The joint most often implicated in lower extremity osteoarthritis (OA) is the knee, where major symptoms include pain and stiffness. Skeletal tissues are regulated by their mechanical environment and receptors within bone and soft tissue that respond to mechanical stimulation are believed to play a major role in joint pain. One potential pathway for the onset and progression of OA is due to abnormal joint kinematics, resulting in elevated joint stress and cartilage damage. Treatments that alter mechanical stresses and metabolic activity in bone may be an effective strategy to alleviate pain in these patients. However, clinicians are unable to diagnose or treat these `pathomechanics' as they lack the tools to assess weight-bearing knee function and tissue stress. The overarching goal of this research is to develop novel weight-bearing computed tomography (CT) imaging to support a quantitative measure of knee joint health that measures both morphology and mechanics of the joint. As a first step towards this goal, we will research and optimize a new, very high resolution (210 m isotropic), C-arm CT-based imaging test that will measure cartilage deformation as a function of time with the subject standing in a fully weight-bearing position. We hypothesize that a mechanical model of the deformation-load curve will provide a sensitive and early imaging biomarker of OA status due to differences in cartilage material properties and their response to mechanical loading. We will optimize the acquisition of the deformation-time curve in ex vivo cadaver knees, and conduct a 40-subject preliminary study to demonstrate the potential sensitivity of the new imaging biomarker to distinguish between non-OA and different stages of OA progression. We believe that our new joint health test will enable testing of patient-specific treatment strategies that may slow or reverse the progression of knee OA.

Public Health Relevance

Osteoarthritis (OA) is the leading cause of functional decline and disability in aging populations and affects about 49.3 million adults in the US at an annual cost of $186 billion. The joint that most often is diagnosed is the knee, where major symptoms include pain and stiffness. We are developing a new, non-invasive, quantitative, 3-dimensional image-based test that will evaluate the health of cartilage in the knee joint while a subject is standing in a weight-bearing position.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR065248-02
Application #
9042244
Study Section
Biomedical Imaging Technology Study Section (BMIT)
Program Officer
Lester, Gayle E
Project Start
2015-04-01
Project End
2019-02-28
Budget Start
2016-03-01
Budget End
2017-02-28
Support Year
2
Fiscal Year
2016
Total Cost
$475,715
Indirect Cost
$163,406
Name
Stanford University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94304
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