Osteoarthritis is a leading cause of disability, and a major public health issue. Progressive loss of articular cartilage due to injury and degeneration are important etiological factors in the development of osteoarthritis. While laboratory studies show a potential to reverse pathological changes in articular cartilage prior to breakdown of the articular surface, a major barrier to clinical translation of these findings is the lack of reliable clinical methods to diagnose and stage subsurface articular cartilage injury and degeneration. This translational clinical study will continue to test the central hypothesis that novel cross-sectional quantitative imaging technologies can be used clinically to improve diagnosis and staging of human articular cartilage injury and degeneration prior to breakdown of the articular surface. During the initial funding period, we completed bench to bedside clinical translational studies of two novel imaging technologies: Optical Coherence Tomography (OCT) and MRI ultrashort echo time (UTE) enhanced T2* mapping in identifying structural changes to injured and degenerating articular cartilage appearing undamaged to visual inspection. The proposed aims build logically on the clinical data and publications achieved during the initial funding period. These published and ongoing longitudinal studies show that we have the potential to validate, through continuation of this R01, 3 new imaging technologies for clinical use to (1) identify subjects with still intact cartilage that is "at risk" for progressive degeneration, and (2) provide in vivo metrics of subsurface injury and degeneration in human cartilage prior to surface breakdown. To achieve this, we propose the following Aims.
Aim 1 will test the hypothesis intra-operative OCT detectable microstructural changes predict progressive cartilage loss as determined by changes to cartilage thickness measured on 3.0T MRI 2 and 5 years after surgery.
Aim 2 will test the hypothesis that UTE-enhanced T2* (UTE-T2*) map values predict cartilage injury and degeneration as assessed by conventional arthroscopy.
Aim 3 will test the hypothesis that changes in quantitative MRI T2 relaxation times six months after surgery predict cartilage loss as determined by morphometric MRI measurements 2 years after surgery. The proposed Aims will be achieved using the same two carefully selected populations of individuals who do not yet have osteoarthritis but are at high risk for progressive cartilage degeneration studied previously: (1) the "pre- osteoarthritic" degenerative meniscus tear (DMT) cohort and (2) the "post-joint injury" anterior cruciate ligament tear (ACLT) cohort. Achieving the aims will provide new quantitative clinical diagnostic tools to support a clinical paradigm shift towards treatment of cartilage injury and degeneration years before what is currently possible. Potential advantages of earlier treatment include the possibility of delaying or preventing the onset of disabling osteoarthritis.

Public Health Relevance

Osteoarthritis is a leading cause of disability and a major public health issue. This study will provide new quantitative clinical diagnostic tools to support a clinical paradigm shift towards treatment of cartilage injury and degeneration years before what is currently possible. Potential advantages of earlier treatment include the possibility of delaying or even preventing the onset of disabling osteoarthritis

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR052784-07
Application #
8293113
Study Section
Special Emphasis Panel (ZRG1-MOSS-S (02))
Program Officer
Lester, Gayle E
Project Start
2005-07-01
Project End
2013-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
7
Fiscal Year
2012
Total Cost
$471,126
Indirect Cost
$127,772
Name
University of Pittsburgh
Department
Orthopedics
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
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
Urish, Kenneth L; Williams, Ashley A; Durkin, John R et al. (2013) Registration of Magnetic Resonance Image Series for Knee Articular Cartilage Analysis: Data from the Osteoarthritis Initiative. Cartilage 4:20-27
Qian, Yongxian; Williams, Ashley A; Chu, Constance R et al. (2012) High-resolution ultrashort echo time (UTE) imaging on human knee with AWSOS sequence at 3.0 T. J Magn Reson Imaging 35:204-10
Williams, A; Qian, Y; Golla, S et al. (2012) UTE-T2? mapping detects sub-clinical meniscus injury after anterior cruciate ligament tear. Osteoarthritis Cartilage 20:486-94
Williams, A; Qian, Y; Chu, C R (2011) UTE-T2ýýý mapping of human articular cartilage in vivo: a repeatability assessment. Osteoarthritis Cartilage 19:84-8
Chu, Constance R; Beynnon, Bruce D; Buckwalter, Joseph A et al. (2011) Closing the gap between bench and bedside research for early arthritis therapies (EARTH): report from the AOSSM/NIH U-13 Post-Joint Injury Osteoarthritis Conference II. Am J Sports Med 39:1569-78
Chu, Constance R; Williams, Ashley; Tolliver, David et al. (2010) Clinical optical coherence tomography of early articular cartilage degeneration in patients with degenerative meniscal tears. Arthritis Rheum 62:1412-20
Bear, David M; Szczodry, Michal; Kramer, Scott et al. (2010) Optical coherence tomography detection of subclinical traumatic cartilage injury. J Orthop Trauma 24:577-82
Bear, David M; Williams, Ashley; Chu, Charleen T et al. (2010) Optical coherence tomography grading correlates with MRI T2 mapping and extracellular matrix content. J Orthop Res 28:546-52
Qian, Yongxian; Williams, Ashley A; Chu, Constance R et al. (2010) Multicomponent T2* mapping of knee cartilage: technical feasibility ex vivo. Magn Reson Med 64:1426-31

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