# Clinical Brain Monitoring with Time Domain NIRS: A Review and Future Perspectives
## 6 Conclusions  
The use of NIRS technology has drawn a great deal of attention in the last four decades, due to its potential to continuously monitor the brain tissue physiology non-invasively, in real-time and at the patient bedside. However, the lack of reference values of brain tissue oxygen saturation coupled with the inherent limitations of the commonly-used CW-NIRS systems, in terms of accuracy and capability to differentiate non-cortical and cortical tissues, have hindered the popularity of NIRS. On the other hand, TD-NIRS systems have not been as popular because of their complexity and the lack of system availability commercially, with only one company selling instruments. However, in recent years, a few publications have reported successful clinical work using TD-NIRS. Indeed, this technique presents the unique advantage of measuring the distribution of the time of flight of photons. The amount of information contained in those DTOFs enables us to retrieve the optical properties (\(\mu_{a}\) and \(\mu\
u_{s}\)) of the tissue, even with only one channel. Having access to the absolute optical properties allows us to retrieve absolute concentration of haemoglobin and tissue saturation that are more robust than the those acquired via CW-NIRS systems, which only assume a constant, non-patient-specific \(\mu\
u_{s}\).  
Moreover, it has also been shown that \(\mu\
u_{s}\) could be used as a biomarker of TBI and that it was possible to follow the development of brain atrophy, for example in patients with neurodegenerative disease, by looking at the distribution of the late photons of the TPSF. These works reinforce the importance of the information acquired with TD-NIRS, which has the potential to not only measure brain oxygenation accurately, but also to give some insights to the brain tissue structure.  
It is worth mentioning that TD-NIRS can be coupled with DCE and/or DCS in order to monitor brain perfusion. The use of the moments allows DCE-TD-NIRS to extract an in-depth measure of the brain perfusion, improving the accuracy of its estimation over DCE-CW-NIRS. Additionally, combining DCE-TD-NIRS with DCS allows us to continuously monitor the brain perfusion, reported in physiological units, which facilitates better clinical interpretation.  
Finally, both the cost and the size of the TD-NIRS instruments have repeatedly been reported as the main disadvantages of this technique. However, the recent instrumental developments allow the reduction of both the cost and the size of the TD-NIRS systems. Therefore, we have no doubt that these improvements, coupled with the great possibilities offered by TD-NIRS to extract accurate brain oxygenation information, together with insights of the brain tissue structure, will enhance and further facilitate the popularity of TD-NIRS in clinical environments.  
The following are available online at [[http://www.mdpi.com/2076-3417/9/8/1612/s1](http://www.mdpi.com/2076-3417/9/8/1612/s1)]([http://www.mdpi.com/2076-3417/9/8/1612/s1](http://www.mdpi.com/2076-3417/9/8/1612/s1)), Video SI. Depth sensitivity of the gating method.  
[PERSON] and [PERSON] conceived and designed the study. [PERSON] conducted the literature search and drafted the first version of the paper. [PERSON] and [PERSON] commented on, revised and approved the manuscript.  
This research was funded by The Wellcome Trust (grant number 104580/Z/14/Z).  
The authors would like to thank [PERSON] for providing the video presented in the supplementary material.  
The authors declare no conflict of interest.