Father-infant interactions and infant regional brain volumes: A cross-sectional MRI study.

Fathers play a crucial role in their children's socio-emotional and cognitive development. A plausible intermediate phenotype underlying this association is father's impact on infant brain. However, research on the association between paternal caregiving and child brain biology is scarce, particularly during infancy. Thus, we used magnetic resonance imaging (MRI) to investigate the relationship between observed father-infant interactions, specifically paternal sensitivity, and regional brain volumes in a community sample of 3-to-6-month-old infants (N = 28). We controlled for maternal sensitivity and examined the moderating role of infant communication on this relationship. T2-weighted MR images were acquired from infants during natural sleep. Higher levels of paternal sensitivity were associated with smaller cerebellar volumes in infants with high communication levels. In contrast, paternal sensitivity was not associated with subcortical grey matter volumes in the whole sample, and this was similar in infants with both high and low communication levels. This preliminary study provides the first evidence for an association between father-child interactions and variation in infant brain anatomy.

Familial risk of autism alters subcortical and cerebellar brain anatomy in infants and predicts the emergence of repetitive behaviors in early childhood.

Autism spectrum disorder (ASD) is a common neurodevelopmental condition, and infant siblings of children with ASD are at a higher risk of developing autistic traits or an ASD diagnosis, when compared to those with typically developing siblings. Reports of differences in brain anatomy and function in high-risk infants which predict later autistic behaviors are emerging, but although cerebellar and subcortical brain regions have been frequently implicated in ASD, no high-risk study has examined these regions. Therefore, in this study, we compared regional MRI volumes across the whole brain in 4-6-month-old infants with (high-risk, n = 24) and without (low-risk, n = 26) a sibling with ASD. Within the high-risk group, we also examined whether any regional differences observed were associated with autistic behaviors at 36 months. We found that high-risk infants had significantly larger cerebellar and subcortical volumes at 4-6-months of age, relative to low-risk infants; and that larger volumes in high-risk infants were linked to more repetitive behaviors at 36 months. Our preliminary observations require replication in longitudinal studies of larger samples. If correct, they suggest that the early subcortex and cerebellum volumes may be predictive biomarkers for childhood repetitive behaviors. Autism Res 2019, 12: 614-627. © 2019 The Authors. Autism Research published by International Society for Autism Research published byWiley Periodicals, Inc. LAY SUMMARY: Individuals with a family history of autism spectrum disorder (ASD) are at risk of ASD and related developmental difficulties. This study revealed that 4-6-month-old infants at high-risk of ASD have larger cerebellum and subcortical volumes than low-risk infants, and that larger volumes in high-risk infants are associated with more repetitive behaviors in childhood.

Automated processing pipeline for neonatal diffusion MRI in the developing Human Connectome Project.

The developing Human Connectome Project is set to create and make available to the scientific community a 4-dimensional map of functional and structural cerebral connectivity from 20 to 44 weeks post-menstrual age, to allow exploration of the genetic and environmental influences on brain development, and the relation between connectivity and neurocognitive function. A large set of multi-modal MRI data from fetuses and newborn infants is currently being acquired, along with genetic, clinical and developmental information. In this overview, we describe the neonatal diffusion MRI (dMRI) image processing pipeline and the structural connectivity aspect of the project. Neonatal dMRI data poses specific challenges, and standard analysis techniques used for adult data are not directly applicable. We have developed a processing pipeline that deals directly with neonatal-specific issues, such as severe motion and motion-related artefacts, small brain sizes, high brain water content and reduced anisotropy. This pipeline allows automated analysis of in-vivo dMRI data, probes tissue microstructure, reconstructs a number of major white matter tracts, and includes an automated quality control framework that identifies processing issues or inconsistencies. We here describe the pipeline and present an exemplar analysis of data from 140 infants imaged at 38-44 weeks post-menstrual age.

The developing human connectome project: A minimal processing pipeline for neonatal cortical surface reconstruction.

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.

An efficient sequence for fetal brain imaging at 3T with enhanced T1 contrast and motion robustness.

