In this paper, we propose DeepCut, a method to obtain pixelwise object segmentations given an image dataset labelled weak annotations, in our case bounding boxes. It extends the approach of the ...well-known GrabCut1 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 naïve 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.
Fetal ventriculomegaly is the most common antenatally-diagnosed brain abnormality. Imaging studies in antenatal isolated ventriculomegaly demonstrate enlarged ventricles and cortical overgrowth which ...are also present in children with autism-spectrum disorder/condition (ASD). We investigate the presence of ASD traits in a cohort of children (n = 24 20 males/4 females) with isolated fetal ventriculomegaly, compared with 10 controls (n = 10 6 males/4 females). Neurodevelopmental outcome at school age included IQ, ASD traits (ADOS-2), sustained attention, neurological functioning, behaviour, executive function, sensory processing, co-ordination, and adaptive behaviours. Pre-school language development was assessed at 2 years. 37.5% of children, all male, in the ventriculomegaly cohort scored above threshold for autism/ASD classification. Pre-school language delay predicted an ADOS-2 autism/ASD classification with 73.3% specificity/66.7% sensitivity. Greater pre-school language delay was associated with more ASD symptoms. In this study, the neurodevelopment of children with isolated fetal ventriculomegaly, associated with altered cortical development, includes ASD traits, difficulties in sustained attention, working memory and sensation-seeking behaviours.
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.
Cortical maturation was studied in 65 infants between 27 and 46 wk postconception using structural and diffusion magnetic resonance imaging. Alterations in neural structure and complexity were ...inferred from changes in mean diffusivity and fractional anisotropy, analyzed by sampling regions of interest and also by a unique whole-cortex mapping approach. Mean diffusivity was higher in gyri than sulci and in frontal compared with occipital lobes, decreasing consistently throughout the study period. Fractional anisotropy declined until 38 wk, with initial values and rates of change higher in gyri, frontal and temporal poles, and parietal cortex; and lower in sulcal, perirolandic, and medial occipital cortex. Neuroanatomical studies and experimental diffusion–anatomic correlations strongly suggested the interpretation that cellular and synaptic complexity and density increased steadily throughout the period, whereas elongation and branching of dendrites orthogonal to cortical columns was later and faster in higher-order association cortex, proceeding rapidly before becoming undetectable after 38 wk. The rate of microstructural maturation correlated locally with cortical growth, and predicted higher neurodevelopmental test scores at 2 y of age. Cortical microstructural development was reduced in a dose-dependent fashion by longer premature exposure to the extrauterine environment, and preterm infants at term-corrected age possessed less mature cortex than term-born infants. The results are compatible with predictions of the tension theory of cortical growth and show that rapidly developing cortical microstructure is vulnerable to the effects of premature birth, suggesting a mechanism for the adverse effects of preterm delivery on cognitive function.
•E-consent may support research to be conducted remotely.•E-consent may enhance the consent process for participants and researchers.•E-consent approaches could facilitate diversity in research ...participation.•E-consent is a feasible alternative to traditional informed consent processes.•Successful implementation is dependent on key practice and ethical considerations.
Electronic approaches are becoming more widely used to obtain informed consent for research participation. Electronic consent (e-consent) provides an accessible and versatile approach to the consenting process, which can be enhanced with audio-visual and interactive features to improve participant engagement and comprehension of study procedures. Best practice guidance underpinned by ethical principles is required to ensure effective implementation of e-consent for use in research.
To identify the key considerations for successful and ethical implementation of e-consent in the recruitment of participants to research projects which are conducted remotely.
Electronic database searches of CINAHL, Medline, Embase, DARE, HTA, PubMed, the Cochrane Library, Scopus, Web of Science, NHS Evidence, and hand-searches of reference lists were performed. Primary research studies of adult (≥ 18 years old) research participants using e-consent, published in English language, peer-reviewed journals between 2010−2020 were eligible for inclusion.
Of the initial 665 identified studies, 18 met the inclusion criteria: 6 cohort studies, 5 qualitative studies, 4 randomised control trials, 2 mixed-methods studies and one case-control study. Critical appraisal of included studies using Critical Appraisal Skills Program (CASP) tools suggested a low to moderate risk of bias in most studies (n = 15). Key practice recommendations for researchers using e-consent were identified around five primary themes: 1) accessibility and user-friendliness of e-consent, 2) user engagement and comprehension, 3) customisability to participant preferences and demographics, 4) data security and 5) impact on research teams.
E-consenting approaches are generally well received by participants, with most studies reporting user-friendly interfaces and sufficient participant comprehension of consenting documentation.
E-consent may facilitate remotely-conducted research by offering a feasible and robust alternative to face-to-face consenting approaches, however paper-based options should still be offered, based on participant preference. Customising e-consenting platforms may improve accessibility for individuals with specific needs, and increase engagement with study information. Research teams must offer prospective participants opportunities to discuss study information in real-time.
