**5. Angiogenesis and radiological assessment techniques**

Neoangiogenesis, the formation of new blood vessels from a pre-existing vascular net‐ work, is essential for tumor growth, tumor proliferation and metastasis. The angiogene‐ sis process is regulated by different proangiogenic and antiangiogenic factors, being the primary stimulus of new vessel formation the hypoxia induced by expansion of the growing tumor mass [59].

Tumor angiogenesis is an attractive target for anticancer therapy, and a wide range of novel therapies directed against tumor vascularity has been developed. Because many antiangiogenic agents are not cytotoxic but instead produce disease stabilization, meas‐ urement of tumor size alone may be not informative regarding therapeutic effects. For that reason, there has been great interest in the use of physiologic, rather than solely anatomic, imaging techniques [60]. Tumor vascularity has different features that are char‐ acteristic of malignancy, such as spatial heterogeneity, chaotic structure, fragility and high permeability to macromolecules. These structural abnormalities of new tumor ves‐ sels lead to pathophysiologic changes within the neoplastic tissue, including an increase in capillary permeability, volume of extravascular-extracellular space, and tumor perfu‐ sion, that permit distinction of malignant from benign vascularity with functional imag‐ ing techniques.

Several commonly available imaging modalities, including magnetic resonance (MR), com‐ puted tomography (CT), ultrasound and positron emission tomography (PET), have been used to indirectly assess the angiogenic status of human tumors [61]. But perfusion imaging with MR, and specially CT, are the most useful in clinical practice. They have the advantage of good spatial resolution, minimal invasiveness and rapid acquisition of data. Both techni‐ ques sequentially demonstrate passage of a bolus of contrast medium through a region of interest and allow quantification of the profile of tissue enhancement.
