Abstract.SignificanceShort-separation (SS) regression and diffuse optical tomography (DOT) image reconstruction, two widely adopted methods in functional near-infrared spectroscopy (fNIRS), were demonstrated to individually facilitate the separation of brain activation and physiological signals, with further improvement using both sequentially. We hypothesized that doing both simultaneously would further improve the performance.AimMotivated by the success of these two approaches, we propose a method, SS-DOT, which applies SS and DOT simultaneously.ApproachThe method, which employs spatial and temporal basis functions to represent the hemoglobin concentration changes, enables us to incorporate SS regressors into the time series DOT model. To benchmark the performance of the SS-DOT model against conventional sequential models, we use fNIRS resting state data augmented with synthetic brain response as well as data acquired during a ball squeezing task. The conventional sequential models comprise performing SS regression and DOT.ResultsThe results show that the SS-DOT model improves the image quality by increasing the contrast-to-background ratio by a threefold improvement. The benefits are marginal at small brain activation.ConclusionsThe SS-DOT model improves the fNIRS image reconstruction quality.