FUNCTIONAL PET/MRI OF KNEE SYNOVIAL MACROPHAGE ACTIVITY BEFORE AND AFTER TOTAL KNEE ARTHROPLASTY

Total knee arthroplasty (TKA) is a surgery with high success rates and good patient outcomes. However, 6.9% of knee replacement surgeries are revisions of old implants due to ongoing pain, stiffness, and loosening. Revision TKA is more expensive and has worse patient outcomes. Recent studies have begun to explore the role of the inflammatory response in poor TKA outcomes. Inflammation is an important predictor of pain in osteoarthritis (OA) and synovial inflammation may play a role in knee stiffness after TKA. Macrophages are the dominant immune cells of the synovium and regulate knee inflammation, and when activated, they upregulate mitochondrial translocator protein (TSPO) expression. Current standard of care features Magnetic Resonance Imaging (MRI) to assess structural changes in the joint. Positron Emission Tomography (PET) can be used to image important biological processes at the cellular level. [18F]FEPPA is a PET tracer that targets TSPO with high specificity. The goal of this work was to validate the use of [18F]FEPPA PET/MRI in the assessment of macrophage activation in knee synovial tissue. This method may allow non-invasive imaging of important inflammatory processes and understand the role of activated macrophages in ongoing pain, stiffness, and loosening after TKA . To validate the use of [18F]FEPPA in imaging activated macrophages in vivo, synovial tissue was gathered from 12 participants with end stage OA who underwent primary TKA. Knee synovial tissue was sectioned and embedded on slides. Tissue sections were incubated in [18F]FEPPA and imaged by autoradiography for 6 hours. Adjacent tissue sections were incubated with DAPI, CD68 antibody, and TSPO antibody for immunofluorescent analysis of the actual macrophage activation. 6 of the full cohort were imaged in a 3T hybrid PET/MRI after injection with [18F]FEPPA and a 45-minute uptake period. MR of both knee joints was performed with sequences including 3D Dual Echo Steady State (DESS), Bilateral T1 weighted and Fast Spin Echo (FSE) with metal artifact reduction if contralateral TKA was present. Standardized Uptake Values (SUV) were calculated from the measured PET signal, injected dose, and patient mass. [18F]FEPPA tracer uptake calculated from autoradiography correlated to the true macrophage activation measured through TSPO+ immunofluorescence with r = 0.85 and p = 0.0029. SUV calculated from PET/MRI was correlated to true macrophage activation found through immunofluorescence with r = 0.90 and p = 0.083. Attenuation correction maps corrected for metal artefacts enabled visualization and measurement of tracer uptake surrounding the femoral and tibial components. Understanding the role of knee joint inflammation may be important in managing pain and stiffness after TKA. The underlying cause of poor TKA outcomes are often unclear.[18F]FEPPA PET/MRI uptake in knee synovial tissue was validated to correlate to the true macrophage activity. This tool may be able to diagnosis a cellular response as the cause of pain or dissatisfaction after TKA. Future work using [18F]FEPPA PET/MRI could assess different reaction types to metal or plastic implant debris, joint stiffness and fibrosis, and periprosthetic infection.