Structural connectivity at term equivalent age and language in preterm children at 2 years corrected.

We previously reported interhemispheric structural hyperconnectivity bypassing the corpus callosum in children born extremely preterm (<28 weeks) versus term children. This increased connectivity was positively associated with language performance at 4-6 years of age in our prior work. In the present study, we aim to investigate whether this extracallosal connectivity develops in extremely preterm infants at term equivalent age by leveraging a prospective cohort study of 350 very and extremely preterm infants followed longitudinally in the Cincinnati Infant Neurodevelopment Early Prediction Study. For this secondary analysis, we included only children born extremely preterm and without significant brain injury (n = 95). We use higher-order diffusion modelling to assess the degree to which extracallosal pathways are present in extremely preterm infants and predictive of later language scores at 22-26 months corrected age. We compare results obtained from two higher-order diffusion models: generalized q-sampling imaging and constrained spherical deconvolution. Advanced MRI was obtained at term equivalent age (39-44 weeks post-menstrual age). For structural connectometry analysis, we assessed the level of correlation between white matter connectivity at the whole-brain level at term equivalent age and language scores at 2 years corrected age, controlling for post-menstrual age, sex, brain abnormality score and social risk. For our constrained spherical deconvolution analyses, we performed connectivity-based fixel enhancement, using probabilistic tractography to inform statistical testing of the hypothesis that fibre metrics at term equivalent age relate to language scores at 2 years corrected age after adjusting for covariates. Ninety-five infants were extremely preterm with no significant brain injury. Of these, 53 had complete neurodevelopmental and imaging data sets that passed quality control. In the connectometry analyses adjusted for covariates and multiple comparisons (P < 0.05), the following tracks were inversely correlated with language: bilateral cerebellar white matter and middle cerebellar peduncles, bilateral corticospinal tracks, posterior commissure and the posterior inferior fronto-occipital fasciculus. No tracks from the constrained spherical deconvolution/connectivity-based fixel enhancement analyses remained significant after correction for multiple comparisons. Our findings provide critical information about the ontogeny of structural brain networks supporting language in extremely preterm children. Greater connectivity in more posterior tracks that include the cerebellum and connections to the regions of the temporal lobes at term equivalent age appears to be disadvantageous for language development.

Fetal magnetic resonance imaging, ultrasound, and echocardiography findings in twin reversed arterial perfusion sequence.

BACKGROUND: Twin reversed arterial perfusion (TRAP) sequence is a rare complication of monochorionic multiple gestation pregnancies, in which the pump twin provides hemodynamic support to a nonviable co-twin (acardius). Fetal magnetic resonance imaging (MRI) is used to detect pump twin abnormalities, particularly brain ischemia, prior to fetal intervention to interrupt umbilical blood flow to the acardius. OBJECTIVE: To summarize the imaging findings of TRAP sequence pregnancies in a large series. MATERIALS AND METHODS: A single-center retrospective review was performed of all TRAP sequence pregnancies referred for fetal MRI (2004-2021). Fetal MRI, ultrasound, and echocardiography data were collected. RESULTS: Eighty-eight TRAP sequence pregnancies with MRI were included (mean gestational age, 19.8±2.8 weeks). Demise of the pump twin was noted in two pregnancies at the time of MRI. By MRI, 12% (10/86) of live pump twins had abnormalities, including 3% (3/86) with brain abnormalities and 9% (8/86) with extra-cranial abnormalities. By echocardiography, 7% (6/86) of pump twins had structural cardiac abnormalities. Three acardius morphological subtypes were identified by MRI: acephalus (55%, 48/88), anceps (39%, 34/88), and amorphous (7%, 6/88). The mean ultrasound acardius to pump twin ratio A/P ratio, calculated for each twin pair as the ratio of the acardius trunk (and head, if present) plus limb volume to the pump twin estimated fetal weight) differed among the three acardius subtypes (P=.03). The mean A/P ratio moderately correlated with pump twin cardiothoracic ratio and combined cardiac output (Pearson's r=0.45 and 0.48, respectively, both P<.001). CONCLUSION: Fetal MRI of TRAP sequence pregnancies found anomalies in a substantial number of pump twins. The three acardius subtypes differed in A/P ratio, which moderately correlated with the pump twin cardiothoracic ratio and combined cardiac output.

Prenatal Opioid Exposure and Risk for Adverse Brain and Motor Outcomes in Infants Born Premature.

