Folarin, A.A.; (2008) Analysis of tumour angio-architecture and blood flow using microcomputed tomography and lattice Boltzmann simulations. Doctoral thesis , University of London.

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Abstract

The precise architecture of the vascular system is critical to its many specialised functions. In sharp contrast tumour vascular architecture is highly disorganised and dysfunctional. The reason for this is the grossly abnormal angiogenic signalling prevalent in the tumour microenvironment. Aberrant tumour vasculature is a key determinant of spatial and temporal heterogeneities of blood flows. Additionally, irregularities in the tumour vascular wall, a lack of functional lymphatics and a severely retarded trans-mural hydrostatic pressure gradient also diminish convective transport out of the vessels. Diffusion therefore remains the dominant transport mode in tumours and presents a considerable barrier to macromolecular therapy (e.g. Antibody-directed enzyme prodrug therapy (ADEPT)). A number of recent studies of vascular morphology in both clinical and xenograft tumours have demonstrated the existence of type-specific architectures. Precisely how these type-specific architectures translate to blood flow through the vascular system had not been determined. To address this we have developed a method for studying the 3D architecture of the tumour and simulating flows through it. This technique uses corrosion casts to capture the 3D tumour vascular system. 3D morphometry was determined by stereoimaging and X-ray micro-computed tomography. A computational fluid dynamics model was then used to study the hydrodynamics of the vascular networks. My results show that vessel structure and architecture varies in clinical colon cancers, but these differences were substantially smaller than those of two human colorectal xenografts (LS147T and SW1222) commonly used in pre-clinical studies. The results also provide evidence that LS147T is, in general, a closer model to most clinical colorectal tumours than SW1222. To our knowledge this is the first attempt to utilise X-ray micro-computed tomography to study vascular corrosion casts of tumours, and using this data, produce 3D flow profiles.

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