Author ORCID Identifier

https://orcid.org/0000-0002-8082-0863

Date of Award

Spring 6-11-2023

Document Type

Thesis (Ph.D.)

Department or Program

Engineering Sciences

First Advisor

Jonathan Elliott

Abstract

Orthopaedic surgery is one of the most common surgical categories. In particular, lower extremity injuries sustained from trauma can be complex and life-threatening injuries that are addressed through orthopaedic trauma surgery. Timely evaluation and surgical debridement following lower extremity injury is essential, because devitalized bones and tissues will result in high surgical site infection rates. However, the current clinical judgment of what constitutes “devitalized tissue” is subjective and dependent on surgeon experience, so it is necessary to develop imaging techniques for guiding surgical debridement, in order to control infection rates and to improve patient outcome.

In this thesis work, computational models of fluorescence-guided debridement in lower extremity injury surgery will be developed, by quantifying bone perfusion intraoperatively using Dynamic contrast-enhanced fluorescence imaging (DCE-FI) system. Perfusion is an important factor of tissue viability, and therefore quantifying perfusion is essential for fluorescence-guided debridement. In Chapters 3-7 of this thesis, we explore the performance of DCE-FI in quantifying perfusion from benchtop to translation: We proposed a modified fluorescent microsphere quantification technique using cryomacrotome in animal model. This technique can measure bone perfusion in periosteal and endosteal separately, and therefore to validate bone perfusion measurements obtained by DCE-FI; We developed pre-clinical rodent contaminated fracture model to correlate DCE-FI with infection risk, and compare with multi-modality scanning; Furthermore in clinical studies, we investigated first-pass kinetic parameters of DCE-FI and arterial input functions for characterization of perfusion changes during lower limb amputation surgery; We conducted the first in-human use of dynamic contrast-enhanced texture analysis for orthopaedic trauma classification, suggesting that spatiotemporal features from DCE-FI can classify bone perfusion intraoperatively with high accuracy and sensitivity; We established clinical machine learning infection risk predictive model on open fracture surgery, where pixel-scaled prediction on infection risk will be accomplished.

In conclusion, pharmacokinetic and spatiotemporal patterns of dynamic contrast-enhanced imaging show great potential for quantifying bone perfusion and prognosing bone infection. The thesis work will decrease surgical site infection risk and improve successful rates of lower extremity injury surgery.

Original Citation

Han, X., Demidov, V., Wirth, D., Byrd, B., Davis, S., Gitajn, L., & Elliott, J. (2022, March). Validation of dynamic contrast-enhanced bone blood flow imaging technique with fluorescent microspheres. In Molecular-Guided Surgery: Molecules, Devices, and Applications VIII (Vol. 11943, pp. 118-123). SPIE.

Han, X., Demidov, V., Wirth, D., Byrd, B., Davis, S. C., Gitajn, I. L., & Elliott, J. T. (2022, May). Initial experience of perfusion assessment in a rabbit model of orthopaedic trauma surgery using fluorescent microspheres and hyperspectral imaging cryomacrotome. In Clinical Biophotonics II (Vol. 12146, pp. 44-50). SPIE.

Han, X., Demidov, V., Vaze, V. S., Jiang, S., Gitajn, I. L., & Elliott, J. T. (2022). Spatial and temporal patterns in dynamic-contrast enhanced intraoperative fluorescence imaging enable classification of bone perfusion in patients undergoing leg amputation. Biomedical Optics Express, 13(6), 3171-3186.

Han, X., Bateman, L. M., Werth, P. M., Jiang, S., Gitajn, I. L., & Elliott, J. T. (2023, March). Risk prediction on orthopaedic trauma patients for fracture-associated infection using dynamic contrast enhanced-fluorescence imaging. In Molecular-Guided Surgery: Molecules, Devices, and Applications IX (Vol. 12361, pp. 55-62). SPIE.

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