# Optics Based Label-Free Techniques and Applications in Brain Monitoring
## 1 Introduction  
Conducting brain studies by electroencephalography (EEG), magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) is a common practice in modern neuroimaging. Using EEG and MEG, signals generated by the neuronal activities can be measured with a time resolution of less than one millisecond. MEG has a spatial accuracy of a few millimeters under favorable conditions, whereas EEG has a spatial resolution on the centimeter scale [1, 2]. Since the discovery of the blood oxygen level dependent (BOLD) contrast by [PERSON] in 1990 [3], BOLD imaging using fMRI leads neuroimaging. Moreover, new fMRI scanning techniques have enabled improvements also in fMRI time resolution, e.g., magnetic resonance encephalopathy (MREG), offering ten times higher time resolution than before [4, 5]. However, one major weakness of fMRI and MEG is the fact that the subject has to stay unmoving inside the scanner. Consequently, there is still a strong need for methods that do not suffer from this restriction. For this, optical techniques, in addition to EEG, offer high potential due to their portability and adaptability [6]. Complementing each other, these two methods have a growing interest especially to be utilized in wearable brain monitoring applications [7].  
Within the last two decades, optics based brain monitoring has grown intensively. In general, the sensing principle is based on light absorption and scattering, which are responsive to functional changes in tissue [8]. Light can also reveal information on the morphological structure of the brain, however, still very limitedly in human brain imaging, because of strong light scattering and absorption caused by human skull and scalp [9]. In functional monitoring of the human cerebral cortex, optical techniques have many advantages over other neuroimaging methods. Generally,they are safe, more cost-effective and commonly do not require a special environment, thus in this regard can be easily translated to clinical applications [10]. Importantly, it is also possible to exploit different optical modalities in parallel to gather various neuronal functions and blood flow-related parameters simultaneously.  
In particular, functional near-infrared spectroscopy (fNIRS) is already becoming a common method in human neuroimaging. In contrast to fMRI BOLD, it provides a possibility to monitor cortical neural activity related dynamics of both oxy-hemoglobin (HbO) and deoxy-hemoglobin (HbR), also in wearable applications [11]. Closely related to fNIRS, diffuse correlations spectroscopy (DCS) provides a direct measure of blood flow dynamics, based on detection of scattering of photons due to red blood cells (RBCs) in blood flow [12]. However, both fNIRS and DCS still have a limited spatial resolution. Photoacoustic imaging (PAI) is a relatively new method for brain monitoring, which has both advantages of the high contrast of optical imaging and high spatial resolution of ultrasound [13]. PAI has achieved success in animal research based on an increasing amount of publications but is still rarely used in human brain imaging because of the thick skull effect. Optical coherence tomography (OCT) [14] can provide accurate spatial information as well as good temporal resolution, but because of limited penetration depth it is in practice not used in human brain studies. Even so, PAI and OCT play an essential role in translational medical research when imaging and quantifying brain morphology and brain function on a microscopic scale. These are commonly performed using rodent models, e.g., to study diseased brain.  
In this paper, we review the current stage of fNIRS, DCS, PAI and OCT techniques in brain monitoring, see Table 1. We highlight the specific advantages of these techniques and review their currently most potential clinical applications for the 2020s. In addition, wearable use of optical techniques in brain monitoring are discussed.