Analyzing Femorotibial Cartilage Thickness Using Anatomically Standardized Maps: Reproducibility and Reference Data.

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 -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.

Anatomically Standardized Maps Reveal Distinct Patterns of Cartilage Thickness With Increasing Severity of Medial Compartment Knee Osteoarthritis.

While cartilage thickness alterations are a central element of knee osteoarthritis (OA), differences among disease stages are still incompletely understood. This study aimed to quantify the spatial-variations in cartilage thickness using anatomically standardized thickness maps and test if there are characteristic patterns in patients with different stages of medial compartment knee OA. Magnetic resonance images were acquired for 75 non-OA and 100 OA knees of varying severities (Kellgren and Lawrence (KL) scores 1-4). Three-dimensional cartilage models were reconstructed and a shape matching technique was applied to convert the models into two-dimensional anatomically standardized thickness maps. Difference thickness maps and statistical parametric mapping were used to compare the four OA and the non-OA subgroups. This analysis showed distinct thickness patterns for each clinical stage that formed a coherent succession from the non-OA to the KL 4 subgroups. Interestingly, the only significant difference for early stage (KL 1) was thicker femoral cartilage. With increase in disease severity, typical patterns developed, including thinner cartilage in the anterior area of the medial condyle (significant for KL 3 and 4) and thicker cartilage in the posterior area of the medial and lateral condyles (significant for all OA subgroups). The tibial patterns mainly consisted of thinner cartilage for both medial and lateral compartments (significant for KL 2-4). Comparing anatomically standardized maps allowed identifying patterns of thickening and thinning over the entire cartilage surface, consequently improving the characterization of thickness differences associated with OA. The results also highlighted the value of anatomically standardized maps to analyze spatial variations in cartilage thickness. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2442-2451, 2017.

Evidence for joint moment asymmetry in healthy populations during gait.

The purpose of this study was to determine the presence and prevalence of asymmetry in lower extremity joint moments within and across healthy populations during overground walking. Bilateral gait data from several studies performed at two institutions were pooled from 182 healthy, pain-free subjects. Four distinct populations were identified based on age, activity level and body mass index. Mean peak external joint moments were calculated from three to six trials of level overground walking at self-selected speed for each subject. Right and left limb moments were reclassified as "greater" or "lesser" moment for each subject to prevent obscuring absolute asymmetry due to averaging over positive and negative asymmetries across subjects. A clinically relevant asymmetry measure was calculated from the peak joint moments with an initial chosen cutoff value of 10%. Confidence intervals for the proportion of subjects with greater than 10% asymmetry between limbs were estimated based on the binomial distribution. We found a high amount of asymmetry between the limbs in healthy populations. More than half of our overall population exceeded 10% asymmetry in peak hip and knee flexion and adduction moments. Group medians exceeded 10% asymmetry for all variables in all populations. This may have important implications on gait evaluations, particularly clinical evaluations or research studies where asymmetry is used as an outcome. Additional research is necessary to determine acceptable levels of joint moment asymmetry during gait and to determine whether asymmetrical joint moments influence the development of symptomatic pathology or success of lower extremity rehabilitation.

Age and obesity alter the relationship between femoral articular cartilage thickness and ambulatory loads in individuals without osteoarthritis.

Articular cartilage is sensitive to mechanical loading, so increased risk of osteoarthritis in older or obese individuals may be linked to changes in the relationship between cartilage properties and extrinsic joint loads. A positive relationship has been reported between ambulatory loads and cartilage thickness in young individuals, but whether this relationship exists in individuals who are older or obese is unknown. This study examined the relationship between femoral cartilage thickness and load, measured by weight × height and the peak adduction moment, in young normal-weight (28 subjects, age: 28.0 ± 3.8 years, BMI: 21.9 ± 1.9 kg/m(2)), middle-aged normal-weight (27 subjects, 47.0 ± 6.5 years, 22.7 ± 1.7 kg/m(2)), young overweight/obese (27 subjects, 28.4 ± 3.6 years, 33.3 ± 4.6 kg/m(2)), and middle-aged overweight/obese (27 subjects, 45.8 ± 7.2 years, 31.9 ± 4.4 kg/m(2)) individuals. On the lateral condyle, cartilage thickness was positively correlated with weight × height for all groups (R(2) = 0.26-0.20) except the middle-aged overweight/obese. On the medial condyle, weight × height was significantly correlated only in young normal-weight subjects (R(2) = 0.19), as was the case for the correlation between adduction moment and medial-lateral thickness ratio (R(2) = 0.20). These results suggest that aging and obesity are both associated with a loss of the positive relationship between cartilage thickness and ambulatory loads, and that the relationship is dependent on the compartment and whether the load is generated by body size or subject-specific gait mechanics.

A visual motion detection circuit suggested by Drosophila connectomics.

Animal behaviour arises from computations in neuronal circuits, but our understanding of these computations has been frustrated by the lack of detailed synaptic connection maps, or connectomes. For example, despite intensive investigations over half a century, the neuronal implementation of local motion detection in the insect visual system remains elusive. Here we develop a semi-automated pipeline using electron microscopy to reconstruct a connectome, containing 379 neurons and 8,637 chemical synaptic contacts, within the Drosophila optic medulla. By matching reconstructed neurons to examples from light microscopy, we assigned neurons to cell types and assembled a connectome of the repeating module of the medulla. Within this module, we identified cell types constituting a motion detection circuit, and showed that the connections onto individual motion-sensitive neurons in this circuit were consistent with their direction selectivity. Our results identify cellular targets for future functional investigations, and demonstrate that connectomes can provide key insights into neuronal computations.

