3D modelling of angiogenesis and vascular tumour growth

This paper was presented at the 3rd Micro and Nano Flows Conference (MNF2011), which was held at the Makedonia Palace Hotel, Thessaloniki in Greece. The conference was organised by Brunel University and supported by the Italian Union of Thermofluiddynamics, Aristotle University of Thessaloniki, University of Thessaly, IPEM, the Process Intensification Network, the Institution of Mechanical Engineers, the Heat Transfer Society, HEXAG - the Heat Exchange Action Group, and the Energy Institute

Chaste: an open source C++ library for computational physiology and biology

Chaste - Cancer, Heart And Soft Tissue Environment - is an open source C++ library for the computational simulation of mathematical models developed for physiology and biology. Code development has been driven by two initial applications: cardiac electrophysiology and cancer development. A large number of cardiac electrophysiology studies have been enabled and performed, including high performance computational investigations of defibrillation on realistic human cardiac geometries. New models for the initiation and growth of tumours have been developed. In particular, cell-based simulations have provided novel insight into the role of stem cells in the colorectal crypt. Chaste is constantly evolving and is now being applied to a far wider range of problems. The code provides modules for handling common scientific computing components, such as meshes and solvers for ordinary and partial differential equations (ODEs/PDEs). Re-use of these components avoids the need for researchers to "re-invent the wheel" with each new project, accelerating the rate of progress in new applications. Chaste is developed using industrially-derived techniques, in particular test-driven development, to ensure code quality, re-use and reliability. In this article we provide examples that illustrate the types of problems Chaste can be used to solve, which can be run on a desktop computer. We highlight some scientific studies that have used or are using Chaste, and the insights they have provided. The source code, both for specific releases and the development version, is available to download under an open source Berkeley Software Distribution (BSD) licence at http://www.cs.ox.ac.uk/chaste, together with details of a mailing list and links to documentation and tutorials

Adhesion Failures Determine the Pattern of Choroidal Neovascularization in the Eye: A Computer Simulation Study

Choroidal neovascularization (CNV) of the macular area of the retina is the major cause of severe vision loss in adults. In CNV, after choriocapillaries initially penetrate Bruch's membrane (BrM), invading vessels may regress or expand (CNV initiation). Next, during Early and Late CNV, the expanding vasculature usually spreads in one of three distinct patterns: in a layer between BrM and the retinal pigment epithelium (sub-RPE or Type 1 CNV), in a layer between the RPE and the photoreceptors (sub-retinal or Type 2 CNV) or in both loci simultaneously (combined pattern or Type 3 CNV). While most studies hypothesize that CNV primarily results from growth-factor effects or holes in BrM, our three-dimensional simulations of multi-cell model of the normal and pathological maculae recapitulate the three growth patterns, under the hypothesis that CNV results from combinations of impairment of: 1) RPE-RPE epithelial junctional adhesion, 2) Adhesion of the RPE basement membrane complex to BrM (RPE-BrM adhesion), and 3) Adhesion of the RPE to the photoreceptor outer segments (RPE-POS adhesion). Our key findings are that when an endothelial tip cell penetrates BrM: 1) RPE with normal epithelial junctions, basal attachment to BrM and apical attachment to POS resists CNV. 2) Small holes in BrM do not, by themselves, initiate CNV. 3) RPE with normal epithelial junctions and normal apical RPE-POS adhesion, but weak adhesion to BrM (e.g. due to lipid accumulation in BrM) results in Early sub-RPE CNV. 4) Normal adhesion of RBaM to BrM, but reduced apical RPE-POS or epithelial RPE-RPE adhesion (e.g. due to inflammation) results in Early sub-retinal CNV. 5) Simultaneous reduction in RPE-RPE epithelial binding and RPE-BrM adhesion results in either sub-RPE or sub-retinal CNV which often progresses to combined pattern CNV. These findings suggest that defects in adhesion dominate CNV initiation and progression

New laser design for NIR lidar applications

Recently, we quantified the very high spatio-temporal short term variability of tropospheric water vapor in a three dimensional study [1]. From a technical point of view this also depicted the general requirement of short integration times for recording water-vapor profiles with lidar. For this purpose, the only suitable technique is the differential absorption lidar (DIAL) working in the near-infrared (NIR) spectral region. The laser emission of most water vapor DIAL systems is generated by Ti:sapphire or alexandrite lasers. The water vapor absorption band at 817 nm is predominated for the use of Ti:sapphire. We present a new concept of transversely pumping in a Ti:Sapphire amplification stage as well as a compact laser design for the generation of single mode NIR pulses with two different DIAL wavelengths inside a single resonator. This laser concept allows for high output power due to repetitions rates up to 100Hz or even more. It is, because of its compactness, also suitable for mobile applications

