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Journal of the American Academy of Orthopaedic Surgeons 2 Interest in cartilage imaging has increased recently for many rea- sons. As the mean age of the popu- lation has risen, the incidence of osteoarthritis has increased. Articular cartilage abnormalities are common, with nearly 75% of persons over age 75 years having osteoarthritis. 1 The advent of arthroscopy has brought a greater demand for accurate preoperative evaluation. Identification of isolated articular cartilage injuries with magnetic resonance (MR) imaging prior to arthroscopy is important because articular cartilage injuries can clinically mimic meniscal tears. 2 In addition, prearthro- scopic evaluation of articular cartilage allows better prediction of prognosis for planned interventions because of the association of articular cartilage defects with a less satis- factory clinical outcome. 3 The most important reason for the increased interest in accurate imaging evaluation of articular cartilage is the development of cartilage replacement therapies. Detec- tion of articular cartilage defects is necessary to identify patients for whom such therapies are appropriate. Magnetic resonance imaging allows surgeons to evaluate treatment options on the basis of knowl- edge of the size and location of articular cartilage derangements before arthroscopy or surgery. Further- more, MR imaging offers the potential for follow-up of patients in trials of these new cartilage replacement therapies. A noninvasive alternative for articular cartilage evaluation is important because these patients are often unwilling to undergo follow- up arthroscopy to determine success of treatment. The ability to visualize articular cartilage with MR imaging has advanced with the development of new sequences, receiver coils, and gradient technology, which have improved image quality, spatial resolution, and speed of imaging. 4 These improvements have resulted in the ability to use MR imaging to detect moderate- and high-grade articular cartilage abnormalities with a high degree of accuracy. Cartilage Structure and Function The structure of hyaline cartilage is critical to its function. Understand- ing this structure helps explain the imaging appearance of normal and abnormal cartilage and has been essential to the development of new imaging techniques. Normal articular cartilage is composed of hyaline cartilage. Chondrocytes account for 1% of Dr. McCauley is Associate Professor of Diagnostic Radiology and Chief of MRI, Yale University School of Medicine, New Haven, Conn. Dr. Disler is Associate Clinical Pro- fessor of Radiology, Virginia Commonwealth University, Richmond, and is in private prac- tice with Commonwealth Radiology, Richmond. Reprint requests: Dr. McCauley, Diagnostic Radiology, Yale University School of Medicine, Box 208042, 333 Cedar Street, New Haven, CT 06520-8042. Copyright 2001 by the American Academy of Orthopaedic Surgeons. Abstract Recently developed magnetic resonance (MR) imaging techniques allow accurate detection of moderate- and high-grade articular cartilage defects. There has been increased interest in MR imaging of articular cartilage in part because it is useful in identifying patients who may benefit from new articular cartilage replacement therapies, including chondrocyte transplantation, improved techniques for osteochondral transplantation, chondroprotective agents, and cartilage growth stimulation factors. The modality also has the potential to play an important role in the follow-up of patients during and after treatment. Detection of articular cartilage defects is beneficial for patients undergoing arthroscopy for other injuries, such as meniscal tears, because the presence of articular cartilage injury worsens prognosis and may modify therapy options. J Am Acad Orthop Surg 2001;9:2-8 Magnetic Resonance Imaging of Articular Cartilage of the Knee Thomas R. McCauley, MD, and David G. Disler, MD Perspectives on Modern Orthopaedics Thomas R. McCauley, MD, and David G. Disler, MD Vol 9, No 1, January/February 2001 3 hyaline cartilage volume; a hydro- philic matrix, which is 80% water, constitutes the remaining 99% of cartilage volume. The matrix serves three major functions: providing a nearly frictionless surface, distrib- uting forces to underlying subchondral bone with little deforma- tion, and transporting nutrients to the chondrocytes. 5 After water, the two largest constituents of the hyaline cartilage matrix are collagen (which makes up 60% of the dry weight of cartilage) and proteoglycan aggregates (30% of the dry weight). 