Mark S. Graham

Walter H. L. Pinaya, Mark S. Graham, Eric Kerfoot et al.

Recent advances in generative AI have brought incredible breakthroughs in several areas, including medical imaging. These generative models have tremendous potential not only to help safely share medical data via synthetic datasets but also to perform an array of diverse applications, such as anomaly detection, image-to-image translation, denoising, and MRI reconstruction. However, due to the complexity of these models, their implementation and reproducibility can be difficult. This complexity can hinder progress, act as a use barrier, and dissuade the comparison of new methods with existing works. In this study, we present MONAI Generative Models, a freely available open-source platform that allows researchers and developers to easily train, evaluate, and deploy generative models and related applications. Our platform reproduces state-of-art studies in a standardised way involving different architectures (such as diffusion models, autoregressive transformers, and GANs), and provides pre-trained models for the community. We have implemented these models in a generalisable fashion, illustrating that their results can be extended to 2D or 3D scenarios, including medical images with different modalities (like CT, MRI, and X-Ray data) and from different anatomical areas. Finally, we adopt a modular and extensible approach, ensuring long-term maintainability and the extension of current applications for future features.

Mark S. Graham, Walter H. L. Pinaya, Petru-Daniel Tudosiu et al.

Out-of-distribution detection is crucial to the safe deployment of machine learning systems. Currently, unsupervised out-of-distribution detection is dominated by generative-based approaches that make use of estimates of the likelihood or other measurements from a generative model. Reconstruction-based methods offer an alternative approach, in which a measure of reconstruction error is used to determine if a sample is out-of-distribution. However, reconstruction-based approaches are less favoured, as they require careful tuning of the model's information bottleneck - such as the size of the latent dimension - to produce good results. In this work, we exploit the view of denoising diffusion probabilistic models (DDPM) as denoising autoencoders where the bottleneck is controlled externally, by means of the amount of noise applied. We propose to use DDPMs to reconstruct an input that has been noised to a range of noise levels, and use the resulting multi-dimensional reconstruction error to classify out-of-distribution inputs. We validate our approach both on standard computer-vision datasets and on higher dimension medical datasets. Our approach outperforms not only reconstruction-based methods, but also state-of-the-art generative-based approaches. Code is available at https://github.com/marksgraham/ddpm-ood.

Petru-Daniel Tudosiu, Walter Hugo Lopez Pinaya, Mark S. Graham et al.

Human anatomy, morphology, and associated diseases can be studied using medical imaging data. However, access to medical imaging data is restricted by governance and privacy concerns, data ownership, and the cost of acquisition, thus limiting our ability to understand the human body. A possible solution to this issue is the creation of a model able to learn and then generate synthetic images of the human body conditioned on specific characteristics of relevance (e.g., age, sex, and disease status). Deep generative models, in the form of neural networks, have been recently used to create synthetic 2D images of natural scenes. Still, the ability to produce high-resolution 3D volumetric imaging data with correct anatomical morphology has been hampered by data scarcity and algorithmic and computational limitations. This work proposes a generative model that can be scaled to produce anatomically correct, high-resolution, and realistic images of the human brain, with the necessary quality to allow further downstream analyses. The ability to generate a potentially unlimited amount of data not only enables large-scale studies of human anatomy and pathology without jeopardizing patient privacy, but also significantly advances research in the field of anomaly detection, modality synthesis, learning under limited data, and fair and ethical AI. Code and trained models are available at: https://github.com/AmigoLab/SynthAnatomy.

Mark S Graham, Petru-Daniel Tudosiu, Paul Wright et al.

In a clinical setting it is essential that deployed image processing systems are robust to the full range of inputs they might encounter and, in particular, do not make confidently wrong predictions. The most popular approach to safe processing is to train networks that can provide a measure of their uncertainty, but these tend to fail for inputs that are far outside the training data distribution. Recently, generative modelling approaches have been proposed as an alternative; these can quantify the likelihood of a data sample explicitly, filtering out any out-of-distribution (OOD) samples before further processing is performed. In this work, we focus on image segmentation and evaluate several approaches to network uncertainty in the far-OOD and near-OOD cases for the task of segmenting haemorrhages in head CTs. We find all of these approaches are unsuitable for safe segmentation as they provide confidently wrong predictions when operating OOD. We propose performing full 3D OOD detection using a VQ-GAN to provide a compressed latent representation of the image and a transformer to estimate the data likelihood. Our approach successfully identifies images in both the far- and near-OOD cases. We find a strong relationship between image likelihood and the quality of a model's segmentation, making this approach viable for filtering images unsuitable for segmentation. To our knowledge, this is the first time transformers have been applied to perform OOD detection on 3D image data. Code is available at github.com/marksgraham/transformer-ood.

Mark S. Graham, Walter Hugo Lopez Pinaya, Paul Wright et al.

Methods for out-of-distribution (OOD) detection that scale to 3D data are crucial components of any real-world clinical deep learning system. Classic denoising diffusion probabilistic models (DDPMs) have been recently proposed as a robust way to perform reconstruction-based OOD detection on 2D datasets, but do not trivially scale to 3D data. In this work, we propose to use Latent Diffusion Models (LDMs), which enable the scaling of DDPMs to high-resolution 3D medical data. We validate the proposed approach on near- and far-OOD datasets and compare it to a recently proposed, 3D-enabled approach using Latent Transformer Models (LTMs). Not only does the proposed LDM-based approach achieve statistically significant better performance, it also shows less sensitivity to the underlying latent representation, more favourable memory scaling, and produces better spatial anomaly maps. Code is available at https://github.com/marksgraham/ddpm-ood

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.

