Depth relationships and measures of tissue thickness in dorsal midbrain.

Dorsal human midbrain contains two nuclei with clear laminar organization, the superior and inferior colliculi. These nuclei extend in depth between the superficial dorsal surface of midbrain and a deep midbrain nucleus, the periaqueductal gray matter (PAG). The PAG, in turn, surrounds the cerebral aqueduct (CA). This study examined the use of two depth metrics to characterize depth and thickness relationships within dorsal midbrain using the superficial surface of midbrain and CA as references. The first utilized nearest-neighbor Euclidean distance from one reference surface, while the second used a level-set approach that combines signed distances from both reference surfaces. Both depth methods provided similar functional depth profiles generated by saccadic eye movements in a functional MRI task, confirming their efficacy for delineating depth for superficial functional activity. Next, the boundaries of the PAG were estimated using Euclidean distance together with elliptical fitting, indicating that the PAG can be readily characterized by a smooth surface surrounding PAG. Finally, we used the level-set approach to measure tissue depth between the superficial surface and the PAG, thus characterizing the variable thickness of the colliculi. Overall, this study demonstrates depth-mapping schemes for human midbrain that enables accurate segmentation of the PAG and consistent depth and thickness estimates of the superior and inferior colliculi.

Neurocomputational Consequences of Evolutionary Connectivity Changes in Perisylvian Language Cortex.

The human brain sets itself apart from that of its primate relatives by specific neuroanatomical features, especially the strong linkage of left perisylvian language areas (frontal and temporal cortex) by way of the arcuate fasciculus (AF). AF connectivity has been shown to correlate with verbal working memory-a specifically human trait providing the foundation for language abilities-but a mechanistic explanation of any related causal link between anatomical structure and cognitive function is still missing. Here, we provide a possible explanation and link, by using neurocomputational simulations in neuroanatomically structured models of the perisylvian language cortex. We compare networks mimicking key features of cortical connectivity in monkeys and humans, specifically the presence of relatively stronger higher-order "jumping links" between nonadjacent perisylvian cortical areas in the latter, and demonstrate that the emergence of working memory for syllables and word forms is a functional consequence of this structural evolutionary change. We also show that a mere increase of learning time is not sufficient, but that this specific structural feature, which entails higher connectivity degree of relevant areas and shorter sensorimotor path length, is crucial. These results offer a better understanding of specifically human anatomical features underlying the language faculty and their evolutionary selection advantage.SIGNIFICANCE STATEMENT Why do humans have superior language abilities compared to primates? Recently, a uniquely human neuroanatomical feature has been demonstrated in the strength of the arcuate fasciculus (AF), a fiber pathway interlinking the left-hemispheric language areas. Although AF anatomy has been related to linguistic skills, an explanation of how this fiber bundle may support language abilities is still missing. We use neuroanatomically structured computational models to investigate the consequences of evolutionary changes in language area connectivity and demonstrate that the human-specific higher connectivity degree and comparatively shorter sensorimotor path length implicated by the AF entail emergence of verbal working memory, a prerequisite for language learning. These results offer a better understanding of specifically human anatomical features for language and their evolutionary selection advantage.

Numerical Cerebrospinal System Modeling in Fluid-Structure Interaction.

OBJECTIVE: Cerebrospinal fluid (CSF) stroke volume in the aqueduct is widely used to evaluate CSF dynamics disorders. In a healthy population, aqueduct stroke volume represents around 10% of the spinal stroke volume while intracranial subarachnoid space stroke volume represents 90%. The amplitude of the CSF oscillations through the different compartments of the cerebrospinal system is a function of the geometry and the compliances of each compartment, but we suspect that it could also be impacted be the cardiac cycle frequency. To study this CSF distribution, we have developed a numerical model of the cerebrospinal system taking into account cerebral ventricles, intracranial subarachnoid spaces, spinal canal and brain tissue in fluid-structure interactions. MATERIALS AND METHODS: A numerical fluid-structure interaction model is implemented using a finite-element method library to model the cerebrospinal system and its interaction with the brain based on fluid mechanics equations and linear elasticity equations coupled in a monolithic formulation. The model geometry, simplified in a first approach, is designed in accordance with realistic volume ratios of the different compartments: a thin tube is used to mimic the high flow resistance of the aqueduct. CSF velocity and pressure and brain displacements are obtained as simulation results, and CSF flow and stroke volume are calculated from these results. RESULTS: Simulation results show a significant variability of aqueduct stroke volume and intracranial subarachnoid space stroke volume in the physiological range of cardiac frequencies. CONCLUSIONS: Fluid-structure interactions are numerous in the cerebrospinal system and difficult to understand in the rigid skull. The presented model highlights significant variations of stroke volumes under cardiac frequency variations only.

