Detection of Rheumatoid Arthritis Using Non-Specific Contrast Enhanced Fluorescence Imaging Thomas Fischer, MD, Bernd Ebert, PhD, Jan Voigt, GE, Rainer Macdonald, PhD, Udo Schneider, MD, Anke Thomas, MD, Bernd Hamm, MD, and Kay-Geert A. Hermann, MD 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. Key Words: Rheumatoid arthritis; fluorescence; imaging; ICG; MRI; gadolinium DTPA. ªAUR, 2010 T he early identification of destructive proliferative syno- vitis in inflammatory joint diseases is crucial for both prognosis and treatment strategy for rheumatoid arthritis. However, a major disadvantage of conventional radi- ography, the current standard of reference for the diagnosis of this disease, is its lack of sensitivity in detecting early changes (1,2). Regrettably, many patients develop joint damage within the first year of disease (3). Typically, it affects the small joints first, including the joints of the hands and feet. More than one joint is usually affected, and symptoms often appear bilaterally. Precise validation is crucial for treatment efficacy and predicts the success of therapy. Over the past decade, there has been increasing interest in optical imaging techniques. Only little attention, however, has been paid to developing near-infrared (NIR) imaging techniques focused on the detection of rheumatoid arthritis. In an initial approach (4), changes in the scattering of light transmitted through finger joints were proposed to monitor early stages of this disease. This approach was evaluated in a clinical study of patients with rheumatoid arthritis (5). The investigators found that it is not yet possible to definitely distinguish between a healthy and an inflamed joint in different individuals by laser imaging on the basis of changes in scattering. Optical tomography has been applied to improve the differentiation between healthy and inflamed joints (6,7). The classification problem of rheumatic arthritis in finger joints was investigated recently by Klose et al (8) using all possible combinations of absorption (m a ) and scat- tering (m 0 s ) values. Receiver-operating characteristic curve analysis for the best fit yielded an area under the curve of 0.72. These techniques without contrast enhancement are still time consuming and therefore not suited for routine application. Absorption spectroscopy in the visible and NIR spectral ranges has been applied as well to characterize the synovium of small finger joints in both early and late rheumatoid arthritis (9). The investigators found that differences occurred in spec- tral regions that reflected tissue oxygenation status. At the same time, a Cy5.5-labeled antibody against macrophages was successfully used to label specifically inflammatory Acad Radiol 2010; 17:375–381 From Institut fu ¨ r Radiologie (T.F., A.T., B.H., K.-G.A.H.) and Institut fu ¨r Rheumatologie (U.S.), Charite ´ - University Berlin, Campus Charite ´ Mitte, Charite ´ platz 1, 10117 Berlin, Germany; and Physikalisch-Technische Bundesanstalt, Berlin, Germany (B.E., J.V., R.M.). This work was supported by the European Regional Development Fund and by the Investitionsbank Berlin (Berlin, Germany). Address correspondence to: T.F. e-mail: thom. fischer@charite.de ªAUR, 2010 doi:10.1016/j.acra.2009.09.016 375