5 Collagen provides the structural framework, tensional stability, and covering surface of cartilage. Proteoglycan aggregates are extremely large macromole- cules that contain many hydroxyl and negatively charged moieties. These attract water and cations, thereby creating osmotic, ionic, and Donnan forces that result in a swelling pressure in the collagen framework, which resists compression. 6 There is a highly ordered structure to the collagen in cartilage, which is critical to its biomechanical function. This structure can be divided into four zones, or laminae, on the basis of the collagen orientation seen microscopically. 7 The most superficial portion of the cartilage is the tangential zone, which contains collagen fibers oriented parallel to the articular surface. The second, or transitional, zone contains fibers oriented oblique to the cartilage surface. In the third, or radial, zone, the fibers are oriented perpendicular to the cartilage surface and are thicker than in the more superficial zones. The fourth zone, the zone of calcified cartilage, is present at the interface of the cartilage with the underlying bone. The arcadelike configuration of the collagen fibers provides even dis- tribution of forces to underlying bone and resists shearing forces. The swelling pressure created by the proteoglycans provides the main resistance to compressive loads. 6 The biomechanical properties of cartilage are lost when there is damage to this highly ordered structure. Cartilage Damage and Repair Osteoarthritis and trauma are the most common causes of cartilage damage. Inflammatory arthritis is less common. There are three stages of osteoarthritis. 8 In the first stage, there is disruption of the collagen framework with softening associated with decreased proteoglycan content and increased water content. In the second stage, there is repair with proliferation of chondrocytes and increased anabolic activity. Thickening of cartilage may occur in this stage; however, the thickened cartilage has abnormal mechanical properties. In the third stage, the repair mechanisms can no longer be sustained, and decreased cellular proliferation and anabolic activity of the chondrocytes occurs, resulting in articular cartilage loss, fibril- lation, erosion, and cracking. 8 When articular cartilage defects form due to osteoarthritis or trauma, there may be repair; however, normal hyaline cartilage does not re- generate. Repair generally does not occur when there are partial- thickness cartilage defects, as the repair response is usually initiated only with damage extending to subchondral bone, as occurs in full- thickness defects. 6 Full-thickness defects initiate repair by filling with fibrin clot and inflammatory cells, which release growth factors and other proteins that stimulate repair. Unfortunately, fibrocartilage usually only partially fills the defects in the articular cartilage surface. The fibrocartilage does not have the same mechanical properties as normal hyaline cartilage because of abnormal collagen structure and because of produc- tion of smaller chain lengths and smaller amounts of proteoglycan aggregates, which decreases the attraction for water. The fibrocartilage usually begins to degenerate within a year after formation because of its abnormal biomechanical properties. 6 Pain is not directly caused by cartilage damage because articular cartilage is aneural. Cartilage abnormalities and associated bone abnormalities likely cause forces that act on the subchondral bone, joint capsule, menisci, and other supporting structures of the joint, resulting in pain. 9 MR Imaging of Articular Cartilage The accuracy of articular cartilage assessment with MR imaging has greatly improved with the recent development of imaging sequences designed specifically for hyaline cartilage. The two most widely used imaging techniques are the T1- weighted fat-suppressed three- dimensional spoiled gradient-echo technique and the T2-weighted fast spin-echo technique. Cartilage is well visualized with these techniques due to the differences in T1 and T2 between articular cartilage and fluid. Cartilage is higher in signal intensity than fluid on T1- weighted images and is lower in signal intensity than fluid on T2- weighted images. Magnetic resonance arthrography with injection of contrast material into the joint is not generally necessary for articular cartilage evaluation. The accuracy of MR arthrography has not been found to be higher than that of imaging techniques that do not entail contrast injection. 10,11 However, MR arthrography is useful in a subset of patients for whom assessment of MR Imaging of Articular Cartilage of the Knee Journal of the American Academy of Orthopaedic Surgeons 4 cartilage integrity over osteochondral defects 12 or identification of loose bodies is necessary. 