# Clinical Brain Monitoring with Time Domain NIRS: A Review and Future Perspectives
## 5 Current Developments in TD-NIRS and Clinical Pertinence
### Development of New Methodologies  
In parallel with these technical developments, new methodologies have emerged that could be relevant in clinical applications, by improving the data quality, extracting more information or facilitating the operation of TD-NIRS system. For example, one of the particularities of TD measurements is the need to acquire an IRF to calibrate the measurement. This operation is time-consuming and is not always suitable in a clinical environment. A recent work by [PERSON] and colleagues [132] reported a method based on a multi-distance TD-NIRS measurement that eliminates the need for the IRF. The removal of this extra measurement step would definitely benefit its adoption by the clinical community. Other new methodological developments arise from hardware improvements. For example, the development of the new sources and detectors is not only beneficial in terms of miniaturisation, but also improves the quality of the raw signal. Indeed, one of the drawbacks of the TD-NIRS instrumentations over CW-NIRS systems is that it is more difficult to obtain a TPSF with a good SNR [49]. However, the newly developed sources and detectors can be used to perform a null source-detector distance measurement [133]. This approach is based on the fact that, unlike the CW technique, the source-detector distance does not influence the penetration depth in a TD measurement. Therefore, the sources and detectors can be positioned close together to increase the number of photons acquired, which greatly increases the SNR. Recently, [PERSON] and colleagues reviewed the new developments in the concept and hardware of TD-NIRS [134], and showed not only that the SNR of TD-NIRS measurements would not be a problem anymore, but also that the new instrumentation and methodologies can help to improve the resolution, the contrast, or the depth sensitivity of the TD-NIRS measurement. Thus, measurements to assess structures deeper than 5-6 cm are reportedly  
Figure 6: Examples of new TD-NIRS instrumentation. (**a**) Laser diode for compact systems (from [124]). (**b**) A compact probe holder based on a SiPM detector. No optical fibre is needed, and the detector is placed in direct contact with the skin. Extracted from [128]. (**c**) Compact SiPM detector. Extracted from [129]. (**d**) Fibreless TD-NIRS system. Extracted from [130]. (**e**) Compact all-in-one single channel TD-NIRS system. Extracted from [131]. possible [133]. Although these possibilities are still to be demonstrated practically, this could allow access to subcortical regions which would be a considerable asset in fields like TBI or stroke monitoring. Another exciting development is the broadband or multi-wavelength TD-NIRS, which enables true spectroscopic analysis. Indeed, the systems presented in this review rarely use more than three wavelengths, which is enough to assess the haemoglobin content. However, being able to quantify other chromophores, like water or lipids, can help to increase the accuracy of the oxygen saturation, by actually quantifying contributions that were either assumed (i.e., water content) or not taken into account (i.e., fat content). [PERSON] and colleagues [120] have reported the development of a TD-NIRS instrument with a broadband capability, acquiring data from 600-1350 nm. This system has a slow acquisition speed (i.e., minutes per spectra) but could still be used to assess the brain status of patients at the bedside. [PERSON] and colleagues [135] reported the development of a multiwavelength TD-NIRS system, capable of acquiring data at a rate compatible with a typical hemodynamic response, with 16 wavelengths in the range 650 to 870 nm. This system has been designed in order to target haemodynamic as well as CCO. This capability could be of interest in the clinic, as CCO has been shown to be a potential marker of brain injury in HIE [136]. In the context of HIE, some interesting work has been reported recently, using a TD-NIRS instrument to non-invasively monitor the brain temperature [137].