Finite element simulation of ionic electrodiffusion in cellular geometries

Our preprint on Finite element simulation of ionic electrodiffusion in cellular geometries is now out on arxiv!

Our mathematical model accounting for ionic electrodiffusion predicts weaker ephaptic coupling effects compared to previous models.

Mathematical models for excitable cells are commonly based on cable theory, which considers a homogenized domain and spatially constant ionic concentrations. Although such models provide valuable insight, the effect of altered ion concentrations or detailed cell morphology on the electrical potentials cannot be captured. In this paper, we discuss an alternative approach to detailed modelling of electrodiffusion in neural tissue. The mathematical model describes the distribution and evolution of ion concentrations in a geometrically-explicit representation of the intra- and extracellular domains. As a combination of the electroneutral Kirchhoff-Nernst-Planck (KNP) model and the Extracellular-Membrane-Intracellular (EMI) framework, we refer to this model as the KNP-EMI model. Here, we introduce and numerically evaluate a new, finite element-based numerical scheme for the KNP-EMI model, capable of efficiently and flexibly handling geometries of arbitrary dimension and arbitrary polynomial degree. Moreover, we compare the electrical potentials predicted by the KNP-EMI and EMI models. Finally, we study ephaptic coupling induced in an unmyelinated axon bundle and demonstrate how the KNP-EMI framework can give new insights in this setting.

Abstractions and algorithms for mixed domain and mixed dimensional finite elements

Our preprint on Abstractions and automated algorithms for mixed domain finite element methods is now out on arXiv!

Mixed dimensional partial differential equations (PDEs) are equations coupling unknown fields defined over domains of differing topological dimension. Such equations naturally arise in a wide range of scientific fields including geology, physiology, biology and fracture mechanics. Mixed dimensional PDEs are also commonly encountered when imposing non-standard conditions over a subspace of lower dimension e.g. through a Lagrange multiplier. In this paper, we present general abstractions and algorithms for finite element discretizations of mixed domain and mixed dimensional PDEs of co-dimension up to one (i.e. nD-mD with |n-m| <= 1). We introduce high level mathematical software abstractions together with lower level algorithms for expressing and efficiently solving such coupled systems. The concepts introduced here have also been implemented in the context of the FEniCS finite element software. We illustrate the new features through a range of examples, including a constrained Poisson problem, a set of Stokes-type flow models and a model for ionic electrodiffusion.

Paper quantifying uncertainties of tracer distribution in the brain published in FBCNS

Our paper on “Uncertainty quantification of parenchymal tracer distribution using random diffusion and convective velocity fields” is now published in Fluids and Barrier of the Central Nervous System. Our main findings are:

  • Uncertainty in diffusion parameters substantially impact the amount of tracer in gray and white matter, and the average tracer concentration in gray and white subregions.
  • Even with an uncertainty in the diffusion coefficient of a factor three, and a resulting fourfold variation in white matter tracer enhancement, discrepancies between simulations of diffusion and experimental data are too large to be attributed to uncertainties in the diffusion coefficient alone.
  • A convective velocity field modelling the glymphatic theory did not increase tracer enhancement in the brain parenchyma compared to pure diffusion. However, when a large-scale directional structure was added to this glymphatic velocity field, tracer inflow increased.
Illustration of velocity field modelling large-scale directionality associated with a glymphatic circulation

New (old) paper published on automated adjoints of coupled PDE-ODE systems!

Our paper on Automated adjoints of coupled PDE-ODE systems is now published online in the SIAM Journal on Scientific Computing (SISC). Mathematical models that couple partial differential equations (PDEs) and spatially distributed ordinary differential equations (ODEs) arise in biology, medicine, chemistry, and many other fields. In this paper we discuss an extension to the FEniCS finite element software for expressing and efficiently solving such coupled systems. Given an ODE described using an augmentation of the Unified Form Language (UFL) and a discretization described by an arbitrary Butcher tableau, efficient code is automatically generated for the parallel solution of the ODE. The high-level description of the solution algorithm also facilitates the automatic derivation of the adjoint and tangent linearization of coupled PDE-ODE solvers. We demonstrate the capabilities of the approach on examples from cardiac electrophysiology and mitochondrial swelling.

