Altered functional connectivity in preterm neonates with intraventricular hemorrhage assessed using functional near-infrared spectroscopy.

Intraventricular hemorrhage (IVH) is a common neurological injury following very preterm birth. Resting-state functional connectivity (RSFC) using functional magnetic resonance imaging (fMRI) is associated with injury severity; yet, fMRI is impractical for use in intensive care settings. Functional near-infrared spectroscopy (fNIRS) measures RSFC through cerebral hemodynamics and has greater bedside accessibility than fMRI. We evaluated RSFC in preterm neonates with IVH using fNIRS and fMRI at term-equivalent age, and compared fNIRS connectivity between healthy newborns and those with IVH. Sixteen very preterm born neonates were scanned with fMRI and fNIRS. Additionally, fifteen healthy newborns were scanned with fNIRS. In preterms with IVH, fNIRS and fMRI connectivity maps were compared using Euclidean and Jaccard distances. The severity of IVH in relation to fNIRS-RSFC strength was examined using generalized linear models. fNIRS and fMRI RSFC maps showed good correspondence. Connectivity strength was significantly lower in healthy newborns (p-value = 0.023) and preterm infants with mild IVH (p-value = 0.026) compared to infants with moderate/severe IVH. fNIRS has potential to be a new bedside tool for assessing brain injury and monitoring cerebral hemodynamics, as well as a promising biomarker for IVH severity in very preterm born infants.

Open access segmentations of intraoperative brain tumor ultrasound images.

PURPOSE: Registration and segmentation of magnetic resonance (MR) and ultrasound (US) images could play an essential role in surgical planning and resectioning brain tumors. However, validating these techniques is challenging due to the scarcity of publicly accessible sources with high-quality ground truth information. To this end, we propose a unique set of segmentations (RESECT-SEG) of cerebral structures from the previously published RESECT dataset to encourage a more rigorous development and assessment of image-processing techniques for neurosurgery. ACQUISITION AND VALIDATION METHODS: The RESECT database consists of MR and intraoperative US (iUS) images of 23 patients who underwent brain tumor resection surgeries. The proposed RESECT-SEG dataset contains segmentations of tumor tissues, sulci, falx cerebri, and resection cavity of the RESECT iUS images. Two highly experienced neurosurgeons validated the quality of the segmentations. DATA FORMAT AND USAGE NOTES: Segmentations are provided in 3D NIFTI format in the OSF open-science platform: https://osf.io/jv8bk. POTENTIAL APPLICATIONS: The proposed RESECT-SEG dataset includes segmentations of real-world clinical US brain images that could be used to develop and evaluate segmentation and registration methods. Eventually, this dataset could further improve the quality of image guidance in neurosurgery.

Evaluating normalized registration and preprocessing methodologies for the analysis of brain MRI in pediatric patients with shunt-treated hydrocephalus.

Introduction: Registration to a standardized template (i.e. "normalization") is a critical step when performing neuroimaging studies. We present a comparative study involving the evaluation of general-purpose registration algorithms for pediatric patients with shunt treated hydrocephalus. Our sample dataset presents a number of intersecting challenges for registration, representing the potentially large deformations to both brain structures and overall brain shape, artifacts from shunts, and morphological differences corresponding to age. The current study assesses the normalization accuracy of shunt-treated hydrocephalus patients using freely available neuroimaging registration tools. Methods: Anatomical neuroimages from eight pediatric patients with shunt-treated hydrocephalus were normalized. Four non-linear registration algorithms were assessed in addition to the preprocessing steps of skull-stripping and bias-correction. Registration accuracy was assessed using the Dice Coefficient (DC) and Hausdorff Distance (HD) in subcortical and cortical regions. Results: A total of 592 registrations were performed. On average, normalizations performed using the brain extracted and bias-corrected images had a higher DC and lower HD compared to full head/ non-biased corrected images. The most accurate registration was achieved using SyN by ANTs with skull-stripped and bias corrected images. Without preprocessing, the DARTEL Toolbox was able to produce normalized images with comparable accuracy. The use of a pediatric template as an intermediate registration did not improve normalization. Discussion: Using structural neuroimages from patients with shunt-treated pediatric hydrocephalus, it was demonstrated that there are tools which perform well after specified pre-processing steps were taken. Overall, these results provide insight to the performance of registration programs that can be used for normalization of brains with complex pathologies.

