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BACKGROUND: Congenital heart disease (CHD) has been linked to impaired placental and fetal brain development. Assessing the placenta and fetal brain in parallel may help further our understanding of the relationship between development of these organs. HYPOTHESIS: 1) Placental and fetal brain oxygenation are correlated, 2) oxygenation in these organs is reduced in CHD compared to healthy controls, and 3) placental structure is altered in CHD. STUDY TYPE: Retrospective case-control. POPULATION: Fifty-one human fetuses with CHD (32 male; median [IQR] gestational age [GA] = 32.0 [30.9-32.9] weeks) and 30 from uncomplicated pregnancies with normal birth outcomes (18 male; median [IQR] GA = 34.5 [31.9-36.7] weeks). FIELD STRENGTH/SEQUENCE: 1.5 T single-shot multi-echo-gradient-echo echo-planar imaging. ASSESSMENT: Masking was performed using an automated nnUnet model. Mean brain and placental T2* and quantitative measures of placental texture, volume, and morphology were calculated. STATISTICAL TESTS: Spearman's correlation coefficient for determining the association between brain and placental T2*, and between brain and placental characteristics with GA. P-values for comparing brain T2*, placenta T2*, and placental characteristics between groups derived from ANOVA. Significance level P < 0.05. RESULTS: There was a significant positive association between placental and fetal brain T2* (â´ = 0.46). Placental and fetal brain T2* showed a significant negative correlation with GA (placental T2* â´ = -0.65; fetal brain T2* â´ = -0.32). Both placental and fetal brain T2* values were significantly reduced in CHD, after adjusting for GA (placental T2*: control = 97 [±24] msec, CHD = 83 [±23] msec; brain T2*: control = 218 [±26] msec, CHD = 202 [±25] msec). Placental texture and morphology were also significantly altered in CHD (Texture: control = 0.84 [0.83-0.87], CHD = 0.80 [0.78-0.84]; Morphology: control = 9.9 [±2.2], CHD = 10.8 [±2.0]). For all fetuses, there was a significant positive association between placental T2* and placental texture (â´ = 0.46). CONCLUSION: Placental and fetal brain T2* values are associated in healthy fetuses and those with CHD. Placental and fetal brain oxygenation are reduced in CHD. Placental appearance is significantly altered in CHD and shows associations with placental oxygenation, suggesting altered placental development and function may be related. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.
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BACKGROUND: In double aortic arch (DAA) one of the arches can demonstrate atretic portions postnatally, leading to diagnostic uncertainty due to overlap with isolated right aortic arch (RAA) variants. The main objective of this study is to demonstrate the morphological evolution of different DAA phenotypes from prenatal to postnatal life using 3D fetal cardiac magnetic resonance imaging (CMR) and postnatal CT/CMR imaging. METHODS: 3D fetal CMR was undertaken in fetuses with suspected DAA over a six-year period (Jan 2016 - Jan 2022). All cases with surgical confirmation of DAA were retrospectively studied and morphology on fetal CMR was compared to postnatal CT/CMR and surgical findings. RESULTS: 32 fetuses with surgically confirmed DAA underwent fetal CMR. All demonstrated a complete DAA with left-sided arterial duct. The RAA was dominant in 30/32 (94%). Postnatal CT/CMR was undertaken at median age of 3.3months (IQR 2.0-3.9) demonstrating DAA with patency of both arches in 9/32 (28%), with 6 showing signs of coarctation of the left aortic arch (LAA). The LAA isthmus was not present on CT/CMR in 22/32(69%), the transverse arch between left carotid and left subclavian artery was not present in 1 case. CONCLUSIONS: Fetal CMR provides novel insights into perinatal evolution of DAA. The smaller LAA can develop coarctation or atresia related to postnatal constriction of the arterial duct, making diagnosis of DAA challenging with contrast-enhanced CT/CMR. This highlights the potentially important role for prenatal 3D vascular imaging and might improve intepretation of postnatal imaging.
