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Editorial
 Magnetic Resonance Imaging of Articular Cartilage: Toward a Redefinition of "Primary" Knee Osteoarthritis and Its Progression JEAN-PIERRE RAYNAULD, MD, FRCPC, Head, Osteoarthritis Clinical Research Program, Montreal Rheumatology Institute and Centre Hospitalier de l'Université de Montréal — Hôpital Notre-Dame, Assistant Professor, Department of Medicine, University of Montréal, Montréal, Québec, Canada. Address reprint requests to Dr. J-P. Raynauld, Osteoarthritis Research Unit, 1551 East Ontario St., Montreal, Quebec, Canada H2L 1S6. Assessment of structural damage of the articular cartilage is important for monitoring the progression of osteoarthritis (OA) and evaluating therapeutic response. For years, clinical studies of drug interventions for symptomatic knee OA have focused mainly on clinical variables such as pain and joint function using self-administered questionnaires like the WOMAC1 but without assessing the effect of treatment on structural changes caused by the disease or the role of treatment in preventing cartilage degradation. Recently, attempts have been made to evaluate cartilage damage and its progression in OA. Serial radiographs of affected joints appear to be a logical means of documenting the progression of OA over time, providing that a validated, reliable, and easily reproducible technique is used2. Although improvements in the standardization and interpretation of radiographs have produced good measures of the joint space width (JSW) and the progression of joint space narrowing3,4, the sensitivity to change of this measure is such that a minimum followup of 2 years in large numbers of patients are necessary to establish an effect of pharmacological interventions on OA progression. Moreover, measurement of JSW does not capture information on the cartilage changes alone but is also dependent on integrity of surrounding tissue, especially the meniscus. For instance, enucleation of the knee internal meniscus, which may occur during longitudinal studies, can dramatically change the JSW and affect the reliability of such measurement5, potentially impairing its use in the assessment of cartilage degradation over time. Finally, JSW progression provides only one measurement point, which considerably restricts the statistical power of this technique and gives no indication of cartilage volume and only an approximate measure of the overall thickness of the articular cartilage. The use of arthroscopy to assess a larger area of cartilage appears reliable and sensitive to change at one year6. However, only the cartilage surface can be evaluated; moreover, the method is semiquantitative and, above all, invasive. Large studies are, therefore, difficult to conduct. Magnetic resonance imaging (MRI) allows precise visualization of joint structures such as cartilage, bone, synovium, ligaments, and meniscus and their pathological changes. MRI acquisitions are noninvasive and nonradiant, providing a clear advantage over arthroscopy and fluoroscopy. Recent advances in this technology have led to significant improvement in spatial resolution and contrast, enabling researchers to evaluate anatomical damage of all these joint structures across both cross-sectional and longitudinal planes. Although anatomical changes can be seen, quantification of these changes has long been the real challenge. Initial attempts at quantitative measurement of cartilage were possible only in healthy subjects7 or in animal models8. Recently, improvement in image analysis led to reliable quantitative measurement of cartilage volume and thickness. Methods for measuring cartilage volume for the complete joint (femur and tibia) are now under evaluation for measuring the status of the knee cartilage over time. Research teams are using specific MRI acquisitions combined with semiautomated computer software to obtain valuable information on cartilage volume in healthy subjects and patients with OA9-11. Moreover, standard cartilage views can be anatomically segmented, allowing evaluation of cartilage volume and thickness in anatomical subregions and specific focal defects, since OA progression is more likely to be localized to specific areas. Studies are now under way to validate this MRI technology for the assessment of change in cartilage volume of the knee over time in OA patients, and to correlate the changes with standardized radiographic analytic tools and validated clinical variables. Obviously, the main reason for quantifying cartilage thickness and volume in OA is to evaluate medications that may slow down cartilage degradation, so-called "chondroprotective" agents. However, to be practical in clinical research, such MR technology must be based on conventional MR acquisitions using variables that are easily reproducible by any conventional MR machine. The technology is then exportable to other centers with comparable MR facilities and can be used in multicenter trials. Moreover, because