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Imaging in inflammatory arthritis: progress towards precision medicine

Nature Reviews Rheumatology volume 19, pages 650–665 (2023)Cite this article

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Abstract

Imaging techniques such as ultrasonography and MRI have gained ground in the diagnosis and management of inflammatory arthritis, as these imaging modalities allow a sensitive assessment of musculoskeletal inflammation and damage. However, these techniques cannot discriminate between disease subsets and are currently unable to deliver an accurate prediction of disease progression and therapeutic response in individual patients. This major shortcoming of today’s technology hinders a targeted and personalized patient management approach. Technological advances in the areas of high-resolution imaging (for example, high-resolution peripheral quantitative computed tomography and ultra-high field MRI), functional and molecular-based imaging (such as chemical exchange saturation transfer MRI, positron emission tomography, fluorescence optical imaging, optoacoustic imaging and contrast-enhanced ultrasonography) and artificial intelligence-based data analysis could help to tackle these challenges. These new imaging approaches offer detailed anatomical delineation and an in vivo and non-invasive evaluation of the immunometabolic status of inflammatory reactions, thereby facilitating an in-depth characterization of inflammation. By means of these developments, the aim of earlier diagnosis, enhanced monitoring and, ultimately, a personalized treatment strategy looms closer.

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Fig. 1: Pathological joint changes detected by conventional and advanced imaging modalities.
Fig. 2: Important milestones in morphological and molecular imaging of inflammatory arthritis188,189,190,191,192,193,194.
Fig. 3: Bone damage in rheumatoid arthritis by HR-pQCT.
Fig. 4: Ultra-high field MRI in RA.
Fig. 5: 68Ga-FAPI-04 PET–CT imaging in psoriatic arthritis and rheumatoid arthritis.
Fig. 6: Applying artificial intelligence to MRI in RA.

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References

  1. Schett, G., McInnes, I. B. & Neurath, M. F. Reframing immune-mediated inflammatory diseases through signature cytokine hubs. N. Engl. J. Med. 385, 628–639 (2021).

    Article  CAS  PubMed  Google Scholar 

  2. McInnes, I. B. & Schett, G. The pathogenesis of rheumatoid arthritis. N. Engl. J. Med. 365, 2205–2219 (2011).

    Article  CAS  PubMed  Google Scholar 

  3. Tak, P. P. A personalized medicine approach to biologic treatment of rheumatoid arthritis: a preliminary treatment algorithm. Rheumatology 51, 600–609 (2012).

    Article  CAS  PubMed  Google Scholar 

  4. Van de Putte, L. et al. Efficacy and safety of adalimumab as monotherapy in patients with rheumatoid arthritis for whom previous disease modifying antirheumatic drug treatment has failed. Ann. Rheum. Dis. 63, 508–516 (2004).

    Article  PubMed  PubMed Central  Google Scholar 

  5. Cohen, S. B. et al. Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy: results of a multicenter, randomized, double‐blind, placebo‐controlled, phase III trial evaluating primary efficacy and safety at twenty‐four weeks. Arthritis Rheum. 54, 2793–2806 (2006).

    Article  CAS  PubMed  Google Scholar 

  6. Genovese, M. C. et al. Abatacept for rheumatoid arthritis refractory to tumor necrosis factor α inhibition. N. Engl. J. Med. 353, 1114–1123 (2005).

    Article  CAS  PubMed  Google Scholar 

  7. Grabner, M. et al. Costs associated with failure to respond to treatment among patients with rheumatoid arthritis initiating TNFi therapy: a retrospective claims analysis. Arthritis Res. Ther. 19, 1–12 (2017).

    Article  Google Scholar 

  8. Pitzalis, C., Choy, E. H. S. & Buch, M. H. Transforming clinical trials in rheumatology: towards patient-centric precision medicine. Nat. Rev. Rheumatol. 16, 590–599 (2020).

    Article  PubMed  Google Scholar 

  9. European Society of Radiology. Medical imaging in personalised medicine: a white paper of the research committee of the European Society of Radiology (ESR). Insights Imaging 6, 141–155 (2015).

    Article  Google Scholar 

  10. Herold, C. J. et al. Imaging in the age of precision medicine: summary of the proceedings of the 10th biannual symposium of the international society for strategic studies in radiology. Radiology 279, 226–238 (2016).

    Article  PubMed  Google Scholar 

  11. Baraliakos, X. et al. Imaging in rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, and osteoarthritis: an international viewpoint on the current knowledge and future research priorities. Eur. J. Rheumatol. 6, 38 (2019).

    PubMed  Google Scholar 

  12. Aydin, S. Z. et al. Imaging in the diagnosis and management of peripheral psoriatic arthritis. Best. Pract. Res. Clin. Rheumatol. 34, 101594 (2020).

    Article  PubMed  Google Scholar 

  13. Tan, Y. K. et al. Ultrasound versus high field magnetic resonance imaging in rheumatoid arthritis. Clin. Exp. Rheumatol. 32, S99–S105 (2014).

    PubMed  Google Scholar 

  14. Ostergaard, M. & Boesen, M. Imaging in rheumatoid arthritis: the role of magnetic resonance imaging and computed tomography. Radiol. Med. 124, 1128–1141 (2019).

    Article  PubMed  Google Scholar 

  15. Weber, U. et al. The impact of MRI on the clinical management of inflammatory arthritides. Skeletal Radiol. 40, 1153–1173 (2011).

    Article  PubMed  Google Scholar 

  16. D’Agostino, M. A. et al. Scoring ultrasound synovitis in rheumatoid arthritis: a EULAR-OMERACT ultrasound taskforce-Part 1: definition and development of a standardised, consensus-based scoring system. RMD Open 3, e000428 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  17. Ostergaard, M. et al. The OMERACT psoriatic arthritis magnetic resonance imaging scoring system (PsAMRIS): definitions of key pathologies, suggested MRI sequences, and preliminary scoring system for PsA Hands. J. Rheumatol. 36, 1816–1824 (2009).

    Article  PubMed  Google Scholar 

  18. Ostergaard, M. et al. The OMERACT rheumatoid arthritis magnetic resonance imaging (MRI) scoring system: updated recommendations by the OMERACT MRI in Arthritis Working Group. J. Rheumatol. 44, 1706–1712 (2017).

