Near-infrared diffuse optical tomography (DOT), one of the most sophisticated optical imaging techniques for observations through biological tissue, allows 3-D quantitative imaging of optical properties, which include functional and anatomical information. With DOT, it is expected to be possible to overcome the limitations of conventional near-infrared spectroscopy (NIRS) as well as offering the potential for diagnostic optical imaging. However, DOT has been under development for more than 30 years, and the difficulties in development are attributed to the fact that light is strongly scattered and that diffusive photons are used for the image reconstruction. The DOT algorithm is based on the techniques of inverse problems. The radiative transfer equation accurately describes photon propagation in biological tissue, while, because of its high computation load, the diffusion equation (DE) is often used as the forward model. However, the DE is invalid in low-scattering and/or highly absorbing regions and in the vicinity of light sources. The inverse problem is inherently ill-posed and highly undetermined. Here, we first summarize NIRS and then describe various approaches in the efforts to develop accurate and efficient DOT algorithms and present some examples of clinical applications. Finally, we discuss the future prospects of DOT.

This article reviews the past and current statuses of time-domain near-infrared spectroscopy (TD-NIRS) and imaging. Although time-domain technology is not yet widely employed due to its drawbacks of being cumbersome, bulky, and very expensive compared to commercial continuous wave (CW) and frequency-domain (FD) fNIRS systems, TD-NIRS has great advantages over CW and FD systems because time-resolved data measured by TD systems contain the richest information about optical properties inside measured objects. This article focuses on reviewing the theoretical background, advanced theories and methods, instruments, and studies on clinical applications for TD-NIRS including some clinical studies which used TD-NIRS systems. Major events in the development of TD-NIRS and imaging are identified and summarized in chronological tables and figures. Finally, prospects for TD-NIRS in the near future are briefly described.

A noninvasive measurement method is proposed and examined to continuously predict blood glucose contents using near-infrared diffuse reflection difference spectra measured at the skin tissue without using multivariate analyses. Using the modified Beer’s law, the difference spectra are assumed to be synthesized from four major components in the human skin (water, protein, glucose, and fat) and a scattering equivalent component called baseline. As a result, one of the origins of the errors in blood glucose prediction using near-infrared is found to be the similarity of the shapes of the absorption spectrum between glucose and baseline. After separating the glucose contributions from the difference spectra at the characteristic wavelengths of baseline and fat, an imaginary component combining baseline and fat is introduced by considering that both the change in the fat contribution and the generation of baseline originate from the change in scattering in the skin. The imaginary component enables us to reduce the errors in blood glucose prediction. In contrast to the methods using multivariate analyses, the calculation process of the blood glucose contents from the measured reflection spectra is clear in this method, thus, it is easy to estimate the origins of the changes and contributions of the components in the measured difference spectra. The proposed method may become a useful tool for realization of noninvasive blood glucose prediction using near-infrared spectroscopy.

This work reviews our research during the past several years on time-resolved (TR) near-infrared diffuse optical tomography (DOT). Following an introduction of the measuring modes, two proposed schemes of image reconstruction in TR-DOT are described: one utilizes the full TR data, and the other, referred to as the modified generalized pulse spectrum technique (GPST), uses the featured data extracted from the TR measurement. The performances of the two algorithms in quantitativeness and spatial resolution are comparatively investigated with 2-D simulated data. TR-DOT images are then presented for phantom experiments, which are obtained by using a 16-channel time-correlated single photon counting system, and the factors affecting the quantification of the reconstruction are discussed. Finally, in vitro and in vivo imaging examples are illustrated for validating the capibility of TR-DOT to provide not only the anatomical but also the physiological information of the objects.

We try a new approach with near-IR time-resolved spectroscopy, to separate optical signals originated in the upper layer from those in the lower layer and to selectively determine the absorption coefficient $(μa)$ of each layer in a two-layered turbid medium. The difference curve in the temporal profiles of light attenuation between a target and a reference medium is divided into segments along the time axis, and a slope of each segment is calculated to determine the depth-dependent $μa$. The depth-dependent $μa$ values are estimated under various conditions in which $μa$ and the reduced scattering coefficient $(μs′)$ of each layer are changed with a Monte Carlo simulation and in phantom experiments. Temporal variation of them represents the difference in $μa$ between two layers when $μs′$ of a reference is the same as that of the upper layer of the target. The discrepancies between calculated $μa$ and the real $μa$ depend on the ratio of the real $μa$ of the upper layer to that of the lower layer, and our approach enables us to estimate the ratio of $μa$ between the two layers. These results suggest the potential that $μa$ of the lower layer can be determined by our procedure.

Tomographic images of the optical properties can be reconstructed using inversion algorithms for diffuse optical tomography (DOT); however, changes in the optode coupling that occurs while obtaining an object's measurements may often lead to the presence of artifacts in the reconstructed images. To reduce the number of artifacts induced by optode coupling, previous studies have introduced (unknown) coupling coefficients in reconstruction algorithms, which were found to be effective for continuous wave- and frequency-domain DOT. This study aims to investigate the effects of optode calibration on the reconstructed images of time-domain DOT. Here, coupling coefficients are incorporated into the time-domain DOT algorithm based on a modified generalized pulse spectrum technique. The images of the absorption coefficient are reconstructed in various numerical simulations, phantom experiments, and in vivo experiments of time-domain DOT. As a result, the artifacts resulting from changes in optode coupling are reduced in the reconstructed images of the absorption coefficient, thereby demonstrating that introduction of coupling coefficients is effective in time-domain DOT. Moreover, numerical simulations, phantom experiments, and in vivo studies have validated this algorithm.