New laser design for NIR lidar applications

Recently, we quantified the very high spatio-temporal short term variability of tropospheric water vapor in a three dimensional study [1]. From a technical point of view this also depicted the general requirement of short integration times for recording water-vapor profiles with lidar. For this purpose, the only suitable technique is the differential absorption lidar (DIAL) working in the near-infrared (NIR) spectral region. The laser emission of most water vapor DIAL systems is generated by Ti:sapphire or alexandrite lasers. The water vapor absorption band at 817 nm is predominated for the use of Ti:sapphire. We present a new concept of transversely pumping in a Ti:Sapphire amplification stage as well as a compact laser design for the generation of single mode NIR pulses with two different DIAL wavelengths inside a single resonator. This laser concept allows for high output power due to repetitions rates up to 100Hz or even more. It is, because of its compactness, also suitable for mobile applications

3D hybrid modelling of vascular network formation

We develop an off-lattice, agent-based model to describe vasculogenesis, the de novo formation of blood vessels from endothelial progenitor cells during development. The endothelial cells that comprise our vessel network are viewed as linearly elastic spheres that move in response to the forces they experience. We distinguish two types of endothelial cells: vessel elements are contained within the network and tip cells are located at the ends of vessels. Tip cells move in response to mechanical forces caused by interactions with neighbouring vessel elements and the local tissue environment, chemotactic forces and a persistence force which accounts for their tendency to continue moving in the same direction. Vessel elements are subject to similar mechanical forces but are insensitive to chemotaxis. An angular persistence force representing interactions with the local tissue is introduced to stabilise buckling instabilities caused by cell proliferation. Only vessel elements proliferate, at rates which depend on their degree of stretch: elongated elements have increased rates of proliferation, and compressed elements have reduced rates. Following division, the fate of the new cell depends on the local mechanical environment: the probability of forming a new sprout is increased if the parent vessel is highly compressed and the probability of being incorporated into the parent vessel increased if the parent is stretched. Simulation results reveal that our hybrid model can reproduce the key qualitative features of vasculogenesis. Extensive parameter sensitivity analyses show that significant changes in network size and morphology are induced by varying the chemotactic sensitivity of tip cells, and the sensitivities of the proliferation rate and the sprouting probability to mechanical stretch. Varying the chemotactic sensitivity directly influences the directionality of the networks. The degree of branching, and thereby the density of the networks, is influenced by the sprouting probability. Glyphs that simultaneously depict several network properties are introduced to show how these and other network quantities change over time and also as model parameters vary. We also show how equivalent glyphs constructed from in vivo data could be used to discriminate between normal and tumour vasculature and, in the longer term, for model validation. We conclude that our biomechanical hybrid model can generate vascular networks that are qualitatively similar to those generated from in vitro and in vivo experiments

3D hybrid modelling of vascular network formation

We develop an off-lattice, agent-based model to describe vasculogenesis, the de novo formation of blood vessels from endothelial progenitor cells during development. The endothelial cells that comprise our vessel network are viewed as linearly elastic spheres that move in response to the forces they experience. We distinguish two types of endothelial cells: vessel elements are contained within the network and tip cells are located at the ends of vessels. Tip cells move in response to mechanical forces caused by interactions with neighbouring vessel elements and the local tissue environment, chemotactic forces and a persistence force which accounts for their tendency to continue moving in the same direction. Vessel elements are subject to similar mechanical forces but are insensitive to chemotaxis. An angular persistence force representing interactions with the local tissue is introduced to stabilise buckling instabilities caused by cell proliferation. Only vessel elements proliferate, at rates which depend on their degree of stretch: elongated elements have increased rates of proliferation, and compressed elements have reduced rates. Following division, the fate of the new cell depends on the local mechanical environment: the probability of forming a new sprout is increased if the parent vessel is highly compressed and the probability of being incorporated into the parent vessel increased if the parent is stretched. Simulation results reveal that our hybrid model can reproduce the key qualitative features of vasculogenesis. Extensive parameter sensitivity analyses show that significant changes in network size and morphology are induced by varying the chemotactic sensitivity of tip cells, and the sensitivities of the proliferation rate and the sprouting probability to mechanical stretch. Varying the chemotactic sensitivity directly influences the directionality of the networks. The degree of branching and thereby the density of the networks is influenced by the sprouting probability. Glyphs that simultaneously depict several network properties are introduced to show how these and other network quantities change over time and also as model parameters vary. We also show how equivalent glyphs constructed from in vivo data could be used to discriminate between normal and tumour vasculature and, in the longer term, for model validation. We conclude that our biomechanical hybrid model can generate vascular networks that are qualitatively similar to those generated from in vitro and in vivo experiments.</p