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

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

Magn Reson Med

To improve motion robustness of functional fetal MRI scans by developing an intrinsic real-time motion correction method. MRI provides an ideal tool to characterize fetal brain development and growth. It is, however, a relatively slow imaging technique and therefore extremely susceptible to subject motion, particularly in functional MRI experiments acquiring multiple Echo-Planar-Imaging-based repetitions, for example, diffusion MRI or blood-oxygen-level-dependency MRI. A 3D UNet was trained on 125 fetal datasets to track the fetal brain position in each repetition of the scan in real time. This tracking, inserted into a Gadgetron pipeline on a clinical scanner, allows updating the position of the field of view in a modified echo-planar imaging sequence. The method was evaluated in real-time in controlled-motion phantom experiments and ten fetal MR studies (17 + 4-34 + 3 gestational weeks) at 3T. The localization network was additionally tested retrospectively on 29 low-field (0.55T) datasets. Our method achieved real-time fetal head tracking and prospective correction of the acquisition geometry. Localization performance achieved Dice scores of 84.4% and 82.3%, respectively for both the unseen 1.5T/3T and 0.55T fetal data, with values higher for cephalic fetuses and increasing with gestational age. Our technique was able to follow the fetal brain even for fetuses under 18 weeks GA in real-time at 3T and was successfully applied "offline" to new cohorts on 0.55T. Next, it will be deployed to other modalities such as fetal diffusion MRI and to cohorts of pregnant participants diagnosed with pregnancy complications, for example, pre-eclampsia and congenital heart disease

High resolution and contrast 7 tesla MR brain imaging of the neonate

IntroductionUltra-high field MR imaging offers marked gains in signal-to-noise ratio, spatial resolution, and contrast which translate to improved pathological and anatomical sensitivity. These benefits are particularly relevant for the neonatal brain which is rapidly developing and sensitive to injury. However, experience of imaging neonates at 7T has been limited due to regulatory, safety, and practical considerations. We aimed to establish a program for safely acquiring high resolution and contrast brain images from neonates on a 7T system.MethodsImages were acquired from 35 neonates on 44 occasions (median age 39 + 6 postmenstrual weeks, range 33 + 4 to 52 + 6; median body weight 2.93 kg, range 1.57 to 5.3 kg) over a median time of 49 mins 30 s. Peripheral body temperature and physiological measures were recorded throughout scanning. Acquired sequences included T2 weighted (TSE), Actual Flip angle Imaging (AFI), functional MRI (BOLD EPI), susceptibility weighted imaging (SWI), and MR spectroscopy (STEAM).ResultsThere was no significant difference between temperature before and after scanning (p = 0.76) and image quality assessment compared favorably to state-of-the-art 3T acquisitions. Anatomical imaging demonstrated excellent sensitivity to structures which are typically hard to visualize at lower field strengths including the hippocampus, cerebellum, and vasculature. Images were also acquired with contrast mechanisms which are enhanced at ultra-high field including susceptibility weighted imaging, functional MRI, and MR spectroscopy.DiscussionWe demonstrate safety and feasibility of imaging vulnerable neonates at ultra-high field and highlight the untapped potential for providing important new insights into brain development and pathological processes during this critical phase of early life