Diffusion Weighted Imaging of the Neonatal Brain

Although in the last decades advances in fetal and neonatal medicine have reduced mortality in neonatal intensive care units in the Western world, the morbidity due to brain injury remains high. Patterns of neonatal brain injury can be roughly divided in (1) term and (2) preterm patterns. Table 1 shows the number of infants admitted to the NICU in the Sophia Children’s Hospital between March 2008 and March 2010 with a typical ‘neurological’ diagnosis. The table highlights differences in diagnoses between preterm and term infants in relation to gender. In preterm infants the most common diagnoses are: persistent flaring (hypersignal intensity seen in periventricluar white matter using cranial ultrasound), intraventricular haemorrhage and venous infarction. In term infants perinatal asphyxia and perinatal stroke are most often reported

A normative spatiotemporal MRI atlas of the fetal brain for automatic segmentation and analysis of early brain growth.

Longitudinal characterization of early brain growth in-utero has been limited by a number of challenges in fetal imaging, the rapid change in size, shape and volume of the developing brain, and the consequent lack of suitable algorithms for fetal brain image analysis. There is a need for an improved digital brain atlas of the spatiotemporal maturation of the fetal brain extending over the key developmental periods. We have developed an algorithm for construction of an unbiased four-dimensional atlas of the developing fetal brain by integrating symmetric diffeomorphic deformable registration in space with kernel regression in age. We applied this new algorithm to construct a spatiotemporal atlas from MRI of 81 normal fetuses scanned between 19 and 39 weeks of gestation and labeled the structures of the developing brain. We evaluated the use of this atlas and additional individual fetal brain MRI atlases for completely automatic multi-atlas segmentation of fetal brain MRI. The atlas is available online as a reference for anatomy and for registration and segmentation, to aid in connectivity analysis, and for groupwise and longitudinal analysis of early brain growth

PRETERM BIRTH RESULTS IN ALTERATIONS IN NEURAL CONNECTIVITY AT AGE 16 YEARS

Very low birth weight preterm (PT) children are at high risk for brain injury. This study investigates microstructural differences in the brains of PT adolescents relative to term control subjects using diffusion tensor imaging (DTI), as well as studying their neurodevelopmental outcomes. Forty-four PT subjects (600 - 1250 grams birth weight) without neonatal brain injury and 41 term controls were evaluated at age 16 years with DTI, the Wechsler Intelligence Scale for Children - III (WISC), the Peabody Picture Vocabulary Test - Revised (PPVT), and the Comprehensive Test of Phonological Processing (CTOPP). PT subjects scored lower than term subjects on WISC full scale (p = 0.002), verbal (p = 0.027), and performance IQ tests (p = 0.001), as well as CTOPP phonological awareness (p = 0.005), but scored comparably to term subjects on PPVT and CTOPP Rapid Naming tests. PT subjects had lower fractional anisotropy (FA) values, suggestive of white matter disorganization, in multiple regions including bilateral uncinate fasciculi (left: p = 0.004; right: p = 0.002), bilateral external capsules (left: p \u3c 0.0001; right: p = 0.001), the splenium of the corpus callosum (p = 0.014), and white matter serving the inferior frontal gyrus bilaterally (left: p \u3c 0.0001; right: p = 0.005). FA values in both the left and right uncinate fasciculi correlated with PPVT scores (a semantic language task) in the PT subjects (left: R = 0.314, p = 0.038; right: R = 0.336, p = 0.026). FA values in the left and right arcuate fasciculi correlated with CTOPP Rapid Naming scores (a phonologic task) in the PT subjects (left: R = 0.424, p = 0.004; right: R = 0.301, p = 0.047). These data support for the first time that the recently proposed concept of dual pathways underlying language function are present in PT adolescents. These include a left-sided dorsal pathway associated with phonological and articulatory processing (arcuate fasciculus), and a bilateral ventral pathway for semantic, receptive language processing (uncinate fasciculus). The striking bilateral dorsal correlations for the PT group suggest that prematurely born subjects rely more heavily on the right hemisphere than typically developing adolescents for performance of phonological language tasks. These findings may represent either a delay in maturation or the engagement of alternative neural pathways for language in the developing PT brain

Univariate and multivariate pattern analysis of preterm subjects: a multimodal neuroimaging study