Cerebrospinal fluid and blood flow patterns in idiopathic normal pressure hydrocephalus.

OBJECTIVES: Increased aqueduct cerebrospinal fluid (CSF) flow pulsatility and, recently, a reversed CSF flow in the aqueduct have been suggested as hallmarks of idiopathic normal pressure hydrocephalus (INPH). However, these findings have not been adequately confirmed. Our objective was to investigate the flow of blood and CSF in INPH, as compared to healthy elderly, in order to clarify which flow parameters are related to the INPH pathophysiology. MATERIALS AND METHODS: Sixteen INPH patients (73 years) and 35 healthy subjects (72 years) underwent phase-contrast magnetic resonance imaging (MRI). Measurements included aqueduct and cervical CSF flow, total arterial inflow (tCBF; i.e. carotid + vertebral arteries), and internal jugular vein flow. Flow pulsatility, net flow, and flow delays were compared (multiple linear regression, correcting for sex and age). RESULTS: Aqueduct stroke volume was higher in INPH than healthy (148±95 vs 90±50 mL, P<.05). Net aqueduct CSF flow was similar in magnitude and direction. The cervical CSF stroke volume was lower (P<.05). The internal carotid artery net flow was lower in INPH (P<.05), although tCBF was not. No differences were found in internal jugular vein flow or flow delays. CONCLUSIONS: The typical flow of blood and CSF in INPH was mainly characterized by increased CSF pulsatility in the aqueduct and reduced cervical CSF pulsatility. The direction of mean net aqueduct CSF flow was from the third to the fourth ventricle. Our findings may reflect the altered distribution of intracranial CSF volume in INPH, although the causality of these relationships is unclear.

Inspiration is the major regulator of human CSF flow.

The mechanisms behind CSF flow in humans are still not fully known. CSF circulates from its primary production sites at the choroid plexus through the brain ventricles to reach the outer surface of the brain in the subarachnoid spaces from where it drains into venous bloodstream and cervical lymphatics. According to a recent concept of brain fluid transport, established in rodents, CSF from the brain surface also enters the brain tissue along para-arterial routes and exits through paravenous spaces again into subarachnoid compartments. This unidirectional flow is mainly driven by arterial pulsation. To investigate how CSF flow is regulated in humans, we applied a novel real-time magnetic resonance imaging technique at high spatial (0.75 mm) and temporal (50 ms) resolution in healthy human subjects. We observed significant CSF flow exclusively with inspiration. In particular, during forced breathing, high CSF flow was elicited during every inspiration, whereas breath holding suppressed it. Only a minor flow component could be ascribed to cardiac pulsation. The present results unambiguously identify inspiration as the most important driving force for CSF flow in humans. Inspiratory thoracic pressure reduction is expected to directly modulate the hydrostatic pressure conditions for the low-resistance paravenous, venous, and lymphatic clearance routes of CSF. Furthermore, the experimental approach opens new clinical opportunities to study the pathophysiology of various forms of hydrocephalus and to design therapeutic strategies in relation to CSF flow alterations.

Aqueductal cerebrospinal fluid pulsatility in healthy individuals is affected by impaired cerebral venous outflow.

