Diffuse white matter abnormality in very preterm infants at term reflects reduced brain network efficiency.
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ABSTRACT:
SUBMITTER: Kline JE
PROVIDER: S-EPMC8378797 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo externally validate the independent value of objectively diagnosed diffuse white matter abnormality (DWMA; also known as diffuse excessive high signal intensity) volume to predict neurodevelopmental outcomes in very preterm infants (≤31 weeks of gestational age).Study designA prospective, multicenter, regional population-based cohort study in 98 very preterm infants without severe brain injury on magnetic resonance imaging (MRI). DWMA volume was diagnosed objectively on structural MRI at term-equivalent age using our published algorithm. Multivariable linear regression was used to assess the value of DWMA volume to predict cognitive and language scores on the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) at 2 years corrected age.ResultsOf the infants who returned for follow-up (n = 74), the mean (SD) gestational age was 28.2 (2.4) weeks, and 42 (56.8%) were boys. In bivariable analyses, DWMA volume was a significant predictor of Bayley-III cognitive and language scores. In multivariable analyses, controlling for known predictors of Bayley-III scores (ie, socioeconomic status, gestational age, sex, and global brain abnormality score), DWMA volume remained a significant predictor of cognitive (P < .001) and language (P = .04) scores at 2 years. When dichotomized, objectively diagnosed severe DWMA was a significant predictor of cognitive and language impairments, whereas visual qualitative diagnosis of DWMA was a poor predictor.ConclusionsIn this multicenter, prospective cohort study, we externally validated our previous findings that objectively diagnosed DWMA is an independent predictor of cognitive and language development in very preterm infants. We also demonstrated again that visually-diagnosed DWMA is not predictive of neurodevelopmental outcomes.
| S-EPMC7583652 | biostudies-literature
Project description:Diffuse white matter abnormality (DWMA), or diffuse excessive high signal intensity is observed in 50-80% of very preterm infants at term-equivalent age. It is subjectively defined as higher than normal signal intensity in periventricular and subcortical white matter in comparison to normal unmyelinated white matter on T2-weighted MRI images. Despite the well-documented presence of DWMA, it remains debatable whether DWMA represents pathological tissue injury or a transient developmental phenomenon. Manual tracing of DWMA exhibits poor reliability and reproducibility and unduly increases image processing time. Thus, objective and ideally automatic assessment is critical to accurately elucidate the biologic nature of DWMA. We propose a deep learning approach to automatically identify DWMA regions on T2-weighted MRI images. Specifically, we formulated DWMA detection as an image voxel classification task; that is, the voxels on T2-weighted images are treated as samples and exclusively assigned as DWMA or normal white matter voxel classes. To utilize the spatial information of individual voxels, small image patches centered on the given voxels are retrieved. A deep convolutional neural networks (CNN) model was developed to differentiate DWMA and normal voxels. We tested our deep CNN in multiple validation experiments. First, we examined DWMA detection accuracy of our CNN model using computer simulations. This was followed by in vivo assessments in a cohort of very preterm infants (N = 95) using cross-validation and holdout validation. Finally, we tested our approach on an independent preterm cohort (N = 28) to externally validate our model. Our deep CNN model achieved Dice similarity index values ranging from 0.85 to 0.99 for DWMA detection in the aforementioned validation experiments. Our proposed deep CNN model exhibited significantly better performance than other popular machine learning models. We present an objective and automated approach for accurately identifying DWMA that may facilitate the clinical diagnosis of DWMA in very preterm infants.
| S-EPMC6591530 | biostudies-literature
Project description:ObjectiveTo identify perinatal clinical diseases and treatments that are associated with the development of objectively diagnosed diffuse white matter abnormality (DWMA) on structural magnetic resonance imaging (MRI) at term-equivalent age in infants born very preterm.Study designA prospective cohort of 392 infants born very preterm (≤32 weeks of gestational age) was enrolled from 5 level III/IV neonatal intensive care units between September 2016 and November 2019. MRIs of the brain were collected at 39 to 45 weeks of postmenstrual age to evaluate DWMA volume. A predefined list of pertinent maternal characteristics, pregnancy/delivery data, and neonatal intensive care unit data were collected for enrolled patients to identify antecedents of objectively diagnosed DWMA.ResultsOf the 392 infants in the cohort, 377 (96%) had high-quality MRI data. Their mean (SD) gestational age was 29.3 (2.5) weeks. In multivariable linear regression analyses, pneumothorax (P = .027), severe bronchopulmonary dysplasia (BPD) (P = .009), severe retinopathy of prematurity (P < .001), and male sex (P = .041) were associated with increasing volume of DWMA. The following factors were associated with decreased risk of DWMA: postnatal dexamethasone therapy for severe BPD (P = .004), duration of caffeine therapy for severe BPD (P = .009), and exclusive maternal milk diet at neonatal intensive care unit discharge (P = .049).ConclusionsSevere retinopathy of prematurity and BPD exhibited the strongest adverse association with development of DWMA. We also identified treatments and nutritional factors that appear protective against the development of DWMA that also have implications for the clinical care of infants born very preterm.
