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.
•Subject motion in dMRI leads to a set of scattered slices with unique contrast.•We introduce a slice-to-volume reconstruction framework for multi-shell HARDI data•Based on a data-driven ...representation as spherical harmonics and radial decomposition (SHARD).•The method is evaluated in test-retest scans and in the neonatal dHCP cohort.•Results show robust reconstruction in severely motion-corrupted scans.
Diffusion MRI offers a unique probe into neural microstructure and connectivity in the developing brain. However, analysis of neonatal brain imaging data is complicated by inevitable subject motion, leading to a series of scattered slices that need to be aligned within and across diffusion-weighted contrasts. Here, we develop a reconstruction method for scattered slice multi-shell high angular resolution diffusion imaging (HARDI) data, jointly estimating an uncorrupted data representation and motion parameters at the slice or multiband excitation level. The reconstruction relies on data-driven representation of multi-shell HARDI data using a bespoke spherical harmonics and radial decomposition (SHARD), which avoids imposing model assumptions, thus facilitating to compare various microstructure imaging methods in the reconstructed output. Furthermore, the proposed framework integrates slice-level outlier rejection, distortion correction, and slice profile correction. We evaluate the method in the neonatal cohort of the developing Human Connectome Project (650 scans). Validation experiments demonstrate accurate slice-level motion correction across the age range and across the range of motion in the population. Results in the neonatal data show successful reconstruction even in severely motion-corrupted subjects. In addition, we illustrate how local tissue modelling can extract advanced microstructure features such as orientation distribution functions from the motion-corrected reconstructions.
Thiamine metabolism dysfunction syndrome-4 (THMD4) includes episodic encephalopathy, often associated with a febrile illness, causing transient neurologic dysfunction and a slowly progressive axonal ...polyneuropathy. Until now only two mutations (G125S and S194P) have been reported in the SLC25A19 gene as causative for this disease and a third mutation (G177A) as related to the Amish lethal microcephaly. In this work, we describe the clinical and molecular features of a patient carrying a novel mutation (c.576G>C; Q192H) on SLC25A19 gene. Functional studies on this mutation were performed explaining the pathogenetic role of c.576G>C in affecting the translational efficiency and/or stability of hMTPPT protein instead of the mRNA expression. These findings support the pathogenetic role of Q192H (c.576G>C) mutation on SLC25A19 gene. Moreover, despite in other patients the thiamine supplementation leaded to a substantial improvement of peripheral neuropathy, our patient did not show a clinical improvement.
Primary adrenal insufficiency (PAI) in children is an uncommon but severe condition which can be either inherited or acquired. It consists in clinical manifestation of defective production or ...ineffective action of endogenous glucocorticoids; deficiency in mineralocorticoids and adrenal androgens may coexist. Diagnosis of PAI in children and young people can be challenging; while adrenal crisis (acute decompensation) is a life-threatening condition, with patient presenting with characteristic features of hypoglycemia, hypotension, collapse and coma, chronic adrenal insufficiency may present with vague and non-specific symptoms, making the diagnosis more difficult.
Gastroenteritis and Syndrome of Inappropriate Secretion of Antidiuretic hormone (SIADH) are the most frequent reported misdiagnosis in patients with adrenal insufficiency (AI). While intravenous fluid replacement in the suspect of a gastroenteritis would be beneficial, a SIADH misdiagnosis can be harmful since the treatment of this condition is based primarily on fluid restriction.
We report the case of a child admitted to the emergency department whose condition was ultimately diagnosed as autoimmune adrenal insufficiency after few hours of inappropriate fluid restriction following a SIADH misdiagnosis.
AI is a rare condition in children and the diagnosis can be challenging. A missed diagnosis of AI or an inadequate treatment may cause severe complications, especially if a SIADH is erroneously diagnosed. Emergency physicians and pediatricians should be familiar with this diagnosis to enhance early recognition of this potentially life-threatening condition.
The Developing Human Connectome Project is an Open Science project that provides the first large sample of neonatal functional MRI data with high temporal and spatial resolution. These data enable ...mapping of intrinsic functional connectivity between spatially distributed brain regions under normal and adverse perinatal circumstances, offering a framework to study the ontogeny of large-scale brain organization in humans. Here, we characterize in unprecedented detail the maturation and integrity of resting state networks (RSNs) at term-equivalent age in 337 infants (including 65 born preterm). First, we applied group independent component analysis to define 11 RSNs in term-born infants scanned at 43.5-44.5 weeks postmenstrual age (PMA). Adult-like topography was observed in RSNs encompassing primary sensorimotor, visual and auditory cortices. Among six higher-order, association RSNs, analogues of the adult networks for language and ocular control were identified, but a complete default mode network precursor was not. Next, we regressed the subject-level datasets from an independent cohort of infants scanned at 37-43.5 weeks PMA against the group-level RSNs to test for the effects of age, sex and preterm birth. Brain mapping in term-born infants revealed areas of positive association with age across four of six association RSNs, indicating active maturation in functional connectivity from 37 to 43.5 weeks PMA. Female infants showed increased connectivity in inferotemporal regions of the visual association network. Preterm birth was associated with striking impairments of functional connectivity across all RSNs in a dose-dependent manner; conversely, connectivity of the superior parietal lobules within the lateral motor network was abnormally increased in preterm infants, suggesting a possible mechanism for specific difficulties such as developmental coordination disorder, which occur frequently in preterm children. Overall, we found a robust, modular, symmetrical functional brain organization at normal term age. A complete set of adult-equivalent primary RSNs is already instated, alongside emerging connectivity in immature association RSNs, consistent with a primary-to-higher order ontogenetic sequence of brain development. The early developmental disruption imposed by preterm birth is associated with extensive alterations in functional connectivity.
