Nelly Padilla

Brain Growth Gains and Losses in Extremely Preterm Infants at Term

Premature exposure to the extrauterine environment negatively affects the brains developmental trajectory. Our aim was to determine whether extremely preterm (EPT) infants, with no evidence of focal brain lesions, show morphological brain differences when compared with term-born infants. Additionally, we investigated associations between perinatal factors and neuroanatomical alterations. Conventional magnetic resonance imaging was acquired at term-equivalent age (TEA) from 47 EPT infants born before 27 weeks of gestation, and 15 healthy, term-born controls. Automatic segmentation and voxel-based morphometry-Diffeomorphic Anatomical Registration through Exponentiated Lie algebra (DARTEL) were used. Compared with controls, EPT infants displayed global reductions in cortical and subcortical gray matter, brainstem, and an increased cerebrospinal fluid volume. Regionally, they showed decreased volumes of all brain tissues, in particular cortical gray matter. Increased volumes of cortical gray and white matter were observed in regions involved in visual processing. Increasing prematurity, intraventricular hemorrhage grade I-II, and patent ductus arteriosus ligation were associated with decreased volumes and had a particular effect on the cerebellum. Concluding, EPT infants without focal brain lesions had an altered brain growth at TEA that particularly affected the gray matter, and varied when it came to the presence of perinatal risk factors. Brain growth gains in EPT infants may be related to a longer extrauterine experience.

Sex differences in outcome and associations with neonatal brain morphology in extremely preterm children

OBJECTIVEnTo investigate sex differences in neurologic and developmental outcomes in extremely preterm (EPT) children and explore associations with neonatal brain morphology.nnnSTUDY DESIGNnA population-based cohort of infants born at <27 weeks gestation underwent magnetic resonance imaging (MRI) at term equivalent age (n = 107). Voxel-based morphometry (n = 27) and tract-based spatial statistics (n = 29) were performed in infants with normal MRI findings. Neurologic and developmental assessment (using the Bayley Scales of Infant and Toddler Development-Third Edition [BSITD-III]) was performed at 30 months corrected age (n = 91).nnnRESULTSnEPT boys had lower mean cognitive composite scores (P = .03) and lower mean language composite scores (P = .04) compared with EPT girls. Rates of cerebral palsy were similar in the 2 sexes. No perinatal factor explained the variance in outcomes. Visual inspection of T1- and T2-weighted MRI images found that delayed myelination was found more frequently in boys, whereas cerebellar abnormalities were more common in girls. In the subgroup of children with normal MRI findings (n = 27), boys had poorer cognitive function (P = .015) and language function (P = .008), despite larger volumes of cerebellar tissue (P = .029). In boys, cerebellar volume was positively correlated with BSITD-III cognitive and motor scores (P = .04 for both). In girls, white matter volume (P = .02) and cortical gray matter volume (P = .03) were positively correlated with BSITD-III language score. At the regional level, significant correlations with outcomes were found only in girls.nnnCONCLUSIONnCognitive and language outcomes at age 30 months were poorer in boys. Sex-related differences were observed on neonatal structural MRI, including differences in the patterns of correlations between brain volumes and developmental scores at both global and regional levels.

Fetal Brain MRI Texture Analysis Identifies Different Microstructural Patterns in Adequate and Small for Gestational Age Fetuses at Term

Objectives: We tested the hypothesis whether a texture analysis (TA) algorithm applied to MRI brain images identified different patterns in small for gestational age (SGA) fetuses as compared with adequate for gestational age (AGA). Study Design: MRI was performed on 83 SGA and 70 AGA at 37 weeks GA. Texture features were quantified in the frontal lobe, basal ganglia, mesencephalon, cerebellum and cingulum. A classification algorithm based on discriminative models was used to correlate texture features with clinical diagnosis. Results: Region of interest delineation in all areas was achieved in 61 SGA (12 vasodilated) and 52 AGA; this was the sample for TA feature extraction which allowed classifying SGA from AGA with accuracies ranging from 90.9 to 98.9% in SGA versus AGA comparison and from 93.6 to 100% in vasodilated SGA versus AGA comparison. Conclusions: This study demonstrates that TA can detect brain differences in SGA fetuses. This supports the existence of brain microstructural changes in SGA fetuses.

