# Clinical Brain Monitoring with Time Domain NIRS: A Review and Future Perspectives
## 1 Introduction  
Over the last two decades, the near-infrared spectroscopy (NIRS) field has gained lots of attention as more and more instruments are used in patients within the hospitals [1]. NIRS relies on the fact that light, in the range of 600 to 1000 nm, can penetrate deep into the biological tissue, because in that wavelength range absorption is low, and scattering is the dominant interaction process. Moreover, each absorber, called chromophore, has a specific absorption or extinction coefficient [2]. It is thus possible to quantify the contribution of each chromophore and to resolve its concentration in the tissue. One of the main chromophores in tissue that is oxygen dependent is haemoglobin; NIRS can quantify the in vivo concentrations of oxygenated (HbO\({}_{2}\)) and deoxygenated (HHb) haemoglobin and hence monitor tissue oxygenation non-invasively, and in real-time. Since its first introduction by [PERSON] in 1977 [3], this technique has been used to probe various types of tissue, such as brain and muscle [4] and breast [5]. From a methodological point of view, a NIRS measurement can be achieved in three different detection modes: continuous wave (CW), frequency domain (FD), and time domain (TD). These modes differ by their level of complexity and the amount of information that they can retrieve. We discussthe details of these techniques in Section 2, and Table 1 lists their main characteristics. Of those three techniques, the CW-NIRS mode is the most widespread and has already been used extensively in the hospitals. Indeed, several reviews can be found in the literature that discuss the use of NIRS in the context of clinical brain monitoring. In particular, a recent review by [PERSON] discusses the use of NIRS in neuroscience, and the clinical areas of cerebrovascular disease, epileptic disorders, and in the evaluation of the functional activation of the diseased brain [6]. The use of NIRS for monitoring, traumatic brain injury (TBI) [7] and clinical interventions, including the use of the technique in anaestbiology [8; 9], neonatology [10] and psychiatry [11; 12; 13; 14], have also been reviewed. While these reviews demonstrate the potential and popularity of the NIRS technique; there is still debate on whether NIRS can be used reliably in a clinical context. Most NIRS instruments used in hospitals are CW devices due to their commercial availability and simplicity of operation; however, these instruments have several limitations, mainly their lack of brain-specificity and the large variability in absolute quantification of oxygenation [15]. TD-NIRS can resolve these issues and enable an in-depth measurement of absolutes values (see next section). TD-NIRS technology is often viewed as more complicated when compared to CW-NIRS and is not widely available. Indeed, the society for functional Near Infrared Spectroscopy website lists companies providing NIRS instruments [16] and out of the 14 companies listed, only Hamamatsu Photonics K.K., Hamamatsu, Japan) provides commercial TD-NIRS instruments  
The goal of the present work is to review the current use of TD-NIRS for clinical applications, with a particular focus on brain monitoring. We will begin with a brief description of the NIRS basics in terms of methodology and technology. Then, we will review the reported work on clinical brain monitoring with TD-NIRS. Finally, we will highlight some recent TD-NIRS developments that we believe will have a direct impact on the clinical popularity of the technique.