Imperial College London

DrWenjiaBai

Faculty of MedicineDepartment of Brain Sciences

Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 7594 8291w.bai Website

 
 
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Location

 

Room 212, Data Science InstituteWilliam Penney LaboratorySouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
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154 results found

Qin C, Wang S, Chen C, Bai W, Rueckert Det al., 2022, Generative myocardial motion tracking via latent space exploration with biomechanics-informed prior., Med Image Anal, Vol: 83

Myocardial motion and deformation are rich descriptors that characterize cardiac function. Image registration, as the most commonly used technique for myocardial motion tracking, is an ill-posed inverse problem which often requires prior assumptions on the solution space. In contrast to most existing approaches which impose explicit generic regularization such as smoothness, in this work we propose a novel method that can implicitly learn an application-specific biomechanics-informed prior and embed it into a neural network-parameterized transformation model. Particularly, the proposed method leverages a variational autoencoder-based generative model to learn a manifold for biomechanically plausible deformations. The motion tracking then can be performed via traversing the learnt manifold to search for the optimal transformations while considering the sequence information. The proposed method is validated on three public cardiac cine MRI datasets with comprehensive evaluations. The results demonstrate that the proposed method can outperform other approaches, yielding higher motion tracking accuracy with reasonable volume preservation and better generalizability to varying data distributions. It also enables better estimates of myocardial strains, which indicates the potential of the method in characterizing spatiotemporal signatures for understanding cardiovascular diseases.

Journal article

Kart T, Fischer M, Winzeck S, Glocker B, Bai W, Buelow R, Emmel C, Friedrich L, Kauczor H-U, Keil T, Kroencke T, Mayer P, Niendorf T, Peters A, Pischon T, Schaarschmidt BM, Schmidt B, Schulze MB, Umutle L, Voelzke H, Kuestner T, Bamberg F, Schoelkopf B, Rueckert D, Gatidis Set al., 2022, Automated imaging-based abdominal organ segmentation and quality control in 20,000 participants of the UK Biobank and German National Cohort Studies, SCIENTIFIC REPORTS, Vol: 12, ISSN: 2045-2322

Journal article

Chen C, Qin C, Ouyang C, Li Z, Wang S, Qiu H, Chen L, Tarroni G, Bai W, Rueckert Det al., 2022, Enhancing MR image segmentation with realistic adversarial data augmentation, Medical Image Analysis, Vol: 82, Pages: 1-15, ISSN: 1361-8415

The success of neural networks on medical image segmentation tasks typicallyrelies on large labeled datasets for model training. However, acquiring andmanually labeling a large medical image set is resource-intensive, expensive,and sometimes impractical due to data sharing and privacy issues. To addressthis challenge, we propose AdvChain, a generic adversarial data augmentationframework, aiming at improving both the diversity and effectiveness of trainingdata for medical image segmentation tasks. AdvChain augments data with dynamicdata augmentation, generating randomly chained photo-metric and geometrictransformations to resemble realistic yet challenging imaging variations toexpand training data. By jointly optimizing the data augmentation model and asegmentation network during training, challenging examples are generated toenhance network generalizability for the downstream task. The proposedadversarial data augmentation does not rely on generative networks and can beused as a plug-in module in general segmentation networks. It iscomputationally efficient and applicable for both low-shot supervised andsemi-supervised learning. We analyze and evaluate the method on two MR imagesegmentation tasks: cardiac segmentation and prostate segmentation with limitedlabeled data. Results show that the proposed approach can alleviate the needfor labeled data while improving model generalization ability, indicating itspractical value in medical imaging applications.

Journal article

Basaran B, Matthews PM, Bai W, 2022, New lesion segmentation for multiple sclerosis brain images with imaging and lesion-aware augmentation, Frontiers in Neuroscience, Vol: 16, ISSN: 1662-453X

Multiple sclerosis (MS) is an inflammatory and demyelinating neurological disease of the central nervous system. Image-based biomarkers, such as lesions defined on magnetic resonance imaging (MRI), play an important role in MS diagnosis and patient monitoring. The detection of newly formed lesions provides crucial information for assessing disease progression and treatment outcome. Here, we propose a deep learning-based pipeline for new MS lesion detection and segmentation, which is built upon the nnU-Net framework. In addition to conventional data augmentation, we employ imaging and lesion-aware data augmentation methods, axial subsampling and CarveMix, to generate diverse samples and improve segmentation performance. The proposed pipeline is evaluated on the MICCAI 2021 MS new lesion segmentation challenge (MSSEG-2) dataset. It achieves an average Dice score of 0.510 and F1 score of 0.552 on cases with new lesions, and an average false positive lesion number nFP of 0.036 and false positive lesion volume VFP of 0.192 mm3 on cases with no new lesions. Our method outperforms other participating methods in the challenge and several state-of-the-art network architectures.

