Fluorescence optical imaging for treatment monitoring in patients with early and active rheumatoid arthritis in a 1-year follow-up period

BACKGROUND: Fluorescence optical imaging (FOI) enables visualization of inflammation in the hands in rheumatic joint diseases with currently a lack of long-term follow-up studies. OBJECTIVE: To investigate FOI for treatment monitoring in a homogenous cohort of patients with early (disease duration  3.2) RA over a period of 12 months. METHODS: Thirty-five RA patients (24 (68.6%) females, mean age 53.3 years (SD 13.6)) were investigated clinically by DAS28, tender joint count (TJC) and swollen joint count (SJC) and by FOI in phases 1-3 and PrimaVistaMode (PVM) before therapy change and after 12 months. The FOI activity score (FOIAS) was calculated based on individual joint scores from 0 to 3 in 30 joints per patient, adding up to a sum score (0-90). RESULTS: We found a statistically significant reduction of FOIAS in phase 1 from baseline (median 5.0, IQR 24.96) to follow-up (median 1.0, IQR 4.0) in all patients (p = 0.0045), both in responders and non-responders according to EULAR response criteria by DAS28. Statistically significant reductions over 12 months were found for median DAS28(ESR) 5.61 to 3.31, TJC 7.0 to 1.0, and SJC 5.0 to 1.0 (each p <  0.001). No statistically significant correlations were detected between the FOIAS change in phase 1 and DAS28(ESR), TJC, or SJC. Correlations between the other phases and clinical outcomes were weak to moderate. CONCLUSION: Reduced early enhancement in FOI phase 1 can be observed in clinically responding and non-responding early RA patients under treatment. Regarding potential marker performance, FOI probably shows a reduction of inflammation more objectively

a pilot study

Background Utilising 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. Methods In 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. Results Healthy 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. Conclusions FOI 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

a comparative study with ultrasonography

Background Valid 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. Methods FOI 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. Results For 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. Conclusions Dependent 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 registration Deutsches Register Klinischer Studien DRKS00012572. Registered 31 July 2017

Analyse der Verteilung und Schweregrade von Gelenkentzündungen bei Patienten mit Osteoarthrose oder Rheumatoider Arthritis durch ICG-verstärkte fluoreszenzoptische Bildgebung und Gelenkultraschall

