Patient-specific blood flow modelling in diagnosis of coronary artery disease

This thesis presents the approach for development of patient-specific coronary blood flow models in 3D and 0D domains based on coronary artery geometries reconstructed from Coronary Computed Tomography Angiography datasets (CCTA). The computed flow patterns extend the diagnostic value of CCTA, which, being noninvasive imaging modality, provides only static information on the anatomy of epicardial arteries. The clinical indices extracted from the virtual blood flow can be potentially employed in the assessment of the haemodynamic severity of Coronary Artery Disease (CAD) lesions as well at the analysis of the underlying mechanisms of formation and localisation of atherosclerotic plaques. However, the existing patient-specific coronary blood flow modelling approaches are generally characterised by relatively high levels of uncertainty and instability due to a number of unknown factors and modelling assumptions. Analysis and comparison of the impact of various modelling assumptions has the potential to reduce this uncertainty. The overarching contributions of this thesis are the thorough analysis and investigation of the existing issues in patient-specific coronary blood flow simulations and the provision of the guidelines for the design and implementation of blood flow models in order to improve and ensure the reliability and accuracy of the numerical results. In addition, a novel approach for the implementation of spatially extended patient-specific 0D blood flow models was proposed, which significantly decreases the high computational costs generally associated with 3D blood flow simulations. While the classical 0D models based on the electrical–hydraulic analogy use the lumped-parameter representation of major vessel tree structures and are thus characterised by limited spatial characteristics, the proposed method for modelling of individual vessel tree branches through a series of 0D elements provides the means for correlation of the computed flow with the precise location along a vessel. Therefore, this extends the applicability of 0D modelling in patient-specific blood flow simulations for the assessment of functional stenosis severity

Multi-task learning for joint weakly-supervised segmentation and aortic arch anomaly classification in fetal cardiac MRI

Congenital Heart Disease (CHD) is a group of cardiac malformations present already during fetal life, representing the prevailing category of birth defects globally. Our aim in this study is to aid 3D fetal vessel topology visualisation in aortic arch anomalies, a group which encompasses a range of conditions with significant anatomical heterogeneity. We present a multi-task framework for automated multi-class fetal vessel segmentation from 3D black blood T2w MRI and anomaly classification. Our training data consists of binary manual segmentation masks of the cardiac vessels' region in individual subjects and fully-labelled anomaly-specific population atlases. Our framework combines deep learning label propagation using VoxelMorph with 3D Attention U-Net segmentation and DenseNet121 anomaly classification. We target 11 cardiac vessels and three distinct aortic arch anomalies, including double aortic arch, right aortic arch, and suspected coarctation of the aorta. We incorporate an anomaly classifier into our segmentation pipeline, delivering a multi-task framework with the primary motivation of correcting topological inaccuracies of the segmentation. The hypothesis is that the multi-task approach will encourage the segmenter network to learn anomaly-specific features. As a secondary motivation, an automated diagnosis tool may have the potential to enhance diagnostic confidence in a decision support setting. Our results showcase that our proposed training strategy significantly outperforms label propagation and a network trained exclusively on propagated labels. Our classifier outperforms a classifier trained exclusively on T2w volume images, with an average balanced accuracy of 0.99 (0.01) after joint training. Adding a classifier improves the anatomical and topological accuracy of all correctly classified double aortic arch subjects.Comment: Accepted for publication at the Journal of Machine Learning for Biomedical Imaging (MELBA) https://melba-journal.org/2023:01

3D T2w fetal body MRI:automated organ volumetry, growth charts and population-averaged atlas

Structural fetal body MRI provides true 3D information required for volumetry of fetal organs. However, current clinical and research practice primarily relies on manual slice-wise segmentation of raw T2-weighted stacks, which is time consuming, subject to inter- and intra-observer bias and affected by motion-corruption. Furthermore, there are no existing standard guidelines defining a universal approach to parcellation of fetal organs. This work produces the first parcellation protocol of the fetal body organs for motion-corrected 3D fetal body MRI. It includes 10 organ ROIs relevant to fetal quantitative volumetry studies. We also introduce the first population-averaged T2w MRI atlas of the fetal body. The protocol was used as a basis for training of a neural network for automated organ segmentation. It showed robust performance for different gestational ages. This solution minimises the need for manual editing and significantly reduces time. The general feasibility of the proposed pipeline was also assessed by analysis of organ growth charts created from automated parcellations of 91 normal control 3T MRI datasets that showed expected increase in volumetry during 22-38 weeks gestational age range. In addition, the results of comparison between 60 normal and 12 fetal growth restriction datasets revealed significant differences in organ volumes.</p

Craniofacial phenotyping with fetal MRI:A feasibility study of 3D visualisation, segmentation, surface-rendered and physical models

