Fetal and Postnatal Brain Imaging for the Detection of ZIKV Encephalopathy in the Fetus/Newborn

Abstract Background Up to 15% of pregnancies complicated by maternal ZIKV infection result in Zika-virus associated brain abnormalities in the fetus/newborn. Fetal ultrasound (feUS) is the standard imaging modality for the evaluation of fetal anatomy and for brain changes from congenital infection. Fetal MRI (feMRI) may be a useful adjunct. Methods We performed a prospective longitudinal neuroimaging study of fetuses/newborns of pregnant women with clinical and/or lab confirmed (RT-PCR and/or IgM/PRNT) diagnosis of Zika infection in Barranquilla, Colombia (endemic) and in Washington, DC, USA (travel-related). Gestational age (GA) at exposure and timing between ZIKV exposure/symptoms and imaging was documented. Subjects had one to two feMRIs and feUS, depending upon GA at enrollment. The feMRI and feUS protocols were standardized between sites and studies were centrally interpreted at Children’s National. Postnatally, infants received an unsedated brain MRI and head US. Results Forty-eight, ZIKV exposed/infected in first or second trimester pregnant women were enrolled (46 Colombia, 2 USA). Subjects had symptoms of ZIKV infection at mean of 8.4±5.7 week GA. The first feMRI and feUS were performed at 25.1±6.3 week GA. Thirty-six infants had a second feMRI and feUS at 31.1±4.2 week GA. Three of 48 (6%) cases had an abnormal feMRI: (1) heterotopias and abnormal cortical indent; (2) parietal encephalocele and Chiari II; (3) thin corpus callosum, dysplastic brainstem, temporal cysts, subependymal heterotopias, and generalized cerebral/cerebellar atrophy. FeUS in these three cases found (1) normal study; (2) parietal encephalocele and Chiari II; (3) significant ventriculomegaly with decreasing percentiles of head circumference from 32 to 36 week GA (38% to 3.6%). Postnatal head US revealed findings not seen on feUS: choroid plexus or germinal matrix cysts in nine infants and lenticulostriate vasculopathy in one infant. Conclusion FeMRI and feUS provide complimentary information in the assessment of fetal brain changes in ZIKV. In cases of abnormal brain structure, feMRI reveals more extensive areas of brain damage than is seen by US. Further studies are needed to determine whether cystic changes on postnatal head US are related to ZIKV infection, or are incidental findings. Disclosures All authors: No reported disclosures.

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In utero MRI identifies consequences of early-gestation alcohol drinking on fetal brain development in rhesus macaques

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1919048117 ◽

2020 ◽

Vol 117 (18) ◽

pp. 10035-10044

Author(s):

Xiaojie Wang ◽

Verginia C. Cuzon Carlson ◽

Colin Studholme ◽

Natali Newman ◽

Matthew M. Ford ◽

...

Keyword(s):

White Matter ◽

Brain Development ◽

Ex Vivo ◽

Early Recognition ◽

Brain Mri ◽

Fetal Brain ◽

Fetal Mri ◽

Diffusion Anisotropy ◽

Self Administration ◽

White Matter Tracts

One factor that contributes to the high prevalence of fetal alcohol spectrum disorder (FASD) is binge-like consumption of alcohol before pregnancy awareness. It is known that treatments are more effective with early recognition of FASD. Recent advances in retrospective motion correction for the reconstruction of three-dimensional (3D) fetal brain MRI have led to significant improvements in the quality and resolution of anatomical and diffusion MRI of the fetal brain. Here, a rhesus macaque model of FASD, involving oral self-administration of 1.5 g/kg ethanol per day beginning prior to pregnancy and extending through the first 60 d of a 168-d gestational term, was utilized to determine whether fetal MRI could detect alcohol-induced abnormalities in brain development. This approach revealed differences between ethanol-exposed and control fetuses at gestation day 135 (G135), but not G110 or G85. At G135, ethanol-exposed fetuses had reduced brainstem and cerebellum volume and water diffusion anisotropy in several white matter tracts, compared to controls. Ex vivo electrophysiological recordings performed on fetal brain tissue obtained immediately following MRI demonstrated that the structural abnormalities observed at G135 are of functional significance. Specifically, spontaneous excitatory postsynaptic current amplitudes measured from individual neurons in the primary somatosensory cortex and putamen strongly correlated with diffusion anisotropy in the white matter tracts that connect these structures. These findings demonstrate that exposure to ethanol early in gestation perturbs development of brain regions associated with motor control in a manner that is detectable with fetal MRI.

