Simple Patient-Based Transmantle Pressure and Shear Estimate From Cine Phase-Contrast MRI in Cerebral Aqueduct

From measurements of the oscillating flux of the cerebrospinal fluid (CSF) in the aqueduct of Sylvius, we elaborate a patient-based methodology for transmantle pressure (TRP) and shear evaluation. High-resolution anatomical magnetic resonance imaging first permits a precise 3-D anatomical digitalized reconstruction of the Sylvius’s aqueduct shape. From this, a very fast approximate numerical flow computation, nevertheless consistent with analytical predictions, is developed. Our approach includes the main contributions of inertial effects coming from the pulsatile flow and curvature effects associated with the aqueduct bending. Integrating the pressure along the aqueduct longitudinal center-line enables the total dynamic hydraulic admittances of the aqueduct to be evaluated, which is the pre-eminent contribution to the CSF pressure difference between the lateral ventricles and the subarachnoidal spaces also called the TRP. The application of the method to 20 healthy human patients validates the hypothesis of the proposed approach and provides a first database for normal aqueduct CSF flow. Finally, the implications of our results for modeling and evaluating intracranial cerebral pressure are discussed

New Mechanics of Traumatic Brain Injury

The prediction and prevention of traumatic brain injury is a very important aspect of preventive medical science. This paper proposes a new coupled loading-rate hypothesis for the traumatic brain injury (TBI), which states that the main cause of the TBI is an external Euclidean jolt, or SE(3)-jolt, an impulsive loading that strikes the head in several coupled degrees-of-freedom simultaneously. To show this, based on the previously defined covariant force law, we formulate the coupled Newton-Euler dynamics of brain's micro-motions within the cerebrospinal fluid and derive from it the coupled SE(3)-jolt dynamics. The SE(3)-jolt is a cause of the TBI in two forms of brain's rapid discontinuous deformations: translational dislocations and rotational disclinations. Brain's dislocations and disclinations, caused by the SE(3)-jolt, are described using the Cosserat multipolar viscoelastic continuum brain model. Keywords: Traumatic brain injuries, coupled loading-rate hypothesis, Euclidean jolt, coupled Newton-Euler dynamics, brain's dislocations and disclinationsComment: 18 pages, 1 figure, Late

Spatial model of convective solute transport in brain extracellular space does not support a "glymphatic" mechanism.

A "glymphatic system," which involves convective fluid transport from para-arterial to paravenous cerebrospinal fluid through brain extracellular space (ECS), has been proposed to account for solute clearance in brain, and aquaporin-4 water channels in astrocyte endfeet may have a role in this process. Here, we investigate the major predictions of the glymphatic mechanism by modeling diffusive and convective transport in brain ECS and by solving the Navier-Stokes and convection-diffusion equations, using realistic ECS geometry for short-range transport between para-arterial and paravenous spaces. Major model parameters include para-arterial and paravenous pressures, ECS volume fraction, solute diffusion coefficient, and astrocyte foot-process water permeability. The model predicts solute accumulation and clearance from the ECS after a step change in solute concentration in para-arterial fluid. The principal and robust conclusions of the model are as follows: (a) significant convective transport requires a sustained pressure difference of several mmHg between the para-arterial and paravenous fluid and is not affected by pulsatile pressure fluctuations; (b) astrocyte endfoot water permeability does not substantially alter the rate of convective transport in ECS as the resistance to flow across endfeet is far greater than in the gaps surrounding them; and (c) diffusion (without convection) in the ECS is adequate to account for experimental transport studies in brain parenchyma. Therefore, our modeling results do not support a physiologically important role for local parenchymal convective flow in solute transport through brain ECS

Analysis of Growing Tumor on the Flow Velocity of Cerebrospinal Fluid in Human Brain Using Computational Modeling and Fluid-Structure Interaction

