Brain development in fetal growth restriction: A volumetric approach using fetal MRI

Fetal growth restriction is the failure of a fetus to achieve its full growth potential, resulting in a neonate that is small for its gestational age. The aetiology of fetal growth restriction is varied and fetal growth restriction secondary to placental insufficiency is attributed to a failure of trophoblast invasion leading to under perfusion of the uteroplacental bed. In response to the adverse conditions in-utero, fetuses tend to compensate by increasing blood flow to the essential organs such as the brain, heart, and adrenals, at the expense of other organs (cerebral redistribution). As a consequence, growth tends to be asymmetric, with maintenance of the head growth velocity while the other growth parameters tail off; an effect which is also known as the ‘brain sparing effect’. Despite this apparent brain sparing effect, children who were growth restricted in utero are at increased risk of developmental delay and behavioural problems. 30 growth restricted and 48 normally grown fetuses were recruited into this study and were imaged using both conventional ultrasound with Doppler assessment, as well as fetal MRI with ssFSE sequences through the feto-placental unit and fetal brain. A dynamic approach was taken when imaging the fetal brain to compensate for the presence of fetal motion. MR imaging of the feto-placental unit detected significant differences in placental appearance, significantly smaller volumes of intra-abdominal and intra-thoracic organs, and significantly smaller regional brain growth among growth restricted fetuses. MR studies of the placenta in fetal growth restriction demonstrated a placental phenotype in growth restricted pregnancies that is characterised by smaller placental volumes, a significant increase in the placental volume affected by apparent pathology on MRI and a thickened, globular placenta. Although placental volume increased with gestation in both groups, the placental volume remained significantly smaller in the growth restricted fetuses (p = 0.003). There was also a significant correlation between the percentage of placental volume affected by abnormal heterogeneity and the severity of fetal growth restriction (r = 0.82, p < 0.001), and an increase in the maximal placental thickness to placental volume ratio above the 95th centile for gestational age was associated with fetal and early neonatal mortality (relative risk = 7, 95%CI = 2.96 – 16.55, p < 0.001) (figure 3.6) MR studies of fetal intra-thoracic and intra-abdominal volumes showed that although the volume of the intra-thoracic and intra-abdonimal organs (heart, lungs, thymus, liver and kidney) increased as gestation increased in both groups, the volumes of all three structures remained smaller in growth restricted fetuses (p < 0.01) (Figures 4.7 - 4.9) compared with normally grown fetuses. MR studies of the fetal brain demonstrated smaller intracranial volume, total brain volume and cerebellar volume in growth restricted fetuses. In addition, growth restricted fetuses with early onset fetal growth restriction demonstrated smaller vermis height and a corresponding increase in the tegmento-vermian angle. Growth restricted fetuses also demonstrated a disproportionate decrease in extra- and intra-cerebral fluid. This thesis showed evidence of changes in regional and global organ growth in growth restricted fetuses using high resolution fetal MRI. It is hoped that future imaging studies could offer useful insights into the origins and clinical significance of these findings and its consequences for later neurodevelopment

PVR: Patch-to-Volume Reconstruction for Large Area Motion Correction of Fetal MRI

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.Comment: 10 pages, 13 figures, submitted to IEEE Transactions on Medical Imaging. v2: wadded funders acknowledgements to preprin

DeepCut: Object Segmentation from Bounding Box Annotations using Convolutional Neural Networks

In this paper, we propose DeepCut, a method to obtain pixelwise object segmentations given an image dataset labelled with bounding box annotations. It extends the approach of the well-known GrabCut method to include machine learning by training a neural network classifier from bounding box annotations. We formulate the problem as an energy minimisation problem over a densely-connected conditional random field and iteratively update the training targets to obtain pixelwise object segmentations. Additionally, we propose variants of the DeepCut method and compare those to a naive approach to CNN training under weak supervision. We test its applicability to solve brain and lung segmentation problems on a challenging fetal magnetic resonance dataset and obtain encouraging results in terms of accuracy

Perinatal brain injury

Perinatal brain injury is an important cause of both early and long term morbidity and mortality. The pathophysiology of perinatal brain injury is complex, and often gestation dependent. Ultrasound has traditionally been the imaging modality of choice used to diagnose these lesions; however, the advent of Magnetic Resonance Imaging (MRI) has improved diagnosis and has enabled the correlation of lesions in the neonatal period with longer term neurodevelopmental sequelae. This review aims to address injury in both the term and pre-term brain, its relationship with long term outcome as well as discussing potential treatment strategies which may be deployed in the future

Brain development in fetal growth restriction : a volumetric approach using fetal MRI