13 The fat-suppressed three-dimensional spoiled gradient-echo sequence provides high accuracy, with a sensitivity of 86%, specificity of 97%, and accuracy of 91% for detection of cartilage lesions in the knee (data are for detection of cartilage lesions excluding softening without cartilage loss) 2 (Figs. 1–3). T2-weighted fast spin-echo techniques, both without and with fat suppression, have recently been shown to result in similarly high accuracy, with a sensitivity of 87%, specificity of 94%, and accuracy of 92% 14,15 (Fig. 2). As with other MR techniques, accuracy is highest in the patellofemoral joint, likely due to the thickness of the patellar cartilage. 2 In addition, high-grade abnormalities with thinning or focal defects in cartilage are detected with greater accuracy than low-grade cartilage abnormalities, in which there is little or no loss of cartilage thickness. 2 The two imaging techniques have different advantages and dis- advantages. The T2-weighted fast spin-echo technique is less suscep- tible to metal artifacts, which can be an advantage when imaging patients after surgery. The fat-suppressed three-dimensional spoiled gradient- echo sequence provides thinner sections, which has been found advan- tageous in identifying morphologic defects. T2-weighted sequences can better visualize signal abnormalities within cartilage and thus may allow detection of lower grades of cartilage abnormality, especially in the patellar cartilage (Fig. 4). These two techniques for detection of defects have not yet been directly com- pared. Neither has the ability of these techniques to accurately measure the area of defects, which can influence selection of cartilage replacement therapies, been investigated. Both the fat-suppressed three- dimensional spoiled gradient-echo technique and the T2-weighted fast spin-echo technique have been val- idated in patients at 1.5 T. 2,14,15 Lower accuracies would be expected at lower field strengths because of the lower signal-to-noise ratio available at those field strengths, 16 along with decreased reliability or unavailability of fat suppression. No direct comparison has been per- formed at different field strengths; however, in a recent study, 17 the accuracy of evaluation of cadaveric patellar articular cartilage at 0.2 T A B C D Figure 1 Full-thickness traumatic articular cartilage defect in the knee of a 14-year-old soccer player seen on fat-suppressed three-dimensional spoiled gradient-echo images. Cartilage appears as high signal intensity; fluid and other tissues appear as low signal intensity. A, Sagittal image (repetition time [TR] = 60 msec; echo time [TE] = 5 msec) shows articular cartilage defect in the lateral femoral condyle at the trochlear groove (solid arrow). Note low-signal lamina due to truncation artifact in adjacent normal cartilage (open arrow). B, Sagittal image (TR/TE = 60/5) obtained lateral to A shows cartilage frag- ment in suprapatellar recess (arrow). C, Surface rendering of the defect from an anterior perspective, created from the three-dimensional image set. D, Arthroscopic image of trochlear groove as seen from below confirms the presence of the articular cartilage defect seen with MR imaging. (Part A reproduced with permission from Disler DG, McCauley TR, Wirth CR, Fuchs MD: Detection of knee hyaline cartilage defects using fat-suppressed three-dimensional spoiled gradient-echo MR imaging: Comparison with standard MR imaging and correlation with arthroscopy. AJR Am J Roentgenol 1995;165:377-382. Parts C and D reproduced with permission from McCauley TR, Disler DG: MR imaging of articular cartilage. Radiology 1998;209:629-640.) Thomas R. McCauley, MD, and David G. Disler, MD Vol 9, No 1, January/February 2001 5 was lower than that obtained in evaluation of patellar cartilage with 1.5-T magnets. 2 In addition to high- quality equipment, the appropriate pulse sequences and imaging pa- rameters must be used (Table 1). In our experience, radiologists are better able to identify articular cartilage injuries with increased experience, including feedback based on arthroscopic findings from re- ferring orthopaedic surgeons. A number of factors may influence the appearance of articular cartilage at MR imaging. Articular cartilage has uniform high signal intensity on fat-suppressed three- dimensional spoiled gradient-echo images 2 ; however, artifactual low- signal laminae may be visualized in the center of cartilage due to truncation artifact 18 (Fig. 1). This artifact occurs due to undersampling of signal from small objects with high contrast. The location and appearance of truncation artifact is pre- dictable. Truncation artifact can be decreased by increasing the in- plane resolution; however, increasing resolution typically increases imaging time. This artifact is usually easily recognized and does not im- pede visualization of cartilage defects; it can even be helpful in de- termining the depth of the defects. High-resolution T2-weighted MR imaging can demonstrate a nonarti- factual laminar signal-intensity pat- tern in cartilage, predominantly due to the laminar structure of the collagen fiber orientation. 