Delmiro Fernandez-Reyes

Hongxiang Lin, Matteo Figini, Felice D'Arco et al.

Low-field (<1T) magnetic resonance imaging (MRI) scanners remain in widespread use in low- and middle-income countries (LMICs) and are commonly used for some applications in higher income countries e.g. for small child patients with obesity, claustrophobia, implants, or tattoos. However, low-field MR images commonly have lower resolution and poorer contrast than images from high field (1.5T, 3T, and above). Here, we present Image Quality Transfer (IQT) to enhance low-field structural MRI by estimating from a low-field image the image we would have obtained from the same subject at high field. Our approach uses (i) a stochastic low-field image simulator as the forward model to capture uncertainty and variation in the contrast of low-field images corresponding to a particular high-field image, and (ii) an anisotropic U-Net variant specifically designed for the IQT inverse problem. We evaluate the proposed algorithm both in simulation and using multi-contrast (T1-weighted, T2-weighted, and fluid attenuated inversion recovery (FLAIR)) clinical low-field MRI data from an LMIC hospital. We show the efficacy of IQT in improving contrast and resolution of low-field MR images. We demonstrate that IQT-enhanced images have potential for enhancing visualisation of anatomical structures and pathological lesions of clinical relevance from the perspective of radiologists. IQT is proved to have capability of boosting the diagnostic value of low-field MRI, especially in low-resource settings.

Robert Carruthers, Isabel Straw, James K Ruffle et al.

Equity is widely held to be fundamental to the ethics of healthcare. In the context of clinical decision-making, it rests on the comparative fidelity of the intelligence -- evidence-based or intuitive -- guiding the management of each individual patient. Though brought to recent attention by the individuating power of contemporary machine learning, such epistemic equity arises in the context of any decision guidance, whether traditional or innovative. Yet no general framework for its quantification, let alone assurance, currently exists. Here we formulate epistemic equity in terms of model fidelity evaluated over learnt multi-dimensional representations of identity crafted to maximise the captured diversity of the population, introducing a comprehensive framework for Representational Ethical Model Calibration. We demonstrate use of the framework on large-scale multimodal data from UK Biobank to derive diverse representations of the population, quantify model performance, and institute responsive remediation. We offer our approach as a principled solution to quantifying and assuring epistemic equity in healthcare, with applications across the research, clinical, and regulatory domains.

Petru Manescu, Priya Narayanan, Christopher Bendkowski et al.

While optical microscopy inspection of blood films and bone marrow aspirates by a hematologist is a crucial step in establishing diagnosis of acute leukemia, especially in low-resource settings where other diagnostic modalities might not be available, the task remains time-consuming and prone to human inconsistencies. This has an impact especially in cases of Acute Promyelocytic Leukemia (APL) that require urgent treatment. Integration of automated computational hematopathology into clinical workflows can improve the throughput of these services and reduce cognitive human error. However, a major bottleneck in deploying such systems is a lack of sufficient cell morphological object-labels annotations to train deep learning models. We overcome this by leveraging patient diagnostic labels to train weakly-supervised models that detect different types of acute leukemia. We introduce a deep learning approach, Multiple Instance Learning for Leukocyte Identification (MILLIE), able to perform automated reliable analysis of blood films with minimal supervision. Without being trained to classify individual cells, MILLIE differentiates between acute lymphoblastic and myeloblastic leukemia in blood films. More importantly, MILLIE detects APL in blood films (AUC 0.94+/-0.04) and in bone marrow aspirates (AUC 0.99+/-0.01). MILLIE is a viable solution to augment the throughput of clinical pathways that require assessment of blood film microscopy.

Petru Manescu, Joseph Geradts, Delmiro Fernandez-Reyes

Hypoxia occurs when tumour cells outgrow their blood supply, leading to regions of low oxygen levels within the tumour. Calculating hypoxia levels can be an important step in understanding the biology of tumours, their clinical progression and response to treatment. This study demonstrates a novel application of deep learning to evaluate hypoxia in the context of breast cancer histomorphology. More precisely, we show that Weakly Supervised Deep Learning (WSDL) models can accurately detect hypoxia associated features in routine Hematoxylin and Eosin (H&E) whole slide images (WSI). We trained and evaluated a deep Multiple Instance Learning model on tiles from WSI H&E tissue from breast cancer primary sites (n=240) obtaining on average an AUC of 0.87 on a left-out test set. We also showed significant differences between features of hypoxic and normoxic tissue regions as distinguished by the WSDL models. Such DL hypoxia H&E WSI detection models could potentially be extended to other tumour types and easily integrated into the pathology workflow without requiring additional costly assays.

Gabriel Ansah, Eden Ruffell, Delmiro Fernandez-Reyes et al.

