Fetal whole-heart 4D imaging using motion-corrected multi-planar real-time MRI

Purpose: To develop a MRI acquisition and reconstruction framework for volumetric cine visualisation of the fetal heart and great vessels in the presence of maternal and fetal motion. Methods: Four-dimensional depiction was achieved using a highly-accelerated multi-planar real-time balanced steady state free precession acquisition combined with retrospective image-domain techniques for motion correction, cardiac synchronisation and outlier rejection. The framework was evaluated and optimised using a numerical phantom, and evaluated in a study of 20 mid- to late-gestational age human fetal subjects. Reconstructed cine volumes were evaluated by experienced cardiologists and compared with matched ultrasound. A preliminary assessment of flow-sensitive reconstruction using the velocity information encoded in the phase of dynamic images is included. Results: Reconstructed cine volumes could be visualised in any 2D plane without the need for highly-specific scan plane prescription prior to acquisition or for maternal breath hold to minimise motion. Reconstruction was fully automated aside from user-specified masks of the fetal heart and chest. The framework proved robust when applied to fetal data and simulations confirmed that spatial and temporal features could be reliably recovered. Expert evaluation suggested the reconstructed volumes can be used for comprehensive assessment of the fetal heart, either as an adjunct to ultrasound or in combination with other MRI techniques. Conclusion: The proposed methods show promise as a framework for motion-compensated 4D assessment of the fetal heart and great vessels

Foetal echocardiographic segmentation

Congenital heart disease affects just under one percentage of all live births [1]. Those defects that manifest themselves as changes to the cardiac chamber volumes are the motivation for the research presented in this thesis. Blood volume measurements in vivo require delineation of the cardiac chambers and manual tracing of foetal cardiac chambers is very time consuming and operator dependent. This thesis presents a multi region based level set snake deformable model applied in both 2D and 3D which can automatically adapt to some extent towards ultrasound noise such as attenuation, speckle and partial occlusion artefacts. The algorithm presented is named Mumford Shah Sarti Collision Detection (MSSCD). The level set methods presented in this thesis have an optional shape prior term for constraining the segmentation by a template registered to the image in the presence of shadowing and heavy noise. When applied to real data in the absence of the template the MSSCD algorithm is initialised from seed primitives placed at the centre of each cardiac chamber. The voxel statistics inside the chamber is determined before evolution. The MSSCD stops at open boundaries between two chambers as the two approaching level set fronts meet. This has significance when determining volumes for all cardiac compartments since cardiac indices assume that each chamber is treated in isolation. Comparison of the segmentation results from the implemented snakes including a previous level set method in the foetal cardiac literature show that in both 2D and 3D on both real and synthetic data, the MSSCD formulation is better suited to these types of data. All the algorithms tested in this thesis are within 2mm error to manually traced segmentation of the foetal cardiac datasets. This corresponds to less than 10% of the length of a foetal heart. In addition to comparison with manual tracings all the amorphous deformable model segmentations in this thesis are validated using a physical phantom. The volume estimation of the phantom by the MSSCD segmentation is to within 13% of the physically determined volume

Magnetic Resonance Imaging of the fetal cardiovascular system and congenital heart disease

