Pre-Operative QCT Planning Protocol for Treating the Structural Deficiency of Spi

描述(申请人提供)：脊柱是最常受转移性乳腺癌影响的骨骼部位，17%-50%的脊柱转移患者会发生脊椎骨折。全身使用细胞毒剂、激素操作、双膦酸盐和/或局部放射治疗和/或手术稳定治疗构成了可用于乳腺癌骨转移患者的各种治疗方法。然而，没有客观的方法来选择哪种治疗方法最能降低患者持续病理性骨折的风险，并监测患者对治疗的反应。因此，建立评价受累椎体承载能力的客观标准，既可用于监测反映肿瘤与宿主骨相互作用的骨结构变化，又可用于指导骨折预防治疗。客观衡量骨折风险将加强患者管理和资源利用。我们的总体假设是，使用基于CT的结构分析方案评估的肿瘤诱导的骨溶解导致的脊柱结构完整性的丧失，可以使用以微创方式部署的结构聚合物来恢复。在目标1中，在一系列体外测试中，将在生理载荷条件下量化基于QCT的结构分析方案对具有模拟临界溶骨缺陷的胸腰椎脊柱骨折风险的分类能力。为椎骨计算的预测断裂载荷将与通过机械测试测量的失效载荷进行比较。脊柱韧带在影响预测的失效载荷中的作用将被调查。在目标2中，将开发一种新的基于图像的算法，并将其集成到CT结构分析方案中，以提供受影响椎体预防性增强的术前计划。具体的解剖学和物质细节计算模型将用于优化包含在基于图像的模块中的设计规则，以实现受影响脊椎结构完整性的恢复。利用一系列的体外研究，我们将表征治疗椎体的机械性能与可注射生物聚合物的材料特性和溶解缺陷的几何特性的依赖关系。我们将把这种性能与使用聚甲基丙烯酸甲酯水泥进行比较。在目标3中，将量化开发的基于CT的术前分析、预测和增强系统在恢复有模拟松解缺陷的胸腰椎结构完整性方面的有效性。综上所述，根据结构工程学的原理，将开发一种基于CT的新的术前分析、预测和增强系统，以实现对有严重松解缺陷的人胸腰段脊柱预防性增强的术前计划。

DESCRIPTION (provided by applicant): The spine is the skeletal site most often affected by metastatic breast cancer, and 17-50% of patients with spinal metastasis sustain a vertebral fracture. Systemic treatments with cytotoxic agents, hormone manipulation, bisphosphonates and/or local treatment with radiation and/or surgical stabilization, constitute the range of therapies available to breast cancer patients with skeletal metastasis. However, there are no objective methods for selecting which treatment will best reduce the patient's risk for sustaining a pathologic fracture and for monitoring the patient's response to therapy. Therefore, establishing objective criteria to evaluate the load carrying capacity of the involved vertebrae can be used both to monitor changes in bone structure that reflect the interaction of the tumor with the host bone, and to guide treatment for fracture prevention. Objective measures of fracture risk will both enhance patient management and resource utilization. Our overall hypothesis is that the loss of structural integrity of the spine due to tumor induced osteolysis, assessed using CT based structural analysis protocol, can be restored using structural polymers deployed in a minimally invasive manner. In Aim 1, in a series of in vitro tests, the ability of a QCT based structural analysis protocol to classify the fracture risk of thoracolumbar human spines with simulated critical osteolytic defects will be quantified under physiological loading conditions. Predicated fracture load, computed for the vertebrae, will be compared to the failure load measured by mechanical testing. The role of spinal ligaments in effecting the predicted failure load will be investigated. In Aim 2, a novel image-based algorithm will be developed and integrated within the CT structural analysis protocol, to provide pre-operative planning for prophylactic augmentation of the affected vertebra. Specific anatomically and materially detailed computational models will be used to optimize the design rules incorporated within the image based module to achieve restoration of the structural integrity of the affected vertebra. Using a series of in vitro studies, we will characterize the dependencies of the mechanical properties of treated vertebrae on the material properties of the injectable biopolymer and the geometrical properties of the lytic defect. We will compare this performance to the use of Polymethylmetacrylate cement. In Aim 3, the efficacy of the developed CT based pre-operative analysis, prediction and augmentation system, in restoring the structural integrity of thoracolumbar spines with simulated lytic defects, will be quantified. In summary, Drawing on principles of structural engineering, a novel CT based pre-operative analysis, prediction and augmentation system, will be developed to allow pre-operative planning for prophylactic augmentation of the human thoracolumbar spines with critical lytic defects.