Automated blood morphology analysis can support hematological diagnostics in low- and middle-income countries (LMICs) but remains sensitive to dataset shifts from staining variability, imaging differences, and rare morphologies. Building centralized datasets to capture this diversity is often infeasible due to privacy regulations and data-sharing restrictions. We introduce a federated learning framework for white blood cell morphology analysis that enables collaborative training across institutions without exchanging training data. Using blood films from multiple clinical sites, our federated models learn robust, domain-invariant representations while preserving complete data privacy. Evaluations across convolutional and transformer-based architectures show that federated training achieves strong cross-site performance and improved generalization to unseen institutions compared to centralized training. These findings highlight federated learning as a practical and privacy-preserving approach for developing equitable, scalable, and generalizable medical imaging AI in resource-limited healthcare environments.

Jeremiah Fadugba, Petru Manescu, Bolanle Oladejo et al.

Uncertainty estimation is critical for reliable medical image segmentation, particularly in retinal vessel analysis, where accurate predictions are essential for diagnostic applications. Deep Ensembles, where multiple networks are trained individually, are widely used to improve medical image segmentation performance. However, training and testing costs increase with the number of ensembles. In this work, we propose Ensemble Distillation as a robust alternative to commonly used uncertainty estimation techniques by distilling the knowledge of multiple ensemble models into a single model. Through extensive experiments on the DRIVE and FIVES datasets, we demonstrate that Ensemble Distillation achieves comparable performance via calibration and segmentation metrics, while significantly reducing computational complexity. These findings suggest that Ensemble distillation provides an efficient and reliable approach for uncertainty estimation in the segmentation of the retinal vessels, making it a promising tool for medical imaging applications.

Matteo Figini, Hongxiang Lin, Godwin Ogbole et al.

1.5T or 3T scanners are the current standard for clinical MRI, but low-field (<1T) scanners are still common in many lower- and middle-income countries for reasons of cost and robustness to power failures. Compared to modern high-field scanners, low-field scanners provide images with lower signal-to-noise ratio at equivalent resolution, leaving practitioners to compensate by using large slice thickness and incomplete spatial coverage. Furthermore, the contrast between different types of brain tissue may be substantially reduced even at equal signal-to-noise ratio, which limits diagnostic value. Recently the paradigm of Image Quality Transfer has been applied to enhance 0.36T structural images aiming to approximate the resolution, spatial coverage, and contrast of typical 1.5T or 3T images. A variant of the neural network U-Net was trained using low-field images simulated from the publicly available 3T Human Connectome Project dataset. Here we present qualitative results from real and simulated clinical low-field brain images showing the potential value of IQT to enhance the clinical utility of readily accessible low-field MRIs in the management of epilepsy.

Hongxiang Lin, Matteo Figini, Ryutaro Tanno et al.

MR images scanned at low magnetic field ($<1$T) have lower resolution in the slice direction and lower contrast, due to a relatively small signal-to-noise ratio (SNR) than those from high field (typically 1.5T and 3T). We adapt the recent idea of Image Quality Transfer (IQT) to enhance very low-field structural images aiming to estimate the resolution, spatial coverage, and contrast of high-field images. Analogous to many learning-based image enhancement techniques, IQT generates training data from high-field scans alone by simulating low-field images through a pre-defined decimation model. However, the ground truth decimation model is not well-known in practice, and lack of its specification can bias the trained model, aggravating performance on the real low-field scans. In this paper we propose a probabilistic decimation simulator to improve robustness of model training. It is used to generate and augment various low-field images whose parameters are random variables and sampled from an empirical distribution related to tissue-specific SNR on a 0.36T scanner. The probabilistic decimation simulator is model-agnostic, that is, it can be used with any super-resolution networks. Furthermore we propose a variant of U-Net architecture to improve its learning performance. We show promising qualitative results from clinical low-field images confirming the strong efficacy of IQT in an important new application area: epilepsy diagnosis in sub-Saharan Africa where only low-field scanners are normally available.

Lydia Neary-Zajiczek, Clara Essmann, Neil Clancy et al.

Structural and mechanical differences between cancerous and healthy tissue give rise to variations in macroscopic properties such as visual appearance and elastic modulus that show promise as signatures for early cancer detection. Atomic force microscopy (AFM) has been used to measure significant differences in stiffness between cancerous and healthy cells owing to its high force sensitivity and spatial resolution, however due to absorption and scattering of light, it is often challenging to accurately locate where AFM measurements have been made on a bulk tissue sample. In this paper we describe an image registration method that localizes AFM elastic stiffness measurements with high-resolution images of haematoxylin and eosin (H\&E)-stained tissue to within 1.5 microns. Color RGB images are segmented into three structure types (lumen, cells and stroma) by a neural network classifier trained on ground-truth pixel data obtained through k-means clustering in HSV color space. Using the localized stiffness maps and corresponding structural information, a whole-sample stiffness map is generated with a region matching and interpolation algorithm that associates similar structures with measured stiffness values. We present results showing significant differences in stiffness between healthy and cancerous liver tissue and discuss potential applications of this technique.

Biobele J. Brown, Alexander A. Przybylski, Petru Manescu et al.

