Magnetic resonance imaging (MRI) and musculoskeletal ultrasound (MSUS) may have an important role in the management of patients with rheumatoid arthritis (RA), as both imaging modalities may be helpful in making a diagnosis of RA at a very early stage, influence treatment decisions, and predict disease course, according to a review published in Current Opinion in Rheumatology.

With improved ultrasound machines that are more suitable for the assessment of musculoskeletal disease, along with evidence indicating the benefits of early diagnosis and treatment of RA, there has been a rise in recent years in the use of MSUS for RA.1 

While there is uncertainty regarding the best imaging modality for early diagnosis of RA, a growing body of evidence supports the use of MSUS and MRI, as both were shown to be sensitive and useful for the diagnosis of RA and monitoring response to treatment. Furthermore, both imaging modalities can predict radiographic progression, clinical outcomes, and support decisions on treatment modifications and adjustments.2,3


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Diagnosis

The diagnosis of RA is based on clinical features, but imaging modalities may support the diagnosis by confirming the presence and extent of inflammation. While plain film radiograph was used to be the first imaging modality for the assessment of patients with suspected RA, in recent years MSUS has been increasingly selected as the imaging modality for the diagnosis of RA.4

Ultrasound provides direct visualization of joint structures and can identify pathological changes associated with RA, including signs of acute inflammation, such as synovial and tenosynovial effusion, synovial hypertrophy, or soft tissue edema, as well as structural damage, such as bone erosions, cartilage loss, or tendon tears.1 Augmenting MSUS with amplitude color Doppler imaging has also provided clinically useful information in the assessment of RA and can differentiate between seropositive and seronegative RA.5

Recent ARCTIC (Aiming for Remission in rheumatoid arthritis: a randomized trial examining the benefit of ultrasound in a Clinical TIght Control regimen) and TaSER (Targeting ultrasound remission in early rheumatoid arthritis) studies reported that adding MSUS data to clinically active joints likely will not confer additional information.6,7 However, other studies have supported the role of MSUS for confirming the early diagnosis of RA, as well as the consideration of differential diagnoses.2, 8-9

Evidence for extra-capsular inflammation on US, including tenosynovitis, peri-articular inflammation, and peri-tendonitis, can differentiate RA from other rheumatic conditions.9

Similar to MSUS, MRI is also superior to clinical assessment for detecting inflammation and can support the diagnosis of RA.3 MRI is more sensitive than conventional radiography to detect structural lesions, especially in early disease.10 The advantages of MRI include the potential visualization of bone marrow edema, which has strong prognostic value, the option to store images and compare serial MRIs, and to complete an assessment of all joints and enthuses (whole-body MRI).3

While both MSUS and MRI were included in the European League Against Rheumatism 2013 recommendations on the use of imaging in RA, in the 2016 updated recommendations for the management of early arthritis, only MSUS was recommended, while it was suggested that MRI should be reserved for difficult cases.11 The American College of Rheumatology recommends performing MSUS to elucidate the diagnosis of symptomatic joints.12

Predicting Disease Outcome

Imaging may predict radiographic progression and response to treatment and can also support adjustments, tapering or discontinuation of RA therapy.13

Data suggest that the presence of MSUS subclinical synovitis and high baseline MSUS scores in RA patients in clinical remission may predict disease flare after treatment tapering/discontinuation.14-15 Power Doppler score was also reported to be a potential predictor of radiographic outcome.16-18 Moreover, it has been reported that Doppler activity may predict tapering failure and flares in patients with RA.19-20

MRI changes seen as early as 1 month after treatment initiation for RA can predict long-term radiographic progression.21 Zhang et al. reported that MRI is a potential strong predictor of future radiographic progression of bone erosions in patients with persistent clinical remission.22