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Automatic linear measurements of the fetal brain on MRI with deep neural networks

10.21203/rs.3.rs-161025/v1 ◽

2021 ◽

Author(s):

Netanell Avisdris ◽

Bossmat Yehuda ◽

Ori Ben-Zvi ◽

Daphna Link-Sourani ◽

Liat Ben-Sira ◽

...

Keyword(s):

Human Error ◽

Brain Mri ◽

Fetal Brain ◽

Region Of Interest ◽

Fetal Mri ◽

Brain Structures ◽

Automatic Method ◽

Linear Measurements ◽

Biparietal Diameter ◽

Reliable Assessment

Abstract Purpose: Timely, accurate and reliable assessment of fetal brain development is essential to reduce short and long-term risks to fetus and mother. Fetal MRI is increasingly used for fetal brain assessment. Three key biometric linear measurements important for fetal brain evaluation are Cerebral Biparietal Diameter (CBD), Bone Biparietal Diameter (BBD), and Trans-Cerebellum Diameter (TCD), obtained manually by expert radiologists on reference slices, which is time consuming and prone to human error. The aim of this study was to develop a fully automatic method computing the CBD, BBD and TCD measurements from fetal brain MRI.Methods: The input is fetal brain MRI volumes which may include the fetal body and the mother's abdomen. The outputs are the measurement values and reference slices on which the measurements were computed. The method, which follows the manual measurements principle, consists of five stages: 1) computation of a Region Of Interest that includes the fetal brain with an anisotropic 3D U-Net classifier; 2) reference slice selection with a Convolutional Neural Network; 3) slice-wise fetal brain structures segmentation with a multiclass U-Net classifier; 4) computation of the fetal brain midsagittal line and fetal brain orientation, and; 5) computation of the measurements. Results: Experimental results on 214 volumes for CBD, BBD and TCD measurements yielded a mean difference of 1.55mm, 1.45mm and 1.23mm respectively, and a Bland-Altman 95% confidence interval (I of 3.92mm, 3.98mm and 2.25mm respectively. These results are similar to the manual inter-observer variability, and are consistent across gestational ages and brain conditions.Conclusions: The proposed automatic method for computing biometric linear measurements of the fetal brain from MR imaging achieves human level performance. It has the potential of being a useful method for the assessment of fetal brain biometry in normal and pathological cases, and of improving routine clinical practice.

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4252 Automated Fetal Brain Volumetry on Clinical Fetal MRI Using Convolutional Neural Network

Journal of Clinical and Translational Science ◽

10.1017/cts.2020.169 ◽

2020 ◽

Vol 4 (s1) ◽

pp. 45-46

Author(s):

Carol Tran ◽

Orit Glenn ◽

Christopher Hess ◽

Andreas Rauschecker

Keyword(s):

