Detection of Rheumatoid Arthritis Using Non-Specific Contrast Enhanced Fluorescence Imaging

doi:10.1016/j.acra.2009.09.016

Academic Radiology

Volume 17, Issue 3, March 2010, Pages 375-381

https://doi.org/10.1016/j.acra.2009.09.016 Get rights and content

Rationale and Objectives

The aim of this study was to develop a new tool for the early detection of inflammatory joint diseases using fluorescence imaging in the near-infrared (NIR) spectral range following the intravenous administration of an unspecific contrast agent.

Materials and Methods

A laser-supported system for fluorescence imaging of finger joints was designed and constructed. Five patients and a corresponding number of volunteers were examined using 0.1 mg/kg by weight of indocyanine green as an unspecific contrast agent. Fluorescence images were acquired continuously over a period of 15 minutes. As a control, 1 day before optical imaging, all patients and volunteers underwent contrast-enhanced magnetic resonance imaging (MRI) at 0.2 T. On the basis of MRI findings, all examined joints were divided into four groups: no change and mild, moderate, and severe synovitis. The emitted fluorescence photons were quantified in different regions of interest covering the finger joints and finger tips. The normalized fluorescence intensity of contrast agents was compared with MRI findings as a proven standard.

Results

NIR dyes of the cyanine class are enriched in inflammatory joints and show a different kinetic behavior compared to normal joints after bolus injection. These findings demonstrate clearly the capability of contrast-enhanced fluorescence imaging to detect early changes caused by rheumatoid arthritis in finger joints. The NIR results were correlated with MRI findings (r = 0.84).

Conclusion

Contrast-enhanced fluorescence imaging provides adequate information for the evaluation of inflammatory involvement of finger joints comparable to low-field MRI.

Section snippets

Study Design and Patients

This study was a prospective trial including five patients and five volunteers. The imaging equipment was installed in a clinical environment. All patients and volunteers underwent contrast-enhanced MRI investigation 1 day before optical examination. To perform optical investigations, a dose of 0.1 mg/kg by weight of indocyanine green (ICG) was administered, which is lower than that used for other diagnostic applications. Measurements on patients were performed with the approval of the local

Clinical Parameters

All patients and healthy volunteers could be included in the study. The mean age of volunteers was 30 years, and that of patients was 45 years. Two women and three men were investigated in the group of volunteers, whereas all investigated patients were men.

The laboratory diagnostic tests for healthy volunteers at the time of investigation were without pathologic findings; neither ESR (7.0 ± 2.7 mm/h) nor CRP (0.4 ± 0.1 mg/dL) was increased. The clinical investigation of finger joints also

Discussion

On the basis of results obtained in animal studies by our group (14), our aim in this study was to determine whether normal and inflammatory joints can be differentiated by means of the pharmacokinetic behavior of nonspecific dyes, determined by NIR. The application of this technique was elaborated in a clinical study for the first time. The rationale for investigating nonspecific dyes in the present study in humans was not only to evaluate the potential of NIR imaging but also to study the use

