Spatial frequency domain imaging for assessment of scleroderma skin involvement

Systemic sclerosis (SSc) is an autoimmune disease characterized by the widespread deposition of excess collagen in the skin and internal organs, as well as vascular dysfunction. The current standard of care technique used to quantify the extent of skin fibrosis in SSc patients is the modified Rodnan skin score (mRSS), which is an assessment of skin thickness based on clinical palpation. Despite being considered the gold standard, mRSS testing requires a trained physician and suffers from high inter-observer variability. In this study, we evaluated the use of Spatial Frequency Domain Imaging (SFDI) as a more quantitative and reliable method for assessing skin fibrosis in SSc patients. SFDI is a wide-field and non-contact imaging technique that utilizes spatially modulated light to generate a map of optical properties in biological tissue. The SFDI data were collected at 6 measurement sites (left and right forearms, hands, and fingers) of eight control subjects and ten SSc patients. mRSS were assessed by a physician, and skin biopsies were collected from subject’s forearms and used to assess for markers of skin fibrosis. Our results indicate that SFDI is sensitive to skin changes even at an early stage, as we found a significant difference in the measured optical scattering (μ_s^') between healthy controls and SSc patients with a local mRSS score of zero (no appreciable skin fibrosis by gold standard). Furthermore, we found a strong correlation between the diffuse reflectance (R_d) at spatial frequency of 0.2 mm^(-1) and the total mRSS between all subjects (Spearman correlation coefficient = -0.73, p-value < 0.0028), as well as high correlation with histology results. The healthy volunteer results show an excellent inter- and intra-observer reliability (ICC > 0.8). Our results suggest that the measurement of tissue μ_s^' and R_d at specific spatial frequencies and wavelengths can provide an objective and quantitative assessment of skin involvement in SSc patients, which could greatly improve the accuracy and efficiency of monitoring disease progression and evaluating drug efficacy.