Semiquantitative assessment of subchondral bone marrow edema-like lesions and subchondral cysts of the knee at 3T MRI: A comparison between intermediate-weighted fat-suppressed spin echo and Dual Echo Steady State sequences

Subjects included in the present study were participants in the Joints On Glucosamine (JOG) cohort. The JOG study is a 6-month double-blind randomized controlled trial to examine the efficacy of oral glucosamine supplementation. Two hundred and one participants, aged 35 to 65, with mild to moderate chronic, frequent knee pain (Western Ontario and McMaster Universities (WOMAC) score ≥ 25 [10]) were recruited at the University of Pittsburgh, Pittsburgh, PA. Subjects were excluded from JOG if they screened positive for rheumatoid arthritis; had ankylosing spondylitis, psoriatic arthritis, chronic reactive arthritis, or renal insufficiency that required hemo- or peritoneal dialysis; were taking bisphosphonates or dietary supplements for knee pain in the 6 months prior to study entry; had a history of cancer (except for non-melanoma skin cancer); had or planned to have bilateral knee replacement surgery; or were unable to walk without assistance. No BMLs of non-degenerative origin (e.g. trauma) were found in this study.

The baseline and follow-up MRI examinations of both knees, when possible, of the 177 subjects who completed the study were examined. Due to previous total knee arthroplasty or the presence of radiographic end-stage OA, eight participants had only one knee scanned, leaving 346 knees that were included in the analyses. Although the JOG Study itself was a longitudinal study, the present study only involves a cross-sectional analysis based on the MRI examinations taken at the baseline.

Institutional Review Board approval and all participants' written informed consent were obtained for this study.

3 T MRI (Siemens Trio, Erlangen, Germany) was acquired on the same MRI scanner that is used at the Pittsburgh site of the OAI. The identical pulse sequence protocol used for the OAI was applied in the JOG study, excluding the FLASH sequence and the Multi-Echo Spin Echo T2 mapping sequence. Details of the full OAI pulse sequence protocol and the sequence parameters have been published [11]. The protocol included a sagittal 3D DESS sequence with water excitation (WE) (slice thickness = 0.7 mm, interslice gap = 0 mm, repetition time (TR) = 16.3 ms, echo time (TE) = 4.7 ms, flip angle = 25°, field of view (FOV) = 140 mm × 140 mm, matrix = 384 × 307 pixels, echo train length = 1, number of slices = 35, bandwidth = 185 Hz/pixel, number of excitations = 1, anterior/posterior phase encoding axis, acquisition time = 10 minutes 23 seconds), and the sagittal intermediate-weighted (IW) fat-suppressed (fs) 2D turbo spin echo (TSE) sequence (slice thickness = 3 mm, interslice gap = 0 mm, TR = 30 ms, TE = 3,200 ms, flip angle = 180°, FOV = 160 mm × 160 mm, matrix = 313 × 448 pixels, echo train length = 5, number of slices = 37, bandwidth = 248 Hz/pixel, number of excitations = 1, anterior/posterior phase encoding axis, acquisition time = 4 minutes 42 seconds).

One musculoskeletal radiologist (FWR) with 7 years experience of standardized semiquantitative assessment of knee OA, blinded to clinical data, read the baseline MR images of all 346 knees using all 5 available sequences. The MRI evaluation in JOG included the joint features of subchondral BMLs, subchondral cysts, cartilage, meniscus, effusion and synovitis using the Whole Organ Magnetic Resonance Imaging Score (WORMS) method [12]. WORMS is a validated research tool for semiquantitative assessment of knee OA. In WORMS, subchondral BMLs are scored from 0 to 3 based on the extent of subregional involvement (0 = none; 1 = < 25% of the subregion; 2 = 25-50%; 3 = > 50%, Figure 1, 2a). Similarly, subchondral cysts are also scored from 0 to 3 based on the lesion extent in regard to subregional involvement (0 = none; 1 = < 25% of the subregion; 2 = 25-50%; 3 = > 50%, Figure 2b) at baseline. Thus, the WORMS score for subchondral BMLs and cysts is a sum of percentage of subregion for each type of lesion and does not give information on the number of lesions. In the following, we will use the term subchondral BML and subchondral cyst interchangeably for "percentage of the area occupied by BML and cyst within a subregion" as defined in WORMS. Altogether 654 subregions exhibiting subchondral BMLs were observed in 262 knees. Two hundred subregions exhibiting subchondral BMLs from 63 knees of 42 subjects in the primary reading were randomly chosen for the consequent direct sequence comparison. One hundred and ten of these 200 subregions also exhibited subchondral cysts.

In a second consensus reading by two experienced musculoskeletal radiologists (FWR, AG) with 7 and 9 years experience in standardized semiquantitative MR assessment of knee OA, these 200 subregions were re-evaluated using the sagittal 3D DESS and sagittal IW fs TSE sequences only. Readings for both sequences were performed separately with a time interval of 4 weeks to avoid recognition bias. All subregions were re-evaluated for lesion size of subchondral BMLs and cysts. Further, confidence of the differentiation between these two types of lesions was rated on a 0-3 scale (0 = unable to differentiate; 1 = doubtful differentiation; 2 = may be able to differentiate with some confidence; 3 = able to differentiate with definite confidence). Wilcoxon signed-rank tests for paired comparisons of clustered data were used to examine if there were statistically significant differences between the two sequences, and clustering by person was controlled [13]. All analyses were performed using SAS_® software (Version 9.2 for Windows; SAS Institute, Cary, NC).