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Cartilage Imaging pp 205–211Cite as

Cartilage as a Biomarker

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Abstract

Traditionally biomarkers have been defined as biochemical substances that in addition to disease diagnosis allow classification of disease severity, risk of onset and progression, as well as assessment of the efficacy of a treatment [1]. The meaning of the generic term biomarkers, however, has been greatly expanded and applied to all detection methods used in the life sciences and may be defined as any detectable biologic parameter, whether biochemical, genetic, histologic, anatomic, physical, functional, or metabolic [2]. Development of biomarkers has been a major focus of the National Institutes of Health (NIH), in particular during the American Recovery and Reinvestment Act of 2009, and biomarkers were defined as measurements that define early biochemical and structural changes of a disease process such as osteoarthritis that may be applied as markers during longitudinal studies and provide information on disease progression. Eventually, these could be used for both preventive intervention and as preliminary indications for pathways of disease pathogenesis to guide therapeutic development (J. McGowan in http://orwh.od.nih.gov/recovery/). According to the US Food and Drug Administration (FDA), biomarkers ideally would serve as surrogate markers synonymous with primary outcome measures in definitive effectiveness trials of new therapeutic agents [3].

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References

  1. Bauer DC, Hunter DJ, Abramson SB, Attur M, Corr M, Felson D, et al. Classification of osteoarthritis biomarkers: a proposed approach. Osteoarthritis Cartilage. 2006;14(8):723–7.

    Article  PubMed  CAS  Google Scholar 

  2. Smith JJ, Sorensen AG, Thrall JH. Biomarkers in imaging: realizing radiology’s future. Radiology. 2003;227(3):633–8.

    Article  PubMed  Google Scholar 

  3. Katz R. Biomarkers and surrogate markers: an FDA perspective. NeuroRx. 2004;1(2):189–95.

    Article  PubMed  Google Scholar 

  4. Kellgren J, Lawrence J. Radiological assessment of osteoarthritis. Ann Rheum Dis. 1957;16:494–501.

    Article  PubMed  CAS  Google Scholar 

  5. Kellgren J, Jeffrey M, Ball J. The epidemiology of chronic rheumatism: atlas of standard radiographs of arthritis. Oxford, UK: Blackwell; 1963.

    Google Scholar 

  6. Kothari M, Guermazi A, von Ingersleben G, Miaux Y, Sieffert M, Block JE, et al. Fixed-flexion radiography of the knee provides reproducible joint space width measurements in osteoarthritis. Eur Radiol. 2004;14(9):1568–73.

    Article  PubMed  Google Scholar 

  7. Peterfy CG, Guermazi A, Zaim S, Tirman PF, Miaux Y, White D, et al. Whole-Organ Magnetic Resonance Imaging Score (WORMS) of the knee in osteoarthritis. Osteoarthritis Cartilage. 2004;12(3):177–90.

    Article  PubMed  CAS  Google Scholar 

  8. Hunter DJ, Lo GH, Gale D, Grainger AJ, Guermazi A, Conaghan PG. The reliability of a new scoring system for knee osteoarthritis MRI and the validity of bone marrow lesion assessment: BLOKS (Boston Leeds Osteoarthritis Knee Score). Ann Rheum Dis. 2008;67(2):206–11.

    Article  PubMed  CAS  Google Scholar 

  9. Kornaat PR, Ceulemans RY, Kroon HM, Riyazi N, Kloppenburg M, Carter WO, et al. MRI assessment of knee osteoarthritis: Knee Osteoarthritis Scoring System (KOSS)–inter-observer and intra-observer reproducibility of a compartment-based scoring system. Skeletal Radiol. 2005;34(2):95–102.

    Article  PubMed  Google Scholar 

  10. Recht M, Kramer J, Marcelis S, Pathria M, Trudell D, Haghigi P, et al. Abnormalities of articular cartilage in the knee: analysis of available MR techniques. Radiology. 1993;187:473–8.

    PubMed  CAS  Google Scholar 

  11. Recht M, Piraino D, Paletta G, Schils J, Belhobek G. Accuracy of fat-suppressed three-dimensional spoiled gradient-echo FLASH MR Imaging in the detection of patellofemoral articular cartilage abnormalities. Radiology. 1996;198:209–12.

