Intrauterine fetal MR versus postmortem MR imaging after therapeutic termination of pregnancy: evaluation of the concordance in the detection of brain abnormalities at early gestational stage.

BACKGROUND AND PURPOSE: Fetal postmortem MR Imaging (pmMRI) has been recently used as an adjuvant tool to conventional brain autopsy after termination of pregnancy (TOP). Our purpose was to compare the diagnostic performance of intrauterine MRI (iuMRI) and pmMRI in the detection of brain anomalies in fetuses at early gestational age (GA). MATERIAL AND METHODS: We retrospectively collected 53 fetuses who had undergone iuMRI and pmMRI for suspected brain anomalies. Two pediatric neuroradiologists reviewed iuMRI and pmMRI examinations separately and then together. We used Cohen's K to assess the agreement between pmMRI and iuMRI. Using the combined evaluation iuMRI+pMRI as the reference standard, we calculated the "correctness ratio." We used Somers' D to assess the cograduation between postmortem image quality and time elapsed after fetus expulsion. RESULTS: Our data showed high agreement between iuMRI and pmMRI considering all the categories together, for both observers (K1 0.84; K2 0.86). The correctness ratio of iuMRI and pmMRI was 79% and 45% respectively. The major disagreements between iuMRI and pmMRI were related to postmortem changes as the collapse of liquoral structures and distorting phenomena. We also found a significant cograduation between the time elapsed from expulsion and pmMRI contrast resolution and distortive phenomena (both p < 0.001). CONCLUSIONS: Our study demonstrates an overall high concordance between iuMRI and pmMRI in detecting fetal brain abnormalities at early GA. Nevertheless, for the correct interpretation of pmMRI, the revision of fetal examination seems to be crucial, in particular when time elapsed from expulsion is longer than 24 h. KEY POINTS: • IuMRI and pmMRI showed overall high concordance in detecting fetal brain abnormalities at early GA. • PmMRI corroborated the antemortem diagnosis and it could be a valid alternative to conventional brain autopsy, only when the latter cannot be performed. • Some caution should be taken in interpreting pmMR images when performed after 24 h from fetal death.

The Combined Use of Ultrasound and Fetal Magnetic Resonance Imaging for a Comprehensive Fetal Neurological Assessment in Fetal Congenital Cardiac Defects: Scientific Impact Paper No. 60.

Heart problems are common in newborn babies, affecting approximately 5-10 in 1000 babies. Some are more serious than others, but most babies born with heart problems do not have other health issues. Of those babies who have a serious heart problem, almost 1 in 4 will have heart surgery in their first year. In the UK, pregnant women are offered a scan at around 20 weeks to try and spot any heart problems. In most cases there is not a clear reason for the problem, but sometimes other issues, such as genetic conditions, are discovered. In recent years the care given to these babies after they are born has improved their chances of surviving. However, it is recognised that babies born with heart problems have a risk of delays in their learning and development. This may be due to their medical condition, or as a result of surgery and complications after birth. In babies with heart problems, there is a need for more research on ultrasound and magnetic resonance imaging (MRI) to understand how the brain develops and why these babies are more likely to have delays in learning and development. This paper discusses the way ultrasound and MRI are used in assessing the baby's brain. Ultrasound is often used to spot any problems, looking at how the baby's brain develops in pregnancy. Advances in ultrasound technologies have made this easier. MRI is well-established and safe in pregnancy, and if problems in the brain have been seen on ultrasound, MRI may be used to look at these problems in more detail. While it is not always clear what unusual MRI findings can mean for the baby in the long term, increased understanding may mean parents can be given more information about possible outcomes for the baby and may help to improve the counselling they are offered before their baby's birth.

The rate of brain abnormalities on in utero MRI studies in fetuses with normal ultrasound examinations of the brain and calculation of indicators of diagnostic performance.