PURPOSE: Ultrafast single-shot T2 -weighted images are common practice in fetal MR exams. However, there is limited experience with fetal T1 -weighted acquisitions. This study aims at establishing a robust framework that allows fetal T1 -weighted scans to be routinely acquired in utero at 3T. METHODS: A 2D gradient echo sequence with an adiabatic inversion was optimized to be robust to fetal motion and maternal breathing optimizing grey/white matter contrast at the same time. This was combined with slice to volume registration and super resolution methods to produce volumetric reconstructions. The sequence was tested on 22 fetuses. RESULTS: Optimized grey/white matter contrast and robustness to fetal motion and maternal breathing were achieved. Signal from cerebrospinal fluid (CSF) and amniotic fluid was nulled and 0.75 mm isotropic anatomical reconstructions of the fetal brain were obtained using slice-to-volume registration and super resolution techniques. Total acquisition time for a single stack was 56 s, all acquired during free breathing. Enhanced sensitivity to normal anatomy and pathology with respect to established methods is demonstrated. A direct comparison with a 3D spoiled gradient echo sequence and a controlled motion experiment run on an adult volunteer are also shown. CONCLUSION: This paper describes a robust framework to perform T1 -weighted acquisitions and reconstructions of the fetal brain in utero. Magn Reson Med 80:137-146, 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 NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Distortion Correction in Fetal EPI Using Non-Rigid Registration With a Laplacian Constraint.

Geometric distortion induced by the main B0 field disrupts the consistency of fetal echo planar imaging (EPI) data, on which diffusion and functional magnetic resonance imaging is based. In this paper, we present a novel data-driven method for simultaneous motion and distortion correction of fetal EPI. A motion-corrected and reconstructed T2 weighted single shot fast spin echo (ssFSE) volume is used as a model of undistorted fetal brain anatomy. Our algorithm interleaves two registration steps: estimation of fetal motion parameters by aligning EPI slices to the model; and deformable registration of EPI slices to slices simulated from the undistorted model to estimate the distortion field. The deformable registration is regularized by a physically inspired Laplacian constraint, to model distortion induced by a source-free background B0 field. Our experiments show that distortion correction significantly improves consistency of reconstructed EPI volumes with ssFSE volumes. In addition, the estimated distortion fields are consistent with fields calculated from acquired field maps, and the Laplacian constraint is essential for estimation of plausible distortion fields. The EPI volumes reconstructed from different scans of the same subject were more consistent when the proposed method was used in comparison with EPI volumes reconstructed from data distortion corrected using a separately acquired B0 field map.

Fetal cardiac cine imaging using highly accelerated dynamic MRI with retrospective motion correction and outlier rejection.

PURPOSE: Development of a MRI acquisition and reconstruction strategy to depict fetal cardiac anatomy in the presence of maternal and fetal motion. METHODS: The proposed strategy involves i) acquisition and reconstruction of highly accelerated dynamic MRI, followed by image-based ii) cardiac synchronization, iii) motion correction, iv) outlier rejection, and finally v) cardiac cine reconstruction. Postprocessing entirely was automated, aside from a user-defined region of interest delineating the fetal heart. The method was evaluated in 30 mid- to late gestational age singleton pregnancies scanned without maternal breath-hold. RESULTS: The combination of complementary acquisition/reconstruction and correction/rejection steps in the pipeline served to improve the quality of the reconstructed 2D cine images, resulting in increased visibility of small, dynamic anatomical features. Artifact-free cine images successfully were produced in 36 of 39 acquired data sets; prolonged general fetal movements precluded processing of the remaining three data sets. CONCLUSIONS: The proposed method shows promise as a motion-tolerant framework to enable further detail in MRI studies of the fetal heart and great vessels. Processing data in image-space allowed for spatial and temporal operations to be applied to the fetal heart in isolation, separate from extraneous changes elsewhere in the field of view. Magn Reson Med 79:327-338, 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.

Impaired development of the cerebral cortex in infants with congenital heart disease is correlated to reduced cerebral oxygen delivery.

