Research

 

Biomechanics of brain ageing

My research project focuses on the role of intracranial vessel pulsation in neurodegenerative diseases. Thanks to a close collaboration with mathematicians, physicists, clinicians and biologists, I am highlighting how measurements of the intracranial fluid dynamics combined with  mathematical modelling approaches can help to better understand and characterise brain ageing.

Focus: intracranial pulsatility

During brain ageing, we can observe modifications of the brain structure, microstructure, mechanical properties and fluid dynamics.

I am convinced that alteration of brain pulsatility reflects an accumulation of brain pathologies and can be used to better understand and characterize brain ageing.

Approach: use of mathematical models

My original approach is to use mathematical models based on fundamental physical laws

  •  to interpret in vivo observations;
  •  to explore sub-millimetre phenomena that cannot be assessed by imaging alone;
  •  to extrapolate animal models observations up to the human scale.

The brain tissue is represented as a poroelastic medium where the cells are the solid part and the interstitial fluid is the fluid part. The vascular network is represented as a network of 1D pipes. The cerebrospinal fluid around the brain and in the perivascular space is strongly coupled to both tissue and vasculature.  Describing this system necessitate complex multi-physics multi-scale modeling tools which I am developing and validating.

Objectives :

Analysis of brain pulsatility should lead to a better understanding of the underlying mechanisms in neurodegenerative diseases and ultimately provide a new, outside-the-box diagnostic approach relevant for preventive strategies and patient follow up.

Impact :

Worldwide, more than 50 million people have dementia, meaning they have severe cognitive alterations that reduce their independence in daily life activities. However, in most cases, no cure exists. If we show that managing intracranial vessel pulsation is a preventive strategy for dementia, it would open new opportunities for prevention programs. I also expect to discover early markers related to brain fluid dynamics that help identify persons at risk for dementia.

Modelling techniques gallery

 

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Current projects

 

Fluid dynamics and mass transport in the brain.  Recently, a new pathway for waste removal and nutrient supply has been discovered around blood vessels in the brain. The deformation of vessels might play an unexpectedly important role in brain physiology. With S. Lorthois (expert in cerebral microcirculation, FR) I developed a new model of blood flow in deformable vessels (1D finite volume code based on Riemann invariants) to show the significance of vessel deformation at all scales in the brain. Through a collaboration between K. Mardal’s team (UiO, NO) and R. Enger’s team (biologists at the Institute of Basic Medical Sciences, UiO, NO), we are demonstrating that oscillations of vessel walls enhance brain clearance during sleep. I discretized flow and mass transport equations with the finite element method (using FEniCS simulation tools) to interpret in-vivo measurements in sleeping and awake mice. I am demonstrating, using a multiple time scale homogenisation technique and analytical solutions, that in addition to Taylor dispersion, Shuttle dispersion enhances solute transport even when the Peclet number is small.

Fluid-structure interactions around cerebral vessels. We are comparing three approaches to describe fluid-poroelastic interactions: a monolithic scheme, a loosely coupled two-domain scheme and a single-domain multi-phase scheme. Those tools are used to describe the coupling between fluid in perivascular spaces and surrounding tissues. I am developing a porous and deformable membrane model, as a shell, to describe the interaction of the fluid with the glial cells at the fluid/tissue interface. We are interpreting in-vivo data in both mice (from R. Enger’s team) and humans (MRI data from P.K. Eide and G.A. Ringstad, Rikshospitalet, Oslo NO).

Biological processes involved in brain fluid dynamics. Thanks to the collaboration of neurosurgeons, neurologists, radiologists and physicists (FR, UK, NL), we showed that brain mechanical response to intracranial vessel pulsation is associated with health deficit accumulation in a cohort of older adults with various neuropathologies. I am currently working with a PhD student in Pharmacy (Toulouse hospital) on biochemical and proteomic data from the same cohort of patients. I am using data science technologies – eg. unsupervised clustering, neural network modelling – to highlight the proteomic signature associated with abnormal CSF dynamics. Our preliminary results show that homocysteinemia and micro-clots might be involved in the alteration of brain fluid dynamics.

Previous and ongoing projects

 

2020 2021

Reduced mathematical model of the CSF transport in the space between blood vessels and the brain

Researcher recently observed that the cerebrospinal fluid (CSF) penetrates the brain through perivascular spaces around the vessels and travels through the parenchyma thus having the potential of clearing the brain wastes. However, those observations are not well understood. The driving mechanisms, flow velocities and even transport direction are still controversial.

Within the the research project of Kent Mardal (University of Oslo), I will model the CSF transport combining a 1D network description of blood and CSF flow and a 3D poroelastic description of the surrounding tissues. Numerical experiments with this model will help understanding the brain clearance system and its implication in Alzheimer's disease.

2020

Clinical assessment of brain biomechanics

A model of blood pulsatility coupled to the cereborspinal fluid dynamics is used to describe a clinical test assessing in vivo the brain biomechanical response. Our approach provide a more precise and robust interpretation of the test, which will be useful both in clinics and research investigations.

2019 2020

Development of a model of cerebral blood pulsatility couple to CSF dynamics

As part of the ERC-funded BRAINMICROFLOW project (PI S. Lorthois), the coupling between the vascular system and the cerebrospinal fluid is described at the mesoscale level with a network approach.

2018

Demonstration of the biomechanical approach relevence

A simplified model of the brain biomechanics was used to interpret data from a cohort of 100 patients. The brain biomechanical response was significantly (p<0.05) associated with an index of frailty (cognitive and physical impairment). This is a first evidence that brain biomechanical response could be a new marker of pathological brain aging [Vallet et al. , Journal of Neurology,accepted, to be published].

Host Institutions

I acknowledge the institutes that hosted my research and believed in the strong potential of the interdisciplinary approach of brain aging.

Funding opportunities for highrisk fundamental project in clinical research field are rare.

The results obtained are promising and I am constantly applying for new funding opportunities in order to pursue the project.