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Review article: Biomedical intelligence

Vol. 142 No. 0102 (2012)

Imaging in arthritis: quantifying effects of therapeutic intervention using MRI and molecular imaging

  • MA Cimmino
  • F Barbieri
  • G Zampogna
  • D Camellino
  • F Paparo
  • M Parodi
DOI
https://doi.org/10.57187/smw.2012.13326
Cite this as:
Swiss Med Wkly. 2012;142:w13326
Published
01.01.2012

Summary

Modern imaging techniques are becoming increasingly important in assessing the course of arthritis and in permitting measurement of response to treatment as part of the follow-up of patients. They include ultrasonography (US), MRI, PET/CT, and biofluorescence. In patients with rheumatoid arthritis, clinical evaluation is significantly less sensitive than either US or MRI in detecting synovitis. As a result, imaging is a useful alternative to achieving proper assessment of disease activity. The different areas in which the new imaging techniques could help practicing rheumatologists and internal physicians include the following: early and differential diagnosis of arthritis, evaluation of disease activity, prognosis, assessment of treatment efficacy, assessment of remission, and evaluation of subclinical disease. MRI is probably the best imaging method to study disease activity in RA, because it can study all the joints with similar efficacy, has been sufficiently standardised, and yields data on inflammation that can be quantified. Different methods, developed to score synovitis activity, are increasingly used in clinical trials. The main application of PET/CT in rheumatology is the diagnosis and follow-up of large vessel vasculitis. More recently, also RA disease activity has been evaluated, allowing a panoramic view of the patient. Molecular imaging studies molecular and cellular processes in intact living organisms in a non-invasive fashion. In fluorescence, dyes, that emit light upon excitation by a light source and are read by a camera, can be used to show inflamed areas where neoangiogenesis, vasodilatation, and increased vessel permeability are present. These dyes can be coupled with different compounds including antibodies and drugs.

References

  1. Cimmino MA, Grassi W, Cutolo M. Modern imaging techniques: a revolution for rheumatology practice. Best Pract Res Clin Rheumatol. 2008;22:951–9. DOI: https://doi.org/10.1016/j.berh.2008.08.007
  2. Cimmino MA, Masocco M, Torre M. Hospital admissions for rheumatoid arthritis dwindled in Italy between 2001 and 2008. Rheumatology (Oxford) 2011 Sep 8. [Epub ahead of print]. DOI: https://doi.org/10.1093/rheumatology/ker279
  3. Szkudlarek M, Klarlund M, Narvestad E, Court-Payen M, Strandberg C, Jensen KE, et al. Ultrasonography of the metacarpophalangeal and proximal interphalangeal joints in rheumatoid arthritis: a comparison with magnetic resonance imaging, conventional radiography and clinical examination. Arthritis Res Ther. 2006;8:R52. DOI: https://doi.org/10.1186/ar1904
  4. Tamai M, Kawakami A, Iwamoto N, Kawashiri SY, Fujikawa K, Aramaki T, et al. Comparative study of the detection of joint injury in early-stage rheumatoid arthritis by magnetic resonance imaging of the wrists and finger joints and physical examination. Arthritis Care Res. 2011;63:436–9. DOI: https://doi.org/10.1002/acr.20395
  5. McGonagle D, Tan AL. What magnetic resonance imaging has told us about the pathogenesis of rheumatoid arthritis – the first 50 years. Arthritis Res Ther. 2008;10:222. DOI: https://doi.org/10.1186/ar2512