Semi-supervised learning framework with shape encoding for neonatal ventricular segmentation from 3D ultrasound.

BACKGROUND: Three-dimensional (3D) ultrasound (US) imaging has shown promise in non-invasive monitoring of changes in the lateral brain ventricles of neonates suffering from intraventricular hemorrhaging. Due to the poorly defined anatomical boundaries and low signal-to-noise ratio, fully supervised methods for segmentation of the lateral ventricles in 3D US images require a large dataset of annotated images by trained physicians, which is tedious, time-consuming, and expensive. Training fully supervised segmentation methods on a small dataset may lead to overfitting and hence reduce its generalizability. Semi-supervised learning (SSL) methods for 3D US segmentation may be able to address these challenges but most existing SSL methods have been developed for magnetic resonance or computed tomography (CT) images. PURPOSE: To develop a fast, lightweight, and accurate SSL method, specifically for 3D US images, that will use unlabeled data towards improving segmentation performance. METHODS: We propose an SSL framework that leverages the shape-encoding ability of an autoencoder network to enforce complex shape and size constraints on a 3D U-Net segmentation model. The autoencoder created pseudo-labels, based on the 3D U-Net predicted segmentations, that enforces shape constraints. An adversarial discriminator network then determined whether images came from the labeled or unlabeled data distributions. We used 887 3D US images, of which 87 had manually annotated labels and 800 images were unlabeled. Training/validation/testing sets of 25/12/50, 25/12/25 and 50/12/25 images were used for model experimentation. The Dice similarity coefficient (DSC), mean absolute surface distance (MAD), and absolute volumetric difference (VD) were used as metrics for comparing to other benchmarks. The baseline benchmark was the fully supervised vanilla 3D U-Net while dual task consistency, shape-aware semi-supervised network, correlation-aware mutual learning, and 3D U-Net Ensemble models were used as state-of-the-art benchmarks with DSC, MAD, and VD as comparison metrics. The Wilcoxon signed-rank test was used to test statistical significance between algorithms for DSC and VD with the threshold being p < 0.05 and corrected to p < 0.01 using the Bonferroni correction. The random-access memory (RAM) trace and number of trainable parameters were used to compare the computing efficiency between models. RESULTS: Relative to the baseline 3D U-Net model, our shape-encoding SSL method reported a mean DSC improvement of 6.5%, 7.7%, and 4.1% with a 95% confidence interval of 4.2%, 5.7%, and 2.1% using image data splits of 25/12/50, 25/12/25, and 50/12/25, respectively. Our method only used a 1GB increase in RAM compared to the baseline 3D U-Net and required less than half the RAM and trainable parameters compared to the 3D U-Net ensemble method. CONCLUSIONS: Based on our extensive literature survey, this is one of the first reported works to propose an SSL method designed for segmenting organs in 3D US images and specifically one that incorporates unlabeled data for segmenting neonatal cerebral lateral ventricles. When compared to the state-of-the-art SSL and fully supervised learning methods, our method yielded the highest DSC and lowest VD while being computationally efficient.

A Canadian National Survey Study of Harassment in Surgery-Still a Long Way to Go.

