Inflammation is increasingly recognized as critical in the pathogenesis of KOA, and effusion-synovitis (ES) on knee MRI has been identified as an important biomarker of OA. Semi-automated software methods offer objective measurements of ES volume on MRI, but efficiency is crucial, especially for studies involving large numbers of scans. We have developed a single-slice quantitative measurement of ES using the single axial slice with the largest area of ES, and compared this to previously validated multi-slice measurements. We evaluated the reliability of a new single-slice quantitative measurement of ES in knees with radiographic OA, and correlated this measurement of ES with a validated multi-slice quantitative measurement of ES, and with a validated semi-quantitative scoring of ES in order to demonstrate that the more efficient single-slice ES method is a valid substitute for the multi-slice approach. OAI participants with radiographic OA (i.e., Kellgren-Lawrence [KL] 2,3) in at least one knee at baseline with prior semi-quantitative assessment of ES by a MSK radiologist were randomly selected (n=50 knees; 1 knee per participant). Four non-expert readers were trained to use custom-designed semi-automated software to measure ES volume on 3T MRI, under the direction of a MSK radiologist, and then read scans from the KL 2,3 sample blinded to prior assessments (twice for 3 readers and once for 1 reader). Intra- and inter-reader reliability was evaluated based on intraclass correlation coefficients (ICC) from a linear mixed model with random effects for knee, reader, and interaction between knee and reader. We assessed agreement with the mean absolute difference (MAD). In a subset of the FNIH study (n=301), one reader measured single-slice ES volume, blinded to prior multi-slice quantitative measurement of ES. We estimated the Spearman correlation coefficient between single-slice and multi-slice volume of ES in the FNIH subset. Validity was evaluated based on Spearman correlation between single-slice ES volume and semi-quantitative ES MRI Osteoarthritis Knee Score (MOAKS) in the KL 2,3 sample and the FNIH subset. 95% confidence intervals (CI) were generated from bias-corrected and acceleration-adjusted bootstrap. In the sample of KL 2,3 knees, the mean single-slice ES volume was 312.8 mm 3 with standard deviation 218.4 mm 3 . The intra-reader ICC was 0.96 (95%CI: 0.93, 0.97), and inter-reader ICC was 0.90 (95%CI: 0.87, 0.95); the intra-reader MAD was 36 mm 3 (95%CI: 28, 44), and inter-reader MAD was 61 mm 3 (95%CI: 48, 75). The estimated correlation between single-slice and multi-slice ES volume was 0.75 (95%CI: 0.68, 0.81; Figure 1). Correlation between single-slice ES volume and MOAKS ES was 0.62 (95%CI: 0.39, 0.79) in the KL 2,3 sample and 0.67 (95%CI: 0.59, 0.73) in the FNIH subset (Figure 2A), while correlation between multi-slice ES volume and MOAKS ES was 0.74 (95%CI: 0.68, 0.79) in the FNIH subset (Figure 2B). Single-slice quantitative measurement of ES had excellent intra-and inter-reader reliability with non-expert readers, and good correlation with both multi-slice quantitative ES measurement and with MOAKS. Single-slice quantitative measurement is an efficient surrogate for multi-slice assessment, having shown similar validity based on comparison to semi-quantitative scoring by MSK radiologists. None CKK is consultant to Regeneron, LG Chem, and Express Scripts. He is principal investigator for pharma sponsored clinical trials to Abbvie, Cumberland, and GSK and DSMB to Kolon TissueGene and Avalor Therapeutics. CORRESPONDENCE ADDRESS: kwoh@arthritis.arizona.edu
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