Cerebrospinal fluid (CSF) plays a pivotal role in normal functioning of Brain. Intracranial compartments such as blood, brain and CSF are incompressible in nature. Therefore, if a volume imbalance in one of the aforenoted compartments is observed, the other reaches out to maintain net change to zero. Whereas, CSF has higher compliance over long term. However, if the CSF flow is obstructed in the ventricles, this compliance may get exhausted early. Brain tumor on the other hand poses a similar challenge towards destabilization of CSF flow by compressing any section of ventricles thereby ensuing obstruction. To avoid invasive procedures to study effects of tumor on CSF flow, numerical-based methods such as Finite element modeling (FEM) are used which provide excellent description of underlying pathological interaction. A 3D fluid-structure interaction (FSI) model is developed to study the effect of tumor growth on the flow of cerebrospinal fluid in ventricle system. The FSI model encapsulates all the physiological parameters which may be necessary in analyzing intraventricular CSF flow behavior. Findings of the model show that brain tumor affects CSF flow parameters by deforming the walls of ventricles in this case accompanied by a mean rise of 74.23% in CSF flow velocity and considerable deformation on the walls of ventricles

Cerebrospinal fluid dynamics

The classical cerebrospinal fluid (CSF) circulation theory has been accepted as an established theory of CSF physiology. It describes bulk CSF flow from production site to absorption site. However, much controversy remains regarding the basic CSF physiology and the mechanisms behind the development of hydrocephalus. In the recent observations made using advanced magnetic resonance imaging (MRI) technique, namely, the time spatial inversion pulse (Time-SLIP) method, CSF was used as internal CSF tracer to trace true CSF movement. Observation of the CSF dynamics using this method reveals aspects of CSF dynamics that are different from those of classical CSF circulation theory. Cerebrospinal fluid shows pulsation but does not show bulk flow from production site to absorption site, a theory that was built upon externally injected tracer studies. Observation of the exogeneous tracer studies were true but misinterpreted. Causes of misinterpretations are the differences between results obtained using the true CSF tracer and exogenous tracers. A better understanding of the real CSF physiology can be significant for the advancement of medical sciences in the future. Revisiting CSF flow physiology is a necessary step toward this goal

Investigation of ventricular cerebrospinal fluid flow phase differences between the foramina of Monro and the aqueduct of Sylvius

In this paper, phase contrast magnetic resonance flow measurements of the foramina of Monro and the aqueduct of Sylvius of seven healthy volunteers are presented. Peak volume flow rates are of the order of 150 mm3/s for the aqueduct of Sylvius and for the foramina of Monro. The temporal shift between these volume flows is analyzed with a high-resolution cross-correlation scheme which reveals high subject-specific phase differences. Repeated measurements show the invariability of the phase differences over time for each volunteer. The phase differences as a fraction of one period range from -0.0537 to 0.0820. A mathematical model of the pressure dynamics is presented. The model features one lumped compartment per ventricle. The driving force of the cerebrospinal fluid is modeled through pulsating choroid plexus. The model includes variations of the distribution of the choroid plexus between the ventricles. The proposed model is able to reproduce the measured phase differences with a very small (5%) variation of the distribution of the choroid plexus between the ventricles and, therefore, supports the theory that the choroid plexus drives the cerebrospinal fluid motio

Human intracranial pulsatility during the cardiac cycle: a computational modelling framework

Background Today’s availability of medical imaging and computational resources set the scene for high-fidelity computational modelling of brain biomechanics. The brain and its environment feature a dynamic and complex interplay between the tissue, blood, cerebrospinal fluid (CSF) and interstitial fluid (ISF). Here, we design a computational platform for modelling and simulation of intracranial dynamics, and assess the models’ validity in terms of clinically relevant indicators of brain pulsatility. Focusing on the dynamic interaction between tissue motion and ISF/CSF flow, we treat the pulsatile cerebral blood flow as a prescribed input of the model. Methods We develop finite element models of cardiac-induced fully coupled pulsatile CSF flow and tissue motion in the human brain environment. The three-dimensional model geometry is derived from magnetic resonance images (MRI) and features a high level of detail including the brain tissue, the ventricular system, and the cranial subarachnoid space (SAS). We model the brain parenchyma at the organ-scale as an elastic medium permeated by an extracellular fluid network and describe flow of CSF in the SAS and ventricles as viscous fluid movement. Representing vascular expansion during the cardiac cycle, a prescribed pulsatile net blood flow distributed over the brain parenchyma acts as the driver of motion. Additionally, we investigate the effect of model variations on a set of clinically relevant quantities of interest. Results Our model predicts a complex interplay between the CSF-filled spaces and poroelastic parenchyma in terms of ICP, CSF flow, and parenchymal displacements. Variations in the ICP are dominated by their temporal amplitude, but with small spatial variations in both the CSF-filled spaces and the parenchyma. Induced by ICP differences, we find substantial ventricular and cranial-spinal CSF flow, some flow in the cranial SAS, and small pulsatile ISF velocities in the brain parenchyma. Moreover, the model predicts a funnel-shaped deformation of parenchymal tissue in dorsal direction at the beginning of the cardiac cycle. Conclusions Our model accurately depicts the complex interplay of ICP, CSF flow and brain tissue movement and is well-aligned with clinical observations. It offers a qualitative and quantitative platform for detailed investigation of coupled intracranial dynamics and interplay, both under physiological and pathophysiological conditions.publishedVersio

