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- 1. Deep Learning for Clinical Brain MRI Segmentation MDC Deep Learning Club Remo Monti May 2018
- 2. Overview • Introduction to MRI • Introduction to Image Segmentation • Brain Ventricle Segmentation • Our Machine Learning Problem • DCNN Architectures for Image Segmentation • U-Net, V-Net • Dice Coefficient and Dice Loss • Results • Discussion
- 3. A Brief Introduction to MRI • MRI = (nuclear) Magnetic resonance imaging • MRI scanners use strong magnetic fields and radio waves to generate images of the organs in the body. • Certain atomic nuclei are able to absorb and emit radio frequency energy when placed in an external magnetic field. • Hydrogen atoms are most often used to generate a detectable radio-frequency signal, that is received by antennas in close proximity to the anatomy being examined. www.healthcare.siemens.ch https://en.wikipedia.org/wiki/Magnetic_resonance_imaging
- 4. A Brief Introduction to MRI • MRI can be divided into Excitation, Relaxation, Acquisition, Computing and Display Excitation • Protons align their magnetic fields (spin axes) in parallel or anti- parallel to the outer magnetic field • Imbalance between parallel and anti- parallel spins leads to NET magnetization • Alignment can be perturbed by a radio-frequency signal. This process is called Excitation. mri:Physics For anyone who does not have a degree in physics (Evert J Blink)
- 5. A Brief Introduction to MRI • T1 images measure the tissue-specific relaxation times after excitation of the induced magnetic field on the Z-axis • During relaxation the hydrogen atoms emit energy in the form of radio-waves, which are measured by nearby sensors. emission Excitation Relaxation (T1) T1 Relaxation Time (tissue specific!) mri:Physics For anyone who does not have a degree in physics (Evert J Blink)
- 6. • T2 images measure the loss of phase in the XY-plane. The process of getting from a total in-phase situation to a total out-of-phase situation is called T2 relaxation. • After excitation the spins of the hydrogen atoms are in phase. The phase is lost over time (A-E). T2 Relaxation Time (tissue specific!) A Brief Introduction to MRI mri:Physics For anyone who does not have a degree in physics (Evert J Blink)
- 7. T1 vs T2 Images • T1 and T2 relaxation are two independent processes, which happen simultaneously. • T1 happens along the Z-axis • T2 happens in the X-Y plane • Different tissues appear bright/dark in T1/T2 images • T1: water = dark • T2: water = bright T1 T2
- 8. A Brief Introduction to Image Segmentation • In image segmentation we assign a class to every input pixel (or voxel) Figure: Pelt, Sethian (PNAS 2018)
- 9. Brain MRI Segmentation – Ventricles • The ventricular system is a set of four interconnected cavities (ventricles) in the brain, where the cerebrospinal fluid (CSF) is produced. • Hypothesis: Ø Ventricles increase size before / during Multiple Sclerosis episodes Ø“Brain inflammation” measurable by looking at ventricles By Polygon data were generated by Life Science Databases(LSDB). - Polygon data are from BodyParts3D., CC BY-SA 2.5, https://commons.wikimedia.org/w/index.php?curid=26756796
- 10. Brain MRI Segmentation – Ventricles T2 ImagesAxial Sagittal Coronal 512 x 512 512 x 44 512 x 44 Voxel Sizes x : 0.5 mm y : 0.5 mm z : 3.0 mm Jason Millward
- 11. Machine Learning Problem • Learn to predict segmentation (drawn using T2 imgs) from T1 imgs • Nscans > 220 , resolution 512 x 512 x 44 (0.5 x 0.5 x 3 mm) • T1 and T2 images + segmentation (Jason Millward) • “MS-dataset” • Model should produce satisfactory results on different dataset “Day2Day” (Filevich, 2017) • T1 images of healthy subjects measured over many time points • resolution 192 x 256 x 256 ( 1 x 1 x 1 mm)
- 12. Machine Learning Problem Learn from this… … predict on this
- 13. DCNN Architectures for Image Segmentation • “Standard” Deep Convolutional Neural Net (DCNN) architectures that rely on pooling in order to aggregate spatial context and deconvolution/upscaling to restore the original image dimensions are not the best choice for image segmentation • The reason for this is the loss of spatial information associated with pooling: 256 x 256 x 1 256 x 256 x nclasses 256 x 256 x c1 128 x 128 x c2 64 x 64 x c3 32 x 32 x c4 c1 < c2 < c3 < c4 Convolution Max Pooling Up-Scaling Number of channels: nrow x ncol x nchannel Input Desired Output
- 14. DCNN Architectures for Image Segmentation • There are multiple ways to tackle the problem of loss of spatial information: • Skip connections • 2D: U-Net, Ronneberger 2015 • 3D: V-Net, Milletari 2016 • Dense Architectures • Huang 2016 Ø Original publication • MSD-Net, Pelt 2017 • HyperDense-Net, Dolz 2018 Ø Recent examples…
- 15. Skip Connections
- 16. Dense Connections
- 17. 2D Models: U-Net • 2 Convolutions without padding at every ”level” of the Network • Skip Connections propagate information from early to later layers (after cropping) Levels 0 1 2 3 4
