Bone marrow lesions in knee osteoarthritis: MR-assessment by manual segmentation and computer-assisted thresholding Purpose The purposes of the study were to evaluate a manual segmentation method and a computer-assisted thresholding technique for estimating bone marrow lesions (BMLs) in knee osteoarthritis (KOA) over time and compare the results with the most used conventional grading systems. In the commonly used grading methods BMLs are evaluated regarding their approximate size of the total area and in three grades. Thus, in the newly published MOAKS method (1), representing a synthesis of the two most common grading tools, WORMS and BLOKS (2;3), there are three grades of BMLs; grade 1=<33% BML of the total area, grade 2=33-66% and grade 3=>66%. Material and Methods A total of 13 patients with medial femorotibial KOA according to the ACR criteria were examined by MRI at baseline and follow-up after 3-12 months. Female/male ratio =12/1; median age 60.5 years (41.1-72.3). Among several sequences performed using a 1.5 T unit (Vision, Siemens, Erlangen, Germany) with a transmit receive four-channel knee coil, the post-contrast sagittal T1 fatsuppressed (T1FS) sequence was analyzed. The technical sequence parameters were: TR/TE = 860/20 ms, FOV = 16 cm, slice thickness/interslice gap = 4.0/0.8 mm, matrix 256 x 256, one excitation, TA 7.23. The dose of Gadolinium (GdDTPA 0.2 mmol/ml) was standardized to 0.1 mmol/kg. BMLs were defined as ill-delineated areas of increased signal intensity (SI) on the post-contrast T1FS images. Volumes (mm3) of BMLs in the medial weight-bearing femoral and tibial condyle (52 observations) were measured/calculated on anonymized images by two observers. The manual segmentation (MS) was performed using Agfa Impax software and 2K Bracho screens. The computer assisted tresholding (CAT) method was performed using a graphical user interface for drawing regions of interest (ROIs) and thresholding images written in MATLAB (the MathWorks, Sweden) by D.P. at the Medico-technical Department, Aarhus University Hospital. The areas/volumes of interest of the femoral condyles were separated from the trochlea area/volume as suggested in BLOKS/MOAKS (Figs. 1-3). The area/volume of the tibia included the proximal 2 cm’s of the tibial condyles (MS only). By both methods the mean SI (gray scale value, GY) plus one standard deviation (STD) of the normal bone marrow of the lateral femoral condyle was used as a relative reference (Figs. 1A and 2). Areas/volumes with contiguous pixels above this gray scale threshold were considered bone marrow lesions. The total volume of BML was obtained by multiplying the BML areas in each section with the section thickness including the intersection gap. By the manual segmentation, the margins of the areas of BML in each section were constructed by a curved line joining the pixels with threshold values. The correct position of the borderline were controlled by a 5 mm2 ROI (Figs. 1B, 6) and the margins were adjusted if necessary. The computer calculated BML area was based on counting (with visual coloring) the number of pixels above the threshold in the ROI (Fig. 3, 4). Small clusters of pixels <5 and areas <3 mm2 were not registered by the CAT and manual method, respectively. The MS and CAT method were tested regarding inter-observer reliability. The results of MS and CAT estimation of BMLs were compared and related to a MOAKS grading of BML. Results The inter-observer agreement for BML volumes by MS was good, linear weighted kappa value 0.88 (CI 0.84-0.93) with no difference regarding femoral and tibial volumes (kappa 0.85), respectively. Based on 24 estimations the inter-observer agreement for BML volume by CAT was also good, linear weighted kappa values 0.84 (CI 0.79-0.89). The CAT method failed in two examinations due to apparently uneven contrastenhancement with varying signal intensity of normal bone across the knee. A consensus was made regarding these examinations by drawing the ROI in close proximity to observed BML and avoiding areas of unwanted signal variation (Figs. 4-6). The consensus results were used in the comparison with the MS results. The BML values obtained by MS and CAT, respectively, were significantly correlated (ơ=0.94 (CI 0.89-0.96)) and the median values were similar. MOAKS grade/percentage BML of the total femoral or tibial condyle volume were 1/<33%: n=19; 2/33-66%: n=4; 3/>66%: n=3. Detected BML changes in volumes during follow-up were: <4%: n=15; <33%: n= 9; 33-66%: n=0; >66%: n=2. Thus, the change over time was only detectable in two knees by MOAKS. Conclusion MS and CAT can estimate BML changes over time not detectable by MOAKS. The CAT method should, however, be used with caution. The presented manual segmentation grading method, though time consuming, can be used without dedicated computer software. It was found to be sensitive to detecting even minor changes in BML volume making it advantageous specifically given the fluctuating nature of BML (4). Thresholding is a popular technique in image segmentation (5;6) in which a number of pixels are selected based on pixel intensity. The results can be obtained fast and the use of computerized thresholding therefore seems encouraging but should be used with caution. In two of the present examinations the CAT method failed due to the signal intensity of normal bone varying from the outside toward the inside of the knee. The source of error is most likely due to partial volume artifact, poor positioning of the knee inside the receiving coil, B1 inhomogeneity or poor shimming. This has not been fully explored. Furthermore, CAT does not differentiate between pathological or physiological entities, including e.g. blood vessels, resulting in a potential overestimation of the BML volume. Due to large and ill-defined transitions of BMLs in KOA, precise area/volume measurements remain a challenge. Additional grading of SI and/or dynamic contrast MR imaging may add to clarify the clinical significance of BMLs in OA. 1: Hunter DJ, Guermazi A, Lo GH, Grainger AJ, Conaghan PG, Boudreau RM, Roemer FW: Evolution of semi-quantitative whole joint assessment of knee OA: MOAKS (MRI Osteoarthritis Knee Score). Osteoarthritis Cartilage 2011, 19(8):990-1002. 2: Peterfy CG, Guermazi A, Zaim S, Tirman PF, Miaux Y, White D, Kothari M, Lu Y, Fye K, Zhao S, Genant HK:Whole-Organ Magnetic Resonance Imaging Score (WORMS) of the knee in osteoarthritis. Osteoarthritis Cartilage 2004, 12(3):177-190. 3: Hunter DJ, Lo GH, Gale D, Grainger AJ, Guermazi A, Conaghan PG: The reliability of a new scoring system for knee osteoarthritis MRI and the validity of bone marrow lesion assessment: BLOKS (Boston Leeds Osteoarthritis Knee Score). Ann Rheum Dis 2008, 67(2):206-211. 4: Kornaat PR, Kloppenburg M, Sharma R, Botha-Scheepers SA, Le Graverand MP, Coene LN, Bloem JL, Watt I: Bone marrow edema-like lesions change in volume in the majority of patients with osteoarthritis; associations with clinical features. Eur Radiol 2007, 17(12):3073-3078. 5: Fotinos-Hoyer AK, Guermazi A, Jara H, Eckstein F, Ozonoff A, Khard H, Norbash A, Bohndorf K, Roemer FW: Assessment of synovitis in the osteoarthritic knee: Comparison between manual segmentation, semiautomated segmentation, and semiquantitative assessment using contrastenhanced fat-suppressed T1-weighted MRI. Magn Reson Med 2010, 64(2):604-609. 6: Mayerhoefer ME, Breitenseher MJ, Kramer J, Aigner N, Norden C, Hofmann S: STIR vs. T1-weighted fat-suppressed gadolinium-enhanced MRI of bone marrow edema of the knee: computer-assisted quantitative comparison and influence of injected contrast media volume and acquisition parameters. J Magn Reson Imaging 2005, 22(6):788-793.