Characterization of Endothelial Cilia Distribution During Cerebral-Vascular Development in Zebrafish ( Danio rerio).

Objective- Endothelial cells (ECs) sense and respond to flow-induced mechanical stress, in part, via microtubule-based projections called primary cilia. However, many critical steps during vascular morphogenesis occur independent of flow. The involvement of cilia in regulating these stages of cranial vascular morphogenesis is poorly understood because cilia have not been visualized in primary head vessels. The objective of this study was to investigate involvement of cilia in regulating the early stages of cranial vascular morphogenesis. Approach and Results- Using high-resolution imaging of the Tg(kdrl:mCherry-CAAX) y171 ;(bactin::Arl13b:GFP) zebrafish line, we showed that cilia are enriched in the earliest formed cranial vessels that assemble via vasculogenesis and in angiogenic hindbrain capillaries. Cilia were more prevalent around the boundaries of putative intravascular spaces in primary and angiogenic vessels. Loss of cardiac contractility and blood flow, because of knockdown of cardiac troponin T type 2a ( tnnt2a) expression, did not affect the distribution of cilia in primary head vasculature. In later stages of development, cilia were detected in retinal vasculature, areas of high curvature, vessel bifurcation points, and during vessel anastomosis. Loss of genes crucial for cilia biogenesis ( ift172 and ift81) induced intracerebral hemorrhages in an EC-autonomous manner. Exposure to high shear stress induced premature cilia disassembly in brain ECs and was associated with intracerebral hemorrhages. Conclusions- Our study suggests a functional role for cilia in brain ECs, which is associated with the emergence and remodeling of the primary cranial vasculature. This cilia function is flow-independent, and cilia in ECs are required for cerebral-vascular stability.

A review of extraaxial developmental venous anomalies of the brain involving dural venous flow or sinuses: persistent embryonic sinuses, sinus pericranii, venous varices or aneurysmal malformations, and enlarged emissary veins.

This paper is a narrative review of extraaxial developmental venous anomalies (eDVAs) of the brain involving dural venous flow or sinuses: persistent embryonic sinuses, sinus pericranii, enlarged emissary veins, and venous varices or aneurysmal malformations. The article highlights the natural history, anatomy, embryology, imaging, clinical implications, and neurosurgical significance of these lesions, which the authors believe represent a continuum, with different entities characterized by distinct embryopathologic features. The indications and surgical management options are discussed for these individual intracranial pathologies with relevant illustrations, and a novel classification is proposed for persistent falcine sinus (PFS). The role of neurointervention and/or microsurgery in specific cases such as sinus pericranii and enlarged emissary veins of the skull is highlighted. A better understanding of the pathophysiology and developmental anatomy of these lesions can reduce treatment morbidity and mortality. Some patients, including those with vein of Galen malformations (VOGMs), can present with the added systemic morbidity of a high-output cardiac failure. Although VOGM is the most studied and classified of the above-mentioned eDVAs, the authors believe that grouping the former with the other venous anomalies/abnormalities listed above would enable the clinician to convey the exact morphophysiological configuration of these lesions, predict their natural history with respect to evolving venous hypertension or stroke, and extrapolate invaluable insights from VOGM treatment to the treatment of other eDVAs. In recent years, many of these symptomatic venous malformations have been treated with endovascular interventions, although these techniques are still being refined. The authors highlight the broad concept of eDVAs and hope that this work will serve as a basis for future studies investigating the role of evolving focal venous hypertension/global intracranial hypertension and possibilities of fetal surgical intervention in these cases.

Nongalenic pial arteriovenous fistula: Prenatal diagnosis.

Pial arteriovenous (AV) fistulae have rarely been diagnosed in utero. They are characterized by one or more pial arteries flowing directly into a cortical vein without any shunt or interposed capillary bed. In the fetus and the newborn up to 2 years of age, the most common clinical manifestation is heart failure resulting from fistula overload. Later on, hydrocephalus, focal neurologic deficits, headaches, seizures, and cerebral hemorrhage are the most common manifestations. We present a case of nongalenic pial AV fistula diagnosed in the 25th week of pregnancy, which resulted in intrauterine fetal death due to congestive heart failure. © 2017 Wiley Periodicals, Inc. J Clin Ultrasound 45:621-625, 2017.

