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Semin Musculoskelet Radiol 2024; 28(01): 026-038
DOI: 10.1055/s-0043-1776429
Review Article

Biomarkers of Cartilage Composition

Maximilian T. Löffler 
1   Department of Radiology and Biomedical Imaging, University of California, San Francisco, California
2   Department of Diagnostic and Interventional Radiology, University Medical Center Freiburg, Freiburg im Breisgau, Germany
3   Department of Diagnostic and Interventional Neuroradiology, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
,
Zehra Akkaya
1   Department of Radiology and Biomedical Imaging, University of California, San Francisco, California
4   Department of Radiology, Faculty of Medicine, Ankara University, Ankara, Turkey
,
Rupsa Bhattacharjee
1   Department of Radiology and Biomedical Imaging, University of California, San Francisco, California
,
Thomas M. Link
1   Department of Radiology and Biomedical Imaging, University of California, San Francisco, California
› Author Affiliations Financial Disclosure Funding for this article was provided by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01-AR078917).
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Abstract

Magnetic resonance imaging (MRI) has significantly advanced the understanding of osteoarthritis (OA) because it enables visualization of noncalcified tissues. Cartilage is avascular and nurtured by diffusion, so it has a very low turnover and limited capabilities of repair. Consequently, prevention of structural and detection of premorphological damage is key in maintaining cartilage health. The integrity of cartilage composition and ultrastructure determines its mechanical properties but is not accessible to morphological imaging. Therefore, various techniques of compositional MRI with and without use of intravenous contrast medium have been developed. Spin-spin relaxation time (T2) and spin-lattice relaxation time constant in rotating frame (T1rho) mapping, the most studied cartilage biomarkers, were included in the recent standardization effort by the Quantitative Imaging Biomarkers Alliance (QIBA) that aims to make compositional MRI of cartilage clinically feasible and comparable. Additional techniques that are less frequently used include ultrashort echo time with T2*, delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), glycosaminoglycan concentration by chemical exchange-dependent saturation transfer (gagCEST), sodium imaging, and diffusion-weighted MRI.

Keywords

knee cartilage - compositional imaging - Quantitative Imaging Biomarkers Alliance - quantitative magnetic resonance imaging - osteoarthritis


Publication History

Article published online:
08 February 2024

© 2024. Thieme. All rights reserved.

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  • References

  • 1 Altman R, Asch E, Bloch D. et al; Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Arthritis Rheum 1986; 29 (08) 1039-1049
    CrossrefPubMedGoogle Scholar
  • 2 Carballo CB, Nakagawa Y, Sekiya I, Rodeo SA. Basic science of articular cartilage. Clin Sports Med 2017; 36 (03) 413-425
    CrossrefPubMedGoogle Scholar
  • 3 Loeser RF, Collins JA, Diekman BO. Ageing and the pathogenesis of osteoarthritis. Nat Rev Rheumatol 2016; 12 (07) 412-420