Journal article

Basaran BD, Qiao M, Matthews P, Bai Wet al., 2022, Subject-specific lesion generation and pseudo-healthy synthesis for multiple sclerosis brain images, SASHIMI: Simulation and Synthesis in Medical Imaging, Publisher: Springer, ISSN: 0302-9743

Understanding the intensity characteristics of brain lesions is key for defining image-based biomarkers in neurological studies and for predicting disease burden and outcome. In this work, we present a novel foreground-based generative method for modelling the local lesion characteristics that can both generate synthetic lesions on healthy images and synthesize subject-specific pseudo-healthy images from pathological images. Furthermore, the proposed method can be used as a data augmentation module to generate synthetic images for training brain image segmentation networks. Experiments on multiple sclerosis (MS) brain images acquired on magnetic resonance imaging (MRI) demonstrate that the proposed method can generate highly realistic pseudo-healthy and pseudo-pathological brain images. Data augmentation using the synthetic images improves the brain image segmentation performance compared to traditional data augmentation methods as well as a recent lesion-aware data augmentation technique, CarveMix. The code will be released at https://github.com/dogabasaran/lesion-synthesis.

Conference paper

Chen C, Li Z, Ouyang C, Sinclair M, Bai W, Rueckert Det al., 2022, MaxStyle: adversarial style composition for robust medical image segmentation, Medical Image Computing and Computer Assisted Interventions (MICCAI) 2022

Convolutional neural networks (CNNs) have achieved remarkable segmentationaccuracy on benchmark datasets where training and test sets are from the samedomain, yet their performance can degrade significantly on unseen domains,which hinders the deployment of CNNs in many clinical scenarios. Most existingworks improve model out-of-domain (OOD) robustness by collecting multi-domaindatasets for training, which is expensive and may not always be feasible due toprivacy and logistical issues. In this work, we focus on improving modelrobustness using a single-domain dataset only. We propose a novel dataaugmentation framework called MaxStyle, which maximizes the effectiveness ofstyle augmentation for model OOD performance. It attaches an auxiliarystyle-augmented image decoder to a segmentation network for robust featurelearning and data augmentation. Importantly, MaxStyle augments data withimproved image style diversity and hardness, by expanding the style space withnoise and searching for the worst-case style composition of latent features viaadversarial training. With extensive experiments on multiple public cardiac andprostate MR datasets, we demonstrate that MaxStyle leads to significantlyimproved out-of-distribution robustness against unseen corruptions as well ascommon distribution shifts across multiple, different, unseen sites and unknownimage sequences under both low- and high-training data settings. The code canbe found at https://github.com/cherise215/MaxStyle.

Conference paper

Francis C, Futschik M, Huang J, Bai W, Sargurupremraj M, Teumer A, Breteler M, Petretto E, SR HO A, Amouyel P, Engelter S, Bülow R, Völker U, Völzke H, Dörr M, Imtiaz M-A, Aziz A, Lohner V, Ware J, Debette S, Elliott P, Dehghan A, Matthews Pet al., 2022, Genome-wide associations of aortic distensibility suggest causality for aortic aneurysms and brain white matter hyperintensities, Nature Communications, Vol: 13, ISSN: 2041-1723

Aortic dimensions and distensibility are key risk factors for aortic aneurysms and dissections, as well as for other cardiovascular and cerebrovascular diseases. We present genome-wide associations of ascending and descending aortic distensibility and area derived from cardiac magnetic resonance imaging (MRI) data of up to 32,590 Caucasian individuals in UK Biobank. We identify 102 loci (including 27 novel associations) tagging genes related to cardiovascular development, extracellular matrix production, smooth muscle cell contraction and heritable aortic diseases. Functional analyses highlight four signalling pathways associated with aortic distensibility (TGF-, IGF, VEGF and PDGF). We identify distinct sex-specific associations with aortic traits. We develop co-expression networks associated with aortic traits and apply phenome-wide Mendelian randomization (MR-PheWAS), generating evidence for a causal role for aortic distensibility in development of aortic aneurysms. Multivariable MR suggests a causal relationship between aortic distensibility and cerebral white matter hyperintensities, mechanistically linking aortic traits and brain small vessel disease.

