Li Zhao1, Xue Feng2, Josepheen Asis-Cruz 1, Yao Wu1, Kushal Kapse1, Axel Ludwig1, Dan Wu3, Kun Qing2, Carig H. Meyer2, and Catherine Limperopoulos1
1Childrens National Hospital, Washington, DC, United States, 2University of Virginia, Charlottesville, VA, United States, 3Zhejiang University, Hanzhou, China
Synopsis
An essential step to accurately quantify fetal brain development is to
reliably segment brain regions and perform volumetric measurements. However,
this task mainly relies on labor intensive manually contouring. In this work, a
3D U-Net method was optimized and evaluated for fetal brain segmentation. 3D
U-Net and 4D atlas-based segmentation methods were compared on 46 fetal brain
MRI scans with gestational age 26.4 to 39.1 weeks. The proposed method resulted
in (1) higher consistency with the manual segmentation, (2) shorter processing
time, and (3) more consistent results across gestational ages, compared to a 4D
atlas-based method.
INTRODUCTION
Accurate assessment of fetal brain anatomy in the second and third
trimester of gestation is important for identifying early impairments in fetal
brain growth (1). However, because of the
active myelination process and water content changes (2), fetal brain images
contain high signal variation within each tissue and show low image contrast (3). In addition, maternal
respiration and irregular fetal movements often result in serious motion
artifacts which corrupt MR images. Although temporal and spatial atlases have
been developed for preterm infants and fetal brains (4), manual segmentation and
correction are often still required.
In recent years, deep convolutional neural networks have shown promising
performance in the automatic processing of fetal MR images. Studies have focused on locating the
interesting regions (e.g., fetal abdomen(5), the whole fetal envelope (6), and the body(7)) and on whole fetal brain
extraction (8–10). Previously, we developed
a 3D U-Net model for fetal brain MRI segmentation. Here, we optimized the
method and compared its performance to a 4D atlas-based segmentation method on 46
healthy fetuses.METHODS
46 MR scans were acquired on healthy fetuses from low-risk pregnancies.
The mean gestational age (GA) at MRI was 33.3±4.0 weeks with a range of 26.4 - 39.1 weeks.
T2-weighted images were acquired prospectively on a 1.5T GE scanner. High-resolution
2D images were acquired in coronal, sagittal and axial planes using single-shot
fast-spin-echo sequences. The reconstruction matrix size was 256x256. TE was
157-163ms and the TR was about 1100ms. The three-plane images were
reconstructed to a high-resolution 3D volume using the slice-to-volume registration
method (11).
Ground truth was provided by the manually corrected segmentation. Fetal
brain regions were segmented automatically by registering to a 4D atlas (4) using ANTS. Six brain
regions were defined, including the cortical grey matter, the white matter, the
cerebrospinal fluid the cerebellum, the deep gray matter and the brain stem.
Each region was manually corrected by an experienced researcher (5 years’
experience) using ITK-SNAP.
A modified 3D U-Net was optimized. First, to avoid overfitting, early termination
was considered by recording the model performance during 40 epochs of training
and validation. Second, because fetal brains develop rapidly with GA, the fetal
brain was resized to 80x110x90 according to the edge of the brain. Third, to
generate realistic augmentation, the patches of fetal brain were` flipped in
the left-right direction. The optimized U-Net was evaluated using 10-fold
cross-validation on two P100 GPUs.
As a reference method, the images were segmented using Draw-EM (33) with
28-CPU parallel computing.
To provide quantitative evaluation, Dice score, 95% Hausdorff distance,
sensitivity and specificity of each brain region were calculated. Wilcoxon
signed-rank test was used to evaluate the performance statistically.RESULTS
The proposed method provided the best performance with 20 epochs,
left-right flip augmentation and resized image. First, the number of epochs was
chosen by noting that the performance of the training continuously improved,
but the cross-entropy and the dice score of the validation approached a stable
stage after 20 epochs. Second, because the brain was left-right symmetric, the left-right flip generated the best validation performance. three-direction flip
generated unrealistic data, which brought noise into the training process and
in turn reduced the performance, as shown in Table 1. Third, because fetal
brain size varies across GA, the image resize step provided a simple
normalization which could reduce the variance between subjects and improve the
performance.
The proposed method (2.5 minutes) was about 9 times faster than the atlas-based
method (22 minutes) to segment each fetal brain.
Fig. 1 and 2 show the results of the fetal brain at 28+2/7 and 35+2/7 weeks
GA. The arrows on the axial/coronal images highlight the mislabeled deep grey
matter/CSF and cortical grey matter regions in the atlas-based method. In
contrast, the proposed method provided high consistency with the manual
segmentation and resulted in more smooth and continuous segmentation in the
cortical grey matter.
In the cross-validation, the proposed method provides more accurate
segmentation than the atlas-based method, with an average Dice score of 0.901
vs 0.820 across the six brain regions (0.903 vs 0.821 in CSF, 0.84 vs 0.736 in
the cortical grey matter, 0.906 vs 0,849 in the white matter, 0.9 vs 0.776 in
the deep grey matter, 0.942 vs 0.885 in the cerebellum, and 0.913 vs 0.851 in
the brain stem), Fig. 3.
The proposed method showed significant improvements compared to the atlas-based
method in each brain region. The Dice score and 95% Hausdorff distance showed
significant improvement (p<0.001). Improved specificity and
sensitivity scores were found in cortical grey matter and white matter regions
(p<0.05).
The proposed method showed consistent performance across GA. As shown in
Fig. 4, the Dice score of each interested region maintained its superior
performance across GA in the proposed method. In the cortical grey matter, the atlas-based
method resulted in reduced accuracy around 35 weeks GA during which the
secondary sulci develop.
DISCUSSION
In summary, our study demonstrated the
superior performance of the 3D U-Net method for fetal brain segmentation,
compared with an atlas-based segmentation method. Its high accuracy, efficiency,
and consistency will provide useful quantification of in-utero regional fetal
brain growth metrics to aid clinical diagnosis and large cohort studies. Acknowledgements
This work was partly supported by R01HL116585 from the NIH National
Heart, Lung and Blood Institute, NIH R21EB022309 from the National Institute of
Biomedical Imaging and Bioengineering, UL1TR001876 and KL2TR001877 from NIH
National Center for Advancing Translation Sciences.References
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