Quantifying Fracture Severity Using a 3-D Puzzle Solving Approach

描述（由申请人提供）：拟议的研究旨在推进用于评估持续粉碎性关节内骨折患者的创新方法。创伤后骨关节炎（PTOA）是一种晚期并发症，伴随着大量的终身发病率和残疾，其风险与伴随这些骨折的关节创伤的强度有关。目前用于评估关节损伤严重程度的方法是有限的、不可再现的，并且通常是定性的，这阻碍了旨在避免PTOA的新治疗的评价。在初始损伤的严重程度能够被客观地测量之前，它将仍然是阻碍有意义的调查的实质性混杂因素。拟议工作的一个全球目标是建立物理基础，非侵入性技术，以量化关节内骨折的严重程度。在给定的骨折中消耗的机械能的CT衍生测量提供了对关节的机械损伤的指数。它们没有考虑到骨折的定位，或骨折块移位和分散，这些是反映PTOA风险的关键因素，因为这需要目前无法获得的关于分散的骨折块最初在完整骨中占据的位置的知识。推导出这些信息，实际上，解决了一个三维（3-D）难题，一个合适的计算算法最近开始出现的任务。这种新功能有可能极大地推进粉碎性关节内骨折的评估方式，促进旨在恢复风险关节组织健康的新治疗方法（主要是生物治疗）的研究。两个具体的目标将追求先进的3-D难题解决方法，用于此用途。具体目标1是在由骨替代材料机加工并包裹在软组织替代材料中的测试样本中生成代表性骨折碎片。碎片体积和表面数据将从CT扫描（预期临床用途）中获得，碎片处于其自发移位/散布位置，重复表面数据将从随后的单个碎片激光扫描中获得（金标准）。根据这些数据，将确定骨折碎片分割的准确性和重建已知骨折前样本几何形状的3-D难题解决方案的准确性。具体目标2是从现有的一系列胫骨平台骨折病例中获得3-D难题解决方案和相关的骨折严重程度指数，这些病例将获得3 - 5年的结局数据。骨折严重度指标将与严重度的临床等级排序相关，进而与PTOA的临床发生率相关，并与功能结局指标相关。 公共卫生相关性：遭受严重肢体创伤的患者，其中骨骼高度破碎并且骨折延伸到关节关节（如踝关节或膝关节），通常预后不良，最终关节炎是常见的致残结局。由于缺乏骨折严重程度的客观测量，外科医生目前依赖于主观印象来指导这些患者的治疗，阻碍了预防创伤后关节炎的进展。一种三维解谜方法产生了新的，客观的关节骨折严重程度的措施，提供了一个新的框架，统计学上强大的临床/翻译研究的新的治疗方法，以减少创伤后关节炎的风险。

DESCRIPTION (provided by applicant): The proposed research aims to advance innovative methods for the evaluation of patients who have sustained comminuted intra-articular fractures. The risk of post-traumatic osteoarthritis (PTOA), a late complication with substantial lifelong morbidity and disability, is related to the intensity of the joint trauma accompanying these fractures. Current methods for assessing the severity of joint injury are limited, irreproducible, and generally qualitative, hindering the evaluation of new treatments aimed at avoiding PTOA. Until the severity of the initial injury can be objectively measured, it will remain a substantial confounder hindering meaningful investigation. A global objective of the proposed work is to establish physically-grounded, non-invasive techniques to quantify intra-articular fracture severity. CT-derived measures of the mechanical energy expended in a given fracture provide an index of the mechanical insult to the joint. They do not account for localization of fragmentation, or fragment displacement and dispersal, critical factors reflecting the risk of PTOA, as this requires presently unavailable knowledge of the positions that the dispersed fragments originally occupied in the intact bone. Deducing this information entails, in effect, solving a three-dimensional (3-D) puzzle, a task for which suitable computational algorithms have recently begun to emerge. This new capability holds the potential to greatly advance the manner in which comminuted intra-articular fractures are assessed, facilitating investigation of new treatments (primarily biologic) aimed at restoring the health of at-risk articular tissues. Two specific aims will be pursued to advance 3-D puzzle solving methods for this use. Specific Aim 1 is to generate representative fracture fragmentation in test specimens machined from a bone surrogate material, and encased in a soft tissue surrogate. Fragment volumetric and surface data will be obtained from CT scans (intended clinical use), with fragments in their spontaneously-displaced/interspersed positions, and duplicate surface data will be obtained from ensuing laser scans of individual fragments (gold standard). Working from these data, the accuracy of fracture fragment segmentation, and 3-D puzzle solution accuracy in reconstructing the known pre- fracture specimen geometry, will be determined. Specific Aim 2 is to obtain 3-D puzzle solutions, and associated fracture severity indices, working from an existing series of tibial plafond fracture cases for which three to five year outcome data will be available. Fracture severity metrics will be correlated with a clinical rank ordering of severity, and in turn with the clinical incidence of PTOA, and with functional outcome measures. PUBLIC HEALTH RELEVANCE: Patients sustaining severe limb trauma in which bones are highly fragmented and the fracture extends into an articular joint such as the ankle or knee, have a generally poor prognosis, with eventual arthritis as a common disabling outcome. Lacking objective measures of fracture severity, surgeons presently rely upon subjective impressions to guide treatment of these patients, hindering progress toward forestalling post-traumatic arthritis. A 3-D puzzle solving approach yields new, objective measures of articular fracture severity, providing a novel framework for statistically robust clinical/translational studies of new treatments to reduce the risk of post-traumatic arthritis.