Journal article

Meng Q, Bai W, Liu T, Simoes Monteiro de Marvao A, O'Regan D, Rueckert Det al., 2022, MulViMotion: shape-aware 3D myocardial motion tracking from multi-view cardiac MRI, IEEE Transactions on Medical Imaging, Vol: 41, Pages: 1961-1974, ISSN: 0278-0062

Recovering the 3D motion of the heart from cine cardiac magnetic resonance (CMR) imaging enables the assessment of regional myocardial function and is important for understanding and analyzing cardiovascular disease. However, 3D cardiac motion estimation is challenging because the acquired cine CMR images are usually 2D slices which limit the accurate estimation of through-plane motion. To address this problem, we propose a novel multi-view motion estimation network (MulViMotion), which integrates 2D cine CMR images acquired in short-axis and long-axis planes to learn a consistent 3D motion field of the heart. In the proposed method, a hybrid 2D/3D network is built to generate dense 3D motion fields by learning fused representations from multi-view images. To ensure that the motion estimation is consistent in 3D, a shape regularization module is introduced during training, where shape information from multi-view images is exploited to provide weak supervision to 3D motion estimation. We extensively evaluate the proposed method on 2D cine CMR images from 580 subjects of the UK Biobank study for 3D motion tracking of the left ventricular myocardium. Experimental results show that the proposed method quantitatively and qualitatively outperforms competing methods.

Journal article

Wang Y, Blackie L, Miguel-Aliaga I, Bai Wet al., 2022, Memory-efficient segmentation of high-resolution volumetric MicroCTimages, Publisher: ArXiv

In recent years, 3D convolutional neural networks have become the dominantapproach for volumetric medical image segmentation. However, compared to their2D counterparts, 3D networks introduce substantially more training parametersand higher requirement for the GPU memory. This has become a major limitingfactor for designing and training 3D networks for high-resolution volumetricimages. In this work, we propose a novel memory-efficient network architecturefor 3D high-resolution image segmentation. The network incorporates both globaland local features via a two-stage U-net-based cascaded framework and at thefirst stage, a memory-efficient U-net (meU-net) is developed. The featureslearnt at the two stages are connected via post-concatenation, which furtherimproves the information flow. The proposed segmentation method is evaluated onan ultra high-resolution microCT dataset with typically 250 million voxels pervolume. Experiments show that it outperforms state-of-the-art 3D segmentationmethods in terms of both segmentation accuracy and memory efficiency.

Working paper

Thanaj M, Mielke J, McGurk K, Bai W, Savioli N, Simoes Monteiro de Marvao A, Meyer H, Zeng L, Sohler F, Lumbers T, Wilkins M, Ware J, Bender C, Rueckert D, MacNamara A, Freitag D, O'Regan Det al., 2022, Genetic and environmental determinants of diastolic heart function, Nature Cardiovascular Research, Vol: 1, Pages: 361-371, ISSN: 2731-0590

Diastole is the sequence of physiological events that occur in the heart during ventricular filling and principally depends onmyocardial relaxation and chamber stiffness. Abnormal diastolic function is related to many cardiovascular disease processesand is predictive of health outcomes, but its genetic architecture is largely unknown. Here, we use machine learning cardiacmotion analysis to measure diastolic functional traits in 39,559 participants of the UK Biobank and perform a genome-wideassociation study. We identified 9 significant, independent loci near genes that are associated with maintaining sarcomericfunction under biomechanical stress and genes implicated in the development of cardiomyopathy. Age, sex and diabetes wereindependent predictors of diastolic function and we found a causal relationship between genetically-determined ventricularstiffness and incident heart failure. Our results provide insights into the genetic and environmental factors influencing diastolicfunction that are relevant for identifying causal relationships and potential tractable targets.

Journal article

Zhang D, Barbot A, Seichepine F, Lo FP-W, Bai W, Yang G-Z, Lo Bet al., 2022, Micro-object pose estimation with sim-to-real transfer learning using small dataset, Communications Physics, Vol: 5, ISSN: 2399-3650

Journal article

Davies RH, Augusto JB, Bhuva A, Xue H, Treibel TA, Ye Y, Hughes RK, Bai W, Lau C, Shiwani H, Fontana M, Kozor R, Herrey A, Lopes LR, Maestrini V, Rosmini S, Petersen SE, Kellman P, Rueckert D, Greenwood JP, Captur G, Manisty C, Schelbert E, Moon JCet al., 2022, Precision measurement of cardiac structure and function in cardiovascular magnetic resonance using machine learning, Journal of Cardiovascular Magnetic Resonance, Vol: 24, ISSN: 1097-6647

BackgroundMeasurement of cardiac structure and function from images (e.g. volumes, mass and derived parameters such as left ventricular (LV) ejection fraction [LVEF]) guides care for millions. This is best assessed using cardiovascular magnetic resonance (CMR), but image analysis is currently performed by individual clinicians, which introduces error. We sought to develop a machine learning algorithm for volumetric analysis of CMR images with demonstrably better precision than human analysis.MethodsA fully automated machine learning algorithm was trained on 1923 scans (10 scanner models, 13 institutions, 9 clinical conditions, 60,000 contours) and used to segment the LV blood volume and myocardium. Performance was quantified by measuring precision on an independent multi-site validation dataset with multiple pathologies with n = 109 patients, scanned twice. This dataset was augmented with a further 1277 patients scanned as part of routine clinical care to allow qualitative assessment of generalization ability by identifying mis-segmentations. Machine learning algorithm (‘machine’) performance was compared to three clinicians (‘human’) and a commercial tool (cvi42, Circle Cardiovascular Imaging).FindingsMachine analysis was quicker (20 s per patient) than human (13 min). Overall machine mis-segmentation rate was 1 in 479 images for the combined dataset, occurring mostly in rare pathologies not encountered in training. Without correcting these mis-segmentations, machine analysis had superior precision to three clinicians (e.g. scan-rescan coefficients of variation of human vs machine: LVEF 6.0% vs 4.2%, LV mass 4.8% vs. 3.6%; both P < 0.05), translating to a 46% reduction in required trial sample size using an LVEF endpoint.ConclusionWe present a fully automated algorithm for measuring LV structure and global systolic function that betters human performance for speed and precision.