| S-EPMC8290900 | biostudies-literature
Project description:Our objective was to evaluate the independent prognostic value of a novel MRI biomarker-objectively diagnosed diffuse white matter abnormality volume (DWMA; diffuse excessive high signal intensity)-for prediction of motor outcomes in very preterm infants. We prospectively enrolled a geographically-based cohort of very preterm infants without severe brain injury and born before 32 weeks gestational age. Structural brain MRI was obtained at term-equivalent age and DWMA volume was objectively quantified using a published validated algorithm. These results were compared with visually classified DWMA. We used multivariable linear regression to assess the value of DWMA volume, independent of known predictors, to predict motor development as assessed using the Bayley Scales of Infant & Toddler Development, Third Edition at 3 years of age. The mean (SD) gestational age of the cohort was 28.3 (2.4) weeks. In multivariable analyses, controlling for gestational age, sex, and abnormality on structural MRI, DWMA volume was an independent prognostic biomarker of Bayley Motor scores ([Formula: see text]= -12.59 [95% CI -18.70, -6.48] R2?=?0.41). Conversely, visually classified DWMA was not predictive of motor development. In conclusion, objectively quantified DWMA is an independent prognostic biomarker of long-term motor development in very preterm infants and warrants further study.
| S-EPMC7523012 | biostudies-literature
Project description:Spatial and functional gradients of development have been described for the maturation of cerebral gray and white matter using histological and radiological approaches. We evaluated these patterns in very preterm (VPT) infants using diffusion tensor imaging. Data were obtained from 3 groups: 1) 22 VPT infants without white matter injury (WMI), of whom all had serial MRI studies during the neonatal period, 2) 19 VPT infants with WMI, of whom 3 had serial MRI studies and 3) 12 healthy, term-born infants. Regions of interest were placed in the cortical gray and adjacent white matter in primary motor, primary visual, visual association, and prefrontal regions. From the MRI data at term-equivalent postmenstrual age, differences in mean diffusivity were found in all areas between VPT infants with WMI and the other 2 groups. In contrast, minimal differences in fractional anisotropy were found between the 3 groups. These findings suggest that cortical maturation is delayed in VPT infants with WMI when compared with term control infants and VPT infants without WMI. From the serial MRI data from VPT infants, synchronous development between gray and white matter was evident in all areas and all groups, with maturation in primary motor and sensory regions preceding that of association areas. This finding highlights the regionally varying but locally synchronous nature of the development of cortical gray matter and its adjacent white matter.
| S-EPMC4961016 | biostudies-literature
Project description:Preterm infants are at risk for white matter (WM) injury and adverse neurodevelopmental outcomes.Serial diffusion tensor magnetic resonance imaging data were obtained from very preterm infants (N = 78) born <30?wk gestation imaged up to four times from 26-42?wk postmenstrual age. Slopes were calculated for fractional anisotropy (FA) and mean diffusivity (MD) within regions of interest for infants with ?2 scans (N = 50). Sixty-five children underwent neurodevelopmental testing at 2 y of age.FA slope for the posterior limb of the internal capsule was greater than other regions. The anterior limb of the internal capsule (ALIC), corpus callosum, and optic radiations demonstrated greater FA slope with increasing gestational age. Infants with patent ductus arteriosus had lower FA slope in the ALIC. MD slope was lower with prolonged ventilation or lack of antenatal steroids. At 2 y of age, lower motor scores were associated with lower FA in the left but higher FA in the right inferior temporal lobe at term-equivalent age. Better social-emotional competence was related to lower FA in the left cingulum bundle.This study demonstrates regional variability in the susceptibility/sensitivity of WM maturation to perinatal factors and relationships between altered diffusion measures and developmental outcomes in preterm neonates.
| S-EPMC4724306 | biostudies-literature
Project description:Increasing evidence suggests that abnormal white matter is central to the pathophysiology and, potentially, the pathogenesis of schizophrenia (SCZ). The spatial distribution of observed abnormalities and the type of white matter involved remain to be elucidated. Seventeen chronically ill individuals with SCZ and 17 age- and gender-matched controls were studied using a 3T magnetic resonance imaging diffusion tensor imaging protocol designed to examine the abnormalities of white matter by region and by level of architectural infrastructure as assessed by fractional anisotropy (FA) in native space. After assessing whole-brain FA, FA was divided into quartiles, capturing all brain regions with FA values from 0 to 0.25, 0.25 to 0.5, 0.5 to 0.75, and 0.75 to 1.0. Mean whole-brain FA was 4.6% smaller in the SCZ group than in healthy controls. This difference was largely accounted for by FA values from the second quartile (between 0.25 and 0.5). Second quartile FA was decreased in all 130 brain regions of the template in the SCZ group, with the difference reaching statistical significance in 41 regions. Correspondingly, the amount of brain tissue with an FA of ?0.4 was significantly reduced in the SCZ group, while the amount of brain tissue falling in the lowest quartile of FA was increased. These findings strongly imply a diffuse loss of white matter integrity in SCZ. Our finding that the loss of integrity disproportionately involves white matter of low to moderate organization suggests an approach to the specificity of white matter abnormalities in SCZ based on microstructure rather than spatial distribution.
