In order for a solid tumor to metastasize, individual tumor cells must first interact with, and penetrate, the tumor extracellular matrix (ECM). My laboratory focuses on the study of this key process in vivo, i.e. in the living intact tumor. Due to a lack of intrinsic contrast, the ECM has been difficult to study in the living tumor, and as a result our understanding of the tumor ECM has been limited primarily to indirect measures such as diffusive hindrance or ex vivo studies using excision, fixing, and staining procedures which preclude dynamic information. Through our ongoing program of developing and applying novel optical tools to study tumor pathophysiology, we have found that second harmonic generation (SHG) provides a quantitative, non-invasive optical signal primarily generated by the fibrillar collagen in the ECM of tumors. We are currently exploiting this window into the tumor extracellular matrix in order to study the dynamic properties of the tumor ECM. We are specifically focusing on exploring the photophysical properties of this contrast mechanism, with the goal of understanding what it can teach us about tumor tissue and utilizing that information to improve patient diagnosis and treatment.