PURPOSE: To investigate cerebrospinal fluid (CSF) dynamics in the aqueduct of Sylvius (AoS) in chronic cerebrospinal venous insufficiency (CCSVI)-positive and -negative healthy individuals using cine phase contrast imaging. MATERIALS AND METHODS: Fifty-one healthy individuals (32 CCSVI-negative and 19 age-matched CCSVI-positive subjects) were examined using Doppler sonography (DS). Diagnosis of CCSVI was established if subjects fulfilled ≥2 venous hemodynamic criteria on DS. CSF flow and velocity measures were quantified using a semiautomated method and compared with clinical and routine 3T MRI outcomes. RESULTS: CCSVI was associated with increased CSF pulsatility in the AoS. Net positive CSF flow was 32% greater in the CCSVI-positive group compared with the CCSVI-negative group (P = 0.008). This was accompanied by a 28% increase in the mean aqueductal characteristic signal (ie, the AoS cross-sectional area over the cardiac cycle) in the CCSVI-positive group compared with the CCSVI-negative group (P = 0.021). CONCLUSION: CSF dynamics are altered in CCSVI-positive healthy individuals, as demonstrated by increased pulsatility. This is accompanied by enlargement of the AoS, suggesting that structural changes may be occurring in the brain parenchyma of CCSVI-positive healthy individuals.

Validating the accuracy of real-time phase-contrast MRI and quantifying the effects of free breathing on cerebrospinal fluid dynamics.

BACKGROUND: Understanding of the cerebrospinal fluid (CSF) circulation is essential for physiological studies and clinical diagnosis. Real-time phase contrast sequences (RT-PC) can quantify beat-to-beat CSF flow signals. However, the detailed effects of free-breathing on CSF parameters are not fully understood. This study aims to validate RT-PC's accuracy by comparing it with the conventional phase-contrast sequence (CINE-PC) and quantify the effect of free-breathing on CSF parameters at the intracranial and extracranial levels using a time-domain multiparametric analysis method. METHODS: Thirty-six healthy participants underwent MRI in a 3T scanner for CSF oscillations quantification at the cervical spine (C2-C3) and Sylvian aqueduct, using CINE-PC and RT-PC. CINE-PC uses 32 velocity maps to represent dynamic CSF flow over an average cardiac cycle, while RT-PC continuously quantifies CSF flow over 45-seconds. Free-breathing signals were recorded from 25 participants. RT-PC signal was segmented into independent cardiac cycle flow curves (Qt) and reconstructed into an averaged Qt. To assess RT-PC's accuracy, parameters such as segmented area, flow amplitude, and stroke volume (SV) of the reconstructed Qt from RT-PC were compared with those derived from the averaged Qt generated by CINE-PC. The breathing signal was used to categorize the Qt into expiratory or inspiratory phases, enabling the reconstruction of two Qt for inspiration and expiration. The breathing effects on various CSF parameters can be quantified by comparing these two reconstructed Qt. RESULTS: RT-PC overestimated CSF area (82.7% at aqueduct, 11.5% at C2-C3) compared to CINE-PC. Stroke volumes for CINE-PC were 615 mm³ (aqueduct) and 43 mm³ (spinal), and 581 mm³ (aqueduct) and 46 mm³ (spinal) for RT-PC. During thoracic pressure increase, spinal CSF net flow, flow amplitude, SV, and cardiac period increased by 6.3%, 6.8%, 14%, and 6%, respectively. Breathing effects on net flow showed a significant phase difference compared to the other parameters. Aqueduct-CSF flows were more affected by breathing than spinal-CSF. CONCLUSIONS: RT-PC accurately quantifies CSF oscillations in real-time and eliminates the need for cardiac synchronization, enabling the quantification of the cardiac and breathing components of CSF flow. This study quantifies the impact of free-breathing on CSF parameters, offering valuable physiological references for understanding the effects of breathing on CSF dynamics.

Seismic response analysis of double-trough aqueduct considering fluid-structure interaction effect.