    Article  PubMed  Google Scholar 

  19. D’Agostino, M. A. et al. Novel algorithms for the pragmatic use of ultrasound in the management of patients with rheumatoid arthritis: from diagnosis to remission. Ann. Rheum. Dis. 75, 1902–1908 (2016).

    Article  PubMed  Google Scholar 

  20. D’Agostino, M. A. et al. Response to secukinumab on synovitis using Power Doppler ultrasound in psoriatic arthritis: 12-week results from a phase III study, ULTIMATE. Rheumatology 61, 1867–1876 (2022).

    Article  PubMed  Google Scholar 

  21. Østergaard, M. et al. The OMERACT MRI in arthritis working group — update on status and future research priorities. J. Rheumatol. 42, 2470–2472 (2015).

    Article  PubMed  Google Scholar 

  22. Narvaez, J. et al. Can magnetic resonance imaging of the hand and wrist differentiate between rheumatoid arthritis and psoriatic arthritis in the early stages of the disease? Semin. Arthritis Rheum. 42, 234–245 (2012).

    Article  PubMed  Google Scholar 

  23. Schoellnast, H. et al. Psoriatic arthritis and rheumatoid arthritis: findings in contrast-enhanced MRI. AJR Am. J. Roentgenol. 187, 351–357 (2006).

    Article  PubMed  Google Scholar 

  24. D’Agostino, M. A. et al. Assessment of peripheral enthesitis in the spondylarthropathies by ultrasonography combined with power Doppler: a cross-sectional study. Arthritis Rheum. 48, 523–533 (2003).

    Article  PubMed  Google Scholar 

  25. Zabotti, A. et al. Differentiation between early rheumatoid and early psoriatic arthritis by the ultrasonographic study of the synovio-entheseal complex of the small joints of the hands. Clin. Exp. Rheumatol. 34, 459–465 (2016).

    PubMed  Google Scholar 

  26. El Miedany, Y. et al. Tailored approach to early psoriatic arthritis patients: clinical and ultrasonographic predictors for structural joint damage. Clin. Rheumatol. 34, 307–313 (2015).

    Article  PubMed  Google Scholar 

  27. Conaghan, P. G. et al. Elucidation of the relationship between synovitis and bone damage: a randomized magnetic resonance imaging study of individual joints in patients with early rheumatoid arthritis. Arthritis Rheum. 48, 64–71 (2003).

    Article  PubMed  Google Scholar 

  28. Ostergaard, M. 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. 48, 2128–2131 (2003).

    Article  PubMed  Google Scholar 

  29. Tinazzi, I. et al. Preliminary evidence that subclinical enthesopathy may predict psoriatic arthritis in patients with psoriasis. J. Rheumatol. 38, 2691–2692 (2011).

    Article  PubMed  Google Scholar 

  30. Nam, J. L. et al. Ultrasound findings predict progression to inflammatory arthritis in anti-CCP antibody-positive patients without clinical synovitis. Ann. Rheum. Dis. 75, 2060–2067 (2016).

    Article  PubMed  Google Scholar 

  31. Salaffi, F. et al. A clinical prediction rule combining routine assessment and power Doppler ultrasonography for predicting progression to rheumatoid arthritis from early-onset undifferentiated arthritis. Clin. Exp. Rheumatol. 28, 686–694 (2010).

    CAS  PubMed  Google Scholar 

  32. Faustini, F. et al. Subclinical joint inflammation in patients with psoriasis without concomitant psoriatic arthritis: a cross-sectional and longitudinal analysis. Ann. Rheum. Dis. 75, 2068–2074 (2016).

    Article  PubMed  Google Scholar 

  33. Kleyer, A. et al. High prevalence of tenosynovial inflammation before onset of rheumatoid arthritis and its link to progression to RA-A combined MRI/CT study. Semin. Arthritis Rheum. 46, 143–150 (2016).

    Article  CAS  PubMed  Google Scholar 

  34. Werner, D. et al. Early changes of the cortical micro-channel system in the bare area of the joints of patients with rheumatoid arthritis. Arthritis Rheumatol. 69, 1580–1587 (2017).

    Article  PubMed  Google Scholar 

  35. Simon, D. et al. Analysis of periarticular bone changes in patients with cutaneous psoriasis without associated psoriatic arthritis. Ann. Rheum. Dis. 75, 660–666 (2016).

    Article  CAS  PubMed  Google Scholar 

  36. Gough, A. K. et al. Generalised bone loss in patients with early rheumatoid arthritis. Lancet 344, 23–27 (1994).

    Article  CAS  PubMed  Google Scholar 

  37. Ritchlin, C. T., Colbert, R. A. & Gladman, D. D. Psoriatic arthritis. N. Engl. J. Med. 376, 2095–2096 (2017).

    Article  PubMed  Google Scholar 

  38. Lee, C. H. et al. Correlation of structural abnormalities of the wrist and metacarpophalangeal joints evaluated by high‐resolution peripheral quantitative computed tomography, 3 Tesla magnetic resonance imaging and conventional radiographs in rheumatoid arthritis. Int. J. Rheum. Dis. 18, 628–639 (2015).

    Article  PubMed  Google Scholar 

  39. Biswas, D. et al. Radiation exposure from musculoskeletal computerized tomographic scans. J. Bone Jt. Surg. 91, 1882–1889 (2009).

    Article  Google Scholar 

  40. Peters, M. et al. Assessment of cortical interruptions in the finger joints of patients with rheumatoid arthritis using HR-pQCT, radiography, and MRI. J. Bone Min. Res. 33, 1676–1685 (2018).

    Article  Google Scholar 

  41. Regensburger, A. et al. A comparative analysis of magnetic resonance imaging and high-resolution peripheral quantitative computed tomography of the hand for the detection of erosion repair in rheumatoid arthritis. Rheumatology 54, 1573–1581 (2015).

    Article  CAS  PubMed  Google Scholar 

  42. Peters, M. et al. Prospective follow-up of cortical interruptions, bone density, and micro-structure detected on HR-pQCT: a study in patients with rheumatoid arthritis and healthy subjects. Calcif. Tissue Int. 104, 571–581 (2019).

    Article  CAS  PubMed  Google Scholar 

  43. Brunet, S. et al. Heterogenous bone response to biologic DMARD therapies in rheumatoid arthritis patients and their relationship to functional indices. Scand. J. Rheumatol. 50, 417–426 (2021).

