Associations between mother's depressive symptoms during pregnancy and newborn's brain functional connectivity.

Depression during pregnancy is common and the prevalence further increased during the COVID pandemic. Recent findings have shown potential impact of antenatal depression on children's neurodevelopment and behavior, but the underlying mechanisms are unclear. Nor is it clear whether mild depressive symptoms among pregnant women would impact the developing brain. In this study, 40 healthy pregnant women had their depressive symptoms evaluated by the Beck Depression Inventory-II at ~12, ~24, and ~36 weeks of pregnancy, and their healthy full-term newborns underwent a brain MRI without sedation including resting-state fMRI for evaluation of functional connectivity development. The relationships between functional connectivities and maternal Beck Depression Inventory-II scores were evaluated by Spearman's rank partial correlation tests using appropriate multiple comparison correction with newborn's gender and gestational age at birth controlled. Significant negative correlations were identified between neonatal brain functional connectivity and mother's Beck Depression Inventory-II scores in the third trimester, but not in the first or second trimester. Higher depressive symptoms during the third trimester of pregnancy were associated with lower neonatal brain functional connectivity in the frontal lobe and between frontal/temporal lobe and occipital lobe, indicating a potential impact of maternal depressive symptoms on offspring brain development, even in the absence of clinical depression.

MRI Findings in Third-Trimester Opioid-Exposed Fetuses, With Focus on Brain Measurements: A Prospective Multicenter Case-Control Study.

BACKGROUND. The opioid epidemic has profoundly affected infants born in the United States, as in utero opioid exposure increases the risk of cognitive and behavioral problems in childhood. Scarce literature has evaluated prenatal brain development in fetuses with opioid exposure in utero (hereafter opioid-exposed fetuses). OBJECTIVE. The purpose of this study is to compare opioid-exposed fetuses and fetuses without opioid exposure (hereafter unexposed fetuses) in terms of 2D biometric measurements of the brain and additional pregnancy-related assessments on fetal MRI. METHODS. This prospective case-control study included patients in the third trimester of pregnancy who underwent investigational fetal MRI at one of three U.S. academic medical centers from July 1, 2020, through December 31, 2021. Fetuses were classified as opioid exposed or unexposed in utero. Fourteen 2D biometric measurements of the fetal brain were manually assessed and used to derive four indexes. Measurements and indexes were compared between the two groups by use of multivariable linear regression models, which were adjusted for gestational age (GA), fetal sex, and nicotine exposure. Additional pregnancy-related findings on MRI were evaluated. RESULTS. The study included 65 women (mean age, 29.0 ± 5.5 [SD] years). A total of 28 fetuses (mean GA at the time of MRI, 32.2 ± 2.5 weeks) were opioid-exposed, and 37 fetuses (mean GA at the time of MRI, 31.9 ± 2.7 weeks) were unexposed. In the adjusted models, seven measurements were smaller (p < .05) in opioid-exposed fetuses than in unexposed fetuses: cerebral frontooccipital diameter (93.8 ± 7.4 vs 95.0 ± 8.6 mm), bone biparietal diameter (79.0 ± 6.0 vs 80.3 ± 7.1 mm), brain biparietal diameter (72.9 ± 7.7 vs 74.1 ± 8.6 mm), corpus callosum length (37.7 ± 4.0 vs 39.4 ± 3.7 mm), vermis height (18.2 ± 2.7 vs 18.8 ± 2.6 mm), anteroposterior pons measurement (11.6 ± 1.4 vs 12.1 ± 1.4 mm), and transverse cerebellar diameter (40.4 ± 5.1 vs 41.4 ± 6.0 mm). In addition, in the adjusted model, the frontoocccipital index was larger (p = .02) in opioid-exposed fetuses (0.04 ± 0.02) than in unexposed fetuses (0.04 ± 0.02). Remaining measures and indexes were not significantly different between the two groups (p > .05). Fetal motion, cervical length, and deepest vertical pocket of amniotic fluid were not significantly different (p > .05) between groups. Opioid-exposed fetuses, compared with unexposed fetuses, showed higher frequencies of both breech position (21% vs 3%, p = .03) and increased amniotic fluid volume (29% vs 8%, p = .04). CONCLUSION. Fetuses with opioid exposure in utero had a smaller brain size and altered fetal physiology. CLINICAL IMPACT. The findings provide insight into the impact of prenatal opioid exposure on fetal brain development.

