment is the role of the trabecular bone and cortical shell in the load-carrying capacity of the vertebral body. MATERIALS AND METHODS: High-resolution microCT-based finite element models were developed for 13 elderly human vertebrae (age range: 54-87 years; 74.6 +/- 9.4 years), and parameter studies-with and without endplates-were performed to determine the role of the shell versus trabecular bone and the effect of model assumptions. RESULTS: Across vertebrae, whereas the average thickness of the cortical shell was only 0.38 +/- 0.06 mm, the shell mass fraction (shell mass/total bone mass)-not including the endplates-ranged from 0.21 to 0.39. The maximum load fraction taken by the shell varied from 0.38 to 0.54 across vertebrae and occurred at the narrowest section. The maximum load fraction taken by the trabecular bone varied from 0.76 to 0.89 across vertebrae and occurred near the endplates. Neither the maximum shell load fraction nor the maximum trabecular load fraction depended on any of the densitometric or morphologic properties of the vertebra, indicating the complex nature of the load sharing mechanism. The variation of the shell load-carrying capacity across vertebrae was significantly altered by the removal of endplates, although these models captured the overall trend within a vertebra. CONCLUSIONS: The biomechanical role of the thin cortical shell in the vertebral body can be substantial, being about 45% at the midtransverse section but as low as 15% close to the endplates. As a result of the complexity of load sharing, sampling of only midsection trabecular bone as a strength surrogate misses important biomechanical information. A more integrative approach that combines the structural role of both cortical and trabecular bone should improve noninvasive assessment of vertebral bone strength in vivo.

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