Handheld spatial frequency domain imager for noninvasive Sjögren's syndrome labial salivary gland biopsy

A labial salivary gland biopsy (LSGB) plays an essential role in diagnosing Sjögren's syndrome (SS), but its clinical application is limited due to its invasiveness. Here, we present a handheld single snapshot multiple-frequency demodulation-spatial frequency domain imaging (SSMD-SFDI) device for a rapid optical biopsy of labial salivary glands noninvasively. The structural and physiological parameters of lower lip mucosa were obtained from the light reflectance of the layered oral mucosa. The recovered parameters were found to correlate strongly with the progression of SS. In our pilot study on 15 healthy subjects and 183 SS patients, a support vector machine (SVM) classifier using the measured parameters distinguished healthy subjects, LSGB I, II, III, and IV patients in sequence with AUCs of 0.979, 0.898, 0.906, and 0.978, respectively. Critical structural and physiological alterations in the mucosa due to SS were further identified and used to assess its risk using an explainable neural network. The handheld spatial frequency domain imager may serve as a valuable label-free and noninvasive tool for early diagnosing and surveying SS.