Skeletal Radiology

, Volume 37, Issue 3, pp 201–207 | Cite as

Changes underlying the dynamic contrast-enhanced MRI response to treatment in rheumatoid arthritis

  • Richard J. HodgsonEmail author
  • Theresa Barnes
  • Sylvia Connolly
  • Brian Eyes
  • Robert S. D. Campbell
  • Robert Moots
Scientific Article



Dynamic contrast-enhanced MRI of patients with rheumatoid arthritis has shown a decrease in the early enhancement rate (EER) of synovitis after treatment. The purpose of this work was to investigate the underlying changes.


3D dynamic contrast-enhanced images were acquired from 13 patients before and 1–2 weeks after anti-TNFα treatment. The EER of the inflamed synovium was measured. The T1 relaxation time of the synovitis was calculated from images at different flip angles. The time course of the arrival of gadolinium at the radial artery was determined. The gadolinium enhancement of the inflamed synovium was modeled to calculate the fractional plasma volume (vp), the fractional extravascular, extracellular fluid volume (ve), and the volume transfer constant (Ktrans). Pre- and post-treatment values were compared and the dependence of the EER on each parameter was assessed.


There was a decrease in the EER measured over 26 s after treatment (29%, p = 0.002). Reductions in T1 (12%, p = 0.001), Ktrans (31%, p = 0.002), and vp (43%, p = 0.01) contributed to this; however, the EER was relatively insensitive to changes in ve.


The decrease in EER after anti-TNFα treatment is largely caused by reductions in the volume transfer constant Ktrans, the fractional plasma volume vp, and the T1 relaxation time. Only the contributions from Ktrans and vp directly reflect synovial vascularity.


Magnetic resonance imaging Rheumatoid arthritis Tumor necrosis factor-alpha 



The authors acknowledge Dr Marta Garcia-Finana and Mrs Susanna Dodd for professional statistical guidance, and the Royal College of Radiologists, UK, for a Research Fellowship.