This study explores the potential of 3D Slice-to-Volume Registration (SVR) motion-corrected fetal MRI for craniofacial assessment, traditionally used only for fetal brain analysis. In addition, we present the first description of an automated pipeline based on 3D Attention UNet trained for 3D fetal MRI craniofacial segmentation, followed by surface refinement. Results of 3D printing of selected models are also presented.Qualitative analysis of multiplanar volumes, based on the SVR output and surface segmentations outputs, were assessed with computer and printed models, using standardised protocols that we developed for evaluating image quality and visibility of diagnostic craniofacial features. A test set of 25, postnatally confirmed, Trisomy 21 fetal cases (24–36 weeks gestational age), revealed that 3D reconstructed T2 SVR images provided 66–100% visibility of relevant craniofacial and head structures in the SVR output, and 20–100% and 60–90% anatomical visibility was seen for the baseline and refined 3D computer surface model outputs respectively. Furthermore, 12 of 25 cases, 48%, of refined surface models demonstrated good or excellent overall quality with a further 9 cases, 36%, demonstrating moderate quality to include facial, scalp and external ears. Additional 3D printing of 12 physical real-size models (20–36 weeks gestational age) revealed good/excellent overall quality in all cases and distinguishable features between healthy control cases and cases with confirmed anomalies, with only minor manual adjustments required before 3D printing.Despite varying image quality and data heterogeneity, 3D T2w SVR reconstructions and models provided sufficient resolution for the subjective characterisation of subtle craniofacial features. We also contributed a publicly accessible online 3D T2w MRI atlas of the fetal head, validated for accurate representation of normal fetal anatomy.Future research will focus on quantitative analysis, optimizing the pipeline, and exploring diagnostic, counselling, and educational applications in fetal craniofacial assessment

Fully automated planning for anatomical fetal brain MRI on 0.55T

Purpose: Widening the availability of fetal MRI with fully automatic real-time planning of radiological brain planes on 0.55T MRI. Methods: Deep learning-based detection of key brain landmarks on a whole-uterus EPI scan enables the subsequent fully automatic planning of the radiological single-shot Turbo Spin Echo acquisitions. The landmark detection pipeline was trained on over 120 datasets from varying field strength, echo times and resolutions and quantitatively evaluated. The entire automatic planning solution was tested prospectively in nine fetal subjects between 20 and 37 weeks. Comprehensive evaluation of all steps, the distance between manual and automatic landmarks, the planning quality and the resulting image quality was conducted. Results: Prospective automatic planning was performed in real-time without latency in all subjects. The landmark detection accuracy was 4.21+-2.56 mm for the fetal eyes and 6.47+-3.23 for the cerebellum, planning quality was 2.44/3 (compared to 2.56/3 for manual planning) and diagnostic image quality was 2.14 compared to 2.07 for manual planning. Conclusions: Real-time automatic planning of all three key fetal brain planes was successfully achieved and will pave the way towards simplifying the acquisition of fetal MRI thereby widening the availability of this modality in non-specialist centres.Comment: 17 pages, 8 figures, 1 table, MR

Dynamics of T2* and deformation in the placenta and myometrium during pre-labour contractions

Pre-labour uterine contractions, occurring throughout pregnancy, are an important phenomenon involving the placenta in addition to the myometrium. They alter the uterine environment and thus potentially the blood supply to the fetus and may thus provide crucial insights into the processes of labour. Assessment in-vivo is however restricted due to their unpredictability and the inaccessible nature of the utero-placental compartment. While clinical cardiotocography (CTG) only allows global, pressure-based assessment, functional magnetic resonance imaging (MRI) provides an opportunity to study contractile activity and its effects on the placenta and the fetus in-vivo. This study aims to provide both descriptive and quantitative structural and functional MR assessments of pre-labour contractions in the human uterus. A total of 226 MRI scans (18–41 weeks gestation) from ongoing research studies were analysed, focusing on free-breathing dynamic quantitative whole uterus dynamic T2* maps. These provide an indirect measure of tissue properties such as oxygenation. 22 contractile events were noted visually and both descriptive and quantitative analysis of the myometrial and placental changes including volumetric and T2* variations were undertaken. Processing and analysis was successfully performed, qualitative analysis shows distinct and highly dynamic contraction related characteristics including; alterations in the thickness of the low T2* in the placental bed and other myometrial areas, high intensity vessel-like structures in the myometrium, low-intensity vessel structures within the placental parenchyma and close to the chorionic plate. Quantitative evaluation shows a significant negative correlation between T2* in both contractile and not-contractile regions with gestational age (p 0.5). The quantitative and qualitative description of uterine pre-labour contractions including dynamic changes and key characteristics aims to contribute to the sparsely available in-vivo information and to provide an in-vivo tool to study this important phenomenon. Further work is required to analyse the origins of these subclinical contractions, their effects in high-risk pregnancies and their ability to determine the likelihood of a successful labour. Assessing T2* distribution as a marker for placental oxygenation could thus potentially complement clinically used cardiotocography measurements in the future