Weiwei Zhao1, Fangfang Zhou1, Yida Wang1, Yang Song1, Gaiying Li1, Xu Yan2, Yi Wang3, Guang Yang1, and Jianqi Li1
1Shanghai Key Laboratory of Magnetic Resonance, School of Physics and Electronic Science, East China Normal University, Shanghai, China, 2MR Collaboration NE Asia, Siemens Healthcare, Shanghai, China, Shanghai, China, 3Department of Radiology, Weill Medical College of Cornell University, New York, NY, United States
Synopsis
Accurate
and automated segmentation of substantia nigra (SN), the subthalamic nucleus
(STN), and the red nucleus (RN) in quantitative susceptibility mapping (QSM)
images has great significance in many neuroimaging studies. In the present
study, we present a novel segmentation method by using convolution neural
networks (CNN) to produce automated segmentations of the SN, STN, and RN. The
model was validated on manual segmentations from 21 healthy subjects. Average
Dice scores were 0.82±0.02 for the SN, 0.70±0.07
for the STN and 0.85±0.04 for the RN.
Background and Purpose
The substantia nigra (SN),
subthalamic nucleus (STN), and red nucleus (RN) are deep gray nuclei of great importance
in studying Parkinson’s disease and movement disorder1-3. Segmentation of these structures in
magnetic resonance imaging (MRI) is required and typically performed by tedious
manual segmentation in quantitative assessments. Automatic segmentation of these
midbrain structures is much desired but is challenging due to their fine structures
and positions. The high iron contents of these structures result in high
contrasts on quantitative susceptibility mapping (QSM) images4, 5, which makes it possible to automatedly
segment midbrain structures using a QSM+T1 multi-atlas approach6, 7. However, the high-resolution
T1-weighted images are required, and the robust performance is desired. Recently,
segmentation algorithms that employ deep convolutional neural
networks (CNN) have emerged as a promising solution in segmentation
studies8-10. Therefore, we propose a CNN-based
method for automated segmentation of SN, STN and RN in high resolution susceptibility
maps.Materials and Methods
This
study was approved by the local ethical committee and each participant signed
an informed consent form. A total of 38 healthy subjects (28.4 ± 5.6 years old,
16 males and 22 females) underwent MRI on a clinical 3T system (MAGNETOM Prisma
Fit; Siemens Healthcare, Erlangen, Germany) with a 20- channel head matrix
coil. QSM was generated from a 3D spoiled multi-echo gradient-echo (GRE)
sequence with the following imaging parameters: readout gradient mode =
bipolar, TR = 31ms, TE1 = 4.07ms, ΔTE = 4.35ms, echoes number = 6, flip angle =
12˚, FOV = 240*288 mm2, in-plane resolution= 0.83*0.83 mm2,
slice thickness = 0.8 mm, number of slices = 192. To observe the midbrain structures
with minimal partial volume effects, an oblique-axial slab paralleling to the
AC-PA line was chosen. QSM maps were reconstructed using the Morphology Enabled
Dipole Inversion with automatic uniform cerebrospinal fluid zero reference
(MEDI+0) algorithm11. The bilateral head of the SN, STN and RN were drawn manually on all QSM
datasets by an experienced investigator. These steps were executed using ITK-SNAP
(http://www.itk-snap.org).
The datasets
were split into three cohorts: 15 cases for training cohort, 2 cases for validation
cohort, and 21 cases for testing cohort. Limited by the number of
the cases, a slice-based CNN model was built for segmentation. The midbrain
structures were located according to the brain atlas. Blocks of 64x64 size were
extracted in the coronal slices. All
slices including three nuclei and their adjacent slices were selected as the
data set. To utilize the shape information, 3 contiguous slices were combined as
the input of one sample, and the segmentation of the middle slice was labeled as
the output (Figure 1)12. All slices were normalized by
subtracting the mean value and dividing the standard deviation. 384 slices of
training cohort and 111 slices of validation cohort were used to train the CNN
model. The CNN model based on the U-Net was designed as shown in Figure 213. 3 slices were stacked in the channel
direction and the segmentation result was encoded as one-hot format
(Background, RN, SN, STN). To increase the robustness of the model, the augmentation
involved randomly shifting, zooming, rotating, and shearing for each sample.
