Jöbsis was the first to describe the in vivo application of near-infrared spectroscopy (NIRS), also called diffuse optical spectroscopy (DOS). NIRS was originally designed for the clinical monitoring of tissue oxygenation, and today it has also become a useful tool for neuroimaging studies (functional near-infrared spectroscopy, fNIRS). However, difficulties in the selective and quantitative measurements of tissue hemoglobin (Hb), which have been central in the NIRS field for over 40 years, remain to be solved. To overcome these problems, time-domain (TD) and frequency-domain (FD) measurements have been tried. Presently, a wide range of NIRS instruments are available, including commonly available commercial instruments for continuous wave (CW) measurements, based on the modified Beer–Lambert law (steady-state domain measurements). Among these measurements, the TD measurement is the most promising approach, although compared with CW and FD measurements, TD measurements are less common, due to the need for large and expensive instruments with poor temporal resolution and limited dynamic range. However, thanks to technological developments, TD measurements are increasingly being used in research, and also in various clinical settings. This Special Issue highlights issues at the cutting edge of TD DOS and diffuse optical tomography (DOT). It covers all aspects related to TD measurements, including advances in hardware, methodology, the theory of light propagation, and clinical applications.

Theory/Algorithm/Modeling; Instrumentation and Technology I; Fluorescence Imaging/Spectroscopy (algorithm/model/tomography); Fluorescence Imaging/Image Reconstruction (Experimental); Instrumentation and Technology II; Fluorescence Imaging Technology I; Fluorescence Imaging Technology II; Fluorescence Imaging Technology III; Network for Translational Research in Optical Imaging: Breast Cancer Diffuse Optical Imaging; Breast II - Instrumentation & New Analysis Method; Breast III - Clinical Study; Pre-Clinical/Animal; Instrumentation and Technology III; Clinical/Human Subject Studies.

Through simulations, we first show the inaccuracy of near-infrared spectroscopy (NIRS) in quantifying local perturbations in the absorption coefficient of turbid medium and showed that DOT is required for quantitative study of such local changes.