OBJECTIVES: Previous literature has consistently documented harassment and discrimination in surgery. These experiences may contribute to the continuing gender inequity in surgical fields. The objective of our study was to survey Canadian surgeons and surgical trainees to gain a greater understanding of the experience of harassment across genders, career stage, and specialty. METHODS: A cross-sectional, online survey was distributed to Canadian residents, fellows, and practicing surgeons in general surgery, plastic surgery, and neurosurgery through their national society email lists and via social media posts. RESULTS: There were 194 included survey respondents (60 residents, 11 fellows, and 123 staff) from general surgery (44.8%), plastic surgery (42.7%), and neurosurgery (12.5%). 59.8% of women reported having experienced harassment compared to only 26.0% of men. Women were significantly more likely to be harassed by colleagues and patients/families compared to men. Residents (62.5%) were two times more likely to report being harassed compared to fellows/staff (38.3%). Residents were significantly more likely to be harassed by patients/families while fellows/staff were more likely to be harassed by colleagues. There were no significant differences in self-reported harassment across the three surgical specialties. There was no significant difference in rates of reported harassment between current residents (62.5%), and fellow/staff recollections of their experiences of harassment during residency (59.2%). CONCLUSIONS: The prevalence of gender-based discrimination remains high and harassment prevalence remains largely unchanged from when current staff were in residency. Our findings highlight a need to implement systemic changes to support the increasing number of women entering surgery, and to improve surgical culture to continue to attract the best and brightest to the field.

Clinical trainee performance on task-based AR/VR-guided surgical simulation is correlated with their 3D image spatial reasoning scores.

This paper describes a methodology for the assessment of training simulator-based computer-assisted intervention skills on an AR/VR-guided procedure making use of CT axial slice views for a neurosurgical procedure: external ventricular drain (EVD) placement. The task requires that trainees scroll through a stack of axial slices and form a mental representation of the anatomical structures in order to subsequently target the ventricles to insert an EVD. The process of observing the 2D CT image slices in order to build a mental representation of the 3D anatomical structures is the skill being taught, along with the cognitive control of the subsequent targeting, by planned motor actions, of the EVD tip to the ventricular system to drain cerebrospinal fluid (CSF). Convergence is established towards the validity of this assessment methodology by examining two objective measures of spatial reasoning, along with one subjective expert ranking methodology, and comparing these to AR/VR guidance. These measures have two components: the speed and accuracy of the targeting, which are used to derive the performance metric. Results of these correlations are presented for a population of PGY1 residents attending the Canadian Neurosurgical "Rookie Bootcamp" in 2019.

Evaluating the Current State of Epilepsy Care in the Province of Ontario.

There are numerous challenges pertaining to epilepsy care across Ontario, including Epilepsy Monitoring Unit (EMU) bed pressures, surgical access and community supports. We sampled the current clinical, community and operational state of Ontario epilepsy centres and community epilepsy agencies post COVID-19 pandemic. A 44-item survey was distributed to all 11 district and regional adult and paediatric Ontario epilepsy centres. Qualitative responses were collected from community epilepsy agencies. Results revealed ongoing gaps in epilepsy care across Ontario, with EMU bed pressures and labour shortages being limiting factors. A clinical network advising the Ontario Ministry of Health will improve access to epilepsy care.

Structural Alterations of the Corpus Callosum in Children With Infantile Hydrocephalus.

This study investigates structural alterations of the corpus callosum in children diagnosed with infantile hydrocephalus. We aim to assess both macrostructural (volume) and microstructural (diffusion tensor imaging metrics) facets of the corpus callosum, providing insights into the nature and extent of alterations associated with this condition. Eighteen patients with infantile hydrocephalus (mean age = 9 years) and 18 age- and sex-matched typically developing healthy children participated in the study. Structural magnetic resonance imaging and diffusion tensor imaging were used to assess corpus callosum volume and microstructure, respectively. Our findings reveal significant alterations in corpus callosum volume, particularly in the posterior area, as well as distinct microstructural disparities, notably pronounced in these same segments. These results highlight the intricate interplay between macrostructural and microstructural aspects in understanding the impact of infantile hydrocephalus. Examining these structural alterations provides an understanding into the mechanisms underlying the effects of infantile hydrocephalus on corpus callosum integrity, given its pivotal role in interhemispheric communication. This knowledge offers a more nuanced perspective on neurologic disorders and underscores the significance of investigating the corpus callosum's health in such contexts.

