To evaluate the potential utility of sodium (²³Na) MRI of cartilage for longitudinal studies in patients with knee osteoarthritis (OA). OA is the most common form of arthritis in synovial joints and a leading cause of chronic disability in the elderly population. Osteoarthritis is a degenerative disease of the articular cartilage that can be associated with a reduction in glycosaminoglycan (GAG) concentration, changes in the size and organization of collagen fibers^1,2. Sodium MRI has been shown to strongly correlate with the GAG concentration in cartilage^3,4 and is therefore a good candidate as an imaging biomarker to assess loss of GAG and cartilage degradation over time in patients with OA.

MRI scans: Twelve symptomatic subjects (mean age = 67±11 yr) with knee OA and Kellgren-Lawrence grades 1-3 (7 KL=1, 3 KL=2, 2 KL=3) were scanned at 7 T (Siemens) with a dual-tuned ¹H/²³Na knee coil (birdcage transmit, 8-channel receive) and with 2 sequences: (1) Radial 3D (R3D), with TE 0.4 ms, TR 100 ms, flip angle 90°, FOV 200 mm isotropic, 10,000 projections, dwell time 80 μs, real resolution 3.3 mm isotropic, nominal (reconstructed) resolution 2 mm, TA 16:44 min; (2) Inversion recovery (IR) with adiabatic WURST pulse^5,6 (IRW) for synovial fluid suppression, with the same acquisitions parameters as R3D except TR 140 ms, TI 24 ms, WURST pulse 240 Hz/10 ms, TA 23:25 min. All images were reconstructed offline in Matlab with standard 3D regridding. All subjects were scanned at baseline (scan 1) and 16 months follow-up (scan 2) (mean delay = 478±40 days).

Quantification: Sodium concentration [Na⁺] quantification was calculated from linear regression of the signal intensity of gel phantoms (4% Agar with 100, 150, 200, 250, 300 mM [Na⁺])^4,6. The image of an uniform solution phantom (45 mM NaCl) filling the whole volume inside the coil was acquired with R3D, normalized, and used to correct the cartilage data prior to sodium quantification processing (to correct the receive inhomogeneity from the 8-channel array⁷). Sodium maps were also corrected using T1 and T2* from cartilage⁸ to increase accuracy to cartilage sodium (note that the phantoms [Na⁺] on the maps will therefore be inaccurate).

Measurements: Three regions-of-interest (ROIs) of 40 pixels were drawn on the patellar (PAT), femoro-tibial medial (MED) and femoro-tibial lateral (LAT) cartilage, over 8 consecutive slices. All sodium maps (baseline and follow-up) for each subject were co-registered prior to ROI measurements. The mean and standard deviation (std) over all pixels were then calculated for each ROI (in mM) in each subject.

Statistics: The rank sum test was applied to the summary statistics of means and std in all subjects to assess the significance of the difference of the measures between the baseline and 16 months follow-up scans.

Fig. 1 and 2 show examples of [Na⁺] maps in PAT, MED and LAT, from 2 different OA patients. Sodium maps calculated from R3D (no fluid suppression) present little difference in the ROIs, while data from IRW (fluid suppression that removes partial volume effect from synovial fluid) present significant visual difference in the ROIs.

Fig. 3 shows the boxplots of mean and std [Na⁺] measured in PAT, MED and LAT for each subject and each sequence, at baseline (scan 1) and 16 months follow-up (scan 2). We can observe that, for most of the subjects, mean and std values measured from the follow-up scans were lower than from the baseline scan, and that only measurements from IRW were significantly different between the 2 scans (see Table 1 for the p values). The average decrease of mean [Na⁺] was 70±50 mM over all patients.

Sodium MRI with synovial fluid suppression by IR is more sensitive to the sodium content within cartilage⁴ and allows us to estimate the rate of loss of GAG over time in patients with OA. Due to the small number of subjects, no correlation was found between the decrease in mean and std [Na⁺] and KL grade. More subjects with KL 1 to 4 need to be scanned to assess if the proposed measurements can not only estimate accurately the degree of cartilage degradation, but also predict the rate of degradation.Quantitative sodium MRI with synovial fluid suppression by IR at 7 T could be a potential useful imaging biomarker for follow-up studies of cartilage degradation due to OA, and for assessing the efficiency of disease modifying OD drugs (DMOADs). Future work will involve increasing the acquisition speed and resolution with improved 3D non-Cartesian sequences⁹, and assess the repeatability of the follow-up study on asymptomatic controls¹⁰.