A novel arthritis in vivo fluorescence optical imaging technology pushed to the limits

Abstract

Sir, Fluorescence optical imaging (FOI) is a novel method that is increasingly utilized for visualizing arthritides by detecting local hyperperfusion. We report on a 57-year-old man of Indian heritage, suffering from an ACR criteria-positive RA. At the first visit to our clinic the patient complained of painful and swollen finger joints of several weeks duration. Clinical examination (CE) showed signs of a highly active polyarthritis involving both wrists and multiple small finger joints, which was reflected by a DAS28 score of 6.28. Laboratory evaluation revealed an elevated ESR of 53 mm/h (0–29 mm/h) and elevated CRP of 23 mg/l (≤5.0 mg/l). In addition, the following abnormal laboratory parameters were observed: haemoglobin 12.7 g/l, RF 127 U/ml, anti-CCP 250 U/ml and anti-modified citrullinated vimentin antibodies (anti-MCV) 669 U/ml. Musculoskeletal US (MUS) demonstrated highly active polysynovitis, with a US7 score of 17 [1]. Conventional radiographic examinations revealed no erosions. After obtaining the patient’s consent, a novel in vivo FOI technique was applied that uses the US Food and Drug Administration-approved fluorescence dye indocyanine green (ICG) to determine microperfusion. The FOI examination follows a standardized protocol by placing both hands on a preformed hand rest, followed by injection of an ICG bolus (0.1 mg/kg/body weight i.v.) and subsequent imaging with one image every second for a total of 6 min. Alterations of fluorophore concentration are depicted as alterations in signal intensity. As we observed highly active polysynovitis both clinically and sonographically, we expected to see similar changes in the FOI examination. However, the results did not correlate with the MUS findings or the CE (Fig. 1). FOI images. (A–C) FOI findings in an RA patient of Indian heritage. (D–F) FOI findings in a Caucasian RA patient with comparable disease activity. Under various experimental conditions, FOI proved to correspond to the degree of synovitis [2, 3]. In those experiments, early hyperaemia of inflamed joints could be detected by recording scattering and absorption patterns of light transmitted through inflamed finger joints. This approach has already been tested in humans [4, 5], which led to the development of an FOI system with fixed optical geometry used in our patient (Xiralite X4; Mivenion GmbH, Berlin, Germany). So far only two larger clinical studies that examine the novel FOI method in comparison with established imaging modalities have been published [6, 7]. The study by Werner et al. [6] demonstrated that FOI was more sensitive than CE and had good agreement with MUS utilizing power Doppler and MRI scanning. In contrast, a recent study by Meier et al. [8] indicated more controversial results, where the diagnostic accuracy of FOI compared with MRI imaging was especially limited in mild synovitis, while it performed substantially better in severely inflamed joints. Considering these results and the severe synovitis of multiple finger joints present in our patient as demonstrated by CE and MUS, the FOI results were surprising, indicating almost normal microperfusion. We propose that due to the increased pigmentation in our patient (who was originally from India), the light emitted by the LEDs was not sufficient to penetrate the skin and elicit the fluorescence response in a similar fashion to less pigmented Caucasian patients. This effect has been documented in several studies, demonstrating reduced light absorption due to increased melanin presence in the skin at UV and visible wavelengths [9, 10]. To our knowledge this is the first case report demonstrating a substantial disadvantage of FOI examinations related to skin pigmentation, which should be considered in the interpretation of the FOI findings. In addition, this observation is an important limitation for further clinical studies evaluating the clinical relevance of this novel imaging method and should be incorporated in the design of study protocols. Disclosure statement: The authors have declared no conflicts of interest.