BackgroundIndocyanine green (ICG)-enhanced fluorescence optical imaging (FOI) is an established technology for imaging of inflammation in animal models. In experimental models of arthritis, FOI findings corresponded to histologically proven synovitis. This is the first comparative study of FOI with other imaging modalities in humans with arthritis.Methods252 FOI examinations (Xiralite system, mivenion GmbH, Berlin, Germany; ICG bolus of 0.1 mg/kg/body weight, sequence of 360 images, one image per second) were compared with clinical examination (CE), ultrasonography (US) and MRI of patients with arthritis of the hands.ResultsIn an FOI sequence, three phases could be distinguished (P1–P3). With MRI as reference, FOI had a sensitivity of 76% and a specificity of 54%, while the specificity of phase 1 was 94%. FOI had agreement rates up to 88% versus CE, 64% versus greyscale US, 88% versus power Doppler US and 83% versus MRI, depending on the compared phase and parameter. FOI showed a higher rate of positive results compared to CE, US and MRI. In individual patients, FOI correlated significantly (p<0.05) with disease activity (Disease Activity Score 28, r=0.41), US (r=0.40) and RAMRIS (Rheumatoid Arthritis MRI Score) (r=0.56). FOI was normal in 97.8% of joints of controls.ConclusionICG-enhanced FOI is a new technology offering sensitive imaging detection of inflammatory changes in subjects with arthritis. FOI was more sensitive than CE and had good agreement with CE, US in power Doppler mode and MRI, while showing more positive results than these. An adequate interpretation of an FOI sequence requires a separate evaluation of all phases. For the detection of synovitis and tenosynovitis, FOI appears to be as informative as 1.5 T MRI and US.

Objective. Indocyanine green-enhanced fluorescence optical imaging (FOI) is a novel diagnostic tool for the assessment of inflammation in arthritis. We undertook this study to compare FOI with magnetic resonance imaging (MRI) in 32 patients with early and very early untreated arthritis (mean disease duration 7.1 months).Methods. FOI images were acquired with the commercially available Xiralite system. Image interpretation was done for an early phase (phase 1), an intermediate phase (phase 2), and a late phase (phase 3), and for an electronically generated composite image. The results were compared with those of clinical examination (960 joints) and contrast (gadolinium)-enhanced 1.5T MRI (382 joints) of the clinically more affected hand. Additionally, we evaluated FOI in a control group of 46 subjects without any signs of inflammatory joint disease (1,380 joints).Results. With MRI as the reference method, the sensitivity of FOI was 86% and the specificity was 63%, while the composite image, phase 1, and phase 3 reached high specificities (87%, 90%, and 88%, respectively). The results differed considerably between the composite image and the phases. FOI did not detect inflammation in 11 joint regions that showed palmar tenosynovitis on MRI. Intrareader and interreader agreements were moderate to substantial ( ‫؍‬ 0.55-0.73). In the control group, FOI showed positive findings in 5% of normal joints in phase 2.Conclusion. Further multicenter studies will address the question of whether FOI allows sensitive and reliable detection of inflammatory changes in early arthritis, as suggested by our initial findings. If this is confirmed, FOI has the potential to be a sensitive and valuable tool for monitoring disease activity on site in clinical settings and for serving as an outcome parameter in clinical trials.

FOI remains an interesting diagnostic tool for patients with early RA, although this study revealed limitations concerning the detection of synovitis. Further research is needed to evaluate its full diagnostic potential in rheumatic diseases.