Monitoring

Substantial evidence indicates that due to discordance between clinical and imaging remission, neither MSUS nor MRI should be used to direct a treat-to-target therapeutic strategy in patients with RA. In the TaSER study of 111 patients with early RA, there was no difference in clinical outcome when MSUS was used to assess disease activity and guide treatment.6 No difference was noted in outcomes with the systemic use of MSUS in the follow-up of 238 patients with early RA, compared with a conventional strategy that targeted clinical remission.7

Effect of MRI vs. conventional treat-to-target strategies on disease activity remission and radiographic progression in patients with RA was investigated in the IMAGINE-RA study that included 200 patients with RA. An MRI-guided treat-to-target strategy did not improve the rate of disease remission or radiographic progression.23

Conclusion

Both MSUS and MRI are valuable imaging modalities for diagnosis and monitoring of patients with RA, may predict radiographic progression and tapering failure and identify subclinical inflammation. Available data do not support imaging-guided treat-to-target strategy, as these did not improve the rate of disease remission or radiographic progression.

Several new technologies may have an important role in the future, such as 3-dimensional ultrasound, contrast-enhanced ultrasound, MSUS image reading with convolutional neural network, image fusion and whole-body MRI. 

Experts believe that MSUS and MRI will probably become important parts of a more personalized treatment strategy of patients with RA.

