Determining early markers of disease using Raman spectroscopy in a rat combat-trauma model of heterotopic ossification

Katherine E. Cilwa*, Ammar T. Qureshi, Jonathan A. Forsberg, Thomas A. Davis, Nicole J. Crane

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review

1 Scopus citations


Traumatic heterotopic ossification (HO) is the pathological formation of bone in soft tissue and is a debilitating sequela following acute trauma involving blast-related extremity musculoskeletal injuries, severe burns, spinal cord injury, and traumatic brain injury. Over 60% of combat related injuries and severe burns develop HO; often resulting in reduced mobility, chronic pain, ulceration, tissue entrapment, and reduced ambulation. Detection and prognosis is limited by current clinical imaging modalities (computed tomography, radiography, and ultrasound). This study identifies Raman spectral signatures corresponding to histological changes in a combat-trauma induced rat HO model at early time points prior to radiographic evidence of HO. HO was induced in Sprague-Dawley rats via blast over pressure injury, mid-femoral fracture, soft tissue crush injury, and limb amputation through the zone of injury. Rats were euthanized, and amputated limbs were formalin fixed and embedded in paraffin; 10 μm sections were placed on gold slides, and paraffin was chemically removed. Tissues from sham-treated animals served as controls. Tissue maps consisting of Raman spectra were generated using a Raman microprobe system with an 80-90 μm spot size and 785 nm excitation in regions exhibiting histological evidence of early HO development according to adjacent HE sections. Factors were extracted from mapping data using Band-Target Entropy Minimization algorithms. Areas of early HO were highlighted by a Raman factor indicative of the presence of collagen. Identification of collagen as an early marker of HO prior to radiographic detection in a clinically relevant animal model serves to inform future clinical work.

Original languageEnglish
Title of host publicationPhotonic Therapeutics and Diagnostics XII
EditorsAndreas Mandelis, Bernard Choi, Brian J. F. Wong, Justus F. Ilgner, Laura Marcu, Melissa C. Skala, Nikiforos Kollias, Haishan Zeng, Hyun Wook Kang, Guillermo J. Tearney, Kenton W. Gregory, Paul J. Campagnola
ISBN (Electronic)9781628419245
StatePublished - 2016
Externally publishedYes
EventPhotonic Therapeutics and Diagnostics XII - San Francisco, United States
Duration: 13 Feb 201614 Feb 2016

Publication series

NameProgress in Biomedical Optics and Imaging - Proceedings of SPIE
ISSN (Print)1605-7422


ConferencePhotonic Therapeutics and Diagnostics XII
Country/TerritoryUnited States
CitySan Francisco


  • Heterotopic ossification
  • Raman spectroscopy
  • chondrogenesis
  • collagen
  • extremity amputation
  • mineralization
  • muscle
  • war wounds


Dive into the research topics of 'Determining early markers of disease using Raman spectroscopy in a rat combat-trauma model of heterotopic ossification'. Together they form a unique fingerprint.

Cite this