Objective Systemic sclerosis (SSc) can lead to ischemic complications such as digital ulcers (DUs). The aim of the study was to find predictors of DUs by clinical and new imaging methods. Patients and methods All 79 SSc patients included in the study received a clinical, colour Doppler ultrasound (CDUS), fluorescence optical imaging (FOI) and capillaroscopy examination at baseline, and their capacity to predict new DU development was analysed in 76 patients at 12 months follow-up. Results Twenty-two of 76 patients (28.9%) developed new ulcers during follow-up (diffuse SSc 48.1%; limited SSc 18.4%). Receiver operating characteristic (ROC) curve analysis revealed an area under the curve of 0.7576 for DU development, with a specificity of 87% and a sensitivity of 54.6% ( p = 0.0003, OR = 8.1 [95%CI 2.5–25.6]) at a cut-off of ≥ 21 points (ACR/EULAR classification criteria for SSc). Capillaroscopy and CDUS had high sensitivity (100% and 95.5%) but low specificity (28.9% and 22.2%) for ulcer occurrence when used alone, but better specificity (46.3%) when combined (OR = 18.1 [95%CI 2.3–144.4]; p = 0.0004). Using FOI, fingers with pathologic staining had a higher risk for new ulcer development in the same finger ( p = 0.0153). General future DU (i.e. DU also in other fingers) was associated with a missing FOI signal in the right digit III at baseline ( p = 0.048). Conclusion New imaging modalities can predict digital ulcer development in SSc patients with high sensitivity for capillaroscopy and CDUS and enhanced specificity when combined. A missing signal of FOI in the right digit III at baseline was associated with general future DU.

BackgroundUtilising fluorescence optical imaging (FOI), the distribution of an intravenously applied colouring agent indocyanine green (ICG) can be analysed with the potential to identify malperfusion by little to no tissue enhancement. Systemic sclerosis (SSc) is characterised by the presence of digital ulcers reflecting progressive vasculopathy.The objective was to investigate the potential of FOI in the detection of disturbed microcirculation in the hands and fingers of patients with SSc and to link FOI findings to clinical signs of ischemia such as digital ulcers and pitting scars.MethodsIn this cross-sectional study, 63 patients with SSc and 26 healthy subjects were examined. FOI was performed in all 89 individuals and compared to clinical data and capillaroscopic findings assembled for the SSc cohort.ResultsHealthy subjects showed initial ICG signals in their fingertips in 93.6%, SSc patients in 78.5% (limited SSc) and 43.2% (diffuse SSc). Moreover, in SSc patients, FOI findings were significantly associated with a late capillaroscopic pattern, disseminated SSc features, a diffuse SSc subtype, and the presence of digital ulcers or pitting scars. Intra- and inter-reader reliability for FOI amounted to κ = 0.786 and κ = 0.834, respectively.ConclusionsFOI is able to detect areas of reduced microcirculation in patients with SSc with high association to capillaroscopic findings. The results pave the way for future FOI investigations into its role in the prediction of complications due to an impaired acral perfusion.

Summary Objective Comparison of fluorescence optical imaging (FOI) with grayscale (GS) and power Doppler ultrasound (PDUS) to detect joint inflammation in patients with confirmed or suspected psoriatic arthritis (PsA). Methods Patients (n = 60) with psoriasis and tenderness and/or swelling of joints were separated into two groups: diagnosis confirmed by the treating dermatologist before the start of the study (n = 26), and suspected PsA (n = 34). GS/PDUS of the hand most clinically affected was performed with a dorsal/palmar view (wrist, MCP, PIP, DIP2–5). FOI examination was carried out in a standardized manner by analyzing the predefined Phases 1–3. Results FOI was found to be more sensitive than ultrasound (US) for detection of inflammation in PIP/DIP joints (p = 0.035). Confirmed PsA patients showed more findings in FOI P2 and P3, while suspected PsA patients showed more findings in P1. In the confirmed PsA group, most involved joints were MCP joints, while in the suspected PsA group, more involved wrist joints and DIP joints (p = 0.006) were detected with FOI. Conclusions The differences between the confirmed and suspected groups indicate that FOI is helpful in the detection of early PsA since P1 may correspond to acute inflammation, whereas P2 and P3 enhancement reflect chronic inflammation. Fluorescence optical imaging might therefore be a novel diagnostic tool for early PsA diagnosis.