Altered resting-state functional connectivity in newborns with hypoxic ischemic encephalopathy assessed using high-density functional near-infrared spectroscopy.

Hypoxic-ischemic encephalopathy (HIE) results from a lack of oxygen to the brain during the perinatal period. HIE can lead to mortality and various acute and long-term morbidities. Improved bedside monitoring methods are needed to identify biomarkers of brain health. Functional near-infrared spectroscopy (fNIRS) can assess resting-state functional connectivity (RSFC) at the bedside. We acquired resting-state fNIRS data from 21 neonates with HIE (postmenstrual age [PMA] = 39.96), in 19 neonates the scans were acquired post-therapeutic hypothermia (TH), and from 20 term-born healthy newborns (PMA = 39.93). Twelve HIE neonates also underwent resting-state functional magnetic resonance imaging (fMRI) post-TH. RSFC was calculated as correlation coefficients amongst the time courses for fNIRS and fMRI data, respectively. The fNIRS and fMRI RSFC maps were comparable. RSFC patterns were then measured with graph theory metrics and compared between HIE infants and healthy controls. HIE newborns showed significantly increased clustering coefficients, network efficiency and modularity compared to controls. Using a support vector machine algorithm, RSFC features demonstrated good performance in classifying the HIE and healthy newborns in separate groups. Our results indicate the utility of fNIRS-connectivity patterns as potential biomarkers for HIE and fNIRS as a new bedside tool for newborns with HIE.

T2* Mapping of Placental Oxygenation to Estimate Fetal Cortical and Subcortical Maturation.

This cohort study investigates the association between T2* mapping of placental oxygenation and cortical and subcortical fetal brain volumes in typically developing fetuses scanned longitudinally in the third trimester.

Assessing the impact of infantile hydrocephalus on visuomotor integration through behavioural and neuroimaging studies.

Infantile hydrocephalus considerably impacts neurodevelopment, warranting attention to potential long-term consequences on visuomotor functions. The current study investigated the impact of infantile hydrocephalus on functional connectivity within the posterior cortex. Fourteen patients, who were treated for infantile hydrocephalus, were matched for age and sex with 14 typically-developing controls. Both groups had a mean age of 9 years old. Resting-state functional MRI was used to conduct a functional connectivity analysis within the visuomotor integration network, including the inferior frontal occipital fasciculus, superior longitudinal fasciculus, and frontal aslant tract. Patients had reduced functional connectivity in visuomotor pathways compared to typically-developing children with notable impact on the left and right fusiform gyrus and precuneus. Children with infantile hydrocephalus also performed significantly lower in tasks involving visuomotor integration, visual processing, visuospatial skills, motor coordination, and fine motor manipulation. This study enhances our understanding of the multifaceted impact of infantile hydrocephalus on both neural connectivity and considering behavioral outcomes.

Sex- and age-based differences in fetal and early childhood hippocampus maturation: a cross-sectional and longitudinal analysis.

The hippocampus, essential for cognitive and affective processes, develops exponentially with differential trajectories seen in girls and boys, yet less is known about its development during early fetal life until early childhood. In a cross-sectional and longitudinal study, we examined the sex-, age-, and laterality-related developmental trajectories of hippocampal volumes in fetuses, infants, and toddlers associated with age. Third trimester fetuses (27-38 weeks' gestational age), newborns (0-4 weeks' postnatal age), infants (5-50 weeks' postnatal age), and toddlers (2-3 years postnatal age) were scanned with magnetic resonance imaging. A total of 133 datasets (62 female, postmenstrual age [weeks] M = 69.38, SD = 51.39, range = 27.6-195.3) were processed using semiautomatic segmentation methods. Hippocampal volumes increased exponentially during the third trimester and the first year of life, beginning to slow at approximately 2 years. Overall, boys had larger hippocampal volumes than girls. Lateralization differences were evident, with left hippocampal growth beginning to plateau sooner than the right. This period of rapid growth from the third trimester, continuing through the first year of life, may support the development of cognitive and affective function during this period.

