Metastatic Spine Tumors: Minimally Invasive Fracture Risk Analysis and Treatment - Master

转移性脊柱肿瘤：微创骨折风险分析和治疗 - 硕士

• 批准号: 10585673
• 负责人: Lichun Lu
• 金额: $ 41.44万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2028-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10585673
• 关键词: Activities of Daily Living; Address; Affect; Biocompatible Materials; Biomechanics; Biomimetics; Bone Cements; Cadaver; Calibration; Caring; Cauda Equina; Cementation; Chemicals; Chemistry; Clinic; Clinical; Communities; Complex; Counseling; Data; Decision Making; Defect; Development; Disease; Disseminated Malignant Neoplasm; Elements; Evaluation; Exercise; Failure; Family; Finite Element Analysis; Formulation; Fracture; Future; Grant; Home; Household; Human; Hydrogels; Injectable; Institution; Intervertebral disc structure; Length of Stay; Link; Lytic; Malignant Neoplasms; Mechanics; Methodology; Methods; Modeling; Motion; Nature; Neoplasm Metastasis; Nervous System Trauma; Network-based; Operative Surgical Procedures; Outcome Study; Pain; Paralysed; Patient Care; Patients; Periosteum; Physiological; Polymers; Prevention; Procedures; Process; Protocols documentation; Recommendation; Recovery; Rehabilitation therapy; Reproducibility; Research; Residual state; Retrospective cohort; Risk; Robotics; Scanning; Spinal; Spinal Fractures; Spinal Neoplasms; Spinal nerve structure; Spine surgery; Stretching; Surgical Oncology; System; Techniques; Testing; Time; Vertebral column; Weight-Bearing state; Work; X-Ray Computed Tomography; base; biomaterial compatibility; bone; catalyst; clinical implementation; clinical translation; clinically relevant; computerized; crosslink; fracture risk; grandchild; high risk; improved; indexing; kinematics; mechanical properties; minimally invasive; neural; novel; operation; poly(propylene fumarate); prevent; programs; prophylactic; quantitative computerized tomography based finite element analysis; reconstitution; reconstruction; risk prediction; spinal cord compression; spine bone structure; tumor; vertebra body; virtual; virtual assessment

Project Summary/Abstract The identification of cancer metastases to the bony vertebral column obligates the treating clinician to make a surgical decision. Current spinal stability decision-making is empirical, qualitative, and can be inaccurate. The consequences of that decision for the patient, however, are significant. If the spine is deemed at risk for fracture, then the patient will undergo a major spinal operation. Conversely, the patient whose spine is deemed stable risks fracture and possible paralysis if the analysis was incorrect. This research program addresses both the stability decision and the nature of the treatment. In this renewal application, we will continue our efforts to develop non-invasive, quantitative, and reliable methods to predict the fracture risk of vertebrae with metastatic cancer under physiologically relevant loading conditions, and to optimize minimally invasive techniques using novel biomaterials to reconstitute the load bearing capacity of an affected vertebra. In Aim 1, we propose a novel injectable polymer network that can be self-crosslinked via catalyst-free click chemistry into “click” organic-inorganic nanohybrid (click-ON) bone cement. Compared to our previous injectable system, the novel cement has improved biocompatibility, injectability, and crosslinking efficiency. In Aim 2, we will investigate the efficacy of the optimized click-ON bone cement to both prevent impending fractures and treat existing fractures in cadaveric models using the clinical vertebroplasty and kyphoplasty procedures, respectively (Aim 2a). Intact lumbar spines (L1-S1), spines with simulated lytic defects, and spines with biomaterial augmentation will be tested under accurate and biomimetic loading conditions using a novel robotic testing system. Our previously developed quantitative computerized tomography based finite element analysis (QCT/FEA) models will be expanded to include both kinematic motion evaluation and fracture risk prediction under physiological loading and boundary conditions and validated using the experimental results (Aim 2b). In Aim 3, We will develop a phantom-less calibration technique to account for the effects of QCT protocols on QCT/FEA results (Aim 3a). Using the powerful AnalyzeMD platform, we will implement an automated process to further advance the FEA technique for time efficiency and reproducibility (Aim 3b). We will apply the comprehensive QCT/FEA models in a retrospective cohort of spine metastasis patients and assess the virtual reconstruction using the click-ON bone cement as a first step towards clinical translation. The QCT/FEA technique developed in this work takes into consideration both the quality and quantity of bone and the degeneration status of the intervertebral discs. This technique allows the clinician to counsel her/his patient regarding activities of daily living that can be performed with a low risk of spinal fracture. Our future plans are to expand the clinical implementation of the spinal FEA analysis at Mayo Clinic. We will add FEA evaluation results in our discussion with the patients regarding our recommendations for their care. We will study the outcome results of those recommendations, adjust the decision parameters as necessary, and then extend the analysis to additional institutions.

项目总结/摘要 确定癌症转移到骨脊柱迫使治疗临床医生作出一个 手术决定。目前的脊柱稳定性决策是经验性的、定性的，并且可能是不准确的。的 然而，该决定对患者的后果是显著的。如果脊柱被认为有风险， 骨折，那么病人将接受一个重大的脊柱手术。相反，脊柱被认为 如果分析不正确，稳定的风险是骨折和可能的瘫痪。该研究计划涉及两个 稳定性决定和治疗的性质。在这次续约申请中，我们将继续努力， 开发非侵入性，定量和可靠的方法来预测转移性椎体骨折的风险， 在生理学相关的负荷条件下的癌症，并使用 用于重建受影响椎骨的承载能力的新型生物材料。在目标1中，我们提出了一个 可通过无催化剂点击化学自交联成“点击”的新型可注射聚合物网络 有机-无机纳米混合（点击）骨水泥。与我们以前的注射系统相比， 粘固剂具有改进的生物相容性、可注射性和交联效率。在目标2中，我们将研究 优化click-ON骨水泥预防即将发生的骨折和治疗现有骨折的有效性 分别使用临床椎体成形术和椎体后凸成形术的尸体模型（目的2a）。完整 腰椎（L1-S1）、具有模拟溶解性缺损的脊柱和具有生物材料增强的脊柱将 使用新型机器人测试系统在精确和仿生负载条件下进行测试。我们先前 将开发基于定量计算机断层扫描的有限元分析（QCT/FEA）模型 扩展到包括生理负荷下的运动学运动评估和骨折风险预测 和边界条件，并使用实验结果进行验证（目标2b）。在目标3中，我们将开发一个 考虑QCT方案对QCT/FEA结果影响的无体模校准技术（目标3a）。 使用强大的AnalyzeMD平台，我们将实施自动化流程，以进一步推进FEA 时间效率和再现性技术（目标3b）。我们将应用全面的QCT/FEA模型 在脊柱转移瘤患者的回顾性队列中，使用click-ON 骨水泥作为临床转化的第一步。在这项工作中开发的QCT/FEA技术需要 综合考虑骨的质量和数量以及椎间盘的退变情况。 这种技术允许临床医生就可能被忽视的日常生活活动向她/他的患者提供咨询。 脊柱骨折的风险很低我们未来的计划是扩大临床实施的 马约诊所的脊柱FEA分析。我们将在与患者的讨论中添加FEA评价结果 我们对他们的护理建议。我们将研究这些建议的结果， 根据需要调整决策参数，然后将分析扩展到其他机构。