Petru-Daniel Tudosiu

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, Petru-Daniel Tudosiu, Jessica Dafflon et al.

Deep neural networks have brought remarkable breakthroughs in medical image analysis. However, due to their data-hungry nature, the modest dataset sizes in medical imaging projects might be hindering their full potential. Generating synthetic data provides a promising alternative, allowing to complement training datasets and conducting medical image research at a larger scale. Diffusion models recently have caught the attention of the computer vision community by producing photorealistic synthetic images. In this study, we explore using Latent Diffusion Models to generate synthetic images from high-resolution 3D brain images. We used T1w MRI images from the UK Biobank dataset (N=31,740) to train our models to learn about the probabilistic distribution of brain images, conditioned on covariables, such as age, sex, and brain structure volumes. We found that our models created realistic data, and we could use the conditioning variables to control the data generation effectively. Besides that, we created a synthetic dataset with 100,000 brain images and made it openly available to the scientific community.

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.

Jueqi Wang, Jacob Levman, Walter Hugo Lopez Pinaya et al.

High-resolution (HR) MRI scans obtained from research-grade medical centers provide precise information about imaged tissues. However, routine clinical MRI scans are typically in low-resolution (LR) and vary greatly in contrast and spatial resolution due to the adjustments of the scanning parameters to the local needs of the medical center. End-to-end deep learning methods for MRI super-resolution (SR) have been proposed, but they require re-training each time there is a shift in the input distribution. To address this issue, we propose a novel approach that leverages a state-of-the-art 3D brain generative model, the latent diffusion model (LDM) trained on UK BioBank, to increase the resolution of clinical MRI scans. The LDM acts as a generative prior, which has the ability to capture the prior distribution of 3D T1-weighted brain MRI. Based on the architecture of the brain LDM, we find that different methods are suitable for different settings of MRI SR, and thus propose two novel strategies: 1) for SR with more sparsity, we invert through both the decoder of the LDM and also through a deterministic Denoising Diffusion Implicit Models (DDIM), an approach we will call InverseSR(LDM); 2) for SR with less sparsity, we invert only through the LDM decoder, an approach we will call InverseSR(Decoder). These two approaches search different latent spaces in the LDM model to find the optimal latent code to map the given LR MRI into HR. The training process of the generative model is independent of the MRI under-sampling process, ensuring the generalization of our method to many MRI SR problems with different input measurements. We validate our method on over 100 brain T1w MRIs from the IXI dataset. Our method can demonstrate that powerful priors given by LDM can be used for MRI reconstruction.

Jizhizi Li, Jiayang Ao, Danny Wicks et al.

Many multimodal learning tasks require supervision that remains consistent across edits, viewpoints, and scene-level interventions. However, such supervision is difficult to obtain from observation-level datasets, which do not expose the underlying scene state or how changes propagate through it. We present SceneForge, an intervention-driven framework that generates structured supervision from editable 3D world states. SceneForge represents each scene as a persistent world with semantic, geometric, and physical dependencies. By applying explicit interventions (e.g., object removal or camera variation) and propagating their effects through scene dependencies, SceneForge renders supervision that remains consistent with object structure and scene-level effects. This produces aligned outputs including counterfactual observations, multi-view observations, and effect-aware signals such as shadows and reflections, all derived from a shared world state rather than post hoc image-space processing. We instantiate SceneForge using Infinigen and Blender to construct a licensing-clean indoor supervision resource with a large number of counterfactual pairs and aligned annotations from over 2K scenes, covering both diverse single-view and registered multi-view settings. Under matched training budgets, incorporating SceneForge supervision improves both object removal and scene removal performance across multiple benchmarks in both quantitative and qualitative evaluation. These results indicate that modeling supervision as structured state transitions in editable worlds provides a practical and scalable foundation for intervention-consistent multimodal learning.

Bowen Li, Yongxin Yang, Steven McDonagh et al.

Image editing affords increased control over the aesthetics and content of generated images. Pre-existing works focus predominantly on text-based instructions to achieve desired image modifications, which limit edit precision and accuracy. In this work, we propose an inference-time editing optimisation, designed to extend beyond textual edits to accommodate multiple editing instruction types (e.g. spatial layout-based; pose, scribbles, edge maps). We propose to disentangle the editing task into two competing subtasks: successful local image modifications and global content consistency preservation, where subtasks are guided through two dedicated loss functions. By allowing to adjust the influence of each loss function, we build a flexible editing solution that can be adjusted to user preferences. We evaluate our method using text, pose and scribble edit conditions, and highlight our ability to achieve complex edits, through both qualitative and quantitative experiments.

