Multinuclear MRI to Assess Joint Homeostasis after Knee Injury

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Project Summary Post-traumatic osteoarthritis (PTOA) is a common complication that follows an episode anterior cruciate ligament (ACL) rupture. In the United States, there are over 100,000 ACL ruptures per year, 70% of which occur in physically active subjects under 40 years of age. The prevalence of PTOA is estimated to be in the 50-70% range 10 to 20 years after injury, whether surgical intervention was performed or not. The failure of surgery to prevent PTOA leads to the hypothesis that the acute biological and biomechanical changes in the joint directly following injury trigger a cascade of events leading to PTOA. However, little is known about how these early biological and biomechanical changes are linked to the subsequent joint damage. To assess the loss of joint homeostasis after injury, we propose to optimize and use a novel multinuclear magnetic resonance imaging (MRI) method recently developed by our team, which is based on the simultaneous acquisition of proton (1H) and sodium (23Na) MR fingerprinting (MRF). Simultaneous 1H/23Na MRF will allow us to characterize knee cartilage integrity using both proton (structural information from relaxation times, water content) and sodium (proteoglycan content from sodium concentration and relaxation times) quantitative data. In this study, a complete panel of soluble synovial fluid (SF) biological markers of inflammation and proteolysis, of biomechanical markers (weight-bearing activities, extensor strength), and of quantitative imaging markers such as 1H/23Na MRF, diffusion tensor imaging (DTI), contrast-enhanced (CE) MRI, and T1rho MRI, will be acquired longitudinally on patients with ACL injury. The goal of this study is therefore to develop a predictive model of progression to PTOA using a combination of all these imaging, biological, and biomechanical markers acquired just after ACL injury, and over time after joint repair. This prognostic combination of biomarkers will help identify therapeutic targets and monitor the efficacy of intervention in the development of preventive treatments of PTOA. Two patient cohorts will be recruited: a short-term cohort will be tested at baseline (post-injury), 1-2-year and 3-5-year follow-ups, and a long-term cohort, which is already being being studied in our institution with clinical MRI and SF biomarkers, will be tested at 3-5-year and 6-8-year post-injury follow-ups. In aim 1, we will optimize simultaneous 1H/23Na MRF sequence for its application to knee cartilage imaging. In Aim 2, we will identify imaging, biomechanical and imaging markers, measured at baseline and 1.5 years to predict 3-year progression. In Aim 3, we will identify a set of few biomarkers for prediction of both short-term (3-5 years) and long-term (6-8 years) changes in joint homeostasis.