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The presence of morphometric abnormalities of the lateral ventricles, which can reflect focal or diffuse atrophic changes of nearby brain structures, is not well characterized in methamphetamine dependence. The current study was aimed to examine the size and shape alterations of the lateral ventricles in methamphetamine-dependent subjects.
Measurement of the width of fetal lateral ventricles (LVs) in prenatal ultrasound (US) images is essential for antenatal neuronographic assessment. However, the manual measurement of LV width is highly subjective and relies on the clinical experience of scanners. To deal with this challenge, we propose a computer-aided detection framework for automatic measurement of fetal LVs in two-dimensional US images. First, we train a deep convolutional network on 2,400 images of LVs to perform pixel-wise segmentation. Then, the number of pixels per centimeter (PPC), a vital parameter for quantifying the caliper in US images, is obtained via morphological operations guided by prior knowledge. The estimated PPC, upon conversion to a physical length, is used to determine the diameter of the LV by employing the minimum enclosing rectangle method. Extensive experiments on a self-collected dataset demonstrate that the proposed method achieves superior performance over manual measurement, with a mean absolute measurement error of 1.8 mm. The proposed method is fully automatic and is shown to be capable of reducing measurement bias caused by improper US scanning.
It is becoming increasingly evident that type 2 diabetes mellitus can have effects on global and regional brain morphology. Ventricular enlargement reflecting cerebral atrophy has been reported particularly in elderly type 2 diabetes patients. However, little is known about its timing through the disease course and morphological variability. Using the combined volumetric and advanced three-dimensional morphological approach, we identified differences in size and shape of the lateral ventricles between recent-onset type 2 diabetes patients and healthy individuals. High-resolution T1-weighted images were obtained from 23 type 2 diabetes patients whose illness duration was less than 1 year and 23 carefully matched healthy individuals. By volume measurement, we found enlarged lateral and third ventricles in type 2 diabetes patients, relative to healthy individuals (F(1,41 )= 7.96, P = 0.007; F(1,41) = 11.16, P = 0.002, respectively). Morphological analysis revealed that the expansion of lateral ventricles in the diabetic brain was prominent in the bilateral frontal horns. The current findings suggest that atrophic changes particularly of the anterior frontal lobe can occur as early as the first year after the clinical diagnosis of type 2 diabetes mellitus.
The subependymal zone at the lateral ventricular wall represents a major neurogenic niche of the adult mammalian brain and continuously provides new neurons for the olfactory bulb. A mosaic of stem and progenitor cells in this niche has the potential to respond to multiple signals including growth factors such as EGF. Recent studies using long-term ventricular infusion of EGF demonstrate intense cell proliferation around the ventricular wall, implicating the presence of EGF-reactive cells also outside the classical neurogenic lateral niche. Here we show that intraventricular injection of EGF induces within minutes CREB and ERK phosphorylation in astrocyte-like progenitor cells (type B cells) and EGF receptor-expressing transit-amplifying progenitor cells-both in the striatal and septal ventricular walls. EGF infusion for 6 days induced continued CREB and ERK activation in nestin+ cells paralleled by intense periventricular cell proliferation. In addition, the ependyma became EGF receptor-immunoreactive, revealed intense CREB phosphorylation and underwent partial de-differentiation. Our results demonstrate that intraventricular application of EGF induces CREB and ERK phosphorylation along the entire ventricular walls and thus permits a direct identification of EGF-responsive cell types. They further support the notion that not only the striatal ventricular wall where the SEZ is located but also the septal ventricular wall carries latent potential for the formation of neurons and glial cells.
