Tissue And Vascular Oxygenation Dynamics Determined By Optical Approaches And MRI

Tumor oxygenation is a crucial factor to determine the efficiency of non-surgery therapy, such as radiotherapy and chemotherapy. Therefore, various approaches have been applied to tumor in order to improve the tumor oxygen level. Breathing oxygenrich gas with normobaric or hyperbaric pressure has been demonstrated to overcome hypoxia, but with marginal success. Therefore, the outcome would be improved greatly, if the responsive tumors were identified a priori. Two non-invasive techniques were applied to monitor tumor oxygenation dynamics simultaneously when rats were exposed to hyperoxic gas intervention. 19F MRI provides tumor tissue oxygen tension (pO2) images, while Near Infrared Spectroscopy (NIRS) measures global tumor vascular dynamics. Multiple correlations were examined between the rate and vii magnitudes of vascular and tissue oxygen response. In order to extract more physiological information from tumor vascular oxygen measured by NIRS, a mathematical model, modified from Windkessel model, is used to obtain the tumor blood flow and oxygen consumption rate from hemoglobin concentration. Besides normobaric oxygen intervention, hyperbaric oxygen intervention was also adopted to improve tumor oxygenation because it increases oxygen tensions and oxygen delivery to tissue independent of hemoglobin. Two techniques, FOXY fluorescence quenching oxygen sensor and NIRS, were applied simultaneously to monitor tumor tissue and vascular oxygen during and post hyperbaric oxygen administration, so as to investigate tumor oxygenation achieved with hyperbaric oxygen and the preservation of tumor oxygenation after hyperbaric oxygen intervention. I applied combined administration of doxorubicin and hyperbaric oxygen to tumors and compared the tumor oxygenation dynamics, tumor size, body weight and mortality rate between rats with combined therapy and those with doxorubicin alone. Combined application of MRI and NIRS, and FOXY oxygen sensor are novel methodology, which are complementary. Simultaneous application gives us a better understanding on the patho-physiology of tumor and response to therapeutic intervention.