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BACKGROUND: Congenital heart disease (CHD) is common and is associated with impaired early brain development and neurodevelopmental outcomes, yet the exact mechanisms underlying these associations are unclear. PURPOSE: To utilize MRI data from a cohort of fetuses with CHD as well as typically developing fetuses to test the hypothesis that expected cerebral substrate delivery is associated with total and regional fetal brain volumes. STUDY TYPE: Retrospective case-control study. POPULATION: Three hundred eighty fetuses (188 male), comprising 45 healthy controls and 335 with isolated CHD, scanned between 29 and 37 weeks gestation. Fetuses with CHD were assigned into one of four groups based on expected cerebral substrate delivery. FIELD STRENGTH/SEQUENCE: T2-weighted single-shot fast-spin-echo sequences and a balanced steady-state free precession gradient echo sequence were obtained on a 1.5 T scanner. ASSESSMENT: Images were motion-corrected and reconstructed using an automated slice-to-volume registration reconstruction technique, before undergoing segmentation using an automated pipeline and convolutional neural network that had undergone semi-supervised training. Differences in total, regional brain (cortical gray matter, white matter, deep gray matter, cerebellum, and brainstem) and brain:body volumes were compared between groups. STATISTICAL TESTS: ANOVA was used to test for differences in brain volumes between groups, after accounting for sex and gestational age at scan. PFDR -values <0.05 were considered statistically significant. RESULTS: Total and regional brain volumes were smaller in fetuses where cerebral substrate delivery is reduced. No significant differences were observed in total or regional brain volumes between control fetuses and fetuses with CHD but normal cerebral substrate delivery (all PFDR > 0.12). Severely reduced cerebral substrate delivery is associated with lower brain:body volume ratios. DATA CONCLUSION: Total and regional brain volumes are smaller in fetuses with CHD where there is a reduction in cerebral substrate delivery, but not in those where cerebral substrate delivery is expected to be normal. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.
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BACKGROUND: Image-domain motion correction of black-blood contrast T2-weighted fetal cardiovascular magnetic resonance imaging (CMR) using slice-to-volume registration (SVR) provides high-resolution three-dimensional (3D) images of the fetal heart providing excellent 3D visualisation of vascular anomalies [1]. However, 3D segmentation of these datasets, important for both clinical reporting and the application of advanced analysis techniques is currently a time-consuming process requiring manual input with potential for inter-user variability. METHODS: In this work, we present novel 3D fetal CMR population-averaged atlases of normal and abnormal fetal cardiovascular anatomy. The atlases are created using motion-corrected 3D reconstructed volumes of 86 third trimester fetuses (gestational age range 29-34 weeks) including: 28 healthy controls, 20 cases with postnatally confirmed neonatal coarctation of the aorta (CoA) and 38 vascular rings (21 right aortic arch (RAA), 17 double aortic arch (DAA)). We used only high image quality datasets with isolated anomalies and without any other deviations in the cardiovascular anatomy.In addition, we implemented and evaluated atlas-guided registration and deep learning (UNETR) methods for automated 3D multi-label segmentation of fetal cardiac vessels. We used images from CoA, RAA and DAA cohorts including: 42 cases for training (14 from each cohort), 3 for validation and 6 for testing. In addition, the potential limitations of the network were investigated on unseen datasets including 3 early gestational age (22 weeks) and 3 low SNR cases. RESULTS: We created four atlases representing the average anatomy of the normal fetal heart, postnatally confirmed neonatal CoA, RAA and DAA. Visual inspection was undertaken to verify expected anatomy per subgroup. The results of the multi-label cardiac vessel UNETR segmentation showed 100[Formula: see text] per-vessel detection rate for both normal and abnormal aortic arch anatomy. CONCLUSIONS: This work introduces the first set of 3D black-blood T2-weighted CMR atlases of normal and abnormal fetal cardiovascular anatomy including detailed segmentation of the major cardiovascular structures. Additionally, we demonstrated the general feasibility of using deep learning for multi-label vessel segmentation of 3D fetal CMR images.
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Coartação Aórtica , Cardiopatias Congênitas , Humanos , Lactente , Recém-Nascido , Aorta Torácica/diagnóstico por imagem , Coração Fetal/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética , Valor Preditivo dos TestesRESUMO
The diverse cerebral consequences of preterm birth create significant challenges for understanding pathogenesis or predicting later outcome. Instead of focusing on describing effects common to the group, comparing individual infants against robust normative data offers a powerful alternative to study brain maturation. Here we used Gaussian process regression to create normative curves characterizing brain volumetric development in 274 term-born infants, modeling for age at scan and sex. We then compared 89 preterm infants scanned at term-equivalent age with these normative charts, relating individual deviations from typical volumetric development to perinatal risk factors and later neurocognitive scores. To test generalizability, we used a second independent dataset comprising of 253 preterm infants scanned using different acquisition parameters and scanner. We describe rapid, nonuniform brain growth during the neonatal period. In both preterm cohorts, cerebral atypicalities were widespread, often multiple, and varied highly between individuals. Deviations from normative development were associated with respiratory support, nutrition, birth weight, and later neurocognition, demonstrating their clinical relevance. Group-level understanding of the preterm brain disguises a large degree of individual differences. We provide a method and normative dataset that offer a more precise characterization of the cerebral consequences of preterm birth by profiling the individual neonatal brain.