  1. 1.
    Lee J, Lee SK, Suh JS, et al. Magnetic resonance imaging of the wrist in defining remission of rheumatoid arthritis. J Rheumatol 1997; 24: 1303–1308.PubMedGoogle Scholar
  2. 2.
    Huang J, Stewart N, Crabbe J, et al. A 1-year follow-up study of dynamic magnetic resonance imaging in early rheumatoid arthritis reveals synovitis to be increased in shared epitope-positive patients and predictive of erosions at 1 year. Rheumatology (Oxford) 2000; 39: 407–416.CrossRefGoogle Scholar
  3. 3.
    Ostergaard M, Hansen M, Stoltenberg M, et al. Quantitative assessment of the synovial membrane in the rheumatoid wrist: an easily obtained MRI score reflects the synovial volume. Br J Rheumatol 1996; 35: 965–971.CrossRefGoogle Scholar
  4. 4.
    Konig H, Sieper J, Wolf KJ. Rheumatoid arthritis: evaluation of hypervascular and fibrous pannus with dynamic MR imaging enhanced with Gd-DTPA. Radiology 1990; 176: 473–477.CrossRefGoogle Scholar
  5. 5.
    Ostergaard M, Stoltenberg M, Lovgreen-Nielsen P, et al. Quantification of synovitis by MRI: correlation between dynamic and static gadolinium-enhanced magnetic resonance imaging and microscopic and macroscopic signs of synovial inflammation. Magn Reson Imaging 1998; 16: 743–754.CrossRefGoogle Scholar
  6. 6.
    Ostergaard M, Lorenzen I, Henriksen O. Dynamic gadolinium-enhanced MR imaging in active and inactive immunoinflammatory gonarthritis. Acta Radiol 1994; 35: 275–281.CrossRefGoogle Scholar
  7. 7.
    Gaffney K, Cookson J, Blades S, et al. Quantitative assessment of the rheumatoid synovial microvascular bed by gadolinium-DTPA enhanced magnetic resonance imaging. Ann Rheum Dis 1998; 57: 152–157.CrossRefGoogle Scholar
  8. 8.
    Palosaari K, Vuotila J, Takalo R, et al. Contrast-enhanced dynamic and static MRI correlates with quantitative 99Tcm-labelled nanocolloid scintigraphy. Study of early rheumatoid arthritis patients. Rheumatology (Oxford) 2004; 43: 1364–1373.CrossRefGoogle Scholar
  9. 9.
    Ostergaard M, Stoltenberg M, Henriksen O, et al. Quantitative assessment of synovial inflammation by dynamic gadolinium-enhanced magnetic resonance imaging. A study of the effect of intra-articular methylprednisolone on the rate of early synovial enhancement. Br J Rheumatol 1996; 35: 50–59.CrossRefGoogle Scholar
  10. 10.
    Reece RJ, Kraan MC, Radjenovic A, et al. Comparative assessment of leflunomide and methotrexate for the treatment of rheumatoid arthritis, by dynamic enhanced magnetic resonance imaging. Arthritis Rheum 2002; 46: 366–372.CrossRefGoogle Scholar
  11. 11.
    Kalden-Nemeth D, Grebmeier J, Antoni C, et al. NMR monitoring of rheumatoid arthritis patients receiving anti-TNF-alpha monoclonal antibody therapy. Rheumatol Int 1997; 16: 249–255.CrossRefGoogle Scholar
  12. 12.
    Tam LS, Griffith JF, Yu AB, et al. Rapid improvement in rheumatoid arthritis patients on combination of methotrexate and infliximab: clinical and magnetic resonance imaging evaluation. Clin Rheumatol 2006; 26: 941–946.CrossRefGoogle Scholar
  13. 13.
    Tofts PS. Modeling tracer kinetics in dynamic Gd-DTPA MR imaging. J Magn Reson Imaging 1997; 7: 91–101.CrossRefGoogle Scholar
  14. 14.
    Brookes JA, Redpath TW, Gilbert FJ, et al. Accuracy of T1 measurement in dynamic contrast-enhanced breast MRI using two- and three-dimensional variable flip angle fast low-angle shot. J Magn Reson Imaging 1999; 9: 163–171.CrossRefGoogle Scholar
  15. 15.
    Port RE, Knopp MV, Brix G. Dynamic contrast-enhanced MRI using Gd-DTPA: interindividual variability of the arterial input function and consequences for the assessment of kinetics in tumors. Magn Reson Med 2001; 45: 1030–1038.CrossRefGoogle Scholar
  16. 16.
    Buckley DL, Parker GJM. Measuring contrast agent concentration in T1-weighted dynamic contrast-enhanced MRI. In: Jackson DLBA, Parker GJM, editors. Dynamic contrast enhanced magnetic resonance imaging in oncology. Berlin: Springer; 2003: 69–79.Google Scholar
  17. 17.
    Gold GE, Han E, Stainsby J, et al. Musculoskeletal MRI at 3.0 T: relaxation times and image contrast. AJR Am J Roentgenol 2004; 183: 343–351.CrossRefGoogle Scholar
  18. 18.
    Van Riel PL, Taggart AJ, Sany J, et al. Efficacy and safety of combination etanercept and methotrexate versus etanercept alone in patients with rheumatoid arthritis with an inadequate response to methotrexate: the ADORE study. Ann Rheum Dis 2006; 65: 1478–1483.CrossRefGoogle Scholar
  19. 19.
    Clavel G, Bessis N, Boissier MC. Recent data on the role for angiogenesis in rheumatoid arthritis. Joint Bone Spine 2003; 70: 321–326.CrossRefGoogle Scholar
  20. 20.
    Damle NK, Doyle LV. Stimulation of cloned human T lymphocytes via the CD3 or CD28 molecules induces enhancement in vascular endothelial permeability to macromolecules with participation of type-1 and type-2 intercellular adhesion pathways. Eur J Immunol 1990; 20: 1995–2003.CrossRefGoogle Scholar
  21. 21.
    Konig H, Sieper J, Wolf KJ. [Dynamic magnetic resonance imaging in the differentiation of inflammatory joint lesions]. Rofo 1990; 153: 1–5.CrossRefGoogle Scholar
  22. 22.
    Kirkhus E, Bjornerud A, Thoen J, et al. Contrast-enhanced dynamic magnetic resonance imaging of finger joints in osteoarthritis and rheumatoid arthritis: an analysis based on pharmacokinetic modeling. Acta Radiol 2006; 47: 845–851.CrossRefGoogle Scholar
  23. 23.
    Veale DJ, Reece RJ, Parsons W, et al. Intra-articular primatised anti-CD4: efficacy in resistant rheumatoid knees. A study of combined arthroscopy, magnetic resonance imaging, and histology. Ann Rheum Dis 1999; 58: 342–349.CrossRefGoogle Scholar
  24. 24.
    Rhodes LA, Tan AL, Tanner SF, et al. Regional variation and differential response to therapy for knee synovitis adjacent to the cartilage-pannus junction and suprapatellar pouch in inflammatory arthritis: implications for pathogenesis and treatment. Arthritis Rheum 2004; 50: 2428–2432.CrossRefGoogle Scholar
  25. 25.
    Ling CR, Foster MA. Changes in NMR relaxation time associated with local inflammatory response. Phys Med Biol 1982; 27: 853–860.CrossRefGoogle Scholar
  26. 26.
    Terrier F, Revel D, Reinhold CE, et al. Contrast-enhanced MRI of periarticular soft-tissue changes in experimental arthritis of the rat. Magn Reson Med 1986; 3: 385–396.CrossRefGoogle Scholar

Copyright information

© ISS 2007

Authors and Affiliations

  • Richard J. Hodgson
    • 1
    Email author
  • Theresa Barnes
    • 2
  • Sylvia Connolly
    • 3
  • Brian Eyes
    • 4
  • Robert S. D. Campbell
    • 5
  • Robert Moots
    • 2
  1. 1.MARIARCUniversity of LiverpoolLiverpoolUK
  2. 2.Clinical Rheumatology, School of Clinical SciencesUniversity of AintreeLiverpoolUK
  3. 3.Whiston HospitalMerseysideUK
  4. 4.University Hospital AintreeLiverpoolUK
  5. 5.Royal Liverpool HospitalLiverpoolUK

Personalised recommendations