Developmental venous anomalies of the brain in children -- imaging spectrum and update.

Developmental venous anomalies (DVAs) are the most common vascular malformation of the brain and are commonly identified on routine imaging of the brain. They are typically considered incidental findings, usually with no clinical significance. However the increasing identification of DVAs as a result of improved imaging technology has led to recognition of their association with a variety of abnormal imaging findings and clinically important conditions. This pictorial essay explores the suspected embryological origin, associated imaging features, and proposed pathophysiological mechanisms of DVAs in the pediatric population. This paper emphasizes newer physiological imaging data, which suggest that DVA drainage has less physiological flexibility than otherwise normal venous drainage development.

Ultrasound of the Fetal Veins Part 3: The Fetal Intracerebral Venous System.

The study of the intracerebral venous system in the fetus can only be achieved by means of high-resolution ultrasound equipment with sensitive color Doppler. In the past two decades, there has been a growing interest in the ultrasound examination of the fetal brain with few studies reporting on the brain vasculature during various stages of gestation. In comparison to other fetal venous systems, reports on the assessment of the fetal cerebral venous system are still scarce. This article presents a review on the fetal intracranial venous system with detailed discussions on the anatomy of the superficial and deep cerebral veins. Color Doppler of the main fetal cerebral veins to include the superior sagittal sinus, the straight sinus, the vein of Galen, the internal cerebral veins, the transverse sinuses and others is also discussed. Furthermore, this article highlights abnormal clinical conditions such as aneurysm of the vein of Galen, thrombosis of the dural sinus and variation in the course of some veins such as the straight sinus and falcine sinus. The role of pulsed Doppler examination in normal and growth-restricted fetuses is also discussed.

Bilateral thalamic developmental venous variations (DVVs) draining into same internal cerebral vein: a case report and review with emphasis on DVVs with outflow restriction.

Developmental venous variations (DVVs) are anatomic variations of normal transmedullary veins which are often discovered incidentally. Although they are accepted as benign compensatory venous drainage systems, they may become symptomatic or clinically significant due to flow-related causes. The fragile venous drainage systems increase vulnerability to in-out flow alterations. Increased inflow or decreased outflow causes rise in venous pressure, which may subsequently produce ischemic symptoms. Obstruction or stenosis of the collector vein is the most common cause of decreased outflow of a DVV. However, in the absence of collecting vein stenosis, venous hypertension may still exist due to volume overload. In case of multiple DVVs with single combined drainage pathway, functional outflow restriction may occur due to diminished capability of the vessel to adapt to pressure changes. In this report, we present a case with bilateral thalamic DVVs, which cause parenchymal amorphous calcification and drain into the left internal cerebral vein. A review of the literature on DVVs with outflow restriction including pathophysiological mechanisms is also discussed.

Fetal MRI demonstrating vein of Galen malformations in two successive pregnancies--a previously unreported occurrence.

PURPOSE: Vein of Galen malformations are rare and are usually detected in utero using ultrasonography. No definite genetic predisposition has been described in the literature. We present a case with two successive pregnancies complicated by vein of Galen malformations, which were assessed using fetal MRI. The putative role of genetic mutations is also discussed. METHODS: A 30-year-old primigravida presented in the third trimester with a fetus diagnosed with vein of Galen malformation on sonography. MRI and MR angiography were performed for further assessment. The subsequent pregnancy was again complicated by vein of Galen malformation. In addition to MRI, genetic analysis was carried out on both fetuses and on the parents. RESULTS: MR angiography revealed that both fetuses suffered from the choroidal sub-type of vein of Galen malformation, with multiple arterial feeders fistulating onto a midline venous pouch. The visualised anatomy obtained was far superior than on sonography and allowed categorisation of vein of Galen malformation sub-type. Genetic analysis on the mother and both fetuses showed variant RASA1 gene mutation. CONCLUSIONS: This case demonstrates that fetal MRI is a powerful tool in the investigation of in utero neurovascular malformations. A genetic mutation was identified, but this was of uncertain significance.

