Colorectal carcinoma (CRC) represents an important health burden, being the third leading cause of cancer death in the world. The cancer-stromal cell interaction contributes directly to tumor growth and metastasis by creating an imbalance of positive and negative growth factors and increased microvascular density via angiogenesis. Chemo and biological therapy targeting the angiogenic growth factors offered additional hope for treatment but the exact biological mechanisms are still not clear. Therefore, the long-term goal of the proposed research is to gain improved understanding of the mechanisms by which tumor microvascular networks (MVN) respond to chemotherapy and/or anti-angiogenic therapy. To address this, the first objective is to map the MVN and cellular components of normal colorectal tissue and CRC tumors before and after chemotherapy and/or anti-angiogenic treatment in CRC patients. The MVN biology will be observed with a novel combination of minimally invasive ultrasound and confocal imaging techniques (CE-EUS and CLE) correlated with the type and dosage of therapy. The second objective is to develop computer simulations of blood flow and structural adaptation of the MVN in normal tissues and CRC tumors following chemo- and anti-angiogenic treatment. The project will have a significant scientific and social impact leading to a better categorization and prediction of patientís response to treatment before exposure to chemotherapy or surgery.