Impaired neurogenesis alters brain biomechanics in a neuroprogenitor-based genetic subtype of congenital hydrocephalus

Duy, Phan Q.; Weise, Stefan; Marini, Claudia; Li, Xiaojun; Liang, Dan; Dahl, Peter; Ma, Shaojie; Spajic, Ana; Dong, Weilai; Juusola, Jane; Kiziltug, Emre; Kundishora, Adam J.; Koundal, Sunil; Pedram, Maysam Zamani; Fernández, Lucia Torres; Händler, Kristian; Domenico, Elena De; Becker, Matthias; Ulas, Thomas; Juranek, Stefan; Cuevas, Elisa; Liang, Hao; Jux, Bettina; Sousa, André M. M.; Liu, Fuchen; Kim, Suel Kee; Li, Mingfeng; Yang, Yiying; Takeo, Yutaka; Duque, Alvaro; Nelson‐Williams, Carol; Ha, Yonghyun; Selvaganesan, Kartiga; Robert, Stephanie M.; Singh, Amrita; Allington, Garrett; Furey, Charuta G.; Timberlake, Andrew T.; Reeves, Benjamin C.; Smith, Hannah; Dunbar, Ashley; DeSpenza, Tyrone; Goto, June; Marlier, Arnaud; Moreno-De-Luca, Andrés; Yu, Xin; Butler, William E.; Carter, Bob S.; Lake, Evelyn; Constable, R. Todd; Rakić, Paško; Lin, Haifan; Deniz, Engin; Benveniste, Helene; Malvankar, Nikhil S.; Estrada-Veras, Juvianee; Walsh, Christopher A.; Alper, Seth L.; Schultze, Joachim L.; Paeschke, Katrin; Doetzlhofer, Angelika; Wulczyn, F. Gregory; Jin, Sheng; Lifton, Richard P.; Šestan, Nenad; Kolanus, Waldemar; Kahle, Kristopher T.

doi:10.1038/s41593-022-01043-3

Cited by 62 publications

(77 citation statements)

References 76 publications

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“…We note that our computed ICP curve lies well within the range of clinically reported curves by Ziółkowski et al [62] and closely resembles the in-vitro modelling results by Benninghaus et al [8]. A transmantle pressure gradient is hypothesized to drive the development of hydrocephalus [50,19], though with recent findings also pointing at genetic factors [17].…”

Section: Discussionsupporting

confidence: 86%

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

Causemann

Vinje

Rognes

2022

Preprint

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BackgroundToday’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.MethodsWe develop finite element models of fully coupled cardiac-induced pulsatile CSF flow and tissue motion in the human brain environment. The three-dimensional model geometry is derived from magnetic resonance images (MRI), 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 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.ResultsOur 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.ConclusionsOur 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.

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Section: Discussionsupporting

confidence: 86%

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

Causemann

Vinje

Rognes

2022

Preprint

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“…Previous studies showed the potential impact of brain biomechanics/intracranial compliance as an emerging concept in the pathogenesis of hydrocephalus and other disorders due to altered ICP ( Duy et al, 2022a ; Duy et al, 2022b ). There was also a widely held belief in previous studies that the short-term CSFV–ICP graph is a monoexponential function ( Marmarou et al, 1975 ; Sklar and Elashvili, 1977 ; Szewczykowski et al, 1977 ; Avezaat et al, 1979 ; Shapiro et al, 1980 ; Raksin et al, 2003 ; Gholampour and Bahmani, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

A New Definition for Intracranial Compliance to Evaluate Adult Hydrocephalus After Shunting

Gholampour

Yamini

Droessler

et al. 2022

Front. Bioeng. Biotechnol.

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The clinical application of intracranial compliance (ICC), ∆V/∆P, as one of the most critical indexes for hydrocephalus evaluation was demonstrated previously. We suggest a new definition for the concept of ICC (long-term ICC) where there is a longer amount of elapsed time (up to 18 months after shunting) between the measurement of two values (V1 and V2 or P1 and P2). The head images of 15 adult patients with communicating hydrocephalus were provided with nine sets of imaging in nine stages: prior to shunting, and 1, 2, 3, 6, 9, 12, 15, and 18 months after shunting. In addition to measuring CSF volume (CSFV) in each stage, intracranial pressure (ICP) was also calculated using fluid–structure interaction simulation for the noninvasive calculation of ICC. Despite small increases in the brain volume (16.9%), there were considerable decreases in the ICP (70.4%) and CSFV (80.0%) of hydrocephalus patients after 18 months of shunting. The changes in CSFV, brain volume, and ICP values reached a stable condition 12, 15, and 6 months after shunting, respectively. The results showed that the brain tissue needs approximately two months to adapt itself to the fast and significant ICP reduction due to shunting. This may be related to the effect of the “viscous” component of brain tissue. The ICC trend between pre-shunting and the first month of shunting was descending for all patients with a “mean value” of 14.75 ± 0.6 ml/cm H2O. ICC changes in the other stages were oscillatory (nonuniform). Our noninvasive long-term ICC calculations showed a nonmonotonic trend in the CSFV–ICP graph, the lack of a linear relationship between ICC and ICP, and an oscillatory increase in ICC values during shunt treatment. The oscillatory changes in long-term ICC may reflect the clinical variations in hydrocephalus patients after shunting.

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“…The ciliary motion of the lateral ventricles may play a role in efficiently stirring the CSF and distributing it to every part of the tissues of the lateral ventricles. A recent study also showed that in some instances, brain malformations cause hydrocephalus without primary defects in CSF flow [45]. Although further studies are needed to clarify the relationship between ciliary motility and hydrocephalus, our computational model could help understand CSF flow and related mass transport in cerebral ventricles.…”

Section: Discussionmentioning

confidence: 90%

Effect of cilia-induced surface velocity on cerebrospinal fluid exchange in the lateral ventricles

Yoshida

Ishida

Yamamoto

et al. 2022

J. R. Soc. Interface.

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Ciliary motility disorders are known to cause hydrocephalus. The instantaneous velocity of cerebrospinal fluid (CSF) flow is dominated by artery pulsation, and it remains unclear why ciliary dysfunction results in hydrocephalus. In this study, we investigated the effects of cilia-induced surface velocity on CSF flow using computational fluid dynamics. A geometric model of the human ventricles was constructed using medical imaging data. The CSF produced by the choroid plexus and cilia-induced surface velocity were given as the velocity boundary conditions at the ventricular walls. We developed healthy and reduced cilia motility models based on experimental data of cilia-induced velocity in healthy wild-type and Dpcd-knockout mice. The results indicate that there is almost no difference in intraventricular pressure between healthy and reduced cilia motility models. Additionally, it was found that newly produced CSF from the choroid plexus did not spread to the anterior and inferior horns of the lateral ventricles in the reduced cilia motility model. These findings suggest that a ciliary motility disorder could delay CSF exchange in the anterior and inferior horns of the lateral ventricles.

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Impaired neurogenesis alters brain biomechanics in a neuroprogenitor-based genetic subtype of congenital hydrocephalus

Cited by 62 publications

References 76 publications

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

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

A New Definition for Intracranial Compliance to Evaluate Adult Hydrocephalus After Shunting

Effect of cilia-induced surface velocity on cerebrospinal fluid exchange in the lateral ventricles

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