Project Grant R01AR083018

NOVEL NON-CONTRAST MRI TO ASSESS SYNOVITIS IN OSTEOARTHRITIS - PROJECT SUMMARY OSTEOARTHRITIS (OA) IS A LEADING CAUSE OF DISABILITY THAT REDUCES PRODUCTIVITY AND QUALITY OF LIFE AT TREMENDOUS ECONOMIC COST. DESPITES ITS PREVALENCE AND COST, THERE IS NO THERAPY THAT PREVENTS OR CURES OA. SYNOVIAL INFLAMMATION (SYNOVITIS), HAS BEEN LINKED WITH PAIN, DISEASE SEVERITY AND PROGRESSION OF KNEE OA AND IS INCREASINGLY RECOGNIZED FOR ITS ROLE IN THE ONSET AND PATHOGENESIS OF OA. HOWEVER, STUDIES OF SYNOVITIS IN OA HAVE BEEN LIMITED BY A LACK OF NON-INVASIVE AND NON-CONTRAST METHODS TO EVALUATE ITS ROLE IN WHOLE-JOINT DISEASE, PARTICULARLY IN EARLY PROGRESSION AND IN RESPONSE TO TREATMENT. MRI HAS BECOME THE HALLMARK FOR IMAGING OF OA YET CONVENTIONAL MRI STRUGGLES TO DIFFERENTIATE SYNOVIAL HYPERTROPHY FROM ADJACENT FLUID, THUS MAKING IT DIFFICULT TO IDENTIFY AND CHARACTERIZE SYNOVITIS. CONTRAST-ENHANCED (CE) MRI, FOLLOWING INTRAVENOUS INJECTION OF A GADOLINIUM- BASED CONTRAST-AGENT, PROVIDES CONTRAST TO THE HIGHLY VASCULARIZED SYNOVIUM AND IS THE CURRENT REFERENCE STANDARD FOR IMAGING SYNOVITIS15. HOWEVER, ADDED TIME, COST, AND CONTRAINDICATIONS IN PATIENTS WITH RENAL DYSFUNCTION, HAVE LIMITED USE OF CE-MRI IN OA. THERE REMAINS A CRITICAL NEED FOR NEW, VALIDATED, AND TRANSLATABLE IMAGING TOOLS TO BETTER EVALUATE THE ROLE OF SYNOVITIS IN OA PATHOGENESIS AND RESPONSE TO TREATMENT. MRI HAS SHOWN PROMISE TO USE DIFFERENCES IN RELAXATION AND DIFFUSION PROPERTIES BETWEEN SYNOVIUM AND JOINT FLUID TO NOT ONLY PROVIDE CONTRAST TO SYNOVIUM BUT TO ALSO EVALUATE INFLAMMATORY ACTIVITY WITHOUT CONTRAST INJECTION. HOWEVER, TECHNICAL CHALLENGES REMAIN FOR DETECTION OF LOW-GRADE HYPERTROPHY, AS WELL AS ISOLATING SYNOVIUM AND REDUCING DISTORTIONS IN DIFFUSION MRI. FURTHER, VALIDATION STUDIES ARE NECESSARY TO UNDERSTAND THESE NC MRI MARKERS AND EVALUATE THEIR UTILITY AS A TARGET TO PREDICT AND MONITOR TREATMENT RESPONSE AND OA PROGRESSION THIS PROJECT AIMS TO DEVELOP AND OPTIMIZE NON-CONTRAST MRI METHODS TO ASSESS SYNOVITIS IN KNEE OA, TO VALIDATE THESE METHODS AGAINST HISTOLOGY, AND TO EVALUATE THEIR ABILITY TO PREDICT WHOLE JOINT DISEASE PROGRESSION AND AS A TARGET AND MONITOR OF TREATMENT RESPONSE. OUR SPECIFIC AIMS ARE (1A) TO DEVELOP NON-CONTRAST MRI METHODS FOR ASSESSING SYNOVIAL HYPERTROPHY AND INFLAMMATION ACROSS BOTH KNEES; (1B) TO VALIDATE THE SENSITIVITY AND SPECIFICITY OF THESE APPROACHES AGAINST GOLD STANDARD HISTOLOGIC MEASURES OF HYPERTROPHY AND INFLAMMATORY MARKERS AND REFERENCE CONTRAST-BASED IMAGING METRICS; AND [2] TO EVALUATE THE POTENTIAL OF NC-MRI SYNOVITIS MEASURES TO PREDICT AND CHARACTERIZE TREATMENT RESPONSE TO ANTI-INFLAMMATORY OA TREATMENT (2A) AS WELL AS TO PREDICT OA PROGRESSION AND EVALUATE WHOLE-JOINT SPATIAL TISSUE RELATIONSHIPS (2B). THE SIGNIFICANCE OF THIS WORK IS NEW NON-INVASIVE AND NON-CONTRAST TOOLS THAT GREATLY EXPAND THE ABILITY TO EVALUATE SYNOVITIS IN ALL ASPECTS OF OA: EARLY DIAGNOSIS, PATHOGENESIS AND PROGRESSION, AS WELL AS ENDOTYPE EVALUATION AND TREATMENT MONITORING. THE INNOVATION OF THIS PROJECT IS THE DEVELOPMENT OF NOVEL NC METHODS TO ASSESS SYNOVITIS IN OA AND ITS ROLE IN OA PATHOGENESIS AND RESPONSE TO TREATMENT. OUR INVESTIGATIVE TEAM INCLUDES EXPERTS IN NOVEL IMAGING TECHNIQUES, CLINICAL AND RESEARCH STUDIES OF OA, AND MUSCULOSKELETAL CLINICIANS.