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

• 批准号: 10375430
• 负责人: Ida L Gitajn
• 金额: $ 45.06万
• 依托单位: DARTMOUTH-HITCHCOCK CLINIC
• 依托单位国家: 美国
• 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/10375430
• 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; 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; translational barrier; trauma centers; validation studies

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。 据估计，在美国每年的成本为350亿美元。(https://stacks.cdc.gov/view/cdc/11550)) 30%的复发率高得令人无法接受，导致长期发病率、功能丧失、 和/或失去肢体。血管灌流在骨骼健康中发挥着关键作用，因为它提供了必要的 氧气、营养素、抗生素和内源性免疫细胞。因此，对骨骼感染的管理是 基于积极的，彻底的清创，努力通过视觉和 触觉线索，如颜色，肿胀和软组织剥离的程度。然而，客观上没有 可测量或可量化的方法评估骨灌注和清除失活的成功 骨科手术几乎完全基于外科医生的经验。因此，这项提案的总体目标是发展 并评估了一种基于吲哚青绿(Icg)的动态对比增强荧光成像(dce-fi)。 目的：客观评价骨灌注率，指导外科清创手术。这一提议的科学前提是 是基于我们先前在猪模型中的临床前工作和我们的先导性临床研究的数据 应用ICG-DCE-FI评估骨科手术患者的骨灌注量。在这些 研究表明，DCE-FI可以在可测量、可重复性的情况下定量评估骨的血流灌注。 和可预测的方式，我们开发了区分骨膜和骨膜的分析模型 对总供血量的贡献。然后，这个模型能够有效地区分健康和受损 在临床前猪研究中，具有线性决策边界的骨骼的准确率为89%。为了实现我们的全面 目标，将追求三个目标。在目标1中，我们将评估清创术后骨量的关系。 使用基于ICG的DCE-FI测量的灌注量，以及反复感染/治疗失败。此外，我们 将改进分析模型，评估骨内膜血与骨膜血的相对贡献 补给。在目标2中，我们将探讨动态增强MRI(DCE-MRI)与 DCE-FI提高了DCE-FI的三维解析潜力。在目标3中，我们将开发简化的 将分析工具整合到以用户为中心的界面，从而优化基于ICG的DCE-FI派生数据在 正常的手术流程。基于ICG的DCE-FI的应用具有巨大的革命性潜力 最大限度减少治疗失败和最小限度截骨治疗创伤后感染 并最终彻底改变数百万创伤患者的护理标准。该项目利用了 在荧光引导手术方面的广泛基础设施和经验以及长期的合作 在达特茅斯和R亚当斯·考利休克创伤医院的外科副专科和生物医学工程师之间 中心。