# Brain Extraction Methods in Neonatal Brain MRI and Their Effects on Intracranial Volumes
## 4 Discussion  
This study assessed different BE methods for MRI scans of preterm neonates and their effects on ICVs, showing that automated methods have a similar level of accuracy to that of manual skull stripping in T2w MRI. The study's prerequisites were met regarding the ground truth that was created for BE, because both the intra- and inter-rater showed a high level of agreement (with average DC and ICC values above 0.980), suggesting that the full manual segmentation performed was a reliable method for establishing reference brain masks (in agreement with the findings of other studies [29; 31]). Additionally, the dataset was tested as a whole, since the ICV estimation did not show significant differences in terms of gender and gestational age. Based on the segmentation metrics results, we can interpret the different BE methods (Manual, BET2, SWS, HD-BET, and SynthStrip). According to the voxel-overlap-based metrics, HD-BET followed by SWS obtained the highest results for median DC (0.968 (IQR: 0.965-0.971) and 0.966 (IQR: 0.963-0.969)) and JC (0.938 and 0.934) values, respectively. A similar deduction can be made from the DC assessment for each brain mask subset, considering that the segmentation performance varies between them, due to anatomical differences across slices. The lower segmentation accuracy in the bottom slices might be related to the presence of different brain tissues (the cerebrum, cerebellum, and brain stem), vascular structures, air-filled cavities, and the intricate internal structure of the skull bones. The top slices cover a larger area of the brain, where it merges with the surrounding blood vessels, exterior skull bones, and scalp, challenging the segmentation of the brain from non-brain adjacent structures. HD-BET outperforms the other tested BE methods with median improvements of +0.031 (BET2), +0.002 (SWS), and +0.011 (SynthStrip) points for DC; \(-\)0.786 (BET2), \(-\)0.055 (SWS), and \(-\)0.124 (SynthStrip) mm for MSD; and \(-\)0.44 mm for HD95. Similar results were reported with HD-BET by [PERSON] et al. [19] with different adult MRI datasets and sequences, yielding a median DC of 0.976 (IQR, 0.970-0.980) on T1w, 0.969 (IQR, 0.961-0.974) on cT1w, 0.964 (IQR, 0.952-0.970) on FLAIR, and 0.961 (IQR, 0.952-0.967) on T2w sequences. Since SWS was not validated as a BE tool by [PERSON] et al. [42], there are not studies comparing these results, despite their similarity to results from manual segmentation. However, the same authors proposed a BE method for T1w MRI also based on the watershed transform and validated it in human and macaque brains, showing a mean \(\pm\) standard deviation DC in a pediatric cohort of 0.962 \(\pm\) 0.005 [74], which is very similar to the results obtained in our study. When demonstrating the efficacy of SynthStrip, [PERSON] et al. [26] included a small subset of 10 infants born full-term with T1w images acquired between 0 and 18 months, presenting similarities to our results, with a mean DC of 0.961 \(\pm\) 0.014. Regarding surface-distance-based metrics, HD-BET performed well with a median HD95 of 3.2 mm (IQR: 2.5-3.6 mm), followed by SWS and SynthStrip, which also achieved good results (3.6 mm; IQR: 3.1-3.6 mm). Similar results were reported with HD-BET by [PERSON] et al. [19], yielding a median HD95 of 2.7 mm (IQR: 2.2-3.3 mm) on T1w, 3.2 mm (IQR: 2.8-4.1 mm) on cT1w, 4.2 mm (IQR: 3.4-5.0 mm) on FLAIR, and 4.4 mm (IQR: 3.9-5.0 mm) on T2w sequences. BET2's overestimation of the brain boundary has also been previously reported by [PERSON] [8]. Regarding SynthStrip, our HD95 and MSD results are better than those reported with an infant subset by [PERSON] et al. [26] (38.7 \(\pm\) 22.2 mm and 1.0 \(\pm\) 0.3 mm, respectively) and might be related to the range of ages (0 to 18 months) included. In another study that evaluated twelve BE methods in a neonatal brain MRI dataset (preterms scanned at TEA), [PERSON] et. al.