MR venography of the fetal brain using susceptibility weighted imaging.

PURPOSE: To evaluate the feasibility of performing fetal brain magnetic resonance venography using susceptibility weighted imaging (SWI). MATERIALS AND METHODS: After obtaining informed consent, pregnant women in the second and third trimester were imaged using a modified SWI sequence. Fetal SWI acquisition was repeated when fetal or maternal motion was encountered. The median and maximum number of times an SWI sequence was repeated was four and six respectively. All SWI image data were systematically evaluated by a pediatric neuroradiologist for image quality using an ordinal scoring scheme: 1. diagnostic; 2. diagnostic with artifacts; and 3. nondiagnostic. The best score in an individual fetus was used for further statistical analysis. Visibility of venous vasculature was also scored using a dichotomous variable. A subset of SWI data was re-evaluated by the first and independently by a second pediatric neuroradiologist. Kappa coefficients were computed to assess intra-rater and inter-rater reliability. RESULTS: SWI image data from a total of 22 fetuses were analyzed. Median gestational age and interquartile range of the fetuses imaged were 32 (29.9-34.9) weeks. In 68.2% of the cases (n = 15), there was no artifact; 22.7% (n = 5) had minor artifacts and 9.1% (n = 2) of the data was of nondiagnostic quality. Cerebral venous vasculature was visible in 86.4% (n = 19) of the cases. Substantial agreement (Kappa = 0.73; 95% confidence interval 0.44-1.00)) was observed for intra-rater reliability and moderate agreement (Kappa = 0.48; 95% confidence interval 0.19-0.77) was observed for inter-rater reliability. CONCLUSION: It is feasible to perform fetal brain venography in humans using SWI.

Measuring venous blood oxygenation in fetal brain using susceptibility-weighted imaging.

PURPOSE: To evaluate fetal cerebral venous blood oxygenation, Yv, using principles of MR susceptometry. MATERIALS AND METHODS: A cohort of 19 pregnant subjects, with a mean gestational age of 31.6 ± 4.7 weeks were imaged using a modified susceptibility-weighted imaging (SWI) sequence. Data quality was first assessed for feasibility of oxygen saturation measurement, and data from five subjects (mean ± std gestational age of 33.7 ± 3.6 weeks) were then chosen for further quantitative analysis. SWI phase in the superior sagittal sinus was used to evaluate oxygen saturation using the principles of MR susceptometry. Systematic error in the measured Y(v) values was studied through simulations. RESULTS: Simulations showed that the systematic error in Yv depended upon the assumed angle of the vessel, θ, relative to the main magnetic field and the error in that vessel angle δθ. For the typical vessel angle of θ = 30° encountered in the fetal data analyzed, a δθ as large as ±20° led to an absolute error, δYv, of less than 11%. The measured mean oxygen saturation across the five fetuses was 66% ± 9.4%. This average cerebral venous blood oxygenation value is in close agreement with values in the published literature. CONCLUSION: We have reported the first in vivo measurement of human fetal cerebral venous oxygen saturation using MRI.

Visualizing cerebral veins in fetal brain using susceptibility-weighted MRI.

AIM: To explore the feasibility of two-dimensional (2D) susceptibility-weighted imaging (SWI) in the visualization of cerebral veins in the foetal brain. MATERIALS AND METHODS: Forty-two pregnant healthy women (gestational age: 19-37 weeks, mean: 28.5 ± 7.1 weeks) underwent SWI examination using a 1.5 T MRI system. Two neurologists independently analysed all magnetic resonance imaging (MRI) studies. The relationship between the veins detected and the gestational age was investigated. The prominence of veins was assessed using a categorical score. RESULTS: In total, 167 veins were detected by SWI in 29 subjects with a symmetric hemisphere distribution (p > 0.05). An additional vein was detected by SWI biweekly from 24 weeks of gestation. Most veins of Galen and internal cerebral veins on SWI images were prominent, whereas others were faint or moderate. CONCLUSION: SWI appears to be a feasible method of detecting cerebral veins in the foetal brain.