In rheumatoid arthritis (RA), synovitis of the hands appears especially in wrist, metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints1. In contrast, hand osteoarthritis (OA) presents potential inflammatory changes mainly in PIP and distal interphalangeal (DIP) joints. Inflammatory changes of the wrist and finger joints can be visualized by musculoskeletal ultrasound (US) and fluorescence optical imaging (FOI). The objective of this study was the comparison of the amount and distribution of inflammatory signs in wrist and finger joints of the clinically dominant hand in OA and RA patients by FOI, gray-scale (GSUS) and power Doppler US (PDUS). FOI and GSUS were performed in 1170 joints in 90 patients (67 RA, 23 OA) following a standardized procedure. GSUS and PDUS were applied on dorsal and palmar sides of wrists and MCP, PIP, DIP joints 2-5 of the clinically dominant hand for tenderness and swelling. The examination of both hands via FOI was performed for the automatically generated PrimaVista-Mode (PVM) and three different phases (p1-p3) over an examination time of 360s recording one image per second. Synovitis and tenosynovitis via ultrasound and the distribution of the fluorescence optical dye Indocyanine green (ICG) as signs for joint inflammation were graded by a semi-quantitative score (0-3). The frequency of inflamed joints per grade of the semiquantitative score was calculated in percentage terms in RA and OA for each imaging method. In GSUS, the frequency pattern showed wrist and MCP joints mostly affected in RA. DIP joints were graded more often with 1-3 in OA. More RA joints were graded with 1-3 in PDUS than joints of OA patients. In FOI, RA joints featured inflammatory signals with grades 1-3 more often in phase 1 in contrast to OA joints. In OA, higher grades were reached by DIP, PIP and wrist of OA patients in phase 3 in comparison to RA joints. FOI and US detected inflammation in both RA and OA accenting an inflammatory component of OA. Different inflammatory patterns between RA and OA were determined, especially in phases 1 and 3 in FOI. Hence, an analysis of the phases in FOI is of prime importance. The different shape patterns of ICG-enhancement may offer opportunities to distinguish both diseases.Die Synovitis als krankheitsspezifisches Merkmal tritt bei der Rheumatoiden Arthritis (RA) im Bereich der Hand typischerweise am Handgelenk, an den Metacarpophalangealgelenken (MCP) und den proximalen Interphalangealgelenken (PIP) auf. Dagegen finden sich mögliche sekundär entzündliche Veränderungen bei der Osteoarthrose (OA) der Hand hauptsächlich in PIP und distalen Interphalangealgelenken (DIP). Eine Visualisierung von entzündlichen Veränderungen der Gelenke ist durch den muskuloskelettalen Ultraschall (US) und die Fluoreszenz-optische Bildgebung (FOI) möglich. Ziel dieser Arbeit war der Vergleich der Ausprägung und Verteilung von entzündlichen Veränderungen an den Hand- und Fingergelenken bei Patienten mit RA und OA in der FOI und im US. 1170 Gelenke von 90 Patienten (67 RA, 23 OA) wurden in der FOI und im US untersucht. Dabei wurde der Ultraschall im B-Bild und im Power Doppler-Modus (PDUS) an den Handgelenken, MCP, PIP und DIP 2-5 der für Druckschmerzhaftigkeit und Schwellung klinisch dominanten Hand standardisiert jeweils auf dorsaler und palmarer Schnittebene durchgeführt. Die Untersuchung beider Hände im FOI erfolgte standardisiert über 360 Sekunden mit einer Aufnahme eines Bildes pro Sekunde für einen automatisch generierten PrimaVista-Modus (PVM) und für drei verschiedene Phasen (p1-p3). Die Bewertung von Synovitis und Tenosynovitis im US und die Verteilung des Farbstoffs Indocyaningrün (ICG) im FOI in der klinisch dominanten Hand wurde unter Verwendung eines semi-quantitativen Scores (0-3) vorgenommen. Anschließend wurde die Häufigkeit des Auftretens des semi-quantitativen Scores an den Gelenken in beiden Bildgebungsverfahren für RA und OA prozentual ermittelt. Das Handgelenk und die MCP-Gelenke bei der RA präsentierten im Vergleich zur OA häufiger entzündliche Veränderungen im B-Bild des US. Dagegen zeigten die DIP-Gelenke bei OA-Patienten in Hinblick auf die Gradzahlen häufiger Grad 1-3. Es waren mehr Gelenke von RA-Patienten im PDUS betroffen als Gelenke von Patienten mit OA. Bezüglich der Ergebnisse im FOI zeigten die Gelenke der RA- Patienten häufiger entzündliche Anreicherungen in Phase 1, während die DIP, PIP und Handgelenke der OA-Patienten in Phase 3 mit höheren Gradzahlen bewertet wurden. Mittels FOI und US wurden in beiden Kohorten (RA und OA) entzündliche Veränderungen als Synovitis/Tenosynovitis beziehungsweise ICG- Anreicherungen festgestellt. Daher spielt bei der OA eine entzündliche Komponente ebenfalls eine Rolle. Es zeigten sich im Vergleich zwischen RA und OA phasenabhängig verschiedene Befallsmuster, die sich insbesondere in den Phasen 1 und 3 präsentierten. Daher ist die Analyse der genannten Phasen (p1-p3) in der FOI in der klinischen Praxis von Bedeutung. Zusätzlich scheinen die unterschiedlichen Formmuster der ICG-Anreicherung Möglichkeiten zur Differentialdiagnostik beider Krankheiten zu bieten

Detection of subclinical skin manifestation in patients with psoriasis and psoriatic arthritis by fluorescence optical imaging

