Chang Sub Park

Modelling of pH dynamics in brain cells after stroke

The identification of salvageable brain tissue is a major challenge at stroke presentation. Standard techniques used in this context, such as the perfusion–diffusion mismatch, remain controversial. There is thus a need for new methods to help guide treatment. The potential role of pH imaging in this context is currently being investigated. Intracellular pH varies as a function of local perfusion, intracellular energy stores and time. Low pH triggers the production of free radicals and affects the calcium balance of the cells, which may lead to apoptosis and cell death. Thus, the characterization of pH dynamics may have predictive value for cell death after stroke, particularly when combined with novel imaging techniques. Therefore, we have extended an existing model of brain cellular metabolism to simulate the pH response of cells to ischaemia. Simulation results for conditions of reduced cerebral blood flow show good agreement for the evolution of intracellular pH with previously reported measurements and encourage the development of quantitative pH imaging to validate the predictive value of pH.

A generalized mathematical framework for estimating the residue function for arbitrary vascular networks

The microvasculature plays a vital part in the cardiovascular system. Any impairment to its function can lead to significant pathophysiological effects, particularly in organs such as the brain where there is a very tight coupling between structure and function. However, it is extremely difficult to quantify the health of the microvasculature in vivo, other than by assessing perfusion, using techniques such as arterial spin labelling. Recent work has suggested that the flow distribution within a voxel could also be a valuable measure. This can also be measured clinically, but as yet has not been related to the properties of the microvasculature due to the difficulties in modelling and characterizing these strongly inter-connected networks. In this paper, we present a new technique for characterizing an existing physiologically accurate model of the cerebral microvasculature in terms of its residue function. A new analytical mathematical framework for calculation of the residue function, based on the mass transport equation, of any arbitrary network is presented together with results from simulations. We then present a method for characterizing this function, which can be directly related to clinical data, and show how the resulting parameters are affected under conditions of both reduced perfusion and reduced network density. It is found that the residue function parameters are affected in different ways by these two effects, opening up the possibility of using such parameters, when acquired from clinical data, to infer information about both the network properties and the perfusion distribution. These results open up the possibility of obtaining valuable clinical information about the health of the microvasculature in vivo, providing additional tools to clinicians working in cerebrovascular diseases, such as stroke and dementia.

Modelling the effects of cerebral microvasculature morphology on oxygen transport.

Highlights • Solving for O2 transport using artificial models of the cerebral microvasculature.• O2 extraction is dependent on the transit time distribution.• Metabolic rate is dependent on the transit time distribution.• Transit time has an effect on the response of metabolic rate to step changes.

Quantification of the effects of vasomotion on mass transport to tissue from axisymmetric blood vessels.

The process known as vasomotion, rhythmic oscillations in vessel diameter, has been proposed to act as a protective mechanism for tissue under conditions of reduced perfusion, since it is frequently only observed experimentally when perfusion levels are reduced. This could be due to a resultant increase in oxygen transport from the vasculature to the surrounding tissue, either directly or indirectly. It is thus potentially of significant clinical interest as a warning signal for ischemia. However, there has been little analysis performed to quantify the effects of vessel wall movement on time-averaged mass transport. We thus present a detailed analysis of such mass transport for an axisymmetric vessel with a periodically oscillating wall, by solving the non-linear mass transport equation, and quantify the differences between the time-averaged mass transport under conditions of no oscillation (i.e. the steady-state) and varying wall oscillation amplitude. The results show that if the vessel wall alone is oscillated, with an invariant wall concentration, the time-averaged mass transport is reduced relative to the steady-state, but if the vessel wall concentration is also oscillated, then mass transport is increased, although this is generally only true when these oscillate in phase with each other. The influence of Péclet number and the non-dimensional rate of consumption of oxygen in tissue, as well as the amplitude of oscillations, are fully characterised. We conclude by considering the likely implications of these results in the context of oxygen transport to tissue.

A model of tissue contraction during thermal ablation.

A model of a globular protein is used to describe the contraction of tissue exposed to elevated temperatures. This will be useful in predicting the contraction of tissue that is observed during thermal ablation of tumours, which is a problem when trying to determine the ablation zone in post-operative images. The transitions between the states of the protein can be related to a change in the length of the molecule, which can be directly observed as a change in the length of the tissue. A three state model of a globular protein is used to describe the contraction of tissue exposed to elevated temperatures. A nonlinear fitting algorithm is considered here to fit available experimental data and thus to obtain the values of the model parameters. A sensitivity analysis of the proposed mathematical model is performed to determine the most important parameters in the model. The model parameters were obtained from experimental data of isothermal free shrinkage experiments. The predictions of the complete model show similar agreement with the data, well within the experimental error of 10%. The overall activation energy and frequency factor were found to be 201 kJ mol(-1) and [Formula: see text] s(-1) respectively. The results show that the experimental data were well described by the three state model considered here. Furthermore, it was possible to determine the most sensitive parameters in the model. The model presented here will allow predictions of thermal ablation to be corrected for tissue shrinkage, thus improving mathematical simulations for treatment planning, although clinical translation will require adapting the model from experimentally obtained tendon data to soft tissue data.

