Patterns of Femoral Cartilage Thickness are Different in Asymptomatic and Osteoarthritic Knees and Can be Used to Detect Disease-Related Differences Between Samples

Abstract

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.

A Systems View of Risk Factors for Knee Osteoarthritis Reveals Insights into the Pathogenesis of the Disease

“…Specifically, there is emerging evidence that there are subtle but important changes from normal patterns of ambulation that are common to the primary risk factors (aging, obesity and joint trauma), and these ambulatory changes appear prior to developing clinical knee OA. Further these ambulatory changes have specific kinematic characteristics that taken together with reports 22, 32, 45 that the structure and biology of healthy cartilage adapt to the repetitive patterns of loading, suggest that cartilage health is dependent upon maintaining kinematics within a normal envelope of function.…”

“…Second, individual variations in the normal patterns of normal walking can influence normal variations in cartilage morphology. 22, 32, 45 Third, if ambulation changes in a way that places loading outside of normal ranges (increase or disuse) cartilage can respond negatively 3 Thus it is possible to identify meaningful interactions at the systems level that span across scales from whole body function to the cellular level and thus provide a basis for analyzing the complexity of the factors that influence cartilage health and risk factors for developing OA.…”

“…For example, the reason that current imaging methods have reported limited sensitivity in detecting cartilage changes can be explained by the fact that these methods use mean thickness measurements from predefined regions, 31, 55 and thus cannot account for the substantial individual variations in the regions of cartilage thickness (Figure 3). Recent work 22, 23 has avoided the need for preselecting regions of interest by characterizing patterns of thickness shape 23 . Use of a pattern-based analysis of 140 knees from 60 asymptomatic subjects and four groups of 20 patients with mild to severe medial compartment OA identified a characteristic progression in the thickness map patterns with increasing medial knee OA (Figure 7), and the scoring method allowed for excellent differentiation between disease severities.…”

Age-related differences in sagittal-plane knee function at heel-strike of walking are increased in osteoarthritic patients

“…4 On average, the younger and older asymptomatic groups in the present study differed by 4.1° and the older asymptomatic and severe OA groups by 4.6°. Therefore, since the spatial distribution of cartilage thickness has been shown to be finely conditioned to ambulatory load 4,6,39 and mature cartilage has limited adaptive capacity, 5 it is possible that the differences in knee function around heel-strike are large enough to influence knee OA. This possibility is further supported by reports of high joint load during this portion of the gait cycle in asymptomatic subjects, 40-41 and by altered muscle activations which might even increase the loading at the knee in the older groups.…”

Functional imaging in OA: role of imaging in the evaluation of tissue biomechanics

“…With the appropriate design of MRI pulse sequences, such as the use of fat-suppression pre-pulses, contrast can be enhanced to facilitate visualization and segmentation of the tissue. Cartilage and joint structure and morphology have been assessed using numerous quantities, including contact area [102–104], thickness and volume [99, 105–109], and diffusion-associated structural changes [4, 110]. For example, in a multi-center MRI study of 145 women, cartilage thickness changes approaching −4% were observed 6 months following baseline analysis in the central medial femorotibial joint of subjects showing Kellegren-Lawrence grades of 3, but not 2, suggesting sensitivity of thickness and joint space narrowing to OA progression [99].…”