Robert M. Gray

Walter H. L. Pinaya, Mark S. Graham, Robert Gray et al.

Deep generative models have emerged as promising tools for detecting arbitrary anomalies in data, dispensing with the necessity for manual labelling. Recently, autoregressive transformers have achieved state-of-the-art performance for anomaly detection in medical imaging. Nonetheless, these models still have some intrinsic weaknesses, such as requiring images to be modelled as 1D sequences, the accumulation of errors during the sampling process, and the significant inference times associated with transformers. Denoising diffusion probabilistic models are a class of non-autoregressive generative models recently shown to produce excellent samples in computer vision (surpassing Generative Adversarial Networks), and to achieve log-likelihoods that are competitive with transformers while having fast inference times. Diffusion models can be applied to the latent representations learnt by autoencoders, making them easily scalable and great candidates for application to high dimensional data, such as medical images. Here, we propose a method based on diffusion models to detect and segment anomalies in brain imaging. By training the models on healthy data and then exploring its diffusion and reverse steps across its Markov chain, we can identify anomalous areas in the latent space and hence identify anomalies in the pixel space. Our diffusion models achieve competitive performance compared with autoregressive approaches across a series of experiments with 2D CT and MRI data involving synthetic and real pathological lesions with much reduced inference times, making their usage clinically viable.

Guilherme Pombo, Robert Gray, Amy P. K. Nelson et al.

Causal mapping of the functional organisation of the human brain requires evidence of \textit{necessity} available at adequate scale only from pathological lesions of natural origin. This demands inferential models with sufficient flexibility to capture both the observable distribution of pathological damage and the unobserved distribution of the neural substrate. Current model frameworks -- both mass-univariate and multivariate -- either ignore distributed lesion-deficit relations or do not model them explicitly, relying on featurization incidental to a predictive task. Here we initiate the application of deep generative neural network architectures to the task of lesion-deficit inference, formulating it as the estimation of an expressive hierarchical model of the joint lesion and deficit distributions conditioned on a latent neural substrate. We implement such deep lesion deficit inference with variational convolutional volumetric auto-encoders. We introduce a comprehensive framework for lesion-deficit model comparison, incorporating diverse candidate substrates, forms of substrate interactions, sample sizes, noise corruption, and population heterogeneity. Drawing on 5500 volume images of ischaemic stroke, we show that our model outperforms established methods by a substantial margin across all simulation scenarios, including comparatively small-scale and noisy data regimes. Our analysis justifies the widespread adoption of this approach, for which we provide an open source implementation: https://github.com/guilherme-pombo/vae_lesion_deficit

Chris Foulon, Robert Gray, James K. Ruffle et al.

Ischaemic stroke, a leading cause of death and disability, critically relies on neuroimaging for characterising the anatomical pattern of injury. Diffusion-weighted imaging (DWI) provides the highest expressivity in ischemic stroke but poses substantial challenges for automated lesion segmentation: susceptibility artefacts, morphological heterogeneity, age-related comorbidities, time-dependent signal dynamics, instrumental variability, and limited labelled data. Current U-Net-based models therefore underperform, a problem accentuated by inadequate evaluation metrics that focus on mean performance, neglecting anatomical, subpopulation, and acquisition-dependent variability. Here, we present a high-performance DWI lesion segmentation tool addressing these challenges through optimized vision transformer-based architectures, integration of 3563 annotated lesions from multi-site data, and algorithmic enhancements, achieving state-of-the-art results. We further propose a novel evaluative framework assessing model fidelity, equity (across demographics and lesion subtypes), anatomical precision, and robustness to instrumental variability, promoting clinical and research utility. This work advances stroke imaging by reconciling model expressivity with domain-specific challenges and redefining performance benchmarks to prioritize equity and generalizability, critical for personalized medicine and mechanistic research.

Guilherme Pombo, Robert Gray, Jorge Cardoso et al.

We describe Countersynth, a conditional generative model of diffeomorphic deformations that induce label-driven, biologically plausible changes in volumetric brain images. The model is intended to synthesise counterfactual training data augmentations for downstream discriminative modelling tasks where fidelity is limited by data imbalance, distributional instability, confounding, or underspecification, and exhibits inequitable performance across distinct subpopulations. Focusing on demographic attributes, we evaluate the quality of synthesized counterfactuals with voxel-based morphometry, classification and regression of the conditioning attributes, and the Fréchet inception distance. Examining downstream discriminative performance in the context of engineered demographic imbalance and confounding, we use UK Biobank magnetic resonance imaging data to benchmark CounterSynth augmentation against current solutions to these problems. We achieve state-of-the-art improvements, both in overall fidelity and equity. The source code for CounterSynth is available online.

Guilherme Pombo, Robert Gray, Tom Varsavsky et al.

Deep generative models are rapidly gaining traction in medical imaging. Nonetheless, most generative architectures struggle to capture the underlying probability distributions of volumetric data, exhibit convergence problems, and offer no robust indices of model uncertainty. By comparison, the autoregressive generative model PixelCNN can be extended to volumetric data with relative ease, it readily attempts to learn the true underlying probability distribution and it still admits a Bayesian reformulation that provides a principled framework for reasoning about model uncertainty. Our contributions in this paper are two fold: first, we extend PixelCNN to work with volumetric brain magnetic resonance imaging data. Second, we show that reformulating this model to approximate a deep Gaussian process yields a measure of uncertainty that improves the performance of semi-supervised learning, in particular classification performance in settings where the proportion of labelled data is low. We quantify this improvement across classification, regression, and semantic segmentation tasks, training and testing on clinical magnetic resonance brain imaging data comprising T1-weighted and diffusion-weighted sequences.