Poor Brain Growth in Extremely Preterm Neonates Long Before the Onset of Autism Spectrum Disorder Symptoms

Abstract Preterm infants face an increased risk of autism spectrum disorder (ASD). The relationship between autism during childhood and early brain development remains unexplored. We studied 84 preterm children born at <27 weeks of gestation, who underwent neonatal magnetic resonance imaging (MRI) at term and were screened for ASD at 6.5 years. Full‐scale intelligence quotient was measured and neonatal morbidities were recorded. Structural brain morphometric studies were performed in 33 infants with high‐quality MRI and no evidence of focal brain lesions. Twenty‐three (27.4%) of the children tested ASD positive and 61 (72.6%) tested ASD negative. The ASD‐positive group had a significantly higher frequency of neonatal complications than the ASD‐negative group. In the subgroup of 33 children, the ASD infants had reduced volumes in the temporal, occipital, insular, and limbic regions and in the brain areas involved in social/behavior and salience integration. This study shows that the neonatal MRI scans of extremely preterm children, subsequently diagnosed with ASD at 6.5 years, showed brain structural alterations, localized in the regions that play a key role in the core features of autism. Early detection of these structural alterations may allow the early identification and intervention of children at risk of ASD.

Extremely Preterm-Born Infants Demonstrate Different Facial Recognition Processes at 6-10 Months of Corrected Age

OBJECTIVESnTo compare cortical hemodynamic responses to known and unknown facial stimuli between infants born extremely preterm and term-born infants, and to correlate the responses of the extremely preterm-born infants to regional cortical volumes at term-equivalent age.nnnSTUDY DESIGNnWe compared 27 infants born extremely preterm (<28 gestational weeks) with 26 term-born infants. Corrected age and chronological age at testing were between 6 and 10xa0months, respectively. Both groups were exposed to a gray background, their mothers face, and an unknown face. Cerebral regional concentrations of oxygenated and deoxygenated hemoglobin were measured with near-infrared spectroscopy. In the preterm group, we also performed structural brain magnetic resonance imaging and correlated regional cortical volumes to hemodynamic responses.nnnRESULTSnThe preterm-born infants demonstrated different cortical face recognition processes than the term-born infants. They had a significantly smaller hemodynamic response in the right frontotemporal areas while watching their mothers face (0.13xa0μmol/L vs 0.63xa0μmol/L; Pxa0<xa0.001). We also found a negative correlation between the magnitude of the oxygenated hemoglobin increase in the right frontotemporal cortex and regional gray matter volume in the left fusiform gyrus and amygdala (voxels, 25; rxa0=xa00.86; Pxa0<xa0.005).nnnCONCLUSIONnAt 6-10xa0months corrected age, the preterm-born infants demonstrated a different pattern in the maturation of their cortical face recognition process compared with term-born infants.

Clinical Implications of Diffuse Excessive High Signal Intensity (DEHSI) on Neonatal MRI in School Age Children Born Extremely Preterm.

Objective Magnetic resonance imaging (MRI) of the brain carried out during the neonatal period shows that 55–80% of extremely preterm infants display white matter diffuse excessive high signal intensity (DEHSI). Our aim was to study differences in developmental outcome at the age of 6.5 years in children born extremely preterm with and without DEHSI. Study Design This was a prospective cohort study of 83 children who were born in Stockholm, Sweden, between 2004 and 2007, born at gestational age of < 27 weeks + 0 days and who underwent an MRI scan of their brain at term equivalent age. The outcome measures at 6.5 years included testing 66 children with the modified Touwen neurology examination, the Movement Assessment Battery for Children 2, the Wechsler Intelligence Scale for Children—Fourth Edition, Beery Visual-motor Integration test—Sixth Edition, and the Strengths and Difficulties Questionnaire. Group-wise comparisons were done between children with and without DEHSI using Student t-test, Mann Whitney U test, Chi square test and regression analysis. Results DEHSI was detected in 39 (59%) of the 66 children who were assessed at 6.5 years. The presence of DEHSI was not associated with mild neurological dysfunction, scores on M-ABC assessment, cognition, visual-motor integration, or behavior at 6.5 years. Conclusion The presence of qualitatively defined DEHSI on neonatal MRI did not prove to be a useful predictor of long-term impairment in children born extremely preterm.

Visual–motor integration and fine motor skills at 6½ years of age and associations with neonatal brain volumes in children born extremely preterm in Sweden: a population-based cohort study