In in-utero MRI, motion correction for fetal body and placenta poses a particular challenge due to the presence of local non-rigid transformations of organs caused by bending and stretching. The ...existing slice-to-volume registration (SVR) reconstruction methods are widely employed for motion correction of fetal brain that undergoes only rigid transformation. However, for reconstruction of fetal body and placenta, rigid registration cannot resolve the issue of misregistrations due to deformable motion, resulting in degradation of features in the reconstructed volume. We propose a Deformable SVR (DSVR), a novel approach for non-rigid motion correction of fetal MRI based on a hierarchical deformable SVR scheme to allow high resolution reconstruction of the fetal body and placenta. Additionally, a robust scheme for structure-based rejection of outliers minimises the impact of registration errors. The improved performance of DSVR in comparison to SVR and patch-to-volume registration (PVR) methods is quantitatively demonstrated in simulated experiments and 20 fetal MRI datasets from 28-31 weeks gestational age (GA) range with varying degree of motion corruption. In addition, we present qualitative evaluation of 100 fetal body cases from 20-34 weeks GA range.
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► A new method for reconstruction of 3D fetal brain MRI from 2D slices is proposed. ► The super-resolution reconstruction is interleaved with motion correction. ► Corrupted or ...misaligned slices are automatically excluded. ► Novel intensity matching is shown to be essential for quality of reconstruction. ► Excellent results for clinical and optimized data.
We propose a method for the reconstruction of volumetric fetal MRI from 2D slices, comprising super-resolution reconstruction of the volume interleaved with slice-to-volume registration to correct for the motion. The method incorporates novel intensity matching of acquired 2D slices and robust statistics which completely excludes identified misregistered or corrupted voxels and slices. The reconstruction method is applied to motion-corrupted data simulated from MRI of a preterm neonate, as well as 10 clinically acquired thick-slice fetal MRI scans and three scan-sequence optimized thin-slice fetal datasets. The proposed method produced high quality reconstruction results from all the datasets to which it was applied. Quantitative analysis performed on simulated and clinical data shows that both intensity matching and robust statistics result in statistically significant improvement of super-resolution reconstruction. The proposed novel EM-based robust statistics also improves the reconstruction when compared to previously proposed Huber robust statistics. The best results are obtained when thin-slice data and the correct approximation of the point spread function is used. This paper addresses the need for a comprehensive reconstruction algorithm of 3D fetal MRI, so far lacking in the scientific literature.
Medical imaging has shown that, during early development, the brain undergoes more changes in size, shape and appearance than at any other time in life. A better understanding of brain development ...requires a spatio-temporal atlas that characterizes the dynamic changes during this period. In this paper we present an approach for constructing a 4D atlas of the developing brain, between 28 and 44weeks post-menstrual age at time of scan, using T1 and T2 weighted MR images from 204 premature neonates. The method used for the creation of the average 4D atlas utilizes non-rigid registration between all pairs of images to eliminate bias in the atlas toward any of the original images. In addition, kernel regression is used to produce age-dependent anatomical templates. A novelty in our approach is the use of a time-varying kernel width, to overcome the variations in the distribution of subjects at different ages. This leads to an atlas that retains a consistent level of detail at every time-point. Comparisons between the resulting atlas and atlases constructed using affine and non-rigid registration are presented. The resulting 4D atlas has greater anatomic definition than currently available 4D atlases created using various affine and non-rigid registration approaches, an important factor in improving registrations between the atlas and individual subjects. Also, the resulting 4D atlas can serve as a good representative of the population of interest as it reflects both global and local changes. The atlas is publicly available at www.brain-development.org.
► A new approach for constructing high-definition 4D atlases is presented. ► Multi-modal MR images from 204 preterm neonates (age-range 26–44weeks PMA) are used. ► The resulting atlas retains a consistent level of detail at every time-point. ► The atlas has greater anatomic definition than currently available 4D atlases. ► Such a sharp atlas enables improved registration between the atlas and individuals.
Symptomatic neonatal hypoglycemia may be associated with later neurodevelopmental impairment. Brain injury patterns identified on early MRI scans and their relationships to the nature of the ...hypoglycemic insult and neurodevelopmental outcomes are poorly defined.
We studied 35 term infants with early brain MRI scans after symptomatic neonatal hypoglycemia (median glucose level: 1 mmol/L) without evidence of hypoxic-ischemic encephalopathy. Perinatal data were compared with equivalent data from 229 term, neurologically normal infants (control subjects), to identify risk factors for hypoglycemia. Neurodevelopmental outcomes were assessed at a minimum of 18 months.
White matter abnormalities occurred in 94% of infants with hypoglycemia, being severe in 43%, with a predominantly posterior pattern in 29% of cases. Cortical abnormalities occurred in 51% of infants; 30% had white matter hemorrhage, 40% basal ganglia/thalamic lesions, and 11% an abnormal posterior limb of the internal capsule. Three infants had middle cerebral artery territory infarctions. Twenty-three infants (65%) demonstrated impairments at 18 months, which were related to the severity of white matter injury and involvement of the posterior limb of the internal capsule. Fourteen infants demonstrated growth restriction, 1 had macrosomia, and 2 had mothers with diabetes mellitus. Pregnancy-induced hypertension, a family history of seizures, emergency cesarean section, and the need for resuscitation were more common among case subjects than control subjects.
