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 echo planar imaging 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. A 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 4.2 ± $$ \pm $$ 2.6 mm for the fetal eyes and 6.5 ± $$ \pm $$ 3.2 for the cerebellum, planning quality was 2.4/3 (compared to 2.6/3 for manual planning) and diagnostic image quality was 2.2 compared to 2.1 for manual planning. CONCLUSIONS: Real-time automatic planning of all three key fetal brain planes was successfully achieved and will pave the way toward simplifying the acquisition of fetal MRI thereby widening the availability of this modality in nonspecialist centers.

In vivo T2 measurements of the fetal brain using single-shot fast spin echo sequences.

PURPOSE: We propose a quantitative framework for motion-corrected T2 fetal brain measurements in vivo and validate the single-shot fast spin echo (SS-FSE) sequence to perform these measurements. METHODS: Stacks of two-dimensional SS-FSE slices are acquired with different echo times (TE) and motion-corrected with slice-to-volume reconstruction (SVR). The quantitative T2 maps are obtained by a fit to a dictionary of simulated signals. The sequence is selected using simulated experiments on a numerical phantom and validated on a physical phantom scanned on a 1.5T system. In vivo quantitative T2 maps are obtained for five fetuses with gestational ages (GA) 21-35 weeks on the same 1.5T system. RESULTS: The simulated experiments suggested that a TE of 400 ms combined with the clinically utilized TEs of 80 and 180 ms were most suitable for T2 measurements in the fetal brain. The validation on the physical phantom confirmed that the SS-FSE T2 measurements match the gold standard multi-echo spin echo measurements. We measured average T2s of around 200 and 280 ms in the fetal brain grey and white matter, respectively. This was slightly higher than fetal T2* and the neonatal T2 obtained from previous studies. CONCLUSION: The motion-corrected SS-FSE acquisitions with varying TEs offer a promising practical framework for quantitative T2 measurements of the moving fetus.

Preeclampsia Associated Differences in the Placenta, Fetal Brain, and Maternal Heart Can Be Demonstrated Antenatally: An Observational Cohort Study Using MRI.

BACKGROUND: Preeclampsia is a multiorgan disease of pregnancy that has short- and long-term implications for the woman and fetus, whose immediate impact is poorly understood. We present a novel multiorgan approach to magnetic resonance imaging (MRI) investigation of preeclampsia, with the acquisition of maternal cardiac, placental, and fetal brain anatomic and functional imaging. METHODS: An observational study was performed recruiting 3 groups of pregnant women: those with preeclampsia, chronic hypertension, or no medical complications. All women underwent a cardiac MRI, and pregnant women underwent a placental-fetal MRI. Cardiac analysis for structural, morphological, and flow data were undertaken; placenta and fetal brain volumetric and T2* (which describes relative tissue oxygenation) data were obtained. All results were corrected for gestational age. A nonpregnant cohort was identified for inclusion in the statistical shape analysis. RESULTS: Seventy-eight MRIs were obtained during pregnancy. Cardiac MRI analysis demonstrated higher left ventricular mass in preeclampsia with 3-dimensional modeling revealing additional specific characteristics of eccentricity and outflow track remodeling. Pregnancies affected by preeclampsia demonstrated lower placental and fetal brain T2*. Within the preeclampsia group, 23% placental T2* results were consistent with controls, these were the only cases with normal placental histopathology. Fetal brain T2* results were consistent with normal controls in 31% of cases. CONCLUSIONS: We present the first holistic assessment of the immediate implications of preeclampsia on maternal heart, placenta, and fetal brain. As well as having potential clinical implications for the risk stratification and management of women with preeclampsia, this gives an insight into the disease mechanism.

Widespread, depth-dependent cortical microstructure alterations in pediatric focal epilepsy.

OBJECTIVE: Tissue abnormalities in focal epilepsy may extend beyond the presumed focus. The underlying pathophysiology of these broader changes is unclear, and it is not known whether they result from ongoing disease processes or treatment-related side effects, or whether they emerge earlier. Few studies have focused on the period of onset for most focal epilepsies, childhood. Fewer still have utilized quantitative magnetic resonance imaging (MRI), which may provide a more sensitive and interpretable measure of tissue microstructural change. Here, we aimed to determine common spatial modes of changes in cortical architecture in children with heterogeneous drug-resistant focal epilepsy and, secondarily, whether changes were related to disease severity. METHODS: To assess cortical microstructure, quantitative T1 and T2 relaxometry (qT1 and qT2) was measured in 43 children with drug-resistant focal epilepsy (age range = 4-18 years) and 46 typically developing children (age range = 2-18 years). We assessed depth-dependent qT1 and qT2 values across the neocortex, as well as their gradient of change across cortical depths. We also determined whether global changes seen in group analyses were driven by focal pathologies in individual patients. Finally, as a proof-of-concept, we trained a classifier using qT1 and qT2 gradient maps from patients with radiologically defined abnormalities (MRI positive) and healthy controls, and tested whether this could classify patients without reported radiological abnormalities (MRI negative). RESULTS: We uncovered depth-dependent qT1 and qT2 increases in widespread cortical areas in patients, likely representing microstructural alterations in myelin or gliosis. Changes did not correlate with disease severity measures, suggesting they may represent antecedent neurobiological alterations. Using a classifier trained with MRI-positive patients and controls, sensitivity was 71.4% at 89.4% specificity on held-out MRI-negative patients. SIGNIFICANCE: These findings suggest the presence of a potential imaging endophenotype of focal epilepsy, detectable irrespective of radiologically identified abnormalities.

