Yueqing Gu

Dynamic response of breast tumor oxygenation to hyperoxic respiratory challenge monitored with three oxygen-sensitive parameters

The simultaneous measurement of three oxygen-sensitive parameters [arterial hemoglobin oxygen saturation (SaO2), tumor vascular-oxygenated hemoglobin concentration ([HbO2]), and tumor oxygen tension (pO2)] in response to hyperoxic respiratory challenge is demonstrated in rat breast tumors. The effects of two hyperoxic gases [oxygen and carbogen (5% CO2 and 95% O2)] were compared, by use of two groups of Fisher rats with subcutaneous 13762NF breast tumors implanted in pedicles on the foreback. Two different gas-inhalation sequences were compared, i.e., air-carbogen-air-oxygen-air and air-oxygen-air-carbogen-air. The results demonstrate that both of the inhaled, hyperoxic gases significantly improved the tumor oxygen status. All three parameters displayed similar dynamic response to hyperoxic gas interventions, but with different response times: the fastest for arterial SaO2, followed by biphasic changes in tumor vascular [HbO2], and then delayed responses for pO2. Both of the gases induced similar changes in vascular oxygenation and regional tissue pO2 in the rat tumors, and changes in [HbO2] and mean pO2 showed a linear correlation with large standard deviations, which presumably results from global versus local measurements. Indeed, the pO2 data revealed hetergeneous regional response to hyperoxic interventions. Although preliminary near-infrared measurements had been demonstrated previously in this model, the addition of the pO2 optical fiber probes provides a link between the noninvasive relative measurements of vascular phenomena based on endogenous reporter molecules, with the quantitative, albeit, invasive pO2 determinations.

Near-Infrared Spectroscopy and Imaging of Tumor Vascular Oxygenation

Publisher Summary This chapter elaborates the near-infrared spectroscopy and imaging of tumor vascular oxygenation. A large number of investigations have been conducted in both laboratory and clinical settings to noninvasively monitor tissue vascular oxygenation using near-infrared (NIR) spectroscopy and imaging. The NIR studies of the brain include detection of brain injury or trauma, determination of cerebrovascular hemodynamics and oxygenation, and functional brain imaging in response to a variety of neurologic activations. The elevated oxygenation process is completely reversible upon returning air breathing, but still present 10 to 20 min after the baseline inhalation in many cases. The high reproducibility of results suggests that one can apply repeated interventions to explore the efficacy of interventions designed to alter tumor vascular oxygenation. It is found that a combination of well-perfused and poorly perfused mechanisms in tumor vasculature will result in the coexistence of two time constants. It is found that the concentration changes in oxygenated hemoglobin measured from both breast and prostate tumors often display a very prompt rise, followed by a gradual persistence throughout the intervention.

Estimated fraction of tumor vascular blood contents sampled by near infrared spectroscopy and 19F magnetic resonance spectroscopy.

This study introduces an experimental approach to estimate percentage of hemoglobin content and volume sampled by near infrared spectroscopy (NIRS). Carbogen (5% CO2, 95% O2) respiratory intervention was used to induce physiological changes in a group of six Fisher rat breast tumors. Changes in total hemoglobin concentration, [Hb]total, and in total blood volume, VT-blood, of the tumors were measured by NIRS and 19F magnetic resonance spectroscopy of perflubron, respectively. The ratio of [Hb]total/VT-blood was used to calculate the fraction of hemoglobin contents sampled by NIRS. The results showed that the mean value of estimated fractions is within a range of 15~30% of total hemoglobin content in the tumor tissues. Based on the results, we suggest that NIRS does not sample the entire hemoglobin volume of the tissue vasculature, but is more sensitive to microvasculature. This study helps to understand the blood vascular volume sampled by NIRS, and demonstrates that the low cost, portable NIRS system may be a reliable, non-invasive, real-time, monitoring tool for changes in tumor blood contents.

Nonuniform tumor vascular oxygen dynamics monitored by three-channel near-infrared spectroscopy

In a previous report, we showed that there was distinct heterogeneity in tumor oxygenation dynamics even within the same tumor monitored by F MR pO2 mapping and near-infrared spectroscopy (NIRS). In this study, we applied a three-channel NIRS system to reveal dynamic heterogeneity of tumor vascular oxygenation during respiratory challenges. When the implanted tumors reached ~3 cm, three photo detectors were attached to the surface of the tumor in three different positions to measure changes in oxygenated hemoglobin concentration ([HbO2]), while the inhaled gas was alternated between air and carbogen (95% O2 + 5% CO2). Significant changes in tumor oxygenation were observed at all three detectors accompanying the respiratory challenge, and these changes could be modeled with two exponential components with fast and slow time constants. Time constant, amplitude, vascular coefficient, and the ratio of perfusion rate were obtained from fitting curve of Δ[HbO2]. These parameters revealed that there were indeed different responses of tumor vascular oxygenation during carbogen inhalation at the three different locations. These results clearly reveal that tumors are highly heterogeneous during vascular oxygenation in response to carbogen inhalation. This study demonstrates that the NIR technology can provide an efficient, real-time, non-invasive way for monitoring tumor physiology, and it may have prognostic value, providing insight into tumor vascular development and angiogenesis.

Correlation of NIR spectroscopy with BOLD MR imaging of assessing breast tumor vascular oxygen status

Dynamic changes of oxygenated and deoxygenated hemoglobin concentrations in response to hyperoxic gas interventions on rat breast tumors were simultaneously investigated by near infrared spectroscopy and BOLD (blood oxygenation level dependent) contrast MR imaging.

Breast tumor oxygenation in response to carbogen intervention assessed simultaneously by three oxygen-sensitive parameters

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.

Breast tumor vascular oxygenation and blood volume assessed by near-infrared spectroscopy and magnetic resonance

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.