Patterns of injury associated with symptomatic neonatal hypoglycemia were more varied than described previously. White matter injury was not confined to the posterior regions; hemorrhage, middle cerebral artery infarction, and basal ganglia/thalamic abnormalities were seen, and cortical involvement was common. Early MRI findings were more instructive than the severity or duration of hypoglycemia for predicting neurodevelopmental outcomes.
Down syndrome is the most common genetic developmental disorder in humans and is caused by partial or complete triplication of human chromosome 21 (trisomy 21). It is a complex condition which ...results in multiple lifelong health problems, including varying degrees of intellectual disability and delays in speech, memory, and learning. As both length and quality of life are improving for individuals with Down syndrome, attention is now being directed to understanding and potentially treating the associated cognitive difficulties and their underlying biological substrates. These have included imaging and postmortem studies which have identified decreased regional brain volumes and histological anomalies that accompany early onset dementia. In addition, advances in genome‐wide analysis and Down syndrome mouse models are providing valuable insight into potential targets for intervention that could improve neurogenesis and long‐term cognition. As little is known about early brain development in human Down syndrome, we review recent advances in magnetic resonance imaging that allow non‐invasive visualization of brain macro‐ and microstructure, even in utero. It is hoped that together these advances may enable Down syndrome to become one of the first genetic disorders to be targeted by antenatal treatments designed to ‘normalize’ brain development.
What this paper adds
Magnetic resonance imaging can provide non‐invasive characterization of early brain development in Down syndrome.
Down syndrome mouse models enable study of underlying pathology and potential intervention strategies.
Potential therapies could modify brain structure and improve early cognitive levels.
Down syndrome may be the first genetic disorder to have targeted therapies which alter antenatal brain development.
Resumen
Nuevos enfoques para estudiar el desarrollo cerebral temprano en el síndrome de Down
El síndrome de Down es el trastorno del desarrollo genético más común en los seres humanos y es causado por la triplicación parcial o completa del cromosoma 21 (trisomía 21). Es una condición compleja que se traduce en múltiples problemas de salud a lo largo de toda la vida, incluidos diversos grados de discapacidad intelectual y retrasos en el habla, la memoria y el aprendizaje. Debido a que la duración y la calidad de vida están mejorando para las personas con síndrome de Down, ahora se está prestando atención a la comprensión y al tratamiento de las dificultades cognitivas asociadas y sus sustratos biológicos subyacentes. Estos estudios han incluido estudios de imagen y postmortem que han identificado volúmenes cerebrales regionales disminuidos y anomalías histológicas que acompañan a la demencia de inicio temprano. Además, los avances en el análisis del genoma completo y los modelos de ratones con síndrome de Down brindan información valiosa sobre los posibles objetivos de la intervención que podrían mejorar la neurogénesis y la cognición a largo plazo. Como se sabe poco sobre el desarrollo temprano del cerebro en el síndrome de Down humano, revisamos los avances recientes en imágenes de resonancia magnética que permiten la visualización no invasiva de la macro y microestructura cerebral, incluso en el útero. Se espera que, en conjunto, estos avances puedan permitir que el síndrome de Down se convierta en uno de los primeros trastornos genéticos a los que se aplican tratamientos prenatales diseñados para “encauzar” el desarrollo cerebral.
Resumo
Novas abordagens para o estudo de desenvolvimento cerebral precoce na síndrome de Down
A síndrome de Down é a desordem desenvolvimental de origem genética mais comum em humanos. É causada por triplicação parcial ou completa do cromossomo 21 (trissomia do 21). Trata‐se de uma condição complexa que resulta em múltiplos problemas de saúde ao longo da vida, incluindo graus variados de deficiência intelectual, e atrasos na fala, memória e aprendizagem. Como tanto a duração quanto a qualidade de vida têm melhorado para indivíduos com síndrome de Down, agora a atenção se volta para compreender e potencialmente tratar dificuldades cognitivas associadas e seus substratos biológicos de base. Incluem‐se estudos de imagem e pós‐morte que identificaram menores volumes cerebrais e anomalias histológicas que acompanham a demência de início precoe. Além disso, avanços na análise do genoma em modelos de ratos com síndrome de Down fornecem informações valiosas sobre potenciais alvos para intervenção que podem melhorar a neurogênese e a cognição em longo prazo. Como pouco se sabe sobre o desenvolvimento cerebral precoce na síndrome de Down, nós revisamos avanços recentes em imagens por ressonância magnética que permitem visualização não‐invasiva da macro‐ e micro‐estrutura do cérebro, mesmo no útero. Espera‐se que, juntos, estes avanços possibilitem que a síndrome de Down se torne a primeira desorgem genética a ser alvo de tratamentos antenatais voltados para “normalizar” o desenvolvimento cerebral.
What this paper adds
Magnetic resonance imaging can provide non‐invasive characterization of early brain development in Down syndrome.
Down syndrome mouse models enable study of underlying pathology and potential intervention strategies.
Potential therapies could modify brain structure and improve early cognitive levels.
Down syndrome may be the first genetic disorder to have targeted therapies which alter antenatal brain development.
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