The in vivo pathomechanics of osteoarthritis (OA) at the knee is described in a framework that is based on an analysis of studies describing assays of biomarkers, cartilage morphology, and human function (gait analysis). The framework is divided into an Initiation Phase and a Progression Phase. The Initiation Phase is associated with kinematic changes that shift load bearing to infrequently loaded regions of the cartilage that cannot accommodate the loads. The Progression Phase is defined following cartilage breakdown. During the Progression Phase, the disease progresses more rapidly with increased load. While this framework was developed from an analysis of in vivo pathomechanics, it also explains how the convergence of biological, morphological, and neuromuscular changes to the musculoskeletal system during aging or during menopause lead to the increased rate of idiopathic OA with aging. Understanding the in vivo response of articular cartilage to its physical environment requires an integrated view of the problem that considers functional, anatomical, and biological interactions. The integrated in vivo framework presented here will be helpful for the interpretation of laboratory experiments as well as for the development of new methods for the evaluation of OA at the knee.

The response of healthy and diseased cartilage of the knee to the mechanics of walking is examined, with the goal of providing insight into the relationship between the kinematics and kinetics of the knee during walking and the maintenance of cartilage health. The combination of information from three-dimensional thickness models of cartilage derived from magnetic resonance imaging and the analysis of the interaction between load at the knee and kinematic changes during walking associated with loss of the anterior cruciate ligament demonstrated the importance of considering walking mechanics as an important factor in the initiation and progression of osteoarthritis. In particular, this material suggests that knee cartilage becomes conditioned to loading and to the large number of repetitive cycles of loading that occur during walking and that healthy cartilage homeostasis is maintained as long as there are no changes to the normal patterns of locomotion, the structure of the knee joint, or cartilage biology. Thus, there is the potential for a degenerative pathway to be initiated when a condition such as anterior cruciate ligament injury causes the repetitive loading during walking to shift to a new location. The sensitivity of cartilage to the kinematic changes is illustrated with the anterior cruciate ligament-deficient knee and the regional variations in cartilage morphology. The material presented here supports the conclusion that individual variations in the range of loading and kinematics at the knee during walking can have a profound influence on the initiation and progression of osteoarthritis of the knee.

This review examines a mechanism for the initiation of osteoarthritis after anterior cruciate ligament (ACL) injury by considering the relationship between reported ambulatory changes after ACL injury, cartilage adaptation to load, and the association between cartilage loads during walking and regional variations in cartilage structure and biology. Taken together, these observations suggest that cartilage degeneration after ACL injury could be caused by a kinematic gait change that shifts ambulatory loading applied to cartilage. Such a shift may cause regions of cartilage to become newly loaded, be subjected to altered levels of compression and tension, or become unloaded. The metabolic sensitivity of chondrocytes to such changes in their mechanical environment, combined with the low adaptation potential of mature cartilage, could lead to cartilage degeneration and premature osteoarthritis after ACL injury. This proposed mechanism demonstrates the value of using the ACL injury model to understand the relationship between mechanics and biology, as well as helping to explain the importance of restoring normal ambulatory kinematics after ACL injury to avoid premature osteoarthritis.

We examined the relationship between specific gait changes after anterior cruciate ligament injury and the progression of osteoarthritis at the knee. The study was done using a finite-element model derived from subject specific three-dimensional cartilage volumes created from magnetic resonance images. Cartilage thinning was predicted using an iterative algorithm based on the octahedral shear stress. Simulations were done for a knee with normal alignment and for a knee with an internal tibial rotation offset, as associated with anterior cruciate ligament deficiency. For the healthy knee, the model predicted patterns of cartilage thinning consistent with a previous clinical report of idiopathic osteoarthritis. For the ACL-deficient scenario the model predicted a more rapid rate of cartilage thinning throughout the knee, especially in the medial compartment. The results suggest that the progression of osteoarthritis after anterior cruciate ligament injury is associated with a shift in the normal load bearing regions of the knee joint during normal function due to kinematic changes, and highlight the importance of restoring proper gait during anterior cruciate ligament reconstruction.

A rule-based approach can substantially increase inter-observer reproducibility when measuring cartilage thickness from multiple observers. This improvement in inter-observer reproducibility could be an important consideration for longitudinal studies of disease progression. In quantifying cartilage thickness, central and weight bearing regions on each condyle can provide more accurate measurement than boundary and non-weight bearing regions with average accuracy of +/-0.2-0.3 mm. An important finding of this study was that the weight bearing regions, which are usually of the greatest clinical interest, were measured most accurately by sagittal plane imaging.

