Multimodality evaluation of the pediatric brain: DTI and its competitors

The development of the human brain, from the fetal period until childhood, happens in a series of intertwined neurogenetical and histogenetical events that are influenced by environment. Neuronal proliferation and migration, cell aggregation, axonal ingrowth and outgrowth, dendritic arborisation, synaptic pruning and myelinisation contribute to the ‘plasticity of the developing brain'. These events taken together contribute to the establishment of adult-like neuroarchitecture required for normal brain function. With the advances in technology today, mostly due to the development of non-invasive neuroimaging tools, it is possible to analyze these structural events not only in anatomical space but also longitudinally in time. In this review we have highlighted current ‘state of the art' neuroimaging tools. Development of the new MRI acquisition sequences (DTI, CHARMED and phase imaging) provides valuable insight into the changes of the microstructural environment of the cortex and white matter. Development of MRI imaging tools dedicated for analysis of the acquired images (i) TBSS and ROI fiber tractography, (ii) new tissue segmentation techniques and (iii) morphometric analysis of the cortical mantle (cortical thickness and convolutions) allows the researchers to map the longitudinal changes in the macrostructure of the developing brain that go hand-in-hand with the acquisition of cognitive skills during childhood. Finally, the latest and the newest technologies, like connectom analysis and resting state fMRI connectivity analysis, today, for the first time provide the opportunity to study the developing brain through the prism of maturation of the systems and networks beyond individual anatomical areas. Combining these methods in the future and modeling the hierarchical organization of the brain might ultimately help to understand the mechanisms underlying complex brain structure function relationships of normal development and of developmental disorder

Structural Brain Connectivity in School-Age Preterm Infants Provides Evidence for Impaired Networks Relevant for Higher Order Cognitive Skills and Social Cognition

Extreme prematurity and pregnancy conditions leading to intrauterine growth restriction (IUGR) affect thousands of newborns every year and increase their risk for poor higher order cognitive and social skills at school age. However, little is known about the brain structural basis of these disabilities. To compare the structural integrity of neural circuits between prematurely born controls and children born extreme preterm (EP) or with IUGR at school age, long-ranging and short-ranging connections were noninvasively mapped across cortical hemispheres by connection matrices derived from diffusion tensor tractography. Brain connectivity was modeled along fiber bundles connecting 83 brain regions by a weighted characterization of structural connectivity (SC). EP and IUGR subjects, when compared with controls, had decreased fractional anisotropy-weighted SC (FAw-SC) of cortico-basal ganglia-thalamo-cortical loop connections while cortico-cortical association connections showed both decreased and increased FAw-SC. FAw-SC strength of these connections was associated with poorer socio-cognitive performance in both EP and IUGR childre

Brain Microstructure assessed by CHARMED and NODDI in the newborn

DTI, may be the only feasible technique to study micorstructural changes occurring during the brain development. The main aims of this study was to design a complete new pipeline to perform micro-structural diffusion analysis in neonatal brain and to compare DTI to CHARMED and NODDI, which provides new microstructural metrics such as the intra-cellular volume fraction (nic) and the orientation dispersion index (ODI). High quality subject template was generated using DTI-TK tensor registration tools, which allows the accurate definitions of 13 ROIs. FA, nic and ODI were able to depict fine microstructural differences in early maturation fiber tracts

Optimal method for fetal brain age prediction using multiplanar slices from structural magnetic resonance imaging

The accurate prediction of fetal brain age using magnetic resonance imaging (MRI) may contribute to the identification of brain abnormalities and the risk of adverse developmental outcomes. This study aimed to propose a method for predicting fetal brain age using MRIs from 220 healthy fetuses between 15.9 and 38.7 weeks of gestational age (GA). We built a 2D single-channel convolutional neural network (CNN) with multiplanar MRI slices in different orthogonal planes without correction for interslice motion. In each fetus, multiple age predictions from different slices were generated, and the brain age was obtained using the mode that determined the most frequent value among the multiple predictions from the 2D single-channel CNN. We obtained a mean absolute error (MAE) of 0.125 weeks (0.875 days) between the GA and brain age across the fetuses. The use of multiplanar slices achieved significantly lower prediction error and its variance than the use of a single slice and a single MRI stack. Our 2D single-channel CNN with multiplanar slices yielded a significantly lower stack-wise MAE (0.304 weeks) than the 2D multi-channel (MAE = 0.979

Music processing in preterm and full-term newborns: A psychophysiological interaction (PPI) approach in neonatal fMRI

Neonatal Intensive Care Units (NICU) provide special equipment designed to give life support for the increasing number of prematurely born infants and assure their survival. More recently NICU's strive to include developmentally oriented care and modulate sensory input for preterm infants. Music, among other sensory stimuli, has been introduced into NICUs, but without knowledge on the basic music processing in the brain of preterm infants. In this study, we explored the cortico-subcortical music processing of different types of conditions (Original music, Tempo modification, Key transposition) in newborns shortly after birth to assess the effective connectivity of the primary auditory cortex with the entire newborn brain. Additionally, we investigated if early exposure during NICU stay modulates brain processing of music in preterm infants at term equivalent age. We approached these two questions using Psychophysiological Interaction (PPI) analyses. A group of preterm infants listened to music (Original music) starting from 33 weeks postconceptional age until term equivalent age and were compared to two additional groups without music intervention; preterm infants and full-term newborns. Auditory cortex functional connectivity with cerebral regions known to be implicated in tempo and familiarity processing were identified only for preterm infants with music training in the NICU. Increased connectivity between auditory cortices and thalamus and dorsal striatum may not only reflect their sensitivity to the known music and the processing of its tempo as familiar, but these results are also compatible with the hypothesis that the previously listened music induces a more arousing and pleasant state. Our results suggest that music exposure in NICU's environment can induce brain functional connectivity changes that are associated with music processing

