Abstract
Angiogenesis and neovascularization are biological processes which take place in tissues and that are associated to an increase of the demands in oxygen and nutrients. In healthy adults these processes hardly ever occur. However, in disease conditions, such as inflammations or tumor developments, the VEGF (vascular endothelial growth factor), the signaling protein causing angiogenesis, is highly expressed. Under these circumstances new vessels and capillaries are rapidly formed. This new vasculature network is chaotic and has no normal structure, especially in the case of tumors.
The quantification of the angiogenesis is essential in order to assess the degree of tumor aggressiveness and the effectiveness of treatments. It is necessary to develop reliable and reproducible tools which are sensitive to early changes so that more individualized treatments can be used. In this sense, the pharmacokinetic modeling of perfusion magnetic resonance (MR) images is a valuable tool for the evaluation of the tissue microvascular properties, as it allows calculating parameters such as the capillary permeability, the extraction rate, the interstitial volume and the vascular volume. These models have been extensively used for the analysis of breast, liver and brain tumors; and they have also been proposed as accurate imaging biomarkers, both for the evaluation of a disease and a treatment.
In this thesis, new methodological developments and clinical applications are proposed. Regarding methodological developments, firstly a new model approached is proposed to assess arterial vascularization, based on the introduction an arterial index which quantifies the degree of arterial vascularization of any tissue in comparison to a reference arterial enhancement curve. Secondly, a temporal filter is proposed in order to improve the quality of the enhancement curves. Finally, a set of visualization and statistical tools is also introduced in order to improve the analysis of the results.
Regarding clinical applications, the pharmacokinetic models are implemented and applied in novel scenarios, such as the treatment of the ovarian hyperstimulation syndrome, the assessment of cartilage degeneration and the treatment of osteoarthritis. Then, further applications on the assessment of the arterial contribution of the hepatocellular carcinoma and the multivariate analysis of grade-IV astrocytomas are presented. Finally, the influence of the magnetic field strength on the pharmacokinetic parameters is also assessed.
The proposed developments and clinical applications have shown good results, as they improved the amount of information and the accuracy of the pharmacokinetic models, providing further knowledge for a better assessment of both disease and treatment effects. The new clinical applications have demonstrated the potential and the effectiveness of the pharmacokinetic parameters as imaging biomarkers extracted from perfusion MR images.