Cross-entropy was selected as the loss function. Adam with an initial step 0.0001
was used as the optimizer14. All above were implemented using TensorFlow
1.10. We trained the model with a batch size of 20 on one NVIDIA X Titan graphics
card for an hour. To evaluate the trained model, we segmented each slice of the
testing cohort and then combined the segmentation into the whole brain, and we estimated
the Dice score for each case.Results
Fig. 3 shows a comparison of the
manual and automated segmentations for one example case, which had the Dice
scores of 0.82 for SN, 0.73 for STN and 0.87 for RN compared to the manual
segmentation. The segmentation labels were overlaid on the QSM maps. The
proposed CNN method accurately and consistently segmented the SN, STN and RN on
high resolution susceptibility maps: Average Dice scores comparing the manual
and automated segmentations were 0.82±0.02 for SN, 0.70±0.07
for STN and 0.85±0.04 for RN.Discussion and conclusions
Our
preliminary data demonstrate that the CNN model has the capability to automatically
segment the RN, SN and STN. This automated segmentation will eliminate the tedious
manual labor in the quantitative data analysis of large Parkinson disease
studies.
The accuracy of the segmentation could be improved in the following aspects:
1) The performance of the CNN model may be improved using more training cases, and/or
more cases synthesized by generative adversarial networks (GAN)15; 2) 3D
model may be used to generate more sensitive shape and spatial information of
the midbrain structures; 3) The prior experience may be combined into the model
training, such as transfer learning and deformable statistics16, 17.Acknowledgements
References
1. Lewis MM, Du G, Kidacki
M, et al. Higher iron in the red nucleus marks Parkinson's dyskinesia.
Neurobiol Aging 2013;34:1497-1503.
2. Castrioto A, Lhommee E,
Moro E, Krack P. Mood and behavioural effects of subthalamic stimulation in
Parkinson's disease. Lancet Neurol 2014;13:287-305.
3. Mettler FA. Substantia
Nigra and Parkinsonism. Arch Neurol 1964;11:529-542.
4. Wang Y,
Spincemaille P, Liu Z, et al. Clinical quantitative susceptibility mapping
(QSM): Biometal imaging and its emerging roles in patient care. J Magn Reson
Imaging 2017;46:951-971.
5. Liu T,
Eskreis-Winkler S, Schweitzer AD, et al. Improved subthalamic nucleus depiction
with quantitative susceptibility mapping. Radiology 2013;269:216-223.
6. Garzon B,
Sitnikov R, Backman L, Kalpouzos G. Automated segmentation of midbrain structures
with high iron content. Neuroimage 2018;170:199-209.
7. Li X, Chen L,
Kutten K, et al. Multi-atlas tool for automated segmentation of brain gray
matter nuclei and quantification of their magnetic susceptibility. Neuroimage
2019;191:337-349.
8. Li X, Chen H, Qi
X, Dou Q, Fu CW, Heng PA. H-DenseUNet: Hybrid Densely Connected UNet for Liver
and Tumor Segmentation From CT Volumes. IEEE Trans Med Imaging
2018;37:2663-2674.
9. Liu F, Zhou Z,
Jang H, Samsonov A, Zhao G, Kijowski R. Deep convolutional neural network and
3D deformable approach for tissue segmentation in musculoskeletal magnetic
resonance imaging. Magn Reson Med 2018;79:2379-2391.
10.Chen H, Zhang Y, Kalra MK, et al. Low-Dose CT With a
Residual Encoder-Decoder Convolutional Neural Network. IEEE Trans Med Imaging
2017;36:2524-2535.
11.Liu Z, Spincemaille P, Yao Y, Zhang Y, Wang Y.
MEDI+0: Morphology enabled dipole inversion with automatic uniform
cerebrospinal fluid zero reference for quantitative susceptibility mapping.
Magnetic Resonance in Medicine 2018;79:2795-2803.
12.De Fauw J, Ledsam JR, Romera-Paredes B, et al.
Clinically applicable deep learning for diagnosis and referral in retinal
disease. Nat Med 2018;24:1342-1350.
13.Ronneberger O, Fischer P, Brox T. U-Net:
Convolutional Networks for Biomedical Image Segmentation.
14.Kingma DP, Ba J. Adam: A Method for Stochastic
Optimization. arXiv:14126980 2014.
15.Goodfellow IJ, Pouget-Abadie J, Mirza M, et al.
Generative Adversarial Networks. arXiv:14062661 2014.
16.Dong S, Luo G, Wang K, Cao S, Li Q, Zhang H. A
Combined Fully Convolutional Networks and Deformable Model for Automatic Left
Ventricle Segmentation Based on 3D Echocardiography. Biomed Res Int
2018;2018:5682365.
17.Tan C , Sun F , Kong T , et
al. A Survey on Deep Transfer Learning. arXiv:18080741 2018.