    CrossrefPubMedGoogle Scholar
  • 4 Chalian M, Li X, Guermazi A. et al; RSNA QIBA MSK Biomarker Committee, SNA QIBA MSK Biomarker Committee Members. The QIBA profile for MRI-based compositional imaging of knee cartilage. Radiology 2021; 301 (02) 423-432
    CrossrefPubMedGoogle Scholar
  • 5 QIBA MSK Biomarker Committee. QIBA Profile: MR-based cartilage compositional biomarkers (T1ρ, T2) for the knee. . Profile Stage: Consensus. September 25, 2021. Available from: http://qibawiki.rsna.org/index.php/Profiles
    PubMedGoogle Scholar
  • 6 Gallo MC, Wyatt C, Pedoia V. et al. T1ρ and T2 relaxation times are associated with progression of hip osteoarthritis. Osteoarthritis Cartilage 2016; 24 (08) 1399-1407
    CrossrefPubMedGoogle Scholar
  • 7 Atkinson HF, Birmingham TB, Moyer RF. et al. MRI T2 and T1ρ relaxation in patients at risk for knee osteoarthritis: a systematic review and meta-analysis. BMC Musculoskelet Disord 2019; 20 (01) 182
    CrossrefPubMedGoogle Scholar
  • 8 Guermazi A, Alizai H, Crema MD, Trattnig S, Regatte RR, Roemer FW. Compositional MRI techniques for evaluation of cartilage degeneration in osteoarthritis. Osteoarthritis Cartilage 2015; 23 (10) 1639-1653
    CrossrefPubMedGoogle Scholar
  • 9 Eck BL, Yang M, Elias JJ. et al. Quantitative MRI for evaluation of musculoskeletal disease: cartilage and muscle composition, joint inflammation, and biomechanics in osteoarthritis. Invest Radiol 2023; 58 (01) 60-75
    CrossrefPubMedGoogle Scholar
  • 10 Zijlstra F, Seevinck PR. Multiple-echo steady-state (MESS): extending DESS for joint T2 mapping and chemical-shift corrected water-fat separation. Magn Reson Med 2021; 86 (06) 3156-3165
    CrossrefPubMedGoogle Scholar
  • 11 Luke AC, Stehling C, Stahl R. et al. High-field magnetic resonance imaging assessment of articular cartilage before and after marathon running: does long-distance running lead to cartilage damage?. Am J Sports Med 2010; 38 (11) 2273-2280
    CrossrefPubMedGoogle Scholar
  • 12 Prasad AP, Nardo L, Schooler J, Joseph GB, Link TMT. T1ρ and T2 relaxation times predict progression of knee osteoarthritis. Osteoarthritis Cartilage 2013; 21 (01) 69-76
    CrossrefPubMedGoogle Scholar
  • 13 Nishioka H, Nakamura E, Hirose J, Okamoto N, Yamabe S, Mizuta H. MRI T1ρ and T2 mapping for the assessment of articular cartilage changes in patients with medial knee osteoarthritis after hemicallotasis osteotomy. Bone Joint Res 2016; 5 (07) 294-300
    CrossrefPubMedGoogle Scholar
  • 14 Apprich SR, Schreiner MM, Szomolanyi P. et al. Potential predictive value of axial T2 mapping at 3 Tesla MRI in patients with untreated patellar cartilage defects over a mean follow-up of four years. Osteoarthritis Cartilage 2020; 28 (02) 215-222
    CrossrefPubMedGoogle Scholar
  • 15 Theologis AA, Schairer WW, Carballido-Gamio J, Majumdar S, Li X, Ma CB. Longitudinal analysis of T1ρ and T2 quantitative MRI of knee cartilage laminar organization following microfracture surgery. Knee 2012; 19 (05) 652-657
    CrossrefPubMedGoogle Scholar
  • 16 Welsch GH, Mamisch TC, Domayer SE. et al. Cartilage T2 assessment at 3-T MR imaging: in vivo differentiation of normal hyaline cartilage from reparative tissue after two cartilage repair procedures—initial experience. Radiology 2008; 247 (01) 154-161