OBJECTIVE: To compare brain magnetic resonance imaging (MRI) biomarkers and neurodevelopmental test scores in infants born preterm with and without prenatal opioid exposure (POE). STUDY DESIGN: We examined 395 preterm infants (≤32 weeks gestational age) who had term-equivalent brain MRIs, composite scores from the Bayley Scales of Infant and Toddler Development-III at 2 years corrected age, and POE data. MRI parameters included total/regional brain volumes and severe punctate white matter lesions (PWMLs). We conducted bivariable analysis and multivariable logistic regression analyses. RESULTS: The mean ± SD gestational age was 29.3 ± 2.5 weeks; 35 (8.9%) had POE and 20 (5.1%) had severe PWML. Compared with unexposed infants, those with POE exhibited higher rates of severe PWML (17.1% vs 3.9%, respectively; P = .002); findings remained significant with an OR of 4.16 (95% CI, 1.26-13.68) after adjusting for confounders. On mediation analysis, the significant relationship between POE and severe PWML was not indirectly mediated through preterm birth/gestational age (OR, 0.93; 95% CI, 0.78-1.10), thus suggesting the association was largely driven by a direct adverse effect of POE on white matter. In multivariable analyses, POE was associated with a significantly lower score by -6.2 (95% CI, -11.8 to -0.6) points on the Bayley Scales of Infant and Toddler Development-III Motor subscale compared with unexposed infants. CONCLUSIONS: POE was associated with severe PWML; this outcome may be a direct effect of POE rather than being mediated by premature birth. POE was also associated with worse motor development. Continued follow-up to understand the long-term effects of POE is warranted.

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.

Using MRI-derived observed-to-expected total fetal lung volume to predict lethality in fetal skeletal dysplasia.

BACKGROUND: Pulmonary hypoplasia is the primary cause of perinatal death in lethal skeletal dysplasias. The antenatal ultrasound correlates for lethality are indirect, measuring the thorax (thoracic circumference, TC) or femur compared to the abdomen (TC/AC, FL/AC). A single study has correlated lethality with the observed-to-expected total lung volume (O/E-TFLV) on fetal MRI in 23 patients. OBJECTIVE: Our aim was to define a cutoff value to predict lethality more specifically using MRI-derived O/E-TFLV. MATERIALS AND METHODS: Two large fetal center databases were searched for fetuses with skeletal dysplasia and MRI; O/E-TFLV was calculated. Ultrasound measures were included when available. Each was evaluated as a continuous variable against lethality (stillbirth or death in the first month of life). Logistic regression and receiver operating characteristic (ROC) curve analyses evaluated the prediction ability. AUC, sensitivity, and specificity were calculated. P < 0.05 was considered statistically significant. RESULTS: A total of 80 fetuses met inclusion criteria. O/E-TFLV < 0.49 was a significant risk factor in predicting lethality, with sensitivity and specificity of 0.63 and 0.93, respectively, and an AUC of 0.81 (P < 0.001). FL/AC < 0.129 was also a strong variable with sensitivity, specificity, and AUC of 0.73, 0.88, and 0.78, respectively (P < 0.001). TC/AC and TC percentile were not significant risk factors for lethality. An O/E-TFLV of < 0.38 defines a specificity for lethality at 1.00. CONCLUSION: MRI-derived O/E-TFLV and US-derived FL/AC are significant predictors of lethality in fetuses with skeletal dysplasia. When prognosis is uncertain after ultrasound, calculation of MRI-derived O/E-TFLV may provide additional useful information for prognosis and delivery planning.

Corpus callosum abnormalities at term-equivalent age are associated with language development at two years corrected age in infants born very preterm.

We studied the impact of microstructural abnormalities in the corpus callosum on language development in 348 infants born very prematurely. We discovered that the fractional anisotropy of the corpus callosum anterior midbody was a significant predictor of standardized language scores at two years, independent of clinical and social risk factors.

Diffusion Tensor Imaging to Predict Neurodevelopmental Impairment in Infants after Hypoxic-Ischemic Injury.