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Evaluation of three scoring methods for Fluorescence Optical Imaging in erosive hand osteoarthritis and rheumatoid arthritis
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Fluorescence Optical Imaging (FOI) demonstrates indocyanine green (ICG)-enhanced microcirculation in wrist and finger joints, as a sign of inflammation. We wanted to assess the reliability of three FOI scoring methods from Berlin, Stockholm, and Copenhagen, to assess the validity of FOI with MRI as reference and to compare enhancement in hand joints in erosive hand osteoarthritis (OA) vs. rheumatoid arthritis (RA).
Five readers scored all finger and wrist joints of 26 patients with erosive hand OA and RA on semi-quantitative 0–3 scales using three different FOI scoring methods. To evaluate inter-reader reliability, we calculated the intraclass correlation coefficients (ICC) for sum scores and prevalence and bias adjusted kappa values for ordinal scales (Pabak-OS) on joint level. Enhancement in joint groups in erosive hand OA vs. RA was compared using Mann-Whitney test. Sensitivities and specificities of FOI was calculated with MRI as reference for hand OA patients only.
We found moderate to good inter-reader reliability for all FOI scoring methods (Pabak-OS: 0.50–0.78, ICC: 0.43–0.85) and different patterns of enhancement in erosive hand OA vs. RA with significantly more FOI enhancement in DIP joints in erosive hand OA across all methods. With MRI as reference the different FOI scoring methods reached similar sensitivities (63–65%) and specificities (76–91%).
FOI enhancement can be measured reliably in erosive hand OA and RA using three different scoring methods. More DIP enhancement in erosive hand OA patients and good agreement with MRI support the diagnostic performance of FOI.
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Ex vivo studies performed with five laparoscopic fluorescence systems and one conventional system for open surgery confirmed that it is necessary to optimize the fluorescence system to allow the use of ICG cholangiography as an essential tool for bile duct navigation. Other experimental works support the applicability of ICG for additional purposes, including rheumatoid arthritis (Fischer et al., 2010; Werner et al., 2013), burns and other trauma (Fourman et al., 2014; Kamolz et al., 2006) and muscle perfusion (Habazettl et al., 2010; Vogiatzis et al., 2015), but nowadays ICG plays the main role in the diagnosis and treatments of tumours. On the one hand, ICG imaging permits confirming the targeting of the tumour region.
Indocyanine green (ICG) is a cyanine compound that displays fluorescent properties in the near infrared region. This dye is employed for numerous indications but nowadays its major application field regards tumour diagnosis and treatments. Optical imaging by near infrared fluorescence provides news opportunities for oncologic surgery. The imaging of ICG can be useful for intraoperative identification of several solid tumours and metastases, and sentinel lymph node detection. In addition, ICG can be used as an agent for the destruction of malignant tissue, by virtue of the production of reactive oxygen species and/or induction of a hyperthermia effect under irradiation. Nevertheless, ICG shows several drawbacks, which limit its clinical application. Several formulative strategies have been studied to overcome these problems. The rationale of the development of ICG containing drug delivery systems is to enhance the in vivo stability and biodistribution profile of this dye, allowing tumour accumulation and resulting in better efficacy. In this review, ICG containing nano-sized carriers are classified based on their chemical composition and structure. In addition to nanosystems, different formulations including hydrogel, microsystems and others loaded with ICG will be illustrated. In particular, this report describes the preparation, in vitro characterization and in vivo application of ICG platforms for cancer imaging and treatment. The promising results of all systems confirm their clinical utility but further studies are required prior to evaluating the formulations in human trials.
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These factors will influence light traveling through the tissue and can distinguish between healthy and inflamed joints. The potential of this technique for the detection of synovitis in RA patients has been demonstrated in several settings (2D and 3D) with generally superior performance than clinical examination and moderate-to-high correlation with reference imaging techniques, ultrasound and MRI [146–151]. The light can also be applied from the outside and re-emitted toward the viewer at a different wavelength after intravenous injection of a fluorophore.
Ultrasound and magnetic resonance imaging (MRI) have become established imaging techniques for the management of rheumatoid arthritis. Several publications have pointed out the advantages of these techniques for a more complete evaluation of the inflammation and structural damage at joint level. Recently new imaging techniques as the positron emission tomography (PET) associated with computed tomography (CT) or MRI scan, and the optical imaging have been introduced in the panorama. This article presents the advantages and limitations of each imaging techniques in light with the recent publications.
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Determining light absorption changes in multilayered turbid media through analytically computed photon mean partial pathlengths
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: This work was supported by the European Regional Development Fund and by the Investitionsbank Berlin (Berlin, Germany).

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Original investigationDetection of Rheumatoid Arthritis Using Non-Specific Contrast Enhanced Fluorescence Imaging

Rationale and Objectives

Materials and Methods

Results

Conclusion

Section snippets

Study Design and Patients

Clinical Parameters

Discussion

Acad Radiol

Acad Radiol

Acad Radiol

Arthritis of the finger joints: a comprehensive approach comparing conventional radiography, scintigraphy, ultrasound, and contrast-enhanced magnetic resonance imaging

Arthritis Rheum

The pathogenesis of joint destruction in chronic polyarthritis [article in German]

Radiologe

Therapy of rheumatoid arthritis: new developments and trends

Curr Rheumatol Rep

Entwicklung eines Fingergelenkphantomes zur optischen Simulation früher entzündlich-rheumatischer Veränderungen

Biomed Technik

Assessment of proximal finger joint inflammation in patients with rheumatoid arthritis, using a novel laser-based imaging technique

Arthritis Rheum

Sagittal laser optical tomography for imaging of rheumatoid finger joints

Phys Med Biol

First clinical evaluation of sagittal laser optical tomography for detection of synovitis in arthritic finger joints

Ann Rheum Dis

Multiparameter classifications of optical tomographic images

J Biomed Opt

Original investigation
Detection of Rheumatoid Arthritis Using Non-Specific Contrast Enhanced Fluorescence Imaging