A5.02 Fluorescence optical imaging coupled with ultrasound radiography for detecting subtle hand inflammation in early rheumatoid arthritis

Abstract

ObjectivesFluorescence Optical Imaging (FOI) is an emerging modality that uses an intravenous fluorophore to display altered microcirculation (abnormal perfusion/capillary leakage) in synovial tissues in the hands. FOI can be analyzed visually (FOI-v) or by using automated Disease ACTivity (DACT). Using musculoskeletal ultrasound (MSUS) as a validated reference measure, we previously showed FOI to be highly sensitive and specific in detecting clinically manifest and silent synovitis in patients with various rheumatic diseases. Here, we analyze whether the same is true for early rheumatoid arthritis (eRA).MethodsHands and wrists ineRA patients were assessed by clinical examination, MSUS and FOI-DACT. Active inflammation was defined as having synovial-hypertrophy/effusions and intra-articular Doppler signaling on MSUS, and as increased optical-intensities on FOI-v. Scores on DACT ≥ 1 was considered indicative of disease activity.Results39 eRA patients were studied [72% females, 56% previous/current smokers, 54% RF(+) and 69% ACCP(+)]. Of the 1326 joints in these patients, 303 were inflamed by clinical assessment, 380 by MSUS, and 400 by FOI-v. The percentages of patients and (mean ± SD) joints by clinical, MSUS and FOI-v were 69%(7.8 ± 8.1), 95%(9.7 ± 7.7), and 95%(10.3 ± 7.2), respectively. Using MSUS as reference, FOI-DACT was 95%(35/37) accurate in identifying patients with active disease, 24%(9/37) of whom had erosive RA. Good correlations noted between MSUS and FOI-v (rho = 0.803; p < 0.001), clinical assessment and FOI-v (rho = 0.732; p < 0.001), and MSUS and clinical (rho = 0.793; p < 0.001). The sensitivity, specificity, NPV and PPV of inflammation by FOI-v was 81%(308/380), 90%(854/946), 61%, and 96% respectively. Of the clinically negative but MSUS positive (145/1023) joints, 68%(98/145) were also FOI-v positive. Remarkably, one patient had 15 joints that were FOI-DACT positive and MSUS negative, but a month later, the same joints became MSUS positive. Although the wrists and MCPs were frequently inflamed, DIP joint inflammation was also seen in 34 and 14 joints in 12 patients by FOI-DACT and MSUS, respectively. Nine of these patients had osteoarthritis by conventional radiography.ConclusionsAs reported for established rheumatic diseases, here we show high correlations and agreements between clinical examination, MSUS and FOI-v in detecting subtle inflammation in early RA as well. Moreover, DACT-FOI emerges as a useful automated quantitative scoring method for synovial inflammation in eRA.Reference Kisten Y, Györi N, af Klint E, et al. 2015 Detection of clinically manifest and silent synovitis in the hands and wrists by fluorescence optical imaging. RMD Open. 1: e000106. doi:10.1136/ rmdopen-2015-000106()

Distinct Fluorescence Optical Imaging Patient Clusters Emerge for Seropositive and Seronegative Rheumatoid Arthritis

“…About two thirds of all new RA cases are mainly characterized by the presence of ACPA and RF autoantibodies and have genetic environmental risk factors, cytokine profiles and histology differences, and more joint destruction when left untreated as compared with seronegative RA cases (20). Previous reports also showed that in the presence or absence of RA‐related autoantibodies (ACPA or RF), the utility of imaging, especially radiography, MSUS, and FOI accompanied by the automated DACT‐FOI analysis, reliably supports the rheumatologist's decision‐making (6,8,18,19). Based on this RA subpopulation (Supplementary Figures 3 and 4), we showed the usefulness of FOI in identifying joint inflammation using ultrasound as a reference, to be 81% sensitive and 90% specific, with positive and negative predictive values of 96% and 61%, respectively (8).…”

“…Previous reports also showed that in the presence or absence of RA‐related autoantibodies (ACPA or RF), the utility of imaging, especially radiography, MSUS, and FOI accompanied by the automated DACT‐FOI analysis, reliably supports the rheumatologist's decision‐making (6,8,18,19). Based on this RA subpopulation (Supplementary Figures 3 and 4), we showed the usefulness of FOI in identifying joint inflammation using ultrasound as a reference, to be 81% sensitive and 90% specific, with positive and negative predictive values of 96% and 61%, respectively (8). Notably, FOI was 68% sensitive in detecting silent synovitis defined as not inflamed on CE, but synovitis positive on ultrasound.…”

“…FOI, or “Rheumascan” (Xiralite X4, Mivenion GmbH), is an emerging modality designed for the hands that use an intravenous fluorophore (indocyanine green [ICG]) to identify altered microcirculation in areas of abnormally high perfusion and/or capillary leakage (3–8). The concordance between clinical and ultrasound arthritis has been reported in several articles (9–13); however, there are relatively limited FOI studies in patients with newly diagnosed RA.…”

“…Apart from established imaging techniques that uses x-rays, magnetic resonance, nuclear medicine, and musculoskeletal ultrasound (MSUS), there is also a more recent fluorescence optical imaging (FOI) technology that is gaining recognition as an operator-independent diagnostic tool for early undifferentiated and/or inflammatory arthritis and may serve useful in the management of RA (3)(4)(5). FOI, or "Rheumascan" (Xiralite X4, Mivenion GmbH), is an emerging modality designed for the hands that use an intravenous fluorophore (indocyanine green [ICG]) to identify altered microcirculation in areas of abnormally high perfusion and/or capillary leakage (3)(4)(5)(6)(7)(8). The concordance between clinical and ultrasound arthritis has been reported in several articles (9)(10)(11)(12)(13); however, there are relatively limited FOI studies in patients with newly diagnosed RA.…”

“…Our previous studies showed FOI sensitivity and specificity to range between 73% and 84% and 83% and 95% in detecting clinically manifest or silent synovitis, with positive and negative predictive values of 77% and 97%, respectively, in those with various rheumatic diseases (6). FOI may have higher sensitivity than MSUS for detecting altered microcirculatory changes of inflamed hand tissues in small joints (8) and may contribute to timely detection of subtle inflammatory changes in and around the joint capsule, tendons, and/or skin tissue of patients with rheumatic diseases (4)(5)(6)8). FOI may also have the potential to monitor the effects of therapy using reliable semiquantitative FOI scoring methods (14)(15)(16)(17).…”