Background: Widespread lasting functional connectivity (FC) and brain volume changes in cortices and subcortices after premature birth have been researched in recent studies. However, the relationship remains unclear between spontaneously slow blood oxygen dependent level (BOLD) fluctuations and gray matter volume (GMV) changes in specific brain areas, such as temporal insular cortices, and whether classification methods based on MRI could be successfully applied to the identification of preterm individuals. In this thesis I hypothesized that in prematurely born adults 1. Ongoing neural excitability and brain activity, as estimated by regional functional connectivity of resting state functional MRI (rs-fMRI) is accompanied with altered low-frequency fluctuations and neonatal complications; 2. Altered regional functional connectivity is connected with superimposed cerebral structural reductions; and 3. multivariate neuroanatomical and functional brain patterns could be treated as features to identify preterm subjects from term subjects individually. Methods: To investigate these hypotheses, the principal results of structural alterations were measured with voxel-based morphometry (VBM), while rs-fMRI outcomes were estimated with amplitude of low-frequency fluctuations (ALFF) in analysis with ninety-four very preterm/very low birth weight (VP/VLBW) and ninety-two full-term (FT) born young adults. Results: The results of the thesis support the hypotheses by showing that, in univariate results, first in VP/VLBW grownups, ALFF was decreased in the left lateral temporal cortices no matter with global signal regression, and this reduction was closely associated with neonatal complications and cognitive variables. Second overlapped brain regions were found between reduced ALFF and reduced brain volumes in the left temporal cortices, and positively associated with each other, demonstrating a potential relationship between VBM and ALFF in this brain area. In multimodal multivariate pattern recognition analysis (MVPA), the gray matter volume (GMV) classifier displayed a higher accuracy (80.7%) contrast with the ALFF classifier (77.4%). The late fusion of GMV and ALFF did not outperform single GMV modality classification by reaching 80.4% accuracy. Moderator analysis from both rs-fMRI and structural MRI (sMRI) uncovered that the neuro-prematurity performance was predominantly determined by neonatal complications. Conclusions: In conclusion, these outcomes exhibit the long term effects of premature labour on lateral temporal cortices, which changed in both ongoing BOLD fluctuations and decreased cerebral structural volumes. This thesis further provided evidence that multivariate pattern analysis such as support vector machine (SVM) may identify imaging-based biomarkers and reliably detect signatures of preterm birth

Univariate and multivariate pattern analysis of preterm subjects: a multimodal neuroimaging study

Background: Widespread lasting functional connectivity (FC) and brain volume changes in cortices and subcortices after premature birth have been researched in recent studies. However, the relationship remains unclear between spontaneously slow blood oxygen dependent level (BOLD) fluctuations and gray matter volume (GMV) changes in specific brain areas, such as temporal insular cortices, and whether classification methods based on MRI could be successfully applied to the identification of preterm individuals. In this thesis I hypothesized that in prematurely born adults 1. Ongoing neural excitability and brain activity, as estimated by regional functional connectivity of resting state functional MRI (rs-fMRI) is accompanied with altered low-frequency fluctuations and neonatal complications; 2. Altered regional functional connectivity is connected with superimposed cerebral structural reductions; and 3. multivariate neuroanatomical and functional brain patterns could be treated as features to identify preterm subjects from term subjects individually. Methods: To investigate these hypotheses, the principal results of structural alterations were measured with voxel-based morphometry (VBM), while rs-fMRI outcomes were estimated with amplitude of low-frequency fluctuations (ALFF) in analysis with ninety-four very preterm/very low birth weight (VP/VLBW) and ninety-two full-term (FT) born young adults. Results: The results of the thesis support the hypotheses by showing that, in univariate results, first in VP/VLBW grownups, ALFF was decreased in the left lateral temporal cortices no matter with global signal regression, and this reduction was closely associated with neonatal complications and cognitive variables. Second overlapped brain regions were found between reduced ALFF and reduced brain volumes in the left temporal cortices, and positively associated with each other, demonstrating a potential relationship between VBM and ALFF in this brain area. In multimodal multivariate pattern recognition analysis (MVPA), the gray matter volume (GMV) classifier displayed a higher accuracy (80.7%) contrast with the ALFF classifier (77.4%). The late fusion of GMV and ALFF did not outperform single GMV modality classification by reaching 80.4% accuracy. Moderator analysis from both rs-fMRI and structural MRI (sMRI) uncovered that the neuro-prematurity performance was predominantly determined by neonatal complications. Conclusions: In conclusion, these outcomes exhibit the long term effects of premature labour on lateral temporal cortices, which changed in both ongoing BOLD fluctuations and decreased cerebral structural volumes. This thesis further provided evidence that multivariate pattern analysis such as support vector machine (SVM) may identify imaging-based biomarkers and reliably detect signatures of preterm birth

Efeito de uma intervenção em crianças com hemiparésia espástica ao nível dos ajustes posturais anticipatórios no início da marcha

