Inflammation assessment in patients with arthritis using a novel in vivo fluorescence optical imaging technology

Abstract

Background: Indocyanine 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.

Methods: 252 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.

Results: In 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.

Conclusion: ICG-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.

Figure 1

Schematic display of the Xiralite system. A preformed hand rest is used for reliant positioning of both hands. High-power light-emitting diodes (LEDs) illuminate the field of view with dark red light, whereas a specialised digital camera system (charge-coupled device) records the fluorescence signal intensities in the near-infrared spectrum.

Figure 2

FOI findings in active rheumatoid arthritis (RA). Phase 1 (A) displays focal increases signal intensities until first increased signals in fingertips (early enhancement phase), phase 2 (B) shows increased signal intensities at the same time as signals in fingertips (intermediate phase), and phase 3 (C) is reached after increased signal intensities of fingertips has decreased (late phase).

Figure 3

FOI (CI) and GSUS in psoriatic arthritis (PsA). FOI shows signal intensities in projection of the joints, tendons, osseous and periosteal structures corresponding to clinical dactylitis. Besides, triangular, slightly arcuate enhancements in projection of the nail bed in fingers 3 and 4 of the right hand are seen. GSUS presents an anechoic structure (*) around the hyperechoic flexor tendon (t) corresponding to tenosynovitis. CI, composite image; FOI, fluorescence optical imaging; GSUS, ultrasonography in greyscale mode; PsA, psoriatic arthritis.

Figure 4

Comparison of FOI (CI) and MRI findings. Corresponding signal intensities in FOI and contrast-enhanced (gadolinium) MRI in PIP 2, 3, and 5 of the left hand (A, B). CI, composite image; FOI, fluorescence optical imaging.