# Assessment of fNIRS Signal Processing Pipelines: Towards Clinical Applications
## 4 Discussion  
In this study, we proposed a comparison of the most used artifact reduction strategies in light of the common absence of separate artifact sensing systems using a commercial  
Figure 11: Second-level activation vs. resting condition statistical maps related to the left-hand motor grasp of \(\Delta[HbR]\). Colorbars indicate significant \(t\)-values corrected for multiple comparisons (\(p_{FDR}<0.05\)). Positive t-values indicate locations where the mean of \(\Delta[HbR]\) activation was significantly higher than that in the resting condition, and conversely for negative values. (**a**) SC-MARA-spline, (**b**) MC-MARA-spline, (**c**) SC-MARA-tPCA, (**d**) MC-MARA-tPCA, (**e**) HybridMARA-spline SG, (**f**) HybridMARA-tPCA SG, (**g**) TDDR, and (**h**) Wavelet method. Figure 10: Second-level activation vs. resting condition statistical maps related to the left-hand motor grasp of \(\Delta[HbO_{2}]\). Colorbars indicate significant t-values corrected for multiple comparisons (\(p_{FDR}<0.05\)). Positive t-values indicate locations where the mean of \(\Delta[HbO_{2}]\) activation was significantly higher than that in the resting condition, and conversely for negative values. (**a**) SC-MARA-spline, (**b**) MC-MARA-spline, (**c**) SC-MARA-tPCA, (**d**) MC-MARA-tPCA, (**e**) HybridMARA-spline SG, (**f**) HybridMARA-tPCA SG, (**g**) TDDR, and (**h**) Wavelet method. CW-fNIRS instrumentation. In fact, Frequency or Time Domain fNIRS are still seldom used in clinical procedures because of their higher costs and complexity but indicate a promising method for developing more robust and reliable optical brain imaging methods [14; 15; 51]. Technological developments in optical imaging are moving towards the promotion of High Density Diffuse Optical Tomography (HD-DOT) techniques, which can cope with spatial resolution problems of traditional fNIRS thanks to overlapping measurement channels. HD-DOT allows us to have comparable localization of functional activation to fMRI, and it has already been validated in retinopy, motor, and language paradigms [52]. However, its clinical applications are still confined to specific fields, such as breast, muscle and fluorescence imaging [53], epilepsy, and neonatal/infant brain injuries [52], with very few exceptions in clinical neurology such as Parkinson's Disease [54]. Although CW-fNIRS is still not suitable as a stand-alone diagnostic device, its increasing use in different clinical and experimental domains requires that the technical issues, such as MAs and PCFs, must come after patients' tolerability and the opportunity to perform multiple acquisitions in a clinical rehabilitation context. Moreover, another CW-fNIRS advantage is the possibility of having a complete brain cortex functional mapping, which is crucial when the study's objective is to monitor the brain plasticity mechanism due to rehabilitation programs [55; 56; 57]. Furthermore, for these purposes, the focus is on differential changes in \(\Delta[Hb\mathcal{O}_{2}]\) and \(\Delta[HbR]\) instead of quantification of these chromophores. Nowadays, MA and PCF removal is provided by integrating auxiliary measurements such as short separation channels that have the exceptional advantage of regressing out scalp hemodynamics in first- and second-level analyses [16; 17; 58]. This approach can be integrated with other physiological signals such as blood pressure, movement/accelerometer, respiration, and photo plethysmography measurements [18]. However, these auxiliary measurements are not always available with commercial systems or can be integrated within the experimental clinical set-up. Therefore, a systematic evaluation of employed processing pipelines and related algorithms' effect on optical signals must be carefully considered. Indeed, as shown from our results, the impact on the statistical significance and especially the localization of cortical activation can be greatly affected. This is a severe issue for translating this technique in clinical neuroimaging.