# Clinical Brain Monitoring with Time Domain NIRS: A Review and Future Perspectives
## 2 Basics of NIRS
As this parameter cannot be measured by CW systems, since they cannot distinguish absorption and scattering, this DPF is generally extracted from tabulated values [26] or using a modelling approach [27]. This limits the quantitative accuracy of the measurement since the overall scattering coefficients of the probed tissues is subject-dependent. This is also the reason why single point CW-NIRS only reports changes in haemoglobin concentration. However, some extensions of the CW technique enable us to access some absolute parameters. Indeed, using the spatially resolved spectroscopy (SRS) technique, based on the measurement of the light attenuation at several source/detector separations, the absolute \(\mu_{a}\) of the tissue can be estimated by fitting the distribution of the spatially resolved light attenuation measured, to the solution of the DE in the CW regime [28]. Then, measuring the spatial distribution of the light attenuation at several wavelengths, and assuming (1) that [HbO\({}_{2}\)] and [HHb] are the sole chromophores contributing to theabsorption and (2) an a-priori distribution of \(\mu^{\prime}s\) as a function of wavelength, then one can extract information about the absolute tissue oxygen saturation (referred as tissue oxygenation index (TOI) or tissue saturation (StO\({}_{2}\)) in the literature) [29]. The tissue saturation reflects the ratio between the concentration of [HbO\({}_{2}\)] and the concentration of total haemoglobin ([HbT] = [HbO\({}_{2}\)] + [HHb]). This has been widely exploited by commercial brain oximeters [30]. Moreover, some recent developments in CW system methodology employing a broadband spectrum can be used in order to extract absolute optical properties of the tissue [31]. The use of a broadband spectra can also unlock information on a third chromophore, cytochrome-c-oxidase (CCO), which is a marker of the metabolism. Therefore, the detection of this third chromophore can refine the picture of the tissue status obtained by NIRS, through integration of the metabolic and hemodynamic information [32]. One of the drawbacks of NIRS is its poor spatial resolution due to the inherent properties of light transport in tissue. This drawback can be reduced when using not only one, but several detection channels. Indeed, more complex arrangements have been developed to give access to a topographic (2D) or tomographic (3D) maps of brain haemoglobin concentration (referred as DOT: diffuse optical tomo/topography). This approach has largely been exploited in functional NIRS (fNIRS), where brain activity is being monitored [33]. Recently, the development of high-density DOT proved to have a resolution comparable to MRI [34], marking a new cornerstone in the development of the NIRS technology. The second NIRS technique is frequency domain NIRS (FD-NIRS). In FD-NIRS the light shined onto the tissue is modulated at frequencies in the MHz range. The tissue will attenuate and shift the phase of the reflected light. Analysis of the phase-shift provides information on the total distance that the light has travelled through tissue. To solve the DE and obtain measurements of absorption and scattering, the intensity and phase at two or more, source-detector distances is required [35]. FD-NIRS enables the estimation of absolute brain tissue oxygen saturation and enhances depth resolution comparable to TD-NIRS [36]. However, [PERSON] and colleagues [37] have recently compared CW-NIRS with FD-NIRS in monitoring clinical hypoxia, reporting that there were no advantageous difference observed in parameters recovered from the FD-NIRS compared with those detected by CW-NIRS. Figure 1: Schematic of the three NIRS detection modes. (**a**) TD-NIRS mode, an ultra-short light impulse is shined onto the tissue and the broadened and attenuated re-emitted pulse is measured after passing through the tissue. (**b**) FD-NIRS, a modulated (MHz) continuous light source is shined onto the tissues and the attenuated, phase shifted reemitted light is measured.