An early diagnosis of congenital heart diseases (CHD) has important prognostic impact. Prenatal echocardiography is an indispensable part of prenatal screening in many countries. However, it might provide poor diagnostic quality in some cases. Complementary diagnostic methods for postnatal life are missing prenatally. This work aims to investigate the use of fetal cardiovascular magnetic resonance imaging (MRI) as an adjunct to fetal echocardiography. This manuscript is divided into the anatomical visualization of CHD and the quantification of the impact of fetal motion on cardiovascular flow-measurements. 101 singleton pregnant women carrying fetus with suspected CHD in fetal echocardiography were prospectively recruited for fetal cardiac MRI. In 85 participants 2D and 3D MRI data could be reconstructed successfully and compared to echocardiographic and postnatal data. Furthermore, 10 pregnant women from the first sub study and 10 adult volunteers were recruited. The impact of simulated fetal motion in the adult volunteers was investigated. The artifacts observed during this study were compared to the artefacts in fetal flow-measurements by a three-point scoring system. MRI reconstructions of vascular structures showed a good agreement with 2D-echocardiography, while 3D-MRI reconstructions were superior to 2D-MRI data regarding their quality and diagnostic accuracy. Additional anatomic structures were identified in 10 cases with MRI and could be confirmed postnatally. Flow-measurements corrupted by simulated fetal motion within the middle third of an acquisition showed significant errors in contrast to measurements under motion corruption during the first and last third of the acquisition. The velocity of motion did not have a major impact. A three-point scoring system could readily identify the amount and impact of fetal motion on the later acquisition. 3D fetal cardiac MRI is a reliable imaging method with potential complementary use to fetal echocardiography. Additionally, valid fetal cardiovascular flow-measurements under the face of fetal motion can be reliably identified at the point of their acquisition, already.Die frühe Diagnose angeborener Herzfehler hat eine prognostische Bedeutung. Eine pränatale Echokardiographie ist in vielen Ländern unverzichtbarer Standard pränataler Screening Untersuchungen. Dennoch müssen oft Abstriche bei der Bildqualität gemacht werden. Während postnatal ergänzende Bildgebungstechniken zur Verfügung stehen, fehlen diese Alternativen pränatal. Die vorliegende Arbeit soll die Möglichkeiten der fetalen kardiovaskulären Magnetresonanztomographie (MRT) als ergänzende Diagnostik zur fetalen Echokardiographie untersuchen. Die vorliegende Arbeit ist untergliedert in die anatomische Darstellung angeborener Herzfehler mittels der MRT und die Untersuchung des Einflusses fetaler Bewegung auf kardiovaskuläre Flussmessungen. 101 schwangere Teilnehmerinnen mit Feten mit dem V.a. einen angeborenen Herzfehler in der fetalen Echokardiographie wurden prospektiv für eine fetale Kardio-MRT rekrutiert. 2D und 3D Bilddatenrekonstruktionen von 85 Feten der Teilnehmerinnen konnten mit den echokardiographischen, sowie postnatalen Daten verglichen werden. Weiterhin wurden 10 erwachsene Proband*innen, sowie 10 schwangere Teilnehmerinnen aus der ersten Substudie rekrutiert. Einflüsse simulierter fetaler Bewegung in den erwachsenen Proband*innen wurden untersucht. Beobachtete Artefakte in den gewonnen Flussmessungen wurden mittels eines Bewertungssystems mit denen der fetalen Messungen verglichen. Vaskuläre Strukturen in MRT-Datensätzen zeigten eine gute Übereinstimmung mit Messungen in echokardiographischen 2D-Datensätzen, wobei 3D-MRT Datensätze hinsichtlich Qualität und diagnostischer Genauigkeit den 2D-MRT Daten überlegen waren. In 10 Fällen gelang die Darstellung zusätzlicher anatomischer Gegebenheiten in der MRT, welche postnatal bestätigt werden konnten. Flussmessungen, welche durch simulierte fetale Bewegung im mittleren Drittel einer Aufnahme verzerrt wurden, wiesen signifikante Fehler auf. Dies konnte bei Messungen unter dem Einfluss fetalen Bewegungen im ersten oder letzten Drittel der Aufnahme nicht beobachtet werden. Die Geschwindigkeit der Bewegungen spielte eine untergeordnete Rolle. Das Ausmaß fetaler Bewegung während einer Aufnahme, sowie ihr Einfluss auf die Flussmessungen kann mittels eines Drei-Punkte-Bewertungssystems zuverlässig identifiziert werden. Fetale Kardio-MRT bietet eine zuverlässige Möglichkeit mittels 3D-Darstellung der fetalen Gefäße die pränatale Echokardiographie als bildgebende Methode zu ergänzen. Zudem können valide Flussmessungen trotz Einfluss fetaler Bewegung zuverlässig zum Zeitpunkt der Aufnahme identifiziert werden

Atrioventricular septal defect : advanced imaging from early development to long-term follow-up

The aim of this thesis is to review the current knowledge on atrioventricular septal defect (AVSD) (Part 1), to study the pathogenesis of AVSD (Part 2) and finally to analyze cardiac outcome long-term after AVSD correction (Part 3). Studies are performed with novel imaging techniques. In part 2 it is made plausible that AVSD is a sliding scale and that patients with Down syndrome without AVSD also have abnormalities of the membranous septum and atrioventricular valves. High frequency ultrasound in mouse embryos shows to be a promising technique to study cardiovascular flow in early stages of heart development. In a mouse model with disturbed VEGF signalling, the heart rate is reduced and the sinoatrial node develops abnormally. Finally, in part 3 of this thesis, 4DFlow MRI data reveals that patients with an abnormal left atrioventricular valve (LAVV) after AVSD correction have aberrant intra-cardiac flow patterns. During diastole the inflow into the left ventricle is directed more towards the lateral wall, more towards the apex and vortex formation is abnormal. During systole the dynamic and eccentric regurgitation of the LAVV disturbs the normal recirculating flow patterns in the left atrium.4DFlow MRI can be used to reliably quantify flow over the LAVV.UBL - phd migration 201