Diffusion Tensor MRI of White Matter of Healthy Full-term Newborns: Relationship to Neurodevelopmental Outcomes.

Background It is well known that white matter injuries observed at birth are associated with adverse neurodevelopmental outcomes later in life. Whether white matter developmental variations in healthy newborns are also associated with changes in later neurodevelopment remains to be established. Purpose To evaluate whether developmental variations of white matter microstructures identified by MRI correlate with neurodevelopmental outcomes in healthy full-term infants. Materials and Methods In this prospective study, pregnant women were recruited and their healthy full-term newborns underwent a brain MRI including diffusion tensor imaging at approximately 2 weeks of age. These infants were tested at approximately 2 years of age with the Bayley Scales of Infant Development (BSID). Voxel-wise correlation analyses of fractional anisotropy (FA), measured with diffusion tensor MRI, and neurodevelopmental test scores, measured by using BSID, were performed by using tract-based spatial statistics (TBSS), followed by region-of-interest (ROI) analyses of correlations between mean FA in selected white matter ROIs and each BSID subscale score. Results Thirty-eight full-term infants (20 boys, 18 girls) underwent MRI examination at 2 weeks of age (14.3 days ± 1.6) and BSID measurement at 2 years of age (732 days ± 6). TBSS analyses showed widespread clusters in major white matter tracts, with positive correlations (P ≤ .05, corrected for the voxel-wise multiple comparisons) between FA values and multiple BSID subscale scores. These correlations were largely independent of several demographic parameters as well as family environment. Gestational age at birth appeared to be a confounding factor as TBSS-observed correlations weakened when it was included as a covariate; however, after controlling for gestational age at birth, ROI analyses still showed positive correlations (P ≤ .05, R = 0.35 to 0.48) between mean FA in many white matter ROIs and BSID cognitive, language, and motor scores. Conclusion There were significant associations between white matter microstructure developmental variations in healthy full-term newborns and their neurodevelopmental outcomes. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Hu and McAllister in this issue.

Brain gray and white matter differences in healthy normal weight and obese children.

PURPOSE: To compare brain gray and white matter development in healthy normal weight and obese children. METHODS: Twenty-four healthy 8- to 10-year-old children whose body mass index was either <75(th) percentile (normal weight) or >95(th) percentile (obese) completed an MRI examination which included T1-weighted three-dimensional structural imaging and diffusion tensor imaging (DTI). Voxel-based morphometry was used to compare the regional gray and white matter between the normal weight and obese children, and tract-based spatial statistics was used to compare the water diffusion parameters in the white matter between groups. RESULTS: Compared with normal weight children, obese children had significant (P < 0.05, family wise error corrected) regional gray matter reduction in the right middle temporal gyrus, left and right thalami, left superior parietal gyrus, left pre/postcentral gyri, and left cerebellum. Obese children also had higher white matter (P < 0.05, corrected) in multiple regions in the brain and higher DTI measured fractional anisotropy (FA) values (P < 0.05, corrected) in part of the left brain association and projection fibers. There was no difference in mean diffusivity at P < 0.05, corrected. DTI eigenvalues suggested that the FA differences were likely from decreased radial diffusivity (P < 0.1, corrected) and there was no change in axial diffusivity (corrected P > 0.35 for all voxels). CONCLUSION: Our results indicated that obese but otherwise healthy children have different regional gray and white matter development in the brain and differences in white matter microstructures compared with healthy normal weight children.

Brain ketones detected by proton magnetic resonance spectroscopy in an infant with Ohtahara syndrome treated with ketogenic diet.

Atypical resonances on proton magnetic resonance spectroscopy (MRS) examinations are occasionally found in children undergoing a metabolic evaluation for neurological conditions. While a radiologist's first instinct is to suspect a pathological metabolite, usually the origin of the resonance arises from an exogenous source. We report the appearance of distinct resonances associated with a ketogenic diet in a male infant presenting with Ohtahara syndrome. These resonances can be confused in interpretation with lactate and glutamate. To confirm assignments, the basis set for quantification was supplemented with simulations of ß-hydroxybutyrate, acetone and acetoacetate in LCModel spectroscopy processing software. We were able to quantitate the levels of end products of a ketogenic diet and illustrate how to distinguish these resonances.

Sex-specific association between infant diet and white matter integrity in 8-y-old children.

