Skip to main content

Advertisement

Log in

Characterization of synovial tissue from arthritis patients: a proton magnetic resonance spectroscopic investigation

  • Original Article
  • Published:
Rheumatology International Aims and scope Submit manuscript

Abstract

Hypoxia may contribute to the pathogenesis of synovitis in rheumatoid arthritis (RA). Magnetic resonance spectroscopy (MRS) is a technique that uses radiofrequency waves to generate a signal which allows a qualitative and quantitative assessment of the biochemical composition of tissue. MRS was used to evaluate RA synovial tissue for evidence of hypoxia and anaerobic metabolism. Synovial tissue samples obtained from eighteen RA patients and four osteoarthritis control patients undergoing total knee replacement were analyzed using proton MRS, processed for histopathology and scored for inflammation and vascularity. Spectra from severely and mildly inflamed tissue differed in peak intensity at regions 1.3 ppm (representing lactic acid and lipid), 3.0 ppm (representing creatine), 3.2 ppm (representing choline containing metabolites), and 3.8 ppm (representing carbohydrates, possibly glucose). With increasing inflammation, the intensities of the peak resonance at 1.3 ppm increased and that at 3.8 ppm decreased. The intensities of the 3.8 and 3.0 ppm peaks were reduced in highly vascular tissue. Specific MR spectral features reflect the anaerobic metabolism that is evident with progressively increasing degrees of RA synovial inflammation and vascularity. These features correlate partially with synovial histopathology.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Gaber T, Dziurla R, Tripmacher R et al (2005) Hypoxia inducible factor (HIF) in rheumatology: low O2! See what HIF can do!. Ann Rheum Dis 64(7):971–980. doi:10.1136/ard.2004.031641

    Article  PubMed  CAS  Google Scholar 

  2. Treuhaft PS, MCCarty DJ (1971) Synovial fluid pH, lactate, oxygen and carbon dioxide partial pressure in various joint diseases. Arthritis Rheum 14(4):475–484. doi:10.1002/art.1780140407

    Article  PubMed  CAS  Google Scholar 

  3. Naughton DP, Haywood R, Blake DR et al (1993) A comparative evaluation of the metabolic profiles of normal and inflammatory knee-joint synovial fluids by high resolution proton NMR spectroscopy. FEBS Lett 332(3):221–225. doi:10.1016/0014-5793(93)80636-9

    Article  PubMed  CAS  Google Scholar 

  4. Naughton D, Whelan M, Smith EC et al (1993) An investigation of the abnormal metabolic status of synovial fluid from patients with rheumatoid arthritis by high field proton nuclear magnetic resonance spectroscopy. FEBS Lett 317(1–2):135–138. doi:10.1016/0014-5793(93)81508-W

    Article  PubMed  CAS  Google Scholar 

  5. Lund-Olesen K (1970) Oxygen tension in synovial fluids. Arthritis Rheum 13(6):769–776. doi:10.1002/art.1780130606

    Article  PubMed  CAS  Google Scholar 

  6. Hitchon CA, Ziouzina O, Hart D et al (2002) Are hypoxic synovial fluid conditions associated with measures of synovial angiogenesis? Arthritis Rheum 9(46):S548

    Google Scholar 

  7. Grootveld M, Henderson EB, Farrell A et al (1991) Oxidative damage to hyaluronate and glucose in synovial fluid during exercise of the inflamed rheumatoid joint. Detection of abnormal low-molecular-mass metabolites by proton-n.m.r spectroscopy. Biochem J 273(Pt 2):459–467

    PubMed  CAS  Google Scholar 

  8. Schiller J, Arnhold J, Sonntag K, Arnold K (1996) NMR studies on human, pathologically changed synovial fluids: role of hypochlorous acid. Magn Reson Med 35(6):848–853. doi:10.1002/mrm.1910350610

    Article  PubMed  CAS  Google Scholar 

  9. Hollander AP, Corke KP, Freemont AJ, Lewis CE (2001) Expression of hypoxia-inducible factor 1alpha by macrophages in the rheumatoid synovium: implications for targeting of therapeutic genes to the inflamed joint. Arthritis Rheum 44(7):1540–1544. doi:10.1002/1529-0131(200107)44:7<1540::AID-ART277>3.0.CO;2-7