  6. Haslam KE, McCann LJ, Wyatt S, Wakefield RJ. The detection of subclinical synovitis by ultrasound in oligoarticular juvenile idiopathic arthritis: a pilot study. Rheumatology. (Oxford) 2010;49:123–7. DOI: https://doi.org/10.1093/rheumatology/kep339
  7. Tamai M, Kawakami A, Uetani M, Takao S, Arima K, Iwamoto N, et al. A prediction rule for disease outcome in patients with undifferentiated arthritis using magnetic resonance imaging of the wrists and finger joints and serologic autoantibodies. Arthritis Care Res. 2009;61:772–8. DOI: https://doi.org/10.1002/art.24711
  8. Boyesen P, Haavardsholm EA, Østergaard M, van der Heijde D, Sesseng S, Kvien TK. MRI in early rheumatoid arthritis: synovitis and bone marrow oedema are independent predictors of subsequent radiographic progression. Ann Rheum Dis. 2011;70:428–33. DOI: https://doi.org/10.1136/ard.2009.123950
  9. Sugimoto H, Takeda A, Hyodoh K. Early-stage rheumatoid arthritis: prospective study of the effectiveness of MR imaging for diagnosis. Radiology. 2000;216:569–75. DOI: https://doi.org/10.1148/radiology.216.2.r00au20569
  10. Neogi T, Aletaha D, Silman AJ, Naden RL, Felson DT, Aggarwal R, et al. The 2010 American College of Rheumatology/European League against Rheumatism classification criteria for rheumatoid arthritis: Phase 2 methodological report. Ann Rheum Dis. 2010;62:2582–91. DOI: https://doi.org/10.1002/art.27580
  11. McGonagle D, Gibbon W, Emery P. Classification of inflammatory arthritis by enthesitis. Lancet. 1998;352:1137–40. DOI: https://doi.org/10.1016/S0140-6736(97)12004-9
  12. Cimmino MA, Parodi M, Zampogna G, Paparo F, Silvestri E, Garlaschi G, et al. Magnetic resonance imaging of the hand in psoriatic arthritis. J Rheumatol. (Suppl) 2009;83:39–41. DOI: https://doi.org/10.3899/jrheum.090221
  13. Cimmino MA, Parodi M, Innocenti S, Succio G, Banderali S, Silvestri E, et al. Dynamic magnetic resonance of the wrist in psoriatic arthritis reveals imaging patterns similar to those of rheumatoid arthritis. Arthritis Res Ther. 2005;7:R725–31. DOI: https://doi.org/10.1186/ar1734
  14. Schwenzer NF, Kötter I, Henes JC, Schraml C, Fritz J, Claussen CD. The role of dynamic contrast-enhanced MRI in the differential diagnosis of psoriatic and rheumatoid arthritis. Am J Radiol. 2010;194:715–20. DOI: https://doi.org/10.2214/AJR.09.2671
  15. Scarpa R, Cuocolo A, Peluso R, Atteno M, Gisonni P, Iervolino S, et al. Early psoriatic arthritis: the clinical spectrum. J Rheumatol. 2007;35:137–41.
  16. Cimmino MA, Grassi W. What is new in ultrasound and magnetic resonance imaging for musculoskeletal disorders? Best Pract Res Clin Rheumatol. 2008;22:1141–8. DOI: https://doi.org/10.1016/j.berh.2008.09.012
  17. Barrera P, Oyen WJ, Boerman OC, van Riel PL. Scintigraphic detection of tumour necrosis factor in patients with rheumatoid arthritis. Ann Rheum Dis. 2003;62:825–8. DOI: https://doi.org/10.1136/ard.62.9.825
  18. Hetland ML, Stengaard-Pedersen K, Junker P, Østergaard M, Ejbjerg BJ, Jacobsen S, et al. Radiographic progression and remission rates in early rheumatoid arthritis – MRI bone oedema and anti-CCP predicted radiographic progression in the 5-year extension of the double-blind randomised CIMESTRA trial. Ann Rheum Dis. 2010;69:1789–95. DOI: https://doi.org/10.1136/ard.2009.125534