Journal article

Meng Q, Bai W, Liu T, Simoes Monteiro de Marvao A, O'Regan D, Rueckert Det al., 2022, Multiview Motion Estimation for 3D cardiac motion tracking

Code for paper ''MulViMotion: Shape-aware 3D Myocardial Motion Tracking from Multi-View Cardiac MRI''

Software

Dai C, Wang S, Mo Y, Angelini E, Guo Y, Bai Wet al., 2022, Suggestive annotation of brain MR images with gradient-guided sampling, Medical Image Analysis, Vol: 77, Pages: 1-12, ISSN: 1361-8415

Machine learning has been widely adopted for medical image analysis in recent years given its promising performance in image segmentation and classification tasks. The success of machine learning, in particular supervised learning, depends on the availability of manually annotated datasets. For medical imaging applications, such annotated datasets are not easy to acquire, it takes a substantial amount of time and resource to curate an annotated medical image set. In this paper, we propose an efficient annotation framework for brain MR images that can suggest informative sample images for human experts to annotate. We evaluate the framework on two different brain image analysis tasks, namely brain tumour segmentation and whole brain segmentation. Experiments show that for brain tumour segmentation task on the BraTS 2019 dataset, training a segmentation model with only 7% suggestively annotated image samples can achieve a performance comparable to that of training on the full dataset. For whole brain segmentation on the MALC dataset, training with 42% suggestively annotated image samples can achieve a comparable performance to training on the full dataset. The proposed framework demonstrates a promising way to save manual annotation cost and improve data efficiency in medical imaging applications.

Journal article

Meng Q, Bai W, Liu T, O'Regan DP, Rueckert Det al., 2022, Mesh-Based 3D Motion Tracking in Cardiac MRI Using Deep Learning, 25th International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI), Publisher: SPRINGER INTERNATIONAL PUBLISHING AG, Pages: 248-258, ISSN: 0302-9743

Conference paper

Ouyang C, Wang S, Chen C, Li Z, Bai W, Kainz B, Rueckert Det al., 2022, Improved Post-hoc Probability Calibration for Out-of-Domain MRI Segmentation, Editors: Sudre, Baumgartner, Dalca, Qin, Tanno, VanLeemput, Wells, Publisher: SPRINGER INTERNATIONAL PUBLISHING AG, Pages: 59-69, ISBN: 978-3-031-16748-5

Book chapter

Ouyang C, Chen C, Li S, Li Z, Qin C, Bai W, Rueckert Det al., 2022, Causality-inspired Single-source Domain Generalization for Medical Image Segmentation, IEEE Transactions on Medical Imaging, Pages: 1-1, ISSN: 0278-0062

Journal article

Venkataraman AV, Bai W, Whittington A, Myers JF, Rabiner EA, Lingford-Hughes A, Matthews PMet al., 2021, Boosting the diagnostic power of amyloid-β PET using a data-driven spatially informed classifier for decision support, Alzheimer's Research and Therapy, Vol: 13, Pages: 1-12, ISSN: 1758-9193

BackgroundAmyloid-β (Aβ) PET has emerged as clinically useful for more accurate diagnosis of patients with cognitive decline. Aβ deposition is a necessary cause or response to the cellular pathology of Alzheimer’s disease (AD). Usual clinical and research interpretation of amyloid PET does not fully utilise all information regarding the spatial distribution of signal. We present a data-driven, spatially informed classifier to boost the diagnostic power of amyloid PET in AD.MethodsVoxel-wise k-means clustering of amyloid-positive voxels was performed; clusters were mapped to brain anatomy and tested for their associations by diagnostic category and disease severity with 758 amyloid PET scans from volunteers in the AD continuum from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). A machine learning approach based on this spatially constrained model using an optimised quadratic support vector machine was developed for automatic classification of scans for AD vs non-AD pathology.ResultsThis classifier boosted the accuracy of classification of AD scans to 81% using the amyloid PET alone with an area under the curve (AUC) of 0.91 compared to other spatial methods. This increased sensitivity to detect AD by 15% and the AUC by 9% compared to the use of a composite region of interest SUVr.ConclusionsThe diagnostic classification accuracy of amyloid PET was improved using an automated data-driven spatial classifier. Our classifier highlights the importance of considering the spatial variation in Aβ PET signal for optimal interpretation of scans. The algorithm now is available to be evaluated prospectively as a tool for automated clinical decision support in research settings.

