Longitudinal monitoring of bone fracture healing using diffuse optical and correlation tomography

项目总结 在每年经历骨骼骨折的1500万美国人中，超过10%的人患有 治愈。愈合障碍的发生率高，导致患者的生活质量差，护理总费用高。 蒂恩斯。为了促进骨折愈合，正在开发各种基于再生医学的方法，但 由于目前成像技术的限制，它们的开发速度很慢。例如，血管疏松- 作为骨骼愈合的关键步骤，使用终点方法进行评估，该方法要求对动物进行SacrifiCe/破坏， 这导致了很高的学科间变异性、时间和成本。我们的目标是建立漫反射光学层析成像 (DOT)和相关断层扫描(DCT)作为监测血管形成的无创、纵向研究工具 并预测骨折愈合情况。DOT和DCT这两种3D深层组织血流动力学成像技术是治疗 由于低成本和使用非电离光，经常进行纵向监测。此外，DOT和DCT是 可在临床前应用程序和临床应用程序之间轻松扩展。总而言之，这些方法报告了多个微血管- 循环参数：总血红蛋白浓度、血氧饱和度与血氧饱和度、血fl、血氧饱和度。我们 假设双螺旋CT和双螺旋CT能准确定量测定局部血容量、氧合和fi下降值。 骨及周围软组织，可作为骨愈合质量的替代标志物。三 SPECIfic AIMS旨在验证这些假设：目标1：构建骨折治疗的预测模型 EFfi使用动物骨折模型，目标2：直接比较DOT和DCT与组织形态计量学， fl荧光微球技术与小鼠动态增强磁共振成像 骨折模型，目标3：构建fi第十二跖骨近端骨折骨不连的临床预测模型 基于DOT和DCT测量。这些目标的成功实现将带来巨大的进步 通过提供全面和创新的非侵入性再生医学和肌肉骨骼研究 纵向监测工具。此外，所提出的工作为DOT和DOT的临床翻译奠定了基础 DCT与传统血管评估技术在骨血管监测中的应用 并通过构建骨折愈合不良的临床预测模型。

PROJECT SUMMARY More than 10% of the 15 million Americans who experience skeletal fractures each year suffer from impaired healing. The large incidence of impaired healing results in poor quality of life and high total cost of care for pa- tients. To enhance fracture healing, various regenerative medicine based approaches are being developed, but their development rates are slow due to the limitations of current imaging techniques. For example, vasculariza- tion, a key step in bone healing, is assessed using endpoint methods requiring sacrifice/destruction of animals, leading to high inter-subject variability, time and cost. Our objective is to establish diffuse optical tomography (DOT) and correlation tomography (DCT) as non-invasive, longitudinal research tools to monitor vascularization and predict bone fracture healing. DOT and DCT, 3D deep-tissue hemodynamic imaging techniques, are ideal for frequent longitudinal monitoring due to low cost and the use of non-ionizing light. In addition, DOT and DCT are easily scalable between preclinical and clinical applications. Together, these methods report multiple microvas- cular parameters: total hemoglobin concentration and oxygen saturation with DOT and blood flow with DCT. We hypothesize that DOT and DCT provide accurate quantification of regional blood volume, oxygenation and flow in bone and surrounding soft tissues, which can serve as surrogate markers for the quality of bone healing. Three specific aims are designed to test the hypotheses: Aim 1: Construct a prediction model for bone fracture treatment efficacy using an animal bone fracture model, Aim 2: Directly compare DOT and DCT with histomorphometry, fluorescent microsphere technique and dynamic-contrast-enhanced magnetic resonance imaging in a murine fracture model, Aim 3: Construct clinical prediction model for nonunions in proximal fifth metatarsal fractures based on DOT and DCT measurements. Successful completion of these aims will result in great advances in regenerative medicine and musculoskeletal research by providing a comprehensive and innovative non-invasive longitudinal monitoring tool. In addition, the proposed work lays the foundation for clinical translation of DOT and DCT for bone vascular monitoring by direct comparison with traditional vascularization assessment techniques and by constructing a clinical prediction model for impaired healing in fractures.