At present, the crude fluid-structure interaction analysis model cannot accurately characterize the interaction mechanism between aqueduct and water under earthquake action. In order to solve this problem, this paper analyzes the seismic response of the double-tank aqueduct under the action of earthquake by using the shaker test and the VOF (Volume of Fluid) method considering the free liquid level from the perspective of fluid-solid bidirectional coupling, explores whether the liquid movement in the double tank is consistent and the shock absorption effect of different water levels on the aqueduct, and analyzes the amplitude of free liquid level sloshing and the change of horizontal dynamic pressure caused by water level change from the generation mechanism of TLD (Liquid tuning dampers). The results show that the liquid movement in the two tanks in the double-channel aqueduct is basically the same under the action of earthquake, and the TLD effect of the liquid gradually increases with the increase of the water level in the aqueduct, and the maximum peak shock absorption rate is 63.4% at the maximum peak and 50.4% in numerical simulation. The shaking amplitude of the liquid is positively correlated with the water level height, and the magnitude of the shaking amplitude also reflects the magnitude of the moving water pressure.

Biomechanical effects of hyper-dynamic cerebrospinal fluid flow through the cerebral aqueduct in idiopathic normal pressure hydrocephalus patients.

Normal pressure hydrocephalus (NPH) is an intracranial disease characterized by an abnormal accumulation of cerebrospinal fluid (CSF) in brain ventricles within the normal range of intracranial pressure. Most NPH in aged patients is idiopathic (iNPH) and without any prior history of intracranial diseases. Although an abnormal increase of CSF stroke volume (hyper-dynamic CSF flow) in the aqueduct between the third and fourth ventricles has received much attention as a clinical evaluation index in iNPH patients, the biomechanical effects of this flow on iNPH pathophysiology are poorly understood. This study aimed to clarify the potential biomechanical effects of hyper-dynamic CSF flow through the aqueduct of iNPH patients using magnetic resonance imaging-based computational simulations. Ventricular geometries and CSF flow rates through aqueducts of 10 iNPH patients and 10 healthy control subjects were obtained from multimodal magnetic resonance images, and these CSF flow fields were simulated using computational fluid dynamics. As biomechanical factors, we evaluated wall shear stress on the ventricular wall and the extent of flow mixing, which potentially disturbs the CSF composition in each ventricle. The results showed that the relatively high CSF flow rate and large and irregular shapes of the aqueduct in iNPH resulted in large wall shear stresses localized in relatively narrow regions. Furthermore, the resulting CSF flow showed a stable cyclic motion in control subjects, whereas strong mixing during transport through the aqueduct was found in patients with iNPH. These findings provide further insights into the clinical and biomechanical correlates of NPH pathophysiology.

Quantification of normal CSF flow through the aqueduct using PC-cine MRI at 3T.

INTRODUCTION: Quantification of cerebrospinal fluid (CSF) flow through the cerebral aqueduct is of paramount importance in patients with hydrocephalus. The purpose of this study was to evaluate the normal CSF flow measurements at three different anatomical levels of the aqueduct utilizing 3-Tesla (3 T) magnetic resonance imaging. MATERIALS AND METHODS: The CSF hydrodynamics in 22 healthy volunteers were evaluated. Phase-contrast cine MRI was performed on a 3 T General Electric MR system (GE Medical Systems, Milwaukee, WI, USA). A cardiac-gated, flow-compensated GRE sequence with flow encoding was used, and the aqueduct was visualized using a sagittal T1 FLAIR sequence. Velocity maps were acquired at three different anatomical levels. Region-of-interest (ROI) analysis was performed. RESULTS: CSF flow velocities were slightly increased at the upper in comparison with the lower part of the aqueduct. The mean values for the peak positive and negative velocity and the mean average flow were calculated for both ROIs. DISCUSSION/CONCLUSIONS: CSF peak positive velocity, peak negative velocity, and mean flow through the aqueduct were calculated in 22 young healthy volunteers performed at 3 T. Our measurements did not show significant difference compared with the reported measurements obtained at 1.5 T. Slight differences were observed in the CSF hydrodynamic measurements, depending on the anatomical level of the aqueduct; however, they did not vary significantly.

