Is T1ρ Mapping an Alternative to Delayed Gadolinium-enhanced MR Imaging of Cartilage in the Assessment of Sulphated Glycosaminoglycan Content in Human Osteoarthritic Knees? An in Vivo Validation Study

Published Online:https://doi.org/10.1148/radiol.2015150693

Although the technique is not completely sulphated glycosaminoglycan (sGAG) specific and requires a contrast agent, delayed gadolinium-enhanced MR imaging of cartilage is a validated and robust method for quantifying cartilage sGAG content in human osteoarthritis subjects whereas T1ρ mapping appears not suitable for this purpose.

Purpose

To determine if T1ρ mapping can be used as an alternative to delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) in the quantification of cartilage biochemical composition in vivo in human knees with osteoarthritis.

Materials and Methods

This study was approved by the institutional review board. Written informed consent was obtained from all participants. Twelve patients with knee osteoarthritis underwent dGEMRIC and T1ρ mapping at 3.0 T before undergoing total knee replacement. Outcomes of dGEMRIC and T1ρ mapping were calculated in six cartilage regions of interest. Femoral and tibial cartilages were harvested during total knee replacement. Cartilage sulphated glycosaminoglycan (sGAG) and collagen content were assessed with dimethylmethylene blue and hydroxyproline assays, respectively. A four-dimensional multivariate mixed-effects model was used to simultaneously assess the correlation between outcomes of dGEMRIC and T1ρ mapping and the sGAG and collagen content of the articular cartilage.

Results

T1 relaxation times at dGEMRIC showed strong correlation with cartilage sGAG content (r = 0.73; 95% credibility interval [CI] = 0.60, 0.83) and weak correlation with cartilage collagen content (r = 0.40; 95% CI: 0.18, 0.58). T1ρ relaxation times did not correlate with cartilage sGAG content (r = 0.04; 95% CI: −0.21, 0.28) or collagen content (r = −0.05; 95% CI = −0.31, 0.20).

Conclusion

dGEMRIC can help accurately measure cartilage sGAG content in vivo in patients with knee osteoarthritis, whereas T1ρ mapping does not appear suitable for this purpose. Although the technique is not completely sGAG specific and requires a contrast agent, dGEMRIC is a validated and robust method for quantifying cartilage sGAG content in human osteoarthritis subjects in clinical research.

