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

2020 ◽  
Vol 117 (18) ◽  
pp. 10035-10044
Author(s):  
Xiaojie Wang ◽  
Verginia C. Cuzon Carlson ◽  
Colin Studholme ◽  
Natali Newman ◽  
Matthew M. Ford ◽  
...  

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.

2021 ◽  
Author(s):  
Netanell Avisdris ◽  
Bossmat Yehuda ◽  
Ori Ben-Zvi ◽  
Daphna Link-Sourani ◽  
Liat Ben-Sira ◽  
...  

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.


2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S22-S22
Author(s):  
Sarah Mulkey ◽  
Gilbert Vezina ◽  
Yamil Fourzali ◽  
Dorothy Bulas ◽  
Margarita Arroyave-Wessel ◽  
...  

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.


2020 ◽  
Vol 4 (s1) ◽  
pp. 45-46
Author(s):  
Carol Tran ◽  
Orit Glenn ◽  
Christopher Hess ◽  
Andreas Rauschecker

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.


NeuroImage ◽  
2019 ◽  
Vol 195 ◽  
pp. 23-37 ◽  
Author(s):  
Lana Vasung ◽  
Christine J. Charvet ◽  
Tadashi Shiohama ◽  
Borjan Gagoski ◽  
Jacob Levman ◽  
...  

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012836
Author(s):  
Darius Ebrahimi-Fakhari ◽  
Julian E Alecu ◽  
Marvin Ziegler ◽  
Gregory Geisel ◽  
Catherine Jordan ◽  
...  

Background and Objectives:AP-4-associated hereditary spastic paraplegia (AP-4-HSP: SPG47, SPG50, SPG51, SPG52) is an emerging cause of childhood-onset hereditary spastic paraplegia and mimic of cerebral palsy. This study aims to define the spectrum of brain MRI findings in AP-4-HSP and to investigate radio-clinical correlations.Methods:A systematic qualitative and quantitative analysis of 107 brain MRI studies from 76 individuals with genetically-confirmed AP-4-HSP and correlation with clinical findings including surrogates of disease severity.Results:We define AP-4-HSP as a disorder of gray and white matter and demonstrate that abnormal myelination is common and that metrics of reduced white matter volume correlate with severity of motor symptoms. We identify a common diagnostic imaging signature consisting of (1) a thin splenium of the corpus callosum, (2) an absent or thin anterior commissure, (3) characteristic signal abnormalities of the forceps minor (“ears of the grizzly sign”), and (4) periventricular white matter abnormalities. The presence of two or more of these findings has a sensitivity of ∼99% for detecting AP-4-HSP, while the combination of all four is found in ∼45% of cases. Compared to other HSP with a thin corpus callosum, the absent anterior commissure appears to be specific to AP-4-HSP. Our analysis further identified a subset of AP-4-HSP patients with polymicrogyria, underscoring the role of AP-4 in early brain development. Of clinical importance, these patients displayed a higher prevalence of seizures and status epilepticus, many at a young age.Discussion:Our findings define the MRI spectrum of AP-4-HSP providing opportunities for early diagnosis, identification of individuals at risk for complications, and a window into the role of the AP-4 complex in brain development and neurodegeneration.


Author(s):  
Rupa Radhakrishnan ◽  
Brandon P. Brown ◽  
David M. Haas ◽  
Yong Zang ◽  
Christina Sparks ◽  
...  

NeuroImage ◽  
1996 ◽  
Vol 3 (3) ◽  
pp. S146 ◽  
Author(s):  
V.J. Wedeen ◽  
T.L. Davis ◽  
B.E. Lautrup ◽  
T.G. Reese ◽  
B.R. Rosen

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