Cher Bass, Mariana da Silva, Carole Sudre et al.

An important goal of medical imaging is to be able to precisely detect patterns of disease specific to individual scans; however, this is challenged in brain imaging by the degree of heterogeneity of shape and appearance. Traditional methods, based on image registration to a global template, historically fail to detect variable features of disease, as they utilise population-based analyses, suited primarily to studying group-average effects. In this paper we therefore take advantage of recent developments in generative deep learning to develop a method for simultaneous classification, or regression, and feature attribution (FA). Specifically, we explore the use of a VAE-GAN translation network called ICAM, to explicitly disentangle class relevant features from background confounds for improved interpretability and regression of neurological phenotypes. We validate our method on the tasks of Mini-Mental State Examination (MMSE) cognitive test score prediction for the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort, as well as brain age prediction, for both neurodevelopment and neurodegeneration, using the developing Human Connectome Project (dHCP) and UK Biobank datasets. We show that the generated FA maps can be used to explain outlier predictions and demonstrate that the inclusion of a regression module improves the disentanglement of the latent space. Our code is freely available on Github https://github.com/CherBass/ICAM.

Cher Bass, Mariana da Silva, Carole Sudre et al.

Feature attribution (FA), or the assignment of class-relevance to different locations in an image, is important for many classification problems but is particularly crucial within the neuroscience domain, where accurate mechanistic models of behaviours, or disease, require knowledge of all features discriminative of a trait. At the same time, predicting class relevance from brain images is challenging as phenotypes are typically heterogeneous, and changes occur against a background of significant natural variation. Here, we present a novel framework for creating class specific FA maps through image-to-image translation. We propose the use of a VAE-GAN to explicitly disentangle class relevance from background features for improved interpretability properties, which results in meaningful FA maps. We validate our method on 2D and 3D brain image datasets of dementia (ADNI dataset), ageing (UK Biobank), and (simulated) lesion detection. We show that FA maps generated by our method outperform baseline FA methods when validated against ground truth. More significantly, our approach is the first to use latent space sampling to support exploration of phenotype variation. Our code will be available online at https://github.com/CherBass/ICAM.

Petru-Daniel Tudosiu, Yongxin Yang, Shifeng Zhang et al.

Text-to-image generation has achieved astonishing results, yet precise spatial controllability and prompt fidelity remain highly challenging. This limitation is typically addressed through cumbersome prompt engineering, scene layout conditioning, or image editing techniques which often require hand drawn masks. Nonetheless, pre-existing works struggle to take advantage of the natural instance-level compositionality of scenes due to the typically flat nature of rasterized RGB output images. Towards adressing this challenge, we introduce MuLAn: a novel dataset comprising over 44K MUlti-Layer ANnotations of RGB images as multilayer, instance-wise RGBA decompositions, and over 100K instance images. To build MuLAn, we developed a training free pipeline which decomposes a monocular RGB image into a stack of RGBA layers comprising of background and isolated instances. We achieve this through the use of pretrained general-purpose models, and by developing three modules: image decomposition for instance discovery and extraction, instance completion to reconstruct occluded areas, and image re-assembly. We use our pipeline to create MuLAn-COCO and MuLAn-LAION datasets, which contain a variety of image decompositions in terms of style, composition and complexity. With MuLAn, we provide the first photorealistic resource providing instance decomposition and occlusion information for high quality images, opening up new avenues for text-to-image generative AI research. With this, we aim to encourage the development of novel generation and editing technology, in particular layer-wise solutions. MuLAn data resources are available at https://MuLAn-dataset.github.io/.

Alessandro Fontanella, Petru-Daniel Tudosiu, Yongxin Yang et al.