Neurodevelopmental impairment is the most common comorbidity associated with complex congenital heart disease (CHD), while the underlying biological mechanism remains unclear. We hypothesised that impaired cerebral oxygen delivery in infants with CHD is a cause of impaired cortical development, and predicted that cardiac lesions most associated with reduced cerebral oxygen delivery would demonstrate the greatest impairment of cortical development. We compared 30 newborns with complex CHD prior to surgery and 30 age-matched healthy controls using brain MRI. The cortex was assessed using high resolution, motion-corrected T2-weighted images in natural sleep, analysed using an automated pipeline. Cerebral oxygen delivery was calculated using phase contrast angiography and pre-ductal pulse oximetry, while regional cerebral oxygen saturation was estimated using near-infrared spectroscopy. We found that impaired cortical grey matter volume and gyrification index in newborns with complex CHD was linearly related to reduced cerebral oxygen delivery, and that cardiac lesions associated with the lowest cerebral oxygen delivery were associated with the greatest impairment of cortical development. These findings suggest that strategies to improve cerebral oxygen delivery may help reduce brain dysmaturation in newborns with CHD, and may be most relevant for children with CHD whose cardiac defects remain unrepaired for prolonged periods after birth.

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 patchwise 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, enabling its use in the clinical practice. We evaluate PVR's computational overhead compared with standard methods and observe improved reconstruction accuracy in the presence of affine motion artifacts compared with 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, structural similarity index, and cross correlation with respect to the originally acquired data and provide a method for visual inspection of reconstruction uncertainty. We further evaluate the distance error for selected anatomical landmarks in the fetal head, as well as calculating the mean and maximum displacements resulting from automatic non-rigid registration to a motion-free ground truth image. These experiments demonstrate a successful application of PVR motion compensation to the whole fetal body, uterus, and placenta.

Mother-infant interactions and regional brain volumes in infancy: an MRI study.

It is generally agreed that the human brain is responsive to environmental influences, and that the male brain may be particularly sensitive to early adversity. However, this is largely based on retrospective studies of older children and adolescents exposed to extreme environments in childhood. Less is understood about how normative variations in parent-child interactions are associated with the development of the infant brain in typical settings. To address this, we used magnetic resonance imaging to investigate the relationship between observational measures of mother-infant interactions and regional brain volumes in a community sample of 3- to 6-month-old infants (N = 39). In addition, we examined whether this relationship differed in male and female infants. We found that lower maternal sensitivity was correlated with smaller subcortical grey matter volumes in the whole sample, and that this was similar in both sexes. However, male infants who showed greater levels of positive communication and engagement during early interactions had smaller cerebellar volumes. These preliminary findings suggest that variations in mother-infant interaction dimensions are associated with differences in infant brain development. Although the study is cross-sectional and causation cannot be inferred, the findings reveal a dynamic interaction between brain and environment that may be important when considering interventions to optimize infant outcomes.

An exploration of the potential utility of fetal cardiovascular MRI as an adjunct to fetal echocardiography.

OBJECTIVES: Fetal cardiovascular magnetic resonance imaging (MRI) offers a potential alternative to echocardiography, although in practice, its use has been limited. We sought to explore the need for additional imaging in a tertiary fetal cardiology unit and the usefulness of standard MRI sequences. METHODS: Cases where the diagnosis was not fully resolved using echocardiography were referred for MRI. Following a three-plane localiser, fetal movement was assessed with a balanced steady-state free precession (bSSFP) cine. Single-shot fast spin echo and bSSFP sequences were used for diagnostic imaging. RESULTS: Twenty-two fetal cardiac MRIs were performed over 12 months, at mean gestation of 32 weeks (26-38 weeks). The majority of referrals were for suspected vascular abnormalities (17/22), particularly involving the aortic arch (n = 10) and pulmonary vessels (n = 4). Single-shot fast spin echo sequences produced 'black-blood' images, useful for examining the extracardiac vasculature in these cases. BSSFP sequences were more useful for intracardiac structures. Real-time SSFP allowed for dynamic assessment of structures such as cardiac masses, with enhancement patterns also allowing for tissue characterisation in these cases. CONCLUSIONS: Fetal vascular abnormalities such as coarctation can be difficult to diagnose by using ultrasound. Fetal MRI may have an adjunctive role in the evaluation of the extracardiac vascular anatomy and tissue characterisation. © 2016 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd.

Fast Volume Reconstruction From Motion Corrupted Stacks of 2D Slices.