A thermoelastic deformation model of tissue contraction during thermal ablation

Abstract Purpose: Thermal ablation is an energy-based ablation technique widely used during minimally invasive cancer treatment. Simulations are used to predict the dead tissue post therapy. However, one difficulty with the simulations is accurately predicting the ablation zone in post-procedural images due to the contraction of tissue as a result of exposure to elevated temperatures. Materials and methods: A mathematical model of the thermoelastic deformation for an elastic isotropic material was coupled with a three state thermal denaturation model to determine the contraction of tissue during thermal ablation. A finite difference method was considered to quantify the tissue contraction for a typical temperature distribution during thermal ablation. Results: The simulations show that tissue displacement during thermal ablation was not bound to the tissue heated regions only. Both tissue expansion and contraction were observed at the different stages of the heating process. Tissue contraction of up to 42% was obtained with an applicator temperature of 90 °C. A recovery of around 2% was observed with heating removed as a result of unfolded state proteins returning back to its native state. Poisson’s ratio and the applicator temperature have both been shown to affect the tissue displacement significantly. The maximum tissue contraction was found to increase with both increasing Poisson’s ratio and temperature. Conclusions: The model presented here will allow predictions of thermal ablation to be corrected for tissue contraction, which is an important effect, during comparison with post-procedural images, thus improving the accuracy of mathematical simulations for treatment planning.

Mathematical model of the post-ablation enhancement zone as a tissue-level oedematic response

Abstract Purpose: A hyperdense rim is commonly observed at the periphery of ablation zones during post-ablation imaging (e.g. ultrasound) in tumours. A mathematical model has been developed here to investigate the occurrence of this enhanced rim, caused by the ablated cells, giving an indication of the location of the final ablation region. Materials and methods: The enhanced rim has been assumed here to be due to a tissue-level oedematic response of viable cells, which necessitated coupling multiple modelling elements in a spatially distributed system: thermal cell death, tissue-state dependent ion concentration dynamics, ion transport in the extracellular space, and osmotic cell volume regulation. Results: In response to the imposed temperature function, an ablation zone was predicted, distinguishing the tissue state between ‘dead’ and ‘alive’. A disturbance in intracellular/extracellular ion concentrations was induced due to ion redistribution, which acted as an osmotic stress and contributed to significant cell swelling in a thin rim at the periphery of the ablation zone. It was also found that the rim size only changed slightly with varying lesion size, in response to different temperature profiles. Conclusions: The study presents a novel mathematical model to understand the enhanced rim surrounding the ablation zone by assuming tissue-level cell oedema as the primary potential cause. The model links the direct response to thermal injury to an observable secondary response, which could be of clinical value in that the location of this bright ring could potentially be used for more accurate determination of the extent of the ablation zone.

The effects of non-linearities on shear stress in periodic flow in axi-symmetric vessels

In this paper, a power series and a Fourier series approach is used to solve the governing equations of motion in an elastic axi-symmetric vessel, assuming that blood is an incompressible Newtonian fluid. The time averaged flow has shown to be greater than the steady state flow leading to a larger wall shear stress. Oscillations can also be observed, which is not present in the steady state solution. This is due to the nonlinear momentum terms causing interaction between the harmonics.

The Effects of Non-Linearities on Wave Propagation and Time-Averaged Flow in Elastic Axi-Symmetric Vessels

In this paper, a power series and a Fourier series approach is used to solve the governing equations of motion in an elastic axi-symmetric vessel, assuming that blood is an incompressible Newtonian fluid. For vessels with wall stiffness in the arterial range, the viscosity reduces the wave speed by approximately 10 % and the non-linear terms increases it by approximately 5 % from that predicted by linear wave theory for inviscid fluids. When considering time-averaged flow, spatial perturbations in the flow field were observed, the amplitude being strongly dependent on the amplitude of the temporal perturbations, but only weakly dependent upon the nondimensional groups governing the equations of motion. This variation was strongly non-linear, increasing rapidly at large amplitudes of perturbation. A 10 % change in radius about its steady state value resulted in spatial perturbations of approximately 4 %.