Publications

The developing Human Connectome Project (dHCP) automated resting-state functional processing framework for newborn infants

The developing Human Connectome Project (dHCP) automated resting-state functional processing framework for newborn infants

The developing Human Connectome Project (dHCP) aims to create a detailed 4-dimensional connectome of early life spanning 20–45 weeks post-menstrual age. This is being achieved through the acquisition of multi-modal MRI data from over 1000 in- and ex-utero subjects combined with the development of optimised pre-processing pipelines. In this paper we present an automated and robust pipeline to minimally pre-process highly confounded neonatal resting-state fMRI data, robustly, with low failure rates and high quality-assurance. The pipeline has been designed to specifically address the challenges that neonatal data presents including low and variable contrast and high levels of head motion. We provide a detailed description and evaluation of the pipeline which includes integrated slice-to-volume motion correction and dynamic susceptibility distortion correction, a robust multimodal registration approach, bespoke ICA-based denoising, and an automated QC framework. We assess these components on a large cohort of dHCP subjects and demonstrate that processing refinements integrated into the pipeline provide substantial reduction in movement related distortions, resulting in significant improvements in SNR, and detection of high quality RSNs from neonates.

Model-Based and Data-Driven Strategies in Medical Image Computing

Model-Based and Data-Driven Strategies in Medical Image Computing

Model-based approaches for image reconstruction, analysis, and interpretation have made significant progress over the past decades. Many of these approaches are based on either mathematical, physical, or biological models. A challenge for these approaches is the modeling of the underlying processes (e.g., the physics of image acquisition or the patho-physiology of a disease) with appropriate levels of detail and realism. With the availability of large amounts of imaging data and machine learning (in particular deep learning) techniques, data-driven approaches have become more widespread for use in different tasks in reconstruction, analysis, and interpretation. These approaches learn statistical models directly from labeled or unlabeled image data and have been shown to be very powerful for extracting clinically useful information from medical imaging. While these data-driven approaches often outperform traditional model-based approaches, their clinical deployment often poses challenges in terms of robustness, generalization ability, and interpretability. In this article, we discuss what developments have motivated the shift from model-based approaches toward data-driven strategies and what potential problems are associated with the move toward purely data-driven approaches, in particular deep learning. We also discuss some of the open challenges for data-driven approaches, e.g., generalization to new unseen data (e.g., transfer learning), robustness to adversarial attacks, and interpretability. Finally, we conclude with a discussion on how these approaches may lead to the development of more closely coupled imaging pipelines that are optimized in an end-to-end fashion.

Genetic and functional insights into the fractal structure of the heart

Genetic and functional insights into the fractal structure of the heart

The inner surfaces of the human heart are covered by a complex network of muscular strands that is thought to be a remnant of embryonic development. The function of these trabeculae in adults and their genetic architecture are unknown. Here we performed a genome-wide association study to investigate image-derived phenotypes of trabeculae using the fractal analysis of trabecular morphology in 18,096 participants of the UK Biobank. We identified 16 significant loci that contain genes associated with haemodynamic phenotypes and regulation of cytoskeletal arborization3,4. Using biomechanical simulations and observational data from human participants, we demonstrate that trabecular morphology is an important determinant of cardiac performance. Through genetic association studies with cardiac disease phenotypes and Mendelian randomization, we find a causal relationship between trabecular morphology and risk of cardiovascular disease. These findings suggest a previously unknown role for myocardial trabeculae in the function of the adult heart, identify conserved pathways that regulate structural complexity and reveal the influence of the myocardial trabeculae on susceptibility to cardiovascular disease.

A population-based phenome-wide association study of cardiac and aortic structure and function

A population-based phenome-wide association study of cardiac and aortic structure and function

Differences in cardiac and aortic structure and function are associated with cardiovascular diseases and a wide range of other types of disease. Here we analyzed cardiovascular magnetic resonance images from a population-based study, the UK Biobank, using an automated machine-learning-based analysis pipeline. We report a comprehensive range of structural and functional phenotypes for the heart and aorta across 26,893 participants, and explore how these phenotypes vary according to sex, age and major cardiovascular risk factors. We extended this analysis with a phenome-wide association study, in which we tested for correlations of a wide range of non-imaging phenotypes of the participants with imaging phenotypes. We further explored the associations of imaging phenotypes with early-life factors, mental health and cognitive function using both observational analysis and Mendelian randomization. Our study illustrates how population-based cardiac and aortic imaging phenotypes can be used to better define cardiovascular disease risks as well as heart–brain health interactions, highlighting new opportunities for studying disease mechanisms and developing image-based biomarkers.