BACKGROUND: The American Academy of Pediatrics recommends breastfeeding, which is well known to promote cognitive and behavioral development. The evidence for why this occurs is not well understood. METHODS: Fifty-six 7.5- to 8.5-y-old healthy children were breastfed (BF; n = 22, 10 males) or formula-fed (FF; n = 34, 16 males) as infants. All children were administered: the Reynolds Intellectual Assessment Scale (RIAS); the Clinical Evaluation of Language Fundamentals (CELF-4) tests; and magnetic resonance imaging of the brain. Diffusion tensor imaging (DTI) measured fractional anisotropy (FA) values were correlated with RIAS and CELF-4 scores. RESULTS: DTI tract-based spatial statistics (TBSS) analyses showed multiple white matter regions in the left hemisphere with significantly higher FA (P < 0.05, corrected) values in BF than FF males, but no significant group differences in females. Males who were exclusively BF for at least 1 y appeared to have the greatest differences in FA. Mean FA values positively correlated with composite scores of RIAS (P = 0.03) and CELF-4 (P = 0.02). CONCLUSION: Breastfeeding during infancy was associated with better white matter development at 8 y of age in boys. A similar association was not observed in girls.

Diffusion tensor imaging in extremely low birth weight infants managed with hypercapnic vs. normocapnic ventilation.

BACKGROUND: Permissive hypercapnia is a ventilatory strategy used to prevent lung injury in ventilated extremely low birth weight (ELBW, birth weight ≤1,000 g) infants. However, there is retrospective evidence showing that high CO2 is associated with brain injury. OBJECTIVE: The objective of this study was to compare brain white matter development at term-equivalent age in ELBW infants randomized to hypercapnic vs. normocapnic ventilation during the first week of life and in healthy non-ventilated term newborns. MATERIALS AND METHODS: Twenty-two ELBW infants from a randomized controlled trial were included in this study; 11 received hypercapnic (transcutaneous PCO2 [tcPCO2] 50-60 mmHg) ventilation and 11 normocapnic (tcPCO2 35-45 mmHg) ventilation during the first week of life while still intubated. In addition, ten term healthy newborns served as controls. Magnetic resonance imaging (MRI) with diffusion tensor imaging (DTI) was performed at term-equivalent age for the ELBW infants and at approximately 2 weeks of age for the control infants. White matter injury on conventional MRI was graded in the ELBW and control infants using a scoring system adopted from literature. Tract-based spatial statistics (TBSS) was used to evaluate for differences in DTI measured fractional anisotropy (FA, spatially normalized to a customized template) among the ELBW and term control infants. RESULTS: Conventional MRI white matter scores were not different (7.3 ± 1.7 vs. 6.9 ± 1.4, P = 0.65) between the hypercapnic and normocapnic ELBW infants. TBSS analysis did not show significant differences (P < 0.05, corrected) between the two ELBW infant groups, although before multiple comparisons correction, hypercapnic infants had many regions with lower FA and no regions with higher FA (P < 0.05, uncorrected) compared to normocapnic infants. When compared to the control infants, normocapnic ELBW infants had a few small regions with significantly lower FA, while hypercapnic ELBW infants had more widespread regions with significantly lower FA (P < 0.05, fully corrected for multiple comparisons). CONCLUSIONS: Normocapnic ventilation vs. permissive hypercapnia may be associated with improved white matter development at term-equivalent age in ELBW infants. This effect, however, was small and was not apparent on conventional MRI. Further research is needed using larger sample sizes to assess if permissive hypercapnic ventilation in ELBW infants is associated with worse white matter development.

A Prospective Multi-Institutional Study Comparing the Brain Development in the Third Trimester between Opioid-Exposed and Nonexposed Fetuses Using Advanced Fetal MR Imaging Techniques.

BACKGROUND AND PURPOSE: While the adverse neurodevelopmental effects of prenatal opioid exposure on infants and children in the United States are well described, the underlying causative mechanisms have yet to be fully understood. This study aims to compare quantitative volumetric and surface-based features of the fetal brain between opioid-exposed fetuses and unexposed controls by using advanced MR imaging processing techniques. MATERIALS AND METHODS: This is a multi-institutional IRB-approved study in which pregnant women with and without opioid use during the current pregnancy were prospectively recruited to undergo fetal MR imaging. A total of 14 opioid-exposed (31.4 ± 2.3 weeks of gestation) and 15 unexposed (31.4 ± 2.4 weeks) fetuses were included. Whole brain volume, cortical plate volume, surface area, sulcal depth, mean curvature, and gyrification index were computed as quantitative features by using our fetal brain MR imaging processing pipeline. RESULTS: After correcting for gestational age, fetal sex, maternal education, polysubstance use, high blood pressure, and MR imaging acquisition site, all of the global morphologic features were significantly lower in the opioid-exposed fetuses compared with the unexposed fetuses, including brain volume, cortical volume, cortical surface area, sulcal depth, cortical mean curvature, and gyrification index. In regional analysis, the opioid-exposed fetuses showed significantly decreased surface area and sulcal depth in the bilateral Sylvian fissures, central sulci, parieto-occipital fissures, temporal cortices, and frontal cortices. CONCLUSIONS: In this small cohort, prenatal opioid exposure was associated with altered fetal brain development in the third trimester. This adds to the growing body of literature demonstrating that prenatal opioid exposure affects the developing brain.