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.
Objective
Drug‐resistant focal epilepsy is often caused by focal cortical dysplasias (FCDs). The distribution of these lesions across the cerebral cortex and the impact of lesion location on clinical ...presentation and surgical outcome are largely unknown. We created a neuroimaging cohort of patients with individually mapped FCDs to determine factors associated with lesion location and predictors of postsurgical outcome.
Methods
The MELD (Multi‐centre Epilepsy Lesion Detection) project collated a retrospective cohort of 580 patients with epilepsy attributed to FCD from 20 epilepsy centers worldwide. Magnetic resonance imaging‐based maps of individual FCDs with accompanying demographic, clinical, and surgical information were collected. We mapped the distribution of FCDs, examined for associations between clinical factors and lesion location, and developed a predictive model of postsurgical seizure freedom.
Results
FCDs were nonuniformly distributed, concentrating in the superior frontal sulcus, frontal pole, and temporal pole. Epilepsy onset was typically before the age of 10 years. Earlier epilepsy onset was associated with lesions in primary sensory areas, whereas later epilepsy onset was associated with lesions in association cortices. Lesions in temporal and occipital lobes tended to be larger than frontal lobe lesions. Seizure freedom rates varied with FCD location, from around 30% in visual, motor, and premotor areas to 75% in superior temporal and frontal gyri. The predictive model of postsurgical seizure freedom had a positive predictive value of 70% and negative predictive value of 61%.
Significance
FCD location is an important determinant of its size, the age at epilepsy onset, and the likelihood of seizure freedom postsurgery. Our atlas of lesion locations can be used to guide the radiological search for subtle lesions in individual patients. Our atlas of regional seizure freedom rates and associated predictive model can be used to estimate individual likelihoods of postsurgical seizure freedom. Data‐driven atlases and predictive models are essential for evidence‐based, precision medicine and risk counseling in epilepsy.
Abstract
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.
The MP2RAGE sequence is typically optimized for either T
-weighted uniform image (UNI) or gray matter-dominant fluid and white matter suppression (FLAWS) contrast images. Here, the purpose was to ...optimize an MP2RAGE protocol at 7 Tesla to provide UNI and FLAWS images simultaneously in a clinically applicable acquisition time at <0.7 mm isotropic resolution.
Using the extended phase graph formalism, the signal evolution of the MP2RAGE sequence was simulated incorporating T
relaxation, diffusion, RF spoiling, and B
variability. Flip angles and TI were optimized at different TRs (TR
) to produce an optimal contrast-to-noise ratio for UNI and FLAWS images. Simulation results were validated by comparison to MP2RAGE brain scans of 5 healthy subjects, and a final protocol at TR
= 4000 ms was applied in 19 subjects aged 8-62 years with and without epilepsy.
FLAWS contrast images could be obtained while maintaining >85% of the optimal UNI contrast-to-noise ratio. Using TI
/TI
/TR
of 650/2280/4000 ms, 6/8 partial Fourier in the inner phase-encoding direction, and GRAPPA factor = 4 in the other, images with 0.65 mm isotropic resolution were produced in <7.5 min. The contrast-to-noise ratio was around 20% smaller at TR
= 4000 ms compared to that at TR
= 5000 ms; however, the 20% shorter duration makes TR
= 4000 ms a good candidate for clinical applications example, pediatrics.
FLAWS and UNI images could be obtained in a single scan with 0.65 mm isotropic resolution, providing a set of high-contrast images and full brain coverage in a clinically applicable scan time. Images with excellent anatomical detail were demonstrated over a wide age range using the optimized parameter set.
Aim
The aim of this study was to determine the safety and the efficacy of paediatrician‐administered propofol in children undergoing different painful procedures.
Methods
We conducted a retrospective ...study over a 12‐year period in three Italian hospitals. A specific training protocol was developed in each institution to train paediatricians administering propofol for painful procedures.
Results
In this study, 36 516 procedural sedations were performed. Deep sedation was achieved in all patients. None of the children experienced severe side effects or prolonged hospitalisation. There were six calls to the emergency team (0.02%): three for prolonged laryngospasm, one for bleeding, one for intestinal perforation and one during lumbar puncture. Nineteen patients (0.05%) developed hypotension requiring saline solution administration, 128 children (0.4%) needed O2 ventilation by face mask, mainly during upper endoscopy, 78 (0.2%) patients experienced laryngospasm, and 15 (0.04%) had bronchospasm. There were no differences in the incidence of major complications among the three hospitals, while minor complications were higher in children undergoing gastroscopy.
Conclusion
This multicentre study demonstrates the safety and the efficacy of paediatrician‐administered propofol for procedural sedation in children and highlights the importance of appropriate training for paediatricians to increase the safety of this procedure in children.
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