19,20 The size and signal intensity of the laminae can vary with changes in imaging variables and with changes in orientation of the cartilage with respect to the magnetic field. The latter variation is due to the anisotropy of the collagen fibers in the various layers of the cartilage. 19 Experienced read- ers can recognize normal variation in the laminar appearance and there- fore are not hindered in the detection of cartilage damage. Clinical Importance of Cartilage Imaging The ability to accurately evaluate articular cartilage with MR imaging can provide more complete information with which to make thera- peutic decisions. Articular cartilage injury in the knee is common; in one study, 2 it was visualized on MR images of 32 (67%) of 48 patients who subsequently underwent arthroscopy of the knee. In that study, two thirds of the patients with articular cartilage defects had concur- rent meniscal tears or ligament injuries; however, one third had isolated articular cartilage injuries. Detection of articular cartilage defects with MR imaging can explain symptoms in patients with isolated articular cartilage injuries that might otherwise have eluded Figure 2 Images depicting a near-full-thickness articular cartilage defect in the medial femoral condyle in a 28-year-old man with chronic knee pain. No other abnormality was found in the knee at arthroscopy. A, Sagittal fat-suppressed three-dimensional spoiled gradient-echo image (TR/TE = 40/6) shows a defect (arrow) containing fluid, which appears as low signal intensity. B, Coronal T2-weighted fast spin-echo image (TR/TE = 4,000/96) shows the same defect (arrow) containing fluid, which appears as high signal intensity. A B Figure 3 Sagittal fat-suppressed three-dimensional spoiled gradient-echo images (TR/TE = 40/6) of a 17-year-old girl 1 year after osteochondral transplantation to repair a femoral articular cartilage defect. A, Image obtained at the site of osteochondral plug placement (arrow) shows slight depression of the articular surface. B, Image obtained at the donor site along the lateral margin of the intercondylar notch depicts filling with intermediate- signal-intensity tissue, likely representing repair tissue in the osteochondral defect (arrow). A B MR Imaging of Articular Cartilage of the Knee Journal of the American Academy of Orthopaedic Surgeons 6 detection. Identification of articular cartilage injury with MR imaging in patients with intact menisci is especially useful because symptoms due to isolated cartilage defects often mimic those due to meniscal tears. 2 Identification of cartilage damage is important in patients with associated injuries because the presence of defects can worsen the prognosis after arthroscopic surgery. 3 Iden- tification of defects also facilitates preoperative planning for articular cartilage replacement therapies. Future Developments Currently available techniques allow detection of morphologic defects in articular cartilage with high accuracy. However, low-grade injuries with internal cartilage damage without morphologic change are not accurately visualized. 21 A number of MR techniques for detection of cartilage damage at early stages are being developed. First, Brossmann et al 22 reported that a technique utilizing ultra-short echo times resulted in 100% sensitivity and specificity for detection of cartilage defects with sta- tistically significant higher accuracy than that obtained with a fat- suppressed three-dimensional spoiled gradient-echo technique in a study of 10 human cadaveric patellae. The authors hypothesized that the high sensitivity of this technique was due to signal changes related to disorgani- zation of collagen fibers. Another group has used short-echo-time ac- quisitions to obtain proton spectra in articular cartilage, which has the potential to provide more detailed analysis of biochemical information. 23 Second, imaging techniques are being developed that use magnetization transfer contrast. Magnetiza- tion transfer contrast is dependent predominantly on collagen integrity in cartilage. 24 Unfortunately, these techniques have not yet been found to be superior to other routinely available MR imaging techniques. Third, ionic gadolinium contrast material is being used for detection of early biochemical changes with cartilage degeneration. 