    PubMed  CAS  Google Scholar 

  12. Stahl R, Luke A, Ma CB, Krug R, Steinbach L, Majumdar S, et al. Prevalence of pathologic findings in asymptomatic knees of marathon runners before and after a competition in comparison with physically active subjects-a 3.0 T magnetic resonance imaging study. Skeletal Radiol. 2008;37(7):627–38.

    Article  PubMed  Google Scholar 

  13. Eckstein F, Ateshian G, Burgkart R, Burstein D, Cicuttini F, Dardzinski B, et al. Proposal for a nomenclature for magnetic resonance imaging based measures of articular cartilage in osteoarthritis. Osteoarthritis Cartilage. 2006;14(10):974–83.

    Article  PubMed  CAS  Google Scholar 

  14. Felson DT, Lohmander LS. Whither osteoarthritis biomarkers? Osteoarthritis Cartilage. 2009;17(4):419–22.

    Article  PubMed  CAS  Google Scholar 

  15. Gray ML. Toward imaging biomarkers for glycosaminoglycans. J Bone Joint Surg Am. 2009;91 Suppl 1:44–9.

    Article  PubMed  Google Scholar 

  16. Bredella MA, Tirman PF, Peterfy CG, Zarlingo M, Feller JF, Bost FW, et al. Accuracy of T2-weighted fast spin-echo MR imaging with fat saturation in detecting cartilage defects in the knee: comparison with arthroscopy in 130 patients. AJR Am J Roentgenol. 1999;172(4):1073–80.

    PubMed  CAS  Google Scholar 

  17. Kijowski R, Blankenbaker DG, Davis KW, Shinki K, Kaplan LD, De Smet AA. Comparison of 1.5- and 3.0-T MR imaging for evaluating the articular cartilage of the knee joint. Radiology. 2009;250(3):839–48.

    Article  PubMed  Google Scholar 

  18. Link T, Majumdar S, Peterfy C, Daldrup H, Uffmann M, Dowling C, et al. High resolution MRI of small joints: impact of spatial resolution on diagnostic performance and SNR. Magn Reson Imaging. 1998;16:147–55.

    Article  PubMed  CAS  Google Scholar 

  19. Link TM, Sell CA, Masi JN, Phan C, Newitt D, Lu Y, et al. 3.0 vs 1.5 T MRI in the detection of focal cartilage pathology–ROC analysis in an experimental model. Osteoarthritis Cartilage. 2006;14(1):63–70.

    Article  PubMed  CAS  Google Scholar 

  20. Ristow O, Steinbach L, Sabo G, Krug R, Huber M, Rauscher I, et al. Isotropic 3D fast spin-echo imaging versus standard 2D imaging at 3.0 T of the knee-image quality and diagnostic performance. Eur Radiol. 2009;19:1263–72.

    Article  PubMed  Google Scholar 

  21. Saadat E, Jobke B, Chu B, Lu Y, Cheng J, Li X, et al. Diagnostic performance of in vivo 3T Fast Spin Echo MRI for articular cartilage abnormalities in human osteoarthritic knees using histology as standard of reference. Eur Radiol. 2008;18:2292–302.

    Article  PubMed  Google Scholar 

  22. Potter HG, Linklater JM, Allen AA, Hannafin JA, Haas SB. Magnetic resonance imaging of articular cartilage in the knee. An evaluation with use of fast-spin-echo imaging. J Bone Joint Surg Am. 1998;80(9):1276–84.

    PubMed  CAS  Google Scholar 

  23. Bauer JS, Krause S, Ross C, Mueller D, Majumdar S, Link TM. Accuracy of volumetric cartilage measurements of the knee at 1.5T and 3.0T. RSNA, Chicago; 2005. p. 305.

    Google Scholar 

  24. Peterfy CG, van Dijke CF, Lu Y, Nguyen A, Connick TJ, Kneeland JB, et al. Quantification of the volume of articular cartilage in the metacarpophalangeal joints of the hand: accuracy and precision of three-dimensional MR imaging. AJR Am J Roentgenol. 1995;165(2):371–5.

    PubMed  CAS  Google Scholar 

  25. Bashir A, Gray ML, Hartke J, Burstein D. Nondestructive imaging of human cartilage glycosaminoglycan concentration by MRI. Magn Reson Med. 1999;41(5):857–65.

