Dissertations / Theses on the topic 'Brain – Ventricles'

The intracranial system consists of three main basic components - the brain, the blood and the cerebrospinal fluid. The physiological processes of each of these individual components are complex and they are closely related to each other. Understanding them is important to explain the mechanisms behind neurostructural disorders such as hydrocephalus. This research project consists of three interrelated studies, which examine the mechanical properties of the brain at the macroscopic level, the mechanics of the brain during hydrocephalus and the study of fluid hydrodynamics in both the normal and hydrocephalic ventricles. The first of these characterizes the porous properties of the brain tissues. Results from this study show that the elastic modulus of the white matter is approximately 350Pa. The permeability of the tissue is similar to what has been previously reported in the literature and is of the order of 10-12m4/Ns. Information presented here is useful for the computational modeling of hydrocephalus using finite element analysis. The second study consists of a three dimensional finite element brain model. The mechanical properties of the brain found from the previous studies were used in the construction of this model. Results from this study have implications for mechanics behind the neurological dysfunction as observed in the hydrocephalic patient. Stress fields in the tissues predicted by the model presented in this study closely match the distribution of histological damage, focused in the white matter. The last study models the cerebrospinal fluid hydrodynamics in both the normal and abnormal ventricular system. The models created in this study were used to understand the pressure in the ventricular compartments. In this study, the hydrodynamic changes that occur in the cerebral ventricular system due to restrictions of the fluid flow at different locations of the cerebral aqueduct were determined. Information presented in this study may be important in the design of more effective shunts. The pressure that is associated with the fluid flow in the ventricles is only of the order of a few Pascals. This suggests that large transmantle pressure gradient may not be present in hydrocephalus.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2008.
This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Includes bibliographical references.
The brain ventricles are a conserved system of fluid-filled cavities within the brain that form during the earliest stages of brain development. Abnormal brain ventricle development has been correlated with neurodevelopmental disorders including hydrocephalus and schizophrenia. The mechanisms which regulate formation of the brain ventricles and the embryonic cerebrospinal fluid are poorly understood. Using the zebrafish, I initiated a study of brain ventricle development to define the genes required for this process. The zebrafish neural tube expands into the forebrain, midbrain, and hindbrain ventricles rapidly, over a four-hour window during mid-somitogenesis. In order to determine the genetic mechanisms that affect brain ventricle development, I studied 17 mutants previously-identified as having embryonic brain morphology defects and identified 3 additional brain ventricle mutants in a retroviral-insertion shelf-screen. Characterization of these mutants highlighted several processes involved in brain ventricle development, including cell proliferation, neuroepithelial shape changes (requiring epithelial integrity, cytoskeletal dynamics, and extracellular matrix function), embryonic cerebrospinal fluid secretion, and neuronal development. In particular, I investigated the role of the Na+K+ATPase alpha subunit, Atp1a1, in brain ventricle formation, elucidating novel roles for its function during brain development. This study was facilitated by the snakehead mutant, which has a mutation in the atp1a1 gene and undergoes normal brain ventricle morphogenesis but lacks ventricle inflation. Analysis of the temporal and spatial requirements of atp1a1 revealed an early requirement during formation, but not maintenance, of the neuroepithelium. I also demonstrated a later neuroepithelial requirement for Atp1a1-driven ion pumping that leads to brain ventricle inflation, likely by forming an osmotic gradient that drives fluid flow into the ventricle space.
(cont) Moreover, I have discovered that the forebrain ventricle is particularly sensitive to Na+K+ATPase function, and reducing or increasing Atp1a1 levels leads to a corresponding decrease or increase in ventricle size. Intriguingly, the Na+K+ATPase beta subunit atp1b3a, expressed in the forebrain and midbrain, is specifically required for their inflation, and thus may highlight a distinct regulatory mechanism for the forebrain and midbrain ventricles. In conclusion, my work has begun to define the complex mechanisms governing brain ventricle development, and I suggest that these mechanisms are conserved throughout the vertebrates.
by Laura Anne Lowery.
Ph.D.

Thesis (M.A.)--Georgia State University, 2005.
Title from title screen. Tricia Z. King, committee chair; Robin Morris, Mary Morris, committee members. Electronic text (102 p. : col. ill.) : digital, PDF file. Description based on contents viewed July 17, 2007. Includes bibliographical references (p. 91-102).

