Selective Enzymatic Digestion of Proteoglycans and Collagens Alters Cartilage T1rho and T2 Relaxation Times.

Our objective was to determine the relationship of T1rho and T2 relaxation mapping to the biochemical and biomechanical properties of articular cartilage through selective digestion of proteoglycans and collagens. Femoral condyles were harvested from porcine knee joints and treated with either chondroitinase ABC (cABC) followed by collagenase, or collagenase followed by cABC. Magnetic resonance images were acquired and cartilage explants were harvested for biochemical, biomechanical, and histological analyses before and after each digestion. Targeted enzymatic digestion of proteoglycans with cABC resulted in elevated T1rho relaxation times and decreased sulfated glycosaminoglycan content without affecting T2 relaxation times. In contrast, extractable collagen and T2 relaxation times were increased by collagenase digestion; however, neither was altered by cABC digestion. Aggregate modulus decreased with digestion of both components. Overall, we found that targeted digestion of proteoglycans and collagens had varying effects on biochemical, biomechanical, and imaging properties. T2 relaxation times were altered with changes in extractable collagen, but not changes in proteoglycan. However, T1rho relaxation times were altered with proteoglycan loss, which may also coincide with collagen disruption. Since it is unclear which matrix components are disrupted first in osteoarthritis, both markers may be important for tracking disease progression.

Activities of daily living influence tibial cartilage T1rho relaxation times.

Quantitative T1rho magnetic resonance imaging (MRI) can potentially help identify early-stage osteoarthritis (OA) by non-invasively assessing proteoglycan concentration in articular cartilage. T1rho relaxation times are negatively correlated with proteoglycan concentration. Cartilage compresses in response to load, resulting in water exudation, a relative increase in proteoglycan concentration, and a decrease in the corresponding T1rho relaxation times. To date, there is limited information on changes in cartilage composition resulting from daily activity. Therefore, the objective of this study was to quantify changes in tibial cartilage T1rho relaxation times in healthy human subjects following activities of daily living. It was hypothesized that water exudation throughout the day would lead to decreased T1rho relaxation times. Subjects underwent MR imaging in the morning and afternoon on the same day and were free to go about their normal activities between scans. Our findings confirmed the hypothesis that tibial cartilage T1rho relaxation times significantly decreased (by 7%) over the course of the day with loading, which is indicative of a relative increase in proteoglycan concentration. Additionally, baseline T1rho values varied with position within the cartilage, supporting a need for site-specific measurements of T1rho relaxation times. Understanding how loading alters the proteoglycan concentration in healthy cartilage may hold clinical significance pertaining to cartilage homeostasis and potentially help to elucidate a mechanism for OA development. These results also indicate that future studies using T1rho relaxation times as an indicator of cartilage health should control the loading history prior to image acquisition to ensure the appropriate interpretation of the data.

Determination of the Position of the Knee at the Time of an Anterior Cruciate Ligament Rupture for Male Versus Female Patients by an Analysis of Bone Bruises.

BACKGROUND: The incidence of anterior cruciate ligament (ACL) ruptures is 2 to 4 times higher in female athletes as compared with their male counterparts. As a result, a number of recent studies have addressed the hypothesis that female and male patients sustain ACL injuries via different mechanisms. The efficacy of prevention programs may be improved by a better understanding of whether there are differences in the injury mechanism between sexes. Hypothesis/Purpose: To compare knee positions at the time of a noncontact ACL injury between sexes. It was hypothesized that there would be no differences in the position of injury. STUDY DESIGN: Controlled laboratory study. METHODS: Clinical T2-weighted magnetic resonance imaging (MRI) scans from 30 participants (15 male and 15 female) with a noncontact ACL rupture were reviewed retrospectively. MRI scans were obtained within 1 month of injury. Participants had contusions associated with an ACL injury on both the medial and lateral articular surfaces of the femur and tibia. Three-dimensional models of the femur, tibia, and associated bone bruises were created via segmentation on MRI. The femur was positioned relative to the tibia to maximize bone bruise overlap, thereby predicting the bone positions near the time of the injury. Flexion, valgus, internal tibial rotation, and anterior tibial translation were measured in the predicted position of injury. RESULTS: No statistically significant differences between male and female patients were detected in the position of injury with regard to knee flexion ( P = .66), valgus ( P = .87), internal tibial rotation ( P = .26), or anterior tibial translation ( P = .18). CONCLUSION: These findings suggest that a similar mechanism results in an ACL rupture in both male and female athletes with this pattern of bone bruising. CLINICAL RELEVANCE: This study provides a novel comparison of male and female knee positions at the time of an ACL injury that may offer information to improve injury prevention strategies.

