We measured the changes of oxy-hemoglobin (Δ[HbO2]) and deoxy-hemoglobin concentration (Δ[Hb]) in rat breast 13762NF tumors with respect to oxygen or carbogen inhalation using near-infrared spectroscopy (NIRS). The changes in tumor blood flow can be estimated from the NIRS data provided with certain model assumptions. In the theoretical approach, we modified the Windkessel model so as to associate the mathematical model with such physiological parameters of tumor vasculature as total hemoglobin concentration ([HbT]), tumor blood flow (TBF), and tumor metabolic rate of oxygen (TMRO2). The computational results show that hyperoxic gas administration to the rat tumors always gave rise to improvement of tumor Δ[HbO2], while the same hyperoxic gas intervention could result in different responses in tumor [HbT], TBF, and TMRO2. This preliminary study has demonstrated that NIRS, a noninvasive tool to monitor tumor oxygenation, may also be used to estimate tumor perfusion and oxygen consumption rate in response to therapeutic interventions, if a suitable mathematical model is provided.
The goal of this study is to evaluate the feasibility of Near Infrared Spectroscopy (NIRS) as an in vivo monitoring tool for rat breast tumor oxygenation and vascular blood volume by comparison with the established modalities, magnetic resonance imaging/spectroscopy (MRI/MRS). The changes in oxygenated hemoglobin concentration and total hemoglobin concentration (Δ[HbO2], Δ[Hb]total) with respect to hyperoxic gas interventions were monitored by NIRS. Changes in deoxygenated hemoglobin, a blood oxygenation level dependent (BOLD) contrast, and blood volume on breast tumors were monitored by BOLD MRI and 19F MRS of PFOB, respectively. Results showed strong consistency among the two pairs: Δ[HbO2] versus BOLD signal, Δ[Hb]total versus tumor blood volume. These consistent results demonstrated the ability of NIRS as a valid in-vivo real time monitoring tool for studying the dynamic responses of Δ[HbO2] and Δ[Hb]total to therapeutic interventions applied to rat breast tumors. Furthermore, the results suggested that NIRS and MRS are complimentary with each other in terms of temporal and spatial resolutions.
Photonify’s tissue spectrometer uses Near-Infrared Spectroscopy for real-time, noninvasive measurement of hemoglobin concentration and oxygen saturation [SO2] of biological tissues. The technology was validated by a series of ex vivo and animal studies. In the ex vivo experiment, a close loop blood circulation system was built, precisely controlling the oxygen saturation and the hemoglobin concentration of a liquid phantom. Photonify’s tissue spectrometer was placed on the surface of the liquid phantom for real time measurement and compared with a gas analyzer, considered the gold standard to measure oxygen saturation and hemoglobin concentration. In the animal experiment, the right hind limb of each dog accepted onto the study was surgically removed. The limb was kept viable by connecting the femoral vein and artery to a blood-primed extracorporeal circuit. Different concentrations of hemoglobin were obtained by adding designated amount of saline solution into the perfusion circuit. Photonify’s tissue spectrometers measured oxygen saturation and hemoglobin concentration at various locations on the limb and compared with gas analyzer results. The test results demonstrated that Photonify’s tissue spectrometers were able to detect the relative changes in tissue oxygen saturation and hemoglobin concentration with a high linear correlation compared to the gas analyzer
Three oxygen-sensitive parameters (arterial hemoglobin oxygen saturation SaO2, tumor vascular oxygenated hemoglobin concentration [HbO2], and tumor oxygen tension pO2) were measured simultaneously by three different optical techniques (pulse oximeter, near infrared spectroscopy, and FOXY) to evaluate dynamic responses of breast tumors to carbogen (5% CO2 and 95% O2) intervention. All three parameters displayed similar trends in dynamic response to carbogen challenge, but with different response times. These response times were quantified by the time constants of the exponential fitting curves, revealing the immediate and the fastest response from the arterial SaO2, followed by changes in global tumor vascular [HbO2], and delayed responses for pO2. The consistency of the three oxygen-sensitive parameters demonstrated the ability of NIRS to monitor therapeutic interventions for rat breast tumors in-vivo in real time.
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