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Newborns and preterm infants at term equivalent age: A semi-quantitative assessment of cerebral maturity.

ABSTRACT: BACKGROUND AND PURPOSE:Currently available MRI scoring systems of cerebral maturation in term and preterm infant at term equivalent age do not include the changes of transient fetal compartments that persist to term age. We studied the visibility and the pattern of these structures in healthy term newborns compared to preterm infants at term equivalent age in order to investigate if they can be included in a new MRI score system. We hypothesized that transient fetal compartments are different in both groups, and that these differences can be characterized using the clinical T2-weighted MRIs. MATERIALS AND METHODS:Using 3T MRI T2-weighted brain sequences of 21 full-term and 41 preterm infants (< 32 weeks), scanned at term equivalent age, 3 raters independently scored the maturation level of 3 transient fetal compartments: the periventricular crossroads, von Monakow segments of the white matter, and the subplate compartment. These 3 new items were included in a scoring system along with validated parameters of brain maturation (germinal matrix, bands of migration, subarachnoid space and quality of gyrification). A cumulative maturity score was calculated separately for both groups of newborns by adding together each item. More mature were the brain structures, higher was the cumulative maturity score. RESULTS:Cumulative maturity score distinguished full-term from preterm infants (mean score 41/60 ± 1.4 versus 37/60 ± 2.5 points, p < 0.001), with an increase of 0.5 points for each supplemental gestational week at birth (r?=?0.5, 95% CI 0.5 - 0.85). While a majority of transient fetal compartments were less mature in preterm group at term equivalent age, von Monakow segments of the white matter and subplate compartment presented a more advanced maturational stage in the preterm group compared to the term group. No subject had all scored items in the most mature state. Except a slight intra-rater agreement for von Monakow segment II, inter- and intra-rater agreements were moderate to excellent indicating the potential of the developed scoring system in routine clinical practice. CONCLUSION:Brain transient fetal structures can be assessed on regular T2-weighted MRI in newborns. Their appearance differs between term and preterm babies. However our results suggest a more complex situation, with both delayed and accelerated maturation pattern in preterm infants. It remains to be determined if these differences could be biomarkers of the future neurodevelopment of preterm infants.

SUBMITTER: Pittet MP

PROVIDER: S-EPMC6838895 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Newborns and preterm infants at term equivalent age: A semi-quantitative assessment of cerebral maturity.

Pittet Marie P MP Vasung Lana L Huppi Petra S PS Merlini Laura L

NeuroImage. Clinical 20191019

<h4>Background and purpose</h4>Currently available MRI scoring systems of cerebral maturation in term and preterm infant at term equivalent age do not include the changes of transient fetal compartments that persist to term age. We studied the visibility and the pattern of these structures in healthy term newborns compared to preterm infants at term equivalent age in order to investigate if they can be included in a new MRI score system. We hypothesized that transient fetal compartments are diff ...[more]

PMID: 31683202

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Project description:BackgroundInfants born at 29-36 weeks gestational age (GA) are at risk of experiencing neurodevelopmental challenges. We hypothesize that cerebral hemodynamics and oxygen metabolism measured by bedside optical brain monitoring are potential biomarkers of brain development and are associated with neurological examination at term-equivalent age (TEA).MethodsPreterm infants (N = 133) born 29-36 weeks GA and admitted in the neonatal intensive care unit were enrolled in this prospective cohort study. Combined frequency-domain near infrared spectroscopy (FDNIRS) and diffuse correlation spectroscopy (DCS) were used from birth to TEA to measure cerebral hemoglobin oxygen saturation and an index of microvascular cerebral blood flow (CBF i ) along with peripheral arterial oxygen saturation (SpO2). In combination with hemoglobin concentration in the blood, these parameters were used to derive cerebral oxygen extraction fraction (OEF) and an index of cerebral oxygen metabolism (CMRO2i ). The Amiel-Tison and Gosselin Neurological Assessment was performed at TEA. Linear regression models were used to assess the associations between changes in FDNIRS-DCS parameters from birth to TEA and GA at birth. Logistic regression models were used to assess the associations between changes in FDNIRS-DCS parameters from birth to TEA and neurological examination at TEA.ResultsSteeper increases in CBF i (p < 0.0001) and CMRO2i (p = 0.0003) were associated with higher GA at birth. Changes in OEF, CBF i , and CMRO2i from birth to TEA were not associated with neurological examination at TEA.ConclusionIn this population, cerebral FDNIRS-DCS parameters were not associated with neurological examination at TEA. Larger increases in CBF i and CMRO2i from birth to TEA were associated with higher GA. Non-invasive bedside FDNIRS-DCS monitoring provides cerebral hemodynamic and metabolic parameters that may complement neurological examination to assess brain development in preterm infants.