    Article  PubMed  CAS  Google Scholar 

  10. Giatromanolaki A, Sivridis E, Maltezos E et al (2003) Upregulated hypoxia inducible factor-1alpha and -2alpha pathway in rheumatoid arthritis and osteoarthritis. Arthritis Res Ther 5(4):R193–R201. doi:10.1186/ar756

    Article  PubMed  CAS  Google Scholar 

  11. Hitchon C, Wong K, Ma G et al (2002) Hypoxia-induced production of stromal cell-derived factor 1 (CXCL12) and vascular endothelial growth factor by synovial fibroblasts. Arthritis Rheum 46(10):2587–2597. doi:10.1002/art.10520

    Article  PubMed  CAS  Google Scholar 

  12. Singh D, Nazhat NB, Fairburn K et al (1995) Electron spin resonance spectroscopic demonstration of the generation of reactive oxygen species by diseased human synovial tissue following ex vivo hypoxia–reoxygenation. Ann Rheum Dis 54(2):94–99. doi:10.1136/ard.54.2.94

    Article  PubMed  CAS  Google Scholar 

  13. Peters CL, Morris CJ, Mapp PI et al (2004) The transcription factors hypoxia-inducible factor 1alpha and Ets-1 colocalize in the hypoxic synovium of inflamed joints in adjuvant-induced arthritis. Arthritis Rheum 50(1):291–296. doi:10.1002/art.11473

    Article  PubMed  CAS  Google Scholar 

  14. Lean CL, Newland RC, Ende DA et al (1993) Assessment of human colorectal biopsies by 1H MRS: correlation with histopathology. Magn Reson Med 30(5):525–533. doi:10.1002/mrm.1910300502

    Article  PubMed  CAS  Google Scholar 

  15. Mountford CE, Saunders JK, May GL et al (1986) Classification of human tumours by high-resolution magnetic resonance spectroscopy. Lancet 1(8482):651–653. doi:10.1016/S0140-6736(86)91727-7

    Article  PubMed  CAS  Google Scholar 

  16. Bezabeh T, Somorjai RL, Smith IC et al (2001) The use of 1H magnetic resonance spectroscopy in inflammatory bowel diseases: distinguishing ulcerative colitis from Crohn’s disease. Am J Gastroenterol 96(2):442–448. doi:10.1111/j.1572-0241.2001.03523.x

    Article  PubMed  CAS  Google Scholar 

  17. Smith ICP, Bezabeh T (2000) Tissue NMR ex vivo. In: Young IR (ed) Methods in biomedical magnetic resonance imaging and spectroscopy. Wiley, Chichester, pp 891–897

    Google Scholar 

  18. Bezabeh T, Mowat MR, Jarolim L et al (2001) Detection of drug-induced apoptosis and necrosis in human cervical carcinoma cells using 1H NMR spectroscopy. Cell Death Differ 8(3):219–224. doi:10.1038/sj.cdd.4400802

    Article  PubMed  CAS  Google Scholar 

  19. El-Sayed S, Bezabeh T, Odlum O et al (2002) An ex-vivo study exploring the diagnostic potential of 1H magnetic resonance spectroscopy in squamous cell carcinoma of the head and neck region. Head Neck 24(8):766–772. doi:10.1002/hed.10125

    Article  PubMed  Google Scholar 

  20. Bezabeh T, Smith IC, Krupnik E et al (1996) Diagnostic potential for cancer via 1H magnetic resonance spectroscopy of colon tissue. Anticancer Res 16(3B):1553–1558

    PubMed  CAS  Google Scholar 

  21. Hahn P, Smith IC, Leboldus L et al (1997) The classification of benign and malignant human prostate tissue by multivariate analysis of 1H magnetic resonance spectra. Cancer Res 57(16):3398–3401

    PubMed  CAS  Google Scholar 

  22. Lean CL, Mackinnon WB, Mountford CE (1991) Fucose in 1H COSY spectra of plasma membrane fragments shed from human malignant colorectal cells. Magn Reson Med 20(2):306–311. doi:10.1002/mrm.1910200213

