Pedro Sanchez

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.

Pedro Sanchez, Antanas Kascenas, Xiao Liu et al.

Reducing the requirement for densely annotated masks in medical image segmentation is important due to cost constraints. In this paper, we consider the problem of inferring pixel-level predictions of brain lesions by only using image-level labels for training. By leveraging recent advances in generative diffusion probabilistic models (DPM), we synthesize counterfactuals of "How would a patient appear if X pathology was not present?". The difference image between the observed patient state and the healthy counterfactual can be used for inferring the location of pathology. We generate counterfactuals that correspond to the minimal change of the input such that it is transformed to healthy domain. This requires training with healthy and unhealthy data in DPMs. We improve on previous counterfactual DPMs by manipulating the generation process with implicit guidance along with attention conditioning instead of using classifiers. Code is available at https://github.com/vios-s/Diff-SCM.

Pedro Sanchez, Xiao Liu, Alison Q O'Neil et al.

Discovering causal relations from observational data becomes possible with additional assumptions such as considering the functional relations to be constrained as nonlinear with additive noise (ANM). Even with strong assumptions, causal discovery involves an expensive search problem over the space of directed acyclic graphs (DAGs). \emph{Topological ordering} approaches reduce the optimisation space of causal discovery by searching over a permutation rather than graph space. For ANMs, the \emph{Hessian} of the data log-likelihood can be used for finding leaf nodes in a causal graph, allowing its topological ordering. However, existing computational methods for obtaining the Hessian still do not scale as the number of variables and the number of samples increase. Therefore, inspired by recent innovations in diffusion probabilistic models (DPMs), we propose \emph{DiffAN}\footnote{Implementation is available at \url{https://github.com/vios-s/DiffAN} .}, a topological ordering algorithm that leverages DPMs for learning a Hessian function. We introduce theory for updating the learned Hessian without re-training the neural network, and we show that computing with a subset of samples gives an accurate approximation of the ordering, which allows scaling to datasets with more samples and variables. We show empirically that our method scales exceptionally well to datasets with up to $500$ nodes and up to $10^5$ samples while still performing on par over small datasets with state-of-the-art causal discovery methods. Implementation is available at https://github.com/vios-s/DiffAN .

Xiao Liu, Spyridon Thermos, Pedro Sanchez et al.

Training medical image segmentation models usually requires a large amount of labeled data. By contrast, humans can quickly learn to accurately recognise anatomy of interest from medical (e.g. MRI and CT) images with some limited guidance. Such recognition ability can easily generalise to new images from different clinical centres. This rapid and generalisable learning ability is mostly due to the compositional structure of image patterns in the human brain, which is less incorporated in medical image segmentation. In this paper, we model the compositional components (i.e. patterns) of human anatomy as learnable von-Mises-Fisher (vMF) kernels, which are robust to images collected from different domains (e.g. clinical centres). The image features can be decomposed to (or composed by) the components with the composing operations, i.e. the vMF likelihoods. The vMF likelihoods tell how likely each anatomical part is at each position of the image. Hence, the segmentation mask can be predicted based on the vMF likelihoods. Moreover, with a reconstruction module, unlabeled data can also be used to learn the vMF kernels and likelihoods by recombining them to reconstruct the input image. Extensive experiments show that the proposed vMFNet achieves improved generalisation performance on two benchmarks, especially when annotations are limited. Code is publicly available at: https://github.com/vios-s/vMFNet.

Pedro Sanchez, Jeremy P. Voisey, Tian Xia et al.

Causal machine learning (CML) has experienced increasing popularity in healthcare. Beyond the inherent capabilities of adding domain knowledge into learning systems, CML provides a complete toolset for investigating how a system would react to an intervention (e.g.\ outcome given a treatment). Quantifying effects of interventions allows actionable decisions to be made whilst maintaining robustness in the presence of confounders. Here, we explore how causal inference can be incorporated into different aspects of clinical decision support (CDS) systems by using recent advances in machine learning. Throughout this paper, we use Alzheimer's disease (AD) to create examples for illustrating how CML can be advantageous in clinical scenarios. Furthermore, we discuss important challenges present in healthcare applications such as processing high-dimensional and unstructured data, generalisation to out-of-distribution samples, and temporal relationships, that despite the great effort from the research community remain to be solved. Finally, we review lines of research within causal representation learning, causal discovery and causal reasoning which offer the potential towards addressing the aforementioned challenges.

Antanas Kascenas, Pedro Sanchez, Patrick Schrempf et al.