Abnormal prenatal brain development in Chiari II malformation

IntroductionThe Chiari II is a relatively common birth defect that is associated with open spinal abnormalities and is characterized by caudal migration of the posterior fossa contents through the foramen magnum. The pathophysiology of Chiari II is not entirely known, and the neurobiological substrate beyond posterior fossa findings remains unexplored. We aimed to identify brain regions altered in Chiari II fetuses between 17 and 26 GW.MethodsWe used in vivo structural T2-weighted MRIs of 31 fetuses (6 controls and 25 cases with Chiari II).ResultsThe results of our study indicated altered development of diencephalon and proliferative zones (ventricular and subventricular zones) in fetuses with a Chiari II malformation compared to controls. Specifically, fetuses with Chiari II showed significantly smaller volumes of the diencephalon and significantly larger volumes of lateral ventricles and proliferative zones.DiscussionWe conclude that regional brain development should be taken into consideration when evaluating prenatal brain development in fetuses with Chiari II

Fetal Brain Tissue Annotation and Segmentation Challenge Results

In-utero fetal MRI is emerging as an important tool in the diagnosis and analysis of the developing human brain. Automatic segmentation of the developing fetal brain is a vital step in the quantitative analysis of prenatal neurodevelopment both in the research and clinical context. However, manual segmentation of cerebral structures is time-consuming and prone to error and inter-observer variability. Therefore, we organized the Fetal Tissue Annotation (FeTA) Challenge in 2021 in order to encourage the development of automatic segmentation algorithms on an international level. The challenge utilized FeTA Dataset, an open dataset of fetal brain MRI reconstructions segmented into seven different tissues (external cerebrospinal fluid, grey matter, white matter, ventricles, cerebellum, brainstem, deep grey matter). 20 international teams participated in this challenge, submitting a total of 21 algorithms for evaluation. In this paper, we provide a detailed analysis of the results from both a technical and clinical perspective. All participants relied on deep learning methods, mainly U-Nets, with some variability present in the network architecture, optimization, and image pre- and post-processing. The majority of teams used existing medical imaging deep learning frameworks. The main differences between the submissions were the fine tuning done during training, and the specific pre- and post-processing steps performed. The challenge results showed that almost all submissions performed similarly. Four of the top five teams used ensemble learning methods. However, one team's algorithm performed significantly superior to the other submissions, and consisted of an asymmetrical U-Net network architecture. This paper provides a first of its kind benchmark for future automatic multi-tissue segmentation algorithms for the developing human brain in utero.Comment: Results from FeTA Challenge 2021, held at MICCAI; Manuscript submitte

Analiza kvantitativnih i kvalitativnih promjena fetalnih zona, prikazanih magnetskom rezonancijom, kao pokazatelja glavnih histogenetskih događaja u normalnom razvoju ljudskog mozga

Before the birth the human telencephalon undergoes dynamic changes. The fetal telencephalic wall is built of transient fetal zones. These transient fetal zones are sites of occurence of the most important neurogenetic and histogenetic processes. As a result of intertwined complex neurogenetic events, morphological characteristics of the fetal telencephalon change depending on the age and the stage of development. Imaging of fetal telencephalon using magnetic resonance imaging thus allows quantitative measurements of transient fetal zones of the developing brain. Moreover, as qualitative MRI reflects the microstructural content (cell volume, the amount of fibres and extracellular space), the qualitative MRI information can be used as a basis for quantitative analysis. To determine the most important quantitative indicators, depending on the stage of development, the dominant neurogenetic events are analyzed and reconstructed within the framework of dynamical change in volume of transient fetal zones and their regional three-dimensional changes in thickness. Nineteen post-mortem fetal brains, aged 11 to 40 post-conceptional weeks (PCW), were obtained and scanned using the 3T Siemens MRI device. The MRI images were analyzed using programs developed at McGill University specifically designed for the analysis of postmortem fetal brains. The results obtained by calculating the volume of transient fetal zones suggest that the subplate zone represents the most important zone during the development of human telencephalon. Up to 30 PCW, it occupies about 40% of the total volume of telencephalon. The volume of proliferative zones, during the fetal stage of development (13 - 23 PCW), increases and reaches its peak value at 23 PCW. The increase in the volume of proliferative zones coincides with the dynamics and the peak wave of migration and proliferation of neuronal precursors described in literature. Thus, it can be used as one of biomarkers for the fetal stage of development. Furthermore, correlation matrices derived from regional analysis of subplate zone volumes (reaching the total volume peak at 30 PCW), regional cortical plate volumes (the total volume accelerates and exponentially increases after the 30 PCW) and between them suggest that the interaction of histogenetic changes (indirectly seen as postive and negative correlation between regional volumes), such as the ingrowth of axons in the subplate zone and the ingrowth of axons into the cortical plate, are important for the maturation of the cortex during the fetal stage of prenatal development. In addition, regional differences in the thickness and volume of the subplate zone and their correlation with the regional growth of the cortical plate from 24 PCW, indicate that the subplate zone, the site of the main neurogenetic events crucial for normal growth of axonal pathways, is important for normal growth and maturation of the cerebral cortex. In conclusion, the results of this study confirm the hypothesis that quantitative indicators estimated from MR images of the human postmortem fetal brains may serve as indicators for the main neurogenetic events that occur in transient fetal zones and thus have a clear potential as biomarkers of normal and abnormal human brain development

Process of cortical network formation and impact of early brain damage

The aim is to review mechanisms that are central to the formation of proper cortical circuitry and relevant to perinatal brain injury and premature birth