Capturing an enclosing volume of moving subjects and organs using fast individual image slice acquisition has shown promise in dealing with motion artefacts. Motion between slice acquisitions results in spatial inconsistencies that can be resolved by slice-to-volume reconstruction (SVR) methods to provide high quality 3D image data. Existing algorithms are, however, typically very slow, specialised to specific applications and rely on approximations, which impedes their potential clinical use. In this paper, we present a fast multi-GPU accelerated framework for slice-to-volume reconstruction. It is based on optimised 2D/3D registration, super-resolution with automatic outlier rejection and an additional (optional) intensity bias correction. We introduce a novel and fully automatic procedure for selecting the image stack with least motion to serve as an initial registration target. We evaluate the proposed method using artificial motion corrupted phantom data as well as clinical data, including tracked freehand ultrasound of the liver and fetal Magnetic Resonance Imaging. We achieve speed-up factors greater than 30 compared to a single CPU system and greater than 10 compared to currently available state-of-the-art multi-core CPU methods. We ensure high reconstruction accuracy by exact computation of the point-spread function for every input data point, which has not previously been possible due to computational limitations. Our framework and its implementation is scalable for available computational infrastructures and tests show a speed-up factor of 1.70 for each additional GPU. This paves the way for the online application of image based reconstruction methods during clinical examinations. The source code for the proposed approach is publicly available.

Evaluation of automatic neonatal brain segmentation algorithms: the NeoBrainS12 challenge.

A number of algorithms for brain segmentation in preterm born infants have been published, but a reliable comparison of their performance is lacking. The NeoBrainS12 study (http://neobrains12.isi.uu.nl), providing three different image sets of preterm born infants, was set up to provide such a comparison. These sets are (i) axial scans acquired at 40 weeks corrected age, (ii) coronal scans acquired at 30 weeks corrected age and (iii) coronal scans acquired at 40 weeks corrected age. Each of these three sets consists of three T1- and T2-weighted MR images of the brain acquired with a 3T MRI scanner. The task was to segment cortical grey matter, non-myelinated and myelinated white matter, brainstem, basal ganglia and thalami, cerebellum, and cerebrospinal fluid in the ventricles and in the extracerebral space separately. Any team could upload the results and all segmentations were evaluated in the same way. This paper presents the results of eight participating teams. The results demonstrate that the participating methods were able to segment all tissue classes well, except myelinated white matter.

Motion corrected 3D reconstruction of the fetal thorax from prenatal MRI.

In this paper we present a semi-automatic method for analysis of the fetal thorax in genuine three-dimensional volumes. After one initial click we localize the spine and accurately determine the volume of the fetal lung from high resolution volumetric images reconstructed from motion corrupted prenatal Magnetic Resonance Imaging (MRI). We compare the current state-of-the-art method of segmenting the lung in a slice-by-slice manner with the most recent multi-scan reconstruction methods. We use fast rotation invariant spherical harmonics image descriptors with Classification Forest ensemble learning methods to extract the spinal cord and show an efficient way to generate a segmentation prior for the fetal lung from this information for two different MRI field strengths. The spinal cord can be segmented with a DICE coefficient of 0.89 and the automatic lung segmentation has been evaluated with a DICE coefficient of 0.87. We evaluate our method on 29 fetuses with a gestational age (GA) between 20 and 38 weeks and show that our computed segmentations and the manual ground truth correlate well with the recorded values in literature.

Resting State fMRI in the moving fetus: a robust framework for motion, bias field and spin history correction.

There is growing interest in exploring fetal functional brain development, particularly with Resting State fMRI. However, during a typical fMRI acquisition, the womb moves due to maternal respiration and the fetus may perform large-scale and unpredictable movements. Conventional fMRI processing pipelines, which assume that brain movements are infrequent or at least small, are not suitable. Previous published studies have tackled this problem by adopting conventional methods and discarding as much as 40% or more of the acquired data. In this work, we developed and tested a processing framework for fetal Resting State fMRI, capable of correcting gross motion. The method comprises bias field and spin history corrections in the scanner frame of reference, combined with slice to volume registration and scattered data interpolation to place all data into a consistent anatomical space. The aim is to recover an ordered set of samples suitable for further analysis using standard tools such as Group Independent Component Analysis (Group ICA). We have tested the approach using simulations and in vivo data acquired at 1.5 T. After full motion correction, Group ICA performed on a population of 8 fetuses extracted 20 networks, 6 of which were identified as matching those previously observed in preterm babies.