Pathological brain lesions exhibit diverse appearance in brain images, in terms of intensity, texture, shape, size, and location. Comprehensive sets of data and annotations are difficult to acquire. Therefore, unsupervised anomaly detection approaches have been proposed using only normal data for training, with the aim of detecting outlier anomalous voxels at test time. Denoising methods, for instance classical denoising autoencoders (DAEs) and more recently emerging diffusion models, are a promising approach, however naive application of pixelwise noise leads to poor anomaly detection performance. We show that optimization of the spatial resolution and magnitude of the noise improves the performance of different model training regimes, with similar noise parameter adjustments giving good performance for both DAEs and diffusion models. Visual inspection of the reconstructions suggests that the training noise influences the trade-off between the extent of the detail that is reconstructed and the extent of erasure of anomalies, both of which contribute to better anomaly detection performance. We validate our findings on two real-world datasets (tumor detection in brain MRI and hemorrhage/ischemia/tumor detection in brain CT), showing good detection on diverse anomaly appearances. Overall, we find that a DAE trained with coarse noise is a fast and simple method that gives state-of-the-art accuracy. Diffusion models applied to anomaly detection are as yet in their infancy and provide a promising avenue for further research.

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

Knowledge distillation in neural networks refers to compressing a large model or dataset into a smaller version of itself. We introduce Privacy Distillation, a framework that allows a text-to-image generative model to teach another model without exposing it to identifiable data. Here, we are interested in the privacy issue faced by a data provider who wishes to share their data via a multimodal generative model. A question that immediately arises is ``How can a data provider ensure that the generative model is not leaking identifiable information about a patient?''. Our solution consists of (1) training a first diffusion model on real data (2) generating a synthetic dataset using this model and filtering it to exclude images with a re-identifiability risk (3) training a second diffusion model on the filtered synthetic data only. We showcase that datasets sampled from models trained with privacy distillation can effectively reduce re-identification risk whilst maintaining downstream performance.

Tian Xia, Pedro Sanchez, Chen Qin et al.

Due to the limited availability of medical data, deep learning approaches for medical image analysis tend to generalise poorly to unseen data. Augmenting data during training with random transformations has been shown to help and became a ubiquitous technique for training neural networks. Here, we propose a novel adversarial counterfactual augmentation scheme that aims at finding the most \textit{effective} synthesised images to improve downstream tasks, given a pre-trained generative model. Specifically, we construct an adversarial game where we update the input \textit{conditional factor} of the generator and the downstream \textit{classifier} with gradient backpropagation alternatively and iteratively. This can be viewed as finding the `\textit{weakness}' of the classifier and purposely forcing it to \textit{overcome} its weakness via the generative model. To demonstrate the effectiveness of the proposed approach, we validate the method with the classification of Alzheimer's Disease (AD) as a downstream task. The pre-trained generative model synthesises brain images using age as conditional factor. Extensive experiments and ablation studies have been performed to show that the proposed approach improves classification performance and has potential to alleviate spurious correlations and catastrophic forgetting. Code will be released upon acceptance.

Konstantinos Vilouras, Xiao Liu, Pedro Sanchez et al.

Knowledge distillation enables fast and effective transfer of features learned from a bigger model to a smaller one. However, distillation objectives are susceptible to sub-population shifts, a common scenario in medical imaging analysis which refers to groups/domains of data that are underrepresented in the training set. For instance, training models on health data acquired from multiple scanners or hospitals can yield subpar performance for minority groups. In this paper, inspired by distributionally robust optimization (DRO) techniques, we address this shortcoming by proposing a group-aware distillation loss. During optimization, a set of weights is updated based on the per-group losses at a given iteration. This way, our method can dynamically focus on groups that have low performance during training. We empirically validate our method, GroupDistil on two benchmark datasets (natural images and cardiac MRIs) and show consistent improvement in terms of worst-group accuracy.

Xiao Liu, Pedro Sanchez, Spyridon Thermos et al.

Deep learning models often need sufficient supervision (i.e. labelled data) in order to be trained effectively. By contrast, humans can swiftly learn to identify important anatomy in medical images like MRI and CT scans, with minimal guidance. This recognition capability easily generalises to new images from different medical facilities and to new tasks in different settings. This rapid and generalisable learning ability is largely due to the compositional structure of image patterns in the human brain, which are not well represented in current medical models. In this paper, we study the utilisation of compositionality in learning more interpretable and generalisable representations for medical image segmentation. Overall, we propose that the underlying generative factors that are used to generate the medical images satisfy compositional equivariance property, where each factor is compositional (e.g. corresponds to the structures in human anatomy) and also equivariant to the task. Hence, a good representation that approximates well the ground truth factor has to be compositionally equivariant. By modelling the compositional representations with learnable von-Mises-Fisher (vMF) kernels, we explore how different design and learning biases can be used to enforce the representations to be more compositionally equivariant under un-, weakly-, and semi-supervised settings. Extensive results show that our methods achieve the best performance over several strong baselines on the task of semi-supervised domain-generalised medical image segmentation. Code will be made publicly available upon acceptance at https://github.com/vios-s.

