Date(s) - 07/11/2013
The occurrence of abnormal angiogenesis and microvasculature with altered function and morphology is characteristic in a wide variety of pathologies, and in many instances, leads to the propagation of these diseases. Specifically in the case of cancer, the identification of the microvasculature as a potential target for tumor treatment has led to drastic increases in research and development of vascular targeting agents (VTAs) in the past decade. Two classes of VTAs have emerged from this research, vascular disrupting agents which directly target the rapidly dividing endothelial cells of tumor vessels to destroy existing vasculature and angiogenic inhibiting agents which halt the formation of new vasculature by disrupting molecular pathways that lead to angiogenesis. Overall as single agents these drugs have failed to produce improved tumor therapy in comparison to current standards of care. However, because of their complementary mechanisms, the investigation into the use of these drugs in combination has become of recent interest. To better characterize the tumor vessel response to these agents and obtain the preclinical data necessary to provide a basis for clinical timing and dosing administration, the use of small animal models and the direct observation of tumor vasculature is essential to analyze the relationship between vessel morphology, blood flow and oxygenation.
We present the novel combination of two widefield imaging techniques, hyperspectral imaging of hemoglobin (Hb) saturation and first pass fluorescence (FPF) imaging in the murine window chamber model, to simultaneously characterize the oxygenation of and blood flow through microvessel networks over time. This combination of imaging techniques enables a unique analysis of blood flow in microvessels that highlights the effects of microvessel network connections on oxygen transport. In this study we focus on the development of the FPF imaging technique, its combination with the established method of hyperspectral imaging of Hb saturation and finally the application of this combination imaging to the evaluation of microvasculature in growing tumors and in response to VTAs.