OBJECTIVE: Magnetic resonance imaging (MRI) is the standard of care for evaluation of brain injury after hypoxic-ischemic encephalopathy (HIE) in term newborns. This study utilizes diffusion tensor imaging (DTI) to (1) identify infants at highest risk of development of cerebral palsy (CP) following HIE and to (2) identify regions of the brain critical to normal fidgety general movements (GMs) at 3 to 4 months of postterm. Absence of these normal, physiological movements is highly predictive of CP. STUDY DESIGN: Term infants treated with hypothermia for HIE from January 2017 to December 2021 were consented for participation and had brain MRI with DTI after rewarming. The Prechtl's General Movements Assessment was performed at 12 to 16 weeks of age. Structural MRIs were reviewed for abnormalities, and DTI data were processed with the FMRIB Software Library. Infants underwent the Bayley Scales of Infant and Toddler Development III test at 24 months. RESULTS: Forty-five infant families were consented; three infants died prior to MRI and were excluded, and a fourth infant was excluded due to diagnosis of a neuromuscular disorder. Twenty-one infants were excluded due to major movement artifact on diffusion images. Ultimately, 17 infants with normal fidgety GMs were compared with 3 infants with absent fidgety GMs with similar maternal and infant characteristics. Infants with absent fidgety GMs had decreased fractional anisotropy of several important white matter tracts, including the posterior limb of the internal capsule, optic radiations, and corpus callosum (p < 0.05). All three infants with absent fidgety GMs and two with normal GMs went on to be diagnosed with CP. CONCLUSION: This study identifies white matter tracts of the brain critical to development of normal fidgety GMs in infants at 3 to 4 months of postterm using advanced MRI techniques. These findings identify those at highest risk for CP among infants with moderate/severe HIE prior to hospital discharge. KEY POINTS: · HIE has devastating impacts on families and infants.. · Diffusion MRI identifies infants at highest risk for developing neurodevelopmental impairment.. · Normal general movements of infancy are generated by key white matter tracts..

Early surgery in very preterm infants is associated with brain abnormalities on term MRI: a propensity score analysis.

OBJECTIVE: To investigate the association between exposure to surgery under general anesthesia and brain abnormalities and neurodevelopmental outcomes in very preterm infants. STUDY DESIGN: This prospective observational study includes 392 infants born at or below 32 weeks' gestational age. Participants completed brain MRI at term-equivalent age and Bayley-III assessment at 2 years corrected age. We evaluated the independent effects of surgery on brain MRI abnormalities and neurodevelopmental outcomes after propensity score matching. RESULTS: All infants completed brain MRI, and 341 (87%) completed neurodevelopmental testing. Forty-five received surgery. Surgery was associated with worse MRI abnormalities (p < 0.0001) but with none of the developmental outcomes after propensity score matching. The global brain abnormality score was associated with the Bayley Cognitive (p = 0.005) and Motor (p = 0.028) composite scores. CONCLUSIONS: Very preterm infants exposed to surgery under general anesthesia were at higher risk of brain abnormalities on MRI at term.

Prenatal tobacco smoke exposure and risk of brain abnormalities on magnetic resonance imaging at term in infants born very preterm.

BACKGROUND: Prenatal tobacco smoke exposure and preterm birth are associated with abnormal brain and neurodevelopmental outcomes in infants. Studies that can disentangle indirect mediating effects from direct effects of prenatal tobacco smoke exposure on sensitive early brain magnetic resonance imaging biomarkers in very preterm infants are needed. OBJECTIVE: This study aimed to determine whether prenatal tobacco smoke exposure in preterm infants posed any direct effects on magnetic resonance imaging-determined global brain abnormality score and secondary measures of brain abnormalities after removing any indirect mediating effects of preterm birth on neurostructural outcomes. STUDY DESIGN: We examined brain magnetic resonance imaging findings collected at 39 to 44 weeks postmenstrual age from a prospective cohort of 395 infants born very preterm (gestational age of ≤32 weeks). The primary outcome was global brain abnormality score, and the secondary outcomes were global efficiency of structural connectome, diffuse white matter abnormality volume, total brain tissue volume, total gray and white matter volumes, and cerebellar volume. Maternal reports of smoking during pregnancy were obtained. We performed multivariable linear regression analyses to examine the association between prenatal tobacco smoke exposure and our magnetic resonance imaging outcomes, controlling for prospectively collected confounders. Moreover, we performed a mediation analysis to estimate the direct effects of prenatal tobacco smoke exposure on brain abnormalities and any indirect effects through preterm birth. RESULTS: Overall, 12.6% of infants had prenatal tobacco smoke exposure. Infants with prenatal tobacco smoke exposure had a higher median global brain abnormality score than nonexposed infants (7 [interquartile range, 0-41] vs 5 [interquartile range, 0-34]; P≤.001); the findings remained significant (P<.001) after controlling for antenatal confounders. Global efficiency (P<.001), diffuse white matter volume (P=.037), and total brain tissue volume (P=.047) were significantly different between TSE groups in multivariable analyses. On mediation analysis, preterm birth mediated between 0% and 29% of the indirect effect of prenatal tobacco smoke exposure on several measures of brain abnormality outcomes. Thus, prenatal tobacco smoke exposure had a direct adverse effect between 71% and 100% on brain injury or abnormal development. CONCLUSION: Our study has identified multiple adverse effects of prenatal tobacco smoke exposure on sensitive and objective measures of neonatal brain injury and abnormal development; most cases seemed to be a direct effect of prenatal tobacco smoke exposure on fetal brain development. The results underscored the significant adverse neurostructural effects of prenatal tobacco smoke exposure to tobacco smoke pollutants.

