Osteoarthritis is expected to reach epidemic proportions worldwide. One of the keys to prevention is to diagnose cartliage degenerative processes early enough for disease modifying treatment. Optical coherence tomography (OCT) is a novel imaging technology that can image human articular cartilage at microscopic resolutions without damaging or removing the tissue. Preliminary data shows that loss of OCT detectable cartilage form birefringence was predictive of potentially reversible early metabolic changes that have been implicated in the pathogenesis of osteoarthritis. The PI has also successfully used a clinical fiberoptic OCT system to assess the microstructure and form birefringence of human articular cartilage in vivo. The central hypothesis of this proposal is that OCT can be used clinically to improve arthroscopic diagnosis of early articular cartilage degeneration. Three related specific aims are proposed: (1) To test the hypothesis that OCT enhances the sensitivity and specificity of conventional arthroscopic diagnosis of early cartilage degeneration in humans. (2) To test the hypothesis that OCT detectable microstructural damage is prevalent in grossly normal appearing weight bearing cartilage of human subjects undergoing arthroscopy to treat degenerative meniscal tears. (3) To test the hypothesis that OCT can be used clinically to predict the development of progressive cartilage degeneration as determined by serial MRI after acute anterior cruciate ligament (ACL) injury. Accomplishing the proposed aims will introduce valuable new data on the early changes in human osteoarthritis as discernible by novel imaging technology (OCT), 3.0 T MRI, and conventional arthroscopy. Preliminary data shows that OCT can identify human cartilage degeneration prior to the development of irreversible changes. As such, the proposal is highly innovative and significant in that achieving the aims can provide the diagnostic capability to potentially support a clinical paradigm shift towards treatment of cartilage degenerative processes years before what is currently possible. Potential advantages of earlier treatment include the possibility of delaying or even preventing the onset of disabling osteoarthritis.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Research Project (R01)
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Skeletal Biology Structure and Regeneration Study Section (SBSR)
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Lester, Gayle E
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University of Pittsburgh
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Erhart-Hledik, Jennifer C; Chu, Constance R; Asay, Jessica L et al. (2017) Gait mechanics 2 years after anterior cruciate ligament reconstruction are associated with longer-term changes in patient-reported outcomes. J Orthop Res 35:634-640
Erhart-Hledik, Jennifer C; Asay, Jessica L; Clancy, Caitlin et al. (2017) Effects of active feedback gait retraining to produce a medial weight transfer at the foot in subjects with symptomatic medial knee osteoarthritis. J Orthop Res 35:2251-2259
Williams, Ashley; Winalski, Carl S; Chu, Constance R (2017) Early articular cartilage MRI T2 changes after anterior cruciate ligament reconstruction correlate with later changes in T2 and cartilage thickness. J Orthop Res 35:699-706
Chu, Constance R (2016) Defining Pre-Osteoarthritis Is Key to Prevention. Cartilage 7:204
Chu, Constance R; Andriacchi, Thomas P (2015) Dance between biology, mechanics, and structure: A systems-based approach to developing osteoarthritis prevention strategies. J Orthop Res 33:939-47
Titchenal, Matthew R; Asay, Jessica L; Favre, Julien et al. (2015) Effects of high heel wear and increased weight on the knee during walking. J Orthop Res 33:405-11
Chu, Constance R (2015) The Challenge and the Promise of Bone Marrow Cells for Human Cartilage Repair. Cartilage 6:36S-45S
Chu, Constance R; Millis, Michael B; Olson, Steven A (2014) Osteoarthritis: From Palliation to Prevention: AOA Critical Issues. J Bone Joint Surg Am 96:e130
Chu, Constance R; Williams, Ashley A; West, Robin V et al. (2014) Quantitative Magnetic Resonance Imaging UTE-T2* Mapping of Cartilage and Meniscus Healing After Anatomic Anterior Cruciate Ligament Reconstruction. Am J Sports Med 42:1847-56
Friel, Nicole A; Chu, Constance R (2013) The role of ACL injury in the development of posttraumatic knee osteoarthritis. Clin Sports Med 32:1-12

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