# Clinical Brain Monitoring with Time Domain NIRS: A Review and Future Perspectives
## 4 Discussion  
We have summarized the clinical application of TD-NIRS and reported its use (1) in the neonatology unit to follow neonates with various conditions, (2) in the ICU to monitor stroke or TBI patients, or to communicate with patients with locked-in syndrome, (3) in the operating room to follow brain oxygenation during surgery, and (4) in more \"standard\" neuroscience environments for studies focusing on patients with psychiatric disorders. Historically, the first clinical application of TD-NIRS was in imaging the brain of premature infants; in particular obtaining 3D tomographical images of their brains in the neonatal intensive care unit. The 17% of TD-NIRS publications exploring TD-DOT are only focused on neonates. However, optical brain tomographs require resolving significant hardware and software challenges, and after a prolific number of publications in early 2000, this field has been less active on the clinical side even though methodological developments are still being made. The reduction in activity might also be explained by the significant improvements made by CW-NIRS-DOT [61]. Most of the TD-NIRS instruments used in clinical applications are multi-channel (81% of the TD-NIRS). Multichannel systems can probe both hemispheres at the same time, which is very important when a comparison is needed between hemispheres. On the other hand, some specific clinical applications, such as in perioperative care where the brain responses are global, do not require monitoring of several brain locations. The other interesting metric of this review is that the distribution between commercial and in-house developed system was fairly balanced, with 52% of papers reporting commercial system use. However, it is worth mentioning that only Hamamatsu can provide commercial TD-NIRS systems, and that most of the work reported with these systems was originating from Japan. The use of three different versions of their research systems has been reported here (TRS-10/20/21). The use of a NIRO-TRS1 have also been reported, although it is worth noting that it is a research device which is not available for sale. Lastly, we can note that the tNIRS-1 has been approved for use as a medical device in Japan but has not obtained approval outside Japan as of March 2019 ([PERSON] personal communication). Nevertheless, this approval in Japan is a great step towards the translation of the technique in the clinic. Indeed, the limited availability of these clinically-approved commercial systems is undoubtfully one of the main pitfalls of TD-NIRS, hindering its use in the hospital. Regarding the data produced by TD-NIRS systems, it has been seen that a variety of information can be retrieved, as illustrated in Figure 5. Information could be extracted about (1) the absolute optical properties of tissue and path length; (2) the absolute value of haemoglobin and tissue saturation, either as a snapshot tomographic image, or as a time-course at specific locations to follow spontaneous changes, or changes due to a brain activation; (3) the in-depth kinetics of an ICG bolus time to assess perfusion; and (4) the perfusion measured by a DCS system and calibrated with a TD-NIRS system. In order to produce this information, different processing methods of the TPSF were used. It seems that the fitting approach is the most widespread in order to extract the optical properties of tissues. This is partly because this method is the one implemented in the Hamamatsu systems. When using in-house instruments, the moment method tends to be used, especially when ICG is used. Indeed, in the case of bolus tracking, the moments can be used directly to follow the kinetics of the contrast agent. Moreover, the different depth-sensitivity of the moments enables the bolus to be tracked in-depth. To date, there is no consensus on what the best method to extract the TPSF information content is, and it might also depend on the application.