AIM: To estimate the rate of unexpected brain abnormalities detected by in utero magnetic resonance imaging (iuMRI) in fetuses without abnormalities at ultrasonography (USS). MATERIALS AND METHODS: A prospective cohort study of pregnant women whose fetus had no structural brain (or body) abnormalities recognised on antenatal ultrasonography. Women were recruited from 12 centres across the UK and underwent iuMRI at 18 gestational weeks or more in the [blinded for review]. The imaging studies were reviewed by an experienced neuroradiologist. The positive and negative predictive values of both USS and iuMRI have been calculated by combining the results of this study with the results from the main [blinded for review] study. RESULTS: One hundred and ninety-eight pregnant women were recruited and underwent iuMRI of 205 fetuses. Brain abnormalities were shown on iuMRI in two fetuses that were not recognised on USS (one case of a focal cortical abnormality and one case of mild ventriculomegaly). The negative predictive value for USS was 99.5% and 100% for iuMRI. CONCLUSIONS: To the authors' knowledge, this is the first study comparing USS and iuMRI in low-risk pregnancies. USS has a comparatively high rule-out for fetal brain abnormalities and should remain the screening tool of choice.

Clinical outcomes following prenatal diagnosis of asymmetric ventriculomegaly, interhemispheric cyst, and callosal dysgenesis (AVID).

OBJECTIVES: When identified prenatally, the imaging triad of asymmetric ventriculomegaly, interhemispheric cyst, and dysgenesis of the corpus callosum (AVID) can indicate a more serious congenital brain anomaly. In this follow-up series of 15 fetuses, we present the neurodevelopmental outcomes of a single institution cohort of children diagnosed prenatally with AVID. METHODS: Our fetal ultrasound database was queried for cases of AVID between 2000 and 2016. All available fetal MR imaging studies were reviewed for the presence of (a) interhemispheric cysts or ventricular diverticula and (b) dysgenesis or agenesis of the corpus callosum. Clinical records were reviewed for perinatal management, postnatal surgical management, and neurodevelopmental outcomes. RESULTS: Fifteen prenatal cases of AVID were identified. Twelve were live-born and three pregnancies were terminated. Of the 12 patients, 11 underwent neurosurgical intervention. Of the eight patients surviving past infancy, seven of eight have moderate to severe neurodevelopmental delays or disabilities, encompassing both motor and language skills, and all have variable visual abnormalities. CONCLUSION: In our cohort of 15 prenatally diagnosed fetuses with AVID, eight survived past infancy and all have neurodevelopmental disabilities, including motor and language deficits, a wide range of visual defects, craniofacial abnormalities, and medical comorbidities.

An evaluation of fetal heart rate characteristics associated with neonatal encephalopathy: a case-control study.

OBJECTIVE: We sought to identify fetal heart rate (FHR) characteristics that are associated with neonatal encephalopathy (NE). DESIGN: Retrospective case-control study. SETTING: A single medical centre in Shanghai, China, 2006-2015. SAMPLE: Women delivering a singleton, non-anomalous infant at ≥36 weeks' gestation diagnosed with NE (cases, n = 109) were compared with a group of women with unaffected infants (controls, n = 233). METHODS: Two physicians blinded to the outcome independently reviewed FHR tracings during the last 30 minutes of tracing prior to delivery. FHR characteristics were compared in the two groups and multivariable logistic regression was used to adjust for confounding. MAIN OUTCOME MEASURES: Adjusted odds ratio (aOR) and 95% confidence interval (CI) for the presence of specific FHR categories and characteristics. RESULTS: Category II FHR tracings were observed in 89% of women prior to delivery and were not independently associated with NE. Notably, a category III FHR was observed in 17.4% of women in the NE group compared with 0.9% of women in the control group (aOR 44.99, 95% CI 7.23-279.97). Bradycardia, minimal/absent variability, late decelerations and prolonged decelerations were independently associated with NE, whereas accelerations were protective. Similar findings were found when the cases were limited to NE with arterial cord pH <7.1 and in a subgroup analysis of women with category II tracings. CONCLUSIONS: Category III tracings, while infrequent, are not uncommon prior to delivery among fetuses who develop NE. In contrast, most FHR tracings are category II prior to delivery; however, individual FHR characteristics within this category are associated with NE. FUNDING: This research was supported by the Interdisciplinary Programme of Shanghai Jiao Tong University. TWEETABLE ABSTRACT: Category III tracings are not uncommon prior to delivery among fetuses who develop neonatal encephalopathy.

