Background/Purpose: To prospectively evaluate quantitative assessment of indocyanine green (ICG)-enhanced fluorescence optical imaging (FOI) for differentiation of synovitic from non-synovitic joints in patients suffering from rheumatoid arthritis (RA). 

Methods: FOI of the hands was performed in patients with active RA as recommended by the manufacturer (Xiralite system, Mivenion GmbH, Berlin, Germany; ICG bolus of 0.1 mg/kg/ body weight, sequence of 360 images, one image per second, stratified fluorescence readout (FLRO) of 3 phases (I: 1 – 120 s; II: 121 – 240 s; III: 241 to 360 s)). To dissect the effect of the overall perfusion of the hand from the perfusion due to active synovitis, a fluorescence ratio (FLRA) was calculated for each individual joint dividing the readout of the joint by the readout of the eponychium of the index finger. For comparison, absence or presence of synovitis in 5 joints of the clinical predominant hand (carpal joint, metacarpophalangeal and proximal interphalangeal joints of digits II & III) were analyzed using grayscale (GSUS) and power Doppler (PDUS) ultrasonography, or magnetic resonance imaging (MRI). The mean FLRO and FLRA were compared between joints with absent vs. present synovitis determined by GSUS, PDUS and MRI using student’s t-test.

Results: Ninety joints of 18 patients (8 female (44%), mean (± SD) age 63±10 years) with RA were included. The quantitative analysis for individual joints yielded values for the FLRO ranging from 4.4 to 49.0 x 10³, and the FLRA ranging from 0.37 to 2.27. A comparison of mean (±SD) of FLRO and FLRA is depicted in table 1. Overall, the analyses based on the FLRA revealed a higher discrimination than the analyses related to the FLRO. The most significant differences were observed for mean values of phases II & III. A sensitivity of 26/39 (67%) and a specificity of 31/40 (77%) were calculated for the FLRA of phase III using a cut-off value of more than 1.2 to detect MRI-diagnosed synovitis with FOI.

Conclusion: ICG enhanced FOI has a potential for visualizing synovitis in subjects with RA. For adequate FOI interpretation, phases II & III appear to be most relevant. Utilizing the presented quantitative approach, significant differences of the mean FLRO and particularly of the FLRA could be demonstrated comparing synovitic to non-synovitic joints in patients with active RA. However, a definitive cut-off value for either analytic method could not be established.

Table 1. Mean fluorescence readout and fluorescence ratios for joints with vs. without evidence of synovitis determined by established imaging techniques. Fluorescence readout results are displayed for better readability divided by 10³, FOI= fluorescence optical imaging, GSUS=grey scale ultrasonography, PDUS=power Doppler ultrasonography, MRI=magnetic resonance imaging;  ^§11 joints could not be evaluated with MRI; ns comparison was not significant (p≥.05) with student’s t-test.

		phase I 1 – 120 s		phase II 121 – 240 s		phase III 241 – 360 s
Synovitis	n	mean ± SD	p	mean ± SD	p	mean ± SD	p
		FOI readout		FOI readout		FOI readout
GSUS yes	39	21.0 ± 11.4	ns	23.5 ± 10.4	<.01	15.8 ± 7.9	<.01
GSUS no	51	17.7 ± 7.5		16.6 ± 6.8		10.5 ± 4.8
PDUS yes	23	24.1 ± 12.3	<.05	23.8 ± 9.3	<.05	15.0 ± 5.9	ns
PDUS no	67	17.5 ± 7.7		18.2 ± 8.7		12.0 ± 7.0
MRI yes	39§	20.9 ± 10.1	ns	22.3 ± 9.5	<.05	14.8 ± 7.3	<.05
MRI no	40§	17.8 ± 9.6		17.2 ± 9.2		10.9 ± 6.5
		FOI ratio		FOI ratio		FOI ratio
GSUS yes	39	1.06 ± 0.47	ns	1.33 ± 0.48	<.05	1.37 ± 0.48	<.01
GSUS no	51	0.91 ± 0.32		1.10 ± 0.26		1.12 ± 0.26
PDUS yes	23	1.22 ± 0.46	<.01	1.52 ± 0.52	<.01	1.53 ± 0.53	<.01
PDUS no	67	0.89 ± 0.33		1.09 ± 0.26		1.12 ± 0.26
MRI yes	39§	1.11 ± 0.46	<.01	1.38 ± 0.47	<.001	1.41 ± 0.46	<.001
MRI no	40§	0.86 ± 0.33		1.06 ± 0.26		1.08 ± 0.26

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/quantitative-assessment-of-synovitis-in-patients-with-rheumatoid-arthritis-using-fluorescence-optical-imaging/