Patterns of femoral cartilage thickness are different in asymptomatic and osteoarthritic knees and can be used to detect disease-related differences between samples.

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.

Adduction moment increases with age in healthy obese individuals.

There is a need to understand how obesity and aging interact to cause an increased risk of medial knee osteoarthritis (OA). This study tested whether the knee adduction and flexion moments increase with age in healthy normal-weight and obese adults, as well as the mechanism of this increase. We analyzed whether ground reaction force magnitude, knee alignment, step width, toe-out angle, body volume distribution, and limb position (knee position relative to the pelvis center) are associated with the adduction moment and whether these variables also change with age. Ninety-six healthy volunteers (60 normal-weight and 36 obese) were tested using marker-based gait analysis; knee alignment was based on marker positions during quiet standing. Adduction moment increased with age in obese (R(2) = 0.19), but not in normal-weight individuals (R(2) = 0.01); knee flexion moment did not change with age in either group. In the obese, only knee alignment and limb position were related to the adduction moment (R(2) = 0.19 and 0.51), but only limb position changed with age (R(2) = 0.26). The resulting increase in adduction moment suggests greater medial compartment loads, which may combine with elevated levels of inflammation to contribute to the increased risk of medial OA in this population.

Mechanics of the anterior interval of the knee using open dynamic MRI.

BACKGROUND: The anterior interval of the knee has been defined as the space between the infrapatellar fat pad and patellar tendon anteriorly, and the anterior border of the tibia and the transverse meniscal ligament posteriorly. Investigation of the normal kinematics of this region is necessary as we begin to appreciate the significant impact that pathologic processes of the anterior interval have on the knee. METHODS: Non-weight bearing and weight bearing dynamic MRIs of 20 healthy knees were evaluated at 30 degrees intervals from 0 degrees to 120 degrees flexion. The angle subtended by the patellar tendon and the anterior tibia was measured at each interval of flexion by three independent observers. The amount of angular change over each interval of flexion was also evaluated and the differences between the relative weight bearing conditions were statistically evaluated. FINDINGS: The angle formed by the anterior tibia and the patellar tendon decreases with knee flexion (45.2 degrees (SD 10.1 degrees ) at full extension vs. 1.2 degrees (SD 2.1 degrees ) at full flexion). The average patellar tendon-tibial angle excursion was significantly reduced with full-weight bearing, 43.1 degrees (SD 11.2 degrees ) from 0 degrees to 120 degrees of flexion, compared to non-weight bearing, 30.9 degrees (SD 6.1 degrees ) over the same range of motion (P<0.001). Full-weight bearing decreased the angle excursion by 28% compared to non-weight bearing. INTERPRETATION: The observed changes in the anterior interval are influenced by multiple factors including load, knee architecture, tendon elasticity and tibio-femoral and patello-femoral kinematics. The impact of load on the mechanics of the anterior interval is most pronounced between 0 degrees and 30 degrees of flexion.

Graft orientation influences the knee flexion moment during walking in patients with anterior cruciate ligament reconstruction.

BACKGROUND: Anterior cruciate ligament graft orientation has been proposed as a potential mechanism for failure of single-bundle anterior cruciate ligament reconstruction and has been considered important in the restoration of normal ambulatory knee mechanics. PURPOSE: To evaluate the possibility that patients adapt their mechanics of walking to the orientation of the anterior cruciate ligament graft. This was determined by testing the hypothesis that peak external knee flexion moment (net quadriceps moment) during walking in patients with anterior cruciate ligament reconstruction is correlated with coronal and sagittal anterior cruciate ligament graft orientations. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Gait analysis was performed to assess dynamic knee function during walking in 17 subjects with unilateral anterior cruciate ligament reconstructions. Magnetic resonance imaging was used to measure coronal and sagittal anterior cruciate ligament graft orientations. RESULTS: A negative correlation was observed between peak external knee flexion moment during walking and coronal angle of the anterior cruciate ligament graft (1.0 m/s walking speed, r = -0.87, P < .001; 1.3 m/s, r = -0.66, P = .004; 1.6 m/s, r = -0.24, P > .05); no correlation was found with the sagittal graft angle (1.0 m/s walking speed, r = 0.21, P > .05; 1.3 m/s, r = 0.20, P > .05; 1.6 m/s, r = 0.13, P > .05). CONCLUSION: The negative correlation between peak external knee flexion moment during walking and the coronal angle of the anterior cruciate ligament graft indicates that as the anterior cruciate ligament graft is placed in a more vertical coronal orientation, patients reduce their net quadriceps usage during walking. CLINICAL RELEVANCE: This finding supports the hypothesis that graft placement plays a critical role in the restoration of normal ambulatory mechanics after anterior cruciate ligament reconstruction and thus could provide a partial explanation for the increased incidence of premature osteoarthritis at long-term follow-up in patients with anterior cruciate ligament reconstruction.