Objectives: To investigate the frequency of subclinical skin inflammation in both hands by fluorescence optical imaging (FOI) in patients with psoriasis/psoriatic arthritis (Pso/PsA) vs. rheumatoid arthritis (RA) and healthy individuals, and to correlate these findings with cardiovascular (CV) risk factors. Patients and methods: The FOI scans were analyzed retrospectively to detect clinically invisible skin enhancement (0-3 scale) in both hands without relationship to underlying joints or blood vessels. We further characterized the FOI patterns and sorted the scans into groups based on the assumed diagnosis (Pso/PsA, RA, and healthy controls), which was compared with the physician's diagnosis. Furthermore, the associations between CV risk factors and imaging findings were investigated by regression analyses. Results: We included FOI scans of patients with Pso/PsA (n = 80), RA (n = 78), and healthy controls (n = 25). Subclinical skin enhancement on the back of their hands was more common in Pso/PsA (72.5%) than in RA patients (20.5%) and healthy individuals (28.0%) (p < 0.001). Based on the FOI pattern, the majority of patients with Pso/PsA (72.5%), RA (76.9%), and healthy controls (68.0%) were classified correctly using the physician-based diagnosis as reference (overall agreement of 74%, kappa = 0.57). No CV risk factors except body weight (kg) were associated with subclinical skin enhancement (OR 1.04, 95% CI 1.02-1.06;p < 0.001). Conclusion: Subclinical subdermal skin inflammation was common in Pso/PsA patients using FOI. Based on the FOI pattern, most patients with Pso/PsA and were classified with the correct diagnosis. We demonstrated an important influence of the body weight on our FOI results. FOI may be a helpful novel tool to study microcirculation in rheumatic diseases with skin involvement

Follow-Up Comparison of Fluorescence Optical Imaging With Musculoskeletal Ultrasound for Early Detection of Psoriatic Arthritis

Objectives: Early diagnosis of psoriatic arthritis (PsA) is crucial for a patient outcome but hampered by heterogenous manifestation and a lack of specific biomarkers. We recently showed that fluorescence optical imaging (FOI) can differentiate between patients with confirmed and suspected PsA. This study aims to follow-up (FU) patients with confirmed and suspected PsA focusing on patients with a change from suspected to confirmed PsA by the use of FOI in comparison with musculoskeletal ultrasound (MSUS). Methods: Follow-up examination of patients included in the study performed by Erdmann-Keding et al. in which FOI of both hands was performed in a standardized manner using three predefined phases (p1–p3) and PrimaVista Mode (PVM). The comparison was drawn to grayscale–power Doppler (GS/PD) MSUS of the clinically dominant hand (wrist, MCP, PIP, DIP 2–5) from dorsal or palmar. Results: Patients with a change from suspected to diagnosed PsA showed an increased prevalence of joints with pathological enhancement in FOI (p = 0.046) with an unchanged joint distribution pattern, especially with a dominant involvement of DIP joints. Compared to the baseline, these patients were three times more common to show enhancement in FOI p3 at FU. Newly detected pathologic joints by FOI (PVM, p2) and MSUS at FU were positively associated with the change of diagnosis from suspected to confirmed PsA (FOI: AUC 0.78; GSUS: AUC 0.77). Conclusion: Fluorescence optical imaging appears to be a helpful tool to detect early PsA and to distinguish between acute and chronic disease stages. It could thereby become a suitable tool as a screening method to select psoriasis patients with an indication for further rheumatological evaluation

Fluorescence optical imaging:Ready for prime time?

The novel technique of fluorescence optical imaging (FOI, Xiralite), which is approved in the European Union and the USA for clinical use, has been the object of studies since 2009. Indocyanine green-based FOI can demonstrate an impaired microcirculation caused by inflammation in both hands in one examination. Several studies have investigated FOI for detection of joint inflammation by comparing FOI to magnetic resonance imaging (MRI) and/or musculoskeletal ultrasound (MSUS). The results have shown a generally good agreement (>80%) between FOI and clinical examination, MRI and MSUS by power Doppler in inflammatory joint diseases. Moreover, characteristic enhancements in skin and nails are seen in PsA, which potentially can be useful in the diagnostic process of early undifferentiated arthritis. Furthermore, FOI has been investigated for the visualisation of a disturbed microcirculation in the hands and fingers of patients with systemic sclerosis (SSc), highlighting the potential of monitoring vascular changes in SSc and other vasculopathies. The available data indicate that it is time to consider FOI as a useful part of the imaging repertoire in rheumatology clinical practice, particularly where MSUS and MRI are not easily available

Disturbed microcirculation in the hands of patients with systemic sclerosis detected by fluorescence optical imaging: a pilot study

Abstract Background Utilising 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. Methods In 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. Results Healthy 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. Conclusions FOI 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