Plasmodium falciparum malaria still poses one of the greatest threats to human life with over 200 million cases globally leading to half-million deaths annually. Of these, 90% of cases and of the mortality occurs in sub-Saharan Africa, mostly among children. Although malaria prediction systems are central to the 2016-2030 malaria Global Technical Strategy, currently these are inadequate at capturing and estimating the burden of disease in highly endemic countries. We developed and validated a computational system that exploits the predictive power of current Machine Learning approaches on 22-years of prospective data from the high-transmission holoendemic malaria urban-densely-populated sub-Saharan West-Africa metropolis of Ibadan. Our dataset of >9x104 screened study participants attending our clinical and community services from 1996 to 2017 contains monthly prevalence, temporal, environmental and host features. Our Locality-specific Elastic-Net based Malaria Prediction System (LEMPS) achieves good generalization performance, both in magnitude and direction of the prediction, when tasked to predict monthly prevalence on previously unseen validation data (MAE<=6x10-2, MSE<=7x10-3) within a range of (+0.1 to -0.05) error-tolerance which is relevant and usable for aiding decision-support in a holoendemic setting. LEMPS is well-suited for malaria prediction, where there are multiple features which are correlated with one another, and trading-off between regularization-strength L1-norm and L2-norm allows the system to retain stability. Data-driven systems are critical for regionally-adaptable surveillance, management of control strategies and resource allocation across stretched healthcare systems.

Petru Manescu, Lydia Neary- Zajiczek, Michael J. Shaw et al.

Fast accurate diagnosis of malaria is still a global health challenge for which automated digital-pathology approaches could provide scalable solutions amenable to be deployed in low-to-middle income countries. Here we address the problem of Extended Depth-of-Field (EDoF) in thick blood film microscopy for rapid automated malaria diagnosis. High magnification oil-objectives (100x) with large numerical aperture are usually preferred to resolve the fine structural details that help separate true parasites from distractors. However, such objectives have a very limited depth-of-field requiring the acquisition of a series of images at different focal planes per field of view (FOV). Current EDoF techniques based on multi-scale decompositions are time consuming and therefore not suited for high-throughput analysis of specimens. To overcome this challenge, we developed a new deep learning method based on Convolutional Neural Networks (EDoF-CNN) that is able to rapidly perform the extended depth-of-field while also enhancing the spatial resolution of the resulting fused image. We evaluated our approach using simulated low-resolution z-stacks from Giemsa-stained thick blood smears from patients presenting with Plasmodium falciparum malaria. The EDoF-CNN allows speed-up of our digital-pathology acquisition platform and significantly improves the quality of the EDoF compared to the traditional multi-scaled approaches when applied to lower resolution stacks corresponding to acquisitions with fewer focal planes, large camera pixel binning or lower magnification objectives (larger FOV). We use the parasite detection accuracy of a deep learning model on the EDoFs as a concrete, task-specific measure of performance of this approach.

Viivi Uurtio, João M. Monteiro, Jaz Kandola et al.

Canonical correlation analysis is a family of multivariate statistical methods for the analysis of paired sets of variables. Since its proposition, canonical correlation analysis has for instance been extended to extract relations between two sets of variables when the sample size is insufficient in relation to the data dimensionality, when the relations have been considered to be non-linear, and when the dimensionality is too large for human interpretation. This tutorial explains the theory of canonical correlation analysis including its regularised, kernel, and sparse variants. Additionally, the deep and Bayesian CCA extensions are briefly reviewed. Together with the numerical examples, this overview provides a coherent compendium on the applicability of the variants of canonical correlation analysis. By bringing together techniques for solving the optimisation problems, evaluating the statistical significance and generalisability of the canonical correlation model, and interpreting the relations, we hope that this article can serve as a hands-on tool for applying canonical correlation methods in data analysis.

Dimitrios Athanasakis, John Shawe-Taylor, Delmiro Fernandez-Reyes

Recent non-linear feature selection approaches employing greedy optimisation of Centred Kernel Target Alignment(KTA) exhibit strong results in terms of generalisation accuracy and sparsity. However, they are computationally prohibitive for large datasets. We propose randSel, a randomised feature selection algorithm, with attractive scaling properties. Our theoretical analysis of randSel provides strong probabilistic guarantees for correct identification of relevant features. RandSel's characteristics make it an ideal candidate for identifying informative learned representations. We've conducted experimentation to establish the performance of this approach, and present encouraging results, including a 3rd position result in the recent ICML black box learning challenge as well as competitive results for signal peptide prediction, an important problem in bioinformatics.

Dimitrios Athanasakis, John Shawe-Taylor, Delmiro Fernandez-Reyes

Feature selection plays a pivotal role in learning, particularly in areas were parsimonious features can provide insight into the underlying process, such as biology. Recent approaches for non-linear feature selection employing greedy optimisation of Centred Kernel Target Alignment(KTA), while exhibiting strong results in terms of generalisation accuracy and sparsity, can become computationally prohibitive for high-dimensional datasets. We propose randSel, a randomised feature selection algorithm, with attractive scaling properties. Our theoretical analysis of randSel provides strong probabilistic guarantees for the correct identification of relevant features. Experimental results on real and artificial data, show that the method successfully identifies effective features, performing better than a number of competitive approaches.