Physical phantom of craniospinal hydrodynamics.

INTRODUCTION: Inside the craniospinal system, blood, and cerebrospinal fluid (CSF) interactions occurring through volume exchanges are still not well understood. We built a physical model of this global hydrodynamic system. The main objective was to study, in controlled conditions, CSF-blood interactions to better understand the phenomenon underlying pathogenesis of hydrocephalus. MATERIALS AND METHODS: A structure representing the cranium is connected to the spinal channel. The cranium is divided into compartments mimicking anatomical regions such as ventricles or aqueduct cerebri. Resistive and compliant characteristics of blood and CSF compartments can be assessed or measured using pressure and flow sensors incorporated in the model. An arterial blood flow input is generated by a programmable pump. Flows and pressures inside the system are simultaneously recorded. RESULTS: Preliminary results show that the model can mimic venous and CSF flows in response to arterial pressure input. Pulse waveforms and volume flows were measured and confirmed that they partially replicated the data previously obtained with phase-contrast magnetic resonance imaging. The phantom shows that CSF oscillations directly result from arteriovenous flow, and intracranial pressure measurements show that the model obeys an exponential relationship between pressure and intracranial volume expansion. CONCLUSION: The phantom will be useful to investigate the hydrodynamic hypotheses underlying development of hydrocephalus.

Parasagittal dural space and cerebrospinal fluid (CSF) flow across the lifespan in healthy adults.

BACKGROUND: Recent studies have suggested alternative cerebrospinal fluid (CSF) clearance pathways for brain parenchymal metabolic waste products. One fundamental but relatively under-explored component of these pathways is the anatomic region surrounding the superior sagittal sinus, which has been shown to have relevance to trans-arachnoid molecular passage. This so-called parasagittal dural (PSD) space may play a physiologically significant role as a distal intracranial component of the human glymphatic circuit, yet fundamental gaps persist in our knowledge of how this space changes with normal aging and intracranial bulk fluid transport. METHODS: We re-parameterized MRI methods to assess CSF circulation in humans using high resolution imaging of the PSD space and phase contrast measures of flow through the cerebral aqueduct to test the hypotheses that volumetric measures of PSD space (1) are directly related to CSF flow (mL/s) through the cerebral aqueduct, and (2) increase with age. Multi-modal 3-Tesla MRI was applied in healthy participants (n = 62; age range = 20-83 years) across the adult lifespan whereby phase contrast assessments of CSF flow through the aqueduct were paired with non-contrasted T1-weighted and T2-weighted MRI for PSD volumetry. PSD volume was extracted using a recently validated neural networks algorithm. Non-parametric regression models were applied to evaluate how PSD volume related to tissue volume and age cross-sectionally, and separately how PSD volume related to CSF flow (significance criteria: two-sided p < 0.05). RESULTS: A significant PSD volume enlargement in relation to normal aging (p < 0.001, Spearman's-[Formula: see text] = 0.6), CSF volume (p < 0.001, Spearman's-[Formula: see text] = 0.6) and maximum CSF flow through the aqueduct of Sylvius (anterograde and retrograde, p < 0.001) were observed. The elevation in PSD volume was not significantly related to gray or white matter tissue volumes. Findings are consistent with PSD volume increasing with age and bulk CSF flow. CONCLUSIONS: Findings highlight the feasibility of quantifying PSD volume non-invasively in vivo in humans using machine learning and non-contrast MRI. Additionally, findings demonstrate that PSD volume increases with age and relates to CSF volume and bi-directional flow. Values reported should provide useful normative ranges for how PSD volume adjusts with age, which will serve as a necessary pre-requisite for comparisons to persons with neurodegenerative disorders.

Cerebrospinal fluid flow in normal beagle dogs analyzed using magnetic resonance imaging.