Neural Network ◽

Deep Learning ◽

Convolutional Neural Network ◽

Network Architecture ◽

Brain Volume ◽

Brain Mri ◽

Fetal Brain ◽

Fetal Mri ◽

Total Brain Volume ◽

Brain Volumes

OBJECTIVES/GOALS: We seek to develop an automated deep learning-based method for segmentation and volumetric quantification of the fetal brain on T2-weighted fetal MRIs. We will evaluate the performance of the algorithm by comparing it to gold standard manual segmentations. The method will be used to create a normative sample of brain volumes across gestational ages. METHODS/STUDY POPULATION: We will adapt a U-Net convolutional neural network architecture for fetal brain MRIs using 3D volumes. After re-sampling 2D fetal brain acquisitions to 3mm3 3D volumes using linear interpolation, the network will be trained to perform automated brain segmentation on 40 randomly-sampled, normal fetal brain MRI scans of singleton pregnancies. Training will be performed in 3 acquisition planes (axial, coronal, sagittal). Performance will be evaluated on 10 test MRIs (in 3 acquisition planes, 30 total test samples) using Dice scores, compared to radiologists’ manual segmentations. The algorithm’s performance on measuring total brain volume will also be evaluated. RESULTS/ANTICIPATED RESULTS: Based on the success of prior U-net architectures for volumetric segmentation tasks in medical imaging (e.g. Duong et al., 2019), we anticipate that the convolutional neural network will accurately provide segmentations and associated volumetry of fetal brains in fractions of a second. We anticipate median Dice scores greater than 0.8 across our test sample. Once validated, the method will retrospectively generate a normative database of over 1500 fetal brain volumes across gestational ages (18 weeks to 30 weeks) collected at our institution. DISCUSSION/SIGNIFICANCE OF IMPACT: Quantitative estimates of brain volume, and deviations from normative data, would be a major advancement in objective clinical assessments of fetal MRI. Such data can currently only be obtained through laborious manual segmentations; automated deep learning methods have the potential to reduce the time and cost of this process.

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Fetal MRI, lower acceptance by women in research vs. clinical setting

Journal of Perinatal Medicine ◽

10.1515/jpm-2016-0360 ◽

2018 ◽

Vol 46 (9) ◽

pp. 983-990 ◽

Cited By ~ 4

Author(s):

Bloeme J. van der Knoop ◽

Roland J. Vermeulen ◽

Jonathan I.M.L. Verbeke ◽

Lourens R. Pistorius ◽

Johanna I.P. de Vries

Keyword(s):

At Risk ◽

Pregnant Women ◽

Brain Damage ◽

Clinical Setting ◽

Fetal Brain ◽

Fetal Mri ◽

Clinical Group ◽

Study Participation ◽

Mri Examination ◽

Clinical Cases

Abstract Aim: To determine acceptance of pregnant women to undergo fetal magnetic resonance imaging (MRI) examination in research and clinical setting. Methods: A prospective study included a research group [part of a study comparing brain ultrasound (US) to MRI in fetuses at risk for acquired brain damage] and a clinical group [fetuses with suspected (brain) anomalies after structural US examination] from 2011 to 2014. All women were advised to use sedatives. MRI declinations, use of sedation, MRI duration and imaging quality were compared between both groups. Results: Study participation was accepted in 57/104 (55%) research cases. Fetal MRI was performed in 34/104 (33%) research and 43/44 (98%) clinical cases. Reasons to decline study participation were MRI related in 41%, and participation was too burdensome in 46%. Acceptance was highest for indication infection and lowest in alloimmune thrombocytopenia and monochorionic twin pregnancy. Sedatives were used in 14/34 research and 43/43 clinical cases. Scan duration and quality were comparable (21 and 20 min in research and clinical cases, respectively, moderate/good quality in both groups). Conclusions: Pregnant women consider MRI more burdensome than professionals realize. Two-third of women at risk for fetal brain damage decline MRI examination. Future studies should evaluate which information about fetal MRI is supportive.

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Added Value of Fetal MRI in the Evaluation of Fetal Anomalies of the Corpus Callosum: A Retrospective Analysis of 78 Cases

Ultraschall in der Medizin - European Journal of Ultrasound ◽

10.1055/s-0043-113820 ◽

2018 ◽

Vol 39 (05) ◽

pp. 513-525 ◽

Cited By ~ 1

Author(s):

Mirra Manevich-Mazor ◽

Alina Weissmann-Brenner ◽

Omer Bar Yosef ◽

Chen Hoffmann ◽

Roei Mazor ◽

...