    CrossrefPubMedGoogle Scholar
  • 17 Holtzman DJ, Theologis AA, Carballido-Gamio J, Majumdar S, Li X, Benjamin C. T(1ρ) and T(2) quantitative magnetic resonance imaging analysis of cartilage regeneration following microfracture and mosaicplasty cartilage resurfacing procedures. J Magn Reson Imaging 2010; 32 (04) 914-923
    CrossrefPubMedGoogle Scholar
  • 18 Baum T, Joseph GB, Arulanandan A. et al. Association of magnetic resonance imaging-based knee cartilage T2 measurements and focal knee lesions with knee pain: data from the Osteoarthritis Initiative. Arthritis Care Res (Hoboken) 2012; 64 (02) 248-255
    CrossrefPubMedGoogle Scholar
  • 19 Dautry R, Bousson V, Manelfe J. et al. Correlation of MRI T2 mapping sequence with knee pain location in young patients with normal standard MRI. JBR-BTR 2014; 97 (01) 11-16
    PubMedGoogle Scholar
  • 20 Su F, Pedoia V, Teng H-L. et al. The association between MR T1ρ and T2 of cartilage and patient-reported outcomes after ACL injury and reconstruction. Osteoarthritis Cartilage 2016; 24 (07) 1180-1189
    CrossrefPubMedGoogle Scholar
  • 21 van der Heijden RA, Oei EHG, Bron EE. et al. No difference on quantitative magnetic resonance imaging in patellofemoral cartilage composition between patients with patellofemoral pain and healthy controls. Am J Sports Med 2016; 44 (05) 1172-1178
    CrossrefPubMedGoogle Scholar
  • 22 Jungmann PM, Kraus MS, Nardo L. et al. T(2) relaxation time measurements are limited in monitoring progression, once advanced cartilage defects at the knee occur: longitudinal data from the osteoarthritis initiative. J Magn Reson Imaging 2013; 38 (06) 1415-1424
    CrossrefPubMedGoogle Scholar
  • 23 Sharafi A, Zibetti MVW, Chang G, Cloos M, Regatte RR. 3D magnetic resonance fingerprinting for rapid simultaneous T1, T2, and T1ρ volumetric mapping of human articular cartilage at 3 T. NMR Biomed 2022; 35 (12) e4800
    CrossrefPubMedGoogle Scholar
  • 24 Joseph GB, McCulloch CE, Nevitt MC. et al. A reference database of cartilage 3 T MRI T2 values in knees without diagnostic evidence of cartilage degeneration: data from the osteoarthritis initiative. Osteoarthritis Cartilage 2015; 23 (06) 897-905
    CrossrefPubMedGoogle Scholar
  • 25 Chang EY, Du J, Chung CB. UTE imaging in the musculoskeletal system. J Magn Reson Imaging 2015; 41 (04) 870-883
    CrossrefPubMedGoogle Scholar
  • 26 Cheng KY, Moazamian D, Ma Y. et al. Clinical application of ultrashort echo time (UTE) and zero echo time (ZTE) magnetic resonance (MR) imaging in the evaluation of osteoarthritis. Skeletal Radiol 2023; 52 (11) 2149-2157
    CrossrefPubMedGoogle Scholar
  • 27 Du J, Diaz E, Carl M, Bae W, Chung CB, Bydder GM. Ultrashort echo time imaging with bicomponent analysis. Magn Reson Med 2012; 67 (03) 645-649
    CrossrefPubMedGoogle Scholar
  • 28 Bae WC, Dwek JR, Znamirowski R. et al. Ultrashort echo time MR imaging of osteochondral junction of the knee at 3 T: identification of anatomic structures contributing to signal intensity. Radiology 2010; 254 (03) 837-845
    CrossrefPubMedGoogle Scholar
  • 29 Du J, Carl M, Bae WC. et al. Dual inversion recovery ultrashort echo time (DIR-UTE) imaging and quantification of the zone of calcified cartilage (ZCC). Osteoarthritis Cartilage 2013; 21 (01) 77-85
