Cardiac mechanical model personalisation and its clinical applications

An increasingly important research area within the field of cardiac modelling is the development and study of methods of model-based parameter estimation from clinical measurements of cardiac function. This provides a powerful approach for the quantification of cardiac function, with the potential to ultimately lead to the improved stratification and treatment of individuals with pathological myocardial mechanics. In particular, the diastolic function (i.e., blood filling) of left ventricle (LV) is affected by its capacity for relaxation, or the decay in residual active tension (AT) whose inhibition limits the relaxation of the LV chamber, which in turn affects its compliance (or its reciprocal, stiffness). The clinical determination of these two factors, corresponding to the diastolic residual AT and passive constitutive parameters (stiffness) in the cardiac mechanical model, is thus essential for assessing LV diastolic function. However these parameters are difficult to be assessed in vivo, and the traditional criterion to diagnose diastolic dysfunction is subject to many limitations and controversies. In this context, the objective of this study is to develop model-based applicable methodologies to estimate in vivo, from 4D imaging measurements and LV cavity pressure recordings, these clinically relevant parameters (passive stiffness and active diastolic residual tension) in computational cardiac mechanical models, which enable the quantification of key clinical indices characterising cardiac diastolic dysfunction.
Firstly, a sequential data assimilation framework has been developed, covering various types of existing Kalman filters, outlined in chapter 3. Based on these developments, chapter 4 demonstrates that the novel reduced-order unscented Kalman filter can accurately retrieve the homogeneous and regionally varying constitutive parameters from the synthetic noisy motion measurements. This work has been published in Xi et al. 2011a.
Secondly, this thesis has investigated the development of methods that can be applied to clinical practise, which has, in turn, introduced additional difficulties and opportunities. This thesis has presented the first study, to our best knowledge, in literature estimating human constitutive parameters using clinical data, and demonstrated, for the first time, that while an end-diastolic MR measurement does not constrain the mechanical parameters uniquely, it does provide a potentially robust indicator of myocardial stiffness. This work has been published in Xi et al. 2011b. However, an unresolved issue in patients with diastolic dysfunction is that the estimation of myocardial stiffness cannot be decoupled from diastolic residual AT because of the impaired ventricular relaxation during diastole. To further address this problem, chapter 6 presents the first study to estimate diastolic parameters of the left ventricle (LV) from cine and tagged MRI measurements and LV cavity pressure recordings, separating the passive myocardial constitutive properties and diastolic residual AT. We apply this framework to three clinical cases, and the results show that the estimated constitutive parameters and residual active tension appear to be a promising candidate to delineate healthy and pathological cases. This work has been published in Xi et al. 2012a. Nevertheless, the need to invasively acquire LV pressure measurement limits the wide application of this approach. Chapter 7 addresses this issue by analysing the feasibility of using two kinds of non-invasively available pressure measurements for the purpose of inverse parameter estimation. The work has been submitted for publication in Xi et al. 2012b.

Keywords: cardiac modelling
computational biology
biomechanics
Advisor: Smith, N
Lamata, P