Keyword(s):

Decision Making ◽

Corpus Callosum ◽

Clinical Decision Making ◽

Brain Mri ◽

Fetal Brain ◽

Fetal Mri ◽

Clinical Decision ◽

Added Value ◽

Callosal Agenesis

Abstract Objective To evaluate the added value of fetal MRI to ultrasound in detecting and specifying callosal anomalies, and its impact on clinical decision making. Methods Fetuses with a sonographic diagnosis of an anomalous corpus callosum (CC) who underwent a subsequent fetal brain MRI between 2010 and 2015 were retrospectively evaluated and classified according to the severity of the findings. The findings detected on ultrasound were compared to those detected on MRI. An analysis was performed to assess whether fetal MRI altered the group classification, and thus the management of these pregnancies. Results 78 women were recruited following sonographic diagnoses of either complete or partial callosal agenesis, short, thin or thick CC. Normal MRI studies were obtained inµ19 cases (24 %). Among these, all children available for follow-up received an adequate adaptive score in their Vineland II adaptive behavior scale assessment. Analysis of the concordance between US and MRI demonstrated a substantial level of agreement for complete callosal agenesis (kappa: 0.742), moderate agreement for thin CC (kappa: 0.418) and fair agreement for all other callosal anomalies. Comparison between US and MRI-based mild/severe findings classifications revealed that MRI contributed to a change in the management for 28 fetuses (35.9 %), mostly (25 fetuses, 32.1 %) in favor of pregnancy preservation. Conclusion Fetal MRI effectively detects callosal anomalies and enables satisfactory validation of the presence or absence of callosal anomalies identified by ultrasound and adds valuable data that improves clinical decision making.

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A Case of Apert Syndrome: Early Detection of Temporal Lobe Abnormalities and Scalp Cyst in Fetal Brain MRI

Iranian Journal of Pediatrics ◽

10.5812/ijp.103841 ◽

2020 ◽

Vol 30 (6) ◽

Author(s):

Ahmad Reza Tahmasebpour ◽

Behnaz Moradi ◽

Mohammad Ali Kazemi

Keyword(s):

Temporal Lobe ◽

Brain Mri ◽

Fetal Brain ◽

Fetal Mri ◽

First Trimester ◽

Apert Syndrome ◽

Imaging Features ◽

Calvarial Bone ◽

First Case ◽

Fgfr2 Gene

Introduction: Apert Syndrome is one of the severe forms of craniosynostosis syndromes. Here we present the first case of 20 weeks fetus with temporal lobe abnormalities with a scalp cyst in fetal MRI. Case Presentation: A 34-year-old woman at 19 weeks of pregnancy presented with normal first trimester scan and with acrocephaly, mild ventriculomegaly (10.5 mm), hypertelorism, and mitten glove syndactyly of hands of the fetus in second trimester ultrasound scan. Also a scalp cyst without calvarial bone defect was found. One week later, fetal brain MRI on 1.5 T scanner confirmed 2D ultrasound findings. Also bilateral temporal lobe overconvolution and low set ears were detected by MRI. These imaging features strongly suggested Apert or a related craniosynostosis syndrome. Amniocentesis result revealed the heterozygous FGFR2 gene mutation consistent with Apert syndrome. Conclusions: Fetal MRI and ultrasound are complementary tools for full evaluation of different aspects of a syndromic condition in fetus that is very important for proper genetic testing and counseling.

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The Reliability of Fetal MRI in the Assessment of Brain Malformations

Fetal Diagnosis and Therapy ◽

10.1159/000363652 ◽

2014 ◽

Vol 37 (2) ◽

pp. 93-101 ◽

Cited By ~ 6

Author(s):

Nora Frick ◽

Claudius Fazelnia ◽

Kathrin Kanzian ◽

Wolfgang Hitzl ◽

Thorsten Fischer ◽

...