  19. Scirè CA, Montecucco C, Codullo V, Epis O, Todoerti M, Caporali R. Ultrasonographic evaluation of joint involvement in early rheumatoid arthritis in clinical remission: power Doppler signal predicts short-term relapse. Rheumatology. (Oxford) 2009;48:1092–7. DOI: https://doi.org/10.1093/rheumatology/kep171
  20. Duer-Jensen A, Horslev-Petersen K, Hetland ML, Bak L, Ejbjerg BJ, Hansen MS, et al. Bone edema on magnetic resonance imaging is an independent predictor of rheumatoid arthritis development in patients with early undifferentiated arthritis. Arthritis Rheum. 2011;63:2192–202. DOI: https://doi.org/10.1002/art.30396
  21. Narváez J, Sirvent E, Narváez JA, Bas J, Gómez-Vaquero C, Reina D, et al. Usefulness of magnetic resonance imaging of the hand versus anticyclic citrullinated peptide antibody testing to confirm the diagnosis of clinically suspected early rheumatoid arthritis in the absence of rheumatoid factor and radiographic erosions. Semin Arthritis Rheum. 2008;38:101–9. DOI: https://doi.org/10.1016/j.semarthrit.2007.10.012
  22. Felson DT, Smolen JS, Wells G, Zhang B, van Tuyl LH, Funovits J, et al. American College of Rheumatology/European League Against Rheumatism provisional definition of remission in rheumatoid arthritis for clinical trials. Arthritis Rheum. 2011;63:573–86. DOI: https://doi.org/10.1002/art.30552
  23. Brown AK, Conaghan PG, Karim Z, Quinn MA, Ikeda K, Peterfy CG, et al. An explanation for the apparent dissociation between clinical remission and continued structural deterioration in rheumatoid arthritis. Arthritis Rheum. 2008;58:2958–67. DOI: https://doi.org/10.1002/art.23945
  24. Gisondi P, Tinazzi I, El-Dalati G, Gallo M, Biasi D, Barbara LM, et al. Lower limb enthesopathy in patients with psoriasis without clinical signs of arthropathy: a hospital-based case-control study. Ann Rheum Dis. 2008;67:26–30. DOI: https://doi.org/10.1136/ard.2007.075101
  25. Offidani A, Cellini A, Valeri G, Giovagnoni A. Subclinical joint involvement in psoriasis: magnetic resonance imaging and X-ray findings. Acta dermatol Venereol. 1998;78:463–5. DOI: https://doi.org/10.1080/000155598442809
  26. Machado PM, Koevoets R, Bombardier C, van der Heijde DM. The value of magnetic resonance imaging and ultrasound in undifferentiated arthritis: a systematic review. J Rheumatol. (Suppl) 2011;87:31–7. DOI: https://doi.org/10.3899/jrheum.101072
  27. Weber U, Hodler J, Kubik RA, Rufibach K, Lambert RG, Kissling RO, et al. Sensitivity and specificity of spinal inflammatory lesions assessed by whole-body magnetic resonance imaging in patients with ankylosing spondylitis or recent-onset inflammatory back pain. Arthritis Rheum. 2009;61:900–8. DOI: https://doi.org/10.1002/art.24507
  28. Cimmino MA, Bountis C, Silvestri E, Garlaschi G, Accardo S. An appraisal of magnetic resonance imaging of the wrist in rheumatoid arthritis. Semin Arthritis Rheum. 2000;30:180–95. DOI: https://doi.org/10.1053/sarh.2000.9204
  29. Cimmino MA, Innocenti S, Livrone F, Magnaguagno F, Silvestri E, Garlaschi G. Dynamic gadolinium-enhanced magnetic resonance imaging of the wrist in patients with rheumatoid arthritis can discriminate active from inactive disease. Arthritis Rheum. 2003;48:1207–13. DOI: https://doi.org/10.1002/art.10962
  30. Ostergaard M, Peterfy C, Conaghan P, McQueen F, Bird P, Ejbjerg B, et al. OMERACT rheumatoid arthritis magnetic resonance imaging studies. Core set of MRI acquisitions, joint pathology definitions, and the OMERACT RA-MRI scoring system. J Rheumatol. 2003;30:1385–6.
