Application of magnetic resonance elastography to atherosclerosis

Abstract

Atherosclerosis is the root cause of a wide range of cardiovascular diseases. Although it is a global arterial disease, some of the most severe consequences, heart attack and stroke, are caused by ischemia due to local plaque rupture. The risk of rupture is related to the mechanical properties of the plaque. Magnetic resonance elastography (MRE) images tissue elasticity by inverting, externally excited, harmonic wave displacement into a stiffness map, known as an elastogram. The aim of this thesis is to computationally and experimentally investigate the application of MRE to image the mechanical properties of atherosclerotic plaques. The cardiac cycle, lumen boundary, size and inhomogeneous nature of atherosclerotic plaques pose additional complications compared to more well-established MRE applications. Computational modelling allowed these complications to be assessed in a controlled and simplified environment, prior to experimental studies. Computational simulation of MRE was proposed by combining steady state shear waves, yielded by finite element analysis, with the 2D Helmholtz inversion algorithm. The accuracy and robustness of this technique was ascertained through models of homogeneous tissue. A computational sensitivity study was conducted through idealised atherosclerotic plaques, incorporating the effects of disease variables and mechanical, imaging and inversion parameters on the wave images and elastograms. Subject to parameter optimisation, a change in local plaque shear modulus with composition was established. Amongst other variables, an increase of the lipid pool volume in 10mm3 increments was shown to decrease the predicted shear modulus for stenosis sizes between 50% and 80%. The limitations of the Helmholtz inversion algorithm were demonstrated. A series of arterial phantoms containing plaques of various size and stiffness were developed to test the experimental feasibility of the technique. The lumen was identifiable in the wave images and elastograms. However the experimental wave propagation, noise and resolution left the vessel wall and plaque unresolvable. A computational replica of the phantoms yielded clearer wave images and elastograms, indicating that changes to the experimental procedure could lead to more successful results. The comparison also highlighted certain areas for improvement in the computational work. Imaging protocol for in vivo MRE through the peripheral arteries of healthy volunteers and peripheral artery disease patients was developed. The presence of physiological motion and low signal to noise ratios made the vessel anatomy unidentifiable. The application of MRE to atherosclerotic plaques through simulations, arterial phantoms, healthy volunteers and patients has shown that although there is the potential to identify a change in shear modulus with composition, the addition of realistic experimental complications are severely limiting to the technique. The gradual addition of complications throughout the thesis has allowed their impact to be assessed and in turn has highlighted areas for future research.