The pulsating brain: A review of experimental and clinical studies of intracranial pulsatility

The maintenance of adequate blood flow to the brain is critical for normal brain function; cerebral blood flow, its regulation and the effect of alteration in this flow with disease have been studied extensively and are very well understood. This flow is not steady, however; the systolic increase in blood pressure over the cardiac cycle causes regular variations in blood flow into and throughout the brain that are synchronous with the heart beat. Because the brain is contained within the fixed skull, these pulsations in flow and pressure are in turn transferred into brain tissue and all of the fluids contained therein including cerebrospinal fluid. While intracranial pulsatility has not been a primary focus of the clinical community, considerable data have accrued over the last sixty years and new applications are emerging to this day. Investigators have found it a useful marker in certain diseases, particularly in hydrocephalus and traumatic brain injury where large changes in intracranial pressure and in the biomechanical properties of the brain can lead to significant changes in pressure and flow pulsatility. In this work, we review the history of intracranial pulsatility beginning with its discovery and early characterization, consider the specific technologies such as transcranial Doppler and phase contrast MRI used to assess various aspects of brain pulsations, and examine the experimental and clinical studies which have used pulsatility to better understand brain function in health and with disease

Whole-brain mapping of cerebrospinal fluid velocity and displacement over the cardiac cycle using phase contrast MRI and optimization of a DENSE sequence

