Monitoring angiogenesis using magnetic resonance methods

When a tumor reaches a certain size it can no longer rely on passive perfusion for nutrition. The tumor therefore emits signaling molecules which stimulating surrounding vessels to divide and grow towards the tumor, a process known as angiogenesis. Very little angiogenesis is present in healthy adults where it is primaily found in wound healing, pregnancy and during the menstrual cycle. This thesis focus on the negative consequences of angiogenesis in cancer. It consists of a an initial overview followed by four manuscripts. The overview gives a short introduction to the process of angiogenesis and the involved signaling molecules. Subsequently, a short review of contrast agents and perfusion measurements is given. Finally, methods for monitoring angiogenesis using magnetic resonance imaging are reviewed. A method for monitoring early stages of angiogenesis as well as the effect of anti-angiogenic treatment is presented in the first manuscript. In the second and third manuscript, two separate methods of quantifying perfusion, blood volume and vessel permeability are presented. The methods are used to show that drug delivery to a xenografted tumor is plausible and to show possible vascular maturation in a transgenic mouse model. The last manuscript presents a new method for in vivo cell labeling. This method could find use in studying the metastatic spread of cancer cells throughout the body.