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

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 在美国，估计每年的成本为350亿美元。（https：//stacks.cdc.gov/view/cdc/11550） 复发感染率高达30%，令人无法接受，导致长期发病，功能丧失， 和/或失去肢体。血管灌注在骨骼健康中起着至关重要的作用， 氧气营养素抗生素和内源性免疫细胞因此，骨感染的管理是 基于积极的彻底清创，努力通过视觉和视觉来清除所有灌注不良的骨， 触觉线索，如颜色，肿胀和软组织剥离的程度。然而，客观上， 可测量或可量化的方法来评估骨灌注和去除失活的成功 几乎完全取决于外科医生的经验。因此，本提案的总体目标是发展 并评估基于吲哚菁绿色（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。这项提议的科学前提是 是由我们先前在猪模型中的临床前工作和我们的初步临床研究的数据支持的 应用基于ICG的DCE-FI评估骨科手术患者的骨灌注。在这些 研究中，我们建立了DCE-FI可以定量评估骨灌注在一个可测量的，可重复的， 和可预测的方式，我们开发了分析模型区分骨内膜和骨膜 对血液供应总量的贡献。然后，该模型能够有效地区分健康与受损 在临床前猪研究中，具有线性决策边界的骨，准确度为89%。为了达到我们的整体 目标，将追求三个目标。在目标1中，我们将评估清创术后骨 使用基于ICG的DCE-FI测量的灌注和复发性感染/治疗失败。另外我们 将完善分析模型，评估骨内膜与骨膜血液的相对贡献 用品.在目标2中，我们将探讨动态对比增强MRI（DCE-MRI）与 DCE-FI，以提高DCE-FI的三维分析潜力。在目标3中，我们将开发精简的 将分析工具整合到以用户为中心的界面中，优化基于ICG的DCE-FI衍生数据的使用， 正常的手术流程基于ICG的DCE-FI应用具有巨大的革命潜力 通过最小化治疗失败和最小化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。该项目利用了 广泛的基础设施和荧光引导手术的经验以及长期的合作 达特茅斯和R亚当斯考利休克创伤的外科专科和生物医学工程师之间 中心

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.