    Article  CAS  PubMed  Google Scholar 

  44. Klose-Jensen, R. et al. High-resolution peripheral quantitative computed tomography for bone evaluation in inflammatory rheumatic disease. Front. Med. 7, 337 (2020).

    Article  Google Scholar 

  45. Klose-Jensen, R. et al. Diagnostic accuracy of high-resolution peripheral quantitative computed tomography and X-ray for classifying erosive rheumatoid arthritis. Rheumatology 61, 963–973 (2022).

    Article  PubMed  Google Scholar 

  46. Finzel, S. et al. A comparative study of periarticular bone lesions in rheumatoid arthritis and psoriatic arthritis. Ann. Rheum. Dis. 70, 122–127 (2011).

    Article  PubMed  Google Scholar 

  47. Simon, D. et al. Microstructural bone changes are associated with broad-spectrum autoimmunity and predict the onset of rheumatoid arthritis. Arthritis Rheumatol. 74, 418–426 (2022).

    Article  CAS  PubMed  Google Scholar 

  48. Simon, D., Schett, G. & Kleyer, A. Development of joint erosions in the preclinical phase of rheumatoid arthritis depicted by cinematic rendering. Arthritis Rheumatol. 71, 1592 (2019).

    Article  PubMed  Google Scholar 

  49. Kleyer, A. et al. Bone loss before the clinical onset of rheumatoid arthritis in subjects with anticitrullinated protein antibodies. Ann. Rheum. Dis. 73, 854–860 (2014).

    Article  PubMed  Google Scholar 

  50. Hecht, C. et al. Additive effect of anti-citrullinated protein antibodies and rheumatoid factor on bone erosions in patients with RA. Ann. Rheum. Dis. 74, 2151–2156 (2015).

    Article  CAS  PubMed  Google Scholar 

  51. Keller, K. et al. Local bone loss in patients with anti-citrullinated peptide antibody and arthralgia, evaluated with high-resolution peripheral quantitative computed tomography. Scand. J. Rheumatol. 47, 110–116 (2018).

    Article  CAS  PubMed  Google Scholar 

  52. Keller, K. K. et al. One-year progression of erosive disease in patients with anti-citrullinated peptide antibodies and arthralgia. Jt. Bone Spine 87, 181–183 (2020).

    Article  CAS  Google Scholar 

  53. Simon, D. et al. A comparative analysis of articular bone in large cohort of patients with chronic inflammatory diseases of the joints, the gut and the skin. Bone 116, 87–93 (2018).

    Article  PubMed  Google Scholar 

  54. Stemmler, F. et al. Biomechanical properties of bone are impaired in patients with ACPA-positive rheumatoid arthritis and associated with the occurrence of fractures. Ann. Rheum. Dis. 77, 973–980 (2018).

    Article  CAS  PubMed  Google Scholar 

  55. Finzel, S. et al. Repair of bone erosions in rheumatoid arthritis treated with tumour necrosis factor inhibitors is based on bone apposition at the base of the erosion. Ann. Rheum. Dis. 70, 1587–1593 (2011).

    Article  CAS  PubMed  Google Scholar 

  56. Finzel, S. et al. Comparison of the effects of tocilizumab monotherapy and adalimumab in combination with methotrexate on bone erosion repair in rheumatoid arthritis. Ann. Rheum. Dis. 78, 1186–1191 (2019).

    Article  CAS  PubMed  Google Scholar 

  57. Simon, D. et al. Baricitinib improves bone properties and biomechanics in patients with rheumatoid arthritis–results of the prospective interventional BARE BONE trial. Arthritis Rheumatol. https://doi.org/10.1002/art.42617 (2023).

    Article  PubMed  Google Scholar 

  58. Yue, J. et al. Repair of bone erosion in rheumatoid arthritis by denosumab: a high‐resolution peripheral quantitative computed tomography study. Arthritis Care Res. 69, 1156–1163 (2017).

    Article  CAS  Google Scholar 

  59. Schett, G. et al. Psoriatic arthritis from a mechanistic perspective. Nat. Rev. Rheumatol. 18, 311–325 (2022).

    Article  CAS  PubMed  Google Scholar 

  60. McGonagle, D. et al. The concept of a “synovio-entheseal complex” and its implications for understanding joint inflammation and damage in psoriatic arthritis and beyond. Arthritis Rheum. 56, 2482–2491 (2007).

    Article  PubMed  Google Scholar 

  61. Cambre, I. et al. Mechanical strain determines the site-specific localization of inflammation and tissue damage in arthritis. Nat. Commun. 9, 4613 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  62. Simon, D. et al. Association of structural entheseal lesions with an increased risk of progression from psoriasis to psoriatic arthritis. Arthritis Rheumatol. 74, 253–262 (2022).

    Article  PubMed  Google Scholar 

  63. Simon, D. et al. Simultaneous quantification of bone erosions and enthesiophytes in the joints of patients with psoriasis or psoriatic arthritis — effects of age and disease duration. Arthritis Res. Ther. 20, 203 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  64. Kampylafka, E. et al. Resolution of synovitis and arrest of catabolic and anabolic bone changes in patients with psoriatic arthritis by IL-17A blockade with secukinumab: results from the prospective PSARTROS study. Arthritis Res. Ther. 20, 153 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  65. Kampylafka, E. et al. Disease interception with interleukin-17 inhibition in high-risk psoriasis patients with subclinical joint inflammation-data from the prospective IVEPSA study. Arthritis Res. Ther. 21, 178 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  66. Wu, D. et al. Progressive structural bone changes and their relationship with treatment in patients with psoriatic arthritis: a longitudinal HR-pQCT study. Arthritis Res. Ther. 21, 1–10 (2019).

    Article  Google Scholar 

  67. Simon, D. et al. Effect of disease-modifying anti-rheumatic drugs on bone structure and strength in psoriatic arthritis patients. Arthritis Res. Ther. 21, 162 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  68. Baffour, F. I. et al. Photon-counting detector CT for musculoskeletal imaging: a clinical perspective. Am. J. Roentgenol. 220, 551–560 (2023).

    Article  Google Scholar 

  69. Klintström, B. et al. Photon-counting detector CT and energy-integrating detector CT for trabecular bone microstructure analysis of cubic specimens from human radius. Eur. Radiol. Exp. 6, 31 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  70. Baffour, F. I. et al. Ultra-high-resolution imaging of the shoulder and pelvis using photon-counting-detector CT: a feasibility study in patients. Eur. Radiol. 32, 7079–7086 (2022).