Magnetic Resonance Imaging of the Brain in Moving Subjects. Application of Fetal, Neonatal and Adult Brain Studies

Imaging in the presence of subject motion has been an ongoing challenge for magnetic resonance imaging (MRI). Motion makes MRI data inconsistent, causing artifacts in conventional anatomical imaging as well as invalidating diffusion tensor imaging (DTI) reconstruction. In this thesis some of the important issues regarding the acquisition and reconstruction of anatomical and DTI imaging of moving subjects are addressed; methods to achieve high resolution and high signalto- noise ratio (SNR) volume data are proposed. An approach has been developed that uses multiple overlapped dynamic single shot slice by slice imaging combined with retrospective alignment and data fusion to produce self consistent 3D volume images under subject motion. We term this method as snapshot MRI with volume reconstruction or SVR. The SVR method has been performed successfully for brain studies on subjects that cannot stay still, and in some cases were moving substantially during scanning. For example, awake neonates, deliberately moved adults and, especially, on fetuses, for which no conventional high resolution 3D method is currently available. Fine structure of the in-utero fetal brain is clearly revealed for the first time with substantially improved SNR. The SVR method has been extended to correct motion artifacts from conventional multi-slice sequences when the subject drifts in position during data acquisition. Besides anatomical imaging, the SVR method has also been further extended to DTI reconstruction when there is subject motion. This has been validated successfully from an adult who was deliberately moving and then applied to inutero fetal brain imaging, which no conventional high resolution 3D method is currently available. Excellent fetal brain 3D apparent diffusion coefficient (ADC) maps in high resolution have been achieved for the first time as well as promising fractional Anisotropy (FA) maps. Pilot clinical studies using SVR reconstructed data to study fetal brain development in-utero have been performed. Growth curves for the normally developing fetal brain have been devised by the quantification of cerebral and cerebellar volumes as well as some one dimensional measurements. A Verhulst model is proposed to describe these growth curves, and this approach has achieved a correlation over 0.99 between the fitted model and actual data

Magnetic Resonance Imaging of the Neonatal Cardiovascular System : Impact of Patent Ductus Arteriosus

The incidence of premature birth is increasing in absolute number and as a proportion of all births around the world. Many pathologies seen in this cohort are related to abnormal blood supply. Fetal and premature cardiovascular systems differ greatly as to maintain adequate blood flow to the developing organs in the uterine and extra-uterine environments require very different circulations. Subsequently following preterm birth the immature cardiovascular system undergoes abrupt adaptations, often resulting in the prolonged patency of the fetal shunt, ductus arteriosus. The impact of a patent ductus arteriosus (PDA) is poorly understood. However it is thought that large ductal shunt volumes may result in congestive cardiac failure and systemic hypo-­‐perfusion. Cardiac MRI has contributed greatly to the understanding of many cardiovascular diseases and congenital defects in paediatric and adult patients. Translating these imaging techniques to assess the preterm cardiovascular system requires careful optimization due to their condition, size and significantly increased heart rate. The work presented in this thesis employs multiple functional CMR techniques to investigate the preterm cardiovascular system in the presence and absence of PDA and the resultant cardiac function. A novel technique utilizing PC MRI to quantify PDA shunt volume and its impact on flow distribution is presented. Despite large shunt volumes, systemic circulation remained within normal range, although slight reduction is detectable when assessed at group level. Subsequently the impact of PDA and associated increased work load on left ventricular dimensions and function was then investigated using SSFP imaging. Results indicated that cardiac function was maintained even in the presence of large shunt volumes. Finally 4D PC sequences were employed to evaluate pulse wave velocity and flow regime within the preterm aorta, demonstrating the feasibility of hemodynamic assessment in this cohort. The findings of these studies provide insight into the impact of PDA. The reliable measurement and assessment of preterm cardiovascular system provides the potential to improve the understanding of the development and effects of certain pathologies seen in this cohort.Open Acces