Text-to-image diffusion generative models can generate high quality images at the cost of tedious prompt engineering. Controllability can be improved by introducing layout conditioning, however existing methods lack layout editing ability and fine-grained control over object attributes. The concept of multi-layer generation holds great potential to address these limitations, however generating image instances concurrently to scene composition limits control over fine-grained object attributes, relative positioning in 3D space and scene manipulation abilities. In this work, we propose a novel multi-stage generation paradigm that is designed for fine-grained control, flexibility and interactivity. To ensure control over instance attributes, we devise a novel training paradigm to adapt a diffusion model to generate isolated scene components as RGBA images with transparency information. To build complex images, we employ these pre-generated instances and introduce a multi-layer composite generation process that smoothly assembles components in realistic scenes. Our experiments show that our RGBA diffusion model is capable of generating diverse and high quality instances with precise control over object attributes. Through multi-layer composition, we demonstrate that our approach allows to build and manipulate images from highly complex prompts with fine-grained control over object appearance and location, granting a higher degree of control than competing methods.

Guoxuan Xia, Harleen Hanspal, Petru-Daniel Tudosiu et al.

Enabling image generation models to be spatially controlled is an important area of research, empowering users to better generate images according to their own fine-grained specifications via e.g. edge maps, poses. Although this task has seen impressive improvements in recent times, a focus on rapidly producing stronger models has come at the cost of detailed and fair scientific comparison. Differing training data, model architectures and generation paradigms make it difficult to disentangle the factors contributing to performance. Meanwhile, the motivations and nuances of certain approaches become lost in the literature. In this work, we aim to provide clear takeaways across generation paradigms for practitioners wishing to develop transformer-based systems for spatially-controlled generation, clarifying the literature and addressing knowledge gaps. We perform controlled experiments on ImageNet across diffusion-based/flow-based and autoregressive (AR) models. First, we establish control token prefilling as a simple, general and performant baseline approach for transformers. We then investigate previously underexplored sampling time enhancements, showing that extending classifier-free guidance to control, as well as softmax truncation, have a strong impact on control-generation consistency. Finally, we re-clarify the motivation of adapter-based approaches, demonstrating that they mitigate "forgetting" and maintain generation quality when trained on limited downstream data, but underperform full training in terms of generation-control consistency.

Raman Dutt, Harleen Hanspal, Guoxuan Xia et al.

In this work, we undertake the challenge of augmenting the existing generative capabilities of pre-trained text-only large language models (LLMs) with multi-modal generation capability while satisfying two core constraints: C1 preserving the preservation of original language generative capabilities with negligible performance degradation, and C2 adhering to a small parameter budget to learn the new modality, ensuring scalability and efficiency. In contrast to current approaches that add dedicated modules, thereby significantly increasing the parameter count, we propose a method that leverages the underutilized capacity inherent in deep models. Specifically, we exploit the parameter redundancy within Mixture-of-Experts (MoEs) as a source of additional capacity for learning a new modality, enabling better parameter efficiency (C1). Moreover, we preserve the original language generation capabilities by applying low-rank adaptation exclusively to the tokens of the new modality (C2). Furthermore, we introduce a novel parameter initialization scheme based on the Gromov-Wasserstein distance to improve convergence and training stability. Through an extensive analysis of the routing mechanism, we uncover the emergence of modality-specific pathways and decreased redundancy within the experts that can efficiently unlock multi-modal generative capabilities. Overall, our method can be seamlessly applied to a wide range of contemporary LLMs, providing a new pathway for transitioning from uni-modal to multi-modal architectures.

Walter Hugo Lopez Pinaya, Petru-Daniel Tudosiu, Robert Gray et al.

Pathological brain appearances may be so heterogeneous as to be intelligible only as anomalies, defined by their deviation from normality rather than any specific pathological characteristic. Amongst the hardest tasks in medical imaging, detecting such anomalies requires models of the normal brain that combine compactness with the expressivity of the complex, long-range interactions that characterise its structural organisation. These are requirements transformers have arguably greater potential to satisfy than other current candidate architectures, but their application has been inhibited by their demands on data and computational resource. Here we combine the latent representation of vector quantised variational autoencoders with an ensemble of autoregressive transformers to enable unsupervised anomaly detection and segmentation defined by deviation from healthy brain imaging data, achievable at low computational cost, within relative modest data regimes. We compare our method to current state-of-the-art approaches across a series of experiments involving synthetic and real pathological lesions. On real lesions, we train our models on 15,000 radiologically normal participants from UK Biobank, and evaluate performance on four different brain MR datasets with small vessel disease, demyelinating lesions, and tumours. We demonstrate superior anomaly detection performance both image-wise and pixel-wise, achievable without post-processing. These results draw attention to the potential of transformers in this most challenging of imaging tasks.

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.