  31. Bird P, Conaghan P, Ejbjerg B, McQueen F, Lassere M, Peterfy C, et al. The development of the EULAR-OMERACT rheumatoid arthritis MRI reference image atlas. Ann Rheum Dis. 2005;64(Suppl 1):i8-10. DOI: https://doi.org/10.1136/ard.2004.031807
  32. Haavardsholm EA, Østergaard M, Ejbjerg BJ, Kvan NP, Kvien TK. Introduction of a novel magnetic resonance imaging tenosynovitis score for rheumatoid arthritis: reliability in a multireader longitudinal study. Ann Rheum Dis. 2007;66:1216–20. DOI: https://doi.org/10.1136/ard.2006.068361
  33. Boesen M, Østergaard M, Cimmino MA, Kubassova O, Jensen KE, Bliddal H. MRI quantification of rheumatoid arthritis: current knowledge and future perspectives. Eur J Radiol. 2009;76:438–9. DOI: https://doi.org/10.1016/j.ejrad.2009.04.048
  34. Kubassova O, Boesen M, Cimmino MA, Bliddal H. A computer-aided detection system for rheumatoid arthritis MRI data interpretation and quantification of synovial activity. Eur J Radiol. 2010;74:e67–72. DOI: https://doi.org/10.1016/j.ejrad.2009.04.010
  35. Kubassova O, Boesen M, Peloschek P, Langs G, Cimmino MA, Bliddal H, et al. Quantifying disease activity and damage by imaging in rheumatoid arthritis and osteoarthritis. Ann N Y Acad Sci. 2009;1154:207–38. DOI: https://doi.org/10.1111/j.1749-6632.2009.04392.x
  36. Boesen M, Kubassova O, Parodi M, Bliddal H, Innocenti S, Garlaschi G, et al. Comparison of the manual and computer-aided techniques for evaluation of wrist synovitis using dynamic contrast-enhanced MRI on a dedicated scanner. Eur J Radiol. 2011;77:202–6. DOI: https://doi.org/10.1016/j.ejrad.2010.09.041
  37. Parodi M, Zampogna G, Barbieri F, Paparo F, Garlaschi G, Cutolo M, et al. Short-term follow-up of RA patients treated with rituximab by extremity-dedicated MRI: dynamic MRI is more sensitive than RAMRIS in the evaluation of synovitis. Ann Rheum Dis. 2010;69(Suppl 3):380–1.
  38. Østergaard M, Hansen M, Stoltenberg M, Jensen KE, Szkudlarek M, Pedersen-Zbinden B, et al. New radiographic bone erosions in the wrists of patients with rheumatoid arthritis are detectable with magnetic resonance imaging a median of two years earlier. Arthritis Rheum. 2003;48:2128–31. DOI: https://doi.org/10.1002/art.11076
  39. Oliviero F, Ramonda R, Punzi L. New horizons in osteoarthritis. Swiss Med Wkly 2010;140:w13098. doi: 10.4414/smw.2010.13098. DOI: https://doi.org/10.4414/smw.2010.13098
  40. Barbieri F, Parodi M, Zampogna G, Paparo F, Cimmino MA. Bone ankylosis of the wrist as a possible indicator of treatment efficacy in rheumatoid arthritis. Rheumatology. (Oxford) 2010;49:1414–6. DOI: https://doi.org/10.1093/rheumatology/keq071
  41. Barbieri F, Parodi M, Zampogna G, Paparo F, Cimmino MA. Caveat on the interpretation of metacarpal head erosions seen by magnetic resonance imaging. J Rheumatol. 2010;37:1965–6. DOI: https://doi.org/10.3899/jrheum.100212
  42. Parodi M, Silvestri E, Garlaschi G, Cimmino MA. How normal are the hands of normal controls? A study with dedicated magnetic resonance imaging. Clin Exp Rheumatol. 2006;24:134–41.
