Federated Learning Enables Big Data for Rare Cancer Boundary Detection

Although machine learning (ML) has shown promise in numerous domains, there are concerns about generalizability to out-of-sample data. This is currently addressed by centrally sharing ample, and importantly diverse, data from multiple sites. However, such centralization is challenging to scale (or even not feasible) due to various limitations. Federated ML (FL) provides an alternative to train accurate and generalizable ML models, by only sharing numerical model updates. Here we present findings from the largest FL study to-date, involving data from 71 healthcare institutions across 6 continents, to generate an automatic tumor boundary detector for the rare disease of glioblastoma, utilizing the largest dataset of such patients ever used in the literature (25,256 MRI scans from 6,314 patients). We demonstrate a 33% improvement over a publicly trained model to delineate the surgically targetable tumor, and 23% improvement over the tumor's entire extent. We anticipate our study to: 1) enable more studies in healthcare informed by large and diverse data, ensuring meaningful results for rare diseases and underrepresented populations, 2) facilitate further quantitative analyses for glioblastoma via performance optimization of our consensus model for eventual public release, and 3) demonstrate the effectiveness of FL at such scale and task complexity as a paradigm shift for multi-site collaborations, alleviating the need for data sharing.

Transductive image segmentation: Self-training and effect of uncertainty estimation

Semi-supervised learning (SSL) uses unlabeled data during training to learn better models. Previous studies on SSL for medical image segmentation focused mostly on improving model generalization to unseen data. In some applications, however, our primary interest is not generalization but to obtain optimal predictions on a specific unlabeled database that is fully available during model development. Examples include population studies for extracting imaging phenotypes. This work investigates an often overlooked aspect of SSL, transduction. It focuses on the quality of predictions made on the unlabeled data of interest when they are included for optimization during training, rather than improving generalization. We focus on the self-training framework and explore its potential for transduction. We analyze it through the lens of Information Gain and reveal that learning benefits from the use of calibrated or under-confident models. Our extensive experiments on a large MRI database for multi-class segmentation of traumatic brain lesions shows promising results when comparing transductive with inductive predictions. We believe this study will inspire further research on transductive learning, a well-suited paradigm for medical image analysis.

Learning from Partially Overlapping Labels: Image Segmentation under Annotation Shift

Scarcity of high quality annotated images remains a limiting factor for training accurate image segmentation models. While more and more annotated datasets become publicly available, the number of samples in each individual database is often small. Combining different databases to create larger amounts of training data is appealing yet challenging due to the heterogeneity as a result of differences in data acquisition and annotation processes, often yielding incompatible or even conflicting information. In this paper, we investigate and propose several strategies for learning from partially overlapping labels in the context of abdominal organ segmentation. We find that combining a semi-supervised approach with an adaptive cross entropy loss can successfully exploit heterogeneously annotated data and substantially improve segmentation accuracy compared to baseline and alternative approaches.

Confidence-based Out-of-Distribution Detection: A Comparative Study and Analysis

Image classification models deployed in the real world may receive inputs outside the intended data distribution. For critical applications such as clinical decision making, it is important that a model can detect such out-of-distribution (OOD) inputs and express its uncertainty. In this work, we assess the capability of various state-of-the-art approaches for confidence-based OOD detection through a comparative study and in-depth analysis. First, we leverage a computer vision benchmark to reproduce and compare multiple OOD detection methods. We then evaluate their capabilities on the challenging task of disease classification using chest X-rays. Our study shows that high performance in a computer vision task does not directly translate to accuracy in a medical imaging task. We analyse factors that affect performance of the methods between the two tasks. Our results provide useful insights for developing the next generation of OOD detection methods.

Distributional Gaussian Process Layers for Outlier Detection in Image Segmentation

We propose a parameter efficient Bayesian layer for hierarchical convolutional Gaussian Processes that incorporates Gaussian Processes operating in Wasserstein-2 space to reliably propagate uncertainty. This directly replaces convolving Gaussian Processes with a distance-preserving affine operator on distributions. Our experiments on brain tissue-segmentation show that the resulting architecture approaches the performance of well-established deterministic segmentation algorithms (U-Net), which has never been achieved with previous hierarchical Gaussian Processes. Moreover, by applying the same segmentation model to out-of-distribution data (i.e., images with pathology such as brain tumors), we show that our uncertainty estimates result in out-of-distribution detection that outperforms the capabilities of previous Bayesian networks and reconstruction-based approaches that learn normative distributions.

Analyzing Overfitting under Class Imbalance in Neural Networks for Image Segmentation

Class imbalance poses a challenge for developing unbiased, accurate predictive models. In particular, in image segmentation neural networks may overfit to the foreground samples from small structures, which are often heavily under-represented in the training set, leading to poor generalization. In this study, we provide new insights on the problem of overfitting under class imbalance by inspecting the network behavior. We find empirically that when training with limited data and strong class imbalance, at test time the distribution of logit activations may shift across the decision boundary, while samples of the well-represented class seem unaffected. This bias leads to a systematic under-segmentation of small structures. This phenomenon is consistently observed for different databases, tasks and network architectures. To tackle this problem, we introduce new asymmetric variants of popular loss functions and regularization techniques including a large margin loss, focal loss, adversarial training, mixup and data augmentation, which are explicitly designed to counter logit shift of the under-represented classes. Extensive experiments are conducted on several challenging segmentation tasks. Our results demonstrate that the proposed modifications to the objective function can lead to significantly improved segmentation accuracy compared to baselines and alternative approaches.

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.

Domain Generalization via Model-Agnostic Learning of Semantic Features

Generalization capability to unseen domains is crucial for machine learning models when deploying to real-world conditions. We investigate the challenging problem of domain generalization, i.e., training a model on multi-domain source data such that it can directly generalize to target domains with unknown statistics. We adopt a model-agnostic learning paradigm with gradient-based meta-train and meta-test procedures to expose the optimization to domain shift. Further, we introduce two complementary losses which explicitly regularize the semantic structure of the feature space. Globally, we align a derived soft confusion matrix to preserve general knowledge about inter-class relationships. Locally, we promote domain-independent class-specific cohesion and separation of sample features with a metric-learning component. The effectiveness of our method is demonstrated with new state-of-the-art results on two common object recognition benchmarks. Our method also shows consistent improvement on a medical image segmentation task.