Molecular investigations of development and diseases of the brain of higher mammals using the ferret.

The brains of higher mammals such as primates and carnivores contain well-developed unique brain structures. Uncovering the physiological functions, developmental mechanisms and evolution of these brain structures would greatly facilitate our understanding of the human brain and its diseases. Although the anatomical and electrophysiological features of these brain structures have been intensively investigated, our knowledge about their molecular bases is still limited. To overcome this limitation, genetic techniques for the brains of carnivores and primates have been established, and molecules whose expression patterns correspond to these brain structures were identified recently. To investigate the functional roles of these molecules, rapid and efficient genetic manipulation methods for higher mammals have been explored. In this review, recent advances in molecular investigations of the brains of higher mammals are discussed, mainly focusing on ferrets (Mustela putorius furo).

The anterior complex: A visual mnemonic to aid in identification of normal structures.

The anterior complex of the fetal brain is a group of structures that are important to evaluate during the routine anatomic survey to exclude several serious brain malformations. These structures include the cavum septum pellucidum, anterior horns, interhemispheric fissure, callosal sulcus, and corpus callosum. The relationship between these structures is easily remembered with the presented visual cartoon. © 2017 Wiley Periodicals, Inc. J Clin Ultrasound 45:477-479, 2017.

5D CNS+ Software for Automatically Imaging Axial, Sagittal, and Coronal Planes of Normal and Abnormal Second-Trimester Fetal Brains.

The purpose of this study was to test new 5D CNS+ software (Samsung Medison Co, Ltd, Seoul, Korea), which is designed to image axial, sagittal, and coronal planes of the fetal brain from volumes obtained by 3-dimensional sonography. The study consisted of 2 different steps. First in a prospective study, 3-dimensional fetal brain volumes were acquired in 183 normal consecutive singleton pregnancies undergoing routine sonographic examinations at 18 to 24 weeks' gestation. The 5D CNS+ software was applied, and the percentage of adequate visualization of brain diagnostic planes was evaluated by 2 independent observers. In the second step, the software was also tested in 22 fetuses with cerebral anomalies. In 180 of 183 fetuses (98.4%), 5D CNS+ successfully reconstructed all of the diagnostic planes. Using the software on healthy fetuses, the observers acknowledged the presence of diagnostic images with visualization rates ranging from 97.7% to 99.4% for axial planes, 94.4% to 97.7% for sagittal planes, and 92.2% to 97.2% for coronal planes. The Cohen κ coefficient was analyzed to evaluate the agreement rates between the observers and resulted in values of 0.96 or greater for axial planes, 0.90 or greater for sagittal planes, and 0.89 or greater for coronal planes. All 22 fetuses with brain anomalies were identified among a series that also included healthy fetuses, and in 21 of the 22 cases, a correct diagnosis was made. 5D CNS+ was efficient in successfully imaging standard axial, sagittal, and coronal planes of the fetal brain. This approach may simplify the examination of the fetal central nervous system and reduce operator dependency.

Three-dimensional ultrasound of the fetus: how does it help?

Three-dimensional ultrasonography (3-D US) was introduced to the field of fetal imaging in the early 1990s. Since then several publications have described potential applications for the diagnosis of congenital malformations as well as organ volumetry. This article reviews basic principles of 3-D US as well as its clinical applicability to prenatal diagnosis of abnormalities involving the face, spine and skeletal system, as well as potential applications of 3-D US for fetal cardiovascular and neuroimaging. Limitations related to motion artifacts, acoustic shadowing and barriers to clinical implementation of 3-D US in clinical practice are addressed.

[Neu-Laxova syndrome: Three case reports and a review of the literature]. / Syndrome de Neu-Laxova : rapport de trois cas et revue de la littérature.