Journal article

De Marvao A, McGurk K, Zheng S, Thanaj M, Bai W, Duan J, Halliday B, Pantazis A, Prasad S, Rueckert D, Walsh R, Ho C, Cook S, Ware J, O'Regan Det al., 2021, Outcomes and phenotypic expression of rare variants in hypertrophic cardiomyopathy genes in over 200,000 adults, ESC Congress 2021, Publisher: European Society of Cardiology, Pages: 1731-1731, ISSN: 0195-668X

BackgroundHypertrophic cardiomyopathy (HCM) is caused by rare variants in sarcomere-encoding genes, but little is known about the clinical significance of these variants in the general population.PurposeTo determine the population prevalence of HCM-associated sarcomeric variants, characterise their phenotypic manifestations, estimate penetrance, and identify associations between sarcomeric variants and clinical outcomes, we performed an observational study of 218,813 adults in the UK Biobank (UKBB), of whom 200,584 have whole exome sequencing (WES).MethodsWe carried out an integrated analysis of WES and cardiac magnetic resonance (CMR) imaging in UK Biobank participants stratified by sarcomere-encoding variant status. Computer vision techniques were used to automatically segment the four chambers of the heart (Figure 1). Cardiac motion analysis was used to derive strain and strain rates. Regional analysis of left ventricular wall thickness was performed using three-dimensional modelling of these segmentations.ResultsMedian age at recruitment was 58 (IQR 50–63 years), and participants were followed up for a median of 10.8 years (IQR 9.9–11.6 years) with a total of 19,507 primary clinical events reported.The prevalence of rare variants (allele frequency <0.ehab724.17314) in HCM-associated sarcomere-encoding genes in 200,584 participants was 2.9% (n=5,727; 1 in 35), and the prevalence of pathogenic or likely pathogenic variants (SARC-P/LP) was 0.24% (n=474, 1 in 423).SARC-P/LP variants were associated with increased risk of death or major adverse cardiac events (MACE) compared to controls (HR 1.68, 95% CI 1.37–2.06, p<0.001), mainly due to heart failure endpoints (Figure 2: cumulative hazard curves with zoomed plots for lifetime risk of A) death and MACE or B) heart failure, stratified by genotype; genotype negative (SARC-NEG), carriers of indeterminate sarcomeric variants (SARC-IND) or SARC-P/LP; C) Forest plot of comparative lifetime risk of c

Conference paper

Chen C, Hammernik K, Ouyang C, Qin C, Bai W, Rueckert Det al., 2021, Cooperative training and latent space data augmentation for robust medical image segmentation, International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI)

Conference paper

Wang S, Qin C, Savioli N, Chen C, O'Regan D, Cook S, Guo Y, Rueckert D, Bai Wet al., 2021, Joint motion correction and super resolution for cardiac segmentationvia latent optimisation, International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI), Publisher: Springer, Pages: 14-24

In cardiac magnetic resonance (CMR) imaging, a 3D high-resolution segmentation of the heart is essential for detailed description of its anatomical structures. However, due to the limit of acquisition duration andrespiratory/cardiac motion, stacks of multi-slice 2D images are acquired inclinical routine. The segmentation of these images provides a low-resolution representation of cardiac anatomy, which may contain artefacts caused by motion. Here we propose a novel latent optimisation framework that jointly performs motion correction and super resolution for cardiac image segmentations. Given a low-resolution segmentation as input, the framework accounts for inter-slice motion in cardiac MR imaging and super-resolves the input into a high-resolution segmentation consistent with input. A multi-view loss is incorporated to leverage information from both short-axis view and long-axis view of cardiac imaging. To solve the inverse problem, iterative optimisation is performed in a latent space, which ensures the anatomical plausibility. This alleviates the need of paired low-resolution and high-resolution images for supervised learning. Experiments on two cardiac MR datasets show that the proposed framework achieves high performance, comparable to state-of-the-art super-resolution approaches and with better cross-domain generalisability and anatomical plausibility.

