# Assessment of fNIRS Signal Processing Pipelines: Towards Clinical Applications
###### Abstract
This method is characterized by a good spatial resolution (i.e., order of 10 mm) in functional mapping without any depth resolution limits due to the ability to map the whole cortex as well as subcortical and spinal gray matter layers. However, particularly in clinical setups, fMRI presents applicative short comes of MRI scanner complexity and costs, difficulties with non-cooperating subjects, claustrophobia, and high sensitivity to motion artifacts. In addition, the high magnetic field environment causes problematic multi-modal integration with EEG. Conversely, fNIRS presents clinical application potentials which may overcome some of the fMRI limitations. With respect to poorly cooperating subjects, fNIRS cannot be performed, which represents a real opportunity to overcome the motion artifact sensitivity and practical or environmental eligibility, such as the presence of mental implants or suffering from claustrophobia [9; 10]. This technology measures attenuation changes of at least two NIR-wavelengths around the isosbestic point at 805 nm, where \(HbO_{2}\) and \(HbR\) absorbances are equal. In this way, depending on the employed fNIRS technology, either absolute or relative concentration changes can be measured and employed to estimate HRF associated with functional activation. The main advantage of using fNIRS in clinical applications compared to fMRI is its higher tolerability. Indeed, functional measurements are acquired in an open environment and by only employing an EEG cap coupled to NIR-optodes, namely, either sources or detectors. This approach allows us to map brain activity according to measurement channels given by neighboring source and detector pairs, hence having a spatial resolution of 3-4 cm. Although movement related artifacts are still an issue, they are reduced to the sole coupling between a subject's scalp and fNIRS-cap, thus avoiding the rigid head binding imposed by a fMRI setup. As a result, fNIRS functional and resting-state acquisitions can be also performed in impaired subjects who cannot prevent head movements. Patients' watching and care is also not restricted as in an MRI tunnel, and claustrophobic distress is avoided. Conversely, the main fNIRS limitation is related to its surface approach opposed to the volumetric sensitivity of fMRI. Hence, only the sub-cranial cortex is sensed by NIR-light,leaving out activations in the mesial cortex, in deep scissures, and in all the deep gray matter nuclei. Interestingly, the cortex areas sensed by fNIRS and EEG are almost the same, and the two systems are often integrated with negligible interference. This potential, though beyond the scope of this study, further increases the interest in clinical fNIRS applications [11]. Despite the above technical and portability advantages, fNIRS translation to clinics is still hindered by its limited spatial resolution and SNR due to motion artifacts (MAs) and intrinsic physiological interference over the acquired signal. Moreover, with reference to the signal preprocessing and analysis, a standard procedure is still missing due to a wide heterogeneity of available instrumentation and research objectives, which translates into a poor impact on interpretation and reproducibility of results [12]. Consequently, fNIRS is still not approved for stand-alone diagnostic and therapeutic procedures. Therefore, careful preprocessing of the signal is required prior to HRF estimation. As mentioned before, this process is still opened to active biomedical research and is far from the established standards required by clinics. As will be discussed in Section 2.2, the small contribution of \(HbO_{2}\) and \(HbR\) absorbance in the brain vessels, compared to all the other tissues (such as the scalp, skull, liquor, and meninges) makes fNIRS highly sensitive to motion-related changes and coupling of optodes. Hence, a major problem in fNIRS signal processing is associated with the detection and reduction of related MAs.