of the pain in patients with OA, image acquisition should preferably be completed quickly, but without losing image quality. This is critical for analysis of disease progression over time. MRI should hopefully reduce the number of patients needed, improve retention of these patients, and reduce the overall costs and the length of clinical trials related to OA. Another advantage, compared with conventional imaging technologies, is the ability of MR images to assess all the joint structure, including the cartilage, menisci, synovial tissue, and ligaments. For example, MRI evaluation of cartilage loss can visualize other structures such as meniscal damage or misalignment. In this issue of The Journal12, Cicuttini, et al suggest there was more cartilage loss over time in patients who underwent partial meniscectomy. Their results suggest the strong role of the meniscal apparatus in protecting cartilage, especially in elderly or obese subjects, or those with joint instability. What is not known is whether this is a population at risk that would benefit from the "chondroprotective" agents or whether we should avoid treating a disease course that may be relentless. The implication of the MRI findings about the cartilage and the surrounding tissues may also influence the definition of "primary" OA in the future. The American College of Rheumatology criteria of the primary OA of the knee13 are actually based on clinical and/or radiological findings. Since the cartilage is not vascularized or innervated, the pain experienced in OA is likely to originate from bone, synovial capsule, or ligament damage. "Pure" anatomical cartilage loss over time, if considered to define primary OA, may not be reflected by changes in symptoms, may precede radiological changes considerably, and may be accelerated by unsuspected concomitant meniscal damage. The future of OA research pertaining to anatomical damage and its prevention or repair is similar to the experience in osteoporosis many years ago: significant bone loss was necessary to "see" osteoporosis on plain radiographs. With the advent of osteodensitometry, very small changes of bone mass could be detected. This outcome tool opened the door to clinical research on new therapies to slow or prevent bone mass loss. We know the effect of these medications on osteoporosis today. Similarly, quantification of cartilage loss over time will improve the monitoring of OA and possibly help us develop new interventions to prevent this extremely prevalent disease. 1. Bellamy N, Buchanan WW, Goldsmith H, et al. Validation study of the WOMAC. A health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol 1988;15:1833-40. [MEDLINE] 2. Altman RD, Fries JF, Bloch DA, et al. Radiographic assessment of progression in osteoarthritis. Arthritis Rheum 1987;30:1214-25. [MEDLINE] 3. Buckland-Wright JC. Quantitative radiography of osteoarthritis. Ann Rheum Dis 1994;53:268-75. [MEDLINE] 4. Lequesne M, Glimet T, Masse JP, Orvain J. Speed of the joint narrowing in primary medical osteoarthritis of the knee over 3-5 years. Osteoarthritis Cartilage 1998;1:23. 5. Adams JG, McAlindon T, Dimasi M, Carey J, Eustace S. Contribution of meniscal extrusion and cartilage loss to joint space narrowing in osteoarthritis. Clin Radiol 1999;54:502-6. [MEDLINE] 6. Ayral X, Gueguen A, Ike RW, et al. Inter-observer reliability of the arthroscopic quantification of chondropathy of the knee. Osteoarthritis Cartilage 1998;6:160-6. [MEDLINE] 7. Eckstein F, Westhoff J, Sittek H, et al. In vivo reproducibility of three-dimensional cartilage volume and thickness measurements with MR imaging. AJR Am J Roentgenol 1998;170:593-7. [MEDLINE] 8. Calvo E, Palacios I, Delgado E, et al. High-resolution MRI detects cartilage swelling at the early stages of experimental osteoarthritis. Osteoarthritis Cartilage 2001;9:463-72. [MEDLINE] 9. Burgkart R, Glaser C, Hyhlik-Durr A, Englmeier KH, Reiser M, Eckstein F. Magnetic resonance imaging-based assessment of cartilage loss in severe osteoarthritis: accuracy, precision, and diagnostic value. Arthritis Rheum 2001;44:2072-7. [MEDLINE] 10. Peterfy CG, van Dijke CF, Janzen DL, et al. Quantification of articular cartilage in the knee with pulsed saturation transfer subtraction and fat-suppressed MR imaging: optimization and validation. Radiology 1994;192:485-91. [MEDLINE] 11. Raynauld JP, Pelletier JP, Beaudoin G, et al. Two-year study in osteoarthritis patients: following the progression of the disease by magnetic resonance imaging using a novel quantification imaging system [abstract]. European Congress of Rheumatology, EULAR 2002, Stockholm, Sweden, June 12-15, 2002: Abstract SAT0253. 12. Cicuttini FM, Forbes A, Yuanyuan W, Rush G, Stuckey SL. Rate of knee cartilage loss after partial meniscectomy. J Rheumatol 2002;29:1954-6. 13. Altman RD, Asch E, Bloch DA, et al. Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Arthritis Rheum 1986;29:1039-49. [MEDLINE]
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