# Brain Extraction Methods in Neonatal Brain MRI and Their Effects on Intracranial Volumes
## 3 Results
### Comparison of Manual vs. Automated Brain Extraction Methods
#### 3.3.2 Intracranial Volume Estimation
If the majority of values consistently fall above/below zero, it suggests that one method consistently produces higher/lower measurements than the other. This pattern indicates that the disagreement is not random but rather systematic [71; 72; 73]. Furthermore, by analysing the data, we can also identify whether distinct patterns of disagreement exist among subjects with lower or higher ICVs [71; 72; 73]. The ICV mean differences (95% CI) or bias were as follows: 32.4 (12.8 to 52.0) mL for BET2 -- Manual; \(-6.5\) (\(-23.0\) to 10.0) mL for SWS -- Manual; 12.1 (\(-1.2\) to 25.4) mL for HD-BET-- Manual; and 1.8 (\(-25.4\) to 28.9) mL for SynthStrip-- Manual. These results  
Figure 3: Bland–Altman analysis of the mean of (\(x\)-axis) and the difference between (\(y\)-axis) the automated BE methods and manually segmented ICVs. (**a**) BET2—Manual, (**b**) SWS—Manual, (**c**) HD-BET—Manual, and (**d**) SynthStrip—Manual. The full lines (blue, red, green, and purple) indicate the mean difference, the dotted lines (blue, red, green, and purple) indicate upper and lower limits of agreement (\(\pm 1.96\) standard deviations), the thinner dotted lines in grey represent zero (no difference), and the linear regression line is shown in black. \begin{table}
\begin{tabular}{c c c c c c c} \hline \hline  & & & & & **95\% Confidence Interval for Mean** \\ \hline
**Brain Extraction Method** & **Mean** & **Standard Deviation** & **Minimum** & **Maximum** & **Lower Bound** & **Upper Bound** \\ \hline Manual & 463.0 & 50.1 & 388.7 & 575.6 & 440.8 & 485.3 \\ \hline BET2 & 495.4 & 47.0 & 423.2 & 610.8 & 474.6 & 516.3 \\ \hline SWS & 456.5 & 52.2 & 377.1 & 571.2 & 433.4 & 479.6 \\ \hline HD-BET & 475.2 & 46.0 & 403.9 & 581.2 & 454.8 & 495.6 \\ \hline SynthStrip & 464.8 & 40.2 & 395.7 & 554.4 & 447.0 & 482.6 \\ \hline \hline \end{tabular}
\end{table} 
Table 8: Descriptive statistics of intracranial volumes (mL) obtained with different brain extraction methods. can be visually perceived in some slices of Figure 2, with masks exceeding the brain area (e.g., BET2 and HD-BET) or the opposite (e.g., SWS and SynthStrip), as identified in the Bland-Altman analysis. Most differences in the ICVs from the Bland-Altman analysis (Figure 3) were within the limits of agreement, with a range both above and below the mean difference; however, the differences were not always evenly distributed as ideally expected, so a linear regression analysis [71; 73] was performed to assess the presence of proportional bias. The regression analysis was the statistical procedure used for examining the predictive relationship among the difference in ICVs between each automated and manual BE method (dependent--criterion--variable) and the mean ICV estimated by those methods (independent--predictor--variable). The results for the ICV mean differences of HD-BET--Manual (R = 0.608; \(p\) = 0.003) and SynthStrip--Manual (R = 0.719; \(p\) < 0.001) showed heteroscedasticity. However, the homoscedasticity of BET2--Manual (R = 0.317; \(p\) = 0.151) and SWS--Manual (R = 0.240; \(p\) = 0.283) did not indicate the same tendency of error with the increase in ICV. The correlational trend line of HD-BET demonstrates that for certain higher ICVs, the magnitude of positive differences tends to slightly decrease, approaching that of manual segmentation (in which the differences are closer to zero). Conversely, the regression line of SynthStrip reflects a tendency for the negative differences to increase for higher ICVs, showing a larger variability in the ICV estimations. Converting the difference between methods to percentages results in a mean bias of 6.76% for BET2; \(-\)1.42% for SWS; 2.59% for HD-BET; and 0.38% for SynthStrip. The RMSE and CVRMSE values for each automated method relative to the reference were as follows: 33.8 mL (7.31%) for BET2; 10.5 mL (2.27%) for SWS; 13.8 mL (2.99%) for HD-BET; and 13.6 mL (2.95%) for SynthStrip.