Avinash Kori, Pedro Sanchez, Konstantinos Vilouras et al.

Unsupervised representation learning with variational inference relies heavily on independence assumptions over latent variables. Causal representation learning (CRL), however, argues that factors of variation in a dataset are, in fact, causally related. Allowing latent variables to be correlated, as a consequence of causal relationships, is more realistic and generalisable. So far, provably identifiable methods rely on: auxiliary information, weak labels, and interventional or even counterfactual data. Inspired by causal discovery with functional causal models, we propose a fully unsupervised representation learning method that considers a data generation process with a latent additive noise model (ANM). We encourage the latent space to follow a causal ordering via loss function based on the Hessian of the latent distribution.

Xiao Liu, Spyridon Thermos, Pedro Sanchez et al.

Learning disentangled representations requires either supervision or the introduction of specific model designs and learning constraints as biases. InfoGAN is a popular disentanglement framework that learns unsupervised disentangled representations by maximising the mutual information between latent representations and their corresponding generated images. Maximisation of mutual information is achieved by introducing an auxiliary network and training with a latent regression loss. In this short exploratory paper, we study the use of the Hilbert-Schmidt Independence Criterion (HSIC) to approximate mutual information between latent representation and image, termed HSIC-InfoGAN. Directly optimising the HSIC loss avoids the need for an additional auxiliary network. We qualitatively compare the level of disentanglement in each model, suggest a strategy to tune the hyperparameters of HSIC-InfoGAN, and discuss the potential of HSIC-InfoGAN for medical applications.

Thomas Melistas, Nikos Spyrou, Nefeli Gkouti et al.

Generative AI has revolutionised visual content editing, empowering users to effortlessly modify images and videos. However, not all edits are equal. To perform realistic edits in domains such as natural image or medical imaging, modifications must respect causal relationships inherent to the data generation process. Such image editing falls into the counterfactual image generation regime. Evaluating counterfactual image generation is substantially complex: not only it lacks observable ground truths, but also requires adherence to causal constraints. Although several counterfactual image generation methods and evaluation metrics exist, a comprehensive comparison within a unified setting is lacking. We present a comparison framework to thoroughly benchmark counterfactual image generation methods. We integrate all models that have been used for the task at hand and expand them to novel datasets and causal graphs, demonstrating the superiority of Hierarchical VAEs across most datasets and metrics. Our framework is implemented in a user-friendly Python package that can be extended to incorporate additional SCMs, causal methods, generative models, and datasets for the community to build on. Code: https://github.com/gulnazaki/counterfactual-benchmark.

Raman Dutt, Pedro Sanchez, Ondrej Bohdal et al.

In this work, we present compelling evidence that controlling model capacity during fine-tuning can effectively mitigate memorization in diffusion models. Specifically, we demonstrate that adopting Parameter-Efficient Fine-Tuning (PEFT) within the pre-train fine-tune paradigm significantly reduces memorization compared to traditional full fine-tuning approaches. Our experiments utilize the MIMIC dataset, which comprises image-text pairs of chest X-rays and their corresponding reports. The results, evaluated through a range of memorization and generation quality metrics, indicate that PEFT not only diminishes memorization but also enhances downstream generation quality. Additionally, PEFT methods can be seamlessly combined with existing memorization mitigation techniques for further improvement. The code for our experiments is available at: https://github.com/Raman1121/Diffusion_Memorization_HPO

Pedro Sanchez, Sotirios A. Tsaftaris

We consider the task of counterfactual estimation from observational imaging data given a known causal structure. In particular, quantifying the causal effect of interventions for high-dimensional data with neural networks remains an open challenge. Herein we propose Diff-SCM, a deep structural causal model that builds on recent advances of generative energy-based models. In our setting, inference is performed by iteratively sampling gradients of the marginal and conditional distributions entailed by the causal model. Counterfactual estimation is achieved by firstly inferring latent variables with deterministic forward diffusion, then intervening on a reverse diffusion process using the gradients of an anti-causal predictor w.r.t the input. Furthermore, we propose a metric for evaluating the generated counterfactuals. We find that Diff-SCM produces more realistic and minimal counterfactuals than baselines on MNIST data and can also be applied to ImageNet data. Code is available https://github.com/vios-s/Diff-SCM.