    CrossrefPubMedGoogle Scholar
  • 30 Lane LB, Bullough PG. Age-related changes in the thickness of the calcified zone and the number of tidemarks in adult human articular cartilage. J Bone Joint Surg Br 1980; 62 (03) 372-375
    CrossrefPubMedGoogle Scholar
  • 31 Oegema Jr TR, Carpenter RJ, Hofmeister F, Thompson Jr RC. The interaction of the zone of calcified cartilage and subchondral bone in osteoarthritis. Microsc Res Tech 1997; 37 (04) 324-332
    CrossrefPubMedGoogle Scholar
  • 32 Radin EL, Burr DB, Caterson B, Fyhrie D, Brown TD, Boyd RD. Mechanical determinants of osteoarthrosis. Semin Arthritis Rheum 1991; 21 (3, Suppl 2): 12-21
    CrossrefPubMedGoogle Scholar
  • 33 Titchenal MR, Williams AA, Chehab EF. et al. Cartilage subsurface changes to magnetic resonance imaging UTE-T2* 2 years after anterior cruciate ligament reconstruction correlate with walking mechanics associated with knee osteoarthritis. Am J Sports Med 2018; 46 (03) 565-572
    CrossrefPubMedGoogle Scholar
  • 34 Finkenstaedt T, Biswas R, Abeydeera NA. et al. Ultrashort time to echo magnetic resonance evaluation of calcium pyrophosphate crystal deposition in human menisci. Invest Radiol 2019; 54 (06) 349-355
    CrossrefPubMedGoogle Scholar
  • 35 Mackay JW, Low SBL, Houston GC, Toms AP. Ultrashort TE evaluation of the osteochondral junction in vivo: a feasibility study. Br J Radiol 2016; 89 (1059) 20150493
    CrossrefPubMedGoogle Scholar
  • 36 Chu CR, Williams AA, West RV. et al. Quantitative magnetic resonance imaging UTE-T2* mapping of cartilage and meniscus healing after anatomic anterior cruciate ligament reconstruction. Am J Sports Med 2014; 42 (08) 1847-1856
    CrossrefPubMedGoogle Scholar
  • 37 Rehnitz C, Do T, Klaan B. et al. Feasibility of using half-dose Gd-BOPTA for delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) at the knee, compared with standard-dose Gd-DTPA. J Magn Reson Imaging 2020; 51 (01) 144-154
    CrossrefPubMedGoogle Scholar
  • 38 Lesperance LM, Gray ML, Burstein D. Determination of fixed charge density in cartilage using nuclear magnetic resonance. J Orthop Res 1992; 10 (01) 1-13
    CrossrefPubMedGoogle Scholar
  • 39 Williams A, Gillis A, McKenzie C. et al. Glycosaminoglycan distribution in cartilage as determined by delayed gadolinium-enhanced MRI of cartilage (dGEMRIC): potential clinical applications. AJR Am J Roentgenol 2004; 182 (01) 167-172
    CrossrefPubMedGoogle Scholar
  • 40 Hangaard S, Gudbergsen H, Skougaard M. et al. Point of no return for improvement of cartilage quality indicated by dGEMRIC before and after weight loss in patients with knee osteoarthritis: a cohort study. Acta Radiol 2018; 59 (03) 336-340
    CrossrefPubMedGoogle Scholar
  • 41 Neuman P, Owman H, Müller G, Englund M, Tiderius CJ, Dahlberg LE. Knee cartilage assessment with MRI (dGEMRIC) and subjective knee function in ACL injured copers: a cohort study with a 20 year follow-up. Osteoarthritis Cartilage 2014; 22 (01) 84-90
    CrossrefPubMedGoogle Scholar
  • 42 Tiderius CJ, Svensson J, Leander P, Ola T, Dahlberg L. dGEMRIC (delayed gadolinium-enhanced MRI of cartilage) indicates adaptive capacity of human knee cartilage. Magn Reson Med 2004; 51 (02) 286-290
    CrossrefPubMedGoogle Scholar