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Biology, 2004.
Includes bibliographical references (leaves 36-38).
The process by which the neural tube expands into three brain ventricles can be understood through genetic mutant analysis. Within the framework of a characterization of zebrafish mutants with brain ventricle phenotypes, I have developed an assay that looks for evidence of compromised gene expression patterns. I have shown that a cocktail of krox20, pax2a, shh, and zicl antisense RNA probes hybridizes to domains in the developing brain that reflect anterior, posterior, dorsal, and ventral axis specification. In addition, I have investigated the choroid plexus (CP) cells lining the brain ventricles in the zebrafish. Though we were unable to clearly identify the CP in the adult brain, we did identify two homologues in zebrafish of a conserved gene expressed in CP of vertebrates. We found that one of these genes, Drcpllb, was expressed from tailbud into early larva stage. Further, Drcpllb is expressed in neurula stage embryos in the anterior neural plate. Through these studies, we established an assay to analyze positional identity of cells in the neural tube and discovered a potential choroid plexus marker, shown its expression time course, and outlined its early expression pattern in the zebrafish.
by Catherine D. Wolf.
S.M.

As pediatric brain tumor survival rates increase, research has begun to further explore the influence of brain tumors and their treatment on functioning. The current study explored the ability of attention, learning, and memory abilities as measured by the Rey Auditory Verbal Learning Test and receptive language abilities as measured by the Peabody Picture Vocabulary Test to predict adaptive functioning on the Vineland Adaptive Behavior Scales. Children with tumors of the cerebellar region were hypothesized to display relative impairments in attention, whereas children with tumors of the third ventricle region were hypothesized to display relative impairments in learning and memory. The cognitive measures also were hypothesized to be differentially predictive of adaptive functioning performance. No significant differences were found between the groups on cognitive performance, but attention was the best predictor of adaptive functioning in the cerebellar group, whereas receptive verbal knowledge was the best predictor for the third ventricle group.

The third ventricle region houses several neuroanatomical structures that are primary components of the human memory system, and provides pathways through which these brain regions communicate with critical regions of the frontal and medial temporal lobes. Archival data was obtained for 42 children with cerebellar or third ventricle tumors, and was examined for tumor and treatment related confounds. Children with third ventricle tumors were hypothesized to exhibit; 1) better performance on a measure of auditory attention, 2) greater impairment in learning across trials, 3) greater memory loss over a 20-minute delay, and 4) greater impairment across delayed memory tests than the cerebellar group. Children with third ventricle tumors demonstrated significantly better auditory attention, but greater impairments in verbal learning, and greater verbal memory loss following a 20-minute delay. In contrast, children with third ventricle tumors did not demonstrate significantly greater memory impairments across long delay memory tests.

In an average year more than 1.7 million people will experience a traumatic brain injury (TBI) in the United States. It is known that atrophy occurs across a spectrum for TBI patients, ranging from mild to severe. Current conventional magnetic resonance imaging (MRI) methods are inconsistent in detecting this atrophy on the milder end of the spectrum. Also more contemporary imaging tools, although efficient, are too time consuming for clinical applicability. It is for these reasons that a quick and efficient measurement for detecting this atrophy is needed by clinicians. The measuring of third ventricle width had the potential to be this measurement, since it is known that ventricular dilation is an indirect measure of brain atrophy. This study used two different data sets acquired at multiple sites. A total of 152 TBI patients' MRI scans were analyzed with diagnosis ranging from mild to severe. They have been age matched with 97 orthopedic injury controls. All scans were analyzed using Freesurfer® auto-segmentation software to acquire cortical, subcortical, and ventricular volumes. These metrics were then used as a standard of efficacy which we tested the new third ventricle width protocol against. There was no statistically significant difference between the overall TBI group and OI group (Welch's F(1,238.435) = 1.091, p= .267). The complicated mild injury subgroup was significantly increased from the mild subgroup (p= .001, d= .87). The grand average third ventricle width measurement was the best prognosticator of all measures analyzed despite only predicting 35.1% of cases correctly. The findings suggest that the third ventricle width measurement is insensitive to atrophy between all groups as hypothesized.