Conference paper

Simoes Monteiro de Marvao A, McGurk K, Zheng S, Thanaj M, Bai W, Duan J, Biffi C, Mazzarotto F, Statton B, Dawes T, Savioli N, Halliday B, Xu X, Buchan R, Baksi A, Quinlan M, Tokarczuk P, Tayal U, Francis C, Whiffin N, Theotokis A, Zhang X, Jang M, Berry A, Pantazis A, Barton P, Rueckert D, Prasad S, Walsh R, Ho C, Cook S, Ware J, O'Regan Det al., 2021, Phenotypic expression and outcomes in individuals with rare genetic variants of hypertrophic cardiomyopathy, Journal of the American College of Cardiology, Vol: 78, Pages: 1097-1110, ISSN: 0735-1097

Background: Hypertrophic cardiomyopathy (HCM) is caused by rare variants in sarcomereencoding genes, but little is known about the clinical significance of these variants in thegeneral population.Objectives: To compare lifetime outcomes and cardiovascular phenotypes according to thepresence of rare variants in sarcomere-encoding genes amongst middle-aged adults.Methods: We analysed whole exome sequencing and cardiac magnetic resonance (CMR)imaging in UK Biobank participants stratified by sarcomere-encoding variant status.Results: The prevalence of rare variants (allele frequency <0.00004) in HCM-associatedsarcomere-encoding genes in 200,584 participants was 2.9% (n=5,712; 1 in 35), and theprevalence of variants pathogenic or likely pathogenic for HCM (SARC-HCM-P/LP) was0.25% (n=493, 1 in 407). SARC-HCM-P/LP variants were associated with increased risk ofdeath or major adverse cardiac events compared to controls (HR 1.69, 95% CI 1.38 to 2.07,p<0.001), mainly due to heart failure endpoints (HR 4.23, 95% CI 3.07 to 5.83, p<0.001). In21,322 participants with CMR, SARC-HCM-P/LP were associated with asymmetric increasein left ventricular maximum wall thickness (10.9±2.7 vs 9.4±1.6 mm, p<0.001) buthypertrophy (≥13mm) was only present in 18.4% (n=9/49, 95% CI 9 to 32%). SARC-HCMP/LP were still associated with heart failure after adjustment for wall thickness (HR 6.74,95% CI 2.43 to 18.7, p<0.001).Conclusions: In this population of middle-aged adults, SARC-HCM-P/LP variants have lowaggregate penetrance for overt HCM but are associated with increased risk of adversecardiovascular outcomes and an attenuated cardiomyopathic phenotype. Although absoluteevent rates are low, identification of these variants may enhance risk stratification beyondfamilial disease.

Journal article

Thanaj M, Mielke J, McGurk KA, Bai W, Savioli N, de Marvao A, Meyer HV, Zeng L, Sohler F, Wilkins MR, Ware JS, Bender C, Rueckert D, MacNamara A, Freitag DF, ORegan DPet al., 2021, Genetic and environmental determinants of diastolic heart function, Publisher: Cold Spring Harbor Laboratory

<jats:title>ABSTRACT</jats:title><jats:p>Diastole is the sequence of physiological events that occur in the heart during ventricular filling and principally depends on myocardial relaxation and chamber stiffness. Abnormal diastolic function is related to many cardiovascular disease processes and is predictive of health outcomes, but its genetic architecture is largely unknown. Here, we use machine learning cardiac motion analysis to measure diastolic functional traits in 39,559 participants of UK Biobank and perform a genome-wide association study. We identified 9 significant, independent loci near genes that are associated with maintaining sarcomeric function under biomechanical stress and genes implicated in the development of cardiomyopathy. Age, sex and diabetes were independent predictors of diastolic function and we found a causal relationship between ventricular stiffness and heart failure. Our results provide novel insights into the genetic and environmental factors influencing diastolic function that are relevant for identifying causal relationships and tractable targets in heart failure.</jats:p>

Working paper

Evangelou E, Suzuki H, Bai W, Pazoki R, Gao H, Matthews P, Elliott Pet al., 2021, Alcohol consumption in the general population is associated with structural changes in multiple organ systems., eLife, Vol: 10, Pages: 1-15, ISSN: 2050-084X

Background:Excessive alcohol consumption is associated with damage to various organs, but its multi-organ effects have not been characterised across the usual range of alcohol drinking in a large general population sample.Methods:We assessed global effect sizes of alcohol consumption on quantitative magnetic resonance imaging phenotypic measures of the brain, heart, aorta, and liver of UK Biobank participants who reported drinking alcohol.Results:We found a monotonic association of higher alcohol consumption with lower normalised brain volume across the range of alcohol intakes (–1.7 × 10−3 ± 0.76 × 10−3 per doubling of alcohol consumption, p=3.0 × 10−14). Alcohol consumption was also associated directly with measures of left ventricular mass index and left ventricular and atrial volume indices. Liver fat increased by a mean of 0.15% per doubling of alcohol consumption.Conclusions:Our results imply that there is not a ‘safe threshold’ below which there are no toxic effects of alcohol. Current public health guidelines concerning alcohol consumption may need to be revisited.

