An investigation into diffusion tensor imaging-derived metrics in arterial tissue as biomarkers for disease progression, plaque rupture and graft recellularisation

Abstract

Non-invasive imaging offers great potential for several clinical applications, both in disease and treatment monitoring. Specifically, within vascular tissue better clinical indicators for vulnerable atherosclerotic plaque, as well as tracking of vascular graft integration, could benefit from insights gained using non-invasive imaging. The aim of this thesis was to establish a non-invasive characterisation technique, diffusion tensor imaging (DTI), within vascular tissue for a multitude of applications.

To achieve this, the sensitivity of DTI-derived metrics to specific microstructural changes in arterial tissue models was first investigated. Of note, a strong sensitivity to cell and elastin content was discovered establishing that the measurable anisotropic diffusion within arterial tissue is predominantly driven by these components. This sensitivity was then explored within human atherosclerotic tissue for anatomical, microstructural, morphological, and mechanical characterisations. Within human cadaveric carotid arteries, a strong correlation between DTI-derived metrics and elastin content was found a significant finding for any pathology driven by changes in elastin content. DTI-derived metrics were also explored in early atherosclerosis and found to identify the thickened intima. Tractography yielded significant insight into the mechanical integrity of mechanically tested fresh human atherosclerotic plaques, whereby it was able to differentiate between more stable microstructures and those which would be more vulnerable to failure at lower stresses and strains. The sensitivity to cell content was revisited and demonstrated clearly in cultured vascular grafts which were characterised non-invasively and non-destructively. Tractography and DTI-derived fractional anisotropy were able to distinguish between acellular and recellularised vascular grafts and tracked that recellularisation over two weeks.

Together, the investigations presented in this thesis not only establish DTI within vascular tissue but also highlight its potential in disease diagnosis, tissue engineering, and even in the foreign body response around device integration.