Environ 15 millions d’enfants naissent prématurément chaque année dans le monde. Ces patients peuvent présenter des anomalies du développement cérébral qui peuvent causer des troubles du neuro-développement : paralysie cérébrale, surdité, cécité, retard du développement intellectuel, … Des études ont montrées que la quantification du volume des structures cérébrales est un bon indicateur qui permet de réduire ces risques et de les pronostiquer pour orienter les patients dans des parcours de soins adaptés pendant l’enfance. Cette thèse a pour objectif de montrer que l’échographie 3D pourrait être une alternative à l’IRM qui permettrait de quantifier le volume des structures cérébrales chez 100 % des prématurés. Ce travail se focalise plus particulièrement sur la segmentation des ventricules latéraux (VL) et des Thalami, il apporte trois contributions principales : le développement d’un algorithme de création de données échographiques 3D à partir d’échographie transfontanellaire 2D du cerveau du prématuré, la segmentation des ventricules latéraux et des thalami dans un temps clinique et l’apprentissage par des réseaux de neurones convolutionnels (CNN) de la position anatomique des ventricules latéraux. En outre, nous avons créé plusieurs bases de données annotées en partenariat avec le CH d’Avignon. L’algorithme de création de données échographiques 3D a été validé in-vivo où une précision de 0.69 ± 0.14 mm a été obtenue sur le corps calleux. Les VL et les thalami ont été segmentés par apprentissage profond avec l’architecture V-net. Les segmentations ont été réalisées en quelques secondes par ce CNN et des Dice respectifs de 0.828 ± 0.044 et de 0.891 ± 0.016 ont été obtenus. L’apprentissage de la position anatomique des VL a été réalisée via un CPPN (Compositional Pattern Producing Network), elle a permis d’améliorer significativement la précision de V-net lorsqu’il était composé de peu de couches, faisant passer le Dice de 0.524 ± 0.076 à 0.724 ± 0.107 dans le cas d’un réseau V-net à 7 couches. Cette thèse montre qu’il est possible de segmenter automatiquement, avec précision et dans un temps clinique, des structures cérébrales de l’enfant prématuré dans des données échographiques 3D. Cela montre qu’une échographie 3D de haute qualité pourrait être utilisée en routine clinique pour quantifier le volume des structures cérébrales et ouvre la voie aux études d’évaluation de son bénéfice pour les patients
About 15 million children are born prematurely each year worldwide. These patients are likely to suffer from brain abnormalities that can cause neurodevelopmental disorders: cerebral palsy, deafness, blindness, intellectual development delay, … Studies have shown that the volume of brain structures is a good indicator which enables to reduce and predict these risks in order to guide patients through appropriate care pathways during childhood. This thesis aims to show that 3D ultrasound could be an alternative to MRI that would enable to quantify the volume of brain structures in all premature infants. This work focuses more particularly on the segmentation of the lateral ventricles (VL) and thalami. Its four main contributions are: the development of an algorithm which enables to create 3D ultrasound data from 2D transfontanellar ultrasound of the premature brain, the segmentation of thigh quality he lateral ventricles and thalami in clinical time and the learning by a convolutional neural networks (CNN) of the anatomical position of the lateral ventricles. In addition, we have created several annotated databases in partnership with the CH of Avignon. Our reconstruction algorithm was used to reconstruct 25 high-quality ultrasound volumes. It was validated in-vivo where an accuracy 0.69 ± 0.14 mm was obtained on the corpus callosum. The best segmentation results were obtained with the V-net, a 3D CNN, which segmented the CVS and the thalami with respective Dice of 0.828± 0.044 and 0.891±0.016 in a few seconds. Learning the anatomical position of the CVS was achieved by integrating a CPPN (Compositional Pattern Producing Network) into the CNNs. It significantly improved the accuracy of CNNs when they had few layers. For example, in the case of the 7-layer V-net network, the Dice has increased from 0.524± 0.076 to 0.724±0.107. This thesis shows that it is possible to automatically segment brain structures of the premature infant into 3D ultrasound data with precision and in a clinical time. This proves that high quality 3D ultrasound could be used in clinical routine to quantify the volume of brain structures and paves the way for studies to evaluate its benefit to patients