Journal article

Balaban G, Halliday B, Bradley P, Bai W, Nygaard S, Owen R, Hatipoglu S, Ferreira ND, Izgi C, Tayal U, Corden B, Ware J, Pennell D, Rueckert D, Plank G, Rinaldi CA, Prasad SK, Bishop Met al., 2021, Late-gadolinium enhancement interface area and electrophysiological simulations predict arrhythmic events in non-ischemic dilated cardiomyopathy patients, JACC: Clinical Electrophysiology, Vol: 7, Pages: 238-249, ISSN: 2405-5018

BACKGROUND: The presence of late-gadolinium enhancement (LGE) predicts life threatening ventricular arrhythmias in non-ischemic dilated cardiomyopathy (NIDCM); however, risk stratification remains imprecise. LGE shape and simulations of electrical activity may be able to provide additional prognostic information.OBJECTIVE: This study sought to investigate whether shape-based LGE metrics and simulations of reentrant electrical activity are associated with arrhythmic events in NIDCM patients.METHODS: CMR-LGE shape metrics were computed for a cohort of 156 NIDCM patients with visible LGE and tested retrospectively for an association with an arrhythmic composite end-point of sudden cardiac death and ventricular tachycardia. Computational models were created from images and used in conjunction with simulated stimulation protocols to assess the potential for reentry induction in each patient’s scar morphology. A mechanistic analysis of the simulations was carried out to explain the associations. RESULTS: During a median follow-up of 1611 [IQR 881-2341] days, 16 patients (10.3%) met the primary endpoint. In an inverse probability weighted Cox regression, the LGE-myocardial interface area (HR:1.75; 95% CI:1.24-2.47; p=0.001), number of simulated reentries (HR: 1.4; 95% CI: 1.23-1.59; p<0.01) and LGE volume (HR:1.44; 95% CI:1.07-1.94; p=0.02) were associated with arrhythmic events. Computational modeling revealed repolarisation heterogeneity and rate-dependent block of electrical wavefronts at the LGE-myocardial interface as putative arrhythmogenic mechanisms directly related to LGE interface area.CONCLUSION: The area of interface between scar and surviving myocardium, as well as simulated reentrant activity, are associated with an elevated risk of major arrhythmic events in NIDCM patients with LGE and represent novel risk predictors.

Journal article

de Marvao A, McGurk KA, Zheng SL, Thanaj M, Bai W, Duan J, Biffi C, Mazzarotto F, Statton B, Dawes TJW, Savioli N, Halliday BP, Xu X, Buchan RJ, Baksi AJ, Quinlan M, Tokarczuk P, Tayal U, Francis C, Whiffin N, Theotokis PI, Zhang X, Jang M, Berry A, Pantazis A, Barton PJR, Rueckert D, Prasad SK, Walsh R, Ho CY, Cook SA, Ware JS, ORegan DPet al., 2021, Outcomes and phenotypic expression of rare variants in hypertrophic cardiomyopathy genes amongst UK Biobank participants, Publisher: Cold Spring Harbor Laboratory

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Hypertrophic cardiomyopathy (HCM) is caused by rare variants in sarcomere-encoding genes, but little is known about the clinical significance of these variants in the general population.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We compared outcomes and cardiovascular phenotypes in UK Biobank participants with whole exome sequencing stratified by sarcomere-encoding variant status.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The prevalence of rare variants (allele frequency &lt;0.00004) in HCM-associated sarcomere-encoding genes in 200,584 participants was 2.9% (n=5,727; 1 in 35), of which 0.24% (n=474, 1 in 423) were pathogenic or likely pathogenic variants (SARC-P/LP). SARC-P/LP variants were associated with increased risk of death or major adverse cardiac events compared to controls (HR 1.68, 95% CI 1.37-2.06, p&lt;0.001), mainly due to heart failure (HR 4.40, 95% CI 3.22-6.02, p&lt;0.001) and arrhythmia (HR 1.55, 95% CI 1.18-2.03, p=0.002). In 21,322 participants with cardiac magnetic resonance imaging, SARC-P/LP were associated with increased left ventricular maximum wall thickness (10.9±2.7 vs 9.4±1.6 mm, p&lt;0.001) and concentric remodelling (mass/volume ratio: 0.63±0.12 vs 0.58±0.09 g/mL, p&lt;0.001), but hypertrophy (≥13mm) was only present in 16% (n=7/43, 95% CI 7-31%). Other rare sarcomere-encoding variants had a weak effect on wall thickness (9.5±1.7 vs 9.4±1.6 mm, p=0.002) with no combined excess cardiovascular risk (HR 1.00 95% CI 0.92-1.08, p=0.9).</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>In the general population, SARC-P/LP variants have low aggregate penetrance for overt HCM bu

