# Brain Extraction Methods in Neonatal Brain MRI and Their Effects on Intracranial Volumes
## 4 Discussion
[29] showed that the developed ALFA method [29] had a better performance than our tested methods, with a mean DC of 0.989 and an HD of 3.4 mm (for the T2w images). We intended to include this method in our study; however, it was no longer accessible, and therefore could not be tested with our dataset. Ten of the other tested methods [29] performed worse than HD-BET and SWS, namely, 3 DSS (DC = 0.922), BET (DC = 0.792), BSE (DC = 0.714), LABEL (DC = 0.935), ROBEX (DC = 0.910), MV (DC = 0.951), STAPLE (DC = 0.948), SBA (DC = 0.960), BW (DC = 0.774), and BEAST (DC = 0.939). We also obtained different results when optimizing BET parameters, as [PERSON] et. al. [29] showed a DC of 0.792, whereas in our study, it was 0.937, which is a massive improvement that suggests our parameters were better suited. The BE accuracy within a neonatal group (0.8 \(\pm\) 0.3 months old) using the LABEL [31] method developed by [PERSON] et. al. showed an average JC of 0.948 and their method performed better when compared with other BE methods (BET (JC = 0.920), BSE (JC = 0.884), ROBEX (JC = 0.886), GCUT (JC = 0.916), Majority voting (JC = 0.911), and STAPLE (JC = 0.934)). The LABEL results are slightly higher than those of HD-BET and SWS, but this could be due to the age of the dataset, since this method has a tendency for the JC to increase with the age of the sample [31]. Finally, the HSS method developed by [PERSON] et. al. [33] showed worse similarity metrics (DC = 0.954 and JC = 0.913) than HD-BET, SWS, and SynthStrip, as well as the other BE methods (FSL, BrainSuite, MRIcroN, and SPM8) they tested in their dataset. Regarding ICV estimation, our Bland-Altman analysis indicated good agreement between some automated and manual BE methods, with the identification of patterns of disagreement that can be used as correction factors. BET2 consistently estimates higher ICVs than manual segmentation; this pattern is less prominent with HD-BET and with a tendency to approach to minor differences when the ICVs increase. On the other hand, SWS mostly estimates lower ICVs than manual segmentation. SynthStrip shows the largest variability, with a tendency to overestimate at lower ICVs and underestimate at higher ICVs. The ICV difference discrepancies between our study and the infant's dataset by [PERSON] et al. [26] (7.4 \(\pm\) 3.5%) might be related to the wide variation in brain size between 0 and 18 months, the range of ages included in the test subset of SynthStrip. The error between automated and manual ICVs is small (<3%) for all the methods, except for BET2, indicating good agreement between the segmentation methods. However, the error obtained for BET2 was similar to that previously reported by [PERSON] [8] when developing this widely used BE method; nonetheless, special awareness should be given when using this BE method in neonates due to the impact of a 7% measurement error when studying such small brains. SWS and HD-BET provide a level of agreement that is likely to be acceptable for experimental and clinical applications due to the smaller ICV mean differences (\(-\)6.5 mL (\(-\)1.42%) and 12.1 mL (2.59%)), median VS (2.61% and \(-\)2.03%), RMSE (10.5 mL and 13.8 mL), and CVRMSE (2.27% and 2.99%) values. This means that if the ICVs estimated from the automated BE methods are corrected by a factor of +1.42% (SWS) or \(-\)2.59% (HD-BET), it should be close to the real ICV with a small estimation error (\(\pm\)1.13% for SWS and \(\pm\)1.49% for HD-BET). The estimates might be considered suitable considering the neonatal volume variation per week. According to [PERSON] et al. (2015), 6.1% per week is a typical ICV developmental change during the neonatal period in a term-born dataset (37-45 weeks). Moreover, between 32 and 42 weeks, [PERSON] et al. (2016) reported a brain growth of 11.2% per week. Furthermore, [PERSON] et al. (2017) and [PERSON] et al. (2018) depicted an average ICV growth rate of 27.2 mL and 24.0 mL per week in cohorts of premature infants that were assessed at birth and later at TEA, respectively.