Clinical Research Fellow, King's College London
Developing imaging techniques for a detailed profile of fetal cardiovascular health and development
My research involves developing novel MRI techniques which correct for fetal motion to allow for detailed 3D reconstructions of the fetal heart whilst still in the womb, even when just a few centimetres in size. By combining these images with other advanced ultrasound and MRI methods to measure blood flow through the heart and lungs, the developing brain, and the placenta, I can then generate a detailed anatomical and physiological profile of fetal cardiovascular system. These techniques have never been used together in this way.
Currently the research involves MRI sequence development, application and development of post-processing techniques and clinical validation with both ultrasound and postnatal follow-up. To date over 100 women have been recruited. The next step is to use other safe, non-invasive diagnostic tests such as maternal oxygen to investigate the responses in normal and abnormal cases, adding another important level of detail to these assessments.
This research has already had an immediate clinical impact for congenital cardiac conditions which have traditionally been difficult to diagnose before birth, and is already helping to better inform pre- and postnatal management in some cases. We have received some referrals to the research from other fetal centres around the UK for particularly challenging clinical cases.
Ultimately, I hope that this research will not only to aid the antenatal diagnosis of severe congenital heart disease, but also, to also provide a more detailed understand of other aspects of long term health, such brain growth, neurodevelopment and long term cardiovascular health.
Abstract: Fetal cardiovascular MRI offers a potential alternative to echocardiography, although in practice its use has been limited. We sought to explore the need for additional imaging in a tertiary fetal cardiology unit, and the usefulness of standard MRI sequences.Cases where the diagnosis was not fully resolved using echocardiography were referred for MRI. Following a three-plane localiser, fetal movement was assessed with a balanced steady-state free precession (bSSFP) cine. Single-shot fast spin echo (SSFSE) and bSSFP sequences were used for diagnostic imaging.22 fetal cardiac MRIs were performed over 12 months, at mean gestation 32 weeks (26 - 38 weeks). The majority of referrals were for suspected vascular abnormalities (17/22), particularly involving the aortic arch (n = 10) and pulmonary vessels (n = 4). SSFSE sequences produced "black-blood" images, useful for examining the extracardiac vasculature in these cases. BSSFP sequences were more useful for intracardiac structures. Real-time SSFP allowed for dynamic assessment of structures such as cardiac masses, with enhancement patterns also allowing for tissue characterisation in these cases.Fetal vascular abnormalities such as coarctation can be difficult to diagnose using ultrasound. Fetal MRI may have an adjunctive role in the evaluation of the extracardiac vascular anatomy and tissue characterisation.
Pub.: 16 Aug '16, Pinned: 06 Jun '17
Abstract: As survival after cardiac surgery continues to improve, an increasing number of patients with hypoplastic left heart syndrome are reaching school age and beyond, with growing recognition of the wide range of neurodevelopmental challenges many survivors face. Improvements in fetal detection rates, coupled with advances in fetal ultrasound and MRI imaging, are contributing to a growing body of evidence that abnormal brain architecture is in fact present before birth in hypoplastic left heart syndrome patients, rather than being solely attributable to postnatal factors. We present an overview of the contemporary data on neurodevelopmental outcomes in hypoplastic left heart syndrome, focussing on imaging techniques that are providing greater insight into the nature of disruptions to the fetal circulation, alterations in cerebral blood flow and substrate delivery, disordered brain development, and an increased potential for neurological injury. These susceptibilities are present before any intervention, and are almost certainly substantial contributors to adverse neurodevelopmental outcomes in later childhood. The task now is to determine which subgroups of patients with hypoplastic left heart syndrome are at particular risk of poor neurodevelopmental outcomes and how that risk might be modified. This will allow for more comprehensive counselling for carers, better-informed decision making before birth, and earlier, more tailored provision of neuroprotective strategies and developmental support in the postnatal period.
Pub.: 09 Nov '16, Pinned: 06 Jun '17
Abstract: In this paper we present a novel method for the correction of motion artifacts that are present in fetal Magnetic Resonance Imaging (MRI) scans of the whole uterus. Contrary to current slice-to-volume registration (SVR) methods, requiring an inflexible anatomical enclosure of a single investigated organ, the proposed patch-to-volume reconstruction (PVR) approach is able to reconstruct a large field of view of non-rigidly deforming structures. It relaxes rigid motion assumptions by introducing a specific amount of redundant information that is exploited with parallelized patch-wise optimization, super-resolution, and automatic outlier rejection. We further describe and provide an efficient parallel implementation of PVR allowing its execution within reasonable time on commercially available graphics processing units (GPU), enabling its use in the clinical practice. We evaluate PVR's computational overhead compared to standard methods and observe improved reconstruction accuracy in presence of affine motion artifacts of approximately 30% compared to conventional SVR in synthetic experiments. Furthermore, we have evaluated our method qualitatively and quantitatively on real fetal MRI data subject to maternal breathing and sudden fetal movements. We evaluate peak-signal-to-noise ratio (PSNR), structural similarity index (SSIM), and cross correlation (CC) with respect to the originally acquired data and provide a method for visual inspection of reconstruction uncertainty. With these experiments we demonstrate successful application of PVR motion compensation to the whole uterus, the human fetus, and the human placenta.