BACKGROUND: Diseases related to cerebrospinal fluid flow, such as hydrocephalus, syringomyelia, and Chiari malformation, are often found in small dogs. Although studies in human medicine have revealed a correlation with cerebrospinal fluid flow in these diseases by magnetic resonance imaging, there is little information and no standard data for normal dogs. OBJECTIVES: The purpose of this study was to obtain cerebrospinal fluid flow velocity data from the cerebral aqueduct and subarachnoid space at the foramen magnum in healthy beagle dogs. METHODS: Six healthy beagle dogs were used in this experimental study. The dogs underwent phase-contrast and time-spatial labeling inversion pulse magnetic resonance imaging. Flow rate variations in the cerebrospinal fluid were observed using sagittal time-spatial labeling inversion pulse images. The pattern and velocity of cerebrospinal fluid flow were assessed using phase-contrast magnetic resonance imaging within the subarachnoid space at the foramen magnum level and the cerebral aqueduct. RESULTS: In the ventral aspect of the subarachnoid space and cerebral aqueduct, the cerebrospinal fluid was characterized by a bidirectional flow throughout the cardiac cycle. The mean ± SD peak velocities through the ventral and dorsal aspects of the subarachnoid space and the cerebral aqueduct were 1.39 ± 0.13, 0.32 ± 0.12, and 0.76 ± 0.43 cm/s, respectively. CONCLUSIONS: Noninvasive visualization of cerebrospinal fluid flow movement with magnetic resonance imaging was feasible, and a reference dataset of cerebrospinal fluid flow peak velocities was obtained through the cervical subarachnoid space and cerebral aqueduct in healthy dogs.

Connection Input Mapping and 3D Reconstruction of the Brainstem and Spinal Cord Projections to the CSF-Contacting Nucleus.

Objective: To investigate whether the CSF-contacting nucleus receives brainstem and spinal cord projections and to understand the functional significance of these connections. Methods: The retrograde tracer cholera toxin B subunit (CB) was injected into the CSF-contacting nucleus in Sprague-Dawley rats according the previously reported stereotaxic coordinates. After 7-10 days, these rats were perfused and their brainstem and spinal cord were sliced (thickness, 40 µm) using a freezing microtome. All the sections were subjected to CB immunofluorescence staining. The distribution of CB-positive neuron in different brainstem and spinal cord areas was observed under fluorescence microscope. Results: The retrograde labeled CB-positive neurons were found in the midbrain, pons, medulla oblongata, and spinal cord. Four functional areas including one hundred and twelve sub-regions have projections to the CSF-contacting nucleus. However, the density of CB-positive neuron distribution ranged from sparse to dense. Conclusion: Based on the connectivity patterns of the CSF-contacting nucleus receives anatomical inputs from the brainstem and spinal cord, we preliminarily conclude and summarize that the CSF-contacting nucleus participates in pain, visceral activity, sleep and arousal, emotion, and drug addiction. The present study firstly illustrates the broad projections of the CSF-contacting nucleus from the brainstem and spinal cord, which implies the complicated functions of the nucleus especially for the unique roles of coordination in neural and body fluids regulation.

Enhanced in vitro model of the CSF dynamics.

