Author ORCID Identifier

https://orcid.org/my-orcid?orcid=0009-0000-3589-6917

Date of Award

6-2025

Document Type

Thesis (Ph.D.)

Department or Program

Engineering Sciences

First Advisor

Shudong Jiang

Second Advisor

Jonathan T. Elliott

Third Advisor

Ida Leah Gitajn

Abstract

Infection following trauma is one of the most prevalent and challenging complications faced by orthopedic surgeons. Inadequate tissue perfusion plays a critical role in this complication, as poorly perfused bone can be a nidus for bacterial biofilm formation and promote resistance to antibiotic treatments. Consequently, the management of open fractures and fracture-related infections relies on aggressive and thorough debridement to remove all poorly perfused bone. This thesis focuses on developing an indocyanine green (ICG)-based dynamic contrast-enhanced fluorescence imaging (DCE-FI) to objectively measure bone perfusion during open orthopedic surgeries and guide surgical debridement of devitalized bone.

Novel methodologies were developed to address key technical challenges, including an automated motion correction algorithm based on mutual information to eliminate motion artifacts, and patient-specific arterial input functions (AIF) to normalize variations in manual ICG injection. Quantitative perfusion assessment was achieved through kinetic curve analysis and perfusion modeling using the adiabatic approximation to the tissue homogeneity model, yielding critical parameters such as maximum intensity (Imax), blood flow (BF) and volume transfer constant (Ktrans).

To date, DCE-FI from 256 patients were collected, including 15 lower extremity amputations, 106 infections, 120 open fractures, and 15 compartment syndromes. In three infection patients who underwent both DCE-FI and Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI), a strong correlation was found between Imax from DCE-FI and Ktrans from DCE-MRI, validating the feasibility of perfusion assessment by DCE-FI. Data analysis from 256 patients with varying degrees of bone damage revealed the following findings: 1) DCE-FI revealed trauma-induced perfusion changes that correlated with the severity of bone injury; 2) muscle perfusion quantified by DCE-FI was strongly associated with muscle necrosis; and 3) in patients with infections or open fracture, areas of low perfusion (identified by reduced maximum fluorescence intensity and blood flow) were strong predictors of early infection within 90 days post-surgery. Additionally, we developed a portable compact fluorescence imaging system (cBPI) suitable for austere environments and forward operating units near battlefields. These findings demonstrate that DCE-FI has significant prognostic value in assessing bone damage and predicting surgical outcomes. It holds strong potential as an intraoperative tool for guiding real-time debridement decisions.

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