Working paper

Tadros R, Francis C, Xu X, Vermeer AMC, Harper AR, Huurman R, Bisabu KK, Walsh R, Hoorntje ET, te Rijdt WP, Buchan RJ, van Velzen HG, van Slegtenhorst MA, Vermeulen JM, Offerhaus JA, Bai W, de Marvao A, Lahrouchi N, Beekman L, Karper JC, Veldink JH, Kayvanpour E, Pantazis A, Baksi AJ, Whiffin N, Mazzarotto F, Sloane G, Suzuki H, Schneider-Luftman D, Elliott P, Richard P, Ader F, Villard E, Lichtner P, Meitinger T, Tanck MWT, van Tintelen JP, Thain A, McCarty D, Hegele RA, Roberts JD, Amyot J, Dube M-P, Cadrin-Tourigny J, Giraldeau G, L'Allier PL, Garceau P, Tardif J-C, Boekholdt SM, Lumbers RT, Asselbergs FW, Barton PJR, Cook SA, Prasad SK, O'Regan DP, van der Velden J, Verweij KJH, Talajic M, Lettre G, Pinto YM, Meder B, Charron P, de Boer RA, Christiaans I, Michels M, Wilde AAM, Watkins H, Matthews PM, Ware JS, Bezzina CR, Tadros R, Francis C, Xu X, Vermeer AMC, Harper AR, Huurman R, Bisabu KK, Walsh R, Hoorntje ET, te Rijdt WP, Buchan RJ, van Velzen HG, van Slegtenhorst MA, Vermeulen JM, Offerhaus JA, Bai W, de Marvao A, Lahrouchi N, Beekman L, Karper JC, Veldink JH, Kayvanpour E, Pantazis A, Baksi AJ, Whiffin N, Mazzarotto F, Sloane G, Suzuki H, Schneider-Luftman D, Elliott P, Richard P, Ader F, Villard E, Lichtner P, Meitinger T, Tanck MWT, van Tintelen JP, Thain A, McCarty D, Hegele RA, Roberts JD, Amyot J, Dube M-P, Cadrin-Tourigny J, Giraldeau G, L'Allier PL, Garceau P, Tardif J-C, Boekholdt SM, Lumbers RT, Asselbergs FW, Barton PJR, Cook SA, Prasad SK, O'Regan DP, van der Velden J, Verweij KJH, Talajic M, Lettre G, Pinto YM, Meder B, Charron P, de Boer RA, Christiaans I, Michels M, Wilde AAM, Watkins H, Matthews PM, Ware JS, Bezzina CRet al., 2021, Shared genetic pathways contribute to risk of hypertrophic and dilated cardiomyopathies with opposite directions of effect, NATURE GENETICS, Vol: 53, Pages: 128-+, ISSN: 1061-4036

Journal article

Dai C, Wang S, Raynaud H, Mo Y, Angelini E, Guo Y, Bai Wet al., 2021, Self-training for Brain Tumour Segmentation with Uncertainty Estimation and Biophysics-Guided Survival Prediction, Pages: 514-523, ISSN: 0302-9743

Gliomas are among the most common types of malignant brain tumours in adults. Given the intrinsic heterogeneity of gliomas, the multi-parametric magnetic resonance imaging (mpMRI) is the most effective technique for characterising gliomas and their sub-regions. Accurate segmentation of the tumour sub-regions on mpMRI is of clinical significance, which provides valuable information for treatment planning and survival prediction. Thanks to the recent developments on deep learning, the accuracy of automated medical image segmentation has improved significantly. In this paper, we leverage the widely used attention and self-training techniques to conduct reliable brain tumour segmentation and uncertainty estimation. Based on the segmentation result, we present a biophysics-guided prognostic model for the prediction of overall survival. Our method of uncertainty estimation has won the second place of the MICCAI 2020 BraTS Challenge.

Conference paper

Lu P, Bai W, Rueckert D, Noble JAet al., 2021, DYNAMIC SPATIO-TEMPORAL GRAPH CONVOLUTIONAL NETWORKS FOR CARDIAC MOTION ANALYSIS, 18th IEEE International Symposium on Biomedical Imaging (ISBI), Publisher: IEEE, Pages: 122-125, ISSN: 1945-7928

Conference paper

Lu P, Bai W, Rueckert D, Noble JAet al., 2021, Modelling Cardiac Motion via Spatio-Temporal Graph Convolutional Networks to Boost the Diagnosis of Heart Conditions, Pages: 56-65, ISSN: 0302-9743

We present a novel spatio-temporal graph convolutional networks (ST-GCN) approach to learn spatio-temporal patterns of left ventricular (LV) motion in cardiac MR cine images for improving the characterization of heart conditions. Specifically, a novel GCN architecture is used, where the sample nodes of endocardial and epicardial contours are connected as a graph to represent the myocardial geometry. We show that the ST-GCN can automatically quantify the spatio-temporal patterns in cine MR that characterise cardiac motion. Experiments are performed on healthy volunteers from the UK Biobank dataset. We compare different strategies for constructing cardiac structure graphs. Experiments show that the proposed methods perform well in estimating endocardial radii and characterising cardiac motion features for regional LV analysis.

Conference paper

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