    Article  CAS  PubMed  Google Scholar 

  71. FDA. https://www.fda.gov/news-events/press-announcements/fda-clears-first-major-imaging-device-advancement-computed-tomography-nearly-decade (2021).

  72. Barnabe, C. et al. Definition for rheumatoid arthritis erosions imaged with high resolution peripheral quantitative computed tomography and interreader reliability for detection and measurement. J. Rheumatol. 43, 1935–1940 (2016).

    Article  PubMed  Google Scholar 

  73. Stok, K. S. et al. Consensus approach for 3D joint space width of metacarpophalangeal joints of rheumatoid arthritis patients using high-resolution peripheral quantitative computed tomography. Quant. Imaging Med. Surg. 10, 314–325 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  74. Robitaille, P. M. et al. Design and assembly of an 8 Tesla whole-body MR scanner. J. Comput. Assist. Tomogr. 23, 808–820 (1999).

    Article  CAS  PubMed  Google Scholar 

  75. Yacoub, E. et al. Imaging brain function in humans at 7 Tesla. Magn. Reson. Med. 45, 588–594 (2001).

    Article  CAS  PubMed  Google Scholar 

  76. Ladd, M. E. et al. Pros and cons of ultra-high-field MRI/MRS for human application. Prog. Nucl. Magn. Reson. Spectrosc. 109, 1–50 (2018).

    Article  CAS  PubMed  Google Scholar 

  77. Aringhieri, G., Zampa, V. & Tosetti, M. Musculoskeletal MRI at 7 T: do we need more or is it more than enough? Eur. Radiol. Exp. 4, 48 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  78. Welsch, G. H. et al. Magnetic resonance imaging of the knee at 3 and 7 Tesla: a comparison using dedicated multi-channel coils and optimised 2D and 3D protocols. Eur. Radiol. 22, 1852–1859 (2012).

    Article  PubMed  Google Scholar 

  79. Theysohn, J. M. et al. Bilateral hip imaging at 7 Tesla using a multi-channel transmit technology: initial results presenting anatomical detail in healthy volunteers and pathological changes in patients with avascular necrosis of the femoral head. Skeletal Radiol. 42, 1555–1563 (2013).

    Article  CAS  PubMed  Google Scholar 

  80. Springer, E. et al. Comparison of routine knee magnetic resonance imaging at 3 T and 7 T. Invest. Radiol. 52, 42–54 (2017).

    Article  PubMed  Google Scholar 

  81. Chang, G. et al. Reproducibility of subregional trabecular bone micro-architectural measures derived from 7-Tesla magnetic resonance images. MAGMA 24, 121–125 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  82. Krug, R. et al. In vivo ultra-high-field magnetic resonance imaging of trabecular bone microarchitecture at 7 T. J. Magn. Reson. Imaging 27, 854–859 (2008).

    Article  PubMed  Google Scholar 

  83. Chang, G. et al. In vivo estimation of bone stiffness at the distal femur and proximal tibia using ultra-high-field 7-Tesla magnetic resonance imaging and micro-finite element analysis. J. Bone Min. Metab. 30, 243–251 (2012).

    Article  Google Scholar 

  84. Treutlein, C. et al. Comprehensive assessment of knee joint synovitis at 7 T MRI using contrast-enhanced and non-enhanced sequences. BMC Musculoskelet. Disord. 21, 116 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  85. Gassert, F. T. et al. SNR analysis of contrast-enhanced MR imaging for early detection of rheumatoid arthritis. PLoS One 14, e0213082 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Platt, T., Ladd, M. E. & Paech, D. 7 Tesla and beyond: advanced methods and clinical applications in magnetic resonance imaging. Invest. Radiol. 56, 705–725 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  87. Jones, M. A. et al. Molecular imaging of inflammatory disease. Biomedicines 9, 152 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Chapman, N. M. & Chi, H. Metabolic adaptation of lymphocytes in immunity and disease. Immunity 55, 14–30 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Chou, W.-C. et al. Impact of intracellular innate immune receptors on immunometabolism. Cell. Mol. Immunol. 19, 337–351 (2022).

    Article  CAS  PubMed  Google Scholar 

  90. Chi, H. Immunometabolism at the intersection of metabolic signaling, cell fate, and systems immunology. Cell. Mol. Immunol. 19, 299–302 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Wu, B. et al. Succinyl-CoA ligase deficiency in pro-inflammatory and tissue-invasive T cells. Cell Metab. 32, 967–980.e5 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Souto-Carneiro, M. et al. Differences in the serum metabolome and lipidome identify potential biomarkers for seronegative rheumatoid arthritis versus psoriatic arthritis. Ann. Rheum. Dis. 79, 499 (2020).

    Article  CAS  PubMed  Google Scholar 

  93. Martel-Pelletier, J. et al. Osteoarthritis. Nat. Rev. Dis. Prim. 2, 16072 (2016).

    Article  PubMed  Google Scholar 

  94. McQueen, F. M. et al. Magnetic resonance imaging of the wrist in early rheumatoid arthritis reveals a high prevalence of erosions at four months after symptom onset. Ann. Rheum. Dis. 57, 350–356 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Pap, T. & Korb-Pap, A. Cartilage damage in osteoarthritis and rheumatoid arthritis — two unequal siblings. Nat. Rev. Rheumatol. 11, 606–615 (2015).

    Article  PubMed  Google Scholar 

  96. Li, X., Johnson, C. P. & Ellermann, J. Measuring knee bone marrow perfusion using arterial spin labeling at 3 T. Sci. Rep. 10, 5260 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Waterton, J. C. et al. Repeatability and response to therapy of dynamic contrast-enhanced magnetic resonance imaging biomarkers in rheumatoid arthritis in a large multicentre trial setting. Eur. Radiol. 27, 3662–3668 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  98. Guermazi, A. et al. Compositional MRI techniques for evaluation of cartilage degeneration in osteoarthritis. Osteoarthritis Cartilage 23, 1639–1653 (2015).

    Article  CAS  PubMed  Google Scholar 

  99. Wu, B. et al. An overview of CEST MRI for non-MR physicists. EJNMMI Phys. 3, 19 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Maroudas, A. & Venn, M. Chemical composition and swelling of normal and osteoarthrotic femoral head cartilage. II. Swelling. Ann. Rheum. Dis. 36, 399–406 (1977).

