# Clinical Brain Monitoring with Time Domain NIRS: A Review and Future Perspectives
## 3 Clinical Brain Monitoring with TD-NIRS
### Neonatology  
The use of TD-NIRS in neonatology is the area that has been one of the most explored, starting from the very early days of TD-NIRS. This particular population is well-suited to NIRS, allowing DOT to be performed [61]. Indeed, the first papers reporting the use of an in-house developed TD-NIRS instrument (ID: 6 in Table 2) on neonates dates from the late 1990s, by the group of Dr. [PERSON] at Stanford University, USA. In a series of papers [62; 63; 64; 65], they reported the first tomographic images of neonates using TD-NIRS. This team then successfully tomographically-identified intracranial haemorrhage [62; 63] and focal regions of low oxygenation after acute stroke [65]. [PERSON] and colleagues [66] also retrieved a topographic image of the activation of the motor cortex of one infant measured at six days postnatal age. At University College London (UCL), UK, an in-house 32 channel TD-NIRS system was developed. This system was called MONSTIR (for Multi-channel Opto-electronic Near-infrared System for Time-resolved Image Reconstruction) [67; 68]. With this system, tomographic images of healthy infants [69] and infants with intraventricular haemorrhage (IVH) [69; 70] were reconstructed. An example of their reconstructed images is provided in Figure 5a. The image reconstruction required a comparison of the in-vivo data with the data acquired on a phantom with well-known optical properties, producing an image of the differences. The natural extension of this work was to be able to reconstruct images without the necessity to image a reference phantom. [PERSON] and colleagues [71] first demonstrated this possibility on a severely brain-injured 38-week-old newborn. The changes in absorption and scattering coefficient, and in [HbO\({}_{2}\)] and [HHb], resulting from small alterations in ventilator settings could be detected during an imaging session of three hours at two wavelengths. Following that, [PERSON] and colleagues [72], reported the first 3D optical images of entire pre-term babies' heads during motor-evoked response. More recently,  
Figure 4: Summary of the literature review results. (**a**) Summary of the principle TD-NIRS component used in the 52 reviewed publications. (**b**) Graph showing the number of publications using TD-NIRS in brain clinical application since the first study in 1998.  
the UCL team reported the development of the second generation of the TD-DOT-NIRS MONSTIR, called MONSTIR II [68]. [PERSON] and colleagues [73] reported to have successfully scanned a healthy infant with MONSTIR II. This work was largely exploratory to demonstrate the quality of the recording of the data acquired with MONSTIR II in a clinical environment. Moreover, in her PhD thesis [74], [PERSON] reported the use of moments to reconstruct images of babies presenting with perinatal arterial ischemic stroke (PAIS). Here, she explored the possibility of using the calculated moments (intensity, time of flight, variance) as a metric to locate the stroke area. In the literature there is a significant amount of publications using commercial TD-NIRS systems developed by [PERSON] in neonates. [PERSON] and colleagues [75] investigated the effect of blood transfusion on cerebral haemodynamic in preterm infants using a TRS-10 system, suggesting that TD-NIRS can be used for determining the need for transfusion in very-low-birth-weight infants. [PERSON] and colleagues [76] used a TRS-20 system to compare changes in cerebral and systemic perfusion between appropriate- and small-for-gestational-age (AGA and SGA, respectively) infants during the first three days after birth. Also using a TRS-20, [PERSON] and colleagues [77] reported the difference in brain oxygenation between term and preterm infants during the first three days of life. [PERSON] and colleagues [78] used a TRS-10 system to measure 5G\(\mathrm{O}_{2}\) and [HBT] in babies with hypoxic-ischemic encephalopathy (HIE), reporting that neonates with adverse outcomes had higher values within 24 h after birth compared with neonates with a favourable outcome.