- 18. 3D Models: V-Net • Residual blocks of varying depths at every ”level” of the Network • Skip Connections propagate information from early to later layers • ”Down Conv” and “Up Conv” layers between levels (instead of MaxPool and UpScale) • Can be used with 2D input too! • U-Net and V-Net make use of the same idea: Skip connections
- 19. V-Net Building Blocks Residual Block Conv3D k=2, s=2 Conv3DTranspose k=2, s=2 Concatenate Conv3D Add PReLu Keras Layers
- 20. U-Net vs V-Net • One disadvantage of 3D architectures is the large memory footprint • This is especially true if we want to feed the entire scan (i.e. all slices) to the network at once • V-Net : one batch contains (batch-size * nslices ) 2D-images • U-Net: batch-size directly determines number of 2D images in one batch • In other words: • For the U-Net, each slice is one training example • For the V-net, each scan is one training example • Nvnet < Nunet • Is it harder to learn 3D kernels? Ø Convolutions are not rotation-invariant Ø 3D adds an additional rotational axis
- 21. Quality of Predicted Segmentation • Quantitative vs Ground Truth • (weighted) cross-entropy • Dice Coefficient • … • Qualitative • Do the predicted contours look as if they were produced by an expert? • Radiology Turing Test: ØIf there is an attending physician on one side of a wall (A), and a computer or radiologist on the other, can the attending physician tell the difference? ISMRM April 2017 Computer Aided Diagnosis
- 22. The Dice Coefficient … similar to Intersection over Union Let R be the reference segmentation (gold standard) with voxel values rn for the foreground class and voxel n over N image elements. Let P with values pn be the corresponding predicted probabilistic map. !" = 2 ∗ ∑' (')' + + ∑'(('+)') + + Dice Coefficient is between 0 (no overlap) and 1 (perfect overlap).
- 23. Generalized Dice Loss Sum over all voxels Sum over all classes Let R be the reference segmentation (gold standard) with voxel value rln for class l and voxel n over N image elements. Let P with values pln be the corresponding predicted probabilistic map. Sudre 2017
- 24. V-Net: Our Implementation on T1 Scans Milletari 2016 Our Architecture Input Shape x, y, z, nchannel 128, 128, 64, 1 256, 256, 32, 1 Kernel Size x, y, z 5, 5, 5 3, 3, 2 Strides for Up- and Down Conv 2, 2, 2 2, 2, 1 nfilters @ 1 … nlevels 16, 32, 64, 128, 256 32, 64, 128, 256 i.e. one level less Residual Block depth @ 1 … nlevels 1, 2, 2, 2, 3 1, 2, 2, 3 Loss „Dice-based loss“ (?) Generalized Dice Loss
- 25. V-Net: Our Implementation on T1 + T2 Scans • Input has 2 Channels (T1, T2) • First layer finds „useful“ combinations of T1 & T2 Channels Ø Conv3D(filters=32, kernel_size=(1,1,1)) Ø This only works if subject hasn’t moved… … 32 * Conv1,1,1 256, 256, 32, 2 256, 256, 32, 32 Vnet
- 26. Results • Currently, validation is performed on all scans of one single subject (12 timepoints) • None of the scans from that subject are part of the training set Model Input # Param avg DC sd DC Unet* T1 56,442,132 0.824 ± 0.036 Vnet T1 8,074,338 0.855 ± 0.030 Vnet T1+T2 8,092,322 0.869 ± 0.019 * Our implementation of the Unet uses residual blocks and up- and down-convolutions just like the Vnet
- 27. Results per Slice 0 7 15 SliceLocation //2z-axis //2 SliceLocation Nvoxels Ventricle Size
- 28. Results on Validation Set (1 Patient) Vnet T1
- 29. Results on Day2Day data • Not that good. Vnet T1
- 30. Discussion • 3D Deep Convolutional Neural Networks provide state of the art performance for image segmentation • A 3D model with comparable architecture but just 1/8 of the parameters of a 2D model outperforms the 2D model • The performance gain comes at the cost of higher memory needs • Our V-Net does not easily generalize to the Day2Day data • Data Augmentation? • Transfer Learning?
- 31. Acknowledgements AG Niendorf Jason Millward Sonia Waiczies Andreas Pohlmann AG Lippert Christoph Lippert Aiham Taleb Sharyar Khorasani
- 32. References • 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. • Milletari, Fausto, Nassir Navab, and Seyed-Ahmad Ahmadi. "V-net: Fullyconvolutional neural networks for volumetric medical imagesegmentation."3D Vision (3DV), 2016 Fourth International Conference on. IEEE, 2016. • Filevich, Elisa, et al. "Day2day: investigating daily variability of magnetic resonance imaging measures over half a year."BMC neuroscience18.1 (2017): 65. • Huang, G., Z. Liu, and K. Q. Weinberger. "Densely Connected Convolutional Networks. arXiv Preprint, 1–12." (2016). • Dolz, Jose, et al. "HyperDense-Net: A hyper-densely connected CNN for multi-modal image segmentation."arXiv preprint arXiv:1804.02967(2018). • Sudre, Carole H., et al. "Generalised Dice overlap as a deep learning loss function for highly unbalanced segmentations."Deep Learning in Medical Image Analysis and Multimodal Learning for Clinical Decision Support. Springer, Cham, 2017. 240-248. • Pelt, Daniël M., and James A. Sethian. "A mixed-scale dense convolutional neural network for image analysis."Proceedings of the National Academy of Sciences(2017): 201715832.