    Article  CAS  PubMed  Google Scholar 

  101. Ling, W. et al. Assessment of glycosaminoglycan concentration in vivo by chemical exchange-dependent saturation transfer (gagCEST). Proc. Natl Acad. Sci. USA 105, 2266–2270 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Abrar, D. B. et al. Functional MR imaging beyond structure and inflammation-radiographic axial spondyloarthritis is associated with proteoglycan depletion of the lumbar spine. Arthritis Res. Ther. 22, 219 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Love, C. et al. FDG PET of infection and inflammation. Radiographics 25, 1357–1368 (2005).

    Article  PubMed  Google Scholar 

  104. Schonau, V. et al. The value of 18F-FDG-PET/CT in identifying the cause of fever of unknown origin (FUO) and inflammation of unknown origin (IUO): data from a prospective study. Ann. Rheum. Dis. 77, 70–77 (2018).

    Article  PubMed  Google Scholar 

  105. Fletcher, J. W. et al. Recommendations on the use of 18F-FDG PET in oncology. J. Nucl. Med. 49, 480–508 (2008).

    Article  PubMed  Google Scholar 

  106. Zhuang, H. and A. Alavi. 18-Fluorodeoxyglucose positron emission tomographic imaging in the detection and monitoring of infection and inflammation. Semin. Nucl. Med. 32, 47–59 (2002).

    Article  PubMed  Google Scholar 

  107. Ferraz-Amaro, I. et al. ARTICULAR 18fluorodeoxyglucose uptake is associated with clinically assessed swollen joint count in patients with rheumatoid arthritis. J. Rheumatol. 49, 1315–1319 (2022).

    Article  CAS  PubMed  Google Scholar 

  108. Beckers, C. et al. Assessment of disease activity in rheumatoid arthritis with 18F-FDG PET. J. Nucl. Med. 45, 956–964 (2004).

    CAS  PubMed  Google Scholar 

  109. Elzinga, E. H. et al. 18F-FDG PET as a tool to predict the clinical outcome of infliximab treatment of rheumatoid arthritis: an explorative study. J. Nucl. Med. 52, 77–80 (2011).

    Article  PubMed  Google Scholar 

  110. Roivainen, A. et al. Correlation of 18F-FDG PET/CT assessments with disease activity and markers of inflammation in patients with early rheumatoid arthritis following the initiation of combination therapy with triple oral antirheumatic drugs. Eur. J. Nucl. Med. Mol. Imaging 40, 403–410 (2013).

    Article  CAS  PubMed  Google Scholar 

  111. Chaudhari, A. J. et al. High-resolution 18F-FDG PET/CT for assessing disease activity in rheumatoid and psoriatic arthritis: findings of a prospective pilot study. Br. J. Radiol. 89, 20160138 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  112. Takata, T. et al. 18FDG PET/CT is a powerful tool for detecting subclinical arthritis in patients with psoriatic arthritis and/or psoriasis vulgaris. J. Dermatol. Sci. 64, 144–147 (2011).

    Article  CAS  PubMed  Google Scholar 

  113. Joseph, P. & Tawakol, A. Imaging atherosclerosis with positron emission tomography. Eur. Heart J. 37, 2974–2980 (2016).

    Article  PubMed  Google Scholar 

  114. Ogdie, A. et al. Risk of major cardiovascular events in patients with psoriatic arthritis, psoriasis and rheumatoid arthritis: a population-based cohort study. Ann. Rheum. Dis. 74, 326–332 (2015).

    Article  PubMed  Google Scholar 

  115. Rose, S. et al. Psoriatic arthritis and sacroiliitis are associated with increased vascular inflammation by 18-fluorodeoxyglucose positron emission tomography computed tomography: baseline report from the Psoriasis Atherosclerosis and Cardiometabolic Disease Initiative. Arthritis Res. Ther. 16, 1–9 (2014).

    Article  Google Scholar 

  116. Skeoch, S. et al. Evaluation of carotid plaque inflammation in patients with active rheumatoid arthritis using 18f-fluorodeoxyglucose PET-CT and MRI: a pilot study. Lancet 385, S91 (2015).

    Article  PubMed  Google Scholar 

  117. Skeoch, S. et al. Imaging atherosclerosis in rheumatoid arthritis: evidence for increased prevalence, altered phenotype and a link between systemic and localised plaque inflammation. Sci. Rep. 7, 827 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Blanken, A. B., et al. Arterial wall inflammation in rheumatoid arthritis is reduced by anti-inflammatory treatment. Semin. Arthritis Rheum. 51, 457–463 (2021).

    Article  CAS  Google Scholar 

  119. McKenney-Drake, M. L. et al. 18F-NaF and 18F-FDG as molecular probes in the evaluation of atherosclerosis. Eur. J. Nucl. Med. Mol. Imaging 45, 2190–2200 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  120. Høilund-Carlsen, P. F. et al. Atherosclerosis imaging with 18 F-sodium fluoride PET: state-of-the-art review. Eur. J. Nucl. Med. Mol. Imaging 47, 1538–1551 (2020).

    Article  PubMed  Google Scholar 

  121. Seraj, S. M. et al. Assessing the feasibility of NaF-PET/CT versus FDG-PET/CT to detect abdominal aortic calcification or inflammation in rheumatoid arthritis patients. Ann. Nucl. Med. 34, 424–431 (2020).

    Article  CAS  PubMed  Google Scholar 

  122. Reilly, C. C., et al. Diagnosis and monitoring of osteoporosis with 18F-sodium fluoride PET: an unavoidable path for the foreseeable future. Semin. Nucl. Med. 48, 535–540 (2018).

    Article  PubMed  Google Scholar 

  123. Raynor, W. et al. Evolving role of molecular imaging with 18F-sodium fluoride PET as a biomarker for calcium metabolism. Curr. Osteoporos. Rep. 14, 115–125 (2016).

    Article  PubMed  Google Scholar 

  124. Frost, M. L. et al. 18F‐fluoride PET as a noninvasive imaging biomarker for determining treatment efficacy of bone active agents at the hip: a prospective, randomized, controlled clinical study. J. Bone Miner. Res. 28, 1337–1347 (2013).

    Article  CAS  PubMed  Google Scholar 

  125. Frost, M. et al. Regional bone metabolism at the lumbar spine and hip following discontinuation of alendronate and risedronate treatment in postmenopausal women. Osteoporos. Int. 23, 2107–2116 (2012).

