Volume 38, Issue 5

The immune system is a complex distributed system consisting of cells, which circulate through the body, communicate and turnover in response to antigenic perturbations. We discuss new approaches to modelling the functioning of the immune system of humans and experimental animals with a focus on its ‘complexity’. Emerging mathematical and computer models are reviewed to describe the immune system diversity, the cell/cytokine network communication structures, hierarchical regulation, and evolutionary dynamics of immune repertoires.

In this work we present methods and algorithms for construction of a personalized model of coronary haemodynamics based on computed tomography images. This model provides estimations of fractional flow reserve, coronary flow reserve, and instantaneous wave-free ratio taking into account transmural perfusion ratio indices obtained from perfusion images. The presented pipeline consists of the following steps: aorta segmentation, left ventricle wall segmentation, coronary arteries segmentation, construction of 1D network of vessels, partitioning of left ventricle wall, and personalization of the model parameters. We focus on a new technique, which generates specific perfusion zones and computes transmural perfusion ratio according to the quality of available medical images with a limited number of visible terminal coronary vessels. Numerical experiments show that accurate evaluation of stenosis before precutaneous coronary intervention should take into account both fractional flow reserve indices and myocardial perfusion, as well as other indices, in order to avoid misdiagnosis. The presented model provides better understanding of the background of clinical recommendations for possible surgical treatment of a stenosed coronary artery.

A spatially distributed mathematical model is presented that simulates the growth of a non-invasive tumour undergoing treatment by fractionated proton therapy with the use of non-radioactive tumour-specific nanosensitizers. Nanosensitizers are injected intravenously before each irradiation to increase the locally deposited dose via a chain of reactions with therapeutic protons. Modelling simulations show that the use of nanosensitizers allows increasing treatment efficacy. However, their effect is restricted by the necessity of decreasing the energy deposited in tumour in order to comply to the normal damage restrictions. Normalization of tumour microvasculature that accompanies the treatment, also compromises nanosensitizers effect as it impairs their inflow in tumour. It is shown that spatial optimization of irradiation, with conservation of total dose deposited in tumour, can increase tumour cell damage for each single irradiation. However, eventually it may not lead to the overall increase of treatment efficacy, in terms of minimization of the number of remaining viable tumour cells, due to the influence of tumour cell repopulation between irradiations. It is suggested that an efficient way towards minimization of tumour cell repopulation may be the faster suppression of angiogenesis by eradication of metabolically deprived tumour cells. This method can be efficient even despite the fact that it would also cause the decrease of supply of nanosensitizers into the tumour.

We propose a computational framework for a one-dimensional haemodynamic model with the arterial walls described by the fractional-order viscoelastic material constitutive law. This framework is used to compare blood flow characteristics for simulations with elastic and fractional-order viscoelastic walls. We use three well-established benchmark tests: a single pulse wave in a long vessel, flow in a 37-segment network of elastic tubes, and flow in anatomically detailed arterial network consisting of 61 arterial segments. All results for elastic model are in a good agreement with analytical solutions, in vitro data and other well-established approaches. Fractional-order model demonstrates noticeable differences in pulse wave propagation speed and minor differences in pressure and flow profiles. Differences in profiles are negligible in major vessels, but more profound in vessels beyond the third or fourth generation.