Abstract
Solid tumour growth is often associated to the accumulation of mechanical stresses acting on the surrounding host tissue. These forces alter the biomechanics of the adjacent tissue, which can be probed with propagating shear waves and quantified through MRElastography. The reconstructed shear modulus in the peri-tumoural region inherits a signature from the tumour expansion which depends on multiple factors, including the soft tissue constitutive law, stress/strain states in the ensemble and the local wave propagation direction. Here we have used analytical and experimental means based on a simple setup of the tissue-tumour ensemble to investigate the shifts in shear modulus associated to a spherical inflation as a way to bridge to in vivo tissue.Due to tissue nonlinearity, the shear modulus of the tumour environment will change according to the local deformation created by the tumour forces, increasing when undergoing stretch and decreasing when compressed. Shear waves can sense the apparent stiffness along its propagation direction, hence probing a negative change, compared to the background modulus, at the leading edge of the inflated object and a positive variation along the lateral area.
In this thesis we have developed an analytical framework that associates the expected signature pattern to the radial stretch generated by the spherical inflation, using a thickshelled sphere approximation and a specific hyperelastic strain energy density function. A phantom consisting of an inflatable Foley catheter inserted inside a soft tissue-mimicking cuboid was then built to reproduce the tissue-tumour ensemble and to validate the analytical findings. A measuring system based on a pressure sensor was used to quantify the radial stress applied by the inflated balloon onto the surrounding soft plastic material, while the associated strain was instead estimated through an implemented non-rigid image registration strategy, applied to high resolution MR images acquired at the various inflation states. A rheological characterisation of the chosen material confirmed the suitability of the constitutive equation employed in the development of the analytical formulation to model its stress/strain relationship.
Using the developed phantom, inflation experiment were carried out to empirically probe the apparent variation in shear modulus, generated at different balloon inflations, through MRE. The observed anisotropy displayed a satisfactory agreement with the predicted patterns, especially at higher strains, where the nonlinear response of the material was more pronounced, and also showed a good correlation with the deformation sensed by the probing shear waves. A preliminary replicate of this experiment ex vivo also helped to identify the challenges expected in in vivo application.
Overall, we have demonstrated that MRE, in combination with non-linear mechanics, is capable to predict the apparent alteration of shear modulus of soft tissue generated by tumour expansion. These results are expected to provide a significant step towards the development of a noninvasive method to measure and monitor intra- and peri-tumoural stresses as a biomarker for tumour progression and treatment efficacy
| Date of Award | 1 Sept 2019 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Ralph Sinkus (Supervisor) & Gilbert Fruhwirth (Supervisor) |