    Article  CAS  PubMed  Google Scholar 

  126. Watanabe, T. et al. 18F-FDG and 18F-NaF PET/CT demonstrate coupling of inflammation and accelerated bone turnover in rheumatoid arthritis. Mod. Rheumatol. 26, 180–187 (2016).

    Article  CAS  PubMed  Google Scholar 

  127. Kuwert, T. et al. FAPI-PET opens a new window for understanding of immune-mediated inflammatory diseases. J. Nucl. Med. 63, 1136–1137 (2022).

    Article  PubMed  Google Scholar 

  128. Schmidkonz, C. et al. Fibroblast activation protein inhibitor imaging in nonmalignant diseases: a new perspective for molecular imaging. J. Nucl. Med. 63, 1786–1792 (2022).

    Article  CAS  PubMed  Google Scholar 

  129. Bergmann, C. et al. 68Ga-FAPI-04 PET/CT study extension for the assessment of fibroblast activation and risk evaluation in systemic sclerosis-related interstitial lung disease. Ann. Rheum. Dis. 80, 165–166 (2021).

    Article  Google Scholar 

  130. Schmidkonz, C. et al. Disentangling inflammatory from fibrotic disease activity by fibroblast activation protein imaging. Ann. Rheum. Dis. 79, 1485–1491 (2020).

    Article  CAS  PubMed  Google Scholar 

  131. Bartok, B. & Firestein, G. S. Fibroblast-like synoviocytes: key effector cells in rheumatoid arthritis. Immunol. Rev. 233, 233–255 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Huber, L. C. et al. Synovial fibroblasts: key players in rheumatoid arthritis. Rheumatology 45, 669–675 (2006).

    Article  CAS  PubMed  Google Scholar 

  133. Croft, A. P. et al. Distinct fibroblast subsets drive inflammation and damage in arthritis. Nature 570, 246–251 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Dorst, D. N. et al. Targeting of fibroblast activation protein in rheumatoid arthritis patients: imaging and ex vivo photodynamic therapy. Rheumatology 61, 2999–3009 (2022).

    Article  CAS  PubMed  Google Scholar 

  135. Schmidkonz, C. et al. Fibroblast Activation Protein (FAP) PET-CT imaging allows to depict inflammatory joint remodeling in patients with psoriatic arthritis. Ann. Rheum. Dis. 81, 169–169 (2022).

    Article  Google Scholar 

  136. Fagni F, S. D. et al. Fibroblast activation in psoriasis patients assessed by 68Ga-FAPI-04 PET-CT is associated with progression to psoriatic arthritis. Arthritis Rheumatol., 74 abstract 1235 (2022).

    Google Scholar 

  137. Wang, L. V. & Yao, J. A practical guide to photoacoustic tomography in the life sciences. Nat. Methods 13, 627–638 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Wagner, A. L. et al. Precision of handheld multispectral optoacoustic tomography for muscle imaging. Photoacoustics 21, 100220 (2021).

    Article  PubMed  Google Scholar 

  139. Helfen, A. et al. Multispectral optoacoustic tomography: intra- and interobserver variability using a clinical hybrid approach. J. Clin. Med. 8, 63 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Knieling, F. et al. Multispectral optoacoustic tomography for assessment of Crohn’s disease activity. N. Engl. J. Med. 376, 1292–1294 (2017).

    Article  PubMed  Google Scholar 

  141. Regensburger, A. P. et al. Detection of collagens by multispectral optoacoustic tomography as an imaging biomarker for Duchenne muscular dystrophy. Nat. Med. 25, 1905–1915 (2019).

    Article  CAS  PubMed  Google Scholar 

  142. Rosenberg, A. S. et al. Immune-mediated pathology in Duchenne muscular dystrophy. Sci. Transl. Med. 7, 299rv4 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  143. Hallasch, S. et al. Multispectral optoacoustic tomography might be a helpful tool for noninvasive early diagnosis of psoriatic arthritis. Photoacoustics 21, 100225 (2021).

    Article  PubMed  Google Scholar 

  144. Tascilar, K. et al. Non-invasive metabolic profiling of inflammation in joints and entheses by multispectral optoacoustic tomography. Rheumatology 62, 841–849 (2022).

    Article  Google Scholar 

  145. Milz, S. et al. Molecular composition and pathology of entheses on the medial and lateral epicondyles of the humerus: a structural basis for epicondylitis. Ann. Rheum. Dis. 63, 1015–1021 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Biniecka, M. et al. Hypoxia induces mitochondrial mutagenesis and dysfunction in inflammatory arthritis. Arthritis Rheum. 63, 2172–2182 (2011).

    Article  CAS  PubMed  Google Scholar 

  147. Alivernini, S. et al. Synovial features of patients with rheumatoid arthritis and psoriatic arthritis in clinical and ultrasound remission differ under anti-TNF therapy: a clue to interpret different chances of relapse after clinical remission? Ann. Rheum. Dis. 76, 1228–1236 (2017).

    Article  CAS  PubMed  Google Scholar 

  148. Winyard, P. G. et al. Presence of foam cells containing oxidised low density lipoprotein in the synovial membrane from patients with rheumatoid arthritis. Ann. Rheum. Dis. 52, 677–680 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Ntziachristos, V. & Razansky, D. Molecular imaging by means of multispectral optoacoustic tomography (MSOT). Chem. Rev. 110, 2783–2794 (2010).

    Article  CAS  PubMed  Google Scholar 

  150. Granger, D. N. & Senchenkova, E. Inflammation and the Microcirculation (NLM, 2010).

  151. Ohrndorf, S. et al. Fluorescence optical imaging: ready for prime time? RMD Open 7, e001497 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  152. Fischer, T. et al. Detection of rheumatoid arthritis using non-specific contrast enhanced fluorescence imaging. Acad. Radiol. 17, 375–381 (2010).

    Article  PubMed  Google Scholar 

  153. Werner, S. G. et al. Inflammation assessment in patients with arthritis using a novel in vivo fluorescence optical imaging technology. Ann. Rheum. Dis. 71, 504–510 (2012).

    Article  PubMed  Google Scholar 

  154. Werner, S. G. et al. Indocyanine green–enhanced fluorescence optical imaging in patients with early and very early arthritis: a comparative study with magnetic resonance imaging. Arthritis Rheum. 65, 3036–3044 (2013).

