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.

项目概要/摘要 确定癌症转移到骨性脊柱后，治疗临床医生有义务做出以下决定： 目前的脊柱稳定性决策是经验性的、定性的，并且可能不准确。 然而，如果脊柱被认为存在风险，那么该决定对患者的后果将是重大的。 骨折，那么患者将离线接受大型脊柱手术，该患者的脊柱被视为。 如果分析不正确，稳定的风险是骨折和可能的瘫痪，该研究项目解决了这两个问题。 稳定性决定和治疗的性质在此续签申请中，我们将继续努力。 开发非侵入性、定量且可靠的方法来预测转移性椎骨的骨折风险 生理相关负荷条件下的癌症，并使用优化微创技术 在目标 1 中，我们提出了一种新型生物材料来重建受影响椎骨的承载能力。 新型可注射聚合物网络，可以通过无催化剂的点击化学自交联成“点击” 与我们之前的可注射系统相比，这种新颖的有机-无机纳米混合（click-ON）骨水泥。 在目标 2 中，我们将研究水泥改善了生物相容性、可注射性和交联效率。 优化的卡入式骨水泥在预防即将发生的骨折和治疗现有骨折方面的功效 分别使用临床椎体成形术和椎体后凸成形术在尸体模型中进行实验（目标 2a）。 腰椎（L1-S1）、具有模拟溶解缺陷的脊柱以及具有生物材料增强的脊柱将被 我们之前使用新型机器人测试系统在精确和仿生负载条件下进行了测试。 开发的基于计算机定量断层扫描的有限元分析（QCT/FEA）模型将 扩展到包括生理负荷下的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 无体模校准技术，用于解释 QCT 协议对 QCT/FEA 结果的影响（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 时间效率和可重复性技术（目标 3b）我们将应用综合 QCT/FEA 模型。 在脊柱转移患者的回顾性队列中，并使用 click-ON 评估虚拟重建 骨水泥作为临床转化的第一步，需要采用 QCT/FEA 技术。 考虑到骨的质量和数量以及椎间盘的退变状态。 该技术允许临床医生就日常生活活动向她/他的患者提供咨询，这些活动可以是 我们未来的计划是扩大该技术的临床实施。 Mayo Clinic 的脊柱 FEA 分析 我们将在与患者的讨论中添加 FEA 评估结果。 关于我们对他们的护理的建议，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。