25 The contrast medium is introduced into the joint by either direct or intravenous injection. In normal cartilage, the negative charges of proteoglycan aggregates exclude the negatively charged gadolinium chelate. Be- cause proteoglycans are lost early in cartilage degeneration, increased amounts of the negatively charged gadolinium can gain entry into de- generating cartilage, with resulting signal enhancement. A study of cadaveric patellar cartilage found A B Figure 4 Images of a patellar cartilage abnormality due to osteoarthritis in a 46-year-old man. A, Fat-suppressed three-dimensional spoiled gradient-echo image (TR/TE = 40/6) shows cartilage abnormality as decreased signal intensity in the normally high-signal- intensity cartilage with associated surface irregularity (arrows). B, Abnormality is more clearly seen on T2-weighted axial image (TR/TE = 2,000/80) of patella, where it is depicted as increased internal signal within the normally low-signal-intensity cartilage (arrows). (Reproduced with permission from McCauley TR, Disler DG: MR imaging of articular cartilage. Radiology 1998;209:629-640.) Table 1 Suggested Protocols for Articular Cartilage Imaging 2,4,14,15 * Fat-Suppressed Three-Dimensional Technique Spoiled Gradient-Echo Fast (Turbo) Spin-Echo Pulse sequence TR = 30-50 msec; TE = TR = 3,500-5,000 msec; <10 msec (minimum TE = 30-54 msec; echo full echo); 40° flip angle train length = 8-10 Tissue contrast Fat suppression or Fat suppression pref- water excitation erable Field of view, cm 14 12-14 Acquisition matrix 160 × 256 256-512 × 256-384 Section description 1.5-mm sections, 3.5- to 4.0-mm sections; 60 locations gap = 0 to 1 mm Number of excitations 0.75 or 1 2 * Sagittal and axial planes are most useful. Three-dimensional images can be reformatted to obtain high-quality axial images. Thomas R. McCauley, MD, and David G. Disler, MD Vol 9, No 1, January/February 2001 7 that use of gadolinium allowed detection of loss of proteoglycans from mechanically intact articular cartilage, while changes in T2 in cartilage could be used to detect mechanical damage. 26 Fourth, MR imaging of sodium rather than hydrogen has been investigated as a potential method for evaluation of proteoglycan content in articular cartilage. 27 Imaging techniques that detect early biochemical changes can facilitate identification of cartilage abnormalities before morphologic abnormalities occur, which may allow chondroprotective interventions before loss of the morphologic integrity of cartilage occurs. Another area of ongoing development takes advantage of the three-dimensional information available with MR imaging of articular cartilage. Surface models of articular cartilage can be created from MR imaging data sets (Fig. 1, C). Measure- ment of cartilage volume with MR imaging has been shown to be very accurate 28 and may allow quantifi- cation of the progression of arthritis. Studies of the configuration of cartilage surfaces may also provide information on the influence of cartilage configuration on the progression of osteoarthritis. A critical area for future development is the imaging of cartilage after treatment (Fig. 3). Studies of both the normal appearance after repair and the pathologic changes that reflect complications are ongoing. The results of these studies will likely lead to the use of MR imaging as a noninvasive technique for following the results of articular cartilage replacement therapies. Summary New commercially available MR imaging techniques can be used to accurately detect moderate- and high-grade cartilage defects. These techniques have been shown to be highly accurate when images are obtained with state-of-the art equipment and are interpreted by experienced musculoskeletal radiologists. Detection of articular cartilage defects provides useful information on which to base treatment selection, which is increasing in importance because of the ad- vancements in therapies for cartilage damage. In addition, accurate serial assessment of lesions after treatment will facilitate evaluation of these therapies. In the future, MR imaging will likely have an important role in the understand- ing and evaluation of cartilage degeneration and repair, and development of new techniques will increase our ability to accurately assess both morphologic and biochemical abnormalities in articular cartilage. References 1. Lawrence RC, Hochberg MC, Kelsey JL, et al: Estimates of the prevalence of selected arthritic and musculoskeletal diseases in the United States. J Rheumatol 1989;16:427-441. 2. 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