Virginia Fernandez, Walter Hugo Lopez Pinaya, Pedro Borges et al.

In order to achieve good performance and generalisability, medical image segmentation models should be trained on sizeable datasets with sufficient variability. Due to ethics and governance restrictions, and the costs associated with labelling data, scientific development is often stifled, with models trained and tested on limited data. Data augmentation is often used to artificially increase the variability in the data distribution and improve model generalisability. Recent works have explored deep generative models for image synthesis, as such an approach would enable the generation of an effectively infinite amount of varied data, addressing the generalisability and data access problems. However, many proposed solutions limit the user's control over what is generated. In this work, we propose brainSPADE, a model which combines a synthetic diffusion-based label generator with a semantic image generator. Our model can produce fully synthetic brain labels on-demand, with or without pathology of interest, and then generate a corresponding MRI image of an arbitrary guided style. Experiments show that brainSPADE synthetic data can be used to train segmentation models with performance comparable to that of models trained on real data.

Benjamin Murray, Eric Kerfoot, Mark S. Graham et al.

The Covid Symptom Study, a smartphone-based surveillance study on COVID-19 symptoms in the population, is an exemplar of big data citizen science. Over 4.7 million participants and 189 million unique assessments have been logged since its introduction in March 2020. The success of the Covid Symptom Study creates technical challenges around effective data curation for two reasons. Firstly, the scale of the dataset means that it can no longer be easily processed using standard software on commodity hardware. Secondly, the size of the research group means that replicability and consistency of key analytics used across multiple publications becomes an issue. We present ExeTera, an open source data curation software designed to address scalability challenges and to enable reproducible research across an international research group for datasets such as the Covid Symptom Study dataset.

Thomas Varsavsky, Mauricio Orbes-Arteaga, Carole H. Sudre et al.

Convolutional neural networks trained on publicly available medical imaging datasets (source domain) rarely generalise to different scanners or acquisition protocols (target domain). This motivates the active field of domain adaptation. While some approaches to the problem require labeled data from the target domain, others adopt an unsupervised approach to domain adaptation (UDA). Evaluating UDA methods consists of measuring the model's ability to generalise to unseen data in the target domain. In this work, we argue that this is not as useful as adapting to the test set directly. We therefore propose an evaluation framework where we perform test-time UDA on each subject separately. We show that models adapted to a specific target subject from the target domain outperform a domain adaptation method which has seen more data of the target domain but not this specific target subject. This result supports the thesis that unsupervised domain adaptation should be used at test-time, even if only using a single target-domain subject

Mark S. Graham, Carole H. Sudre, Thomas Varsavsky et al.

Many atlases used for brain parcellation are hierarchically organised, progressively dividing the brain into smaller sub-regions. However, state-of-the-art parcellation methods tend to ignore this structure and treat labels as if they are `flat'. We introduce a hierarchically-aware brain parcellation method that works by predicting the decisions at each branch in the label tree. We further show how this method can be used to model uncertainty separately for every branch in this label tree. Our method exceeds the performance of flat uncertainty methods, whilst also providing decomposed uncertainty estimates that enable us to obtain self-consistent parcellations and uncertainty maps at any level of the label hierarchy. We demonstrate a simple way these decision-specific uncertainty maps may be used to provided uncertainty-thresholded tissue maps at any level of the label tree.

Petru-Daniel Tudosiu, Thomas Varsavsky, Richard Shaw et al.

The increasing efficiency and compactness of deep learning architectures, together with hardware improvements, have enabled the complex and high-dimensional modelling of medical volumetric data at higher resolutions. Recently, Vector-Quantised Variational Autoencoders (VQ-VAE) have been proposed as an efficient generative unsupervised learning approach that can encode images to a small percentage of their initial size, while preserving their decoded fidelity. Here, we show a VQ-VAE inspired network can efficiently encode a full-resolution 3D brain volume, compressing the data to $0.825\%$ of the original size while maintaining image fidelity, and significantly outperforming the previous state-of-the-art. We then demonstrate that VQ-VAE decoded images preserve the morphological characteristics of the original data through voxel-based morphology and segmentation experiments. Lastly, we show that such models can be pre-trained and then fine-tuned on different datasets without the introduction of bias.

Kanwal K. Bhatia, Mark S. Graham, Louise Terry et al.

Purpose: To evaluate Pegasus-OCT, a clinical decision support software for the identification of features of retinal disease from macula OCT scans, across heterogenous populations involving varying patient demographics, device manufacturers, acquisition sites and operators. Methods: 5,588 normal and anomalous macular OCT volumes (162,721 B-scans), acquired at independent centres in five countries, were processed using the software. Results were evaluated against ground truth provided by the dataset owners. Results: Pegasus-OCT performed with AUROCs of at least 98% for all datasets in the detection of general macular anomalies. For scans of sufficient quality, the AUROCs for general AMD and DME detection were found to be at least 99% and 98%, respectively. Conclusions: The ability of a clinical decision support system to cater for different populations is key to its adoption. Pegasus-OCT was shown to be able to detect AMD, DME and general anomalies in OCT volumes acquired across multiple independent sites with high performance. Its use thus offers substantial promise, with the potential to alleviate the burden of growing demand in eye care services caused by retinal disease.