Diagnostic Accuracy of Transient Elastography in Hepatosteatosis in Youth With Obesity.

Context: Steatotic liver disease is common but overlooked in childhood obesity; diagnostic methods are invasive or expensive. Objective: We sought to determine the diagnostic accuracy of vibration-controlled transient elastography (VCTE) compared with magnetic resonance imaging (MRI) in adolescents with obesity and high risk for hepatosteatosis. Methods: Baseline data in 3 clinical trials enrolling adolescents with obesity were included (NCT03919929, NCT03717935, NCT04342390). Liver fat was assessed using MRI fat fraction and VCTE-based controlled attenuation parameter (CAP). Hepatosteatosis was defined as MRI fat fraction ≥5.0%. The area under the receiver-operating characteristic curves (AUROCs) for CAP against MRI was calculated, and optimal CAP using the Youden index for hepatosteatosis diagnosis was determined. Results: Data from 82 adolescents (age 15.6 ± 1.4 years, body mass index 36.5 ± 5.9 kg/m2, 81% female) were included. Fifty youth had hepatosteatosis by MRI (fat fraction 9.3% ; 95% CI 6.7, 14.0), and 32 participants did not have hepatosteatosis (fat fraction 3.1%; 95% CI 2.2, 3.9; P < .001). The hepatosteatosis group had higher mean CAP compared with no hepatosteatosis (293 dB/m; 95% CI 267, 325 vs 267 dB/m; 95% CI 248, 282; P = .0120). A CAP of 281 dB/m had the highest sensitivity (60%) and specificity (74%) with AUROC of 0.649 (95% CI 0.51-0.79; P = .04) in the entire cohort. In a subset of participants with polycystic ovary syndrome (PCOS), a CAP of 306 dB/m had the highest sensitivity (78%) and specificity (52%) and AUROC of 0.678 (95% CI 0.45-0.90; P = .108). Conclusion: CAP of 281 dB/m has modest diagnostic performance for hepatosteatosis compared with MRI in youth with significant obesity. A higher CAP in youth with PCOS suggests that comorbidities might affect optimal CAP in hepatosteatosis diagnosis.

The radial diffusivity and magnetization transfer pool size ratio are sensitive markers for demyelination in a rat model of type III multiple sclerosis (MS) lesions.

Determining biophysical sensitivity and specificity of quantitative magnetic resonance imaging is essential to develop effective imaging metrics of neurodegeneration. Among these metrics, apparent pool size ratio (PSR) from quantitative magnetization transfer (qMT) imaging and radial diffusivity (RD) from diffusion tensor imaging (DTI) are both known to relate to histological measure of myelin density and integrity. However their relative sensitivities towards quantitative myelin detection are unknown. In this study, we correlated high-resolution quantitative magnetic resonance imaging measures of subvoxel tissue structures with corresponding quantitative myelin histology in a lipopolysaccharide (LPS) mediated animal model of MS. Specifically, we acquired quantitative magnetization transfer (qMT) and diffusion tensor imaging (DTI) metrics (on the same tissue sample) in an animal model system of type III oligodendrogliopathy which lacked prominent lymphocytic infiltration, a system that had not been previously examined with quantitative MRI. We find that the qMT measured apparent pool size ratio (PSR) showed the strongest correlation with a histological measure of myelin content. DTI measured RD showed the next strongest correlation, and other DTI and relaxation parameters (such as the longitudinal relaxation rate (R1f) or fractional anisotropy (FA)) showed considerably weaker correlations with myelin content.

Multi-tiered analysis of brain injury in neonates with congenital heart disease.