Pub.: 22 Nov '16, Pinned: 06 Jun '17
Abstract: We propose an analytical method for calculating blood hematocrit (Hct) and oxygen saturation (sO2 ) from measurements of its T1 and T2 relaxation times.Through algebraic substitution, established two-compartment relationships describing R1=T1-1 and R2=T2-1 as a function of hematocrit and oxygen saturation were rearranged to solve for Hct and sO2 in terms of R1 and R2 . Resulting solutions for Hct and sO2 are the roots of cubic polynomials.Feasibility of the method was established by comparison of Hct and sO2 estimates obtained from relaxometry measurements (at 1.5 Tesla) in cord blood specimens to ground-truth values obtained by blood gas analysis. Monte Carlo simulations were also conducted to assess the effect of T1 , T2 measurement uncertainty on precision of Hct and sO2 estimates.Good agreement was observed between estimated and ground-truth blood properties (bias = 0.01; 95% limits of agreement = ±0.13 for Hct and sO2 ). Considering the combined effects of biological variability and random measurement noise, we estimate a typical uncertainty of ±0.1 for Hct, sO2 estimates.Results demonstrate accurate quantification of Hct and sO2 from T1 and T2 . This method is applicable to noninvasive fetal vessel oximetry-an application where existing oximetry devices are unusable or require risky blood-sampling procedures. Magn Reson Med, 2017. © 2017 International Society for Magnetic Resonance in Medicine.
Pub.: 14 Feb '17, Pinned: 06 Jun '17
Abstract: The human placenta is essential for the supply of the fetus. To monitor the fetal development, imaging data is acquired using ultrasound (US). Although it is currently the gold-standard in fetal imaging, it might not capture certain abnormalities of the placenta. Magnetic resonance imaging (MRI) is a safe alternative for the in utero examination while acquiring the fetus data in higher detail. Nevertheless, there is currently no established procedure for assessing the condition of the placenta and consequently the fetal health. Due to maternal respiration and inherent movements of the fetus during examination, a quantitative assessment of the placenta requires fetal motion compensation, precise placenta segmentation and a standardized visualization, which are challenging tasks. Utilizing advanced motion compensation and automatic segmentation methods to extract the highly versatile shape of the placenta, we introduce a novel visualization technique that presents the fetal and maternal side of the placenta in a standardized way. Our approach enables physicians to explore the placenta even in utero. This establishes the basis for a comparative assessment of multiple placentas to analyze possible pathologic arrangements and to support the research and understanding of this vital organ. Additionally, we propose a three-dimensional structure-aware surface slicing technique in order to explore relevant regions inside the placenta. Finally, to survey the applicability of our approach, we consulted clinical experts in prenatal diagnostics and imaging. We received mainly positive feedback, especially the applicability of our technique for research purposes was appreciated.
Pub.: 03 Mar '17, Pinned: 06 Jun '17
Abstract: To develop and evaluate a reconstruction framework for high resolution time-resolved CMR of the fetal heart in the presence of motion.Data were acquired using a golden angle radial trajectory in seven fetal subjects and reconstructed as real-time images to detect fetal movement. Data acquired during through-plane motion were discarded whereas in-plane motion was corrected. A fetal cardiac gating signal was extracted to sort the corrected data by cardiac phase, allowing reconstruction of cine images. The quality of motion corrected images and the effect of data undersampling were quantified using separate expressions for spatial blur and image error.Motion corrected reordered cine reconstructions (127 slices) showed improved image quality relative to both uncorrected cines and corresponding real-time images across a range of root-mean-squared (RMS) displacements (0.3-3.7 mm) and fetal heart rates (119-176 bpm). The relative spatial blur between cines with and without motion correction increased with in-plane RMS displacement leading to an effective decrease in the effective spatial resolution for images without motion correction. Image error between undersampled and reference images was less than 10% for reconstructions using 750 or more spokes, yielding a minimum acceptable scan time of approximately 4 s/slice during quiescent through plane motion.By rejecting data corrupted by through-plane motion, and correcting data corrupted by in-plane translation, the proposed reconstruction framework accounts for common sources of motion artifact (gross fetal movement, maternal respiration, fetal cardiac contraction) to produce high quality images of the fetal heart.