Characterisation of placental, fetal brain and maternal cardiac structure and function in pre-eclampsia using MRI.

Background: Pre-eclampsia is a multiorgan disease of pregnancy that has short- and long-term implications for the woman and fetus, whose immediate impact is poorly understood. We present a novel multi-system approach to MRI investigation of pre-eclampsia, with acquisition of maternal cardiac, placental, and fetal brain anatomical and functional imaging. Methods: A prospective study was carried out recruiting pregnant women with pre-eclampsia, chronic hypertension, or no medical complications, and a non-pregnant female cohort. All women underwent a cardiac MRI, and pregnant women underwent a fetal-placental MRI. Cardiac analysis for structural, morphological and flow data was undertaken; placenta and fetal brain volumetric and T2* data were obtained. All results were corrected for gestational age. Results: Seventy-eight MRIs were obtained during pregnancy. Pregnancies affected by pre-eclampsia demonstrated lower placental and fetal brain T2*. Within the pre-eclampsia group, three placental T2* results were within the normal range, these were the only cases with normal placental histopathology. Similarly, three fetal brain T2* results were within the normal range; these cases had no evidence of cerebral redistribution on fetal Dopplers. Cardiac MRI analysis demonstrated higher left ventricular mass in pre-eclampsia with 3D modelling revealing additional specific characteristics of eccentricity and outflow track remodelling. Conclusions: We present the first holistic assessment of the immediate implications of pre-eclampsia on the placenta, maternal heart, and fetal brain. As well as having potential clinical implications for the risk-stratification and management of women with pre-eclampsia, this gives an insight into disease mechanism.

Spatiotemporal tissue maturation of thalamocortical pathways in the human fetal brain.

The development of connectivity between the thalamus and maturing cortex is a fundamental process in the second half of human gestation, establishing the neural circuits that are the basis for several important brain functions. In this study, we acquired high-resolution in utero diffusion magnetic resonance imaging (MRI) from 140 fetuses as part of the Developing Human Connectome Project, to examine the emergence of thalamocortical white matter over the second to third trimester. We delineate developing thalamocortical pathways and parcellate the fetal thalamus according to its cortical connectivity using diffusion tractography. We then quantify microstructural tissue components along the tracts in fetal compartments that are critical substrates for white matter maturation, such as the subplate and intermediate zone. We identify patterns of change in the diffusion metrics that reflect critical neurobiological transitions occurring in the second to third trimester, such as the disassembly of radial glial scaffolding and the lamination of the cortical plate. These maturational trajectories of MR signal in transient fetal compartments provide a normative reference to complement histological knowledge, facilitating future studies to establish how developmental disruptions in these regions contribute to pathophysiology.

The Developing Human Connectome Project Neonatal Data Release.

The Developing Human Connectome Project has created a large open science resource which provides researchers with data for investigating typical and atypical brain development across the perinatal period. It has collected 1228 multimodal magnetic resonance imaging (MRI) brain datasets from 1173 fetal and/or neonatal participants, together with collateral demographic, clinical, family, neurocognitive and genomic data from 1173 participants, together with collateral demographic, clinical, family, neurocognitive and genomic data. All subjects were studied in utero and/or soon after birth on a single MRI scanner using specially developed scanning sequences which included novel motion-tolerant imaging methods. Imaging data are complemented by rich demographic, clinical, neurodevelopmental, and genomic information. The project is now releasing a large set of neonatal data; fetal data will be described and released separately. This release includes scans from 783 infants of whom: 583 were healthy infants born at term; as well as preterm infants; and infants at high risk of atypical neurocognitive development. Many infants were imaged more than once to provide longitudinal data, and the total number of datasets being released is 887. We now describe the dHCP image acquisition and processing protocols, summarize the available imaging and collateral data, and provide information on how the data can be accessed.

Cardiac and placental imaging (CARP) in pregnancy to assess aetiology of preeclampsia.