Tese de mestrado integrado em Engenharia Biomédica e Biofísica (Sinais e Imagens Médicas), Universidade de Lisboa, Faculdade de Ciências, 2021O líquido cefalorraquidiano (LCR) tem um papel essencial na drenagem dos resíduos resultantes do metabolismo cerebral e o constante movimento a que este fluido está sujeito é vital para manter a homeostasia do cérebro. Com feito, alterações neste movimento, geralmente associadas com o envelhecimento ou com doença, levam a perturbações fisiológicas, como a doença de Alzheimer ou a hidrocefalia. Por esta razão, é fundamental consolidar e aprofundar o conhecimento referente a este fluido, nomeadamente perceber como varia a sua velocidade e deslocamento, pois só desta forma será possível desenvolver e aperfeiçoar a prevenção e tratamento destas perturbações. Com efeito, este fluido está em constante movimento e o seu comportamento está intimamente ligado ao ciclo cardíaco. Apesar de estudos anteriores sobre a velocidade e o deslocamento do líquido cefalorraquidiano através de métodos de Ressonância Magnética (RM), ainda não existe uma descrição completa sobre o comportamento deste fluido. O objetivo principal deste estudo, consistiu em obter uma descrição detalhada da velocidade e do deslocamento do LCR através da aquisição de imagens de ressonância magnética obtidas com contraste de fase, um método de referência no que toca ao estudo da velocidade de fluidos No entanto, utilizar RM de contraste de fase para adquirir velocidades mais baixas, como as do LCR, requer tempos de aquisição mais longos e, consequentemente, as imagens obtidas estão mais sujeitas a distorções. Assim, a segunda parte deste projecto partiu dos resultados de deslocamento obtidos através da RM com contraste de fase para otimizar os parâmetros de uma segunda sequência de MR. Esta sequência é relativamente recente e possibilita o estudo do deslocamento sub-milimétrico do LCR associado ao movimento do cérebro através da aplicação de gradientes sucessivos (DENSE). Porém, é necessária uma escolha rigorosa dos parâmetros utilizados de forma a obter resultados que retratem o deslocamento do LCR de uma forma rigorosa e exata. Na primeira parte deste projecto, quatro voluntários foram estudados utilizando RM com contraste de fase, entre outubro de 2019 e fevereiro de 2020, em concordância com as diretrizes éticas da University Medical Center em Utrecth, Países Baixos. As aquisições foram realizadas utilizando um scanner de RM Philips 7 T e dois tipos de contraste foram utilizados: contraste de fase com 1mm de resolução isotrópica e com uma codificação de velocidade de 5m/s, e imagens 3D com ponderação em T1 com 1mm de resolução isotrópica. As imagens foram obtidas para três orientações distintas: anterior posterior, inferior-superior, e direita-esquerda. Na segunda parte deste projecto, dois voluntários foram estudados, de janeiro a fevereiro de 2020, utilizando seis contrastes: contraste de fase com 1mm de resolução isotrópica, e imagens 3D com ponderação em T1 com 1mm de resolução isotrópica, uma sequência básica DENSE com 2mm de resolução isotrópica, uma sequência básica DENSE com 3mm de resolução isotrópica, uma sequência DENSE com uma preparação T2 com 3mm de resolução isotrópica e, finalmente, uma sequência DENSE com tempo de eco prolongado com 3mm de resolução isotrópica. No entanto, e ao contrário das imagens adquiridas na primeira parte deste projecto, as imagens da segunda parte foram obtidas apenas para a orientação inferior-superior. Todas as imagens adquiridas no decorrer desta dissertação foram obtidas com gating cardíaco. O gating cardíaco foi realizado através da utilização de um eletrocardiograma e de um oxímetro de pulso de modo a relacionar o evolução da velocidade e do deslocamento com o ciclo cardíaco. Neste projecto foi também desenvolvida uma pipeline que permite que a partir das imagens adquiridas seja possível estudar a velocidade e o deslocamento do LCR. Esta pipeline inclui diversos passos. O primeiro passo consistiu em realinhar e co-registar as imagens obtidas de forma a permitir uma análise voxel a voxel. Seguidamente, as imagens foram segmentas em três tipos de tecidos: LCR, substância cinzenta, e substância branca. Adicionalmente, as primeiras etapas foram realizadas através da utilização de toolboxs disponíveis no MATLAB como o SPM e o CAT12. Posteriormente, os artefactos presentes nas imagens, tais como as correntes-eddy, foram corrigidos. No decorrer deste projecto diversas regiões foram analisadas e foram divididas em dois grupos: regiões do sistema ventricular, nas quais se incluíram os ventrículos laterais, o terceiro e quarto ventrículo, o aqueduto de Sylvius e a Cisterna Magna; e regiões mais abrangentes, como a região anterior e posterior do cérebro. Estas áreas do cérebro foram selecionadas através da segmentação das imagens anatómicas. Finalmente, a velocidade de cada uma destas regiões foi extraída e integrada ao longo do ciclo cardíaco de maneira a calcular o deslocamento do LCR. Os resultados obtidos relativamente à velocidade mostraram consistência para os quatro voluntários deste projecto. Verificou-se que as regiões do sistema ventricular demonstram valores de velocidade consideravelmente mais elevados do que as regiões mais abrangentes. Com efeito, a região que apresentou valores absolutos de velocidade mais elevados foi o aqueducto de Sylvius. Adicionalmente, verificou-se que as velocidades são superiores na orientação caudal-cranial e inferiores na orientação direita-esquerda. Concluiu-se também que o valor de velocidade escolhido não foi o mais indicado para as regiões mais abrangentes pois a velocidade destas regiões é