BackgroundValid detection of arthritis is essential in differential diagnosis of joint pain. Indocyanin green (ICG)-enhanced fluorescence optical imaging (FOI) is a new imaging method that visualizes inflammation in wrist and finger joints. Objectives of this study were to compare FOI with ultrasonography (US, by gray-scale (GS) and power Doppler (PD)) and clinical examination (CE) and to estimate the predictive power of FOI for discrimination between inflammatory and non-inflammatory juvenile joint diseases.MethodsFOI and GSUS/PDUS were performed in both hands of 76 patients with joint pain (53 with juvenile idiopathic arthritis (JIA), 23 with non-inflammatory joint diseases). Inflammation was graded by a semiquantitative score (grades 0–3) for each imaging method. Joints were defined clinically active if swollen or tender with limited range of motion. Sensitivity and specificity of FOI in three phases dependent on ICG enhancement (P1–P3) were analyzed with CE and GSUS/PDUS as reference.ResultsFor JIA patients, FOI had an overall sensitivity of 67.3%/72.0% and a specificity of 65.0%/58.8% with GSUS/PDUS as reference; specificity was highest in P3 (GSUS 94.3%/PDUS 91.7%). FOI was more sensitive for detecting clinically active joints than GSUS/PDUS (75.2% vs 57.3%/32.5%). In patients with non-inflammatory joint diseases both FOI and US showed positive (i.e., pathological) findings (25% and 14% of joints). The predictive value for discrimination between inflammatory and non-inflammatory joint diseases was 0.79 for FOI and 0.80/0.85 for GSUS/PDUS.ConclusionsDependent on the phase evaluated, FOI had moderate to good agreement with CE and US. Both imaging methods revealed limitations and should be interpreted cautiously. FOI may provide an additional diagnostic method in pediatric rheumatology.Trial registrationDeutsches Register Klinischer Studien DRKS00012572. Registered 31 July 2017.

Hintergrund und Zielsetzung: Die Frühdiagnostik der Psoriasisarthritis stellt eine besondere Herausforderung dar. Das Xiralite®-System, ein neueres fluoreszenzoptisches Bildgebungsverfahren kann dazu mittels Darstellung von Mikrovaskularität und Perfusion einen wichtigen Beitrag leisten. In der vorliegenden Studie wurden erstmals extraartikuläre fluoreszenzoptische Signale an einer großen Psoriasisarthritis-Kohorte systematisch untersucht. Patienten und Methodik: In der Hauptstudie untersuchten und analysierten wir extraartikuläre fluoreszenzoptische Signalmuster bei 241 Sequenzen von 187 Psoriasisarthritis-Patienten. Als Kontrolle dienten 36 fluoreszenzoptische Sequenzen bei 31 Patienten mit rheumatoider Arthritis. In einer Folgestudie wurden 203 konsekutive fluoreszenzoptische Sequenzen bei 54 Psoriasisarthritis-Patienten und 149 Kontrollen mit entzündlich-rheumatischen Erkrankungen retrospektiv ausgewertet, um die Ergebnisse der Hauptstudie hinsichtlich der identifizierten Muster zu validieren. Ergebnisse: In Projektion auf den Nagelbereich ließen sich bei Psoriasisarthritis insgesamt drei fluoreszenzoptische Signalmuster differenzieren, die in bisherigen Untersuchungen nicht beschrieben wurden, darunter insbesondere das von uns so bezeichnete "Green Nail"-Phänomen, das hohe Spezifität (97 %) für die Psoriasisarthritis zeigte. In der Folgestudie lag die Spezifität bei 87 % für die Psoriasisarthritis in Bezug zur Kontrollkohorte. Schlussfolgerungen: In den vorliegenden Untersuchungen erwiesen sich fluoreszenzoptische Signale im Bereich der Nägel als hochspezifisch für die Psoriasisarthritis. Dabei scheint der "Green Nail" von besonderem diagnostischem Interesse zu sein als möglicher Hinweis auf eine Mikrozirkulationsstörung im Bereich des Nagelbettes.