Early brain injury occurs in newborns with congenital heart disease (CHD) placing them at risk for impaired neurodevelopmental outcomes. Predictors for preoperative brain injury have not been well described in CHD newborns. This study aimed to analyze, retrospectively, brain magnetic resonance imaging (MRI) in a heterogeneous group of newborns who had CHD surgery during the first month of life using a detailed qualitative CHD MRI Injury Score, quantitative imaging assessments (regional apparent diffusion coefficient [ADC] values and brain volumes), and clinical characteristics. Seventy-three newborns who had CHD surgery at 8 ± 5 (mean ± SD) days of life and preoperative brain MRI were included; 38 also had postoperative MRI. Thirty-four (34 of 73, 47 %) had at least one type of preoperative brain injury, and 28 of 38 (74 %) had postoperative brain injury. The 5-min APGAR score was negatively associated with preoperative injury, but there was no difference between CHD types. Infants with intraparenchymal hemorrhage, deep gray matter injury, and/or watershed infarcts had the highest CHD MRI Injury Scores. ADC values and brain volumes were not different in infants with different CHD types or in those with and without brain injury. In a mixed group of CHD newborns, brain injury was found preoperatively on MRI in almost 50 %, and there were no significant baseline characteristic differences to predict this early brain injury except 5-min APGAR score. We conclude that all infants, regardless of CHD type, who require early surgery should be evaluated with MRI because they are all at high risk for brain injury.

Maternal Diet Quality during Pregnancy Is Associated with Neonatal Brain White Matter Development.

Maternal diet and nutrient intake are important for fetal growth and development. In this study, we aim to evaluate whether there are associations between maternal diet quality and the offspring's brain white matter development. Healthy pregnant women's (N = 44) nutrition intake was assessed by the Healthy Eating Index-2015 (HEI-2015) during the first, second, and third trimesters, respectively. Correlations between MRI diffusion tensor imaging measured fractional anisotropy (FA) of the neonatal brain and the HEI-2015 scores were evaluated using voxel-wise analysis with appropriate multiple comparisons correction and post hoc analysis based on regions of interest. Significant correlations were found between sodium scores at the first trimester of pregnancy and mean neonatal FA values in parietal white matter (R = 0.39, p = 0.01), anterior corona radiata (R = 0.43, p = 0.006), posterior limb of internal capsule (R = 0.53, p < 0.001), external capsule (R = 0.44, p = 0.004), and temporal white matter (R = 0.50, p = 0.001) of the left hemisphere. No other correlations were identified. In conclusion, the relationships between the maternal sodium intake score and the neonatal white matter microstructural development indicate sodium intake patterns better aligned with the Dietary Guidelines for Americans during early pregnancy are associated with greater white matter development in the offspring's brain.

Effects of short-term supervised exercise training on liver fat in adolescents with obesity: a randomized controlled trial.

OBJECTIVE: The objective of this study was to quantify the effects of a 4-week, supervised, high-intensity interval training (HIIT) on intrahepatic triglyceride content (IHTG, percentage), cardiorespiratory fitness (CRF), and cardiometabolic markers in adolescents with obesity. METHODS: A total of 40 adolescents (age 13-18 y, BMI 36.7 ± 5.8 kg/m2 ) at risk for metabolic dysfunction-associated steatotic liver disease (MASLD) based on obesity and elevated Fibroscan measured controlled attenuation parameter (CAP) scores were randomized to HIIT three times a week for 4 weeks (n = 34) or observation (control; n = 6). Liver magnetic resonance imaging proton-density fat-fraction (MRI-PDFF), CAP, oral glucose tolerance test, serum alanine aminotransferase, dual-energy x-ray absorptiometry, and CRF tests were performed before and after intervention. Within- and between-group differences were compared. RESULTS: A total of 13 (38%) and 4 (66%) children had MASLD by MRI-PDFF (IHTG ≥ 5%) in the HIIT and control groups, respectively. The implemented HIIT protocol had no impact on CRF or IHTG (baseline 5.26%, Δ = -0.31 percentage points, 95% CI: -0.77 to 0.15; p = 0.179), but it decreased the 2-h glucose concentration (baseline 116 mg/dL, Δ = -11 mg/dL; 95% CI: -17.6 to -5.5; p < 0.001). When limiting the analysis to participants with MASLD (n = 17), HIIT decreased IHTG (baseline 8.81%, Δ = -1.05 percentage points, 95% CI: -2.08 to -0.01; p = 0.048). Between-group comparisons were not different. CONCLUSIONS: The implemented exercise protocol did not reduce IHTG, but it led to modest improvement in markers of cardiometabolic health.