    Article  PubMed  CAS  Google Scholar 

  23. Lean CL, Mackinnon WB, Delikatny EJ et al (1992) Cell-surface fucosylation and magnetic resonance spectroscopy characterization of human malignant colorectal cells. Biochemistry 31(45):11095–11105. doi:10.1021/bi00160a020

    Article  PubMed  CAS  Google Scholar 

  24. Mandal A, Mayberry J (2001) Magnetic resonance spectroscopy: a new test for differentiating ulcerative colitis from Crohn’s disease? Am J Gastroenterol 96(2):271–273. doi:10.1111/j.1572-0241.2001.03546.x

    Article  PubMed  CAS  Google Scholar 

  25. Arnett FC, Edworthy SM, Bloch DA et al (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31(3):315–324. doi:10.1002/art.1780310302

    Article  PubMed  CAS  Google Scholar 

  26. Altman R, Asch E, Bloch D et al (1986) Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Arthritis Rheum 29(8):1039–1049. doi:10.1002/art.1780290816

    Article  PubMed  CAS  Google Scholar 

  27. Kuesel AC, Kroft T, Saunders JK et al (1992) A simple procedure for obtaining high-quality NMR spectra of semiquantitative value from small tissue specimens: cervical biopsies. Magn Reson Med 27(2):349–355. doi:10.1002/mrm.1910270215

    Article  PubMed  CAS  Google Scholar 

  28. Tak PP, van der Lubbe PA, Cauli A et al (1995) Reduction of synovial inflammation after anti-CD4 monoclonal antibody treatment in early rheumatoid arthritis. Arthritis Rheum 38(10):1457–1465. doi:10.1002/art.1780381012

    Article  PubMed  CAS  Google Scholar 

  29. Listinsky JJ, Siegal GP, Listinsky CM (1998) Alpha-l-fucose: a potentially critical molecule in pathologic processes including neoplasia. Am J Clin Pathol 110(4):425–440

    PubMed  CAS  Google Scholar 

  30. Somorjai RL, Alexander M, Baumgartner R et al (2004) A data-driven, flexible machine learning strategy for the classification of biomedical data. In: Dubitzky W, Azuaje F (eds) Artificial intelligence methods and tools for systems biology, computational biology series, vol 5. Springer, Berlin, pp 67–85

  31. Higai K, Aoki Y, Azuma Y, Matsumoto K (2005) Glycosylation of site-specific glycans of alpha1-acid glycoprotein and alterations in acute and chronic inflammation. Biochim Biophys Acta 1725(1):128–135

    PubMed  CAS  Google Scholar 

  32. Gornik I, Maravic G, Dumic J et al (1999) Fucosylation of IgG heavy chains is increased in rheumatoid arthritis. Clin Biochem 32(8):605–608. doi:10.1016/S0009-9120(99)00060-0

    Article  PubMed  CAS  Google Scholar 

  33. Wang Y, Holmes E, Comelli EM et al (2007) Topographical variation in metabolic signatures of human gastrointestinal biopsies revealed by high-resolution magic-angle spinning 1H NMR spectroscopy. J Proteome Res 6(10):3944–3951. doi:10.1021/pr0702565

    Article  PubMed  CAS  Google Scholar 

  34. Mountford C, Lean C, Malycha P, Russell P (2006) Proton spectroscopy provides accurate pathology on biopsy and in vivo. J Magn Reson Imaging 24(3):459–477. doi:10.1002/jmri.20668

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We would like to thank Dr. Ian C. P. Smith, Dr. Mike Jackson and Dr. Jan Canvin for their useful discussions and constructive suggestions and Dr. David Lyttle for providing surgical samples. We would also like to thank Gouping Ma, Jasvir Marwaha and Rakesh Patel for their technical assistance and Asma Khan for her editorial assistance. This research was supported by Health Sciences Center Foundation and National Research Council of Canada.

Conflict of interest statement

The authors declare no conflict of interest relating to this work.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Carol A. Hitchon.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hitchon, C.A., El-Gabalawy, H.S. & Bezabeh, T. Characterization of synovial tissue from arthritis patients: a proton magnetic resonance spectroscopic investigation. Rheumatol Int 29, 1205–1211 (2009). https://doi.org/10.1007/s00296-009-0865-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00296-009-0865-z

Keywords

Navigation