References

  1. Di Matteo A, Mankia K, Azukizawa M, Wakefield RJ. The role of musculoskeletal ultrasound in the rheumatoid arthritis continuum. Curr Rheumatol Rep. 2020;22(8):41. doi:10.1007/s11926-020-00911-w
  2. Nieuwenhuis WP, Krabben A, Stomp W, et al. Evaluation of magnetic resonance imaging-detected tenosynovitis in the hand and wrist in early arthritis. Arthritis Rheumatol. 2015;67(4):869-76. doi:10.1002/art.39000. PMID: 25510520
  3. Carstensen SMD, Terslev L, Jensen MP, Østergaard M. Future use of musculoskeletal ultrasonography and magnetic resonance imaging in rheumatoid arthritis. Curr Opin Rheumatol. 2020;32(3):264-272. doi:10.1097/BOR.0000000000000709
  4. Filippucci E, Di Geso L, Grassi W. Progress in imaging in rheumatology. Nat Rev Rheumatol. 2014 Oct;10(10):628-34. doi:10.1038/nrrheum.2014.145
  5. Gadeholt O, Feuchtenberger M, Wech T, Schwaneck EC. Power-Doppler perfusion phenotype in RA patients is dependent on anti-citrullinated peptide antibody status, not on rheumatoid factor. Rheumatol Int. 2019;39(6):1019-1025. doi:10.1007/s00296-019-04256-1
  6. Dale J, Stirling A, Zhang R, et al. Targeting ultrasound remission in early rheumatoid arthritis: the results of the TaSER study, a randomised clinical trial. Ann Rheum Dis. 2016;75(6):1043-50. doi:10.1136/annrheumdis-2015-208941
  7. Haavardsholm EA, Aga AB, Olsen IC, et al. Ultrasound in management of rheumatoid arthritis: ARCTIC randomised controlled strategy trial. BMJ. 2016;354:i4205. doi:10.1136/bmj.i4205
  8. Zou H, Beattie KA, Allen M, Ioannidis G, Larché MJ. Ultrasonography supplements clinical exam to improve early rheumatoid arthritis disease activity monitoring in metatarsophalangeal joints. Clin Rheumatol. 2020;39(5):1483-1491. doi:10.1007/s10067-019-04896-5
  9. Russell AS, Devani A, Maksymowych WP. The role of anti-cyclic citrullinated peptide antibodies in predicting progression of palindromic rheumatism to rheumatoid arthritis. J Rheumatol. 2006;33(7):1240-2
  10. Sundin U, Aga AB, Skare Ø, et al. Conventional versus ultrasound treat to target: no difference in magnetic resonance imaging inflammation or joint damage over 2 years in early rheumatoid arthritis. Rheumatology (Oxford). 2020;59(9):2550-2555. doi:10.1093/rheumatology/kez674
  11. Combe B, Landewe R, Daien CI, et al. 2016 update of the EULAR recommendationsfor the management of early arthritis. Ann Rheum Dis. 2017;76:948–959. doi:10.1136/annrheumdis-2016-210602
  12. McAlindon T, Kissin E, Nazarian L, et al. American College of Rheumatology report on reasonable use of musculoskeletal ultrasonography in rheumatology clinical practice. Arthritis Care Res (Hoboken). 2012;64(11):1625-40. doi:10.1002/acr.21836
  13. Edwards CJ, Kiely P, Arthanari S, et al. Predicting disease progression and poor outcomes in patients with moderately active rheumatoid arthritis: a systematic review. Rheumatol Adv Pract. 2019;3(1):rkz002. doi:10.1093/rap/rkz002
  14. Iwamoto T, Ikeda K, Hosokawa J, et al. Prediction of relapse after discontinuation of biologic agents by ultrasonographic assessment in patients with rheumatoid arthritis in clinical remission: high predictive values of total gray-scale and power Doppler scores that represent residual synovial inflammation before discontinuation. Arthritis Care Res (Hoboken). 2014;66(10):1576-81. doi:10.1002/acr.22303
  15. El Miedany Y, El Gaafary M, Youssef S, et al. Optimizing therapy in inflammatory arthritis: prediction of relapse after tapering or stopping treatment for rheumatoid arthritis patients achieving clinical and radiological remission. Clin Rheumatol. 2016;35:2915–23. doi:10.1007/s10067-016-3413-8
  16. Vreju FA, Filippucci E, Gutierrez M, et al. Subclinical ultrasound synovitis in a particular joint is associated with ultrasound evidence of bone erosions in that same joint in rheumatoid patients in clinical remission. Clin Exp Rheumatol. 2016;34:673–8.
  17. Raffeiner B, Grisan E, Botsios C, et al. Grade and location of power Doppler are predictive of damage progression in rheumatoid arthritis patients in clinical remission by anti-tumour necrosis factor α. Rheumatology (Oxford). 2017;1(56):1320–5. doi:10.1093/rheumatology/kex084
  18. Naredo E, Moller I, Cruz A, et al. Power Doppler ultrasonographic monitoring of response to antitumor necrosis factor therapy in patients with rheumatoid arthritis. Arthritis Rheum. 2008; 58:2248–2256. doi:10.1002/art.23682
  19. Kuettel D, Terslev L, Weber U, et al. Flares in rheumatoid arthritis: do patient-reported swollen and tender joints match clinical and ultrasonography findings? Rheumatology (Oxford). 2020;59(1):129-136. doi:10.1093/rheumatology/kez231
  20. Peluso G, Michelutti A, Bosello S, Gremese E, Tolusso B, Ferraccioli G. Clinical and ultrasonographic remission determines different chances of relapse in early and long standing rheumatoid arthritis. Ann Rheum Dis. 2011;70(1):172-5. doi:10.1136/ard.2010.129924
  21. Conaghan PG, Østergaard M, Troum O, et al. Very early MRI responses to therapy as a predictor of later radiographic progression in early rheumatoid arthritis. Arthritis Res Ther. 2019;21(1):214. doi:10.1186/s13075-019-2000-1
  22. Zhang H, Xu H, Chen S, Mao X. The application value of MRI in the diagnosis of subclinical inflammation in patients with rheumatoid arthritis in remission. J Orthop Surg Res. 2018;13(1):164. doi: 10.1186/s13018-018-0866-2
  23. Møller-Bisgaard S, Hørslev-Petersen K, Ejbjerg B, et al. Effect of magnetic resonance imaging vs conventional treat-to-target strategies on disease activity remission and radiographic progression in rheumatoid arthritis: the IMAGINE-RA randomized clinical trial. JAMA. 2019;321(5):461-472. doi: 10.1001/jama.2018.21362