Neural correlates of sleep quality in children: Sex-specific associations shown by brain diffusion tractography.

BACKGROUND AND PURPOSE: Sleep quality is important for healthy growth and development of children. We aimed to identify associations between sleep disturbances in healthy children without clinical diagnosis of sleep disorders and brain white matter (WM) microstructure using an advanced diffusion-weighted magnetic resonance imaging (DW-MRI) based tractography analysis, and to explore whether there are sex differences in these associations. METHODS: Brain DW-MRI data were collected from sixty-two 8-year-old children (28 boys, 34 girls) whose parents also completed Children's Sleep Habits Questionnaire (CSHQ). Track-weighted imaging (TWI) measures were computed from the DW-MRI data for 37 WM tracts in each subject. Sex-specific partial correlation analyses were performed to evaluate correlations between TWI measures and a set of sleep disturbance scores derived from the CSHQ. RESULTS: Significant correlations (P < .05, FDR-corrected; r: .48-.67) were identified in 13 WM tracts between TWI and sleep disturbance scores. Sexually dimorphic differences in correlations between sleep disturbance scores and WM microstructure measurements were observed. Specifically, in boys, daytime sleepiness positively correlated with track-weighted mean or radial diffusivity in 10 WM tracts (bilateral arcuate fasciculus, left cingulum, right middle longitudinal fasciculus, and three bilateral segments of superior longitudinal fasciculus). In girls, total CSHQ score, night walking, or sleep onset delay negatively correlated with track-weighted fractional anisotropy or axial diffusivity in 4 WM tracts (bilateral inferior longitudinal fasciculus and uncinate fasciculus). CONCLUSIONS: The findings suggest that sleep disturbances without clinical diagnosis of sleep disorders are associated with lower WM microstructural integrity in children. Additionally, the associations possess unique patterns in boys and girls.

Associations Between White Matter Microstructures and Cognitive Functioning in 8-Year-Old Children: A Track-Weighted Imaging Study.

PURPOSE: Quantitative tractography using diffusion-weighted magnetic resonance imaging data is widely used in characterizing white matter microstructure throughout childhood, but more studies are still needed to investigate comprehensive brain-behavior relationships between tract-specific white matter measures and multiple cognitive functions in children. METHODS: In this study, we analyzed diffusion-weighted MRI data of 71 healthy 8-year-old children utilizing white matter tract-specific quantitative measures derived from diffusion-weighted MRI tractography based on a novel track-weighted imaging approach. Track density imaging, average path length map and 4 track-weighted diffusion tensor imaging measures including: mean diffusivity, fractional anisotropy, axial diffusivity, and radial diffusivity were computed for 63 white matter tracts. The track-weighted imaging measures were then correlated with a comprehensive set of neuropsychological test scores in different cognitive domains including intelligence, language, memory, academic skills, and executive functions to identify tract-specific brain-behavior relationships. RESULTS: Significant correlations (P < .05, false discovery rate corrected; r = 0.27-0.57) were found in multiple white matter tracts, with a total of 40 correlations identified between various track-weighted imaging measures including average path length map, track-weighted imaging-fractional anisotropy, and neuropsychological test scores and subscales. Specifically, track-weighted imaging measures indicative of better white matter connectivity and/or microstructural development significantly correlated with higher IQ and better language abilities. CONCLUSION: Our findings demonstrate the ability of track-weighted imaging measures in establishing associations between white matter and cognitive functioning in healthy children and can serve as a reference for normal brain/cognition relationships in young school-age children and further aid in identifying imaging biomarkers predictive of adverse neurodevelopmental outcomes.

Track-weighted imaging analysis of white matter microstructures in healthy children: Sex and hemispheric differences.

