title: Growth and remodelling of the left ventricle post myocardial infarction
Creators: name: Zhuan, Xin
Publisher: name: University of Glasgow
Year: 2018
Subjects: subject: residual stress, multiple-cut opening angle model, myocardial infarction, growth and remodeling, agent-based model.

description: Living organs in human bodies continuously interact with the $in\ vivo$ bio-environment, while reshaping and rearranging 
their constituents, responding to external or internal stimuli through life cycles. For instance, living tissues adjust the growth (or turnover) rates of their constituents to develop (volumetric and mass) changes as the tissues adapt to the pathological or physiological changes in bio-environment. From the perspective of biomechanics, changes in the bio-environment will induce the growth and remodelling (G\&amp;R) process and reset the mechanical environment. Consequently, the mechanical cues will feed back to G\&amp;R processes. In the long run, the interaction between G\&amp;R and the mechanical response of living organs plays an important role in regulating the organ formulation or pathological growth. 

To understand the interaction between the mechanical response and the G\&amp;R process, an important ingredient in evaluating the involved mechanics is knowledge of the solid mechanical properties of the soft tissues. Residual stress, resulting from G\&amp;R of soft tissues, is important in modelling the mechanics of soft tissues, which still presents a modelling challenge for including residual stress in cardiovascular applications. For G\&amp;R of living organs, changes of tissue structure and volume are also important determinants for organ development. This raises academic challenges for the understanding of the evolution of material properties and mechanical response of living tissues within a dynamic environment.

To investigate the stress states (residual strain or residual stress) of living organs, the experimental results showed that the arterial slices would spring open after cutting along the radial directions, which indicates the residual strain in organs estimated by the opening angle. The residual strain, which is the elastic strain between zero-stress and no-load states, indicates the existence of residual stress after removal of the external loads. The residual stress is considered to modulate the growth and remodelling process in living organs. The evolution of residual stress could relieve the information about the history of growth, which could help to better the understanding of the formation of organs and the development of diseases. 

Besides the residual stress, G\&amp;R processes are regulated by other factors, while the principles governing those mechanism are still not fully understood. Obviously, improving knowledge in this particular field will give huge potential for the design and optimization of clinical treatments to efficiently save more lives. 

From a general mechanics perspective to investigate the G\&amp;R process in living tissues, the questions are: How does the residual stress influence the fibre remodelling and the material properties of entire organs? How to determine the combined effects of growth (in the stressed configuration) and remodelling on the fibre structure? How to develop a framework for investigating G\&amp;R processes occurring in the stressed configuration? 

For arteries, multiple layer models are developed to analytically study residual stress in living organs. For the heart, due to its complex structure and geometry, most previous studies used the unloaded configuration or one-cut configuration as the stress-free configuration to estimate the stress state. However, both experimental and theoretical studies have suggested that: 1) residual stress will significantly influence the stress distribution in the heart. 2) a simple (or single) cut does not release all the residual stress in the heart. We build a multi-cut model and show that multiple cuts are required to release the residual stresses in the left ventricle. Our results show that with the 2-cut and 4-cut models (one radial cut followed by circumferential cuts), agreement with the measured opening angles and radii can be greatly improved. This suggests that a multi-cut model should be used to predict the residual stresses in the left ventricle, at least in the middle wall region. We further show that tissue heterogeneity plays a significant role in the model results, and that an inhomogeneous model with combined
 radial and circumferential cuts should be used to estimate the correct order of magnitude of the residual stress in the heart. 

Understanding the healing and remodelling processes induced by myocardial infarction (MI) of the heart is important and the mechanical properties of the myocardium post-MI can be indicative for effective treatments aimed at avoiding eventual heart failure. MI remodelling is a multiscale feedback process between the mechanical loading and cellular adaptation. In this thesis, we use an agent-based model to describe collagen remodelling by fibroblasts regulated by chemical and mechanical cues after acute MI, and upscale into a
finite element (FE) 3D left ventricular model. This enables us to study the scar healing (collagen deposition,
degradation and reorientation) of a rat heart post-MI. Our results, in terms of collagen accumulation and
alignment, compare well to published experimental data. In addition, we show that different shapes of the
MI region can affect the collagen remodelling, and in particular, the mechanical cue plays an important role
in the healing process. 

For volumetric growth, recently, when the idea of growth is applied to study the evolution of organ formations, it's usually assumed that growth always occurs in the natural (reference) configuration. In some researches, it is assumed that the growth could release all the residual stress, and that further growth will start from the updated but stress-free configuration. However, living organs are actually exposed to external loading all the time, while the growth should occur from the residually-stressed current configuration. In this thesis, A theoretical framework is developed to calculate the mechanical behaviour of soft tissue after introducing inhomogeneous growth in a residually-stressed current configuration, which avoids assuming that the growth occurs in a `virtual' reference configuration. Moreover, the theoretical framework is introduced to couple the growth and fibre remodelling process to describe the mechanical behaviour of living tissues.