    Article  CAS  PubMed  Google Scholar 

  155. Hertrampf, S. et al. Monitoring of patients with rheumatoid arthritis by indocyanine green (ICG)-enhanced fluorescence optical imaging treated with anti-TNFα therapy. Arthritis Res. Ther. 24, 1–8 (2022).

    Article  Google Scholar 

  156. Glimm, A.-M. et al. Fluorescence optical imaging for treatment monitoring in patients with early and active rheumatoid arthritis in a 1-year follow-up period. Arthritis Res. Ther. 21, 1–12 (2019).

    Article  Google Scholar 

  157. Frinking, P. et al. Three decades of ultrasound contrast agents: a review of the past, present and future improvements. Ultrasound Med. Biol. 46, 892–908 (2020).

    Article  PubMed  Google Scholar 

  158. Jakobsen, J. Å. et al. Safety of ultrasound contrast agents. Eur. Radiol. 15, 941–945 (2005).

    Article  PubMed  Google Scholar 

  159. Wei, K. et al. The safety of Definity and Optison for ultrasound image enhancement: a retrospective analysis of 78,383 administered contrast doses. J. Am. Soc. Echocardiogr. 21, 1202–1206 (2008).

    Article  PubMed  Google Scholar 

  160. Chung, Y. E. & Kim, K. W. Contrast-enhanced ultrasonography: advance and current status in abdominal imaging. Ultrasonography 34, 3 (2015).

    Article  PubMed  Google Scholar 

  161. Tai, H., Khairalseed, M. & Hoyt, K. 3-D H-scan ultrasound imaging and use of a convolutional neural network for scatterer size estimation. Ultrasound Med. Biol. 46, 2810–2818 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  162. Averkiou, M. A. et al. Imaging methods for ultrasound contrast agents. Ultrasound Med. Biol. 46, 498–517 (2020).

    Article  PubMed  Google Scholar 

  163. Rafailidis, V. et al. Contrast imaging ultrasound for the detection and characterization of carotid vulnerable plaque. Cardiovasc. Diagn. Ther. 10, 965 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  164. Oezdemir, I. et al. Tumor vascular networks depicted in contrast-enhanced ultrasound images as a predictor for transarterial chemoembolization treatment response. Ultrasound Med. Biol. 46, 2276–2286 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  165. Hoyt, K. et al. Ultrasound imaging of breast tumor perfusion and neovascular morphology. Ultrasound Med. Biol. 41, 2292–2302 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  166. Diao, X.-H. et al. Superb microvascular imaging is as sensitive as contrast-enhanced ultrasound for detecting synovial vascularity in rheumatoid arthritis. Quant. Imaging Med. Surg. 12, 2866 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  167. Mouterde, G. et al. Value of contrast‐enhanced ultrasonography for the detection and quantification of enthesitis vascularization in patients with spondyloarthritis. Arthritis Care Res. 66, 131–138 (2014).

    Article  CAS  Google Scholar 

  168. Kim, G.-W. et al. Ultrasonographic imaging and anti-inflammatory therapy of muscle and tendon injuries using polymer nanoparticles. Theranostics 7, 2463 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Tang, X. et al. Nanoscale contrast agents for ultrasound imaging of musculoskeletal system. Diagnostics 12, 2582 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Exner, A. A. & Kolios, M. C. Bursting microbubbles: how nanobubble contrast agents can enable the future of medical ultrasound molecular imaging and image-guided therapy. Curr. Opin. Colloid Interface Sci. 54, 101463 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  171. Brown, K. G. et al. Faster super-resolution ultrasound imaging with a deep learning model for tissue decluttering and contrast agent localization. Biomed. Phys. Eng. Express 7, 065035 (2021).

    Article  Google Scholar 

  172. LeCun, Y., Bengio, Y. & Hinton, G. Deep learning. Nature 521, 436–444 (2015).

    Article  CAS  PubMed  Google Scholar 

  173. Stoel, B. Use of artificial intelligence in imaging in rheumatology — current status and future perspectives. RMD Open 6, e001063 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  174. Savadjiev, P. et al. Demystification of AI-driven medical image interpretation: past, present and future. Eur. Radiol. 29, 1616–1624 (2019).

    Article  PubMed  Google Scholar 

  175. Liew, C. The future of radiology augmented with artificial intelligence: a strategy for success. Eur. J. Radiol. 102, 152–156 (2018).

    Article  PubMed  Google Scholar 

  176. Kann, B. H., Hosny, A. & Aerts, H. Artificial intelligence for clinical oncology. Cancer Cell 39, 916–927 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Bressem, K. K. et al. Deep learning for detection of radiographic sacroiliitis: achieving expert-level performance. Arthritis Res. Ther. 23, 106 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  178. Poddubnyy, D. et al. Detection of radiographic sacroiliitis with an artificial neural network in patients with suspicion of axial spondyloarthritis. Rheumatology 60, 5868–5869 (2021).

    Article  PubMed  Google Scholar 

  179. Lin, K. Y. Y. et al. Deep learning algorithms for magnetic resonance imaging of inflammatory sacroiliitis in axial spondyloarthritis. Rheumatology 61, 4198–4206 (2022).

    Article  PubMed  Google Scholar 

  180. Folle, L. et al. Advanced neural networks for classification of MRI in psoriatic arthritis, seronegative, and seropositive rheumatoid arthritis. Rheumatology 61, 4945–4951 (2022).

    Article  PubMed  Google Scholar 

  181. Folle, L. et al. Deep learning-based classification of inflammatory arthritis by identification of joint shape patterns-how neural networks can tell us where to “Deep Dive” clinically. Front. Med. 9, 850552 (2022).

    Article  Google Scholar 

  182. Andersen, J. K. H. et al. Neural networks for automatic scoring of arthritis disease activity on ultrasound images. RMD Open 5, e000891 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  183. Wang, H. J. et al. Deep learning-based computer-aided diagnosis of rheumatoid arthritis with hand X-ray images conforming to modified total sharp/van der Heijde score. Biomedicines 10, 1355 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  184. Jamshidi, A., Pelletier, J.-P. & Martel-Pelletier, J. Machine-learning-based patient-specific prediction models for knee osteoarthritis. Nat. Rev. Rheumatol. 15, 49–60 (2019).

    Article  PubMed  Google Scholar 

  185. Lazzarini, N. et al. A machine learning approach for the identification of new biomarkers for knee osteoarthritis development in overweight and obese women. Osteoarthritis Cartilage 25, 2014–2021 (2017).