Keyword(s):

Corpus Callosum ◽

Brain Mri ◽

Intraclass Correlation ◽

Fetal Brain ◽

Fetal Mri ◽

Intraobserver Reliability ◽

Mri Findings ◽

The Third ◽

Brain Malformations ◽

Mri Measurements

Objectives: To assess the inter- and intraobserver reliability of different fetal MRI measurements in cases of fetal brain malformations and to examine the concordance between ultrasonography (US) and MRI findings. Methods: Fetal brain MRIs and US findings of 56 pregnant women were retrieved from the institutional database. Standardized fetal brain MRI measurements were performed by 4 observers, and the inter- and intraobserver reliability was determined. Additionally, US and MRI findings were retrospectively compared. Results: The interobserver intraclass correlation coefficient (ICC) was above 0.9 for the cerebellum and posterior horn of the lateral ventricle. The measurements regarding the third ventricle (0.50), the fourth ventricle (0.58), and the corpus callosum (0.63) showed poor reliability. Overall, the intraobserver reliability was greater than the interobserver reliability. US and MRI findings were discordant in 29% of the cases with MRI rendering an extended diagnosis in 18%, a change of diagnosis in 3.6%, and excluding pathological findings suspected on US in 7.1%. Conclusions: Fetal MRI is a valuable complement to US in the investigation of fetal brain malformations. The reliability of most parameters was high, except for the measurements of the third and fourth ventricles and the corpus callosum.

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A Clinical-Based Diagnostic Approach to Cerebellar Atrophy in Children

Applied Sciences ◽

10.3390/app11052333 ◽

2021 ◽

Vol 11 (5) ◽

pp. 2333

Author(s):

Claudia Ciaccio ◽

Chiara Pantaleoni ◽

Franco Taroni ◽

Daniela Di Bella ◽

Stefania Magri ◽

...

Keyword(s):

Muscle Biopsy ◽

Single Gene ◽

Brain Mri ◽

Genetic Defect ◽

Cerebellar Atrophy ◽

Chain Complex ◽

Clinical Findings ◽

Diagnostic Workup ◽

Diagnostic Approach ◽

Disease Definition

Background: Cerebellar atrophy is a neuroradiological definition that categorizes conditions heterogeneous for clinical findings, disease course, and genetic defect. Most of the papers proposing a diagnostic workup for pediatric ataxias are based on neuroradiology or on the literature and experimental knowledge, with a poor participation of clinics in the process of disease definition. Our study aims to offer a different perspective on the way we approach cerebellar atrophy in developmental age, building a clinical-based diagnostic workup to guide molecular diagnosis. Methods: we recruited 52 patients with pediatric-onset cerebellar atrophy and definite disease categorization. Children underwent brain MRI, neurophysiological exams, metabolic investigations, and muscle biopsy with respiratory chain complex study. Single-gene sequencing, next-generation sequencing NGS panels, whole-exome sequencing (WES), and disease-specific techniques have been used to reach genetic confirmation. Results: Brain MRI is the main method of diagnosis, followed by tests on muscle biopsy and peripheral nervous system study. Other exams (e.g., metabolic investigations or evoked potentials) may be useful to narrow the list of diagnostic possibilities. Conclusions: We propose a diagnostic approach to cerebellar atrophy in children based on clinical findings, and support the evidence that a precise phenotypic definition may lead to the formulation of a definite diagnosis or otherwise guide the back phenotyping process derived from large molecular data.

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Effect of routine iron–folic acid supplementation among rural pregnant women living in low- and high-groundwater-iron areas in Bangladesh

Public Health Nutrition ◽

10.1017/s1368980019001617 ◽

2019 ◽

Vol 22 (15) ◽

pp. 2844-2855 ◽

Cited By ~ 1

Author(s):

Faruk Ahmed ◽

Moududur Rahman Khan ◽

Ireen Akhtar Chowdhury ◽

Rubhana Raqib ◽

Anjan Kumar Roy ◽

...

