Purpose: Radiographic joint space width (rJSW) measurement has historically been the preferred measure of disease progression in OA structure modification trials. Magnetic resonance imaging (MRI) can visualise change in multiple tissues, and offers increased sensitivity to change, allowing for shorter trials with fewer patients. In order to compare changes measured using MRI biomarkers with previous studies using rJSW, it is important to understand (1) how well the new biomarkers agree with radiographic measures, and (2) the contribution made by different knee tissues to changes in rJSW. This is challenging, as MR images are normally obtained with the patient in a supine position, while radiographs are taken in a standing position, with the knee slightly flexed. We aimed to assess agreement between accurate 3D MRI measurements of cartilage thickness in the medial tibiofemoral joint and quantified rJSW, in a large dataset. Methods: Analyses were performed on all knees from the Osteoarthritis Initiative at baseline, which had a KL grade and a recorded quantitative measure of joint space width (5726 knees). Cartilage in the central medial regions of the femur and tibia were automatically segmented using a method based on active appearance models, a form of statistical shape model. This method produces highly accurate segmentations (mean accuracy = 0.05 mm, 95th percentile = 0.45, meaning that all errors are less than the average edge length of one voxel). Average thickness of the central medial femur and tibia regions were added to provide a measure of total cartilage thickness. Radiographic JSW measures were provided by the OAI, and were generated using the algorithm-based method of Duryea; for this comparison, we selected a position approximately in the middle of the tibial plateau, also found to be the most responsive in clinical studies (JSW 225). Agreement between the methods was assessed using Bland Altman plots. Results: For KL grades 0, 1 and 2, the systematic bias between rJSW and cartilage thickness was around 1mm, the 95% confidence limits were 1, 1.2 and 1.26 mm respectively (Figure 1). Figure 1 also shows typical examples of MR images for each KL grade within the region in which MR and radiographic measures are taken. For KL grades 0–2, the agreement between measures is close to theoretical agreement limits, which we estimate to be 0.74 mm based on the measurement errors for the methods. In KL3 knees, the bias reduces to 0.4 mm, and the 95% CL increases to 1.69. In KL4 knees, the bias is almost eliminated (0.14 mm). Conclusions: rJSW is composed of various pathologies that are not visualised in radiographs, which consolidate all changes into a single projection. These include cartilage loss, meniscal extrusion and synovial fluid. In healthy knees, and in the early stages of the disease (KL 2), agreement between cartilage thickness and rJSW is excellent – as close as realistically possible in measures of biological systems. The systematic bias of 1mm in KL grade 0–2 knees is most likely contributed by the posterior portion of the medial meniscus which is located within the field of measurement. The decrease in bias at KL3 is probably caused by the increasing damage seen in the menisci, which are less able to keep the bones separate when the patient is standing. At KL4, the meniscus is probably incapable of keeping the bones separate when loaded. The high value for the 95% confidence limits at KL4 are likely due to multiple factors within the knee, including meniscal damage and changes in bone shape, together with the inability of the rJSW method to discriminate the bone edges, once they are very close to each other. Additionally, it can be difficult to position the flexed knee in the radiograph both accurately and reproducibly when there is no clear joint space width, and bone shapes within the joint are altered. There may in fact be 2 groups within the KL4 Bland Altman plot - one group towards the right probably still maintains some joint space width, and perhaps a more competent meniscus, and retains the bias of KL0 to KL3 knees.
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