Abstract. Magnetic resonance elastography is a motion-sensitive image modality that allows to measure in vivo tissue displacement fields in response to mechanical excitations. This paper investigates a data assimilation approach for reconstructing tissue displacement and pressure fields in an in silico brain model from partial elastography data. The data assimilation is based on a parametrized-background data-weak methodology, in which the state of the physical system—tissue displacements and pressure fields—is reconstructed from the available data assuming an underlying poroelastic biomechanics model. For this purpose, a physics-informed manifold is built by sampling the space of parameters describing the tissue model close to their physiological ranges to simulate the corresponding poroelastic problem and computing a reduced basis via proper orthogonal decomposition. Displacements and pressure reconstruction are sought in a reduced space after solving a minimization problem that encompasses both the structure of the reduced-order model and the available measurements. The proposed pipeline is validated using synthetic data obtained after simulating the poroelastic mechanics of a physiological brain. The numerical experiments demonstrate that the framework can exhibit accurate joint reconstructions of both displacement and pressure fields. The methodology can be formulated for an arbitrary resolution of available displacement data from pertinent images. It can also inherently handle uncertainty on the physical parameters of the mechanical model by enlarging the physics-informed manifold accordingly. Moreover, the framework can be used to characterize, in silico, biomarkers for pathological conditions by appropriately training the reduced-order model. A first application for the noninvasive estimation of ventricular pressure as an indicator of abnormal intracranial pressure is shown in this contribution.

MOTIVATION: Agent-based modeling is an indispensable tool for studying complex biological systems. However, existing simulation platforms do not always take full advantage of modern hardware and often have a field-specific software design. RESULTS: We present a novel simulation platform called BioDynaMo that alleviates both of these problems. BioDynaMo features a modular and high-performance simulation engine. We demonstrate that BioDynaMo can be used to simulate use cases in: neuroscience, oncology and epidemiology. For each use case, we validate our findings with experimental data or an analytical solution. Our performance results show that BioDynaMo performs up to three orders of magnitude faster than the state-of-the-art baselines. This improvement makes it feasible to simulate each use case with one billion agents on a single server, showcasing the potential BioDynaMo has for computational biology research. AVAILABILITY AND IMPLEMENTATION: BioDynaMo is an open-source project under the Apache 2.0 license and is available at www.biodynamo.org. Instructions to reproduce the results are available in the supplementary information. SUPPLEMENTARY INFORMATION: Available at https://doi.org/10.5281/zenodo.5121618.

[This corrects the article DOI: 10.1371/journal.pcbi.1006460.].

The delivery of blood-borne therapeutic agents to solid tumours depends on a broad range of biophysical factors. We present a novel multiscale, multiphysics, in-silico modelling framework that encompasses dynamic tumour growth, angiogenesis and drug delivery, and use this model to simulate the intravenous delivery of cytotoxic drugs. The model accounts for chemo-, hapto- and mechanotactic vessel sprouting, extracellular matrix remodelling, mechano-sensitive vascular remodelling and collapse, intra- and extravascular drug transport, and tumour regression as an effect of a cytotoxic cancer drug. The modelling framework is flexible, allowing the drug properties to be specified, which provides realistic predictions of in-vivo vascular development and structure at different tumour stages. The model also enables the effects of neoadjuvant vascular normalisation to be implicitly tested by decreasing vessel wall pore size. We use the model to test the interplay between time of treatment, drug affinity rate and the size of the vessels' endothelium pores on the delivery and subsequent tumour regression and vessel remodelling. Model predictions confirm that small-molecule drug delivery is dominated by diffusive transport and further predict that the time of treatment is important for low affinity but not high affinity cytotoxic drugs, the size of the vessel wall pores plays an important role in the effect of low affinity but not high affinity drugs, that high affinity cytotoxic drugs remodel the tumour vasculature providing a large window for the normalisation of the vascular architecture, and that the combination of large pores and high affinity enhances cytotoxic drug delivery efficiency. These results have implications for treatment planning and methods to enhance drug delivery, and highlight the importance of in-silico modelling in investigating the optimisation of cancer therapy on a personalised setting.

Vascularisation is a key feature of cancer growth, invasion and metastasis. To better understand the governing biophysical processes and their relative importance, it is instructive to develop physiologically representative mathematical models with which to compare to experimental data. Previous studies have successfully applied this approach to test the effect of various biochemical factors on tumour growth and angiogenesis. However, these models do not account for the experimentally observed dependency of angiogenic network evolution on growth-induced solid stresses. This work introduces two novel features: the effects of hapto- and mechanotaxis on vessel sprouting, and mechano-sensitive dynamic vascular remodelling. The proposed three-dimensional, multiscale, in-silico model of dynamically coupled angiogenic tumour growth is specified to in-vivo and in-vitro data, chosen, where possible, to provide a physiologically consistent description. The model is then validated against in-vivo data from murine mammary carcinomas, with particular focus placed on identifying the influence of mechanical factors. Crucially, we find that it is necessary to include hapto- and mechanotaxis to recapitulate observed time-varying spatial distributions of angiogenic vasculature.

We consider robotic analogues of the arms of the octopus, a cephalopod exhibiting a wide variety of dexterous movements and complex shapes, moving in an aquatic environment. Although an invertebrate, the octopus can vary the stiffness of its long arms and generate large forces, while also performing rapid motions within its aquatic environment. Previous studies of elongated robotic systems, moving in fluid environments, have mostly oversimplified the effects of flow and the generated hydrodynamic forces, in their dynamical models. The present paper uses computational fluid dynamic (CFD) analysis to perform high-fidelity numerical simulations of robotic prototypes emulating the morphology of octopus arms. The direction of the flow stream and the arm geometry (e.g., the presence of suckers), were among the parameters that were shown to affect significantly the flow field structure and the resulting hydrodynamic forces, which have a non-uniform distribution along the arm. The CFD results are supported by vortex visualization experiments in a water tank. The results of this investigation are being exploited for the design of soft-bodied robotic systems and the development of related motion control strategies.