INTRODUCTION: The CARP study aims to investigate placental function, cardiac function and fetal growth comprehensively during pregnancy, a time of maximal cardiac stress, to work towards disentangling the complex cardiac and placental interactions presenting in the aetiology of pre-eclampsia as well as predicting maternal Cardiovascular Disease (CVD) risk in later life. BACKGROUND: The involvement of the cardiovascular system in pre-eclampsia, one of the most serious complications of pregnancy, is evident. While the manifestations of pre-eclampsia during pregnancy (high blood pressure, multi-organ disease, and placental dysfunction) resolve after delivery, a lifelong elevated CVD risk remains. METHOD: An assessment including both cardiac and placental Magnetic Resonance Imaging (MRI) optimised for use in pregnancy and bespoke to the expected changes was developed. Simultaneous structural and functional MRI data from the placenta, the heart and the fetus were obtained in a total of 32 pregnant women (gestational ages from 18.1 to 37.5 weeks), including uncomplicated pregnancies and five cases with early onset pre-eclampsia. RESULTS: The achieved comprehensive MR acquisition was able to demonstrate a phenotype associated with pre-eclampsia linking both placental and cardiac factors, reduced mean T2* (p < 0.005), increased heterogeneity (p < 0.005) and a trend towards an increase in cardiac work, larger average mass (109.4 vs 93.65 gr), wall thickness (7.0 vs 6.4 mm), blood pool volume (135.7 vs 127.48 mL) and mass to volume ratio (0.82 vs 0.75). The cardiac output in the controls was, controlling for gestational age, positively correlated with placental volume (p < 0.05). DISCUSSION: The CARP study constitutes the first joint assessment of functional and structural properties of the cardiac system and the placenta during pregnancy. Early indications of cardiac remodelling in pre-eclampsia were demonstrated paving the way for larger studies.

Brain volumetry in fetuses that deliver very preterm: An MRI pilot study.

BACKGROUND: Infants born preterm are at increased risk of neurological complications resulting in significant morbidity and mortality. The exact mechanism and the impact of antenatal factors has not been fully elucidated, although antenatal infection/inflammation has been implicated in both the aetiology of preterm birth and subsequent neurological sequelae. It is therefore hypothesized that processes driving preterm birth are affecting brain development in utero. This study aims to compare MRI derived regional brain volumes in fetuses that deliver < 32 weeks with fetuses that subsequently deliver at term. METHODS: Women at high risk of preterm birth, with gestation 19.4-32 weeks were recruited prospectively. A control group was obtained from existing study datasets. Fetal MRI was performed on a 1.5 T or 3 T MRI scanner: T2-weighted images were obtained of the fetal brain. 3D brain volumetric datsets were produced using slice to volume reconstruction and regional segmentations were produced using multi-atlas approaches for supratentorial brain tissue, lateral ventricles, cerebellum cerebral cortex and extra-cerebrospinal fluid (eCSF). Statistical comparison of control and high-risk for preterm delivery fetuses was performed by creating normal ranges for each parameter from the control datasets and then calculating gestation adjusted z scores. Groups were compared using t-tests. RESULTS: Fetal image datasets from 24 pregnancies with delivery < 32 weeks and 87 control pregnancies that delivered > 37 weeks were included. Median gestation at MRI of the preterm group was 26.8 weeks (range 19.4-31.4) and control group 26.2 weeks (range 21.7-31.9). No difference was found in supra-tentorial brain volume, ventricular volume or cerebellar volume but the eCSF and cerebral cortex volumes were smaller in fetuses that delivered preterm (p < 0.001 in both cases). CONCLUSION: Fetuses that deliver preterm have a reduction in cortical and eCSF volumes. This is a novel finding and needs further investigation. If alterations in brain development are commencing antenatally in fetuses that subsequently deliver preterm, this may present a window for in utero therapy in the future.

T2* placental MRI in pregnancies complicated with fetal congenital heart disease.

BACKGROUND: Congenital heart disease (CHD) is one of the most important and common group of congenital malformations in humans. Concurrent development and close functional links between the fetal heart and placenta emphasise the importance of understanding placental function and its influence in pregnancy outcomes. The aim of this study was to evaluate placental oxygenation by relaxometry (T2*) to assess differences in placental phenotype and function in CHD. METHODS: In this prospective cross-sectional observational study, 69 women with a fetus affected with CHD and 37 controls, whole placental T2* was acquired using a 1.5-Tesla MRI scanner. Gaussian Process Regression was used to assess differences in placental phenotype in CHD cohorts compared to our controls. RESULTS: Placental T2* maps demonstrated significant differences in CHD compared to controls at equivalent gestational age. Mean T2* values over the entire placental volume were lowest compared to predicted normal in right sided obstructive lesions (RSOL) (Z-Score 2.30). This cohort also showed highest lacunarity indices (Z-score -1.7), as a marker of lobule size. Distribution patterns of T2* values over the entire placental volume were positively skewed in RSOL (Z-score -4.69) and suspected, not confirmed coarctation of the aorta (CoA-) (Z-score -3.83). Deviations were also reflected in positive kurtosis in RSOL (Z-score -3.47) and CoA- (Z-score -2.86). CONCLUSION: Placental structure and function appear to deviate from normal development in pregnancies with fetal CHD. Specific patterns of altered placental function assessed by T2* deliver crucial complementary information to antenatal assessments in the presence of fetal CHD.