# Optics Based Label-Free Techniques and Applications in Brain Monitoring
## 2 FNIRS in Human Brain Imaging
### Current Clinical Applications of fNIRS
They showed that fNIRS can potentially detect brain activity associated with single-trial lower limb motor preparation in stroke patients. This opens further investigations of using fNIRS for BCI application for patients' rehabilitation with lower limb motor impairment caused by stroke. FNIRS has been used to explore brain functional connectivity in rest and sleep states [76]. The goal was to create a network based on the correlation coefficient of the hemodynamic response among the 133 fNIRS channels. This study found that fNIRS can be used to study brain connectivity during rest and sleep states. Anesthesia monitoring can also utilize fNIRS by monitoring the changes of cerebral hemodynamic from forehead [77; 78]. Using the frequency-division multiplexing principle, [PERSON] et al. [77] showed that different brain states under propofol and sevoflurane can be spotted based on the HbO, HbR and total hemoglobin (HbT) monitored by fNIRS. Examining signals from 19 subjects, [PERSON] et al. [78] found a significant reduction in a global mean of HbO, HbR and HbT as the subjects transitioned from maintenance to emergence. However, additional fNIRS biomarkers calculated from local hemodynamic changes can be used for real-time monitoring of the emergence from anesthesia with sevoflurane. In addition, fNIRS makes hemodynamic measurement more practical as it is possible to use it in operating room environment. The use of fNIRS shows special potential for children and infants monitoring. [PERSON] et al. [79] and [PERSON] et al. [80] used fNIRS to measure brain hemodynamics from the frontal cortex of infants during language stimulation. From this exploration, they found lateral activation of the cerebral cortex during stimulation. In addition, [PERSON] et al. [81] and [PERSON] et al. [82] found increasing activity of the medial prefrontal cortex when infants interact with their parents and other infants. Using fNIRS for infants requires special attention to the power of the light due to fragility of their skin. Recent studies also show the potential use of fNIRS for animal models. [PERSON] et al. [83] measured hemodynamic activity from the primary visual cortex in anesthetized monkeys during visual stimulation. They found a robust and reliable response to the stimulation. FNIRS can be used in animal models to study specific diseases, which is useful when similar studies are conducted in human. [PERSON] et al. [84] studied hemodynamic changes associated with EEG spike-and-wave discharges in a genetic model of absence epilepsy in rats. The results were consistent with the metabolic studies, fMRI studies and some results in children with an absence of epilepsy. [PERSON] et al. [85] monitored hemodynamic and morphologic response in a mouse model to study brain damage. The results confirmed the potential of using fNIRS as a valuable quantitative non-invasive tool for brain monitoring after brain damage at the bedside and/or on the field. FNIRS recordings are possible to compare between animal and human experiments, e.g., to validate it with combined microscale measurements gathered from animals. In Biocenter Oulu, Finland, researchers are developing a scale-free monitoring concept that enables monitoring physiological signals similarly when performing experiments in mouse and human neuroimaging setups. By combining microscopic imaging, such as photo acoustic microscopy (PAM) and multi photon microscopy, with macroscopic monitoring, such as fNIRS and EEG, in mouse experiments improves possibilities to study correlations between mechanistic cellular data and clinical functional data. Furthermore, when translating new methods to clinical practice, such multiscale concepts enable to validate and optimize macroscopic sensing and imaging techniques [86]. Neurodegenerative disorders such as Alzheimer's disease (AD) are characterized by the accumulation of proteins in the brain before cognitive decline emerges.