Pub.: 21 Mar '17, Pinned: 06 Jun '17
Abstract: Development of a MRI acquisition and reconstruction strategy to depict fetal cardiac anatomy in the presence of maternal and fetal motion.The proposed strategy involves i) acquisition and reconstruction of highly accelerated dynamic MRI, followed by image-based ii) cardiac synchronization, iii) motion correction, iv) outlier rejection, and finally v) cardiac cine reconstruction. Postprocessing entirely was automated, aside from a user-defined region of interest delineating the fetal heart. The method was evaluated in 30 mid- to late gestational age singleton pregnancies scanned without maternal breath-hold.The combination of complementary acquisition/reconstruction and correction/rejection steps in the pipeline served to improve the quality of the reconstructed 2D cine images, resulting in increased visibility of small, dynamic anatomical features. Artifact-free cine images successfully were produced in 36 of 39 acquired data sets; prolonged general fetal movements precluded processing of the remaining three data sets.The proposed method shows promise as a motion-tolerant framework to enable further detail in MRI studies of the fetal heart and great vessels. Processing data in image-space allowed for spatial and temporal operations to be applied to the fetal heart in isolation, separate from extraneous changes elsewhere in the field of view. Magn Reson Med, 2017. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Pub.: 04 Apr '17, Pinned: 06 Jun '17
Abstract: This study aimed to evaluate the feasibility of fetal magnetic resonance imaging (MRI) with steady-state free precession (SSFP) sequences to visualise the normal and pathological appearances of the cardiovascular system.This is a prospective observational study of 83 pregnant women who underwent fetal cardiac MRI: 43 patients (cases) had echocardiographic suspicion of congenital heart disease; 40 patients (controls) did not. Fetal cardiac MRI consisted of a static phase with multiplanar SSFP sequences and a dynamic phase with real-time SSFP sequences. Two radiologists evaluated the diagnostic quality of the SSFP images in both the controls and cases, the MRI morphological and functional features in the controls and the MRI signs of congenital heart disease in the cases.In both groups, SSFP sequences produced goodquality MR images and good visualisation of morphological features. Functional data appeared to be unavailable due to the current small temporal resolution and the technical impossibility of fetal cardiac triggering. MRI detected direct signs of congenital heart disease in 21 fetuses, indirect signs in six and both signs in 15.SSFP sequences are effective in demonstrating the morphological features of the cardiovascular system, whereas dynamic SSFP cine-MRI sequences may provide adjunctive albeit suboptimal functional information.
Pub.: 02 Jul '09, Pinned: 06 Jun '17
Abstract: Phase-contrast magnetic resonance imaging can be used to complement echocardiography for the evaluation of the fetal heart. Cardiac imaging typically requires gating with peripheral hardware; however, a gating signal is not readily available in utero. No successful application of existing technologies to human fetal phase-contrast magnetic resonance imaging has been reported to date in the literature. The purpose of this work is to develop a technique for phase-contrast magnetic resonance imaging of the fetal heart that does not require measurement of a gating signal. Metric optimized gating involves acquiring data without gating and retrospectively determining the proper reconstruction by optimizing an image metric. The effects of incorrect gating on phase contrast images were investigated, and the time-entropy of the series of images was found to provide a good measure of the level of corruption. The technique was validated with a pulsatile flow phantom, experiments with adult volunteers, and in vivo application in the fetal population. Images and flow curves from these measurements are presented. Additionally, numerical simulations were used to investigate the degree to which heart rate variability affects the reconstruction process. Metric optimized gating enables imaging with conventional phase-contrast magnetic resonance imaging sequences in the absence of a gating signal, permitting flow measurements in the great vessels in utero.
Pub.: 16 Jul '10, Pinned: 06 Jun '17
Abstract: Significant congenital heart disease (sCHD) affects 3.6 per 1000 births, and is often associated with extracardiac and chromosomal anomalies. Although early mortality has been substantially reduced and the rate of long-term survival has improved, sCHD is, after preterm birth, the second most frequent cause of neonatal infant death. The prenatal detection of cardiac and vascular abnormalities enables optimal parental counselling and perinatal management. Echocardiography (ECG) is the first-line examination and gold standard by which cardiac malformations are defined. However, adequate examination by an experienced healthcare provider with modern technical imaging equipment is required. In addition, maternal factors and the gestational age may lower the image quality. Fetal magnetic resonance imaging (MRI) has been implemented over the last several years and is already used in the clinical routine as a second-line approach to assess fetal abnormalities. MRI of the fetal heart is still not routinely performed. Nevertheless, fetal cardiac MRI has the potential to complement ultrasound in detecting cardiovascular malformations and extracardiac lesions. The present work reviews the potential of MRI to delineate the anatomy and pathologies of the fetal heart. This work also deals with the limitations and continuing developments designed to overcome the current problems in cardiac imaging, including fast fetal heart rates, the lack of ECG-gating, and the presence of fetal movements.
Pub.: 08 Jun '13, Pinned: 06 Jun '17
Abstract: Fetal echocardiography is the imaging modality of choice for prenatal diagnosis of congenital cardiovascular anomalies. However, echocardiography has limitations. Fetal cardiac magnetic resonance imaging (MRI) has the potential to complement US in detecting congenital cardiovascular anomalies. This article draws on our experience; it describes the transverse aortic arch view on fetal cardiac MRI and important clues on an abnormal transverse view at the level of the aortic arch to the diagnosis of fetal congenital cardiovascular anomalies.
Pub.: 26 Aug '14, Pinned: 06 Jun '17