Objectivos: Verificar o efeito de uma intervenção baseada na abordagem segundo o Conceito de Bobath nos Ajustes Posturais Anticipatórios no Início da Marcha em duas crianças com hemiparésia espástica. Pretendeu-se ainda, verificar o efeito desta abordagem nas actividades e participação, bem como comparar os aspectos individuais das duas crianças com a capacidade de mudança após a intervenção. Metodologia: A avaliação foi realizada antes e três meses após a intervenção através da Electromiografia, da Plataforma de Forças, de um sistema de Câmaras de Vídeo, de uma Máquina Fotográfica e da Classificação Internacional de Funcionalidade para Crianças e Jovens. Resultados: A sequência de activação muscular alterou-se apenas na criança A. A postura na posição de pé, a actividade muscular, o deslocamento do centro de pressão e as actividades e participação modificaram-se em ambas as crianças, sendo que a criança A apresentou maior capacidade de mudança. Conclusão: A intervenção com base numa abordagem segundo o conceito de Bobath induziu mudanças positivas nos Ajustes Posturais Anticipatórios e nas actividades e participação dos casos em estudo.Objectives: This study aimed to evaluate the effect of an intervention-based approach according to the Bobath Concept in Anticipatory Postural Adjustments in Gait Initiation in two children with spastic hemiparesis. It was still intended to verify the effect of this approach in the activities and participation, as well as compare the individual aspects of both children with the ability to change after intervention. Methodology: The evaluation was performed before and three months after intervention by Electromyography, Force Plate, a system for Camcorder, Camera and an International Classification of Functioning for Children and Youth. Results: The sequence of the muscle activation changed only for the child A. The posture in a standing position, muscle activity, the displacement of the center of pressure and the activities and participation have changed in both children, but child A showed a greater capacity for change. Conclusion: The intervention based on an approach according to the Bobath concept has led to positive changes in Anticipatory Postural Adjustments and in activities and participation in the cases under study

Učinak perinatalne hipoksijsko – ishemijske encefalopatije na projekcijske puteve moždanoga debla u nedonoščeta [Impact of hypoxic-ischemic encephalopathy on projection pathways of the premature infant brainstem]

Introduction: Improved perinatal care has led to increased survival of premature infants. These children often have different motoric, cognitive and psychological disorders. Perinatal hypoxic-ischemic encephalopathy (HIE) is a major cause of white matter injury and long-term neurological deficits in children. The aim of this study is to analyze cerebral volumes and DTI parameters as major site of white matter injury and compare them with recipient areas in pons and cerebellum in order to find possible selective vulnerability for corticospinal tracts, corticopontine pathways, medial lemnisci and superior, medial and inferior cerebellar peduncles. Material and methods: In our research we had three groups of participants. The first group consisted of 5 normal term infants (control), the second group included 16 normotypic premature infants without perinatal HIE lesions (normotypic), and the third group included 22 premature infants with perinatal HIE (HIE). Diagnosis of perinatal HIE was based on both MRI and clinical exams. Parental consent for MRI scanning was obtained and all examinations were controlled and approved by the Institutional Review Board of the University of Zagreb School of Medicine. MRI images were obtained using 3T MRI scanner (Magnetom TrioTim, Siemens, Germany), with high resolution T1 MPRAGE sequence in sagittal plane (voxel size = 1x1x1 mm) and dwi sequences (voxel size 1.6x1.6x3 mm). All groups were scanned at two different time points, first at the term or corrected term age and second at the age of two years. Cerebral and cerebellar volumes were measured using semi-automated software (MNI toolbox, Montreal, Canada), and brainstem (mesencephalon, pons, medulla oblongata) was measured using manual segmentation methods (Analyze 8.1, Mayo Clinic, USA). Axonal pathways (corticospinal tracts, corticopontine pathways, medial lemnisci and superior, medial and inferior cerebellar peduncles) were reconstructed and all parameters (volume, FA- fractional anisotropy and ADC-apparent diffusion coefficient) have been measured using Diffusion Toolkit and TrackVis software. Statistical analysis was done using MedCalc v12. Results: Normotypic group showed decreased volumes at corrected term age, but their volumes compensate during growth and at the age of 2 years correspond to control group. Unlike normotypic, group with HIE lesions shows statistically significant reduction of measured volumes during corrected term age comparing with normal group, and also at the age of 2 years comparing with both normal and normotypic group. Volumetric analysis of brainstem parts (mesencephalon, pons, medulla oblongata) and its layers (base, tegmentum, tectum) follows that pattern as well as volumetric analysis of brainstem in general, cerebellum and total brain volume. Parameters measured during DTI analysis (volume, FA- fractional anisotropy and ADC-apparent diffusion coefficient) for named axonal pathways showed similar pattern in observed groups. Conclusion: Origin, trajectory and termination areas of measured axonal pathways are reduced after perinatal HIE. We have found that all measured pathways are regularly damaged in perinatal HIE, as a part of general white matter pathology. Our finding is in the agreement that pathways which are part of the periventricular fiber system and periventricular crossroads are vulnerable in HIE. Also, due to the topographical relationship, damaged periventricular fibers will contribute to reduction of brainstem, expecially pons, as well as cerebellum