  • 43 van Tiel J, Reijman M, Bos PK. et al. Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) shows no change in cartilage structural composition after viscosupplementation in patients with early-stage knee osteoarthritis. PLoS One 2013; 8 (11) e79785
    CrossrefPubMedGoogle Scholar
  • 44 Van Ginckel A, Baelde N, Almqvist KF, Roosen P, McNair P, Witvrouw E. Functional adaptation of knee cartilage in asymptomatic female novice runners compared to sedentary controls. A longitudinal analysis using delayed Gadolinium Enhanced Magnetic Resonance Imaging of Cartilage (dGEMRIC). Osteoarthritis Cartilage 2010; 18 (12) 1564-1569
    CrossrefPubMedGoogle Scholar
  • 45 Multanen J, Rauvala E, Lammentausta E. et al. Reproducibility of imaging human knee cartilage by delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) at 1.5 Tesla. Osteoarthritis Cartilage 2009; 17 (05) 559-564
    CrossrefPubMedGoogle Scholar
  • 46 Peterson P, Tiderius CJ, Olsson E, Lundin B, Olsson LE, Svensson J. Knee dGEMRIC at 7 T: comparison against 1.5 T and evaluation of T1-mapping methods. BMC Musculoskelet Disord 2018; 19 (01) 149
    CrossrefPubMedGoogle Scholar
  • 47 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 U S A 2008; 105 (07) 2266-2270
    CrossrefPubMedGoogle Scholar
  • 48 Zhou J, van Zijl PCM. Chemical exchange saturation transfer imaging and spectroscopy. Prog Nucl Magn Reson Spectrosc 2006; 48: 109-136
    CrossrefPubMedGoogle Scholar
  • 49 Schleich C, Bittersohl B, Miese F. et al. Glycosaminoglycan chemical exchange saturation transfer at 3T MRI in asymptomatic knee joints. Acta Radiol 2016; 57 (05) 627-632
    CrossrefPubMedGoogle Scholar
  • 50 Singh A, Haris M, Cai K. et al. Chemical exchange saturation transfer magnetic resonance imaging of human knee cartilage at 3 T and 7 T. Magn Reson Med 2012; 68 (02) 588-594
    CrossrefPubMedGoogle Scholar
  • 51 Krishnamoorthy G, Nanga RPR, Bagga P, Hariharan H, Reddy R. High quality three-dimensional gagCEST imaging of in vivo human knee cartilage at 7 Tesla. Magn Reson Med 2017; 77 (05) 1866-1873
    CrossrefPubMedGoogle Scholar
  • 52 Brinkhof S, Nizak R, Khlebnikov V, Prompers JJ, Klomp DWJ, Saris DBF. Detection of early cartilage damage: feasibility and potential of gagCEST imaging at 7T. Eur Radiol 2018; 28 (07) 2874-2881
    CrossrefPubMedGoogle Scholar
  • 53 Soellner ST, Welsch GH, Gelse K. et al. gagCEST imaging at 3 T MRI in patients with articular cartilage lesions of the knee and intraoperative validation. Osteoarthritis Cartilage 2021; 29 (08) 1163-1172
    CrossrefPubMedGoogle Scholar
  • 54 Brinkhof S, Nizak R, Sim S. et al. In vivo biochemical assessment of cartilage with gagCEST MRI: correlation with cartilage properties. NMR Biomed 2021; 34 (03) e4463
    CrossrefPubMedGoogle Scholar
  • 55 Watkins LE, Rubin EB, Mazzoli V. et al. Rapid volumetric gagCEST imaging of knee articular cartilage at 3 T: evaluation of improved dynamic range and an osteoarthritic population. NMR Biomed 2020; 33 (08) e4310
    CrossrefPubMedGoogle Scholar
  • 56 Zaric O, Juras V, Szomolanyi P. et al. Frontiers of sodium MRI revisited: from cartilage to brain imaging. J Magn Reson Imaging 2021; 54 (01) 58-75
    CrossrefPubMedGoogle Scholar
