Dynamic contrast-enhanced MRI of synovitis in knee osteoarthritis: repeatability, discrimination and sensitivity to change in a prospective experimental study

Abstract

Objectives Evaluate test-retest repeatability, ability to discriminate between osteoarthritic and healthy participants, and sensitivity to change over 6 months, of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) biomarkers in knee OA. Methods Fourteen individuals aged 40–60 with mild-moderate knee OA and 6 age-matched healthy volunteers (HV) underwent DCE-MRI at 3 T at baseline, 1 month and 6 months. Voxelwise pharmacokinetic modelling of dynamic data was used to calculate DCE-MRI biomarkers including Ktrans and IAUC60. Median DCE-MRI biomarker values were extracted for each participant at each study visit. Synovial segmentation was performed using both manual and semiautomatic methods with calculation of an additional biomarker, the volume of enhancing pannus (VEP). Test-retest repeatability was assessed using intraclass correlation coefficients (ICC). Smallest detectable differences (SDDs) were calculated from test-retest data. Discrimination between OA and HV was assessed via calculation of between-group standardised mean differences (SMD). Responsiveness was assessed via the number of OA participants with changes greater than the SDD at 6 months. Results Ktrans demonstrated the best test-retest repeatability (Ktrans/IAUC60/VEP ICCs 0.90/0.84/0.40, SDDs as % of OA mean 33/71/76%), discrimination between OA and HV (SMDs 0.94/0.54/0.50) and responsiveness (5/1/1 out of 12 OA participants with 6-month change > SDD) when compared to IAUC60 and VEP. Biomarkers derived from semiautomatic segmentation outperformed those derived from manual segmentation across all domains. Conclusions Ktrans demonstrated the best repeatability, discrimination and sensitivity to change suggesting that it is the optimal DCE-MRI biomarker for use in experimental medicine studies. Key Points • Dynamic contrast-enhanced MRI (DCE-MRI) provides quantitative measures of synovitis in knee osteoarthritis which may permit early assessment of efficacy in experimental medicine studies. • This prospective observational study compared DCE-MRI biomarkers across domains relevant to experimental medicine: test-retest repeatability, discriminative validity and sensitivity to change. • The DCE-MRI biomarker Ktransdemonstrated the best performance across all three domains, suggesting that it is the optimal biomarker for use in future interventional studies.

MRI Semi-Quantitative Evaluation of Clinical Features of Cartilage Injury in Patients with Osteoarthritis

“…For example, some scholars have explored the diagnostic value of the total knee MRI scores for knee OA and found that the whole-organ MRI score (WORMS) was positively correlated with Western Ontario and Mc Master University Osteoarthritis Index (WOMAC) score, indicating that the pain, stiffness, and function of patients with the knee OA can be explained by imaging, and multiple linear regression analysis has been confirmed [18,19]. However, some scholars have accurately measured the T2 of cartilage in each area of the knee joint using T2 maps generated by MR sagittal T2 mapping imaging sequences and found that cartilage T2 values were increased and weight-bearing areas were significant in patients with OA, but there was no significant correlation between clinical scores and cartilage T2 changes in all subjects [20]. In summary, further studies and confirmation are needed regarding the correlation between MRI findings and clinical symptoms.…”

3D MRI in Osteoarthritis

“…Using a longitudinal study with up to 6 months of follow-up, MacKay et al determined the repeatability, discriminatory power, and sensitivity to change DCE for imaging synovitis in the knee. 51 They found that for all outcomes, K trans performed the best of all DCE-MRI derived imaging. In the 6month period, 5 of 12 OA patients showed a change in K trans above the smallest detectable difference.…”

Gadolinium‐free assessment of synovitis using diffusion tensor imaging

“…K trans has demonstrated greater test-retest repeatability and ability to detect changes in the inflamed synovium of knees with OA compared with IAUC 60 and STV. 10 Since K trans is a composite measure of blood flow and capillary permeability, 11 which both positively correlate with inflammatory activity, K trans can be used to quantify the intensity of synovitis. However, while DCE-MRI is effective at evaluating synovitis, it requires longer scan times along with increased costs due to the use of contrast agent.…”

“…However, these approaches do not provide any insight into the intensity of synovitis, which may be a more responsive measure and correlate more strongly with symptoms than the extent of synovitis 9 . Dynamic contrast‐enhanced (DCE)‐MRI with administration of GBCA has previously been used to evaluate synovitis in subjects with knee OA 10 using several biomarkers, including the initial area under the time‐concentration curve at 60 s (IAUC 60 ), the synovial tissue volume (STV), and the pharmacokinetic parameter K trans , which is the volume transfer coefficient between blood plasma and the extracellular extravascular space. K trans has demonstrated greater test‐retest repeatability and ability to detect changes in the inflamed synovium of knees with OA compared with IAUC 60 and STV 10 .…”

“…Dynamic contrast‐enhanced (DCE)‐MRI with administration of GBCA has previously been used to evaluate synovitis in subjects with knee OA 10 using several biomarkers, including the initial area under the time‐concentration curve at 60 s (IAUC 60 ), the synovial tissue volume (STV), and the pharmacokinetic parameter K trans , which is the volume transfer coefficient between blood plasma and the extracellular extravascular space. K trans has demonstrated greater test‐retest repeatability and ability to detect changes in the inflamed synovium of knees with OA compared with IAUC 60 and STV 10 . Since K trans is a composite measure of blood flow and capillary permeability, 11 which both positively correlate with inflammatory activity, K trans can be used to quantify the intensity of synovitis.…”