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

Bayesian analysis of the prevalence bias: learning and predicting from imbalanced data

Datasets are rarely a realistic approximation of the target population. Say, prevalence is misrepresented, image quality is above clinical standards, etc. This mismatch is known as sampling bias. Sampling biases are a major hindrance for machine learning models. They cause significant gaps between model performance in the lab and in the real world. Our work is a solution to prevalence bias. Prevalence bias is the discrepancy between the prevalence of a pathology and its sampling rate in the training dataset, introduced upon collecting data or due to the practioner rebalancing the training batches. This paper lays the theoretical and computational framework for training models, and for prediction, in the presence of prevalence bias. Concretely a bias-corrected loss function, as well as bias-corrected predictive rules, are derived under the principles of Bayesian risk minimization. The loss exhibits a direct connection to the information gain. It offers a principled alternative to heuristic training losses and complements test-time procedures based on selecting an operating point from summary curves. It integrates seamlessly in the current paradigm of (deep) learning using stochastic backpropagation and naturally with Bayesian models

Stochastic segmentation networks: modelling spatially correlated aleatoric uncertainty

In image segmentation, there is often more than one plausible solution for a given input. In medical imaging, for example, experts will often disagree about the exact location of object boundaries. Estimating this inherent uncertainty and predicting multiple plausible hypotheses is of great interest in many applications, yet this ability is lacking in most current deep learning methods. In this paper, we introduce stochastic segmentation networks (SSNs), an efficient probabilistic method for modelling aleatoric uncertainty with any image segmentation network architecture. In contrast to approaches that produce pixel-wise estimates, SSNs model joint distributions over entire label maps and thus can generate multiple spatially coherent hypotheses for a single image. By using a low-rank multivariate normal distribution over the logit space to model the probability of the label map given the image, we obtain a spatially consistent probability distribution that can be efficiently computed by a neural network without any changes to the underlying architecture. We tested our method on the segmentation of real-world medical data, including lung nodules in 2D CT and brain tumours in 3D multimodal MRI scans. SSNs outperform state-of-the-art for modelling correlated uncertainty in ambiguous images while being much simpler, more flexible, and more efficient

Bayesian sampling bias correction: training with the right loss function

We derive a family of loss functions to train models in the presence of sampling bias. Examples are when the prevalence of a pathology differs from its sampling rate in the training dataset, or when a machine learning practioner rebalances their training dataset. Sampling bias causes large discrepancies between model performance in the lab and in more realistic settings. It is omnipresent in medical imaging applications, yet is often overlooked at training time or addressed on an ad-hoc basis. Our approach is based on Bayesian risk minimization. For arbitrary likelihood models we derive the associated bias corrected loss for training, exhibiting a direct connection to information gain. The approach integrates seamlessly in the current paradigm of (deep) learning using stochastic backpropagation and naturally with Bayesian models. We illustrate the methodology on case studies of lung nodule malignancy grading

Evaluating reinforcement learning agents for anatomical landmark detection

Automatic detection of anatomical landmarks is an important step for a wide range of applications in medical image analysis. Manual annotation of landmarks is a tedious task and prone to observer errors. In this paper, we evaluate novel deep reinforcement learning (RL) strategies to train agents that can precisely and robustly localize target landmarks in medical scans. An artificial RL agent learns to identify the optimal path to the landmark by interacting with an environment, in our case 3D images. Furthermore, we investigate the use of fixed- and multi-scale search strategies with novel hierarchical action steps in a coarse-to-fine manner. Several deep Q-network (DQN) architectures are evaluated for detecting multiple landmarks using three different medical imaging datasets: fetal head ultrasound (US), adult brain and cardiac magnetic resonance imaging (MRI). The performance of our agents surpasses state-of-the-art supervised and RL methods. Our experiments also show that multi-scale search strategies perform significantly better than fixed-scale agents in images with large field of view and noisy background such as in cardiac MRI. Moreover, the novel hierarchical steps can significantly speed up the searching process by a factor of 4-5 times

Evaluation of 3D GANs for Lung Tissue Modelling in Pulmonary CT

GANs are able to model accurately the distribution of complex, high-dimensional datasets, e.g. images. This makes high-quality GANs useful for unsupervised anomaly detection in medical imaging. However, differences in training datasets such as output image dimensionality and appearance of semantically meaningful features mean that GAN models from the natural image domain may not work `out-of-the-box' for medical imaging, necessitating re-implementation and re-evaluation. In this work we adapt and evaluate three GAN models to the task of modelling 3D healthy image patches for pulmonary CT. To the best of our knowledge, this is the first time that such an evaluation has been performed. The DCGAN, styleGAN and the bigGAN architectures were investigated due to their ubiquity and high performance in natural image processing. We train different variants of these methods and assess their performance using the FID score. In addition, the quality of the generated images was evaluated by a human observer study, the ability of the networks to model 3D domain-specific features was investigated, and the structure of the GAN latent spaces was analysed. Results show that the 3D styleGAN produces realistic-looking images with meaningful 3D structure, but suffer from mode collapse which must be addressed during training to obtain samples diversity. Conversely, the 3D DCGAN models show a greater capacity for image variability, but at the cost of poor-quality images. The 3D bigGAN models provide an intermediate level of image quality, but most accurately model the distribution of selected semantically meaningful features. The results suggest that future development is required to realise a 3D GAN with sufficient capacity for patch-based lung CT anomaly detection and we offer recommendations for future areas of research, such as experimenting with other architectures and incorporation of position-encoding

The effect of the loss on generalization: empirical study on synthetic lung nodule data

Convolutional Neural Networks (CNNs) are widely used for image classification in a variety of fields, including medical imaging. While most studies deploy cross-entropy as the loss function in such tasks, a growing number of approaches have turned to a family of contrastive learning-based losses. Even though performance metrics such as accuracy, sensitivity and specificity are regularly used for the evaluation of CNN classifiers, the features that these classifiers actually learn are rarely identified and their effect on the classification performance on out-of-distribution test samples is insufficiently explored. In this paper, motivated by the real-world task of lung nodule classification, we investigate the features that a CNN learns when trained and tested on different distributions of a synthetic dataset with controlled modes of variation. We show that different loss functions lead to different features being learned and consequently affect the generalization ability of the classifier on unseen data. This study provides some important insights into the design of deep learning solutions for medical imaging tasks

The pitfalls of sample selection: a case study on lung nodule classification

Using publicly available data to determine the performance of methodological contributions is important as it facilitates reproducibility and allows scrutiny of the published results. In lung nodule classification, for example, many works report results on the publicly available LIDC dataset. In theory, this should allow a direct comparison of the performance of proposed methods and assess the impact of individual contributions. When analyzing seven recent works, however, we find that each employs a different data selection process, leading to largely varying total number of samples and ratios between benign and malignant cases. As each subset will have different characteristics with varying difficulty for classification, a direct comparison between the proposed methods is thus not always possible, nor fair. We study the particular effect of truthing when aggregating labels from multiple experts. We show that specific choices can have severe impact on the data distribution where it may be possible to achieve superior performance on one sample distribution but not on another. While we show that we can further improve on the state-of-the-art on one sample selection, we also find that on a more challenging sample selection, on the same database, the more advanced models underperform with respect to very simple baseline methods, highlighting that the selected data distribution may play an even more important role than the model architecture. This raises concerns about the validity of claimed methodological contributions. We believe the community should be aware of these pitfalls and make recommendations on how these can be avoided in future work