Further expansion and confirmation of phenotype in rare loss of YWHAE gene distinct from Miller-Dieker syndrome.

Deletion of 17p13.3 has varying degrees of severity on brain development based on precise location and size of the deletion. The most severe phenotype is Miller-Dieker syndrome (MDS) which is characterized by lissencephaly, dysmorphic facial features, growth failure, developmental disability, and often early death. Haploinsufficiency of PAFAH1B1 is responsible for the characteristic lissencephaly in MDS. The precise role of YWHAE haploinsufficiency in MDS is unclear. Case reports are beginning to elucidate the phenotypes of individuals with 17p13.3 deletions that have deletion of YWHAE but do not include deletion of PAFAH1B1. Through our clinical genetics practice, we identified four individuals with 17p13.3 deletion that include YWHAE but not PAFAH1B1. These patients have a similar phenotype of dysmorphic facial features, developmental delay, and leukoencephalopathy. In a review of the literature, we identified 19 patients with 17p13.3 microdeletion sparing PAFAH1B1 but deleting YWHAE. Haploinsufficiency of YWHAE is associated with brain abnormalities including cystic changes. These individuals have high frequency of epilepsy, intellectual disability, and dysmorphic facial features including prominent forehead, epicanthal folds, and broad nasal root. We conclude that deletion of 17p13.3 excluding PAFAH1B1 but including YWHAE is associated with a consistent phenotype and should be considered a distinct condition from MDS.

Imaging Similarities Between Oral-Facial-Digital Syndrome Type 1 and Aicardi Syndrome: Prenatal and Postnatal Magnetic Resonance Imaging (MRI) Findings in 4 Patients.

Prenatal identification by magnetic resonance imaging (MRI) of callosal anomalies, particularly with accompanying intracranial abnormalities, poses a challenge for accurate prognostication and fetal counseling as outcome can vary widely depending on underlying etiology. In female patients, Aicardi syndrome is an important consideration, and prompt postnatal ophthalmologic assessment to identify ocular stigmata of Aicardi syndrome can aid with anticipatory guidance and greater vigilance for seizures. We present a case of a female with fetal and postnatal MRI findings of agenesis of corpus callosum and type 2b interhemispheric cysts, characteristically found in Aicardi syndrome, but was found to have oral-facial-digital syndrome type 1 (OFD1). We also present 3 other companion cases with pre- and postnatal imaging of patients with Aicardi syndrome. These cases highlight the importance of widening the differential diagnosis to also include OFD1 for female patients with callosal anomalies.

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.

Diffuse excessive high signal intensity in the preterm brain on advanced MRI represents widespread neuropathology.

Preterm brains commonly exhibit elevated signal intensity in the white matter on T2-weighted MRI at term-equivalent age. This signal, known as diffuse excessive high signal intensity (DEHSI) or diffuse white matter abnormality (DWMA) when quantitatively assessed, is associated with abnormal microstructure on diffusion tensor imaging. However, postmortem data are largely lacking and difficult to obtain, and the pathological significance of DEHSI remains in question. In a cohort of 202 infants born preterm at ≤32 weeks gestational age, we leveraged two newer diffusion MRI models - Constrained Spherical Deconvolution (CSD) and neurite orientation dispersion and density index (NODDI) - to better characterize the macro and microstructural properties of DWMA and inform the ongoing debate around the clinical significance of DWMA. With increasing DWMA volume, fiber density broadly decreased throughout the white matter and fiber cross-section decreased in the major sensorimotor tracts. Neurite orientation dispersion decreased in the centrum semiovale, corona radiata, and temporal lobe. These findings provide insight into DWMA's biological underpinnings and demonstrate that it is a serious pathology.