Keyword(s):

Folic Acid ◽

Pregnant Women ◽

Significant Proportion ◽

Significant Risk ◽

Folic Acid Supplementation ◽

Fe Deficiency ◽

Prospective Longitudinal Study ◽

Iron Folic Acid ◽

Hb Concentration ◽

Prospective Longitudinal

AbstractObjective:The present study investigated the risks and benefits of routine Fe–folic acid (IFA) supplementation in pregnant women living in low- and high-groundwater-Fe areas in Bangladesh.Design:A case-controlled prospective longitudinal study design was used to compare the effect of daily Fe (60 mg) and folic acid (400 μg) supplementation for 3·5 months.Setting:A rural community in Bangladesh.Participants:Pregnant women living in low-groundwater-Fe areas (n 260) and high-groundwater-Fe areas (n 262).Results:Mean Hb and serum ferritin concentrations at baseline were significantly higher in pregnant women in the high-groundwater-Fe areas. After supplementation, the mean change in Hb concentration in the women in the low-groundwater-Fe areas (0·10 mg/dl) was higher than that in the pregnant women in the high-groundwater-Fe areas (–0·08 mg/dl; P = 0·052). No significant changes in the prevalence of anaemia or Fe deficiency (ID) in either group were observed after IFA supplementation; however, the prevalence of Fe-deficiency anaemia (IDA) decreased significantly in the women in the low-groundwater-Fe areas. The risk of anaemia, ID and IDA after supplementation did not differ significantly between the groups. None of the participants had Fe overload. However, a significant proportion of the women in the high- and low-groundwater-Fe areas remained anaemic and Fe-deficient after supplementation.Conclusion:IFA supplementation significantly increased the Hb concentration in pregnant women living in the low-groundwater-Fe areas. Routine supplementation with 60 mg Fe and 400 μg folic acid does not pose any significant risk of haemoconcentration or Fe overload. Further research to identify other nutritional and non-nutritional contributors to anaemia is warranted to prevent and treat anaemia.

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Brain MRI and cognitive function seven years after surviving an episode of severe acute malnutrition in a cohort of Malawian children

Public Health Nutrition ◽

10.1017/s1368980018003282 ◽

2018 ◽

Vol 22 (8) ◽

pp. 1406-1414 ◽

Cited By ~ 3

Author(s):

Natasha Lelijveld ◽

Alhaji A Jalloh ◽

Samuel D Kampondeni ◽

Andrew Seal ◽

Jonathan C Wells ◽

...

Keyword(s):

Brain Structure ◽

Severe Acute Malnutrition ◽

School Achievement ◽

Brain Mri ◽

Well Being ◽

Reference Population ◽

Acute Malnutrition ◽

Lower Grade ◽

Economic Implications ◽

Prospective Longitudinal

AbstractObjectiveTo assess differences in cognition functions and gross brain structure in children seven years after an episode of severe acute malnutrition (SAM), compared with other Malawian children.DesignProspective longitudinal cohort assessing school grade achieved and results of five computer-based (CANTAB) tests, covering three cognitive domains. A subset underwent brain MRI scans which were reviewed using a standardized checklist of gross abnormalities and compared with a reference population of Malawian children.SettingBlantyre, Malawi.ParticipantsChildren discharged from SAM treatment in 2006 and 2007 (n 320; median age 9·3 years) were compared with controls: siblings closest in age to the SAM survivors and age/sex-matched community children.ResultsSAM survivors were significantly more likely to be in a lower grade at school than controls (adjusted OR = 0·4; 95 % CI 0·3, 0·6; P < 0·0001) and had consistently poorer scores in all CANTAB cognitive tests. Adjusting for HIV and socio-economic status diminished statistically significant differences. There were no significant differences in odds of brain abnormalities and sinusitis between SAM survivors (n 49) and reference children (OR = 1·11; 95 % CI 0·61, 2·03; P = 0·73).ConclusionsDespite apparent preservation in gross brain structure, persistent impaired school achievement is likely to be detrimental to individual attainment and economic well-being. Understanding the multifactorial causes of lower school achievement is therefore needed to design interventions for SAM survivors to thrive in adulthood. The cognitive and potential economic implications of SAM need further emphasis to better advocate for SAM prevention and early treatment.

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