Structural substrates of sex differences in human function and behavior have been elucidated in previous studies. Diffusion weighted magnetic resonance imaging (DW-MRI) is a widely used non-invasive imaging technique in studying human brain white matter structural organization. While many DW-MRI studies reporting sex differences in WM structure are based on diffusion tensor imaging (DTI) measures, tract specific microstructural differences require further investigation. In this study, we aim to investigate sex differences and sex-specific hemispheric differences in white matter microstructural development in healthy 8-year-old children based on novel track weighted imaging (TWI) analysis. Average pathlength map (APM) is a TWI contrast in which the average length of fibers passing through a voxel is utilized. In this study, we employed tract specific APM measures to evaluate sex differences in WM microstructural development. A total of 37 WM tracts were analyzed including 7 commissural tracts, 9 bilateral association tracts and 6 bilateral projection tracts. APM maps were generated for each tract. Tract-wise group tests were done using the mean values of APM maps. Sex differences were tested using general linear model based group comparisons. Age and total brain volume were included as covariates in the group analysis. Sex specific hemispheric differences were performed for the 15 bilateral tracts. One sample t-tests were done independently for left>right and right>left cases and the APM measures were controlled for age and total cerebral hemispheric volume. P-values<0.05 were considered significant after correcting for multiple comparisons accounting for the total number of tracts. Significant sex differences were revealed in APM measures between boys and girls in 11 WM tracts including rostral body of corpus callosum (CC), left inferior fronto-occipital fasciculus (IFOF), right cingulum, bilateral first and second segments of superior longitudinal fasciculus (SLF), right middle longitudinal fasciculus (MLF), bilateral fronto-pontine (FPT) and right parieto-occipital pontine tracts (POPT). The sex differences showed higher APM values for these 11 tracts in boys as compared to that of girls. In hemispheric differences analysis for both boys and girls, 2 tracts, arcuate fasciculus and optic radiation showed higher APM in left tracts as compared right; 5 tracts, IFOF, MLF, third segment of SLF, FPT and superior thalamic radiation showed higher APM in right tracts as compared to left. This indicates that boys and girls possess similar lateral asymmetries in these 7 tracts. Additionally, anterior thalamic radiation (ATR) showed higher APM in left tract and 4 tracts, first segment of SLF, POPT, inferior longitudinal fasciculus and cortico-spinal tract showed higher APM in right for boys. In girls, second segment of SLF and uncinate fasciculus showed higher APM in right hemisphere. These results indicate different lateral asymmetries between boys and girls for 7 tracts. Overall, boys showed higher average fiber length in most of the tracts, even after controlling for total brain volume.

Circulating microRNAs Are Associated With Metabolic Markers in Adolescents With Hepatosteatosis.

Background: Altered hepatic microRNA (miRNA) expression may play a role in the development of insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD). Circulating miRNAs could mirror the liver metabolism. Objective: This study aimed to assess the relationship between serum miRNA profile in children with obesity, IR, and NAFLD. Methods: Adolescents with obesity (n = 31) were stratified based on insulin resistance and NAFLD status. One-hundred seventy-nine miRNAs were determined in the serum by quantitative RT-PCR. Differentially expressed miRNAs were compared between groups, and log-transformed levels correlated with metabolic markers and intrahepatic triglyceride. Results: Serum miR-21-5p, -22-3p, -150-5p, and -155-5p levels were higher in children with IR and NAFLD, and their expression levels correlated with hepatic fat and serum triglyceride. In patients with NAFLD, miR-155-5p correlated with ALT (r = 0.68, p<0.01) and AST (r = 0.64, p<0.01) and miR-21-5p and -22-3p levels correlated with plasma adiponectin (r = -0.71 and r = -0.75, respectively, p<0.05) and fibroblast growth factor-21 (r = -0.73 and r = -0.89, respectively, p<0.01). miR-27-3a level was higher in children without IR and NAFLD. Conclusions: Several miRNAs are differentially expressed in children with IR and NAFLD. Determining their mechanistic roles may provide newer diagnostic tools and therapeutic targets for pediatric NAFLD.

C-section increases cecal abundance of the archetypal bile acid and glucocorticoid modifying Lachnoclostridium [clostridium] scindens in mice.

In humans and animal models, Cesarean section (C-section) has been associated with alterations in the taxonomic structure of the gut microbiome. These changes in microbiota populations are hypothesized to impact immune, metabolic, and behavioral/neurologic systems and others. It is not clear if birth mode inherently changes the microbiome, or if C-section effects are context-specific and involve interactions with environmental and other factors. To address this and control for potential confounders, cecal microbiota from ~3 week old mice born by C-section (n = 16) versus natural birth (n = 23) were compared under matched conditions for housing, cross-fostering, diet, sex, and genetic strain. A total of 601 unique species were detected across all samples. Alpha diversity richness (i.e., how many species within sample; Chao1) and evenness/dominance (i.e., Shannon, Simpson, Inverse Simpson) metrics revealed no significant differences by birth mode. Beta diversity (i.e., differences between samples), as estimated with Bray-Curtis dissimilarities and Aitchison distances (using log[x + 1]-transformed counts), was also not significantly different (Permutational Multivariate ANOVA [PERMANOVA]). Only the abundance of Lachnoclostridium [Clostridium] scindens was found to differ using a combination of statistical methods (ALDEx2, DESeq2), being significantly higher in C-section mice. This microbe has been implicated in secondary bile acid production and regulation of glucocorticoid metabolism to androgens. From our results and the extant literature we conclude that C-section does not inherently lead to large-scale shifts in gut microbiota populations, but birth mode could modulate select bacteria in a context-specific manner: For example, involving factors associated with pre-, peri-, and postpartum environments, diet or host genetics.