Relationship between T1rho magnetic resonance imaging, synovial fluid biomarkers, and the biochemical and biomechanical properties of cartilage.

Non-invasive techniques for quantifying early biochemical and biomechanical changes in articular cartilage may provide a means of more precisely assessing osteoarthritis (OA) progression. The goals of this study were to determine the relationship between T1rho magnetic resonance (MR) imaging relaxation times and changes in cartilage composition, cartilage mechanical properties, and synovial fluid biomarker levels and to demonstrate the application of T1rho imaging to evaluate cartilage composition in human subjects in vivo. Femoral condyles and synovial fluid were harvested from healthy and OA porcine knee joints. Sagittal T1rho relaxation MR images of the condyles were acquired. OA regions of OA joints exhibited an increase in T1rho relaxation times as compared to non-OA regions. Furthermore in these regions, cartilage sGAG content and aggregate modulus decreased, while percent degraded collagen and water content increased. In OA joints, synovial fluid concentrations of sGAG decreased and C2C concentrations increased compared to healthy joints. T1rho relaxation times were negatively correlated with cartilage and synovial fluid sGAG concentrations and aggregate modulus and positively correlated with water content and permeability. Additionally, we demonstrated the application of these in vitro findings to the study of human subjects. Specifically, we demonstrated that walking results in decreased T1rho relaxation times, consistent with water exudation and an increase in proteoglycan concentration with in vivo loading. Together, these findings demonstrate that cartilage MR imaging and synovial fluid biomarkers provide powerful non-invasive tools for characterizing changes in the biochemical and biomechanical environments of the joint.

Knee Kinematics During Noncontact Anterior Cruciate Ligament Injury as Determined From Bone Bruise Location.

BACKGROUND: The motions causing noncontact anterior cruciate ligament (ACL) injury remain unclear. Tibiofemoral bone bruises are believed to be the result of joint impact near the time of ACL rupture. The locations and frequencies of these bone bruises have been reported, but there are limited data quantifying knee position and orientation near the time of injury based on these contusions. HYPOTHESIS: Knee position and orientation near the time of noncontact ACL injury include extension and anterior tibial translation. STUDY DESIGN: Descriptive laboratory study. METHODS: Magnetic resonance images of 8 subjects with noncontact ACL injuries were acquired within 1 month of injury and were subsequently analyzed. All subjects exhibited bruises on both the femur and tibia in both medial and lateral compartments. The outer margins of bone and the bone bruise surfaces were outlined on each image to create a 3-dimensional model of each subject's knee in its position during magnetic resonance imaging (MRI position). Numerical optimization was used to maximize overlap of the bone bruises on the femur and tibia and to predict the position of injury. Flexion angle, valgus orientation, internal tibial rotation, and anterior tibial translation were measured in both the MRI position and the predicted position of injury. Differences in kinematics between the MRI position, which served as an unloaded reference, and the predicted position of injury were compared by use of paired t tests. RESULTS: Flexion angle was near full extension in both the MRI position and the predicted position of injury (8° vs 12°; P = .2). Statistically significant increases in valgus orientation (5°; P = .003), internal tibial rotation (15°; P = .003), and anterior tibial translation (22 mm; P < .001) were observed in the predicted position of injury relative to the MRI position. CONCLUSION: These results suggest that for the bone bruise pattern studied, landing on an extended knee is a high risk for ACL injury. Extension was accompanied by increased anterior tibial translation (22 mm), internal tibial rotation (15°), and valgus rotation (5°) in the predicted position of injury relative to the MRI position. CLINICAL RELEVANCE: This study provides novel data characterizing the motions associated with ACL injury, information critical to improving strategies aimed at injury prevention.