MAD: Modality Agnostic Distance Measure for Image Registration

Multi-modal image registration is a crucial pre-processing step in many medical applications. However, it is a challenging task due to the complex intensity relationships between different imaging modalities, which can result in large discrepancy in image appearance. The success of multi-modal image registration, whether it is conventional or learning based, is predicated upon the choice of an appropriate distance (or similarity) measure. Particularly, deep learning registration algorithms lack in accuracy or even fail completely when attempting to register data from an "unseen" modality. In this work, we present Modality Agnostic Distance (MAD), a deep image distance}] measure that utilises random convolutions to learn the inherent geometry of the images while being robust to large appearance changes. Random convolutions are geometry-preserving modules which we use to simulate an infinite number of synthetic modalities alleviating the need for aligned paired data during training. We can therefore train MAD on a mono-modal dataset and successfully apply it to a multi-modal dataset. We demonstrate that not only can MAD affinely register multi-modal images successfully, but it has also a larger capture range than traditional measures such as Mutual Information and Normalised Gradient Fields.

Conditional Deformable Image Registration with Spatially-Variant and Adaptive Regularization

Deep learning-based image registration approaches have shown competitive performance and run-time advantages compared to conventional image registration methods. However, existing learning-based approaches mostly require to train separate models with respect to different regularization hyperparameters for manual hyperparameter searching and often do not allow spatially-variant regularization. In this work, we propose a learning-based registration approach based on a novel conditional spatially adaptive instance normalization (CSAIN) to address these challenges. The proposed method introduces a spatially-variant regularization and learns its effect of achieving spatially-adaptive regularization by conditioning the registration network on the hyperparameter matrix via CSAIN. This allows varying of spatially adaptive regularization at inference to obtain multiple plausible deformations with a single pre-trained model. Additionally, the proposed method enables automatic hyperparameter optimization to avoid manual hyperparameter searching. Experiments show that our proposed method outperforms the baseline approaches while achieving spatially-variant and adaptive regularization.

CHeart: A Conditional Spatio-Temporal Generative Model for Cardiac Anatomy

Two key questions in cardiac image analysis are to assess the anatomy and motion of the heart from images; and to understand how they are associated with non-imaging clinical factors such as gender, age and diseases. While the first question can often be addressed by image segmentation and motion tracking algorithms, our capability to model and to answer the second question is still limited. In this work, we propose a novel conditional generative model to describe the 4D spatio-temporal anatomy of the heart and its interaction with non-imaging clinical factors. The clinical factors are integrated as the conditions of the generative modelling, which allows us to investigate how these factors influence the cardiac anatomy. We evaluate the model performance in mainly two tasks, anatomical sequence completion and sequence generation. The model achieves a high performance in anatomical sequence completion, comparable to or outperforming other state-of-the-art generative models. In terms of sequence generation, given clinical conditions, the model can generate realistic synthetic 4D sequential anatomies that share similar distributions with the real data.

Generative Modelling of the Ageing Heart with Cross-Sectional Imaging and Clinical Data

Cardiovascular disease, the leading cause of death globally, is an age-related disease. Understanding the morphological and functional changes of the heart during ageing is a key scientific question, the answer to which will help us define important risk factors of cardiovascular disease and monitor disease progression. In this work, we propose a novel conditional generative model to describe the changes of 3D anatomy of the heart during ageing. The proposed model is flexible and allows integration of multiple clinical factors (e.g. age, gender) into the generating process. We train the model on a large-scale cross-sectional dataset of cardiac anatomies and evaluate on both cross-sectional and longitudinal datasets. The model demonstrates excellent performance in predicting the longitudinal evolution of the ageing heart and modelling its data distribution.

Learn2Reg: comprehensive multi-task medical image registration challenge, dataset and evaluation in the era of deep learning

Image registration is a fundamental medical image analysis task, and a wide variety of approaches have been proposed. However, only a few studies have comprehensively compared medical image registration approaches on a wide range of clinically relevant tasks, in part because of the lack of availability of such diverse data. This limits the development of registration methods, the adoption of research advances into practice, and a fair benchmark across competing approaches. The Learn2Reg challenge addresses these limitations by providing a multi-task medical image registration benchmark for comprehensive characterisation of deformable registration algorithms. A continuous evaluation will be possible at https://learn2reg.grand-challenge.org. Learn2Reg covers a wide range of anatomies (brain, abdomen, and thorax), modalities (ultrasound, CT, MR), availability of annotations, as well as intra- and inter-patient registration evaluation. We established an easily accessible framework for training and validation of 3D registration methods, which enabled the compilation of results of over 65 individual method submissions from more than 20 unique teams. We used a complementary set of metrics, including robustness, accuracy, plausibility, and runtime, enabling unique insight into the current state-of-the-art of medical image registration. This paper describes datasets, tasks, evaluation methods and results of the challenge, and the results of further analysis of transferability to new datasets, the importance of label supervision, and resulting bias.

