Research

Computational Modelling of Tumour Growth

Sprouting Angiogenesis

Sprouting Angiogenesis

Image: A simulation of sprouting angiogenesis in a corneal micropocket assay experiment.

Sprouting angiogenesis is a process in which new vasculature is formed. It is of central importance in the diagnosis and treatment of many cancers. It is a complex combination of biophysical processes, which are the focus of much on-going research. I am interested in the development and application of open source software for multi-scale modelling of this process and integration with intravital imaging data, in collaboration with Prof. Ruth Muschel’s group at the University of Oxford.

Relevant publications:

  • J.A. Grogan, A.J. Connor, B. Markelc, R.J. Muschel, P.K. Maini, H.M. Byrne, J.M. Pitt-Francis, Microvessel Chaste: An Open Library for Spatial Modelling of Vascularized Tissues, In Submission.

Tumour Blood Flow

Blood Flow

Image: A segmented tumour microvessel network and a computer simulation of red blood cells flowing through it (thanks to Dr. Miguel Bernabeu, University of Edniburgh).

The availability of oxygen in tumours affects malignancy and responsiveness to treatments such as radiotherapy. Tumour oxygenation depends on how red blood cells are distributed throughout the microvasculature. Suitable rules for modelling the distribution of red blood cells in the pathological vasculature of tumours have not yet been determined. I am interested in studying how red blood cells distribute at branching points in the tumour, and ultimately making better predictions of oxygenation. This study is in collaboration with Prof. Ruth Muschel’s group at the University of Oxford, Dr. Miguel Bernabeu at the University of Edniburgh and Prof. Tomas Alarcon’s group at the CRM, Barcelona.

Radiotherapy

Radiotherapy

Image: A multi-scale, agent-based simulation of radiotherapy using a real tumour microvessel network.

The reponsiveness of tumours to radiotherapy depends on oxygen availability, which in turn depends on the strucutre of the tumour microvessel network. I am interested in studying the relationship between the 3D structure of the microvasculature and radiotherapy response. This involves simulating tumour growth and radiotherapy using multi-scale, agent-based soft tissue models.

Relevant publications:

  • J.A. Grogan, B. Markelc, A.J. Connor, R.J. Muschel, J.M. Pitt-Franices, P.K. Maini, H.M. Byrne, Predicting the influence of microvascular structure On tumour response to radiotherapy, IEEE Transactions on Biomedical Engineering, In Press, 2016.

Modelling and Design of Medical Devices

Magnesium Corrosion

Radiotherapy

Image: 3D Scanning electron microscopy of a bioaborbable magnesium alloy post corrosion.

A new generation of temporary, bioabsorbable metallic medical devices are showing great promise. New computational techniques are required for simulating the bio-corrosion of these devices and predicting long term performance and risk. I have developed a number of models of magnesium bio-corrosion, based on experimental testing of long-term corrosion of AZ31 alloy under static loading and applied these in the study of bioabsorbable metal stents.

Relevant publications:

  • J.A. Grogan, S.B. Leen, P.E. McHugh, A physical corrosion model for bioabsorbable metallic stents, Acta Biomaterialia, In Press, DOI:10.1016/j.actbio.2013.12.059, 2014.
  • J.A. Grogan, D. Gastaldi, M. Castelletti, F. Migliavacca, G. Dubini, P.E. McHugh, A novel flow chamber for biodegradable alloy assessment in physiologically realistic environments, Review of Scientific Instruments, 34:094301, 2013.
  • J.A. Grogan, S.B. Leen, P.E. McHugh, Optimizing the design of a bioabsorbable metal stent using computer simulation methods, Biomaterials, 34:8049-60, 2013.
  • J.A. Grogan, B.J. O’Brien, S.B. Leen, P.E. McHugh, A corrosion model for bioabsorbable metallic stents, Acta Biomaterialia, 7:3523-33, 2011.

Advanced Stent Deployment

Tracking

Image: Finite element simulation of stent delivery in a stenosed, curved, vessel.

Accurate simulation of coronary stent deployment in the body can reduce reliance on costly experimental testing and accelerate device design. Detailed simulations, including curved, stenosed arteris and folded balloons encompass many challenging areas of solid mechanics. This includes, large deformations of anisotropic elastic materials, finite sliding contanct, and construction of complex 3D geometries. I have developed techniques for high resolution stent deployment modelling, and applied them in studying bioabsorbable magnesium devices.

Relevant publications:

  • J.A. Grogan, S.B. Leen, P.E. McHugh, Optimizing the design of a bioabsorbable metal stent using computer simulation methods, Biomaterials, 34:8049-60, 2013.
  • J.A. Grogan, S.B. Leen, and P.E. McHugh. Comparing coronary stent material performance on a common geometric platform through simulated benchtesting, Journal of Mechanical Behaviour of Biomedical Materials, 12:129-138, 2012.
  • J.A. Grogan, B.J. O’Brien, S.B. Leen, P.E. McHugh, A corrosion model for bioabsorbable metallic stents, Acta Biomaterialia, 7:3523-33, 2011.

Metal Micromechanics

Tracking

Image: A crystal plasticity finite element simulation of a deforming stent strut.

The struts of coronary stents are less thick than a human hair. At this size scale the assumptions of continuum plasticity theory begin to break-down, as metallic grains become comparible in dimension to the sthe strut. Explicitly modelling individual grains when simulating the deformation of stent struts allows ‘statisical size effects’, resulting in unexpectedly low failure strains, to be investigated. I have studied the deformation of stent struts using crystal plasticity theory for a range of candidate stent materials, including magnesium.

Relevant publications:

  • J.A. Grogan, S.B. Leen, P.E. McHugh, Computational micromechanics of bioabsorbable magnesium stents, Journal of Mechanical Behaviour of Biomedical Materials, 34:93-105, 2014.
  • J.A. Grogan, S.B. Leen, P.E. McHugh, Influence of statistical size effects on the plastic deformation of coronary stents, Journal of Mechanical Behaviour of Biomedical Materials, 20:61-76, 2013.

Semi-flexible Polymer Networks

Tracking

Image: A simulation of two cells deforming a semi-flexible network (thanks to Dan Humphries).

The extracellular matrix is a fibre network through which cells can communicate mechanically. The fibrous nature of the network allows cells to communicate over surprisingly large distances. In collaboration with Dan Humphries and Prof. Eamonn Gaffney I interested in exploring how the architecture of these fibre network affects cell-cell communication.

Relevant publications:

  • D.L. Humphries, J.A. Grogan, E.A. Gaffney, Mechanical Cell–Cell Communication in Fibrous Networks: The Importance of Network Geometry, Bulletin of Mathematical Biology, In Press, 10.1007/s11538-016-0242-5, 2017.