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Alterations in cartilage thickness (CTh) are a hallmark of knee osteoarthritis, which remain difficult to characterize at high resolution, even with modern magnetic resonance imaging (MRI), due to a paucity of standardization tools. This study aimed to assess a computational anatomy method producing standardized two-dimensional femorotibial CTh maps. The method was assessed with twenty knees, processed following three common experimental scenarios. Cartilage thickness maps were obtained for the femorotibial cartilages by reconstructing bone and cartilage mesh models in tree-dimension, calculating three-dimensional CTh maps, and anatomically standardizing the maps. The intra-operator accuracy (median (interquartile range, IQR) of &minus, 0.006 (0.045) mm), precision (0.152 (0.070) mm), entropy (7.02 (0.71) and agreement (0.975 (0.020))) results suggested that the method is adequate to capture the spatial variations in CTh and compare knees at varying osteoarthritis stages. The lower inter-operator precision (0.496 (0.132) mm) and agreement (0.808 (0.108)) indicate a possible loss of sensitivity to detect differences in a setting with multiple operators. The results confirmed the promising potential of anatomically standardized maps, with the lower inter-operator reproducibility stressing the need to coordinate operators. This study also provided essential reference data and indications for future research using CTh maps.

Summary Objective To test if sagittal plane gait mechanics parameters and serum inflammation levels differ between healthy asymptomatic subjects and asymptomatic subjects with magnetic resonance imaging (MRI) evidence of cartilage loss. Design Gait mechanics and resting serum tumor necrosis factor-α (TNFα) concentrations were measured for two groups of asymptomatic subjects recruited for a previous study: Pre-Osteoarthritis (OA) subjects had MRI evidence of partial- or full-thickness knee cartilage loss in at least one compartment ( n = 52 (30 female), 1.7 ± 0.1 m, 85.3 ± 18.9 kg, 44 ± 11 years); Control subjects had no MRI features of cartilage loss, osteophytes, bone marrow lesions, nor meniscal pathology in either knee ( n = 26 (13 female), 1.7 ± 0.1 m, 74.6 ± 14.9 kg, 34 ± 10 years). Discrete measures of sagittal plane gait kinematics and kinetics were compared between subject groups and adjusted for age and body mass index (BMI) using analysis of covariance (ANCOVA). Serum TNFα concentrations were compared between groups using bootstrap t -test. Results The Pre-OA group had less extended knees ( P = 0.021) and decreased maximum external knee extension moment ( P = 0.0062) in terminal stance during gait, as well as increased resting serum TNFα concentration ( P = 0.040) as compared to Control subjects. There were no group differences in heel strike flexion angle ( P = 0.14), in maximum knee flexion moment ( P = 0.91), nor in first peak knee adduction moment (KAM) (post-hoc analysis, P = 0.39). Conclusions The finding that asymptomatic subjects with cartilage loss had gait and inflammatory characteristics similar to those previously reported in symptomatic OA patients supports the idea that there are specific mechanical and biological factors that precede the onset of knee pain in the pathogenesis of OA.

s / Osteoarthritis and Cartilage 22 (2014) S57–S489 S97 Results: Table 1 presents the correlation coefficients between the radiographic grading sub scores and kinematic parameters. Correlations with the frontal plane kinematics showed to be the strongest, with R values going from 0.641 to 0.724. Furthermore, joint space demonstrated to be strongly correlated with frontal plane kinematics based on the high weight of this x-ray sub-score in the MLR. Results in the transverse and sagittal planes showed negative correlations ranging from -0.440 to -0.497. Results show that FO is the sub-score that is the most strongly correlated (in this case negative correlation) with kinematic parameters in the transverse plane. A residues analysis was also conducted to confirm a random distribution of the residues around zero (figure 1). The absence of error patterns means that the choice of a linear regression fits well the relationship between the kinematic parameters and radiographic sub scores. Conclusions: The frontal plane presented the strongest correlation between the x-ray grading scale and the knee kinematic parameters. This analysis showed that the higher the x-ray sub scores are, meaning a more advanced state of the disease, the higher the varus angle parameters during gait are. This strengthens the link between a dynamic varus alignment and medial TF compartment OA progression. Interestingly, joint space showed a strong influence on the correlations with kinematic parameters in frontal plane. The transverse and sagittal plane both showed a negative correlation, meaning that the higher the x-ray sub scores are, the lower the kinematic parameters will be. In the sagittal plane this translate to a more fixed flexion adaptation strategy to protect the knee and in the transverse plan to a more internally rotated tibia. An offset towards internal rotation was previously linked to faster progression of OA which could also support the link with higher FO score. Further investigations, with a larger and more homogeneous sample group should lead to stronger correlations and should better define the relationships between the knee 3D kinematic parameters and radiographic grading system. This study supports the involvement of dynamic biomechanical factors in the progression of the disease. Results give new insights to develop personalized treatment plan based on kinematic parameters and x-ray OA grading scales to potentially limit the progression of the disease. Plane Kinematic Parameter Radiographic Scorn (Estimate Coefficient) R^2 R p-value Abduction Adduction (frontal) Mean 0-10% of GC FA_TA (-0.212) JS (1.608) FO (0.971) TE (2.139) 0.383 0.619 0.005 Mean 1030% of GC FA_TA (-0.357) JS (1.663) FO (0.808) TE (1.406) 0.412 0.641 0.002 Mean 3050% of GC FA_TA (-0.268) JS (1.808) FO (1.051) TE (0.865) 0.524 0.724

Measures of mean cartilage thickness over predefined regions in the femoral plate using magnetic resonance imaging have provided important insights into the characteristics of knee osteoarthritis (OA), however, this quantification method suffers from the limited ability to detect OA-related differences between knees and loses potentially important information regarding spatial variations in cartilage thickness. The objectives of this study were to develop a new method for analyzing patterns of femoral cartilage thickness and to test the following hypotheses: (1) asymptomatic knees have similar thickness patterns, (2) thickness patterns differ with knee OA, and (3) thickness patterns are more sensitive than mean thicknesses to differences between OA conditions. Bi-orthogonal thickness patterns were extracted from thickness maps of segmented magnetic resonance images in the medial, lateral, and trochlea compartments. Fifty asymptomatic knees were used to develop the method and establish reference asymptomatic patterns. Another subgroup of 20 asymptomatic knees and three subgroups of 20 OA knees each with a Kellgren/Lawrence grade (KLG) of 1, 2, and 3, respectively, were selected for hypotheses testing. The thickness patterns were similar between asymptomatic knees (coefficient of multiple determination between 0.8 and 0.9). The thickness pattern alterations, i.e., the differences between the thickness patterns of an individual knee and reference asymptomatic thickness patterns, increased with increasing OA severity (Kendall correlation between 0.23 and 0.47) and KLG 2 and 3 knees had significantly larger thickness pattern alterations than asymptomatic knees in the three compartments. On average, the number of significant differences detected between the four subgroups was 4.5 times greater with thickness pattern alterations than mean thicknesses. The increase was particularly marked in the medial compartment, where the number of significant differences between subgroups was 10 times greater with thickness pattern alterations than mean thickness measurements. Asymptomatic knees had characteristic regional thickness patterns and these patterns were different in medial OA knees. Assessing the thickness patterns, which account for the spatial variations in cartilage thickness and capture both cartilage thinning and swelling, could enhance the capacity to detect OA-related differences between knees.