BACKGROUND: Fluid dynamics of the craniospinal system are complex and still not completely understood. In vivo flow and pressure measurements of the cerebrospinal fluid (CSF) are limited. Whereas in silico modeling can be an adequate pathway for parameter studies, in vitro modeling of the craniospinal system is essential for testing and evaluation of therapeutic measures associated with innovative implants relating to, for example, normal pressure hydrocephalus and other fluid disorders. Previously-reported in vitro models focused on the investigation of only one hypothesis of the fluid dynamics rather than developing a modular set-up to allow changes in focus of the investigation. The aim of this study is to present an enhanced and validated in vitro model of the CSF system which enables the future embedding of implants, the validation of in silico models or phase-contrast magnetic resonance imaging (PC-MRI) measurements and a variety of sensitivity analyses regarding pathological behavior, such as reduced CSF compliances, higher resistances or altered blood dynamics. METHODS: The in vitro model consists of a ventricular system which is connected via the aqueduct to the cranial and spinal subarachnoid spaces. Two compliance chambers are integrated to cushion the arteriovenous blood flow generated by a cam plate unit enabling the modeling of patient specific flow dynamics. The CSF dynamics are monitored using three cranial pressure sensors and a spinal ultrasound flow meter. Measurements of the in vitro spinal flow were compared to cervical flow data recorded with PC-MRI from nine healthy young volunteers, and pressure measurements were compared to the literature values reported for intracranial pressure (ICP) to validate the newly developed in vitro model. RESULTS: The maximum spinal CSF flow recorded in the in vitro simulation was 133.60 ml/min in the caudal direction and 68.01 ml/min in the cranial direction, whereas the PC-MRI flow data of the subjects showed 122.82 ml/min in the caudal and 77.86 ml/min in the cranial direction. In addition, the mean ICP (in vitro) was 12.68 mmHg and the pressure wave amplitude, 4.86 mmHg, which is in the physiological range. CONCLUSIONS: The in vitro pressure values were in the physiological range. The amplitudes of the flow results were in good agreement with PC-MRI data of young and healthy volunteers. However, the maximum cranial flow in the in vitro model occurred earlier than in the PC-MRI data, which might be due to a lack of an in vitro dynamic compliance. Implementing dynamic compliances and related sensitivity analyses are major aspects of our ongoing research.

Selective blockade of the rat brain aqueduct with thermogelling hydrogel nanoparticle dispersion.

Experimental methods targeting molecules or drugs to specific neuronal tissue(s) can be important in determining function. In this study we focused on blockade of the small channel or aqueduct connecting the third and fourth ventricles of the rat brain. A cannula was placed into the aqueduct between the third and fourth ventricle. A second cannula was placed into the third or fourth ventricle. An aqueous dispersion of hydrogel nanoparticles, that maintains a liquid state at temperatures below 33 degrees C and solidifies near body temperature (35 degrees C), was infused into the aqueduct. Two interpenetrating polymer networks (IPN) of hydrogel nanoparticles with polymer concentrations at 2% by weight and 3% by weight were separately infused into the aqueduct to block cerebrospinal fluid (CSF) flow. Following infusion of hydrogel CSF was isolated to a particular ventricle as shown by the lack of dye movement between the ventricles. In addition, stress hormone, corticosterone, feeding behavior and blood glucose levels were measured. Results show upon reaching the aqueduct the hydrogel dispersion solidified and restricted the flow of CSF. A higher concentration of dispersion (3% wt.) was more effective in blocking the aqueduct and isolating the third from the fourth ventricle. Over the period of measurement, infusion of the dispersion had no measurable detrimental physiological effects on the animal. We conclude that isolation of ventricles in the brain can be completed for 48-h by using dispersions of hydrogel nanoparticles and the effects of drugs on certain brain tissues can be determined with this method.

Magnetic resonance measurement of blood and CSF flow rates with phase contrast--normal values, repeatability and CO2 reactivity.

BACKGROUND: Similarity in flow pulsatility has been proposed as a basis for semi-automated segmentation of vessel lumens for MR-based flow measurement, but re-examinations of salient aspects of the methodology have not been widely reported. METHODS: 12 normal control subjects underwent repeated (3*Baseline+1*5%CO2) phase contrast measurements of CSF flow through the cerebral aqueduct and foramen magnum, and CBF through the 6 large cranial vessels at the level of the 1st vertebra. Average flows were calculated for regions temporally correlated (0.3 < or = Rthreshold < or = 0.95) to user defined seed points and their 3 x 3 neighbours. RESULTS: Arterial CBF averaged 710ml/min, with low variability (+/- 4%/17%, intra-individual/group CV respectively) and was the only flow to respond significantly to 5%/mmHg CO2. Venous outflow was much smaller (298ml/min +/- 10%/ 72%), possibly due to the weak venous pulse and variable venous anatomy. Average CSF flows exceeded the classical 0.4ml/min CSF production rate and were highly variable--aqueduct: 0.6ml/min (+/- 50%/93%), foramen magnum: -2.7ml/min (+/- 158%/226%). CONCLUSIONS: This preliminary analysis identified procedural steps that can improve the accuracy and repeatability of MR flow measurements, but the process remains user-dependent for the weakly pulsatile foramen magnum CSF and venous flows where variability remains a significant confound even to relatively large perturbations such as CO2 administration.