INTRODUCTION: The Neu-Laxova syndrome (NLS) is a rare autosomal recessive and early lethal disorder. It is characterized by severe intra-uterine growth retardation, abnormal facial features, ichthyotic skin lesions and severe central nervous system malformations, especially microlissencephaly. Others characteristic features associated with fetal hypokinesia sequence, including arthrogryposis, subcutaneous edema and pulmonary hypoplasia, are frequently reported in NLS. PATIENTS AND METHODS: The clinicopathological characteristics of NLS are described in three cases with striking prenatal diagnostic findings and detailed post-mortem examinations. A review of the literature is undertaken with a focus on molecular basis. RESULTS: We present three new patients with NLS: one stillbirth male and two female newborns, delivered at 29, 35 and 40 weeks of gestational age, respectively. Characteristic ultrasound findings included hydramnios, severe intra-uterine growth restriction, craniofacial and cental nervous system anomalies. The cytogenetic study, performed in one case, was normal. The post-mortem examination revealed characteristic abnormalities in all three cases, that allowed to make a prompt diagnosis of the NLS. Data from these patients suggest that the NLS represents a heterogeneous phenotype. This feature has been highlighted in the literature. CONCLUSION: The SNL is a lethal developmental disorder characterized by phenotypic heterogeneity with striking neurological defects. It is underpinned by genetic heterogeneity. It can be caused by mutations in all three genes involved in de novo L-serine biosynthesis: PHGDH, PSAT1 and PSPH. Hence, the NLS constitutes the most severe end of already known human disease, i.e. serine-deficiency disorder.

Prenatal features of isolated subependymal pseudocysts associated with adverse pregnancy outcome.

OBJECTIVES: To identify at prenatal ultrasound (US) the features of apparently isolated subependymal pseudocysts (SEPC) that may indicate underlying pathology and should lead to further investigations. METHODS: This was a retrospective study of cases with SEPC detected on prenatal US and/or magnetic resonance imaging (MRI). Those with apparently isolated SEPC at US were classified into two groups as follows: Group 1 (n = 29): normal prenatal US and MRI (except for SEPC) and normal outcome; Group 2 (n = 12): normal prenatal cerebral US (except for SEPC) and abnormal prenatal cerebral MRI with or without abnormal outcome. A third group (n = 9) included cases with abnormal prenatal US and MRI. The latter cases with obvious cerebral abnormalities at US were excluded from the statistical analysis as they do not represent a diagnostic dilemma for clinicians. Groups 1 and 2 were analyzed, comparing them with respect to their SEPC characteristics (size, number, location in relation to the caudothalamic notch and the ventricular horns and morphology) and extracerebral abnormalities. RESULTS: The mean ± SD SEPC great axis was longer in Group 2 (11.67 ± 5.82 mm) than it was in Group 1 (8.00 ± 5.64 mm) (P = 0.021), suggesting an optimal cut-off for size of SEPC of ≥ 9 mm (sensitivity = 75%, specificity = 62%) to maximize sensitivity for predicting pathological outcome. SEPC adjacent to the temporal horns and SEPC located posterior to the caudothalamic notch were observed more frequently in Group 2, indicating their association with poor outcome (P = 0.003 and P = 0.003, respectively). Atypical morphology and extracerebral abnormalities were observed more frequently in Group 2 (P = 0.013 and P = 0.044, respectively). There was no statistically significant difference between groups for either number or location of cysts along the inferior wall or adjacent to the lateral wall of the frontal horns (P = 0.591 and P = 0.156, respectively). CONCLUSION: When apparently isolated SEPC are observed at prenatal US, further investigations should be performed under the following circumstances: (1) SEPC great axis ≥ 9 mm; (2) SEPC adjacent to the occipital and temporal horns; (3) SEPC located posterior to the caudothalamic notch; (4) SEPC with atypical morphology.

Prenatal diagnosis of colpocephaly with absent corpus callosum.

Colpocephaly is a rare abnormality of the brain, described as persistence of primitive foetal configuration of lateral ventricles. It has been found in association with several abnormalities of the brain. Herein we report a case of colpocephaly with absent corpus callosum, confirmed antenatally with foetal MRI following diagnostic suspicion based on absent septum pellucidum at prenatal sonography.

The Developmental Brain Disorders Database (DBDB): a curated neurogenetics knowledge base with clinical and research applications.