    Article  CAS  PubMed  Google Scholar 

  186. Ho, S. Y. et al. Extensions of the external validation for checking learned model interpretability and generalizability. Patterns 1, 100129 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  187. RSNA. https://www.rsna.org/research/quantitative-imaging-biomarkers-alliance (2023).

  188. Van Holsbeeck, M. et al. Staging and follow‐up of rheumatoid arthritis of the knee. Comparison of sonography, thermography, and clinical assessment. J. Ultrasound Med. 7, 561–566 (1988).

    Article  PubMed  Google Scholar 

  189. Brown, D. G. et al. Magnetic resonance imaging in patients with inflammatory arthritis of the knee. Clin. Rheumatol. 9, 73–83 (1990).

    Article  CAS  PubMed  Google Scholar 

  190. Grassi, W., Tittarelli, E., Pirani, O., Avaltroni, D. & Cervini, C. Ultrasound examination of metacarpophalangeal joints in rheumatoid arthritis. Scand. J. Rheumatol. 22, 243–247 (1993).

    Article  CAS  PubMed  Google Scholar 

  191. Clunie, G. et al. Measurement of synovial lining volume by magnetic resonance imaging of the knee in chronic synovitis. Ann. Rheum. Dis. 56, 526–534 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  192. Oostveen, J. et al. Early detection of sacroiliitis on magnetic resonance imaging and subsequent development of sacroiliitis on plain radiography. A prospective, longitudinal study. J. Rheumatol. 26, 1953–1958 (1999).

    CAS  PubMed  Google Scholar 

  193. Wakefield, R. J. et al. The value of sonography in the detection of bone erosions in patients with rheumatoid arthritis: a comparison with conventional radiography. Arthritis Rheum. 43, 2762–2770 (2000).

    Article  CAS  PubMed  Google Scholar 

  194. Langs, G. et al. Automatic quantification of joint space narrowing and erosions in rheumatoid arthritis. IEEE Trans. Med. Imaging 28, 151–164 (2008).

    Article  Google Scholar 

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Acknowledgements

The work of I.M., A.K., M.Y.-M., F.F., S.K., C.S., A.A., M.P., L.F., F.R., M.W., G.S. and D.S. is supported by the Deutsche Forschungsgemeinschaft (FOR2886, CRC1181, CRC1483), the Bundesministerium für Bildung und Forschung (BMBF; MASCARA), the European Union (ERC Synergy grant 4D Nanoscope) and the IMI-funded projects RTCure and HIPPOCRATES. The work of D.S. is supported by a 2022 GRAPPA Pilot Research Grant. The authors would like to thank Adrian Regensburger and Ferdinand Knieling for their constructive advice on this manuscript.

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Author notes

  1. These authors contributed equally: Ioanna Minopoulou, Arnd Kleyer, Melek Yalcin-Mutlu.

Authors and Affiliations

  1. Department of Internal Medicine 3, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany

    Ioanna Minopoulou, Arnd Kleyer, Melek Yalcin-Mutlu, Filippo Fagni, Stefan Kemenes, Milena Pachowsky, Georg Schett & David Simon

  2. Deutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany

    Ioanna Minopoulou, Arnd Kleyer, Melek Yalcin-Mutlu, Filippo Fagni, Stefan Kemenes, Milena Pachowsky, Maximilian Waldner, Georg Schett & David Simon

  3. Department of Nuclear Medicine, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany

    Christian Schmidkonz & Armin Atzinger

  4. Institute for Medical Engineering, University of Applied Sciences Amberg-Weiden, Weiden, Germany

    Christian Schmidkonz

  5. Siemens Healthineers, Erlangen, Germany

    Klaus Engel

  6. Pattern Recognition Lab, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany

    Lukas Folle

  7. Institute of Radiology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany

    Frank Roemer

  8. Department of Radiology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA

    Frank Roemer

  9. Department of Internal Medicine 1, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany

    Maximilian Waldner

  10. Division of Rheumatology, Catholic University of the Sacred Heart, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy

    Maria-Antonietta D’Agostino

  11. Université Paris-Saclay, UVSQ, Inserm U1173, Infection et Inflammation, Laboratory of Excellence Inflamex, Montigny-Le-Bretonneux, France

    Maria-Antonietta D’Agostino

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Contributions

I.M., A.K., M.Y.-M., G.S. and D.S. researched data for the article and wrote the article. All authors contributed substantially to discussion of the content and reviewed and/or edited the manuscript before submission.

Corresponding author

Correspondence to David Simon.

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Competing interests

K.E. is an employee of Siemens Healthineers (Erlangen, Germany) and was involved in the development of the cinematic rendering technology used to generate Figs. 3 and 5 and Supplementary videos 1 and 2. M.W. is a shared patent holder together with iThera Medical (Munich, Germany) on an optoacoustic imaging system. All other authors declare that they have no competing interests.

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Nature Reviews Rheumatology thanks B. Stoel, A. Alavi, S. Manske and A. Burghardt for their contribution to the peer review of this work.

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41584_2023_1016_MOESM2_ESM.mp4

Supplementary video 1 | 68Ga-FAPI-04 PET–CT in a patient with psoriatic arthritis. Hands of a patient with psoriatic arthritis by 68Ga-FAPI-04 PET–CT imaging, showing increased fibroblast activation proteins inhibitor (FAPI) uptake in the radiocarpal and carpometacarpal, suggestive of synovitis, as well as dactylitis of the third and fifth fingers of the right hand before treatment with a biologic DMARD. Improvement of synovitis and dactylitis evident after 6 months of IL-17 inhibition.

41584_2023_1016_MOESM3_ESM.mp4

Supplementary video 2 | 68Ga-FAPI-04 PET–CT imaging in a patient with rheumatoid arthritis. Hands of a patient with rheumatoid arthritis by 68Ga-FAPI-04 PET–CT, showing increased FAPI uptake in the carpometacarpal joints of both hands and in the metacarpophalangeal joints 2 and 3 of the left hand, indicative of synovitis. Resolution of synovitis evident after treatment with a Janus kinase inhibitor.

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Minopoulou, I., Kleyer, A., Yalcin-Mutlu, M. et al. Imaging in inflammatory arthritis: progress towards precision medicine. Nat Rev Rheumatol 19, 650–665 (2023). https://doi.org/10.1038/s41584-023-01016-1

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