GraDIRN: Learning Iterative Gradient Descent-based Energy Minimization for Deformable Image Registration

We present a Gradient Descent-based Image Registration Network (GraDIRN) for learning deformable image registration by embedding gradient-based iterative energy minimization in a deep learning framework. Traditional image registration algorithms typically use iterative energy-minimization optimization to find the optimal transformation between a pair of images, which is time-consuming when many iterations are needed. In contrast, recent learning-based methods amortize this costly iterative optimization by training deep neural networks so that registration of one pair of images can be achieved by fast network forward pass after training. Motivated by successes in image reconstruction techniques that combine deep learning with the mathematical structure of iterative variational energy optimization, we formulate a novel registration network based on multi-resolution gradient descent energy minimization. The forward pass of the network takes explicit image dissimilarity gradient steps and generalized regularization steps parameterized by Convolutional Neural Networks (CNN) for a fixed number of iterations. We use auto-differentiation to derive the forward computational graph for the explicit image dissimilarity gradient w.r.t. the transformation, so arbitrary image dissimilarity metrics and transformation models can be used without complex and error-prone gradient derivations. We demonstrate that this approach achieves state-of-the-art registration performance while using fewer learnable parameters through extensive evaluations on registration tasks using 2D cardiac MR images and 3D brain MR images.

Uncertainty quantification in non-rigid image registration via stochastic gradient Markov chain Monte Carlo

We develop a new Bayesian model for non-rigid registration of three-dimensional medical images, with a focus on uncertainty quantification. Probabilistic registration of large images with calibrated uncertainty estimates is difficult for both computational and modelling reasons. To address the computational issues, we explore connections between the Markov chain Monte Carlo by backpropagation and the variational inference by backpropagation frameworks, in order to efficiently draw samples from the posterior distribution of transformation parameters. To address the modelling issues, we formulate a Bayesian model for image registration that overcomes the existing barriers when using a dense, high-dimensional, and diffeomorphic transformation parametrisation. This results in improved calibration of uncertainty estimates. We compare the model in terms of both image registration accuracy and uncertainty quantification to VoxelMorph, a state-of-the-art image registration model based on deep learning.

Is MC Dropout Bayesian?

MC Dropout is a mainstream "free lunch" method in medical imaging for approximate Bayesian computations (ABC). Its appeal is to solve out-of-the-box the daunting task of ABC and uncertainty quantification in Neural Networks (NNs); to fall within the variational inference (VI) framework; and to propose a highly multimodal, faithful predictive posterior. We question the properties of MC Dropout for approximate inference, as in fact MC Dropout changes the Bayesian model; its predictive posterior assigns $0$ probability to the true model on closed-form benchmarks; the multimodality of its predictive posterior is not a property of the true predictive posterior but a design artefact. To address the need for VI on arbitrary models, we share a generic VI engine within the pytorch framework. The code includes a carefully designed implementation of structured (diagonal plus low-rank) multivariate normal variational families, and mixtures thereof. It is intended as a go-to no-free-lunch approach, addressing shortcomings of mean-field VI with an adjustable trade-off between expressivity and computational complexity.

Enhancing MR Image Segmentation with Realistic Adversarial Data Augmentation

The success of neural networks on medical image segmentation tasks typically relies on large labeled datasets for model training. However, acquiring and manually labeling a large medical image set is resource-intensive, expensive, and sometimes impractical due to data sharing and privacy issues. To address this challenge, we propose an adversarial data augmentation approach to improve the efficiency in utilizing training data and to enlarge the dataset via simulated but realistic transformations. Specifically, we present a generic task-driven learning framework, which jointly optimizes a data augmentation model and a segmentation network during training, generating informative examples to enhance network generalizability for the downstream task. The data augmentation model utilizes a set of photometric and geometric image transformations and chains them to simulate realistic complex imaging variations that could exist in magnetic resonance (MR) imaging. The proposed adversarial data augmentation does not rely on generative networks and can be used as a plug-in module in general segmentation networks. It is computationally efficient and applicable for both supervised and semi-supervised learning. We analyze and evaluate the method on two MR image segmentation tasks: cardiac segmentation and prostate segmentation. Results show that the proposed approach can alleviate the need for labeled data while improving model generalization ability, indicating its practical value in medical imaging applications.

Learning a Model-Driven Variational Network for Deformable Image Registration

Data-driven deep learning approaches to image registration can be less accurate than conventional iterative approaches, especially when training data is limited. To address this whilst retaining the fast inference speed of deep learning, we propose VR-Net, a novel cascaded variational network for unsupervised deformable image registration. Using the variable splitting optimization scheme, we first convert the image registration problem, established in a generic variational framework, into two sub-problems, one with a point-wise, closed-form solution while the other one is a denoising problem. We then propose two neural layers (i.e. warping layer and intensity consistency layer) to model the analytical solution and a residual U-Net to formulate the denoising problem (i.e. generalized denoising layer). Finally, we cascade the warping layer, intensity consistency layer, and generalized denoising layer to form the VR-Net. Extensive experiments on three (two 2D and one 3D) cardiac magnetic resonance imaging datasets show that VR-Net outperforms state-of-the-art deep learning methods on registration accuracy, while maintains the fast inference speed of deep learning and the data-efficiency of variational model.