| S-EPMC3604770 | biostudies-literature
Project description:Significant physiological switches occur at birth such as the transition from fetal parallel blood flow to a two-circuit serial system with increased arterial oxygenation of blood delivered to all organs including the brain. In addition, the extra-uterine environment exposes premature infants to a host of stimuli. These events could conceivably alter the trajectory of brain development in premature infants. We used in vivo magnetic resonance spectroscopy to measure absolute brain metabolite concentrations in term and premature-born infants without evidence of brain injury at equivalent post-conceptional age. Prematurity altered the developmental time courses of N-acetyl-aspartate, a marker for axonal and neuronal development, creatine, an energy metabolite, and choline, a membrane metabolite, in parietal white matter. Specifically, at term-equivalency, metabolic maturation in preterm infants preceded development in term infants, but then progressed at a slower pace and trajectories merged at ?340-370 post-conceptional days. In parieto/occipital grey matter similar trends were noticed but statistical significance was not reached. The timing of white matter development and synchronization of white matter and grey matter maturation in premature-born infants is disturbed. This may contribute to the greater risk of long-term neurological problems of premature infants and to their higher risk for white matter injury.
| S-EPMC3899075 | biostudies-literature
Project description:Very preterm birth is associated with altered white matter microstructure and language difficulties, which may compromise communication, social function and academic achievement, but the relationship between these two factors is unclear. The aim of this study was to explore associations between white matter microstructure and language domains of semantics, grammar and phonological awareness at 7-years of age on a whole-brain level and within the arcuate fasciculus, an important language pathway, in very preterm and term-born children. Language was assessed in 145 very preterm-born (<30?weeks' gestation and/or <1250?g birth weight) and 33 term-born children aged 7?years. Fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), mean diffusivity (MD), axon orientation dispersion and axon density were estimated from diffusion magnetic resonance images also obtained at 7?years. The correlation between diffusion values and language was assessed using Tract-Based Spatial Statistics (TBSS). The arcuate fasciculus was delineated using constrained spherical deconvolution tractography and diffusion parameters from this tract were related to language measures using linear regression. While there was evidence for widespread associations between white matter microstructure and language, there was little evidence of differences in these associations between very preterm and term-born groups. TBSS analyses revealed that higher FA and lower AD, RD, and MD in major fibre tracts, including those subserving language, were associated with better semantic, grammar and phonological awareness performance. Higher axon density in widespread fibre tracts was also associated with better semantic performance. The tractography analyses of the arcuate fasciculus showed some evidence for associations between white matter microstructure and language outcomes. White matter microstructural organisation in widespread fibre tracts, including language-relevant pathways, was associated with language performance in whole-brain and tract-based analyses. The associations were similar for very preterm and term-born groups, despite very preterm children performing more poorly across language domains.
| S-EPMC6169247 | biostudies-other
Project description:PurposeVery preterm (VPT) infants are at high risk for motor and behavioral deficits. We investigated microstructural differences using diffusion tensor imaging (DTI) among VPT infants with different grades of intraventricular hemorrhage (IVH), their association with early motor function and temperament ratings, and the potential moderating effect of IVH severity on the above structure-function relations.MethodsFifty-seven VPT (≤32 weeks gestational age) infants with IVH (Low Grade (Papile grading I/II): 42; High Grade (III/IV): 15) were studied. DTI was acquired between 39 and 44 weeks postmenstrual age and was analyzed using the tract-based spatial statistics approach. Early motor function and temperament were assessed at 3-month corrected age based on the Hammersmith Infant Neurological Examination (HINE) and Infant Behavioral Questionnaire - Revised, Short Version (IBQ-R-S), respectively.ResultsSignificantly lower fractional anisotropy and higher mean, axial, and/or radial diffusivity were found in VPT infants with High Grade IVH compared to Low Grade IVH (p < 0.05). Significant associations were found between DTI metrics and motor function in both IVH groups and between DTI and Fear temperament ratings in the High Grade IVH Group (all p < 0.05). IVH severity had a significant moderating effect on the relation between DTI and motor and Fear ratings (p < 0.05).ConclusionDTI is a sensitive neuroimaging biomarker providing a refined understanding of the impact and location of differing severities of IVH on the developing white matter of VPT infants. Early motor and behavioral outcomes are associated with microstructural changes that are influenced by severity of IVH.
| S-EPMC8376788 | biostudies-literature