The interplay between prenatal liver growth and lung development in congenital diaphragmatic hernia.

Objective: Liver herniation is a known risk factor for increased severity in CDH and is associated with clinically significant pulmonary hypoplasia and pulmonary hypertension. Better studies are needed to understand the growth of the herniated liver compared to the liver that remains in the abdomen and how this liver growth then affects lung development. Serial hi-resolution fetal MRI enables characterization of liver growth throughout gestation and examination of macroscopic features that may regulate liver growth. Here, we hypothesized that the nature of liver herniation affects liver growth and, in turn, affects lung growth. Methods: Clinical data were retrospectively collected from consecutive cases of prenatally diagnosed isolated left-sided or right-sided CDH from June 2006 to August 2021. Only those cases with MRI lung volumetry for both mid-gestation and late-gestation time points were recruited for analysis. Cases with fetal chromosomal abnormalities and other major structural abnormalities were excluded. Fractional liver volume and liver growth was indexed to estimated fetal weight and compared to lung growth. Results: Data was collected from 28 fetuses with a left liver-down CDH (LLD), 37 left liver-up CDH (LLU) and 9 right liver-up CDH (RLU). Overall, RLU fetuses had greater overall and fractional (intra-thoracic vs. intra-abdominal) liver growth when compared to LLD and LLU fetuses. Additionally, intra-thoracic liver growth was consistently slower than intra-abdominal liver growth for either right- or left-sided CDH. When the liver was not herniated, a positive correlation was seen between liver growth and lung growth. However, when the liver was herniated above the diaphragm, this positive correlation was lost. Conclusion: Right-sided CDH fetuses exhibit greater liver growth compared to left-sided CDH. Liver herniation disrupts the normal positive correlation between liver and lung growth that is seen when the liver is entirely within the abdomen.

Women in pediatric radiology: a call for gender equity.

Pediatric radiology is the only specialty in radiology that is near evenly distributed among genders. Yet the top leadership positions in the field are still mostly occupied by men. In this article we review some of the history of women in pediatric radiology and discuss how to improve women's participation in the highest positions of our subspecialty.

Acute histologic chorioamnionitis independently and directly increases the risk for brain abnormalities seen on magnetic resonance imaging in very preterm infants.

BACKGROUND: The independent risk for neurodevelopmental impairments attributed to chorioamnionitis in premature infants remains controversial. Delayed brain maturation or injury identified on magnetic resonance imaging at term-equivalent age can be used as a surrogate measure of neurodevelopmental impairments that is less confounded by postdelivery neonatal intensive care unit environmental factors to investigate this relationship more clearly. OBJECTIVE: This study aimed to determine whether preterm infants born with moderate to severe acute histologic chorioamnionitis would have a higher magnetic resonance imaging-determined global brain abnormality score, independent of early premature birth, when compared with preterm infants with no or mild chorioamnionitis. STUDY DESIGN: This was a prospective, multicenter cohort study involving infants born very prematurely ≤32 weeks' gestational age with acute moderate to severe histologic chorioamnionitis, graded using standard histologic criteria. Brain abnormalities were diagnosed and scored using a well-characterized, standardized scoring system captured using a high-resolution 3 Tesla magnetic resonance imaging research magnet. In secondary analyses, total brain volume and 4 magnetic resonance imaging metrics of cortical maturation (cortical surface area, sulcal depth, gyral index, and inner cortical curvature) were calculated using an automated algorithm and correlated with chorioamnionitis. The association of funisitis (any grade) with brain abnormalities was also explored. We investigated if premature birth mediated the relationship between histologic chorioamnionitis and brain abnormality score using mediation analysis. RESULTS: Of 353 very preterm infants, 297 infants had mild or no chorioamnionitis (controls), and 56 were diagnosed with moderate to severe acute histologic chorioamnionitis. The primary outcome brain abnormality score was significantly higher in histologic chorioamnionitis-exposed infants than in the controls (median, 4 vs 7; P<.001). Infants with acute histologic chorioamnionitis had significantly lower brain tissue volume (P=.03) and sulcal depth (P=.04), whereas other morphometric indices did not differ statistically. In the multiple regression analysis, we observed persistent significant relationships between moderate to severe acute histologic chorioamnionitis and brain abnormality scores (ß=2.84; 1.51-4.16; P<.001), total brain volume (P=.03), and sulcal depth (P=.02). Funisitis was also significantly associated with brain abnormality score after adjustment for clinical confounders (P=.005). Mediation analyses demonstrated that 50% of brain abnormalities was an indirect consequence of premature birth, and the remaining 50% was a direct effect of moderate to severe acute histologic chorioamnionitis when compared with preterm infants with no or mild chorioamnionitis exposure. Examining gestational age as a mediator, funisitis did not exert a significant direct effect on brain abnormalities after the significant indirect effects of preterm birth were accounted for. CONCLUSION: Acute histologic chorioamnionitis increases the risk for brain injury and delayed maturation, both directly and indirectly, by inducing premature birth.

