Real-time fluorescence-based measurement of bone perfusion in post-traumatic infection

基于实时荧光的创伤后感染骨灌注测量

基本信息

批准号：
10132991
负责人：
Ida L Gitajn
金额：
$ 44.9万
依托单位：
DARTMOUTH-HITCHCOCK CLINIC
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-04-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10132991
关键词：
3-Dimensional Adopted Animals Antibiotics Biomedical Engineering Blood Vessels Blood flow Cells Clinical Clinical Research Collaborations Color Complex Data Data Analytics Debridement Decision Making Defect Evaluation Excision FDA approved Family suidae Fluorescence Fracture Funding Goals Human Image Immune Implant Indocyanine Green Infection Infrastructure Injury Kinetics Magnetic Resonance Imaging Measurable Measurement Measures Methodology Methods Modeling Morbidity - disease rate Nutrient Operating Rooms Operative Surgical Procedures Orthopedic Surgery Orthopedics Osteomyelitis Oxygen Patients Perfusion Phase Play Population Positron-Emission Tomography Procedures Radiology Specialty Recurrence Reproducibility Resolution Role Safety Shock Surface Surgeon Tactile Techniques Time Translating Translations Trauma patient Treatment Failure Variant Vascular blood supply Visual Visualization Work X-Ray Computed Tomography analytical tool base bone bone health clinically relevant contrast enhanced cost data acquisition experience fluorescence imaging fluorescence-guided surgery hemodynamics high risk imaging modality implementation measures improved infection rate infection risk innovation limb loss loss of function metallicity musculoskeletal injury porcine model pre-clinical prevent prospective reconstruction recurrent infection risk minimization soft tissue standard of care success tool trauma centers validation studies

项目摘要

Infection following bony fracture is one of the most prevalent and challenging complications in trauma patients with an estimated annual cost of $35 billion in the US. (https://stacks.cdc.gov/view/cdc/11550) Recurrent infection rates are unacceptably high at 30%, resulting in prolonged morbidity, loss of function, and/or loss of limb. Vascular perfusion plays a critical role in the health of bone by delivering necessary oxygen, nutrients, antibiotics, and endogenous immune cells. The management of bony infection is therefore based on aggressive, thorough debridement in an effort to remove all poorly perfused bone through visual and tactile clues such as color, turgor and extent of soft tissue stripping. However, there are no objectively measurable or quantifiable methods to assess the bone perfusion and the success of removing devitalized bone is based almost entirely on surgeon’s experience. Thus, the overall goal of this proposal is to develop and evaluate an indocyanine green (ICG)-based dynamic contrast-enhanced fluorescence imaging (DCE-FI) to objectively assess bone perfusion and guide surgical debridement. The scientific premise of this proposal is underpinned by data from our prior pre-clinical work in a porcine model and our pilot clinical study applying ICG-based DCE-FI to assess bone perfusion in patients during orthopaedic surgery. In these studies, we established that DCE-FI can quantitatively assess bone perfusion in a measurable, reproducible and predictable manner, and we developed analytic models differentiating the endosteal from periosteal contribution to total blood supply. This model was then able to effectively differentiate healthy from damaged bone with a linear decision boundary with 89% accuracy, in the pre-clinical porcine study. To attain our overall objective, three aims will be pursued. In Aim 1 we will assess the relationship between post-debridement bone perfusion, as measured using ICG-based DCE-FI, and recurrent infection/treatment failure. Additionally, we will refine analytic models that assess the relative contribution of endosteal versus periosteal blood supplies. In Aim 2 we will explore the relationship between dynamic contrast-enhanced MRI (DCE-MRI) and DCE-FI to improve the three-dimensional analytic potential of DCE-FI. In Aim 3 we will develop streamlined analytic tools into a user-centered interface that will optimize use of ICG-based DCE-FI derived data in normal surgical workflow. Application of ICG-based DCE-FI has enormous potential to revolutionize treatment of post-traumatic infections by minimizing treatment failure and minimizing bone resection and ultimately revolutionize the standard of care for millions of trauma patients. This project leverages an extensive infrastructure and experience in fluorescence-guided surgery as well as longstanding collaborations between surgical subspecialties and biomedical engineers at Dartmouth and R Adams Cowley Shock Trauma Center.

骨折后感染是创伤患者最常见和最具挑战性的并发症之一美国每年的成本估计为 350 亿美元 (https://stacks.cdc.gov/view/cdc/11550)。复发性感染率高达 30%，高得令人难以接受，导致长期发病、功能丧失、和/或肢体丧失血管灌注通过提供必要的物质而在骨骼健康中发挥着关键作用。因此，骨感染的治疗需要氧气、营养物质、抗生素和内源性免疫细胞。基于积极、彻底的清创，通过目视和清除所有灌注不良的骨头触觉线索，例如颜色、肿胀度和软组织剥离的程度，但没有客观的线索。可测量或可量化的方法来评估骨灌注和去除失活的成功骨几乎完全基于外科医生的经验，因此，该提案的总体目标是开发。并评估基于吲哚菁绿 (ICG) 的动态对比增强荧光成像 (DCE-FI) 客观评估骨灌注并指导手术清创是该提案的科学前提。以我们之前在猪模型中的临床前工作和我们的试点临床研究的数据为基础应用基于 ICG 的 DCE-FI 评估骨科手术期间患者的骨灌注。研究中，我们确定 DCE-FI 可以以可测量、可重复的方式定量评估骨灌注和可预测的方式，我们开发了区分骨内膜和骨膜的分析模型然后，该模型能够有效区分健康与受损。在临床前猪研究中，线性决策边界的准确度为 89%，以实现我们的总体目标。目标，将追求三个目标在目标 1 中，我们将评估清创后骨骼之间的关系。使用基于 ICG 的 DCE-FI 测量灌注，以及复发性感染/治疗失败。将完善评估骨内膜血液与骨膜血液的相对贡献的分析模型在目标 2 中，我们将探讨动态对比增强 MRI (DCE-MRI) 与供应之间的关系。 DCE-FI 提高 DCE-FI 的三维分析潜力在目标 3 中，我们将开发简化的模型。将分析工具集成到以用户为中心的界面中，该界面将优化基于 ICG 的 DCE-FI 派生数据的使用基于 ICG 的 DCE-FI 的应用具有巨大的变革潜力。通过治疗失败和尽量减少骨切除来治疗创伤后感染并最终彻底改变数百万创伤患者的护理标准。荧光引导手术方面广泛的基础设施和经验以及长期合作达特茅斯学院和 R Adams Cowley 休克创伤外科专业和生物医学工程师之间的合作中心。