Fetal growth restriction is the failure of a fetus to achieve its full growth potential, resulting in a neonate that is small for its gestational age. The aetiology of fetal growth restriction is varied and fetal growth restriction secondary to placental insufficiency is attributed to a failure of trophoblast invasion leading to under perfusion of the uteroplacental bed. In response to the adverse conditions in-utero, fetuses tend to compensate by increasing blood flow to the essential organs such as the brain, heart, and adrenals, at the expense of other organs (cerebral redistribution). As a consequence, growth tends to be asymmetric, with maintenance of the head growth velocity while the other growth parameters tail off; an effect which is also known as the ‘brain sparing effect’. Despite this apparent brain sparing effect, children who were growth restricted in utero are at increased risk of developmental delay and behavioural problems. 30 growth restricted and 48 normally grown fetuses were recruited into this study and were imaged using both conventional ultrasound with Doppler assessment, as well as fetal MRI with ssFSE sequences through the feto-placental unit and fetal brain. A dynamic approach was taken when imaging the fetal brain to compensate for the presence of fetal motion. MR imaging of the feto-placental unit detected significant differences in placental appearance, significantly smaller volumes of intra-abdominal and intra-thoracic organs, and significantly smaller regional brain growth among growth restricted fetuses. MR studies of the placenta in fetal growth restriction demonstrated a placental phenotype in growth restricted pregnancies that is characterised by smaller placental volumes, a significant increase in the placental volume affected by apparent pathology on MRI and a thickened, globular placenta. Although placental volume increased with gestation in both groups, the placental volume remained significantly smaller in the growth restricted fetuses (p = 0.003). There was also a significant correlation between the percentage of placental volume affected by abnormal heterogeneity and the severity of fetal growth restriction (r = 0.82, p < 0.001), and an increase in the maximal placental thickness to placental volume ratio above the 95th centile for gestational age was associated with fetal and early neonatal mortality (relative risk = 7, 95%CI = 2.96 – 16.55, p < 0.001) (figure 3.6) MR studies of fetal intra-thoracic and intra-abdominal volumes showed that although the volume of the intra-thoracic and intra-abdonimal organs (heart, lungs, thymus, liver and kidney) increased as gestation increased in both groups, the volumes of all three structures remained smaller in growth restricted fetuses (p < 0.01) (Figures 4.7 - 4.9) compared with normally grown fetuses. MR studies of the fetal brain demonstrated smaller intracranial volume, total brain volume and cerebellar volume in growth restricted fetuses. In addition, growth restricted fetuses with early onset fetal growth restriction demonstrated smaller vermis height and a corresponding increase in the tegmento-vermian angle. Growth restricted fetuses also demonstrated a disproportionate decrease in extra- and intra-cerebral fluid. This thesis showed evidence of changes in regional and global organ growth in growth restricted fetuses using high resolution fetal MRI. It is hoped that future imaging studies could offer useful insights into the origins and clinical significance of these findings and its consequences for later neurodevelopment.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Proton magnetic resonance spectroscopy in the fetus

Magnetic Resonance Imaging (MRI) has become an established technique in fetal medicine, providing complementary information to ultrasound in studies of the brain. MRI can provide detailed structural information irrespective of the position of the fetal head or maternal habitus. Proton Magnetic Resonance Spectroscopy ( HMRS) is based on the same physical principles as MRI but data are collected as a spectrum, allowing the biochemical and metabolic status of in vivo tissue to be studied in a non-invasive manner. HMRS has been used to assess metabolic function in the neonatal brain but fetal studies have been limited, primarily due to fetal motion. This review will assess the technique and findings from fetal studies to date

Brain metabolism in fetal intrauterine growth restriction: a proton magnetic resonance spectroscopy study

Objective: The purpose of this study was to investigate alterations in brain metabolism in fetuses with intrauterine growth restriction (IUGR) and evidence of cerebral redistribution of blood flow. Study Design: Biometry and Doppler assessment of blood flow was assessed with ultrasound in 28 fetuses with IUGR and cerebral redistribution and in 41 appropriately grown control subjects. Proton magnetic resonance spectroscopy of the fetal brain was then performed to determine the presence of choline (Cho), creatine (Cr), N-acetylaspartate (NAA), and lactate and to generate ratios for NAA:Cho, NAA:Cr, and Cho:Cr. Results: Sixty-five percent of spectra were interpretable: N-acetylaspartate, choline, and creatine peaks were identified in all these spectra; lactate was present in 5 IUGR fetuses and in 3 appropriately grown fetuses. NAA:Cr and NAA:Cho ratios were significantly lower in IUGR fetuses with cerebral redistribution. Conclusion: Cerebral redistribution is associated with altered brain metabolism that is evidenced by a reduction in NAA:Cho and NAA:Cr ratios