Mri Assessment Of Maternal Uteroplacental Circulation In Pregnancy

Hypertensive pregnancy disorders (HPD) such as preeclampsia are highly associated with maternal vascular malperfusion of the placenta, an organ that exchanges nutrients and oxygen between the maternal circulation and the growing fetus. Adverse pregnancy outcomes are difficult to predict because there is insufficient understanding of how poor maternal arterial remodeling leads to disease. There is also a lack of reliable tools to evaluate these changes in early gestation. The hypothesis of this dissertation was that magnetic resonance imaging (MRI) could noninvasively evaluate uteroplacental function in vivo through a combination of arterial spin labeling (ASL), 4D flow, and time-of-flight (TOF) techniques which were already effective in the evalution of other cardiovascular diseases. These flow and perfusion imaging studies were conducted on human pregnant volunteers in their second and third trimesters at 1.5T. Many of them were also examined by conventional Doppler ultrasound (US) and followed through delivery. Flow-sensitive Alternating Inversion Recovery (FAIR) ASL MRI with background suppression was found to be feasible in detecting placental perfusion signal despite the presence of motion artifacts. An important consideration when studying placental ASL was the slow movement of maternal arterial blood in a large cavity called the intervillous space. This was a unique feature of placental anatomy which distinguished it from other organs containing capillaries. It became apparent that traditional models to estimate perfusion from MRI were no longer applicable. In this work, a statistical approach was first developed to filter out motion artifacts, followed by a coordinate transformation to better represent the lobular distribution of blood flow in the intervillous space of the placenta. The uterine arteries (UtAs) are the main maternal blood supply of the placenta and have also long been suspected to be involved in HPD, though US-based measurements have not yet been found to be highly predictive for widespread clinical use. In this work, 4D flow MRI enabled visualization of the tortuous UtAs while measuring volumetric flow rate. Its performance in predicting incidence of preeclampsia and small-for-gestational age births was comparable to Doppler US. When considering the innovative potential of 4D flow MRI to capture complex flow dynamics, this validation demonstrated the value of continuing technical development for improving HPD risk assessment. Furthermore, centerline extraction of the maternal pelvic arteries in TOF MRI, from the descending aorta to the UtAs and external iliac arteries, provided quantitative metrics to characterize the geometry including path length and curvature. Pulse wave velocity (PWV) was estimated using path length by TOF MRI and velocimetry by 2D phase contrast and 4D flow MRI with results showing sensitivity to differences between UtAs and external iliac arteries. These approaches provided physiological metrics to explore and characterize the remodeling process of the uteroplacental arteries. This dissertation demonstrates the feasibility of measuring structure and hemodynamics of the maternal vascular blood supply using non-contrast MRI that can lead to the more reliable biomarkers of adverse pregnancy outcomes needed to diagnose and treat HPD

Application of Advanced MRI to Fetal Medicine and Surgery

Robust imaging is essential for comprehensive preoperative evaluation, prognostication, and surgical planning in the field of fetal medicine and surgery. This is a challenging task given the small fetal size and increased fetal and maternal motion which affect MRI spatial resolution. This thesis explores the clinical applicability of post-acquisition processing using MRI advances such as super-resolution reconstruction (SRR) to generate optimal 3D isotropic volumes of anatomical structures by mitigating unpredictable fetal and maternal motion artefact. It paves the way for automated robust and accurate rapid segmentation of the fetal brain. This enables a hierarchical analysis of volume, followed by a local surface-based shape analysis (joint spectral matching) using mathematical markers (curvedness, shape index) that infer gyrification. This allows for more precise, quantitative measurements, and calculation of longitudinal correspondences of cortical brain development. I explore the potential of these MRI advances in three clinical settings: fetal brain development in the context of fetal surgery for spina bifida, airway assessment in fetal tracheolaryngeal obstruction, and the placental-myometrial-bladder interface in placenta accreta spectrum (PAS). For the fetal brain, MRI advances demonstrated an understanding of the impact of intervention on cortical development which may improve fetal candidate selection, neurocognitive prognostication, and parental counselling. This is of critical importance given that spina bifida fetal surgery is now a clinical reality and is routinely being performed globally. For the fetal trachea, SRR can provide improved anatomical information to better select those pregnancies where an EXIT procedure is required to enable the fetal airway to be secured in a timely manner. This would improve maternal and fetal morbidity outcomes associated with haemorrhage and hypoxic brain injury. Similarly, in PAS, SRR may assist surgical planning by providing enhanced anatomical assessment and prediction for adverse peri-operative maternal outcome such as bladder injury, catastrophic obstetric haemorrhage and maternal death