Precision Molecular Imaging of Osteoarthritis: 18F-FDG PET/MRI of Degenerative Disease in an In Vivo Canine Model

Objectives The aim of this study was to serially assess the metabolic activity in the canine knee using the combination of two imaging modalities, 18F-FDG PET co-registered with MRI in an in vivo anterior cruciate ligament transection (ACLT) model of osteoarthritis.

Methods Background: Osteoarthritis (OA) is characterized by the degradation and loss of articular cartilage and remodeling of underlying bone. Currently, conventional radiography is the standard method for diagnosis and evaluation of severity of OA. The current gold standard for the assessment of inflammation in animal models of arthritis is histopathological evaluation of joint sections. 18F-FDG as a metabolic tracer can demonstrate the site of synovitis and bone marrow lesions associated with OA. The accumulation of 18F-FDG in cells contributing to synovial inflammation could provide a sensitive and non-invasive tool for visualization and quantification of joint inflammation in vivo. Hybrid technologies such as PET-MRI combine functional imaging with high-resolution anatomical imaging. MRI has become a key imaging tool for OA research thanks to its ability to visualize pathologies that are not detected on x-ray radiographs, including articular cartilage, menisci, ligaments, synovium, capsular structures, fluid collections, and bone marrow lesions. The use of multimodal imaging increases the precision in medicine enabling a tailoring diagnosis and monitoring treatments. Five dogs underwent ACLT in one knee via arthroscopy, the contralateral knee served as control. Prior to, 3, 6 and 12 weeks after ACLT, the canine underwent PET/CT and MRI. A 3 Tesla MRI body system (Achieva MT) with an 8-channel coil was used and FDG TOF PET/CT was performed on a Gemini TF 64 30 minutes after 18F-FDG administration (3 mCi). A custom made foam was developed to mimic the MRI knee coil while performing PET/CT scans. The MRI was manually co-registered with the PET and three dimensional regions of interest (ROIs) were traced and analyzed. Regions of interest were assessed using SUVmax, including lateral and medial femur, lateral and medial tibia, lateral and medial meniscus and posterior cruciate ligament (PCL). Linear mixed effect models were used to study the association between the type of treatment (ACLT and control) and the SUVmax at each ROI and time point, and at each ROI across all the time points to capture the intra- and inter-subject correlation. P values <0.05 were considered statistically significant.

Results PET and MRI co-registration was successfully completed for all imaging sessions. 18F-FDG SUVmax ROIs (lateral and medial femur, lateral and medial tibia, lateral and medial meniscus and PCL) were compared between ACLT and control knees across all time points. Each ROI had a significantly higher SUVmax in the ACLT knees than the control knees. At 3 weeks, all the ROIs had a higher SUVmax than baseline, 6 and 12 weeks. Additionally, noticeable increases in the uptake levels of the control knees occurred over the duration of the study.

Conclusions The higher 18F-FDG SUVmax in the ACLT knees compared with the control knees reflects higher metabolic changes in the injured knees over time. Higher SUVmax at 3 weeks reflects higher metabolic activity due to joint inflammation, indicating post-ACLT acute stage. The metabolic activity reported in the control knees may be due to gait alterations and joint unloading created with the ACLT. FDG uptake of the knee in the in vivo ACLT canine model using PET/CT and MRI co-registration demonstrated to be highly sensitive in the detection of metabolic alterations in different structures comprising the knee joint. PET co-registration with the MR permits more accurate spatial resolution evaluation and region of interest delineation for the soft tissue structures in the knee joint. Multimodal PET/MRI imaging may also be beneficial for monitoring drug delivery and outcomes. FDG uptake has the potential to be a biomarker for diagnosis of early OA.