# Time-Domain Near-Infrared Spectroscopy and Imaging: A Review
## 5 Studies toward Clinical Applications of TD-NIRS
### Time-Domain Diffuse Optical Tomography (TD-DOT)
#### 5.3.4 Brain Imaging  
A TD-DOT system developed by [PERSON]'s group was applied to neonatal heads to reconstruct 2D-DOT images of hemoglobin saturation to reveal the existence of hemorrhages in neonatal brains [181]. This system was also applied to adult heads to reveal the focal areas of neuronal activity in the brains [182]. The DOT images were reconstructed using a unique and heuristic curvilinear back-projection algorithm which was very fast in computation at the cost of a low accuracy. Their TD-DOT system, built in the early 1990s, required about 6 h to acquire one dataset for one image.  
[PERSON] et al. reported 3D-DOT images of hemodynamics in premature infant brains with hemorrhage using MONSTIR and custom-made helmets with optodes [49; 183]. They employed a non-linear inversion algorithm for image reconstruction (TOAST) [164]. The reconstructed images of \(C_{total\text{-}HB}\) and \(\text{S}_{\text{O2}}\) indicated the existence of hemorrhage with physiologically reasonable values. [PERSON] et al. also obtained DOT images of ventilated infant brains to show the hemodynamic responses to changes in the oxygen and carbon dioxide partial pressures in the ventilating air [184]. The changes in \(C_{total\text{-}HB}\) and \(\text{S}_{\text{O2}}\) revealed by the DOT images were in qualitative agreement with physiologically expected changes.  
[PERSON] et al. used a 16-channel multi-wavelength reflectance TD-DOT system to obtain DOT images of human brain activity using a reconstruction algorithm based on the microscopic Beer-Lambert law [9; 50]. The algorithm requires calculation of the photon path distribution only for a non-absorbing medium, and the changes in \(\mu_{a}\) are easily reconstructed. Two sets of optodes were attached onto the right and left of the forehead of a subject performing a video game task. The DOT images of \(\Delta C_{oxy\text{-}HB}\), \(\Delta C_{deoxy\text{-}HB}\), and \(\Delta C_{total\text{-}HB}\) overlaid on the MR images of his brain clearly showed the localized activity of the prefrontal cortex as shown in Figure 17, although the hemodynamic changes appeared in the dura mater due to localization errors.  
Figure 17: Hemodynamic changes in the prefrontal cortex observed by TD-DOT images during a video game task. Modified from Reference [50]. Copyright (c) 2005 The Japan Society of Applied Physics.  
Using MONSTIR [49], [PERSON] et al. obtained 3D-DOT images showing the response of a neonate motor cortex to the task of arm movement using a linear algorithm for image reconstruction [185]. It took about 2 h to acquire one dataset for one image, which is too long to obtain images of fast neuronal responses.  
[PERSON] et al. obtained DOT images of ventilated premature infant brains with the help of reducing the artifacts induced by the relative movements of the optodes against the scalp surface [46; 48]. [PERSON] et al. improved the image quality by introducing the coupling coefficients of the optodes as the unknowns in the reconstruction algorithm [46; 47; 186]. Although the quality of these DOT images for infant brains still needs to be improved for clinical use, these results demonstrate the feasibility of the whole-head imaging of neonates by taking advantage of their small head size and skull thickness.  
Imaging of neuronal activities by NIRS technology have recently been greatly advanced using the high-density reflectance CW-domain DOT having a data acquisition speed of 12 frames/s which is fast enough to visualize the hemodynamic response of neuronal activities [187]. Current TD-DOT systems are too slow for that purpose, and advancements in hardware for TD-DOT are highly desired for further applications in neuronal imaging.