TOWARD PATIENT SPECIFIC DENSITY MODELLING OF THE TIBIA

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 (We要求快速审查我和我的研究生Charles Negus一起进行了这项工作，在休息期间，我们想再做一次，以期待一个新项目。摘要如下：虽然机械生物学骨研究开始于细胞水平或低于细胞水平，但它最终应用于改善临床环境中的患者护理。在细胞水平的研究和临床应用之间的桥梁差距的一个关键领域的研究是计算力学。应力性骨折的形成是一种机械介导的病理学，有可能直接得到计算机方法和机械生物学研究的进步的帮助。应力性骨折的病因似乎是一种高度患者特异性的骨负荷相互作用，这些骨负荷来自个体生物力学、骨几何学和骨质量。骨的几何形状和质量将内在地反映遗传影响和先前的功能适应。骨的重复载荷导致疲劳样损伤累积，特别是在高度矿化的脆性骨中，在重复载荷下小裂纹合并成应力性骨折[1]。骨折周围的局部重塑试图清除损伤，如果它发生在持续载荷的存在下，实际上会加剧问题。因此，评估个体应力性骨折的可能性需要评估他们的骨质以及他们在重复载荷下的峰值应力。估计受试者胫骨应力分布表明患者特定的有限元分析，其几何形状理想地基于低辐射剂量，无创成像技术。骨小梁和皮质的密度分布对该模型提出了其他挑战。我们之前已经描述了一种新的，但计算简单的方法来密度重新分布和正交各向异性材料对齐[2]。动态低弹性重塑的灵感来自于目前对细胞机械转导的理解，即基于动态负荷引起的间质液流动。重构算法被纳入一个明确的，动态有限元代码并行使用消息传递接口。重塑发生在离散的，周期性发生的时间步长。皮质和骨小梁表观密度更新的基础上，局部应变率，和重新排列的主要材料方向的驱动下，局部应力张量。应力计算使用路径依赖的亚弹性本构关系，制定与Jaumann应力率。在正常步态和爬楼梯期间，负载条件在峰值施加速率的瞬间附近线性化，假设发生频率足以超过细胞重塑激活的阈值循环次数。涉及股骨近端的模拟结果表明，该动态方法的目标应变率为|D_I| = 1.7%/秒此外，我们将DHR应用于患者特定的胫骨3D模型。在胫骨长度的4%、38%和66%处收集女性受试者左侧胫骨的外周定量计算机断层扫描（pQCT）扫描。基于这三次扫描，通过外推法估计整个胫骨表面的近似3D模型。每个受试者特定的胫骨模型都被分配了来自标准化胫骨项目的通用骨骺，并根据她的人体测量学进行了缩放。然后将pQCT扫描的骨膜边界导入骨干区域，并在骨骺和pQCT边界之间生成3D放样表面。然后用三线六面体单元对三维表面进行网格划分。假设胫骨远端固定，根据每例受试者体重定义的5个斜坡载荷条件应用于内侧和外侧关节面。将DHR预测的骨干密度分布与原始pQCT扫描进行比较，以评估预测的皮质厚度与实际厚度。然后，这些模型可用于进行患者特定的应力分析，这有助于评估可能导致应力性骨折的峰值应力。这项研究说明了现代细胞研究，成像技术和计算方法如何以具有潜在临床实用性的方式整合。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. (We are requesting an expedited review. I conducted this work with my graduate student, Charles Negus, and during the break, we would like to do one more run in anticipation of a new project. The abstract is below: While mechanobiological bone research begins at or below the cellular level, it finds its ultimate application in improving patient care in a clinical setting. A crucial field of study in bridging the gap between the cellular level research and clinical application is computational mechanics. Stress fracture formation is a mechanically mediated pathology that has the potential to be directly aided by advances in computational methods and mechanobiological research. Stress fracture etiology seems to be a highly patient-specific interplay of bone loads arising from an individuals biomechanics, bone geometry, and bone quality. Bone geometry and quality will inherently reflect both genetic influences and prior functional adaptation. Repeated loads to the bone result in fatigue-like damage accumulation, particularly in highly mineralized, brittle bone where small cracks coalesce into stress fractures under repeated loading [1]. Local remodeling around the fracture which attempts to clear the damage, if it occurs in the presence of continued loading, can actually exacerbate the problem. Assessing an individuals stress fracture potential thus entails assessing their bone quality as well as their peak stresses under repeated loads. Estimating a subjects tibial stress profile suggests a patient-specific finite element analysis, whose geometry is ideally based on low radiation dosage, noninvasive imaging techniques. Assigning trabecular and cortical density distributions to this model present other challenges. We have previously described a novel, but computationally simple approach to density redistribution and orthotropic material alignment [2]. Dynamic Hypoelastic Remodeling is inspired by current understanding of cellular mechanotransduction as being predicated on interstitial fluid flow resulting from dynamic loading. The remodeling algorithm is incorporated in an explicit, dynamic finite element code parallelized using Message Passing Interface. Remodeling occurs at discrete, periodically occurring time steps. Cortical and trabecular apparent densities are updated based on local strain rate, and realignment of principal material directions is driven by the local stress tensor. Stress is calculated using a path-dependent hypoelastic constitutive law, formulated with the Jaumann stress rate. Loading conditions were linearized around instants of peak rate of application during normal gait and stair climbing, assumed to occur with sufficient frequency to exceed the threshold cycle number for cellular remodeling activation. Results from simulations involving the proximal femur indicate that a target strain rate for this dynamic approach is |D_I | = 1.7%/sec. Additionally, we apply DHR to patient-specific 3D models of the tibia. Peripheral quantitative computed tomography (pQCT) scans of the left tibia were collected for female subjects at 4%, 38%, and 66% of tibial length. Based on these three scans, approximate 3D models of the entire tibial surface was estimated by extrapolation. Each subject-specific model tibia was assigned generic epiphyses from the Standardized Tibia Project which were scaled according to her anthropometrics. Then the periosteal boundaries of the pQCT scans were imported into the diaphyseal region, and a 3D lofted surface was generated between the epiphyses and pQCT boundaries. The 3D surface was then meshed with trilinear hexahedral elements. The distal end of the tibia was assumed fixed, and five ramped loading conditions, defined based on each subjects body weight, were applied to the medial and lateral articular surfaces. The diaphyseal density distribution predicted by DHR will be compared against the original pQCT scans to assess the predicted cortical thickness against actual thickness. These models can then be used to conduct patient-specific stress analyses which could aid in assessing peak stresses that could lead to stress fracture. This research illustrates how modern cellular research, imaging techniques, and computational methods can be integrated in a manner which has potential clinical practicality.