Specific regions within the adult mammalian brain maintain the ability to generate neurons. The largest of these, the ventricular-subventricular zone (V-SVZ), comprises the entire lateral wall of the lateral ventricles. Here, a subset of glial fibrillary acid protein (GFAP)-positive astrocytes (B cells) gives rise to neurons and oligodendrocytes throughout life. This process of neurogenesis involves quiescent B cells becoming proliferative (epidermal growth factor receptor (EGFR)-positive) and giving rise to neuroblasts via transit amplifying precursors. The neuroblasts then migrate through the rostral migratory stream (RMS) to the olfactory bulbs (OBs), where they mature into neurons. Studying the stem cells in the V-SVZ has been hindered by the shortage of molecular markers to selectively target them. Using microarray and qPCR analysis of putative quiescent neural stem cells we determined that they were enriched for PDGFRβ mRNA. We used immunostaining to determine the in vivo identity of PDGFRβ+ cells, and discovered that only GFAP+ cells within the V-SVZ stem cell lineage express PDGFRβ. Moreover, these PDGFRβ+ B cells contact the ventricle at the center of ependymal pinwheel structures and the vast majority of them are EGFR-. Importantly, the V-SVZ/RMS/OBcore axis was highly enriched for PDGFRβ expression compared with other brain regions. Detailed morphological analyses of PDGFRβ+ B cells revealed primary cilia at their apical process in contact with the ventricle and long radial processes contacting blood vessels deep within the V-SVZ, both of which are characteristics of adult neural stem cells. When PDGFRβ+ cells were lineage traced in vivo they formed olfactory bulb neurons. Using fluorescence-activated cell sorting (FACS) to purify PDGFRβ+ astrocytes we discovered this receptor is expressed by all adult V-SVZ neural stem cells, including a novel population of EGFR+ PDGFRβ+ cells which correspond to the activated neural stem cells. RNA-sequencing analysis of the purified populations revealed that PDGFRβ+ EGFR+ cells possess a transcriptional profile intermediate between quiescent neural stem cells and actively proliferating GFAP- progenitor cells. Finally, when PDGFRβ is deleted in adult GFAP+ NSCs we observe a decrease in EGFR+ and Dcx+ progenitor cells, together with an increase in quiescent GFAP+ astrocytes. A larger proportion of these mutant cells come in contact with the ventricular lumen, suggesting that PDGFRβ is required for V-SVZ astrocytes to act as stem cells, possibly by mediating interactions with their niche. Taken together, these data identify PDGFRβ as a novel marker for adult V-SVZ neural stem cells that is an important regulator of their stem cell capabilities.

Congenital heart disease (CHD) is the most common congenital anomaly, with single ventricle (SV) defects accounting for nearly 10% of all CHD. SV defects tend to be the most severe forms of CHD: all patients born with SV require multiple open heart surgeries, often beginning in the neonatal period, ultimately leading to the Fontan procedure. Due to improvements in surgical procedures and medical care, more patients are surviving into adolescence and adulthood. Brain imaging and pathology studies have shown that patients with SV have differences in brain structure and metabolism even before the first surgery, and as early as in utero. Furthermore, a significant number of patients have new or more severe lesions after the initial surgery, and many still have brain abnormalities into early childhood. However, there are no detailed brain structural data of SV patients in adolescence. Our group recruited a large cohort of post-Fontan SV patients aged 10-19 years. Separate analyses of neuropsychological and behavioral outcomes in these patients show deficits in multiple areas of cognition, increased rates of attention deficit-hyperactivity disorder (ADHD), and increased use of remedial and/or special education services compared to a control group. Post-Fontan adolescents have more gross brain abnormalities, including evidence of chronic ischemic stroke. Furthermore, there are widespread reductions in cortical and subcortical gray matter volume and cortical thickness, some of which are associated with medical and surgical variables. Diffusion tensor imaging (DTI) analyses show widespread areas of altered white matter microstructure in deep subcortical and cerebellar white matter. In this dissertation, I use graph theory methods to characterize structural connectivity based on gray matter (cortical thickness covariance) and white matter (DTI tractography), and examine associations between brain structure and neurodevelopment. I found that brain network connectivity differs in post-Fontan patients compared with controls, both at the global and regional level. Additionally, deficits in overall network structure were associated with impaired neurodevelopment in several domains, including general intelligence, executive function, and visuospatial skills. These data suggest that early neuroprotection should be a major focus in the care of SV patients, with the goal of improving long-term neurodevelopmental outcomes.

