Quantitative assessment of synovitis in patients with rheumatoid arthritis using fluorescence optical imaging

Abstract

IntroductionTo prospectively evaluate quantitative assessment of fluorescence optical imaging (FOI) for differentiation of synovitic from non-synovitic joints in patients suffering from rheumatoid arthritis (RA).MethodsFOI of the hands was performed in patients with active RA, and a stratified quantitative fluorescence readout (FLRO) of 3 phases (1-120 s; 121-240 s; 241-360 s) was generated for 5 individual joints of the clinical predominant hand (carpal joint, metacarpophalangeal and proximal interphalangeal joints of digits II & III). To dissect the effect of the overall perfusion of the hand from the perfusion due to synovitis, a fluorescence ratio (FLRA) was additionally calculated, dividing each FLRO by the readout of the eponychium of digit II. The mean FLRO and FLRA were compared between joints with absent vs. present synovitis determined by clinical examination, grayscale, color Doppler ultrasonography, or magnetic resonance imaging (MRI).ResultsThe analysis for 90 individual joints from 18 patients yielded FLRO ranging from 4.4 to 49.0 × 103, and FLRAs ranging from 0.37 to 2.27. Overall, the analyses based on the FLRA revealed a higher discrimination than the analyses related to the FLRO, demonstrating most significant differences in phases 2 and 3. A sensitivity of 26/39 (67%) and a specificity of 31/40 (77%) were calculated for FLRA of phase 3 using a cut-off value of more than 1.2 to detect MRI-confirmed synovitis with FOI.ConclusionsFOI has a potential for visualizing synovitis in subjects with RA. For adequate FOI interpretation, quantitative analysis should be based on the novel FLRA calculated for phases 2 and 3.

Near-infrared Fluorescence Optical Imaging in Early Rheumatoid Arthritis: A Comparison to Magnetic Resonance Imaging and Ultrasonography

“…Indeed, early enhancement of contrast agents is currently widely discussed as an important marker for synovial vascularity in the context of MRI studies 38,39,40,41 . On the other hand, Schafer, et al found best results for intermediate (P2) and late enhancement (P3), applying dynamic raw data analysis, although their definition of phases substantially differs from this present study, because phases are defined by time only (P1: 0-120 s; P2: 120-240 s, P3: 240-360 s) 23 .…”

“…FOI with IV administration of nonspecific fluorophores, such as ICG, depicts disturbances of microvascularization of the examined area. In studies with animal models, FOI has shown to be an appropriate imaging method for the detection of arthritis 18,19 ; however, only a few in vivo studies have been conducted in humans to evaluate FOI as a diagnostic approach in arthritides 11,13,14,15,17,22,23 . MRI and US are capable of depicting inflammatory thickening and hypervascularization of the synovial membrane in RA, which is suspected of leading to bone and joint destruction in the course of disease 17,32,33,34,35,36,37 .…”

“…The Journal of on June 1, 2015 -Published by www.jrheum.org Downloaded from nonspecific dyes, most commonly indocyanine green (ICG), has become a promising tool for the detection and monitoring of arthritides; it is less expensive than MRI and less time-consuming than both MRI and US 13,14,15,20,21,22,23 . However, to date few data are available to support the wide use of FOI for routine diagnosis of early RA.…”

“…The dynamic analysis of FOI enhancement has shown to be advantageous with regard to a more standardized and objective image analysis 11,17,22,23 . Different approaches have been described so far: 3 studies performed a quantitative analysis of joint enhancement under consideration of the enhancement of the fingertips 11,17,23 and another study compared the rate of early enhancement and areas under the curve for both FOI and MRI, with good to excellent agreement rates also in comparison to the clinical examination 22 .…”

Joint blood flow is more sensitive to inflammatory arthritis than oxyhemoglobin, deoxyhemoglobin, and oxygen saturation

“…Since hypoxia affects both tissue blood content and oxygenation [22,24], near-infrared optical methods-diffuse optical spectroscopy (DOS) and tomography (DOT), and photoacoustic tomography (PAT)-that are sensitive to these physiological parameters are being developed to supplement/replace clinical assessment and radiology for RA monitoring [25][26][27][28][29][30][31][32][33][34]. These emerging techniques, DOS in particular, have the potential to overcome most of the limitations of current RA monitoring methods since they are safe, relatively inexpensive, and have the potential to quickly and objectively assess RA inflammation at the individual joint level [34,35].…”