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Optical tomographic imaging (OTI) was reported to be a novel technique for the early diagnosis and disease activity assessment of rheumatoid arthritis (RA). This study aimed to evaluate the clinical utility of OTI for the detection of hand synovitis of RA patients. Manu-scan was used to perform imaging targeting the proximal interphalangeal (PIP) and metacarpophalangeal (MCP) joints in 12 RA patients and three controls. The enrolled RA patients also underwent magnetic resonance imaging (MRI) and bone scintigraphy (BS) to provide reference images. Of the 181 joints feasible for OTI analysis, 140 joints (111 in RA patients and 29 in controls, 77.3%) in which the difference of the OTI indices in the two measurements was within 20% were evaluated. The OTI indices in RA joints were significantly lower than those in control joints (p < 0.001). Overall, the OTI indices in RA joints decreased as the synovitis grades on MRI or BS increased. Moreover, OTI was able to discriminate between RA and control joints (AUC = 0.815, 95% CI 0.739–0.891), even if RA joints were normal on physical examination (AUC = 0.714, 95% CI 0.594–0.834). OTI was in good agreement (kappa = 0.60) with MRI for evaluating synovitis in RA patients and showed positive results in 11.4% of clinically asymptomatic joints. OTI in this study showed the potential to be a supplementary imaging modality for the quantification of synovial inflammation in PIP and MCP joints of RA patients. Further large-scale trials are needed to confirm these findings. [ABSTRACT FROM AUTHOR]