Association between altered white matter networks and post operative ventricle volume in shunt-treated pediatric hydrocephalus.

OBJECTIVE: The objective of this study was to use probabilistic tractography in combination with white matter microstructure metrics to characterize differences in white matter networks between shunt-treated pediatric hydrocephalus patients relative to healthy controls. We were also able to explore the relationship between these white matter networks and postoperative ventricle volume. METHODS: Network-based statistics was used in combination with whole-brain probabilistic tractography to determine dysregulated white matter networks in a sample of patients with pediatric hydrocephalus (n = 8), relative to controls (n = 36). Metrics such as streamline count (SC), as well as the mean of the fractional anisotropy along a tract, axial diffusivity (AD), mean diffusivity (MD), and radial diffusivity (RD) were assessed. In networks that were found to be significantly different for patients with hydrocephalus, tracts were evaluated to assess their relationship with postoperative lateral ventricle volume. RESULTS: Patients with pediatric hydrocephalus had various networks that were either upregulated or downregulated relative to controls across all white matter measures. Predominately, network dysregulation occurred in tracts involving structures located outside of the frontal lobe. Furthermore tracts with values suggesting decreased white matter integrity were not only found between subcortical structures, but also cortical structures. While there were various tracts with white matter metrics that were initially predicted by lateral ventricle volume, only two tracts remained significant following multiple comparisons. CONCLUSIONS: This cross-sectional study in pediatric patients with hydrocephalus and healthy controls demonstrated using whole-brain probabilistic tractography that there are various networks with dysregulated white matter integrity in hydrocephalus patients relative to controls. These dysregulated networks have tracts connecting structures throughout the brain, and the regions were predominately located centrally and posteriorly. Postoperative ventricle volume did not predict the white matter integrity of many tracts. Future studies with larger sample sizes are needed to further understand these results.

Strabismus outcomes in pediatric patients undergoing disconnective hemispheric surgery for intractable epilepsy: a systematic review.

BACKGROUND: Children undergoing hemispheric surgery for intractable seizures are susceptible to visual complications including strabismus. This systematic review aims to investigate the rates and characteristics of strabismus development after hemispheric surgery and evaluate clinical implications for ophthalmologic care. METHODS: A systematic search of MEDLINE, EMBASE, Cochrane, PsychINFO, and Web of Science databases was performed from database inception to May 2022. Included articles referred to strabismus outcomes in pediatric populations after hemispherectomy or hemispherotomy. Reviews and non-English-language publications were excluded. Risk of bias was assessed using Joanna Briggs Institute critical appraisal tools. Demographic data and characteristics of strabismus were extracted and tabulated. RESULTS: Of 41 articles identified, 10 studies consisting of 384 pediatric participants (48% females) and age at surgery between 6 months and 16 years were included. Preoperative strabismus rates ranged between 3% and 56%, whereas postoperative rates ranged between 38% and 100%. With respect to the site of hemispheric surgery, contralateral exodeviation was the most common (16%-67%; n = 7) and then ipsilateral exodeviation (16%-56%; n = 2), whereas ipsilateral esodeviation was infrequent (4%-9%; n = 3). CONCLUSIONS: Contralateral exotropia and ipsilateral esotropia may occur after hemispheric surgery and may have the potential to be field expanding. Concerns regarding negative social reactions should be balanced with the risk of visual field reduction and (or) diplopia by strabismus surgery. Higher-quality articles with large, homogeneous, and well-described populations (i.e., complete pre- and postoperative ophthalmologic assessments) are required to establish the risks and rates of strabismus development after hemispheric surgery.

