ASSOCIATION OF SYNOVITIS ACTIVITY MEASURED BY SYNOVIAL TISSUE VOLUME (STV) AND DYNAMIC CONTRAST-ENHANCED (DCE)-MRI IN...

Osteoarthritis (OA) is a complex condition influenced by genetic predisposition, mechanical stress and/or inflammatory processes. Synovitis, which is present in more than half of all OA patients, predicts more severe cartilage damage, faster disease progression and has been associated with pain. The quantitative measurement of synovitis using MR imaging requires the use of contrast enhancement (CE) to distinguish it from effusion in the joint. Quantitative measurements of synovitis based on T1w CE sequences include synovial tissue volume (STV), which represents the overall degree of whole joint synovitis or by dynamic contrast-enhanced (DCE)-MRI, which reflects tissue perfusion. However, DCE-MRI is more complex and requires power-injectors, limiting sites that may participate in a multicentre trial.

Our aim was to compare measurements of STV and Ktrans, a marker of synovitis via a measure of capillary permeability derived from DCE-MRI, in a cohort of patients with inflammatory knee OA from a Phase II study (NCT04886258).

Patients were aged 50 to 80 with at least moderate synovitis at screening by 11-site semi-quantitative scoring of T1w CE 3T MRI of the entire knee. Synovitis activity was assessed by acquiring T1-weighted images covering the entire knee at intervals of a few seconds, before and after administration of a contrast agent. To segment the synovial tissue, active appearance models (AAMs) were fitted to the bones in each image together with a 3D synovial region of interest (ROI) mask that encompassed the joint while excluding adjacent tissues and blood vessels. Ktrans was computed within this ROI and calculated for each voxel where the data fit the Tofts model with sufficient accuracy (R² ≥ 0.6). The median Ktrans value was used for comparison to avoid outliers. The ROI was then used together with the pre-contrast and last of the post-contrast low-resolution DCE-MRI images to compute STV as the volume of voxels in the post contrast ROI-masked image enhanced at a greyscale intensity more than the mean plus 3SD of the pre-contrast foreground intensity determined by Otsu thresholding (Figure 1). Fractional volume of STV was calculated as the enhancing volume divided by the entire ROI volume.

106 image sets at baseline and 90 at 12 weeks were available for DCE-MRI and STV comparison. 87 paired baseline-12week image sets were available for difference comparison. Comparison of all baseline and 12-week median Ktrans and fractional STV results showed strong correlation (r = 0.70 and 0.69), with minimal zero Ktrans offset (0.0016 and 0.0028min-1), see Figure 1. Comparison of baseline-12-week changes showed very strong correlation (r = 0.79) again with minimal zero Ktrans offset (-0.0011 min-1), see Figure 2.

Although it may be expected that physiologic measures of synovial perfusion (Ktrans) and morphological measures of STV may be measuring somewhat different constructs, the strong correlations between STV and Ktrans measures here demonstrate the potential for the simpler static CE method to be used for quantitative synovitis assessment in clinical trials. STV is more usually measured using high resolution pre- and post-contrast MR images rather than the low-resolution DCE images employed here, which may further improve the association between these measures.