Investigation of breast tumor hemodynamics by near infrared spectroscopy: Applications to cancer therapy monitoring
Hyperoxic gas interventions using carbogen (95% O2 and 5% CO2) or oxygen has been tried to increase the tumor oxygenation since it will enhance the therapeutic effects on the tumors. Others in the laboratory had previously applied near infrared spectroscopy (NIRS) to monitor the changes in tumor blood oxygenation during hyperoxic gas intervention and found that oxyhemoglobin concentration changes (Δ[HbO2]) during gas intervention can be fitted by a two-exponential equation containing two time constants.
Based on the model, they formed a hypothesis that changes in oxygenated hemoglobin concentration result from well perfused and poorly perfused regions of an animal tumor to explain why there are two different time constants in the Δ[HbO2] data. In this study, the aims were (1) to modify and refine the algorithm for obtaining vascular hemoglobin concentration by near infrared spectroscopy (NIRS), (2) to understand the bi-phasic feature of tumor hemodynamics during hyperoxic gas interventions, and (3) to apply a bi-exponential model to investigate tumor physiology, such as vascular heterogeneity, and to monitor tumor responses to cancer therapy.
For aim 1, blood phantom experiments were performed, and the algorithm was modified empirically. Possible differences in calculated hemoglobin concentration induced by the discrepancy in hemoglobin extinction coefficients were also estimated. For aim 2, a dynamic vascular phantom simulating blood vessels was developed, and the finite element method (FEM) was applied to support the dynamic phantom experiments. To accomplish aim 3, multi-channel LAIRS was utilized to observe the heterogeneity in tumor oxygen dynamics during hyperoxic gas intervention. For therapy monitoring, two chemotherapeutic drugs, a conventional chemotherapeutic agent and a vascular disrupting agent, were administered in tumor-bearing rats. The responses of tumors during oxygen intervention were compared between pre- and post-treatment.
The dynamic vascular phantom experiments and FEM simulations support the previous hypothesis on the bi-phasic feature of tumor hemodynamics, and that the biphasic features of NIRS taken during hyperoxic intervention can be an effective tool to monitor tumor responses to cancer therapy.