The Role of Blood Oxygen Level Dependent Signal Variability in Pediatric Neuroscience: A Systematic Review.

BACKGROUND: As pediatric BOLD Signal Variability (SV) analysis is relatively novel, there is a need to provide a foundational framework that gives researchers an entry point into engaging with the topic. This begins with clarifying the definition of BOLD signal variability by identifying and categorizing the various metrics utilized to measure BOLD SV. METHODS: A systematic review of the literature was conducted. Inclusion criteria were restricted to studies utilizing any metric of BOLD SV and with individuals younger than 18 in the study population. The definition of BOLD SV was any measure of intra-individual variability in the BOLD signal. Five databases were searched: Psychinfo, Healthstar, MEDLINE, Embase, and Scopus. RESULTS: A total of 17 observational studies, including male (n = 1796) and female (n = 1324) pediatric participants were included. Eight studies quantified variability as the amount of deviation from the average BOLD signal, seven used complexity-based metrics, three used correlation measures of variability, and one used the structure of the hemodynamic response function. In this study, 10 methods of quantifying signal variability were identified. Associations and trends in BOLD SV were commonly found with age, factors specific to mental and/or neurological disorders such as attention deficit disorder, epilepsy, psychotic symptoms, and performance on psychological and behavioral tasks. CONCLUSIONS: BOLD SV is a potential biomarker of neurodevelopmental and neurological conditions and symptom severity in mental disorders for defined pediatric populations. Studies that establish clinical trends and identify the mechanisms underlying BOLD SV with a low risk of bias are needed before clinical applications can be utilized by physicians.

Subcortical brain volumes in neonatal hypoxic-ischemic encephalopathy.

BACKGROUND: Despite treatment with therapeutic hypothermia, hypoxic-ischemic encephalopathy (HIE) is associated with adverse developmental outcomes, suggesting the involvement of subcortical structures including the thalamus and basal ganglia, which may be vulnerable to perinatal asphyxia, particularly during the acute period. The aims were: (1) to examine subcortical macrostructure in neonates with HIE compared to age- and sex-matched healthy neonates within the first week of life; (2) to determine whether subcortical brain volumes are associated with HIE severity. METHODS: Neonates (n = 56; HIE: n = 28; Healthy newborns from the Developing Human Connectome Project: n = 28) were scanned with MRI within the first week of life. Subcortical volumes were automatically extracted from T1-weighted images. General linear models assessed between-group differences in subcortical volumes, adjusting for sex, gestational age, postmenstrual age, and total cerebral volumes. Within-group analyses evaluated the association between subcortical volumes and HIE severity. RESULTS: Neonates with HIE had smaller bilateral thalamic, basal ganglia and right hippocampal and cerebellar volumes compared to controls (all, p < 0.02). Within the HIE group, mild HIE severity was associated with smaller volumes of the left and right basal ganglia (both, p < 0.007) and the left hippocampus and thalamus (both, p < 0.04). CONCLUSIONS: Findings suggest that, despite advances in neonatal care, HIE is associated with significant alterations in subcortical brain macrostructure. IMPACT: Compared to their healthy counterparts, infants with HIE demonstrate significant alterations in subcortical brain macrostructure on MRI acquired as early as 4 days after birth. Smaller subcortical volumes impacting sensory and motor regions, including the thalamus, basal ganglia, and cerebellum, were seen in infants with HIE. Mild and moderate HIE were associated with smaller subcortical volumes.

Next-Generation Remote Hand Assessments: Cross-Platform DIGITS Web Application.