The number of single genes associated with neurodevelopmental disorders has increased dramatically over the past decade. The identification of causative genes for these disorders is important to clinical outcome as it allows for accurate assessment of prognosis, genetic counseling, delineation of natural history, inclusion in clinical trials, and in some cases determines therapy. Clinicians face the challenge of correctly identifying neurodevelopmental phenotypes, recognizing syndromes, and prioritizing the best candidate genes for testing. However, there is no central repository of definitions for many phenotypes, leading to errors of diagnosis. Additionally, there is no system of levels of evidence linking genes to phenotypes, making it difficult for clinicians to know which genes are most strongly associated with a given condition. We have developed the Developmental Brain Disorders Database (DBDB: https://www.dbdb.urmc.rochester.edu/home), a publicly available, online-curated repository of genes, phenotypes, and syndromes associated with neurodevelopmental disorders. DBDB contains the first referenced ontology of developmental brain phenotypes, and uses a novel system of levels of evidence for gene-phenotype associations. It is intended to assist clinicians in arriving at the correct diagnosis, select the most appropriate genetic test for that phenotype, and improve the care of patients with developmental brain disorders. For researchers interested in the discovery of novel genes for developmental brain disorders, DBDB provides a well-curated source of important genes against which research sequencing results can be compared. Finally, DBDB allows novel observations about the landscape of the neurogenetics knowledge base.

Modalities of fetal evaluation to detect fetal compromise prior to the development of significant neurological damage.

AIMS: The aim of this study was to clarify the developmental mechanism underlying fetal heart rate (FHR) long-term variability (LTV) and acceleration with respect to fetal brain damage. MATERIAL AND METHODS: The fetal state was deduced from the developmental mechanism of FHR variability analyzed by actocardiogram, animal experiments, and simulations. RESULTS: LTV develops due to minor fetal movements in the fetal midbrain, moderate LTV by fetal periodic movements and triangular accelerations by large fetal movement bursts. Stimulation of the fetal midbrain by sound and light produces fetal movements that lead to FHR acceleration. Severe hypoxia can result in the loss of LTV and neuronal necrosis that may damage the fetal brain. Therefore, a cesarean section is recommended prior to the loss of LTV, rather than after its loss. The vagal center of the fetal medulla oblongata is excited by hypoxia and produces FHR bradycardia. The heart rate of hypoxic rabbits was found to be closely correlated with the PaO2, thus the impact of hypoxia could be estimated by the hypoxia index, which is calculated from the reciprocal of nadir FHR and bradycardia duration. CONCLUSIONS: Analyzing the development of FHR signs could help to diagnose fetal state. An early cesarean section is recommended before the loss of LTV as indicated by the hypoxia index, which will contribute to prevent fetal brain damage and neurological sequels.

Cerebral ultrasound findings in infants exposed to crack cocaine during gestation.

BACKGROUND: Prenatal exposure to cocaine has been associated with a wide spectrum of structural abnormalities in infant brains. The growing use of crack, a smokable and extremely addictive form of cocaine, could exacerbate the situation. OBJECTIVE: The purpose of this study was to determine the frequency, type and severity of cerebral lesions detected by transfontanellar US in newborns exposed to crack during gestation. MATERIALS AND METHODS: This was a retrospective study, involving a review of the medical records of children who were born to crack-using women and who were subjected to transfontanellar US imaging during their first days of life. RESULTS: Transfontanellar US revealed abnormalities in 45/129 newborns examined (34.9%). The changes detected were subependymal cysts in 24 infants (18.6%), lenticulostriate vasculopathy in 18 infants (14%), subependymal hemorrhage in 9 infants (7%), and choroid plexus cysts in 9 infants (7%). CONCLUSION: All of the abnormalities found by US examination were discrete and likely without clinical significance for the babies. However, prospective studies with a long period of tracking are needed to determine whether there are later consequences on the neurodevelopment of children with prenatal exposure to crack.

[Acquired CNS lesions in fetal MRI]. / Erworbene ZNS-Läsionen im fetalen MRT.

Acquired central nervous system (CNS) lesions are often subtle; therefore, the prenatal diagnosis of these lesions is extremely important. The fetal ultrasound examination and magnetic resonance imaging (MRI) are two important imaging methods that give an insight into these types lesions. The method of choice during pregnancy is still fetal ultrasound; however, fetal MRI is important when there are certain pathologies, e.g. periventricular leukomalacia (PVL) or malformations of the vein of Galen. In this manner clinicians can plan further therapy after childbirth in advance (e.g. cerebral angiography or embolization).