A 4D neonatal head model for diffuse optical imaging of pre-term to term infants.

Diffuse optical tomography is most accurate when an individual's MRI data can be used as a spatial prior for image reconstruction and for visualization of the resulting images of changes in oxy- and deoxy-hemoglobin concentration. As this necessitates an MRI scan to be performed for each study, which undermines many of the advantages of diffuse optical methods, the use of registered atlases to model the individual's anatomy is becoming commonplace. Infant studies require carefully age-matched atlases because of the rapid growth and maturation of the infant brain. In this paper, we present a 4D neonatal head model which, for each week from 29 to 44 weeks post-menstrual age, includes: 1) a multi-layered tissue mask which identifies extra-cerebral layers, cerebrospinal fluid, gray matter, white matter, cerebellum and brainstem, 2) a high-density tetrahedral head mesh, 3) surface meshes for the scalp, gray-matter and white matter layers and 4) cranial landmarks and 10-5 locations on the scalp surface. This package, freely available online at www.ucl.ac.uk/medphys/research/4dneonatalmodel can be applied by users of near-infrared spectroscopy and diffuse optical tomography to optimize probe locations, optimize image reconstruction, register data to cortical locations and ultimately improve the accuracy and interpretation of diffuse optical techniques in newborn populations.

Registration of 3D fetal neurosonography and MRI.

We propose a method for registration of 3D fetal brain ultrasound with a reconstructed magnetic resonance fetal brain volume. This method, for the first time, allows the alignment of models of the fetal brain built from magnetic resonance images with 3D fetal brain ultrasound, opening possibilities to develop new, prior information based image analysis methods for 3D fetal neurosonography. The reconstructed magnetic resonance volume is first segmented using a probabilistic atlas and a pseudo ultrasound image volume is simulated from the segmentation. This pseudo ultrasound image is then affinely aligned with clinical ultrasound fetal brain volumes using a robust block-matching approach that can deal with intensity artefacts and missing features in the ultrasound images. A qualitative and quantitative evaluation demonstrates good performance of the method for our application, in comparison with other tested approaches. The intensity average of 27 ultrasound images co-aligned with the pseudo ultrasound template shows good correlation with anatomy of the fetal brain as seen in the reconstructed magnetic resonance image.

Reconstruction of fetal brain MRI with intensity matching and complete outlier removal.

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.

Registration of 3D fetal brain US and MRI.

We propose a novel method for registration of 3D fetal brain ultrasound and a reconstructed magnetic resonance fetal brain volumes. The reconstructed MR volume is first segmented using a probabilistic atlas and an ultrasound-like image volume is simulated from the segmentation of the MR image. This ultrasound-like image volume is then affinely aligned with real ultrasound volumes of 27 fetal brains using a robust block-matching approach which can deal with intensity artefacts and missing features in ultrasound images. We show that this approach results in good overlap of four small structures. The average of the co-aligned US images shows good correlation with anatomy of the fetal brain as seen in the MR reconstruction.

Simultaneous multi-scale registration using large deformation diffeomorphic metric mapping.

In the framework of large deformation diffeomorphic metric mapping (LDDMM), we present a practical methodology to integrate prior knowledge about the registered shapes in the regularizing metric. Our goal is to perform rich anatomical shape comparisons from volumetric images with the mathematical properties offered by the LDDMM framework. We first present the notion of characteristic scale at which image features are deformed. We then propose a methodology to compare anatomical shape variations in a multi-scale fashion, i.e., at several characteristic scales simultaneously. In this context, we propose a strategy to quantitatively measure the feature differences observed at each characteristic scale separately. After describing our methodology, we illustrate the performance of the method on phantom data. We then compare the ability of our method to segregate a group of subjects having Alzheimer's disease and a group of controls with a classical coarse to fine approach, on standard 3D MR longitudinal brain images. We finally apply the approach to quantify the anatomical development of the human brain from 3D MR longitudinal images of pre-term babies. Results show that our method registers accurately volumetric images containing feature differences at several scales simultaneously with smooth deformations.