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Encéfalo/anatomia & histologia , Recém-Nascido Prematuro/fisiologia , Peso ao Nascer , Desenvolvimento Infantil , Cognição , Estudos de Coortes , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido Prematuro/psicologia , Imageamento por Ressonância Magnética , Masculino , Distribuição Normal , Fenótipo , Gravidez , Nascimento Prematuro , Valores de Referência , Caracteres SexuaisRESUMO
OBJECTIVES: To calculate 3D-segmented total lung volume (TLV) in fetuses with thoracic anomalies using deformable slice-to-volume registration (DSVR) with comparison to 2D-manual segmentation. To establish a normogram of TLV calculated by DSVR in healthy control fetuses. METHODS: A pilot study at a single regional fetal medicine referral centre included 16 magnetic resonance imaging (MRI) datasets of fetuses (22-32 weeks gestational age). Diagnosis was CDH (n = 6), CPAM (n = 2), and healthy controls (n = 8). Deformable slice-to-volume registration was used for reconstruction of 3D isotropic (0.85 mm) volumes of the fetal body followed by semi-automated lung segmentation. 3D TLV were compared to traditional 2D-based volumetry. Abnormal cases referenced to a normogram produced from 100 normal fetuses whose TLV was calculated by DSVR only. RESULTS: Deformable slice-to-volume registration-derived TLV values have high correlation with the 2D-based measurements but with a consistently lower volume; bias -1.44 cm3 [95% limits: -2.6 to -0.3] with improved resolution to exclude hilar structures even in cases of motion corruption or very low lung volumes. CONCLUSIONS: Deformable slice-to-volume registration for fetal lung MRI aids analysis of motion corrupted scans and does not suffer from the interpolation error inherent to 2D-segmentation. It increases information content of acquired data in terms of visualising organs in 3D space and quantification of volumes, which may improve counselling and surgical planning.
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Feto , Imageamento por Ressonância Magnética , Feminino , Feto/diagnóstico por imagem , Idade Gestacional , Humanos , Imageamento Tridimensional/métodos , Pulmão/diagnóstico por imagem , Medidas de Volume Pulmonar/métodos , Imageamento por Ressonância Magnética/métodos , Projetos Piloto , GravidezRESUMO
Premature birth occurs during a period of rapid brain growth. In this context, interpreting clinical neuroimaging can be complicated by the typical changes in brain contrast, size and gyrification occurring in the background to any pathology. To model and describe this evolving background in brain shape and contrast, we used a Bayesian regression technique, Gaussian process regression, adapted to multiple correlated outputs. Using MRI, we simultaneously estimated brain tissue intensity on T1- and T2-weighted scans as well as local tissue shape in a large cohort of 408 neonates scanned cross-sectionally across the perinatal period. The resulting model provided a continuous estimate of brain shape and intensity, appropriate to age at scan, degree of prematurity and sex. Next, we investigated the clinical utility of this model to detect focal white matter injury. In individual neonates, we calculated deviations of a neonate's observed MRI from that predicted by the model to detect punctate white matter lesions with very good accuracy (area under the curve > 0.95). To investigate longitudinal consistency of the model, we calculated model deviations in 46 neonates who were scanned on a second occasion. These infants' voxelwise deviations from the model could be used to identify them from the other 408 images in 83% (T2-weighted) and 76% (T1-weighted) of cases, indicating an anatomical fingerprint. Our approach provides accurate estimates of non-linear changes in brain tissue intensity and shape with clear potential for radiological use.