Project description:Very preterm infants (born at less than 32 weeks gestational age) are at high risk for serious motor impairments, including cerebral palsy (CP). The brain network changes that antecede the early development of CP in infants are not well characterized, and a better understanding may suggest new strategies for risk-stratification at term, which could lead to earlier access to therapies. Graph theoretical methods applied to diffusion MRI-derived brain connectomes may help quantify the organization and information transfer capacity of the preterm brain with greater nuance than overt structural or regional microstructural changes. Our aim was to shed light on the pathophysiology of early CP development, before the occurrence of early intervention therapies and other environmental confounders, to help identify the best early biomarkers of CP risk in VPT infants. In a cohort of 395 very preterm infants, we extracted cortical morphometrics and brain volumes from structural MRI and also applied graph theoretical methods to diffusion MRI connectomes, both acquired at term-equivalent age. Metrics from graph network analysis, especially global efficiency, strength values of the major sensorimotor tracts, and local efficiency of the motor nodes and novel non-motor regions were strongly inversely related to early CP diagnosis. These measures remained significantly associated with CP after correction for common risk factors of motor development, suggesting that metrics of brain network efficiency at term may be sensitive biomarkers for early CP detection. We demonstrate for the first time that in VPT infants, early CP diagnosis is anteceded by decreased brain network segregation in numerous nodes, including motor regions commonly-associated with CP and also novel regions that may partially explain the high rate of cognitive impairments concomitant with CP diagnosis. These advanced MRI biomarkers may help identify the highest risk infants by term-equivalent age, facilitating earlier interventions that are informed by early pathophysiological changes.

Project description:Premature infants exhibit widespread insults and delays in white matter maturation that can be sensitively detected early using diffusion tensor imaging. Diffusion tensor tractography facilitates in vivo visualization of white matter tracts and has the potential to be more sensitive than simpler two-dimensional DTI-based measures. However, the reliability and reproducibility of performing tractography for major white matter tracts in preterm infants is not known. The main objective of our study was to develop highly reliable and repeatable methods for ten white matter tracts in extremely low birth weight infants (birth weight ? 1000 g) at term-equivalent age. To demonstrate clinical utility, we also compared fiber microstructural and macrostructural parameters between preterm and healthy term controls. Twenty-nine ELBW infants and a control group of 15 healthy term newborns were studied. A team of researchers experienced in neuroanatomy/neuroimaging established the manual segmentation protocol based on a priori anatomical knowledge and an extensive training period to identify sources of variability. Intra- and inter-rater reliability and repeatability was tested using intra-class correlation coefficient, within-subject standard deviation (SD), repeatability, and Dice similarity index. Our results support our primary goal of developing highly reliable and reproducible comprehensive methods for manual segmentation of 10 white matter tracts in ELBW infants. The within-subject SD was within 1-2% and repeatability within 3-7% of the mean values for all 10 tracts. The intra-rater Dice index was excellent with a range of 0.97 to 0.99, and as expected, the inter-rater Dice index was lower (range: 0.80 to 0.91), but still within a very good reliability range. ELBW infants exhibited fewer fiber numbers and/or abnormal microstructure in a majority of the ten quantified tracts, consistent with injury/delayed development. This protocol could serve as a valuable tool for prompt evaluation of the impact of neuroprotective therapies and as a prognostic biomarker for neurodevelopmental impairments.

Dataset Information

Newborns and preterm infants at term equivalent age: A semi-quantitative assessment of cerebral maturity.

Publications

Newborns and preterm infants at term equivalent age: A semi-quantitative assessment of cerebral maturity.

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