Detection of rheumatoid arthritis by evaluation of normalized variances of fluorescence time correlation functions

Dziekan, Thomas; Weißbach, Carmen; Voigt, J.; Ebert, Bernd; Macdonald, Rainer; Bahner, M. L.; Mahler, Marianne; Schirner, Michael; Berliner, M.; Berliner, Birgitt; Osel, Jens; Osel, Ilka

doi:10.1117/1.3599958

Cited by 17 publications

(36 citation statements)

References 15 publications

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“…So far, different methods for interpreting the FOI results have been deployed [8,19,28]. Werner et al [8] used a semiquantitative score, where the signal enhancement has been graded in percentages.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, another study by Meier et al [19] reported that FOI had a sensitivity of 39.6% and a specificity of 85.2%, compared with MRI demonstrating conflicting results regarding the reliability of this new method. In 2011 Dziekan et al [28] proposed a quantitative analysis of FOI using normalized variances of fluorescence time correlation functions. In their pivotal pilot study, the joints of healthy volunteers and patients with RA were compared, but no other imaging techniques besides FOI were employed.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2013

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2013

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“…Studies have shown that NIRF imaging using these nonspecific dyes has the potential for detection of inflammatory joints. 24,26 In the current study we investigated the enhancement induced by the nonspecific NIRF dye TSC in ankle joints of rats with CIA. TSC is a well-tolerated cyanine dye of similar chemical nature as ICG; however, its in vivo properties (plasma binding, circulation time) are different from those of ICG.…”

Section: Discussionmentioning

confidence: 99%

“…22 A promising nonspecific dye is tetrasulfocyanine (TSC), a modified cyanine dye which was already successfully used for in vivo imaging of subcutaneously growing tumors in animals. 23 Clinical trials are under way to investigate different nonspecific NIRF dyes for the visualization of arthritis [24][25][26] and superficial tumors, e.g., in optical mammography. [27][28][29] TSC was selected for our experimental investigation because this dye exhibits increased hydrophilicity and less plasma protein binding, and therefore may possess improved imaging properties compared with ICG.…”

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confidence: 99%

Near-infrared fluorescence imaging of experimentally collagen-induced arthritis in rats using the nonspecific dye tetrasulfocyanine in comparison with gadolinium-based contrast-enhanced magnetic resonance imaging, histology, and clinical score

et al. 2012

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Abstract. Using 15 rats with collagen-induced arthritis (30 joints) and 7 control rats (14 joints), we correlated the intensity of near-infrared fluorescence (NIRF) of the nonspecific dye tetrasulfocyanine (TSC) with magnetic resonance imaging (MRI), histopathology, and clinical score. Fluorescence images were obtained in reflection geometry using a NIRF camera system. Normalized fluorescence intensity (I NF ) was determined after intravenous dye administration on different time points up to 120 min. Contrast-enhanced MRI using gadodiamide was performed after NIRF imaging. Analyses were performed in a blinded fashion. Histopathological and clinical scores were determined for each ankle joint. I NF of moderate and high-grade arthritic joints were significantly higher (p < 0.005) than the values of control and low-grade arthritic joints between 5 and 30 min after TSC-injection. This result correlated well with post-contrast MRI signal intensities at about 5 min after gadodiamide administration. Furthermore, I NF and signal increase on contrast-enhanced MRI showed high correlation with clinical and histopathological scores. Sensitivities and specificities for detection of moderate and high-grade arthritic joints were slightly lower for NIRF imaging (89%∕81%) than for MRI (100%∕91%). NIRF imaging using TSC, which is characterized by slower plasma clearance compared to indocyanine green (ICG), has the potential to improve monitoring of inflamed joints.

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“…These data are in accordance with our previous findings in humans and experimental arthritis. 11,14,21,22 …”

Section: Arthritis Severity and Nirf Imaging Before Therapymentioning

confidence: 99%

In vivotherapy monitoring of experimental rheumatoid arthritis in rats using near-infrared fluorescence imaging

et al. 2014

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Abstract. An in vivo near-infrared fluorescence (NIRF) imaging technique is described for therapy monitoring of ankle joints affected by collagen-induced arthritis, a model of human rheumatoid arthritis. Arthritis was induced in rats by intradermal injections of collagen and Freund's incomplete adjuvant. For in vivo imaging, the nonspecific NIR dye tetrasulfocyanine (TSC) was used. Prior to and after treatment with a nonsteroidal anti-inflammatory drug, meloxicam, or analgesic drug, tramadol hydrochloride (which served as no-therapy control), normalized fluorescence intensities of each ankle joint were measured. Additionally, each ankle joint was characterized by clinical arthritis scoring and histopathology. Over a 3-week treatment period, a significant difference in disease progression between animals treated with meloxicam and tramadol hydrochloride was detected. A statistically significant improvement in ankle joint pathology from high-or moderate-grade to moderate-or low-grade upon meloxicam therapy, as determined by clinical evaluation, translated into a significant decrease in fluorescence intensity. In contrast, all arthritic joints of the no-therapy control group deteriorated to high-grade arthritis with high-fluorescence intensities in NIRF imaging. © The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.

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Detection of rheumatoid arthritis by evaluation of normalized variances of fluorescence time correlation functions

Cited by 17 publications

References 15 publications

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

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

Near-infrared fluorescence imaging of experimentally collagen-induced arthritis in rats using the nonspecific dye tetrasulfocyanine in comparison with gadolinium-based contrast-enhanced magnetic resonance imaging, histology, and clinical score

In vivotherapy monitoring of experimental rheumatoid arthritis in rats using near-infrared fluorescence imaging

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