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Lesões Encefálicas/patologia , Encéfalo/crescimento & desenvolvimento , Nascimento Prematuro/patologia , Substância Branca/patologia , Encéfalo/patologia , Estudos de Coortes , Imagem de Difusão por Ressonância Magnética/métodos , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Estudos Longitudinais , Neuroimagem/métodos , Gravidez , Substância Branca/crescimento & desenvolvimentoRESUMO
Preterm-born children are at increased risk of lifelong neurodevelopmental difficulties. Group-wise analyses of magnetic resonance imaging show many differences between preterm- and term-born infants but do not reliably predict neurocognitive prognosis for individual infants. This might be due to the unrecognized heterogeneity of cerebral injury within the preterm group. This study aimed to determine whether atypical brain microstructural development following preterm birth is significantly variable between infants. Using Gaussian process regression, a technique that allows a single-individual inference, we characterized typical variation of brain microstructure using maps of fractional anisotropy and mean diffusivity in a sample of 270 term-born neonates. Then, we compared 82 preterm infants to these normative values to identify brain regions with atypical microstructure and relate observed deviations to degree of prematurity and neurocognition at 18 months. Preterm infants showed strikingly heterogeneous deviations from typical development, with little spatial overlap between infants. Greater and more extensive deviations, captured by a whole brain atypicality index, were associated with more extreme prematurity and predicted poorer cognitive and language abilities at 18 months. Brain microstructural development after preterm birth is highly variable between individual infants. This poorly understood heterogeneity likely relates to both the etiology and prognosis of brain injury.
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Encéfalo/patologia , Recém-Nascido Prematuro/crescimento & desenvolvimento , Nascimento Prematuro/patologia , Feminino , Humanos , Recém-Nascido , Masculino , Transtornos do Neurodesenvolvimento/epidemiologia , Transtornos do Neurodesenvolvimento/etiologia , GravidezRESUMO
BACKGROUND: Infants born preterm are at increased risk of pulmonary morbidity. The contribution of antenatal factors to impairments in lung structure/function has not been fully elucidated. This study aimed to compare standardized lung volumes from foetuses that were delivered <32 weeks' gestation with foetuses that were delivered >37 weeks. METHODS: Fourteen women who delivered <32 weeks gestation and 56 women who delivered >37 underwent a foetal MRI. Slice-volume reconstruction was then used and the foetal lungs were then segmented using multi-atlas approaches. Body volumes were calculated by manual segmentation and lung:body volume ratios generated. RESULTS: Mean gestation at MRI of the preterm group was 27+2 weeks (SD 2.9, range 20+6-31+3) and control group 25+3 weeks (SD 4.7 range 20+5-31+6). Mean gestation at delivery of the preterm group was 29+2 weeks (SD 2.6, range 22+0-32+0). Lung:body volume ratios and foetal lung volumes were smaller in foetuses that were delivered preterm both with and without preterm premature rupture of membranes compared to those born at term (p < 0.001 in all cases). CONCLUSIONS: Foetuses that were delivered very preterm had reduced lung volumes when standardized for foetal size, irrespective of ruptured membranes. These are novel findings and suggest an antenatal aetiology of insult and possible focus for future preventative therapies.
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Recém-Nascido Prematuro , Pulmão/diagnóstico por imagem , Imageamento por Ressonância Magnética , Nascimento Prematuro , Adulto , Estudos de Casos e Controles , Feminino , Idade Gestacional , Humanos , Pulmão/fisiopatologia , Medidas de Volume Pulmonar , Pessoa de Meia-Idade , Tamanho do Órgão , Projetos Piloto , Valor Preditivo dos Testes , Gravidez , Estudos Prospectivos , Adulto JovemRESUMO
The Developing Human Connectome Project (dHCP) seeks to create the first 4-dimensional connectome of early life. Understanding this connectome in detail may provide insights into normal as well as abnormal patterns of brain development. Following established best practices adopted by the WU-MINN Human Connectome Project (HCP), and pioneered by FreeSurfer, the project utilises cortical surface-based processing pipelines. In this paper, we propose a fully automated processing pipeline for the structural Magnetic Resonance Imaging (MRI) of the developing neonatal brain. This proposed pipeline consists of a refined framework for cortical and sub-cortical volume segmentation, cortical surface extraction, and cortical surface inflation, which has been specifically designed to address considerable differences between adult and neonatal brains, as imaged using MRI. Using the proposed pipeline our results demonstrate that images collected from 465 subjects ranging from 28 to 45 weeks post-menstrual age (PMA) can be processed fully automatically; generating cortical surface models that are topologically correct, and correspond well with manual evaluations of tissue boundaries in 85% of cases. Results improve on state-of-the-art neonatal tissue segmentation models and significant errors were found in only 2% of cases, where these corresponded to subjects with high motion. Downstream, these surfaces will enhance comparisons of functional and diffusion MRI datasets, supporting the modelling of emerging patterns of brain connectivity.