Abnormal cellular growth and organization have been characterized in postmortem tissue from brains of autistic individuals, suggestive of pathology in a critical neurogenic niche, the subventricular zone (SVZ) of the brain lateral ventricles (LV). We examined cellular organization, cell proliferation, and constituents of the extracellular matrix such as N-sulfated heparan sulfate (HS) and laminin (LAM) in postmortem brain tissue from the LV-SVZ of young to elderly individuals with autism (n=4) and age-matched typically developing (TD) individuals (n=4) using immunofluorescence techniques. Strong and systematic reductions in HS immunofluorescence were observed in the LV-SVZ of the TD individuals with increasing age. For young through mature, but not elderly, autistic pair members, HS was reduced compared to their matched TDs. Cellular proliferation (Ki67+) was higher in the autistic individual of the youngest age-matched pair. These preliminary data suggesting that HS may be reduced in young to mature autistic individuals are in agreement with previous findings from the BTBR T+tf/J mouse, an animal model of autism; from mice with genetic modifications reducing HS; and with genetic variants in HS-related genes in autism. They suggest that aberrant extracellular matrix glycosaminoglycan function localized to the subventricular zone of the lateral ventricles may be a biomarker for autism, and potentially involved in the etiology of the disorder.
Schizophrenia, Schizoaffective, and Bipolar disorders share behavioral and phenomenological traits, intermediate phenotypes, and some associated genetic loci with pleiotropic effects. Volumetric abnormalities in brain structures are among the intermediate phenotypes consistently reported associated with these disorders. In order to examine the genetic underpinnings of these structural brain modifications, we performed genome-wide association analyses (GWAS) on 60 quantitative structural brain MRI phenotypes in a sample of 777 subjects (483 cases and 294 controls pooled together). Genotyping was performed with the Illumina PsychChip microarray, followed by imputation to the 1000 genomes multiethnic reference panel. Enlargement of the Temporal Horns of Lateral Ventricles (THLV) is associated with an intronic SNP of the gene NRXN1 (rs12467877, P = 6.76E-10), which accounts for 4.5% of the variance in size. Enlarged THLV is associated with psychosis in this sample, and with reduction of the hippocampus and enlargement of the choroid plexus and caudate. Eight other suggestively significant associations (P < 5.5E-8) were identified with THLV and 5 other brain structures. Although rare deletions of NRXN1 have been previously associated with psychosis, this is the first report of a common SNP variant of NRXN1 associated with enlargement of the THLV in psychosis.
Platelet-derived growth factor (PDGF) is important in central nervous system (CNS) development, and aberrant expression of PDGF and its receptors has been linked to developmental defects and brain tumorigenesis. We previously found that neural stem and progenitor cells in culture produce PDGF and respond to it by autocrine and/or paracrine signaling. We therefore aimed to examine CNS development after PDGF overexpression in neural stem cells in vivo. Transgenic mice were generated with PDGF-B under control of a minimal nestin enhancer element, which is specific for embryonic expression and will not drive adult expression in mice. The resulting mouse showed increased apoptosis in the developing striatum, which suggests a disturbed regulation of progenitor cells. Later in neurodevelopment, in early postnatal life, mice displayed enlarged lateral ventricles. This enlargement remained into adulthood and it was more pronounced in male mice than in transgenic female mice. Nevertheless, there was an overall normal composition of cell types and numbers in the brain and the transgenic mice were viable and fertile. Adult transgenic males, however, showed behavioral aberrations and locomotor dysfunction. Thus, a tightly regulated expression of PDGF during embryogenesis is required for normal brain development and function in mice.
Abnormalities in the corpus callosum (CC) and the lateral ventricles (LV) are hallmark features of schizophrenia. These abnormalities have been reported in chronic and in first episode schizophrenia (FESZ). Here we explore further associations between CC and LV in FESZ using diffusion tensor imaging (DTI).
Like in other vertebrates, the anterior part of the telencephalon of amphibians mainly consists of the olfactory bulb (OB), but different from higher vertebrates, the lateral telencephalic ventricles of larval Xenopus laevis expand deep into the anterior telencephalon. The neurogenic periventricular zone (PVZ) of the lateral ventricles generates new OB neurons throughout the animal's lifetime. We investigated the ultrastructural organization of the PVZ and found that within a time period of 24 h, 42.54 ± 6.65% of all PVZ cells were actively proliferating. Functional purinergic receptors are widespread in the central nervous system and their activation has been associated with many critical physiological processes, including the regulation of cell proliferation. In the present study we identified and characterized the purinergic system of the OB and the PVZ. ATP and 2MeSATP induced strong [Ca(2+)](i) increases in cells of both regions, which could be attenuated by purinergic antagonists. However, a more thorough pharmacological investigation revealed clear differences between the two brain regions. Cells of the OB almost exclusively express ionotropic P2X purinergic receptor subtypes, whereas PVZ cells express both ionotropic P2X and metabotropic P1 and P2Y receptor subtypes. The P2X receptors expressed in the OB are evidently not involved in the immediate processing of olfactory information.