  43. Peterfy CG. Magnetic resonance imaging of rheumatoid arthritis: the evolution of clinical applications through clinical trials. Semin Arthritis Rheum. 2001;30:375–96. DOI: https://doi.org/10.1053/sarh.2001.22497
  44. Genovese MC, Kavanaugh A, Weinblatt ME, Peterfy C, DiCarlo J, White ML, et al. An oral Syk kinase inhibitor in the treatment of rheumatoid arthritis. Arthritis Rheum. 2011;63:337–45. DOI: https://doi.org/10.1002/art.30114
  45. Mease P, Genovese MC, Gladstein G, Kivits AJ, Ritchlin C, Tak PP, et al. Abatacept in the treatment of patients with psoriatic arthritis. Arthritis Rheum. 2011;63:939–48. DOI: https://doi.org/10.1002/art.30176
  46. Von Schulthess GK, Steinert HC, Hany TF. Integrated PET/CT: current applications and future directions. Radiology. 2006;238:405–22. DOI: https://doi.org/10.1148/radiol.2382041977
  47. Morbelli S, Piccardo A, Villavecchia G, Dessi B, Brugnolo A, Piccini A, et al. Mapping brain morphological and functional conversion patterns in amnestic MCI: a voxel-based MRI and FDG-PET study. Eur J Nucl Med Mol Imaging. 2010;37:36–45. DOI: https://doi.org/10.1007/s00259-009-1218-6
  48. Wunder A, Straub RH, Gay S, Funk J, Müller-Ladner U. Molecular imaging: novel tools in visualizing rheumatoid arthritis. Rheumatology. (Oxford) 2005;44:1341–9. DOI: https://doi.org/10.1093/rheumatology/keh709
  49. Camellino D, Cimmino MA. Imaging of polymyalgia rheumatica: indications on its pathogenesis, diagnosis and prognosis. Rheumatology (Oxford) 2011 May 12 [Epub ahead of print]. DOI: https://doi.org/10.1093/rheumatology/keq450
  50. Camellino D, Morbelli S, Sambuceti G, Cimmino MA. Methotrexate treatment of polymyalgia rheumatica/giant cell arteritis-associated large vessel vasculitis. Clin Exp Rheumatol. 2010;28:288–9.
  51. Kubota K, Ito K, Morooka M, Mitsumoto T, Kurihara K, Yamashita H, et al. Whole-body FDG-PET/CT on rheumatoid arthritis of large joints. Ann Nucl Med. 2009;23:783–91. DOI: https://doi.org/10.1007/s12149-009-0305-x
  52. Elzinga EH, van der Laken CJ, Comans EFI, Lammertsma AA, Dijkmans BAC, Voskuyl AE. 2-Deoxy-2-[F18]fluoro-D-glucose joint uptake on positron emission tomography images: rheumatoid arthritis versus osteoarthritis. Mol Imaging Biol. 2007;9:357–60. DOI: https://doi.org/10.1007/s11307-007-0113-4
  53. Beckers C, Jeukens X, Ribbens C, André B, Marcelis S, Leclercq P, et al. 18F-FDG PET imaging of rheumatoid knee synovitis correlates with dynamic magnetic resonance and sonographic assessments as well as with the serum level of metalloproteinase-3. Eur J Nucl Med Mol Imaging. 2006;33:275–80. DOI: https://doi.org/10.1007/s00259-005-1952-3
  54. Beckers C, Ribbens C, André B, Marcelis S, Kaye O, Mathy L, et al. Assessment of disease activity in rheumatoid arthritis with 18F-FDG PET. J Nucl Med. 2004;45:956–64.
  55. Chaudari AJ, Bowen SL, Burkett GW, Packard NJ, Godinez F, Joshi AA, et al. High resolution 18F-FDG PET with MRI for monitoring response to treatment in rheumatoid arthritis. Eur J Nucl Med Mol Imaging. 2010;37:1047. DOI: https://doi.org/10.1007/s00259-009-1364-x
  56. Vogel WV, van Riel PLCM, Oyen WJG. FDG-PET/CT can visualize the extent of inflammation in rheumatoid arthritis of the tarsus. Eur J Nucl Med Mol Imaging. 2007;34:439. DOI: https://doi.org/10.1007/s00259-006-0246-8
  57. Taniguchi Y, Arii K, Kumon Y, Fukumoto M, Ohnishi T, Horino T, et al. Positron emission tomography/computed tomography: a clinical tool for evaluation of enthesitis in patients with spondyloarthritides. Rheumatology. (Oxford) 2010;49:348–54. DOI: https://doi.org/10.1093/rheumatology/kep379
  58. Palframan R, Airey M, Moore A, Vugler A, Nesbitt A. Use of biofluorescence imaging to compare the distribution of certulizumab pegol, adalimumab, and infliximab in the inflamed paws of rats with collagen-induced arthritis. J Immunol Met. 2009;348:36–41. DOI: https://doi.org/10.1016/j.jim.2009.06.009
  59. Werner S, Ohrndorf S, Langer HE, Bahner M, Schwenke C, Burmester GR, et al. Comparison of xiralite with clinical examination and ultrasonography. Ann Rheum Dis. 2011;70(Suppl 3):361.