Fluorescence optical imaging in pediatric patients with inflammatory and non-inflammatory joint diseases: a comparative study with ultrasonography

Abstract

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.

Keywords: Arthralgia; Fluorescence optical imaging; Imaging; Juvenile idiopathic arthritis; Power Doppler; Ultrasound.

Fig. 1

FOI findings in a patient with arthralgia (group II) without signs of inflammation. P1 describes the period between starting the examination and increased signal intensities in the fingertips, the time point of increased signal intensity in the fingertips is analyzed for evaluation. P2 is defined as the phase with persisting high signal intensities in the fingertips, the time point of a red-colored signal in the fingertips is analyzed for evaluation. P3 begins with the absence of signal intensity in the fingertips, and the time point of a missing (no) signal in the fingertips is analyzed for evaluation. PVM automatically generated Prima Vista Mode, P1–P3 phases 1–3

Fig. 2

FOI findings in a 17-year-old patient with clinically active seronegative polyarthritis (group I). Increased signal intensities as a sign of active inflammation (synovitis) can be seen in both hands especially in P1 as follows: high signal intensities (FOIAS grade 3) in MCP 4 + 5, PIP 3 + 5, and DIP 3 of the right hand; moderate signal intensities (FOIAS grade 2) in MCP 2, PIP 2 + 4, and DIP 2 of the right hand; and FOIAS grade 1 in IP of the right hand and DIP 2 + 3 and PIP 2 + 3 + 5 of the left hand. PVM Prima Vista Mode, P1–P3 FOI phases 1–3

Fig. 3

Gray-scale (GSUS) and power Doppler (PDUS) ultrasonography findings in a 13-year-old patient with clinically active seronegative polyarthritis (group I). a GSUS synovitis grade 3 and PDUS activity grade 2 as a sign of active synovitis in the right wrist (radiocarpal and intercarpal joint). b GSUS synovitis grade 2 and PDUS activity grade 3 (≥50% of the intraarticular area) as a sign of active synovitis in the right PIP3 joint from dorsal. PIP proximal interphalangeal joint

Fig. 4

Comparison of cumulative probability plot of fluorescence optical imaging scores (FOIAS) for patients aged < 13 years and patients aged ≥ 13 years in group I (JIA patients with clinically active arthritis in hand region) and group II (patients with non-inflammatory joint diseases)