To evaluate the error in segmented tissue images and to show the usefulness of the brain image in voxel-based morphometry (VBM) using Statistical Parametric Mapping (SPM) 12 software and 3D T1-weighted magnetic resonance images (3D-T1WIs) processed to simulate idiopathic normal pressure hydrocephalus (iNPH).
Injury to the preterm lateral ventricular perimeter (LVP), which contains the neural stem cells responsible for brain development, may contribute to the neurological sequelae of intraventricular hemorrhage (IVH) and post-hemorrhagic hydrocephalus of prematurity (PHH). This study utilizes diffusion MRI (dMRI) to characterize the microstructural effects of IVH/PHH on the LVP and segmented frontal-occipital horn perimeters (FOHP).
The ventricular system plays a vital role in blood-cerebrospinal fluid (CSF) exchange and interstitial fluid-CSF drainage pathways. CSF is formed in the specialized secretory tissue called the choroid plexus, which consists of epithelial cells, fenestrated capillaries and the highly vascularized stroma. Very little is currently known about the role played by the ventricles and the choroid plexus tissue in aging and Alzheimer's disease (AD).
The mouse Dach1 gene, involved in the development of the neocortex and the hippocampus, is expressed by neural stem cells (NSCs) during early neurogenesis, and its expression also continues in a subpopulation of cells in the dorsal part of the lateral ventricles (LV) of the adult mouse brain. In this study we aimed to elucidate the role of Dach1-expressing cells in adult neurogenesis/gliogenesis under physiological as well as post-ischemic conditions, employing transgenic mice in which the expression of green fluorescent protein (GFP) is controlled by the D6 promotor of the mouse Dach1 gene. A neurosphere-forming assay of GFP⁺ cells isolated from the dorsal part of the LV was carried out with subsequent differentiation in vitro. To elucidate the neurogenic/gliogenic potential of GFP⁺ cells in the dorsal part of the LV, in situ immunohistochemical/electrophysiological analyses of GFP⁺ cells in adult sham-operated brains (controls) and those after middle cerebral artery occlusion (MCAo) were performed. The GFP⁺ cells isolated from the dorsal part of the LV of controls formed neurospheres and differentiated solely into a glial phenotype, while those isolated after MCAo also gave rise to cells with the properties of neuronal precursors. In situ analyses revealed that GFP⁺ cells express the phenotype of adult NSCs or neuroblasts in controls as well as following ischemia. Following MCAo we found a significantly increased number of GFP⁺ cells expressing doublecortin as well as a number of GFP⁺ cells migrating through the rostral migratory stream into the olfactory bulb, where they probably differentiated into calretinin⁺ interneurons. Collectively, our results suggest the involvement of the mouse Dach1 gene in adult neurogenesis; cells expressing this gene exhibit the properties of adult NSCs or neuroblasts and respond to MCAo by enhanced neurogenesis.