    Article  PubMed  CAS  Google Scholar 

  26. Cheng J, Saadat E, Bolbos R, Jobke B, Siddiqui S, Ries M, et al. Detection of proteoglycan content in human osteoarthritic cartilage samples with magnetic resonance T1rho imaging. Toronto: ISMRM; 2008.

    Google Scholar 

  27. David-Vaudey E, Ghosh S, Ries M, Majumdar S. T2 relaxation time measurements in osteoarthritis. Magn Reson Imaging. 2004;22(5):673–82.

    Article  PubMed  Google Scholar 

  28. Mlynarik V, Trattnig S, Huber M, Zembsch A, Imhof H. The role of relaxation times in monitoring proteoglycan depletion in articular cartilage. J Magn Reson Imaging. 1999;10(4):497–502.

    Article  PubMed  CAS  Google Scholar 

  29. Kornaat PR, Bloem JL, Ceulemans RY, Riyazi N, Rosendaal FR, Nelissen RG, et al. Osteoarthritis of the knee: association between clinical features and MR imaging findings. Radiology. 2006;239(3):811–7.

    Article  PubMed  Google Scholar 

  30. Li X, Ma BC, Link TM, Castillo DD, Blumenkrantz G, Lozano J, et al. In vivoT(1rho) and T(2) mapping of articular cartilage in osteoarthritis of the knee using 3T MRI. Osteoarthritis Cartilage. 2007;15:789–97.

    Article  PubMed  CAS  Google Scholar 

  31. Link TM, Steinbach LS, Ghosh S, Ries M, Lu Y, Lane N, et al. Osteoarthritis: MR imaging findings in different stages of disease and correlation with clinical findings. Radiology. 2003;226(2):373–81.

    Article  PubMed  Google Scholar 

  32. Williams A, Sharma L, McKenzie CA, Prasad PV, Burstein D. Delayed gadolinium-enhanced magnetic resonance imaging of cartilage in knee osteoarthritis: findings at different radiographic stages of disease and relationship to malalignment. Arthritis Rheum. 2005;52(11):3528–35.

    Article  PubMed  CAS  Google Scholar 

  33. Stehling C, Lane NE, Nevitt MC, Lynch J, McCulloch CE, Link TM. Subjects with higher physical activity levels have more severe focal knee lesions diagnosed with 3T MRI: analysis of a non-symptomatic cohort of the osteoarthritis initiative. Osteoar­thritis Cartilage. 2010;18(6):776–86.

    Article  PubMed  CAS  Google Scholar 

  34. Stehling C, Liebl H, Krug R, Lane NE, Nevitt MC, Lynch J, et al. Patellar cartilage: T2 values and morphologic abnormalities at 3.0-T MR imaging in relation to physical activity in asymptomatic subjects from the osteoarthritis initiative. Radiology. 2010;254(2):509–20.

    Article  PubMed  Google Scholar 

  35. Stahl R, Luke A, Li X, Carballido-Gamio J, Ma CB, Majumdar S, et al. T1rho, T(2) and focal knee cartilage abnormalities in physically active and sedentary healthy subjects versus early OA patients-a 3.0-Tesla MRI study. Eur Radiol. 2009;19:132–43.

    Article  PubMed  Google Scholar 

  36. Writing group for the ISCD Position Development Conference. Diagnosis of osteoporosis in men, premenopausal women, and children. J Clin Densitom. 2004;7(1):17–26.

    Google Scholar 

  37. Roemer FW, Guermazi A, Javaid MK, Lynch JA, Niu J, Zhang Y, et al. Change in MRI-detected subchondral bone marrow lesions is associated with cartilage loss – the MOST study A longitudinal multicenter study of knee osteoarthritis. Ann Rheum Dis. 2008;68:1461–5.

    Article  PubMed  Google Scholar 

  38. Phan CM, Link TM, Blumenkrantz G, Dunn TC, Ries MD, Steinbach LS, et al. MR imaging findings in the follow-up of patients with different stages of knee osteoarthritis and the correlation with clinical symptoms. Eur Radiol. 2006;16:608–18.

    Article  PubMed  Google Scholar 

  39. Emrani PS, Katz JN, Kessler CL, Reichmann WM, Wright EA, McAlindon TE, et al. Joint space narrowing and Kellgren-Lawrence progression in knee osteoarthritis: an analytic literature synthesis. Osteoarthritis Cartilage. 2008;16(8):873–82.