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Encéfalo/anatomia & histologia , Conectoma/métodos , Processamento de Imagem Assistida por Computador/métodos , Feminino , Humanos , Recém-Nascido , Imageamento por Ressonância Magnética/métodos , MasculinoRESUMO
PURPOSE: Advanced diffusion magnetic resonance imaging benefits from collecting as much data as is feasible but is highly sensitive to subject motion and the risk of data loss increases with longer acquisition times. Our purpose was to create a maximally time-efficient and flexible diffusion acquisition capability with built-in robustness to partially acquired or interrupted scans. Our framework has been developed for the developing Human Connectome Project, but different application domains are equally possible. METHODS: Complete flexibility in the sampling of diffusion space combined with free choice of phase-encode-direction and the temporal ordering of the sampling scheme was developed taking into account motion robustness, internal consistency, and hardware limits. A split-diffusion-gradient preparation, multiband acceleration, and a restart capacity were added. RESULTS: The framework was used to explore different parameters choices for the desired high angular resolution diffusion imaging diffusion sampling. For the developing Human Connectome Project, a high-angular resolution, maximally time-efficient (20 min) multishell protocol with 300 diffusion-weighted volumes was acquired in >400 neonates. An optimal design of a high-resolution (1.2 × 1.2 mm2 ) two-shell acquisition with 54 diffusion weighted volumes was obtained using a split-gradient design. CONCLUSION: The presented framework provides flexibility to generate time-efficient and motion-robust diffusion magnetic resonance imaging acquisitions taking into account hardware constraints that might otherwise result in sub-optimal choices. Magn Reson Med 79:1276-1292, 2018. © 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.
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Encéfalo/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética/métodos , Neuroimagem/métodos , Anisotropia , Conectoma , Humanos , Processamento de Imagem Assistida por Computador , Recém-NascidoRESUMO
Neonatal coarctation of the aorta (CoA) is a common congenital heart defect. Its antenatal diagnosis remains challenging, and its pathophysiology is poorly understood. We present a novel statistical shape modeling (SSM) pipeline to study the role and predictive value of arch shape in CoA in utero. Cardiac magnetic resonance imaging (CMR) data of 112 fetuses with suspected CoA was acquired and motion-corrected to three-dimensional volumes. Centerlines from fetal arches were extracted and used to build a statistical shape model capturing relevant anatomical variations. A linear discriminant analysis was used to find the optimal axis between CoA and false positive cases. The CoA shape risk score classified cases with an area under the curve of 0.907. We demonstrate the feasibility of applying a SSM pipeline to three-dimensional fetal CMR data while providing novel insights into the anatomical determinants of CoA and the relevance of in utero arch anatomy for antenatal diagnosis of CoA.
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Coartação Aórtica , Cardiopatias Congênitas , Recém-Nascido , Feminino , Gravidez , Humanos , Coartação Aórtica/diagnóstico por imagem , Aorta , Feto , Cardiopatias Congênitas/diagnóstico por imagem , Imageamento por Ressonância Magnética , Estudos RetrospectivosAssuntos
Corpo Caloso , Lactente Extremamente Prematuro , Humanos , Lactente , Recém-Nascido , Recém-Nascido PrematuroRESUMO
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 < 0.05) as well as a significant reduction in T2* during contractions. The T2* values in the myometrium were however not correlated to 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.