The choroid plexus and cerebral ventricles are critical structures for the production of cerebral spinal fluid (CSF) and play an important role in regulating ion and metal transport in the brain, however many aspects of its roles in normal physiology and disease states, such as psychiatric illness, remain unknown. The choroid plexus is difficult to examine in vivo, and in situ ex vivo, and as such has typically been examined indirectly with radiolabeled tracers or ex vivo stains, making measurements of the endogenous K+, Cl-, and Ca+ distributions unreliable. In the present study, we directly examined the distribution of endogenous ions and biologically relevant transition metals in the choroid plexus and regions surrounding the ventricles (ventricle wall, cortex, corpus callosum, striatum) using X-ray fluorescence imaging (XFI). We find that the choroid plexus was rich in Cl- and Fe while K+ levels increase further from the ventricle as Cl- levels decrease, consistent with the known role of ion transporters in the choroid plexus CSF production. A polyI:C offspring displayed enlarged ventricles, elevated Cl- surrounding the ventricles, and intraventricular calcifications. These observations fit with clinical findings in patients with schizophrenia and suggest maternal treatment with polyI:C may lead to dysfunctional ion regulation in offspring. This study demonstrates the power of XFI for examining the endogenous elemental distributions of the ventricular system in healthy brain tissue as well as disease models.
Manual segmentation, which is tedious, time-consuming, and operator-dependent, is currently used as the gold standard to validate automatic and semiautomatic methods that quantify geometries from 2D and 3D MR images. This study examines the accuracy of manual segmentation and generalizes a strategy to eliminate its use. Trained individuals manually measured MR lateral ventricles images of normal and hydrocephalus infants from 1 month to 9.5 years of age. We created 3D-printed models of the lateral ventricles from the MRI studies and accurately estimated their volume by water displacement. MRI phantoms were made from the 3D models and images obtained. Using a previously developed artificial intelligence (AI) algorithm that employs four features extracted from the images, we estimated the ventricular volume of the phantom images. The algorithm was certified when discrepancies between the volumes-gold standards-yielded by the water displacement device and those measured by the automation were smaller than 2%. Then, we compared volumes after manual segmentation with those obtained with the certified automation. As determined by manual segmentation, lateral ventricular volume yielded an inter and intra-operator variation up to 50% and 48%, respectively, while manually segmenting saggital images generated errors up to 71%. These errors were determined by direct comparisons with the volumes yielded by the certified automation. The errors induced by manual segmentation are large enough to adversely affect decisions that may lead to less-than-optimal treatment; therefore, we suggest avoiding manual segmentation whenever possible.
Leakage of a small amount of intravenously administered gadolinium-based contrast agents (GBCAs) into the cerebrospinal fluid (CSF) space has been reported, even in healthy subjects without blood-brain barrier disruption. Several candidates including the choroid plexus and cortical veins have been proposed as the source of the leakage. The purpose of this study was to evaluate the distribution of intravenously administered GBCA leakage into the CSF by comparing the contrast enhancement of the cerebral cisterns to the lateral ventricles (LVs).
Structural brain anomalies are present at early phases of psychosis. The objective was to examine the impact of Catechol-O-Methyltransferase (COMT) gene variations on brain morphology in first-episode non-affective psychosis. We hypothesized that the low activity-COMT (COMT(L)) allele would be associated with the presence of structural brain changes as assessed by quantitative magnetic resonance imaging (MRI).
The 22q11.2 deletion syndrome (22q11DS) is a developmental genetic syndrome associated with a 30% risk for developing schizophrenia. Lateral ventricles and subcortical structures are abnormal in this syndrome as well as in schizophrenia. Here, we investigated whether these structures are related in young adults with 22q11DS with and without prodromal symptoms (PS) for schizophrenia and whether abnormalities in volumes are associated with global functioning. MR images were acquired on a 3T scanner from 51 individuals with 22q11DS and 30 healthy controls (mean age: 21±2 years). Correlations were performed to evaluate the relationship between ventricular and subcortical volumes, with Global Assessment of Functioning (GAF) and Premorbid Adjustment Scale (PAS) in each group. Lateral ventricular volumes correlated negatively with subcortical volumes in individuals with 22q11DS. In individuals with 22q11DS with PS only, GAF correlated positively with volumes of the lateral ventricles and negatively with subcortical volumes. PAS correlated negatively with lateral ventricle volumes, and positively with volumes of subcortical structures. The results suggest a common neurodevelopmental mechanism related to the growth of these brain structures. Further, the ratio between the volumes and clinical measures could potentially be used to characterize individuals with 22q11DS and those from the general population for the risk of the development of schizophrenia.
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