碩士
國立成功大學
醫學工程學系
81
In this study, an automated system which can compute the volume ratio of brain parenchyma and cerebral spinal fluid is built for use in clinics as a diagnosis reference. From the results of the phantoms measurements, the average error is about 2.7% for 5 mm scans and 4.3% for 10 mm in a skull filled with 100 cc water ball experiment. However, there's no significant difference between 10 mm and 5 mm scans in the 10 patients measure- ments. Based upon this consequence, it is suggested that the patient may be scanned just by 10 mm interval for saving time and reducing radiation dosage. Some image segmentation methods are also discussed in this thesis, such as pyramid , Laplacian-of-Gaussian operator, and a newly proposed image segmentation scheme, which is so called "Supervised image segmentation scheme." For an image of the size 320x320 , it takes about 10-20 seconds for processing on a DEC 5000/200 workstation with this scheme. After segmentation, the volume measurements of CSF and 3D- display of the brain ventricle are both satisfactorily presented.

The neural cell adhesion molecule L1 is a member of the immunoglobulin superfamily and it mediates many adhesive interactions during brain development. Mutations in the L1 gene are associated with a spectrum of X-linked neurological disorders known as CRASH or L1 syndrome. The objective of this thesis was to use the zebrafish model to investigate the molecular mechanisms of L1 functions and the pathological effects of its mutations. Zebrafish has two L1 homologs, L1.1 and L1.2. Inhibition of L1.1 expression by antisense morpholino oligonucleotides resulted in phenotypes that showed resemblances to L1 patients. However, knockdown of L1.2 expression did not result in notable neural defects. Furthermore, analysis of the expression pattern of L1.1 has led to the discovery of a novel soluble L1.1 isoform, L1.1s. L1.1s is an alternatively spliced form of L1.1, consisting of the first four Ig-like domains and thus a soluble secreted protein. L1.1 morphants exhibited disorganized brain structures with many having an enlarged fourth/hindbrain ventricle. Further characterization revealed aberrations in ventricular polarity, cell patterning and proliferation and helped differentiate the functions of L1.1 and L1.1s. While L1.1 plays a pivotal role in axonal outgrowth and guidance, L1.1s is crucial to brain ventricle formation. Significantly, L1.1s mRNA rescued many anomalies in the morphant brain, but not the trunk phenotypes. Receptor analysis confirmed that L1.1 undergoes heterophilic interactions with neuropilin-1a (Nrp1a). Peptide inhibition studies demonstrated further the involvement of L1.1s in neuroepithelial cell migration during ventricle formation. In the spinal cord, spinal primary motoneurons expressed exclusively the full-length L1.1, and abnormalities in axonal projections of morphants could be rescued only by L1.1 mRNA. Further studies showed that a novel interaction between the Ig3 domain of L1.1 and Unplugged, the zebrafish muscle specific kinase (MuSK), is crucial to motor axonal growth. Together, these results demonstrate that the different parts of L1.1 contribute to the diverse functions of L1.1 in neural development.

Plasma levels of B-type natriuretic peptide (BNP) are a strong and independent predictor of prognosis in patients with advanced heart failure (CHF). However, the importance of this biomarker has been documented only in CHF of common causes such as dilated or ischemic cardiomyopathy. We hypothesized that BNP can serve as a strong predictor of end-stage CHF in group of patients with advanced CHF due to congenital heart disease (CHD) with the right ventricle in systemic position (SRV). The second hypothesis was that BNP monitoring in patients with implanted left ventricular assist device (LVAD) Heart Mate II could detect serious complications which negatively affect prognosis. We performed a retrospective analysis in 28 consecutive patients with severe systolic dysfunction of the SRV (ejection fraction 23 ± 6%) evaluated as heart transplant (HTx) candidates between May 2007 and October 2014. During a median follow-up of 29 months (interquartile range, 9-50), 14 pts reached primary endpoints of the study (death, urgent HTx, and LVAD implantation). We have considered these events equivalent to end-stage CHF. Using ROC analysis, we identified the first measured value of BNP as the strongest predictor of prognosis with the area under the curve (AUC) of 1.00, followed by the New York Heart Association...