# Time-Domain Near-Infrared Spectroscopy and Imaging: A Review
## 3 Instruments for TD-NIRS  
### Overview of TD-NIRS Instruments  
In the mid 1980s, NIRS succeeded in in vivo and non-invasive monitoring of the changes in cerebral hemoglobin concentrations in human heads [33]. However, the monitoring method based on the modified Beer-Lambert law is subject to the problem of quantitativeness due to the unknown optical pathlength which is necessary for applying the modified Beer-Lambert law.  
To cope with this problem in the late 1980s, studies were conducted to estimate the optical pathlengths in biological tissues by measuring TOF distributions of reemitted light after being multiply scattered in tissues using picosecond-pulsed lasers and detected by detectors having picosecond temporal resolutions such as streak cameras. [PERSON] et al. and [PERSON] et al. used an ultrafast dye laser excited by a krypton-laser for a light source (a pulse width less than 6 ps and repetition rate of 76 MHz at wavelengths of 761 nm and 783 nm) and a streak camera for a detector to estimate the mean optical pathlengths from the measured TOF distributions [34; 35], and found that the absorbance changes of the measured transmittance were related to the absorption changes in the media through the estimated mean optical pathlengths. [PERSON] et al. reported that the logarithmic slopes of TOF distributions in the decaying period were proportional to hemoglobin concentrations in biological tissues by TD experiments using two dye lasers excited by the second harmonics of an Nd:YAG laser for pulsed light sources and time-correlated single-photon counting (TCSPC) technique for a detector which was widely employed for measurement of fluorescence life time [36; 37]. Furthermore, [PERSON] et al. measured TOF distributions through rat heads using a Ti-Sapphire laser for a pulsed light source and a streak camera for a detector and concluded that the Beer-Lambert law held every time in the TOF distributions [38].  
These pioneering studies promoted wide use of time-domain near-infrared spectroscopy (TD-NIRS) systems for understanding light propagation and quantitative measurements of hemoglobin concentration in biological tissue. However, the TD-NIRS systems used in these pioneering studies had the disadvantages of being very expensive, large, non-portable, and highly sophisticated, and resultantly, their systems were unacceptable for clinical applications.  
To mitigate the disadvantages stated above, [PERSON] et al. developed a compact dual-wavelength multichannel tissue oximeter using two pulsed-laser diodes (pulse width less than 100 ps, repetition rate of 80 MHz, wavelengths of 672 nm and 818 nm) for light sources and multi-anode photomultiplier tubes (PMTs) for detectors [39]. [PERSON] et al. developed a compact three-wavelength one-channel tissue oxygenation monitor using three pulsed-laser diodes (pulse width less than 100 ps, repetition rate of 5 MHz, wavelengths of 759 nm, 797 nm and 833 nm) for light sources and PMTs for detectors based on the TCSPC technique [40]. This tissue oxygenation monitor was marketed but only in Japan. [PERSON] et al. also developed a single-wavelength single-channel TD optical mammograph using a pulsed laser diode (pulse width of about 400 ps, repetition rate of 80 MHz, wavelength of 785 nm) for light source and a PMT-TCSPC for detector, and measured TR-transmittance through healthy breasts as well as breasts carrying tumor [41].  
Currently, TD-NIRS systems with a few channels employing the TCSPC technique are actively developed for the purpose of applications in clinical usage, and also multi-channel TD-NIRS systems have been developed for TD-DOT.