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

描述（由申请人提供）：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椎体骨折。采用细胞毒性药物、激素控制、双膦酸盐和/或局部放疗和/或手术稳定治疗的系统治疗，构成了骨骼转移的乳腺癌患者可用的治疗范围。然而，目前还没有客观的方法来选择哪种治疗方法能最好地降低患者维持病理性骨折的风险，并监测患者对治疗的反应。因此，建立客观的标准来评估受累椎的承载能力，既可以监测反映肿瘤与宿主骨相互作用的骨结构变化，也可以指导骨折预防治疗。骨折风险的客观测量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，由于肿瘤诱导的骨溶解导致的脊柱结构完整性丧失可以使用结构聚合物以微创方式进行恢复。在Aim 1中，在一系列体外试验中，将量化生理负荷条件下基于QCT的结构分析方案对具有模拟临界溶骨缺陷的胸腰椎人脊柱骨折风险进行分类的能力。计算椎骨的预测断裂载荷将与力学试验测量的失效载荷进行比较。脊柱韧带在影响预期失效载荷中的作用将被研究。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，为患病体的预防性增强提供术前计划。将使用具体的解剖和材料详细计算模型来优化基于图像的模块中包含的设计规则，以实现受影响椎体结构完整性的恢复。通过一系列体外研究，我们将描述治疗后椎骨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之间的依赖关系。我们将把这种性能与聚甲基丙烯酸酯水泥的使用进行比较。在Aim 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具有模拟溶解性缺陷的胸腰椎结构完整性方面的效果。综上所述，根据结构工程原理，将开发一种新的基于CT的术前分析、预测和增强系统，以允许术前计划对具有严重溶解性缺陷的人胸腰椎进行预防性增强。

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.