significativamente inferior e, desta forma, poderá ter existido perda de sinal do LCR. Posteriormente, ao integrar a velocidade obtida através da RM com contraste fase obtiveram-se mapas de deslocamento para as mesmas regiões cerebrais. Estes resultados mostraram-se consistentes e, tal como anteriormente observado, o deslocamento é consideravelmente superior para as regiões do sistema ventricular. A região inferior do cérebro foi a que apresentou valores de deslocamento mais elevados, o que pode ser justificado pelo facto desta região se encontrar mais próxima do coração e, desta maneira, o LCR ser ejetado das regiões que ocupa com maior velocidade. Adicionalmente, verificou-se que as maiores alterações do deslocamento ocorrem imediatamente após a sístole cardíaca. Seguidamente, foi possível, a partir dos valores de deslocamento obtidos, determinar um valor ótimo para a sensibilidade, relativamente ao deslocamento, da sequência DENSE. Contrariamente à primeira parte deste projecto, os resultados obtidos utilizando as sequências DENSE dizem respeito exclusivamente às regiões mais abrangentes. De facto, esta exclusão das regiões do sistema ventricular foi causada pela baixa resolução das imagens obtidas que, desta forma, não permitiram uma segmentação de áreas tão reduzidas com fiabilidade razoável. Os resultados desta análise mostram que a sequência utilizada cujos resultados de deslocamento se assemelham mais aos resultados obtidos através do contraste de fase foi a sequência que utilizou a preparação T2. Por oposição, as sequências básicas utilizadas mostraram semelhança reduzida com o método de comparação. Esta diferença observada foi justifica pela baixa resolução das imagens adquiridas, o que contribui para que não fosse possível eliminar o efeito de volume parcial. Adicionalmente, concluiu-se que o valor de sensibilidade para o deslocamento utilizado não foi o correto para estas regiões e, desta forma, houve perda de sinal adquirido justificando assim às diferenças encontradas entre os dois métodos. Concluindo, esta dissertação cumpriu o objetivo principal proposto, nomeadamente fazer uma descrição completa e quantificar a evolução da velocidade e do deslocamento do líquido cefalorraquidiano ao longo do ciclo cardíaco. Adicionalmente, o método de RM com contraste de fase mostrou ser um método fiável para o estudo do comportamento do LCR mesmo em regiões com velocidades mais lentas. Os resultados de deslocamento obtidos através da utilização do método DENSE permitiram confirmar o potencial desta técnica para medir deslocamentos sub-milimétricos. No entanto, este método ainda necessita de ser otimizado de forma a ser uma alternativa viável ao contraste de fase. Finalmente, os resultados obtidos neste estudo permitem que estudos futuros utilizem os valores máximos de cada região obtida de forma a otimizar futuras sequências.Cerebrospinal fluid (CSF) plays an essential role in the drainage of cerebral waste, and its continuous motion is vital to maintain the brain’s homeostasis. Variations in this motion, associated with aging and disease, are observed in physical and physiological disorders, such as Alzheimer’s Disease. Therefore, a deep understating of this fluid motion, such as its velocity and displacement, is fundamental to strengthen our knowledge of these diseases and might be vital to their prevention and treatment. Despite previous studies reporting CSF velocity and displacement using magnetic resonance imaging techniques, a complete picture of this fluid motion has not yet been obtained. The aim of this study was to, first and foremost, obtain a general picture of CSF velocity and displacement using Phase Contrast (PC) MRI, a method of reference for velocity acquisition. Furthermore, this sequence was also used to optimize the parameters for an MRI technique called Displacement Encoding with Stimulated Echoes (DENSE), a sequence that was modified in order to be capable of measuring small displacements. Four healthy subjects were studied using whole-brain ultra-high field (UHF) MRI at 7 Tesla (T). The volunteers were scanned using two different MRI imaging sequences: Phase Contrast MRI at 1 mm isotropic resolution and 3D T1-weighted (T1w) at 1 mm isotropic resolution. Additionally, two healthy subjects were scanned using PC and four different DENSE acquisitions. Firstly, two basic DENSE sequences with 2mm and 3mm isotropic resolution were acquired. Next, a DENSE acquisition with a T2 prepared magnetization, and a DENSE sequence with a long echo time were acquired to avoid confounding effects from partial volume between tissue and CSF. The image processing pipeline included coregistration, segmentation, eddy current correction. Moreover, mean velocity and displacement maps were calculated for regions of interest previously selected. The results in this study obtained from the PC acquisitions show consistent velocity and displacement values across all subjects. Furthermore, CSF shows higher values for the ventricular regions, such as the aqueduct, and predominant motion in the anterior and feet direction. Comparatively, regions in the periphery of the brain display slower velocities and smaller displacements. The displacement values obtained with PC were used to optimize the displacement sensitivity used in the DENSE acquisition. The DENSE sequence acquired with a T2 magnetization preparation showed the most consistent results when compared to the Phase Contrast. In conclusion, this project managed to study and quantify CSF behavior in the brain, which allows for the optimization of future sequences that desire a more detailed study of this fluid’s in specific brain regions