OBJECTIVE-MRI is the most accurate noninvasive method available to diagnose disorders of articular cartilage. Conventional 2D and 3D approaches show changes in cartilage morphology. Faster 3D imaging methods with isotropic resolution can be reformatted into arbitrary planes for improved detection and visualization of pathology. Unique contrast mechanisms allow us to probe cartilage physiology and detect changes in cartilage macromolecules. CONCLUSION-MRI has great promise as a noninvasive comprehensive tool for cartilage evaluation.Keywords balanced steady-state free precession imaging; bSSFP; cartilage; joint imaging; MRI; osteoarthritis; rapid imaging Articular cartilage pathology may be the result of degeneration or acute injury. Osteoarthritis is an important cause of disability in our society [1][2][3][4][5][6] and is marked by degeneration of articular cartilage [7][8][9]. Acute injury to cartilage can be characterized using MRI [10]. Whether the result is from degeneration or injury, MRI offers a noninvasive means of assessing the degree of damage to cartilage and adjacent bone and of measuring the effectiveness of treatment [11].Many imaging methods are available to assess articular cartilage. Conventional radiography can be used to detect gross loss of cartilage, evident as narrowing of the distance between the two adjacent bones of a joint [12], but it does not image cartilage directly. Secondary changes such as osteophyte formation can be seen, but conventional radiography is insensitive to early chondral damage. Arthrography, alone or combined with conventional radiography or CT, is mildly invasive and provides information limited to the contour of the cartilage surface [13]. MRI, with its excellent soft-tissue contrast, is the best imaging technique currently available for the assessment of articular cartilage [14][15][16][17][18][19]. Imaging regions of cartilage damage has the potential to provide morphologic information, such as fissuring and the presence of partial-or full-thickness cartilage defects. Cartilage lesions on MRI are often graded on a modified Outerbridge or Noyes scale, corresponding to arthroscopic grading [20][21][22]. A common grading scale is shown in Table 1. In addition to morphologic assessment, the many tissue © American Roentgen Ray Society Address correspondence to G. E. Gold (gold@stanford.edu).. An ideal MRI study for cartilage should provide accurate assessment of cartilage thickness and volume, show morphologic changes of the cartilage surface, show internal cartilage signal changes, and allow evaluation of the subchondral bone for signal abnormalities. Also, it would be desirable for MRI to provide an evaluation of the underlying cartilage physiology, including providing information about the status of the glycosaminoglycan (GAG) and collagen matrices. Conventional MRI sequences do not provide a comprehensive assessment of cartilage, lacking either in spatial resolution or specific information about cartilage physiology. NIH Public Access Conventional MRI Met...

The purpose of this study was to test the hypothesis of whether the center of rotation (COR) in the transverse plane of the knee is in the medial side during normal walking in a manner similar to that previously described during non-ambulatory activities. The kinematics for normal knees was obtained from 46 knees during normal walking using the point cluster technique. The center of rotation of the medial-lateral axis of the femur relative to the tibia was determined during the stance phase of walking. The hypothesis that the COR is in the medial side during stance was not supported by this study. The average center of rotation during the stance phase of walking was in the lateral compartment for all 46 knees. In addition, the instantaneous COR occurred on the medial side on average less than 25% of the time during the stance phase. Thus, while the COR is predominantly on the lateral side of the knee during walking, the normal function of the knee during walking is associated with both lateral and medial pivoting. These results also demonstrate the importance of describing knee kinematics in the context of a specific activity or the constraints of the test conditions.

Cartilage contact geometry, along with joint loading, can play an important role in determining local articular cartilage tissue stress. Thus individual variations in cartilage thickness can be associated with both individual variations in joint loading associated with activities of daily living as well as individual differences in the anatomy of the contacting surfaces of the joint. The purpose of this study was to isolate the relationship between cartilage thickness predicted by individual variations in contact surface geometry based on the radii of the femur and tibia vs. cartilage thickness predicted by individual variations in joint loading. Knee magnetic resonance (MR) images and the peak knee adduction moments during walking were obtained from 11 young healthy male subjects (age 30.5+/-5.1 years). The cartilage thicknesses and surface radii of the femoral and tibial cartilage were measured in the weight-bearing regions of the medial and lateral compartments of three-dimensional models from the MR images. The ratio of contact pressure between the medial and lateral compartments was calculated from the radii of tibiofemoral contact surface geometries. The results showed that the medial to lateral pressure ratios were not correlated with the medial to lateral cartilage thickness ratios. However, in general, pressure was higher in the lateral than medial compartments and cartilage was thicker in the lateral than medial compartments. The peak knee adduction moment showed a significant positive linear correlation with medial to lateral thickness ratio in both femur (R(2)=0.43,P<0.01) and tibia (R(2)=0.32,P<0.01). The results of this study suggest that the dynamics of walking is an important factor to describe individual differences in cartilage thickness for normal subjects.