The brain in the belly: what and how of fetal neuroimaging?

This work reviews magnetic resonance imaging in the developing human brain. It focuses on fetal brain imaged in vivo and in utero with complementary sections on abnormalities seen in clinical settings, and on potential of diffusion tensor imaging and of proton magnetic resonance spectroscopy. The main purposes are to illustrate the normal fetal developing brain and its abnormalities commonly encountered in utero, and to emphasize the potential role of adjunct techniques such as diffusion imaging and spectroscopy that may help elucidate fetal brain maturation and its abnormalities.

Sonographic assessment of normal and abnormal patterns of fetal cerebral lamination.

OBJECTIVES: Prenatal development of the brain is characterized by gestational age-specific changes in the laminar structure of the brain parenchyma before 30 gestational weeks. Cerebral lamination patterns of normal fetal brain development have been described histologically, by postmortem in-vitro magnetic resonance imaging (MRI) and by in-vivo fetal MRI. The purpose of this study was to evaluate the sonographic appearance of laminar organization of the cerebral wall in normal and abnormal brain development. METHODS: This was a retrospective study of ultrasound findings in 92 normal fetuses and 68 fetuses with abnormal cerebral lamination patterns for gestational age, at 17-38 weeks' gestation. We investigated the visibility of the subplate zone relative to the intermediate zone and correlated characteristic sonographic findings of cerebral lamination with gestational age in order to evaluate transient structures. RESULTS: In the normal cohort, the subplate zone-intermediate zone interface was identified as early as 17 weeks, and in all 57 fetuses examined up to 28 weeks. In all of these fetuses, the subplate zone appeared anechoic and the intermediate zone appeared homogeneously more echogenic than did the subplate zone. In the 22 fetuses between 28 and 34 weeks, there was a transition period when lamination disappeared in a variable fashion. The subplate zone-intermediate zone interface was not identified in any fetus after 34 weeks (n=13). There were three patterns of abnormal cerebral lamination: (1) no normal laminar pattern before 28 weeks (n=32), in association with severe ventriculomegaly, diffuse ischemia, microcephaly, teratogen exposure or lissencephaly; (2) focal disruption of lamination before 28 weeks (n=24), associated with hemorrhage, porencephaly, stroke, migrational abnormalities, thanatophoric dysplasia, meningomyelocele or encephalocele; (3) increased prominence and echogenicity of the intermediate zone before 28 weeks and/or persistence of a laminar pattern beyond 33 weeks (n=10), associated with Type 1 lissencephaly or CMV infection. There was a mixed focal/diffuse pattern in two fetuses. In CMV infection, the earliest indication of the infection was focal heterogeneity and increased echogenicity of the intermediate zone, which predated the development of microcephaly, ventriculomegaly and intracranial calcification. CONCLUSIONS: The fetal subplate and intermediate zones can be demonstrated reliably on routine sonography before 28 weeks and disappear after 34 weeks. These findings represent normal gestational age-dependent transient laminar patterns of cerebral development and are consistent with histological studies. Abnormal fetal cerebral lamination patterns for gestational age are also visible on sonography, and may indicate abnormal brain development.

[Fetal neurosonography using 3-dimensional multiplanar sonography]. / Fetale Neurosonografie mittels 3-dimensionaler multiplanarer Sonografie.

This review focuses on the examination of the fetal brain, using three-dimensional (3D) ultrasound and the multiplanar rendering mode (MPR). The routine examination of the brain is achieved with axial planes but a dedicated fetal neurosonogram requires additional coronal and sagittal views, in order to provide a complete view of the different brain structures. Because these planes are difficult to obtain under many conditions, the present paper shows how 3D MPR allows one to obtain 1 or multiple reconstructed images from a digital volume. The display can be either as orthogonal planes, tomographic planes with parallel slices or as one single plane of the region of interest, which can be selected by the examiner. This approach allows easily the demonstration of the corpus callosum, the cerebellar vermis, the three-horn view, the foetal hippocampus and other regions. In addition, early neurosonography of the developing brain from the 7th week of pregnancy onwards can be achieved.