Objectives This exploratory study aimed to investigate associations between neonatal brain volumes and visual–motor integration (VMI) and fine motor skills in children born extremely preterm (EPT) when they reached 6½ years of age. Setting Prospective population-based cohort study in Stockholm, Sweden, during 3u2009years. Participants All children born before gestational age, 27 weeks, during 2004–2007 in Stockholm, without major morbidities and impairments, and who underwent MRI at term-equivalent age. Main outcome measures Brain volumes were calculated using morphometric analyses in regions known to be involved in VMI and fine motor functions. VMI was assessed with The Beery-Buktenica Developmental Test of Visual–Motor Integration—sixth edition and fine motor skills were assessed with the manual dexterity subtest from the Movement Assessment Battery for Children—second edition, at 6½ years. Associations between the brain volumes and VMI and fine motor skills were evaluated using partial correlation, adjusted for total cerebral parenchyma and sex. Results Out of 107 children born at gestational age <27 weeks, 83 were assessed at 6½ years and 66/83 were without major brain lesions or cerebral palsy and included in the analyses. A representative subsample underwent morphometric analyses: automatic segmentation (n=34) and atlas-based segmentation (n=26). The precentral gyrus was associated with both VMI (r=0.54, P=0.007) and fine motor skills (r=0.54, P=0.01). Associations were also seen between fine motor skills and the volume of the cerebellum (r=0.42, P=0.02), brainstem (r=0.47, P=0.008) and grey matter (r=−0.38, P=0.04). Conclusions Neonatal brain volumes in areas known to be involved in VMI and fine motor skills were associated with scores for these two functions when children born EPT without major brain lesions or cerebral palsy were evaluated at 6½ years of age. Establishing clear associations between early brain volume alterations and later VMI and/or fine motor skills could make early interventions possible.

National population-based cohort study found that visual-motor integration was commonly affected in extremely preterm born children at six-and-a-half years

This study aimed to explain the relationship between visual‐motor integration (VMI) abilities and extremely preterm (EPT) birth, by exploring the influence of perinatal variables, cognition, manual dexterity and ophthalmological outcomes.

Combined 18F-FDG-PET and diffusion tensor imaging in mesial temporal lobe epilepsy with hippocampal sclerosis

Objectives Several studies using 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) or diffusion tensor imaging (DTI) have found both temporal and extratemporal abnormalities in patients with mesial temporal lobe epilepsy with ipsilateral hippocampal sclerosis (MTLE-HS), but data are lacking about the findings of both techniques in the same patients. We aimed to determine whether the extent of 18F-FDG-PET hypometabolism is related to DTI abnormalities. Methods Twenty-one patients with MTLE-HS underwent comprehensive preoperative evaluation; 18 (86%) of these underwent epilepsy surgery. We analyzed and compared the pattern of white matter (WM) alterations on DTI and cortical hypometabolism on 18F-FDG-PET. Results We found widespread temporal and extratemporal 18F-FDG-PET and DTI abnormalities. Patterns of WM abnormalities and cortical glucose hypometabolism involved similar brain regions, being more extensive in the left than the right MTLE-HS. We classified patients into three groups according to temporal 18F-FDG-PET patterns: hypometabolism restricted to the anterior third (n = 7), hypometabolism extending to the middle third (n = 7), and hypometabolism extending to the posterior third (n = 7). Patients with anterior temporal hypometabolism showed DTI abnormalities in anterior association and commissural tracts while patients with posterior hypometabolism showed WM alterations in anterior and posterior tracts. Conclusions Patients with MTLE-HS have widespread metabolic and microstructural abnormalities that involve similar regions. The distribution patterns of these gray and white matter abnormalities differ between patients with left or right MTLE, but also with the extent of the 18F-FDG-PET hypometabolism along the epileptogenic temporal lobe. These findings suggest a variable network involvement among patients with MTLE-HS.

PO-0850 Resting State Networks In Preterm Infants With And Without Intrauterine Growth Restriction

Background and aims Prematurity and intrauterine growth restriction (IUGR) is associated with deviations of the developmental trajectory of the brain. We aimed to examine resting state networks (RSNs) in preterm infants with and without IUGR during natural sleep at 12 months. Methods We included 30 preterm infants (<34 weeks) without focal brain lesions (12 with IUGR and 18 appropriate for gestational age) and 20 born-term infants that were scanned at 12 months during natural sleep. Structural and functional MRI was acquired in a 3T scanner. To account for head movement we performed frame censoring of the data. RSNs were computed using the MELODIC module (FSL software). Dual regression analysis was used to query between--group differences in RSNs. Results Overall, the degree of movement on functional data was small. In the group we identified nine RSNs encompassing bilaterally the primary visual cortex, auditory cortex, sensori-motor cortex, lateral parietal cortex, precuneus, frontal and a sub-cortical network. Preterm infants had a more prominent cerebellar network compared to term infants. The three groups showed a fragmentized default-mode network. No significant differences were found between groups. Conclusions The spatial patterns of the RSNs observed in preterm and term infants corresponded closely to those observed in adults. These findings may suggest that IUGR and prematurity does not interfere with the normal process of functional brain network development at 12 months of age. The fact that we could not find differences in RSNs does not rule out that alterations could occur later in development.