  • 57 Stobbe R, Beaulieu C. In vivo sodium magnetic resonance imaging of the human brain using soft inversion recovery fluid attenuation. Magn Reson Med 2005; 54 (05) 1305-1310
    CrossrefPubMedGoogle Scholar
  • 58 Zbýň Š, Mlynárik V, Juras V, Szomolanyi P, Trattnig S. Evaluation of cartilage repair and osteoarthritis with sodium MRI. NMR Biomed 2016; 29 (02) 206-215
    CrossrefPubMedGoogle Scholar
  • 59 Trattnig S, Welsch GH, Juras V. et al. 23Na MR imaging at 7 T after knee matrix-associated autologous chondrocyte transplantation preliminary results. Radiology 2010; 257 (01) 175-184
    CrossrefPubMedGoogle Scholar
  • 60 Wheaton AJ, Borthakur A, Shapiro EM. et al. Proteoglycan loss in human knee cartilage: quantitation with sodium MR imaging—feasibility study. Radiology 2004; 231 (03) 900-905
    CrossrefPubMedGoogle Scholar
  • 61 Zbýň Š, Schreiner M, Juras V. et al. Assessment of low-grade focal cartilage lesions in the knee with sodium MRI at 7 T: reproducibility and short-term, 6-month follow-up data. Invest Radiol 2020; 55 (07) 430-437
    CrossrefPubMedGoogle Scholar
  • 62 Barendregt AM, van Gulik EC, Lavini C. et al. Diffusion-weighted imaging for assessment of synovial inflammation in juvenile idiopathic arthritis: a promising imaging biomarker as an alternative to gadolinium-based contrast agents. Eur Radiol 2017; 27 (11) 4889-4899
    CrossrefPubMedGoogle Scholar
  • 63 Sellam J, Berenbaum F. The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis. Nat Rev Rheumatol 2010; 6 (11) 625-635
    CrossrefPubMedGoogle Scholar
  • 64 Sauer A, Li M, Holl-Wieden A, Pabst T, Neubauer H. Readout-segmented multi-shot diffusion-weighted MRI of the knee joint in patients with juvenile idiopathic arthritis. Pediatr Rheumatol Online J 2017; 15 (01) 73
    CrossrefPubMedGoogle Scholar
  • 65 Miller KL, Hargreaves BA, Gold GE, Pauly JM. Steady-state diffusion-weighted imaging of in vivo knee cartilage. Magn Reson Med 2004; 51 (02) 394-398
    CrossrefPubMedGoogle Scholar
  • 66 Tan H, Kang W, Fan Q. et al. Intravoxel incoherent motion diffusion-weighted MR imaging findings of infrapatellar fat pad signal abnormalities: comparison between symptomatic and asymptomatic knee osteoarthritis. Acad Radiol 2023; 30 (07) 1374-1383
    CrossrefPubMedGoogle Scholar
  • 67 Ross BD, Malyarenko D, Heist K. et al. Repeatability of quantitative magnetic resonance imaging biomarkers in the tibia bone marrow of a murine myelofibrosis model. Tomography 2023; 9 (02) 552-566
    CrossrefPubMedGoogle Scholar
  • 68 Huch B, Stumpf K, Bracher A-K. et al. Intravoxel incoherent motion (IVIM) MRI in pediatric patients with synovitis of the knee joint: a prospective pilot study. Pediatr Rheumatol Online J 2022; 20 (01) 99
    CrossrefPubMedGoogle Scholar
  • 69 Barendregt AM, Mazzoli V, van Gulik EC. et al. Juvenile idiopathic arthritis: diffusion-weighted MRI in the assessment of arthritis in the knee. Radiology 2020; 295 (02) 373-380
    CrossrefPubMedGoogle Scholar
  • 70 Rehnitz C, Kupfer J, Streich NA. et al. Comparison of biochemical cartilage imaging techniques at 3-T MRI. Osteoarthritis Cartilage 2014; 22: 1732-1742
    CrossrefPubMedGoogle Scholar
  • 71 Zbýň S, Mlynárik V, Juras V, Szomolanyi P, Trattnig S. Sodium MR imaging of articular cartilage pathologies. Curr Radiol Rep 2014; 2: 41
    CrossrefPubMedGoogle Scholar