Abstract
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Objectives: Abnormal bone physiology is a potential mechanism for the progression of knee osteoarthritis (OA), a disease marked by degradation and loss of soft tissues like cartilage and the development of bone marrow lesions (BML) and osteophytes. Molecular information derived from kinetic modeling of Na[18F]F- ([18F]fluoride) uptake into subchondral bone enables quantitative analysis of bone metabolism that may be altered in the presence of OA features1,2,3. In this work, we evaluate the relationship between observed structural changes in bone and cartilage observed on MRI and quantitative subchondral bone metabolic parameters using hybrid PET/MRI.
Methods: Both knees of twelve subjects with knee osteoarthritis (61.1 ± 8.8 years; BMI 27.1 ± 5.2; 10 female) were scanned using a 3T whole-body hybrid PET/MRI system under an approved IRB protocol. Upon injection of a 2.5 mCi dose of [18F]fluoride, dynamic PET and bilateral MRI data were obtained over 50 minutes. Five subjects were scanned twice, with at least 5 days between visits, to assess repeatability of the technique. MRI Osteoarthritis Knee Score (MOAKS)4 assessment of each knee was performed by a trained musculoskeletal radiologist using sagittal proton-density-weighted IDEAL and coronal T2-weighted fat-saturated images. Dynamic PET data were fit to a 2-tissue kinetic model to calculate the rates of bone perfusion (K1), tissue clearance (k2), and mineralization (k3), as well as tracer extraction fraction (k3/[k2+k3]) and total bone uptake rate (Ki = K1*extraction fraction). Kinetic fitting was performed for regions of interest representing the subchondral bone of the patella; medial and lateral tibia; and anterior, central, and posterior regions of the medial and lateral femur (Figure 2A).
Results: Repeatability analysis showed minimal mean bias in SUVmax and kinetic parameters between visits (Figure 1). In the 24 knees studied, there were two knees without any MOAKS findings and a total of 81 bone regions with no MOAKS findings (“normal-appearing bone”). Within regions where there were one or more MOAKS findings, there were 54 regions with cartilage loss, 35 regions with BMLs, and 76 regions with osteophytes. Fifty-one of these regions had a single feature, while 26 had two features and 18 had all three features. There were no regions with size 3 bone marrow lesions. Representative PET/MRI fusion images are shown in Figure 2. Average and maximum SUV, bone perfusion, tissue clearance, extraction fraction, and total bone uptake rates of the PET tracer were significantly increased in regions with larger osteophytes [MOAKS 2/3] (p < 0.01, Figure 3 A-C); these and mineralization rates were significantly altered in BMLs (p < 0.01, Figure 3 D-F). Elevations in SUV and total bone uptake rates were driven by increased bone perfusion rates compared to other kinetic parameters. Additionally, subchondral bone uptake was significantly elevated in regions with adjacent cartilage lesions (Figure 3 G-I) compared to areas of normal-appearing bone and cartilage.
Conclusions: Kinetic parameters of the delivery and uptake of [18F]fluoride in bone regions with osteophytes, BML, and adjacent cartilage lesions were significantly different than in regions of normal bone. Kinetic parameters of [18F]fluoride uptake suggest that observed elevated tracer uptake in regions of subchondral bone with osteophytes and BMLs is driven by large increases in bone perfusion rates and smaller changes in bone extraction fraction rates. Additionally, cartilage lesion size was associated with altered metabolic parameters in adjacent subchondral bone, suggesting strong spatial relationships between subchondral bone metabolic abnormalities and changes in overlying cartilage. Kinetic parameters of [18F]fluoride uptake in subchondral bone are objective measures of bone metabolism with potential to provide functional information that complements assessments of structural abnormalities observed on MRI.
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