Konstantinos Vilouras, Pedro Sanchez, Alison Q. O'Neil et al.

Localizing the exact pathological regions in a given medical scan is an important imaging problem that traditionally requires a large amount of bounding box ground truth annotations to be accurately solved. However, there exist alternative, potentially weaker, forms of supervision, such as accompanying free-text reports, which are readily available. The task of performing localization with textual guidance is commonly referred to as phrase grounding. In this work, we use a publicly available Foundation Model, namely the Latent Diffusion Model, to perform this challenging task. This choice is supported by the fact that the Latent Diffusion Model, despite being generative in nature, contains cross-attention mechanisms that implicitly align visual and textual features, thus leading to intermediate representations that are suitable for the task at hand. In addition, we aim to perform this task in a zero-shot manner, i.e., without any training on the target task, meaning that the model's weights remain frozen. To this end, we devise strategies to select features and also refine them via post-processing without extra learnable parameters. We compare our proposed method with state-of-the-art approaches which explicitly enforce image-text alignment in a joint embedding space via contrastive learning. Results on a popular chest X-ray benchmark indicate that our method is competitive with SOTA on different types of pathology, and even outperforms them on average in terms of two metrics (mean IoU and AUC-ROC). Source code will be released upon acceptance at https://github.com/vios-s.

Raman Dutt, Pedro Sanchez, Yongchen Yao et al.

We introduce CheXGenBench, a rigorous and multifaceted evaluation framework for synthetic chest radiograph generation that simultaneously assesses fidelity, privacy risks, and clinical utility across state-of-the-art text-to-image generative models. Despite rapid advancements in generative AI for real-world imagery, medical domain evaluations have been hindered by methodological inconsistencies, outdated architectural comparisons, and disconnected assessment criteria that rarely address the practical clinical value of synthetic samples. CheXGenBench overcomes these limitations through standardised data partitioning and a unified evaluation protocol comprising over 20 quantitative metrics that systematically analyse generation quality, potential privacy vulnerabilities, and downstream clinical applicability across 11 leading text-to-image architectures. Our results reveal critical inefficiencies in the existing evaluation protocols, particularly in assessing generative fidelity, leading to inconsistent and uninformative comparisons. Our framework establishes a standardised benchmark for the medical AI community, enabling objective and reproducible comparisons while facilitating seamless integration of both existing and future generative models. Additionally, we release a high-quality, synthetic dataset, SynthCheX-75K, comprising 75K radiographs generated by the top-performing model (Sana 0.6B) in our benchmark to support further research in this critical domain. Through CheXGenBench, we establish a new state-of-the-art and release our framework, models, and SynthCheX-75K dataset at https://raman1121.github.io/CheXGenBench/

Raman Dutt, Linus Ericsson, Pedro Sanchez et al.

Foundation models have significantly advanced medical image analysis through the pre-train fine-tune paradigm. Among various fine-tuning algorithms, Parameter-Efficient Fine-Tuning (PEFT) is increasingly utilized for knowledge transfer across diverse tasks, including vision-language and text-to-image generation. However, its application in medical image analysis is relatively unexplored due to the lack of a structured benchmark for evaluating PEFT methods. This study fills this gap by evaluating 17 distinct PEFT algorithms across convolutional and transformer-based networks on image classification and text-to-image generation tasks using six medical datasets of varying size, modality, and complexity. Through a battery of over 700 controlled experiments, our findings demonstrate PEFT's effectiveness, particularly in low data regimes common in medical imaging, with performance gains of up to 22% in discriminative and generative tasks. These recommendations can assist the community in incorporating PEFT into their workflows and facilitate fair comparisons of future PEFT methods, ensuring alignment with advancements in other areas of machine learning and AI.

Xiao Liu, Pedro Sanchez, Spyridon Thermos et al.

Disentangled representation learning has been proposed as an approach to learning general representations even in the absence of, or with limited, supervision. A good general representation can be fine-tuned for new target tasks using modest amounts of data, or used directly in unseen domains achieving remarkable performance in the corresponding task. This alleviation of the data and annotation requirements offers tantalising prospects for applications in computer vision and healthcare. In this tutorial paper, we motivate the need for disentangled representations, revisit key concepts, and describe practical building blocks and criteria for learning such representations. We survey applications in medical imaging emphasising choices made in exemplar key works, and then discuss links to computer vision applications. We conclude by presenting limitations, challenges, and opportunities.