In this study, spatial frequency domain imaging (SFDI) and temporal frequency domain imaging (TFDI) are combined to observe superficial and deep tissues simultaneously using a time-resolving CMOS image sensor. SFDI is an established non-invasive wide-field imaging method for superficial or shallow tissues. On the other hand, time-resolved spectroscopy based near-infrared spectroscopy (TRS-NIRS) is suitable for deep tissue measurement while it is based on point or multipoint measurement. Recently, time-resolving CMOS image sensors based on the single-photon avalanche diode and charge modulators have emerged. To take advantage of their area-imaging capability, we propose a spatio-temporal frequency domain imaging (STFDI=SFDI+TFDI) method, where pulsed binary stripe patterns with a pitch, p, and a duty ratio of 1/N are sequentially projected onto the tissue. While the projected pattern is shifted N times with a step of p/N, time-resolved images are captured for every shift. SFDI is conducted by performing fast Fourier transform (FFT) at each pixel after integrating them in time for each shift. For TFDI, the detected light in the middle of the stripes is analyzed by FFT in time for each shift. Based on the obtained amplitude and phase for specific harmonics orders, the absorption and scattering coefficients are estimated. This concept was verified by a GPU-based Monte Carlo simulator, MCX, with a two-layer skin model. We also experimentally confirmed the difference in the measured reflectance and phase for SFDI and TFDI when the thickness of the first layer was changed.
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