The intracranial bridging veins: a comprehensive review of their history, anatomy, histology, pathology, and neurosurgical implications.

INTRODUCTION: The intracranial bridging veins are pathways crucial for venous drainage of the brain. They are not only involved in pathological conditions but also serve as important landmarks within neurological surgery. METHODS: The medical literature on bridging veins was reviewed in regard to their historical aspects, embryology, histology, anatomy, and surgery. CONCLUSION: Knowledge on the intracranial bridging veins and their dynamics has evolved over time and is of great significance to the neurosurgeon.

Cerebral venous development in relation to developmental venous anomalies and Vein of Galen aneurysmal malformations.

Cerebrovascular venous development and intracranial vascular malformations are extensive topics for which volumes of text may be devoted. However, a basic knowledge of the embryology of cerebral venous system and venous architecture is essential for understanding of cerebral vascular malformations. The aim of this work is to provide the reader with a brief overview of the development of the cranial venous anatomy. We will highlight the superficial and deep venous systems with special attention to developmental venous anomalies and vein of Galen aneurysmal malformations.

Morphological Pattern and Classification of the Superficial Middle Cerebral Vein by Cadaver Dissections: An Embryological Viewpoint.

In this study, we used 45 adult cadaveric cerebral hemispheres to investigate the anatomical classification of the superficial middle cerebral vein (SMCV) based on the number of stems, course, and anastomosis at the distal portion. We classified the SMCVs into five types based on embryological concept. Type A (18 cases, 40.0%) is that the frontosylvian veins (FSVs) merge with the vein of Trolard (VT) and the vein of Labbé (VL) at the distal portion of the sylvian fissure. Type B (5 cases, 11.1%) is that the temporosylvian veins (TSVs) merge with the VT and the VL at the distal portion. Type C (13 cases, 28.9%) is that no vein merge with the VT and the VL at the distal portion. The VT merges with the SMCV from the FSV and the VL merges with the SMCV from the TSV. They course along the sylvian fissure and merge at the proximal portion. In Type D (eight cases: 17.8%), the VT and the VL merge at the distal portion, and the SMCV from the FSV and the SMCV from the TSV join their confluence without merging. Type E (one case, 2.2%) show an undeveloped SMCV. Formation rate of intravenous anastomoses or bridging veins(BVs) at the distal portion between the frontosylvian trunk (FST) and the temporosylvian trunk (TST), between the FST and the temporal lobe, and between the TST and the frontal lobe was very low, because these formation may be difficult to occur during the embryological process in which the SMCV is formed from the telencephalic vein.

Inactivation of the Sema5a gene results in embryonic lethality and defective remodeling of the cranial vascular system.

The semaphorins are a large family of proteins involved in the patterning of both the vascular and the nervous systems. In order to analyze the function of the membrane-bound semaphorin 5A (Sema5A), we generated mice homozygous for a null mutation in the Sema5a gene. Homozygous null mutants die between embryonic development days 11.5 (E11.5) and E12.5, indicating an essential role of Sema5A during embryonic development. Mutant embryos did not show any morphological defects that could account for the lethality of the mutation. A detailed analysis of the vascular system uncovered a role of Sema5A in the remodeling of the cranial blood vessels. In Sema5A null mutants, the complexity of the hierarchically organized branches of the cranial cardinal veins was decreased. Our results represent the first genetic analysis of the function of a class 5 semaphorin during embryonic development and identify a role of Sema5A in the regional patterning of the vasculature.

Dilated cerebral venous system observed in growth-restricted fetuses.