© RSNA, 2015

References

  • 1. Litwic A, Edwards MH, Dennison EM, Cooper C. Epidemiology and burden of osteoarthritis. Br Med Bull 2013;105:185–199.
  • 2. Hunter DJ. Pharmacologic therapy for osteoarthritis: the era of disease modification. Nat Rev Rheumatol 2011;7(1):13–22.
  • 3. Neu CP. Functional imaging in OA: role of imaging in the evaluation of tissue biomechanics. Osteoarthritis Cartilage 2014;22(10):1349–1359.
  • 4. Oei EH, van Tiel J, Robinson WH, Gold GE. Quantitative radiologic imaging techniques for articular cartilage composition: toward early diagnosis and development of disease-modifying therapeutics for osteoarthritis. Arthritis Care Res (Hoboken) 2014;66(8):1129–1141.
  • 5. Bashir A, Gray ML, Hartke J, Burstein D. Nondestructive imaging of human cartilage glycosaminoglycan concentration by MRI. Magn Reson Med 1999;41(5):857–865.
  • 6. Wang L, Regatte RR. T₁ρ MRI of human musculoskeletal system. J Magn Reson Imaging 2015;41(3):586–600.
  • 7. Regatte RR, Akella SV, Wheaton AJ, et al. 3D-T1ρ relaxation mapping of articular cartilage: in vivo assessment of early degenerative changes in symptomatic osteoarthritic subjects. Acad Radiol 2004;11(7):741–749.
  • 8. Li X, Han ET, Ma CB, Link TM, Newitt DC, Majumdar S. In vivo 3T spiral imaging based multi-slice T1ρ mapping of knee cartilage in osteoarthritis. Magn Reson Med 2005;54(4):929–936.
  • 9. Duvvuri U, Kudchodkar S, Reddy R, Leigh JST. T1ρ relaxation can assess longitudinal proteoglycan loss from articular cartilage in vitro. Osteoarthritis Cartilage 2002;10(11):838–844.
  • 10. Regatte RR, Akella SV, Borthakur A, Reddy R. Proton spin-lock ratio imaging for quantitation of glycosaminoglycans in articular cartilage. J Magn Reson Imaging 2003;17(1):114–121.
  • 11. Keenan KE, Besier TF, Pauly JM, et al. Prediction of glycosaminoglycan content in human cartilage by age, T1ρ and T2 MRI. Osteoarthritis Cartilage 2011;19(2):171–179.
  • 12. Li X, Cheng J, Lin K, et al. Quantitative MRI using T1ρ and T2 in human osteoarthritic cartilage specimens: correlation with biochemical measurements and histology. Magn Reson Imaging 2011;29(3):324–334.
  • 13. Watanabe A, Wada Y, Obata T, et al. Delayed gadolinium-enhanced MR to determine glycosaminoglycan concentration in reparative cartilage after autologous chondrocyte implantation: preliminary results. Radiology 2006;239(1):201–208.
  • 14. Wong CS, Yan CH, Gong NJ, Li T, Chan Q, Chu YC. Imaging biomarker with T1ρ and T2 mappings in osteoarthritis: in vivo human articular cartilage study. Eur J Radiol 2013;82(4):647–650.
  • 15. Nishioka H, Hirose J, Nakamura E, et al. T1ρ and T2 mapping reveal the in vivo extracellular matrix of articular cartilage. J Magn Reson Imaging 2012;35(1):147–155.
  • 16. Kellgren JH, Lawrence JS. Radiological assessment of osteo-arthrosis. Ann Rheum Dis 1957;16(4):494–502.
  • 17. Chen W, Takahashi A, Han ET. 3D quantitative imaging of T1rho and T2 [abstr]. In: Proceedings of the Nineteenth Meeting of the International Society for Magnetic Resonance in Medicine. Berkeley, Calif: International Society for Magnetic Resonance in Medicine, 2011.
  • 18. McKenzie CA, Williams A, Prasad PV, Burstein D. Three-dimensional delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) at 1.5T and 3.0T. J Magn Reson Imaging 2006;24(4):928–933.
  • 19. Tiderius CJ, Olsson LE, de Verdier H, Leander P, Ekberg O, Dahlberg L. Gd-DTPA2− enhanced MRI of femoral knee cartilage: a dose-response study in healthy volunteers. Magn Reson Med 2001;46(6):1067–1071.
  • 20. Tiderius CJ, Olsson LE, Leander P, Ekberg O, Dahlberg L. Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) in early knee osteoarthritis. Magn Reson Med 2003;49(3):488–492.
  • 21. Bron EE, van Tiel J, Smit H, et al. Image registration improves human knee cartilage T1 mapping with delayed gadolinium-enhanced MRI of cartilage (dGEMRIC). Eur Radiol 2013;23(1):246–252.
  • 22. van Tiel J, Bron EE, Tiderius CJ, et al. Reproducibility of 3D delayed gadolinium enhanced MRI of cartilage (dGEMRIC) of the knee at 3.0 T in patients with early stage osteoarthritis. Eur Radiol 2013;23(2):496–504.
  • 23. Klein S, van der Heide UA, Lips IM, van Vulpen M, Staring M, Pluim JP. Automatic segmentation of the prostate in 3D MR images by atlas matching using localized mutual information. Med Phys 2008;35(4):1407–1417.
  • 24. Klein S, Staring M, Murphy K, Viergever MA, Pluim JP. Elastix: a toolbox for intensity-based medical image registration. IEEE Trans Med Imaging 2010;29(1):196–205.
  • 25. Cavassila S, Deval S, Huegen C, van Ormondt D, Graveron-Demilly D. Cramér-Rao bounds: an evaluation tool for quantitation. NMR Biomed 2001;14(4):278–283.
  • 26. Sijbers J, Den Dekker AJ, Raman E, Van Dyck D. Parameter estimation from magnitude MR images. Int J Imaging Syst Technol 1999;10(2):109–114.
  • 27. Rao CR. Minimum variance and the estimation of several parameters. Math Proc Camb Philos Soc 1947;43(2):280–283.
  • 28. Tiderius C, Hori M, Williams A, et al. dGEMRIC as a function of BMI. Osteoarthritis Cartilage 2006;14(11):1091–1097.
  • 29. Farndale RW, Buttle DJ, Barrett AJ. Improved quantitation and discrimination of sulphated glycosaminoglycans by use of dimethylmethylene blue. Biochim Biophys Acta 1986;883(2):173–177.
  • 30. Bank RA, Krikken M, Beekman B, et al. A simplified measurement of degraded collagen in tissues: application in healthy, fibrillated and osteoarthritic cartilage. Matrix Biol 1997;16(5):233–243.
  • 31. Lunn DJ, Thomas A, Best N, Spiegelhalter D. WinBUGS: a Bayesian modelling framework: concepts, structure, and extensibility. Stat Comput 2000;10(4):325–337.
  • 32. Gelman A, Meng XL, Stern H. Posterior predictive assessment of model fitness via realized discrepancies. Stat Sin 1996;6:733–807.
  • 33. Watanabe A, Boesch C, Anderson SE, Brehm W, Mainil Varlet P. Ability of dGEMRIC and T2 mapping to evaluate cartilage repair after microfracture: a goat study. Osteoarthritis Cartilage 2009;17(10):1341–1349.
  • 34. Salo EN, Nissi MJ, Kulmala KA, Tiitu V, Töyräs J, Nieminen MT. Diffusion of Gd-DTPA²⁻ into articular cartilage. Osteoarthritis Cartilage 2012;20(2):117–126.
  • 35. van Tiel J, Kotek G, Reijman M, et al. Delayed gadolinium-enhanced MRI of the meniscus (dGEMRIM) in patients with knee osteoarthritis: relation with meniscal degeneration on conventional MRI, reproducibility, and correlation with dGEMRIC. Eur Radiol 2014;24(9):2261–2270.
  • 36. Mosher TJ, Zhang Z, Reddy R, et al. Knee articular cartilage damage in osteoarthritis: analysis of MR image biomarker reproducibility in ACRIN-PA 4001 multicenter trial. Radiology 2011;258(3):832–842.

Article History

Received March 22, 2015; revision requested April 27; revision received July 19; accepted August 12; final version accepted September 3.
Published online: Nov 20 2015
Published in print: May 2016