Convolutional neural networks (CNNs) have had incredible success solving image segmentation problems. We explore whether CNNs could have a similar level of success on difficult image registration problems. To this end, we developed a modified U-net to remove respiratory motion, but preserve contrast changes in abdominal free breathing dynamic contrast enhanced (DCE)-MRI. We then compared this network to a state of the art iterative registration algorithm. We demonstrate that our modified U-net outperforms iterative methods both in terms of registration quality and speed (600 registrations in <1 sec vs. Elastix in 2 hours)
DCE-MR dataset acquisition
In 2 healthy volunteers, free breathing DCE-MR abdominal data sets were acquired using a motion robust sequence consisting of sliding sagittal 2D slices. This sequence acquires images with short acquisition times, but the image time series is misaligned due to respiratory motion. Imaging parameters: (0.1 mmol/kg gadobenate dimeglumine, Image matrix: 192x144x176, 20 time points, 3T GE scanner, 32 channel, golden ratio sampling, cartesian, resolution=1.5x1.9x4mm3 ,TE/TR=1.3/3.8ms, flip imaging=15°, flipsat=8°, with 2 (ky) x 2 (slice) parallel imaging acceleration, 4s temporal resolution, 8s temporal footprint).
Synthetic Training Set Generation
Collected DCE-MR dataset consist of 176 contrast sequence with each sequence consisting of 20 time points. Contrast sequences are completely misaligned, and have no ground truth deformation fields associated with them. Given these constraints, we developed a synthetic training set by applying known deformations to the first time point from the 30 centrally located contrast sequences. Known deformations consisted of a randomized affine transform followed by a randomized gaussian kernel based non-linear transform to build pairs of reference and moving images with an associated ground truth deformation field. Uncorrelated, randomized magnitude, linear brightness changes were then applied five times to the moving and reference images to train the network to ignore time-dependent contrast changes. Validation data was synthesized in an identical way using 10 central slices (fig 1).
Neural Network Architecture and Training
We used a modified U-net architecture. Notable modifications were the use of cascaded convolution kernels (7X7-->5X5-->3X3), and the use of PReLU activation functions.
Neural Network Testing
Test data were composed of the full time series of contrast sequences from the 2 patients used to build the synthetic data set. Overfitting was not a concern as the synthetic data set for each volunteer was built off the first time point in each contrast sequence, and it was impossible to replicate the nonlinearly varying spatial and temporal contrast changes observed in the test data with our synthetic data set. The quality of these image registrations were compared against Elastix, a state of the art registration tool.
Data Analysis
Standard methods for assessing registration quality rely on either image intensity differences or DICE coefficient. Time dependent contrast data complicates the first approach, while the DICE coefficient does not assess parenchymal distortion. Registration quality was therefore assessed qualitatively (10 blinded raters, 3 example registrations) and quantitatively through principal component analysis (PCA).
CNN based image registration visually appears to exceed state of the art iterative registration techniques in terms of registration quality (figures 3 and 4). Compared to Elastix, CNN-based image registration consistently preserves internal features. Additionally, preliminary data show that trained readers, blind to registration method, rank CNN registration outputs higher than elastix or unregistered outputs (87% vs. 13% vs 0% favor respectively) in terms of motion removal and lack of parenchymal distortion (figure 5). PCA analysis demonstrates the first eigenvalue accounted for .963+/-.010 of image covariance for CNN output compared to .947+/-.004 for Elastix and .901+/-.012 for the unregistered data
1.Brodsky, Ethan K., et al. "High‐spatial and high‐temporal resolution dynamic contrast‐enhanced perfusion imaging of the liver with time‐resolved three‐dimensional radial MRI." Magnetic resonance in medicine 71.3 (2014): 934-941.
2.Goodfellow, Ian, et al. Deep learning. Vol. 1. Cambridge: MIT press, 2016.
3. Lausch, Anthony, Mehran Ebrahimi, and Anne Martel. "Image registration for abdominal dynamic contrast-enhanced magnetic resonance images." Biomedical Imaging: From Nano to Macro, 2011 IEEE International Symposium on. IEEE, 20114 .
4.Melbourne, A., et al. "Registration of dynamic contrast-enhanced MRI using a progressive principal component registration (PPCR)." Physics in Medicine & Biology 52.17 (2007): 5147.
5. Ronneberger, Olaf, Philipp Fischer, and Thomas Brox. "U-net: Convolutional networks for biomedical image segmentation." International Conference on Medical image computing and computer-assisted intervention. Springer, Cham, 2015.