Purpose: We have previously developed DIGITS, a platform for remote evaluation of range of motion, dexterity, and swelling of fingers for reducing barriers to accessing clinical resources. The current study was aimed at evaluating DIGITS across different devices with varied operating systems and camera resolutions using a single person's hands. Methods: Our team has now developed a web application version of the DIGITS platform, which makes it accessible on any device that is equipped with a camera, including computers, tablets, and smartphones. In the present study, we aimed to validate this web application by comparing flexion and extension measurements on the same person's hands using three different devices with cameras of different resolutions. The absolute difference, SD, standard mean error, and intraclass correlation coefficient were calculated. Additionally, equivalency testing was performed using the confidence interval approach. Results: Our findings indicated that the differences in degree measured between the devices ranged from 2° to 3° when digit extension was assessed (all hand landmarks are visible in the camera's direct view) and from 3° to 8° when digit flexion was assessed (some of the hand landmarks are hidden from view). The intraclass correlation coefficient of individual trials ranged from 0.82 to 0.96 for extension and 0.77 to 0.87 for flexion across all devices. Additionally, within a 90% confidence interval, our data showed equivalency with measurements using three different devices. Conclusions: The absolute differences were within an acceptable 9° tolerance for measurements taken between devices for flexion and extension. Equivalency was observed for measurements of finger range of motion taken using DIGITS, regardless of devices, platforms, or camera resolutions. Clinical relevance: In summary, the DIGITS web application has good test-retest reliability to generate data on finger range of motion for hand telerehabilitation. DIGITS can reduce costs to patients, providers, and health care facilities for conducting postoperative follow-up assessments.

Default mode network functional connectivity strength in utero and the association with fetal subcortical development.

The default mode network is essential for higher-order cognitive processes and is composed of an extensive network of functional and structural connections. Early in fetal life, the default mode network shows strong connectivity with other functional networks; however, the association with structural development is not well understood. In this study, resting-state functional magnetic resonance imaging and anatomical images were acquired in 30 pregnant women with singleton pregnancies. Participants completed 1 or 2 MR imaging sessions, on average 3 weeks apart (43 data sets), between 28- and 39-weeks postconceptional ages. Subcortical volumes were automatically segmented. Activation time courses from resting-state functional magnetic resonance imaging were extracted from the default mode network, medial temporal lobe network, and thalamocortical network. Generalized estimating equations were used to examine the association between functional connectivity strength between default mode network-medial temporal lobe, default mode network-thalamocortical network, and subcortical volumes, respectively. Increased functional connectivity strength in the default mode network-medial temporal lobe network was associated with smaller right hippocampal, left thalamic, and right caudate nucleus volumes, but larger volumes of the left caudate. Increased functional connectivity strength in the default mode network-thalamocortical network was associated with smaller left thalamic volumes. The strong associations seen among the default mode network functional connectivity networks and regionally specific subcortical volume development indicate the emergence of short-range connectivity in the third trimester.

Funcmasker-flex: An Automated BIDS-App for Brain Segmentation of Human Fetal Functional MRI data.

Fetal functional magnetic resonance imaging (fMRI) offers critical insight into the developing brain and could aid in predicting developmental outcomes. As the fetal brain is surrounded by heterogeneous tissue, it is not possible to use adult- or child-based segmentation toolboxes. Manually-segmented masks can be used to extract the fetal brain; however, this comes at significant time costs. Here, we present a new BIDS App for masking fetal fMRI, funcmasker-flex, that overcomes these issues with a robust 3D convolutional neural network (U-net) architecture implemented in an extensible and transparent Snakemake workflow. Open-access fetal fMRI data with manual brain masks from 159 fetuses (1103 total volumes) were used for training and testing the U-net model. We also tested generalizability of the model using 82 locally acquired functional scans from 19 fetuses, which included over 2300 manually segmented volumes. Dice metrics were used to compare performance of funcmasker-flex to the ground truth manually segmented volumes, and segmentations were consistently robust (all Dice metrics ≥ 0.74). The tool is freely available and can be applied to any BIDS dataset containing fetal bold sequences. Funcmasker-flex reduces the need for manual segmentation, even when applied to novel fetal functional datasets, resulting in significant time-cost savings for performing fetal fMRI analysis.