Aging effects on cerebral blood and cerebrospinal fluid flows.

Phase-contrast magnetic resonance imaging (PC-MRI) is a noninvasive reliable technique, which enables quantification of cerebrospinal fluid (CSF) and total cerebral blood flows (tCBF). Although it is used to study hydrodynamic cerebral disorders in the elderly group (hydrocephalus), there is no published evaluation of aging effects on both tCBF and CSF flows, and on their mechanical coupling. Nineteen young (mean age 27+/-4 years) and 12 elderly (71+/-9 years) healthy volunteers underwent cerebral MRI using 1.5 T scanner. Phase-contrast magnetic resonance imaging pulse sequence was performed at the aqueductal and cervical levels. Cerebrospinal fluid and blood flow curves were then calculated over the cardiac cycle, to extract the characteristic parameters: mean and peak flows, their latencies, and stroke volumes for CSF (cervical and aqueductal) and vascular flows. Total cerebral blood flow was (P<0.01) decreased significantly in the elderly group when compared with the young subjects with a linear correlation with age observed only in the elderly group (R(2)=0.7; P=0.05). Arteriovenous delay was preserved with aging. The CSF stroke volumes were significantly reduced in the elderly, at both aqueductal (P<0.01) and cervical (P<0.05) levels, whereas aqueduct/cervical proportion (P=0.9) was preserved. This is the first work to study aging effects on both CSF and vascular cerebral flows. Data showed (1) tCBF decrease, (2) proportional aqueductal and cervical CSF pulsations reduction as a result of arterial loss of pulsatility, and (3) preserved intracerebral compliance with aging. These results should be used as reference values, to help understand the pathophysiology of degenerative dementia and cerebral hydrodynamic disorders as hydrocephalus.

Computational investigation of subject-specific cerebrospinal fluid flow in the third ventricle and aqueduct of Sylvius.

The cerebrospinal fluid flow in the third ventricle of the brain and the aqueduct of Sylvius was studied using computational fluid dynamics (CFD) based on subject-specific boundary conditions derived from magnetic resonance imaging (MRI) scans. The flow domain geometry was reconstructed from anatomical MRI scans by manual image segmentation. The movement of the domain boundary was derived from MRI brain motion scans. Velocimetric MRI scans were used to reconstruct the velocity field at the inferior end of the aqueduct of Sylvius based on the theory of pulsatile flow in pipes. A constant pressure boundary condition was assigned at the foramina of Monro. Three main flow features were observed: a fluid jet emerging from the aqueduct of Sylvius, a moderately mobile recirculation zone above the jet and a mobile recirculation below the jet. The flow in the entire domain was laminar with a maximum Reynolds number of 340 in the aqueduct. The findings demonstrate that by combining MRI scans and CFD simulations, subject-specific detailed quantitative information of the flow field in the third ventricle and the aqueduct of Sylvius can be obtained.

The role of left perisylvian cortical regions in spelling.

In order to examine the role of left perisylvian cortex in spelling, 13 individuals with lesions in this area were administered a comprehensive spelling battery. Their spelling of regular words, irregular words, and nonwords was compared with that of individuals with extrasylvian damage involving left inferior temporo-occipital cortex and normal controls. Perisylvian patients demonstrated a lexicality effect, with nonwords spelled worse than real words. This pattern contrasts with the deficit in irregular word spelling, or regularity effect, observed in extrasylvian patients. These findings confirm that damage to left perisylvian cortex results in impaired phonological processing required for sublexical spelling. Further, degraded phonological input to orthographic selection typically results in additional deficits in real word spelling.