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Trabalho de Parto , Miométrio , Feminino , Gravidez , Humanos , Miométrio/diagnóstico por imagem , Placenta/diagnóstico por imagem , Contração Uterina , ÚteroRESUMO
The impact of fetal motion on phase contrast magnetic resonance imaging (PC-MRI) with metric optimized gating (MOG) remains unknown, despite being a known limitation to prenatal MRI. This study aims to describe the effect of motion on fetal flow-measurements using PC-MRI with MOG and to generate a scoring-system that could be used to predict motion-corrupted datasets at the time of acquisition. Ten adult volunteers underwent PC-MRI with MOG using a motion-device to simulate reproducible in-plane motion encountered in fetuses. PC-MRI data were acquired on ten fetuses. All ungated images were rated on their quality from 0 (no motion) to 2 (severe motion). There was no significant difference in measured flows with in-plane motion during the first and last third of sequence acquisition. Movement in the middle section of acquisition produced a significant difference while all referring ungated images were rated with a score of 2. Intra-Class-Correlation (ICC) for flow-measurements in adult and fetal datasets was lower for datasets with scores of 2. For fetal applications, the use of a simple three-point scoring system reliably identifies motion-corrupted sequences from unprocessed data at the time of acquisition, with a high score corresponding to significant underestimation of flow values and increased interobserver variability.
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Feto , Imageamento por Ressonância Magnética , Adulto , Feminino , Feto/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodos , Movimento (Física) , Gravidez , Cuidado Pré-Natal , Reprodutibilidade dos TestesRESUMO
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.
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Doenças Cardiovasculares , Carpas , Pré-Eclâmpsia , Animais , Feminino , Humanos , Placenta/diagnóstico por imagem , Pré-Eclâmpsia/diagnóstico por imagem , Gravidez , Gravidez de Alto RiscoRESUMO
Slice-to-volume registration (SVR) methods allow reconstruction of high-resolution 3D images from multiple motion-corrupted stacks. SVR-based pipelines have been increasingly used for motion correction for T2-weighted structural fetal MRI since they allow more informed and detailed diagnosis of brain and body anomalies including congenital heart defects (Lloyd et al., 2019). Recently, fully automated rigid SVR reconstruction of the fetal brain in the atlas space was achieved in Salehi et al. (2019) that used convolutional neural networks (CNNs) for segmentation and pose estimation. However, these CNN-based methods have not yet been applied to the fetal trunk region. Meanwhile, the existing rigid and deformable SVR (DSVR) solutions (Uus et al., 2020) for the fetal trunk region are limited by the requirement of manual input as well the narrow capture range of the classical gradient descent based registration methods that cannot resolve severe fetal motion frequently occurring at the early gestational age (GA). Furthermore, in our experience, the conventional 2D slice-wise CNN-based brain masking solutions are reportedly prone to errors that require manual corrections when applied on a wide range of acquisition protocols or abnormal cases in clinical setting. In this work, we propose a fully automated pipeline for reconstruction of the fetal thorax region for 21-36 weeks GA range T2-weighted MRI datasets. It includes 3D CNN-based intra-uterine localisation of the fetal trunk and landmark-guided pose estimation steps that allow automated DSVR reconstruction in the standard radiological space irrespective of the fetal trunk position or the regional stack coverage. The additional step for generation of the common template space and rejection of outliers provides the means for automated exclusion of stacks affected by low image quality or extreme motion. The pipeline was quantitatively evaluated on a series of experiments including fetal MRI datasets and simulated rotation motion. Furthermore, we performed a qualitative assessment of the image reconstruction quality in terms of the definition of vascular structures on 100 early (median 23.14 weeks) and late (median 31.79 weeks) GA group MRI datasets covering 21 to 36 weeks GA range.
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Imageamento Tridimensional , Imageamento por Ressonância Magnética , Feminino , Idade Gestacional , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Imageamento por Ressonância Magnética/métodos , Movimento (Física) , Gravidez , Tórax/diagnóstico por imagemRESUMO
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.