    Article  PubMed  CAS  Google Scholar 

  40. Felson DT, Niu J, Guermazi A, Roemer F, Aliabadi P, Clancy M, et al. Correlation of the development of knee pain with enlarging bone marrow lesions on magnetic resonance imaging. Arthritis Rheum. 2007;56(9):2986–92.

    Article  PubMed  Google Scholar 

  41. Dam EB, Loog M, Christiansen C, Byrjalsen I, Folkesson J, Nielsen M, et al. Identification of progressors in osteoarthritis by combining biochemical and MRI-based markers. Arthritis Res Ther. 2009;11(4):R115.

    Article  PubMed  Google Scholar 

  42. Stehling C, Mueller-Hoecker C, Schwaiger BJ, Lane NE, Krug R, Nevitt MC, et al. Cartilage T2 and WORMS MR measurements predict changes in clinical parameters over a period of 2 years: analysis of 217 nonsymptomatic subjects from the osteoarthritis initiative. ECR scientific program 2010, Vienna; 2010. p. S133.

    Google Scholar 

  43. Blumenkrantz G, Carballido-Gamio J, McCulloch C, Lynch J, Link T, Majumdar S. The relationship between the spatial distribution of cartilage MR T2 and longitudinal changes in pain: data from the osteoarthritis initiative. Honolulu, Hawaii: ISMRM; 2009.

    Google Scholar 

  44. Kanis JA, Oden A, Johansson H, Borgstrom F, Strom O, McCloskey E. FRAX and its applications to clinical practice. Bone. 2009;44(5):734–43.

    Article  PubMed  Google Scholar 

  45. Raynauld JP, Martel-Pelletier J, Beaulieu A, Bessette L, Morin F, Choquette D, et al. An open-label pilot study evaluating by magnetic resonance imaging the potential for a disease-modifying effect of celecoxib compared to a modelized historical control cohort in the treatment of knee osteoarthritis. Semin Arthritis Rheum. 2010;40(3):185–92.

    Article  PubMed  CAS  Google Scholar 

  46. Raynauld JP, Martel-Pelletier J, Bias P, Laufer S, Haraoui B, Choquette D, et al. Protective effects of licofelone, a 5-lipoxygenase and cyclo-oxygenase inhibitor, versus naproxen on cartilage loss in knee osteoarthritis: a first multicentre clinical trial using quantitative MRI. Ann Rheum Dis. 2009;68(6):938–47.

    Article  PubMed  CAS  Google Scholar 

  47. Roos EM, Dahlberg L. Positive effects of moderate exercise on glycosaminoglycan content in knee cartilage: a four-month, randomized, controlled trial in patients at risk of osteoarthritis. Arthritis Rheum. 2005;52(11):3507–14.

    Article  PubMed  CAS  Google Scholar 

  48. Liphardt AM, Mundermann A, Koo S, Backer N, Andriacchi TP, Zange J, et al. Vibration training intervention to maintain cartilage thickness and serum concentrations of cartilage oligometric matrix protein (COMP) during immobilization. Osteoarthritis Cartilage. 2009;17(12):1598–603.

    Article  PubMed  Google Scholar 

  49. Borthakur A, Mellon E, Niyogi S, Witschey W, Kneeland JB, Reddy R. Sodium and T1rho MRI for molecular and diagnostic imaging of articular cartilage. NMR Biomed. 2006;19(7):781–821.

    Article  PubMed  CAS  Google Scholar 

  50. Ling W, Regatte RR, Navon G, Jerschow A. Assessment of glycosaminoglycan concentration in vivo by chemical exchange-dependent saturation transfer (gagCEST). Proc Natl Acad Sci USA. 2008;105(7):2266–70.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Radiology and Biomedical Imaging, University of California at San Francisco, 400 Parnassus Ave, A-367, San Francisco, CA, 94131, USA

    Thomas M. Link

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Correspondence to Thomas M. Link .

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  1. Dept. Radiology, University of California, San Francisco, 400 Parnassus Ave., A-367, San Francisco, 94143-0628, California, USA

    Thomas M. Link

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Link, T.M. (2011). Cartilage as a Biomarker. In: Link, T. (eds) Cartilage Imaging. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-8438-8_16

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  • DOI: https://doi.org/10.1007/978-1-4419-8438-8_16

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