PURPOSE: The dilation of the fetal cerebral veins is a rare phenomenon that may be associated to a bad obstetric outcome, and is usually connected to antenatal thrombosis of the posterior dural venous sinuses. There are several descriptions of cerebral vein distension on magnetic resonance imaging (MRI), but all of them are detected postnatally. We present herein two cases of fetal antenatal cerebral dilation of the venous system, without any association to any sign of vein thrombosis, and a systematic review of literature regarding pathogenesis, diagnosis and outcomes associated to the antenatal detection of this condition with the use of MRI. MATERIALS AND METHODS: To identify potentially eligible studies, we searched PubMed, Scopus, Cochrane Library (all from inception to October 20th, 2016) and applied no language restrictions. RESULTS: The electronic database search provided a total of 22,843 results. After the exclusion of duplicates, manuscripts that resulted not relevant to the review based on title and abstract screening, and analysis of manuscripts eligible for full-text assessment, no papers were found related to the subject reported in the present manuscript. CONCLUSIONS: Our report adds importance to MRI as a tool in cases of complex ultrasound finding with the presence of fetal heart failure and deterioration of fetal growth, in order to improve the prognostic evaluation and patient?s counseling.

Confirmation of communication between deep venous drainage and the vein of galen after treatment of a vein of Galen aneurysmal malformation in an infant presenting with severe pulmonary hypertension.

Vein of Galen aneurysmal malformations (VGAM) are characterized by multiple arteriovenous connections draining into a markedly enlarged median draining vein. This ectatic vein is not the vein of Galen, but its embryonic precursor, the median prosencephalic vein of Markowski. During normal development, the posterior portion of the median prosencephalic vein persists as the vein of Galen, while its anterior portion regresses in parallel with the formation of the internal cerebral veins (ICV). It has been traditionally thought that, in children with a VGAM, the deep venous system does not connect to and, a fortiori, does not drain into the ectatic median prosencephalic vein/vein of Galen. This report describes a case of successfully treated VGAM in which the drainage of an ICV into the vein of Galen was only demonstrated by follow-up MR imaging and venography. The potential implications of this finding for the management of VGAMs are discussed.

Proatlantal intersegmental arteries of external carotid artery origin associated with Galen's vein malformation.

Carotid basilar anastomoses can occasionally persist beyond the embryonic period. These anomalies are most often incidentally detected in adulthood, during workups for unrelated pathologies. Persistence of the proatlantal intersegmental arteries is a rare form of primitive carotid-basilar anastomoses. Bilateral proatlantal inter- segmental arteries are an extremely rare occurrence, of which only 3 cases have been reported in the literature. An analysis of vascular anomalies associated with Galen's vein malformations revealed 3 children in whom persistence of type II proatlantal arteries was seen. These included one child in whom proatlantal arteries were persistent bilaterally. We report the clinical and angiographic findings and discuss the embryologic and therapeutic implications of this unique association.

Transvaginal Doppler assessment of fetal intracranial venous flow.

OBJECTIVE: To investigate physiologic blood-flow-velocity waveform patterns of the fetal cerebral venous system during normal pregnancies by transvaginal Doppler studies and to evaluate cases with abnormal venous-flow patterns. METHODS: Internal cerebral veins and the three dural sinuses, those of the superior sagittal sinus, vein of Galen, and straight sinus, were examined in normal cephalic-presenting fetuses of 20-40 weeks' gestation. For analysis, the venous index was defined as maximum minus minimum velocity divided by maximum velocity. Different cases with intracranial abnormalities were evaluated with emphasis on abnormal venous blood-flow patterns. RESULTS: Internal cerebral veins had pulsatile patterns with a venous index of 0.22 in 47.6% of fetuses, whereas all fetuses had pulsations in the dural sinuses. The vein of Galen had a significantly lower venous index (0.31) than the superior sagittal sinus (0.39) and the straight sinus (0.36), indicating that the amplitude of the intracranial venous pulsation might increase as the flow runs from the periphery toward the proximal portion. Significant regression lines of venous index were obtained, indicating the stability of the pulsation during pregnancy. A flat pattern of superior sagittal sinus flow was found in three cases of hydrocephalus and one of craniosynostosis. CONCLUSION: We showed the normal patterns of fetal cerebral venous blood-flow velocity and the abnormal patterns which might be associated with increased intracranial pressure. Doppler assessment of the intracranial venous system enabled us to evaluate intracranial abnormalities accompanied by increased intracranial pressure that might have prognostic clinical importance.