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Doenças Fetais/diagnóstico por imagem , Cardiopatias Congênitas/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Placenta/diagnóstico por imagem , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Gravidez , Estudos ProspectivosRESUMO
BACKGROUND: Identifying fetuses at risk of severe neonatal coarctation of the aorta (CoA) can be lifesaving but is notoriously challenging in clinical practice with a high rate of false positives. Novel fetal 3-dimensional and phase-contrast magnetic resonance imaging (MRI) offers an unprecedented means of assessing the human fetal cardiovascular system before birth. We performed detailed MRI assessment of fetal vascular morphology and flows in a cohort of fetuses with suspected CoA, correlated with the need for postnatal intervention. METHODS: Women carrying a fetus with suspected CoA on echocardiography were referred for MRI assessment between 26 and 36 weeks of gestation, including high-resolution motion-corrected 3-dimensional volumes of the fetal heart and phase-contrast flow sequences gated with metric optimized gating. The relationship between aortic geometry and vascular flows was then analyzed and compared with postnatal outcome. RESULTS: Seventy-two patients (51 with suspected fetal CoA and 21 healthy controls) underwent fetal MRI with motion-corrected 3-dimensional vascular reconstructions. Vascular flow measurements from phase-contrast sequences were available in 53 patients. In the CoA group, 25 of 51 (49%) required surgical repair of coarctation after birth; the remaining 26 of 51 (51%) were discharged without neonatal intervention. Reduced blood flow in the fetal ascending aorta and at the aortic isthmus was associated with increasing angulation (P=0.005) and proximal displacement (P=0.006) of the isthmus and was seen in both true positive and false positive cases. A multivariate logistic regression model including aortic flow and isthmal displacement explained 78% of the variation in outcome and correctly predicted the need for intervention in 93% of cases. CONCLUSIONS: Reduced blood flow though the left heart is associated with important configurational changes at the aortic isthmus in fetal life, predisposing to CoA when the arterial duct closes after birth. Novel fetal MRI techniques may have a role in both understanding and accurately predicting severe neonatal CoA.
Assuntos
Aorta Torácica/diagnóstico por imagem , Coartação Aórtica/diagnóstico por imagem , Coração Fetal/diagnóstico por imagem , Imageamento por Ressonância Magnética , Diagnóstico Pré-Natal , Aorta Torácica/anormalidades , Aorta Torácica/fisiopatologia , Coartação Aórtica/fisiopatologia , Estudos de Casos e Controles , Feminino , Coração Fetal/anormalidades , Coração Fetal/fisiopatologia , Idade Gestacional , Humanos , Modelos Cardiovasculares , Modelagem Computacional Específica para o Paciente , Valor Preditivo dos Testes , Gravidez , Estudos Prospectivos , Fluxo Sanguíneo RegionalRESUMO
Importance: What is inherited or acquired in neurodevelopmental conditions such as autism spectrum disorder (ASD) is not a fixed outcome, but instead is a vulnerability to a spectrum of traits, especially social difficulties. Identifying the biological mechanisms associated with vulnerability requires looking as early in life as possible, before the brain is shaped by postnatal mechanisms and/or the experiences of living with these traits. Animal studies suggest that susceptibility to neurodevelopmental disorders arises when genetic and/or environmental risks for these conditions alter patterns of synchronous brain activity in the perinatal period, but this has never been examined in human neonates. Objective: To assess whether alternation of functional maturation of social brain circuits is associated with a family history of ASD in newborns. Design, Setting, and Participants: In this cohort study of 36 neonates with and without a family history of ASD, neonates underwent magnetic resonance imaging at St Thomas Hospital in London, England, using a dedicated neonatal brain imaging system between June 23, 2015, and August 1, 2018. Neonates with a first-degree relative with ASD (R+) and therefore vulnerable to autistic traits and neonates without a family history (R-) were recruited for the study. Synchronous neural activity in brain regions linked to social function was compared. Main Outcomes and Measures: Regions responsible for social function were selected with reference to a published meta-analysis and the level of synchronous activity within each region was used as a measure of local functional connectivity in a regional homogeneity analysis. Group differences, controlling for sex, age at birth, age at scan, and group × age interactions, were examined. Results: The final data set consisted of 18 R+ infants (13 male; median [range] postmenstrual age at scan, 42.93 [40.00-44.86] weeks) and 18 R- infants (13 male; median [range] postmenstrual age at scan, 42.50 [39.29-44.58] weeks). Neonates who were R+ had significantly higher levels of synchronous activity in the right posterior fusiform (t = 2.48; P = .04) and left parietal cortices (t = 3.96; P = .04). In addition, there was a significant group × age interaction within the anterior segment of the left insula (t = 3.03; P = .04) and cingulate cortices (right anterior: t = 3.00; P = .03; left anterior: t = 2.81; P = .03; right posterior: t = 2.77; P = .03; left posterior: t = 2.55; P = .03). In R+ infants, levels of synchronous activity decreased over 39 to 45 weeks' postmenstrual age, whereas synchronous activity levels increased in R- infants over the same period. Conclusions and Relevance: Synchronous activity is required during maturation of functionally connected networks. This study found that in newborn humans, having a first-degree relative with ASD was associated with higher levels of local functional connectivity and dysmaturation of interconnected regions responsible for processing higher-order social information.