Mother's physical activity during pregnancy and newborn's brain cortical development.

Background: Physical activity is known to improve mental health, and is regarded as safe and desirable for uncomplicated pregnancy. In this novel study, we aim to evaluate whether there are associations between maternal physical activity during pregnancy and neonatal brain cortical development. Methods: Forty-four mother/newborn dyads were included in this longitudinal study. Healthy pregnant women were recruited and their physical activity throughout pregnancy were documented using accelerometers worn for 3-7 days for each of the 6 time points at 4-10, ∼12, ∼18, ∼24, ∼30, and ∼36 weeks of pregnancy. Average daily total steps and daily total activity count as well as daily minutes spent in sedentary/light/moderate/vigorous activity modes were extracted from the accelerometers for each time point. At ∼2 weeks of postnatal age, their newborns underwent an MRI examination of the brain without sedation, and 3D T1-weighted brain structural images were post-processed by the iBEAT2.0 software utilizing advanced deep learning approaches. Cortical surface maps were reconstructed from the segmented brain images and parcellated to 34 regions in each brain hemisphere, and mean cortical thickness for each region was computed for partial correlation analyses with physical activity measures, with appropriate multiple comparison corrections and potential confounders controlled. Results: At 4-10 weeks of pregnancy, mother's daily total activity count positively correlated (FDR corrected P ≤ 0.05) with newborn's cortical thickness in the left caudal middle frontal gyrus (rho = 0.48, P = 0.04), right medial orbital frontal gyrus (rho = 0.48, P = 0.04), and right transverse temporal gyrus (rho = 0.48, P = 0.04); mother's daily time in moderate activity mode positively correlated with newborn's cortical thickness in the right transverse temporal gyrus (rho = 0.53, P = 0.03). At ∼24 weeks of pregnancy, mother's daily total activity count positively correlated (FDR corrected P ≤ 0.05) with newborn's cortical thickness in the left (rho = 0.56, P = 0.02) and right isthmus cingulate gyrus (rho = 0.50, P = 0.05). Conclusion: We identified significant relationships between physical activity in healthy pregnant women during the 1st and 2nd trimester and brain cortical development in newborns. Higher maternal physical activity level is associated with greater neonatal brain cortical thickness, presumably indicating better cortical development.

Diffusion tensor imaging evaluation of white matter in adolescents with myelomeningocele and Chiari II malformation.

BACKGROUND: Macrostructural abnormalities in cerebral white matter in patients with myelomeningocele are well known, but microstructural abnormalities are not as well studied. OBJECTIVE: The aim of this study was to evaluate cerebral white matter in adolescents with myelomeningocele using diffusion tensor imaging (DTI), and to investigate the effects of ventricular dilation and CSF shunt presence on white matter microstructure in these patients. MATERIALS AND METHODS: DTI and T1-weighted 3-D (T1-3-D) MRI were performed on nine adolescents with myelomeningocele and Chiari II malformation and nine age-matched controls. The fractional anisotropy (FA) and mean diffusivity (MD) values were measured and compared. RESULTS: Significantly decreased FA and increased MD values were observed in most white matter regions and fibers in adolescents with myelomeningocele compared to controls. Further analysis in patients revealed significant changes in DTI parameters in hemispheres with enlarged lateral ventricles compared to those with normal ventricle size. In addition, a significant difference in FA values in the posterior limb of the internal capsule was found in the comparison of hemispheres in patients with or without CSF shunt catheters. CONCLUSION: This study revealed widespread microstructural abnormalities in white matter in adolescents with myelomeningocele and Chiari II malformation. Ventricular dilation may have additional effects on white matter microstructure in this patient population. CSF shunt diversion effects on white matter may be multifactorial and need further investigation.