Diffusion-weighted imaging for assessment of synovial inflammation in juvenile idiopathic arthritis: a promising imaging biomarker as an alternative to gadolinium-based contrast agents

Abstract

Objectives: To compare dynamic-contrast-enhanced MRI (DCE) and diffusion-weighted imaging (DWI) in quantifying synovial inflammation in juvenile idiopathic arthritis (JIA).

Methods: Regions of interest (ROI) were drawn in the synovium of JIA patients on T1 DCE and T2 DWI, followed by extraction of the maximum enhancement (ME), maximum initial slope (MIS), time to peak (TTP), % of different time intensity curve shapes (TIC) and apparent diffusion coefficient (ADC) of the ROIs. Mann-Whitney-U test was used for comparing parameters between MRI-active and -inactive patients (defined by the juvenile arthritis MRI scoring system). Spearman's rank was used to analyse the correlation between DCE and DWI.

Results: Thirty-five JIA patients (18 MRI active and 17 MRI inactive) were included. Median age was 13.1 years and 71% were female. ME, MIS, TTP, % TIC 5 and ADC were significantly different in MRI-active versus MRI-inactive JIA with median ADC 1.49 × 10^-3mm²/s in MRI-active and 1.25 × 10^-3mm²/s in MRI-inactive JIA, p = 0.001, 95% confidence interval of difference in medians =0.11-0.53 × 10^-3mm²/s. ADC correlated to ME, MIS and TIC 5 shapes (r = 0.62, r = 0.45, r = -0.51, respectively, all p < 0.05).

Conclusions: Similar to DCE parameters, DWI-derived ADC is significantly different in MRI-active JIA as compared to MRI-inactive JIA. The non-invasiveness of DWI combined with its possibility to detect synovial inflammation shows the potential of DWI.

Key points: • MRI can quantify: dynamic contrast-enhanced and diffusion-weighted MRI can quantify synovitis • Both DWI and DCE can differentiate active from inactive JIA • The DWI-derived apparent diffusion coefficient (ADC) is higher in active JIA • DWI is non-invasive and thus safer and more patient-friendly • DWI is a potentially powerful and non-invasive imaging biomarker for JIA.

Keywords: Arthritis; Diffusion magnetic resonance imaging; Juvenile arthritis; Knee joint; Magnetic resonance imaging.

Fig. 1

MRI example of two patients using a sagittal T1 pre- and post-contrast image and an axial T1 SPIR post-contrast image. MRI-active disease: the upper row represents an 11-year old boy with JIA who had synovial hypertrophy in multiple knee compartments, resulting in a total JAMRIS (Juvenile Arthritis MRI Scoring System) synovial hypertrophy (SH) score of 8. Note the enhancing and thickened synovial membrane in both the sagittal T1 post-contrast slice and the axial T1 SPIR. MRI-inactive disease: the lower row represents a 12-year old girl with JIA with no synovial hypertrophy in the knee (JAMRIS SH 0)

Fig. 2

Visualisation of the seven-time intensity curve (TIC) shapes that were used in the TIC shape analysis. A detailed explanation of the TIC shape analysis can be found in references [25, 26]

Fig. 3

Example of a T1 dynamic contrast-enhanced image and parametric maps (maximum enhancement (ME) and apparent diffusion coefficient (ADC)) of an MRI-active JIA patient (upper row) and MRI-inactive JIA patient (lower row) with demonstration of region of interest (ROI) placement. Arrows point to the ROIs. ROIs were placed in synovial tissue. Joint effusion (if present) was not included in the ROI, as can be seen in the T1 DCE image of the 11-year old boy with MRI-active JIA

Fig. 4

Boxplots of dynamic contrast-enhanced (DCE) and diffusion-weighted imaging (DWI) parameters that were significantly different in MRI-inactive JIA when compared to MRI-active JIA. The y-axis displays a DCE or DWI parameter (ME, MIS, TTP, TIC5 or ADC). The x-axis is divided in two: first, MRI-inactive patients are displayed (filled circles); second patients with MRI-active JIA indicated by a grey, open square. *= p-value < 0.05

Fig. 5

Scatter plot displaying the correlation between dynamic contrast-enhanced (DCE) parameters and apparent diffusion coefficient (ADC) in patients with MRI-inactive JIA. The y-axis represents ADC in mm²/s; the x-axis displays the DCE parameters (ME, TTP and % of TIC 4 shapes). Correlation coefficient 'r' and the associated p-value are displayed within the right corner of each scatter plot. Only statistically significant correlations are shown

Fig. 6

Scatter plot displaying correlation between the dynamic contrast-enhanced (DCE) parameters and apparent diffusion coefficient (ADC) in all patients (MRI-inactive and -active JIA). The y-axis represents ADC in mm²/s; the x-axis displays the DCE parameters (ME, MIS and % of TIC 5 shapes). MRI-inactive patients are represented by filled circles, MRI-active patients by a grey, open square. Correlation coefficient 'r' and the associated p-value are displayed within the right corner of each scatter plot. Only statistically significant correlations are shown