New paper on personalized simulations of cancer treatment published!

Our paper on Towards personalized computer simulation of breast cancer treatment: a multi-scale pharmacokinetic and pharmacodynamic model informed by multi-type patient data has been published online in Cancer Research. (The bioRxiv preprint is also available.) For a popular science account, read about the study in the research magazine Apollon.

cancer-2019-fig1

Abstract: The usefulness of mechanistic models to disentangle complex multi-scale cancer processes such as treatment response has been widely acknowledged. However, a major barrier for multi-scale models to predict treatment outcomes in individual patients lies in their initialization and parametrization which need to reflect individual cancer characteristics accurately. In this study we use multi-type measurements acquired routinely on a single breast tumor, including histopathology, magnetic resonance imaging, and molecular profiling, to personalize parts of a complex multi-scale model of breast cancer treated with chemotherapeutic and anti-angiogenic agents. The model accounts for drug pharmacokinetics and pharmacodynamics. We developed an open-source computer program that simulates cross-sections of tumors under 12-week therapy regimens and use it to individually reproduce and elucidate treatment outcomes of four patients. Two of the tumors did not respond to therapy, and model simulations were used to suggest alternative regimens with improved outcomes dependent on the tumor’s individual characteristics. It was determined that more frequent and lower doses of chemotherapy reduce tumor burden in a low proliferative tumor while lower doses of anti-angiogenic agents improve drug penetration in a poorly perfused tumor. Furthermore, using this model we were able to predict correctly the outcome in another patient after 12 weeks of treatment. In summary, our model bridges multi-type clinical data to shed light on individual treatment outcomes.

What can uncertainty quantification tell us about solute spread in the brain?

Our new preprint on Uncertainty quantification of parenchymal tracer distribution using random diffusion and convective velocity fields is now out on bioRxiv! My first time submitting to bioRxiv rather than good old arXiv.

Over the last decade, there has been a significant renewed interest in the waterscape of the brain; that is, the physiological mechanisms governing cerebrospinal fluid (CSF) and interstitial fluid (ISF) flow in (and around) the brain. A number of new theories have emerged, but a great deal of uncertainty relating to the roles of diffusion, convection and clearance within the brain remains. With this study, we aimed to rigorously quantify how the aforementioned uncertainties in the physiological parameters and in ISF flow affect the spread of a tracer into the brain. We assumed movement of tracer in the brain  to occur by diffusion and/or convection. To account for uncertainty and variability, we circumvented the lack of precise parameter values by modelling velocity and diffusivity as Matérn stochastic fields. We then set up a PDE model with these stochastic (random) fields as coefficients and quantify the uncertainty in the model prediction via the Monte Carlo (MC) method.

 

Waterscales Cécile Daversin-Catty wins Best presentation award at FEniCS’18

oxfordCongratulations to Cécile Daversin-Catty for winning the Best postdoctoral presentation award at the FEniCS’18 conference at the University of Oxford from March 21-23 2018! Cécile, postdoctoral fellow with the Waterscales project, presented her exciting and versatile work on mixed-dimensional coupled finite elements in FEniCS.

Overall, the Waterscales and Waterscape projects were well represented in the FEniCS’18 program with additional talks from Waterscape post doc Travis Thompson (on Stokes-Biot stable H(div)-based mixed finite element methods for generalized poroelasticity), from SUURPh PhD candidate Eleonora Piersanti (on Parameter-robust discretization and preconditioning of the multiple-network poroelasticity equations), and a poster presentation from Waterscales PhD candidate Ada Ellingsrud (on Numerical modelling of the role of glial cells in cerebral interstitial fluid movement). Well done Waterscapers!