Clinical Applications of Fetal MRI in the Brain.

Fetal magnetic resonance imaging (MRI) has become a widely used tool in clinical practice, providing increased accuracy in prenatal diagnoses of congenital abnormalities of the brain, allowing for more accurate prenatal counseling, optimization of perinatal management, and in some cases fetal intervention. In this article, a brief description of how fetal ultrasound (US) and fetal MRI are used in clinical practice will be followed by an overview of the most common reasons for referral for fetal MRI of the brain, including ventriculomegaly, absence of the cavum septi pellucidi (CSP) and posterior fossa anomalies.

Attention-guided deep learning for gestational age prediction using fetal brain MRI.

Magnetic resonance imaging offers unrivaled visualization of the fetal brain, forming the basis for establishing age-specific morphologic milestones. However, gauging age-appropriate neural development remains a difficult task due to the constantly changing appearance of the fetal brain, variable image quality, and frequent motion artifacts. Here we present an end-to-end, attention-guided deep learning model that predicts gestational age with R2 score of 0.945, mean absolute error of 6.7 days, and concordance correlation coefficient of 0.970. The convolutional neural network was trained on a heterogeneous dataset of 741 developmentally normal fetal brain images ranging from 19 to 39 weeks in gestational age. We also demonstrate model performance and generalizability using independent datasets from four academic institutions across the U.S. and Turkey with R2 scores of 0.81-0.90 after minimal fine-tuning. The proposed regression algorithm provides an automated machine-enabled tool with the potential to better characterize in utero neurodevelopment and guide real-time gestational age estimation after the first trimester.

Value of pre- and postnatal magnetic resonance imaging in the evaluation of congenital central nervous system anomalies.

Fetal MRI and neonatal MRI of the central nervous system (CNS) are complementary tools that can help to accurately counsel and direct the management of children with anomalies of the central nervous system. Postnatal MRI can add to fetal MRI by allowing for monitoring of changes in the severity of disease, better delineation of a suspected prenatal anomaly, evaluation for secondary pathologies related to the primary diagnosis, and surgical management direction. In this review we discuss the roles of fetal and neonatal MRI in the diagnosis and treatment of congenital anomalies of the CNS through a series of case examples and how both are important in patient management.

Short- and Long-Term Outcomes of Prenatally Diagnosed Dandy-Walker Malformation, Vermian Hypoplasia, and Blake Pouch Cyst.

Dandy-Walker continuum, which includes Dandy-Walker malformation, vermian hypoplasia, and Blake pouch cyst, is among the most commonly diagnosed posterior fossa malformation by fetal magnetic resonance imaging (MRI). The objective of our retrospective study was to evaluate fetal and postnatal MRI scan and clinical outcomes. Seventy-two patients were identified; 40 patients had postnatal imaging and follow-up (7 Dandy-Walker malformation, 26 vermian hypoplasia, and 7 Blake pouch cyst). Although all patients with Dandy-Walker malformation required ventriculoperitoneal shunts and 66% were intubated at birth, none required tracheostomy tube and 2 of 5 surviving children had no neurologic deficits. Vermian hypoplasia was strongly associated with genetic conditions and cardiac malformations; odds of not ambulating normally were 12 times greater if a syndrome or injury was present. Echocardiogram and genetic screening are recommended with vermian hypoplasia. There is a risk for epilepsy in both Dandy-Walker malformation and vermian hypoplasia. Blake pouch cyst can be complicated by hydrocephalus, but outcome is favorable.