Mengna Xia

Tumour oxygen dynamics measured simultaneously by near-infrared spectroscopy and 19F magnetic resonance imaging in rats*

Simultaneous near-infrared spectroscopy (NIRS) and magnetic resonance imaging (MRI) were used to investigate the correlation between tumour vascular oxygenation and tissue oxygen tension dynamics in rat breast 13762NF tumours with respect to hyperoxic gas breathing. NIRS directly detected global variations in the oxygenated haemoglobin concentration (Delta[HbO(2)]) within tumours and oxygen tension (pO(2)) maps were achieved using (19)F MRI of the reporter molecule hexafluorobenzene. Multiple correlations were examined between rates and magnitudes of vascular (Delta[HbO(2)]) and tissue (pO(2)) responses. Significant correlations were found between response to oxygen and carbogen breathing using either modality. Comparison of results for the two methods showed a correlation between the vascular perfusion rate ratio and the mean pO(2) values (R(2) > 0.7). The initial rates of increase of Delta[HbO(2)] and the slope of dynamic pO(2) response, d(pO(2))/dt, of well-oxygenated voxels in response to hyperoxic challenge were also correlated. These results demonstrate the feasibility of simultaneous measurements using NIRS and MRI. As expected, the rate of pO(2) response to oxygen is primarily dependent upon the well perfused rather than poorly perfused vasculature.

Extinction coefficients of hemoglobin for near-infrared spectroscopy of tissue

Extinction coefficients of hemoglobin have been studied for five decades by clinical chemists and biochemists, particularly for laboratory spectrophotometric measurements. In the last ten to 15 years, near infrared spectroscopy (NIRS) and imaging for tissue vascular oxygenation, breast tumor detection, and functional brain imaging have been intensively developed for in vivo measurements by groups of physicists, biomedical engineers, and mathematicians. In the approach of NIRS, NIR light in the wavelength range of 650-900 nm is utilized to illuminate tissue in vivo, and the transmitted or reflected light through tissue is recorded for the quantification of hemoglobin concentrations of the measured tissue vasculature. In order to achieve mathematical conversion from the detected light intensity at different wavelengths to hemoglobin concentration, extinction coefficients of hemoglobin, /spl epsiv/, must be used. While the engineers and physicists working in the NIR field have found the correct /spl epsiv/ values to use, there has been controversy on what /spl epsiv/ values should be used for in vivo NIRS in comparison with the conventional e/spl epsiv/ that most biochemists have used in the laboratories for in vitro measurements. The purpose of this article is to address this issue and help biomedical engineers and physicists gain a better understanding of e to be used for NIRS and NIR imaging.

Effect of Photothermal Therapy on Breast Tumor Vascular Contents: Noninvasive Monitoring by Near-infrared Spectroscopy¶

Abstract The goal of this study was to investigate the effect of photothermal laser irradiation on rat breast tumor (DMBA-4) vascular contents. An 805-nm diode laser was used in our experiment with a power density ranging from 0.32 to 1.27 W/cm2. The dynamic changes of oxygenated hemoglobin and total hemoglobin concentrations, Δ[HbO2] and Δ[Hb]total, in rat tumors during photothermal irradiation were noninvasively monitored by a near-infrared spectroscopy system. A multichannel thermal detection system was also used simultaneously to record temperatures at different locations within the tumors. Our experimental results showed that: (1) photoirradiation did have the ability to induce hyperthermic effects inside the rat breast tumors in a single exponential trend; (2) the significant changes (P < 0.005) of Δ[HbO2] and Δ[Hb]total in response to a low dosage of laser irradiation (0.32 W/cm2) have a single exponential increasing trend, similar to that seen in the tumor interior temperature; and (3) the increase in magnitude of Δ[HbO2] is nearly two times greater than that of Δ[Hb]total, suggesting that photoirradiation may enhance tumor vascular oxygenation. The last observation may be important to reveal the hidden mechanism of photoirradiation on tumors, leading to improvement of tumor treatment efficiency.

Noninvasive monitoring of estrogen effects against ischemic stroke in rats by near-infrared spectroscopy

The aim of this study was to assess hemodynamic changes by near-infrared spectroscopy (NIRS) during acute focal cerebral ischemia and reperfusion. The study also has evaluated the therapeutic effects of estrogen against vascular dysfunction. Focal cerebral ischemia was induced in nine bilaterally ovariectomized rats, using an endovascular occlusion technique of the middle cerebral artery (MCA). Four out of nine rats had estrogen pretreatment before MCA occlusion (MCAO). The other five rats had MCAO with no pretreatment. The occlusion time was 60 min, followed by 40-60 min of reperfusion. Real-time monitoring of changes in hemoglobin concentrations was performed by a steady-state, two-channel, NIRS system through the period of occlusion and reperfusion. Both changes in total and oxygenated hemoglobin concentrations (D[HbT] and D[HbO(2)]) display apparent periodic fluctuations during occlusion for the rats without estrogen pretreatment, while no rhythmic fluctuation was observed in the rats with the pretreatment. This rhythmic fluctuation is a microvascular dysfunction. Fourier power spectral analysis was performed on the D[HbO(2)] profiles in both rat groups. The results show that the cumulative frequency power of D[HbO(2)] in the range of 0.0025-0.01 Hz for the rats without pretreatment is significantly higher than that with pretreatment. The study implies that the dysfunctional fluctuations disappear in the rats with estrogen pretreatment, demonstrating a new application of NIRS, i.e., to detect focal cerebral ischemia and to monitor cerebral responses to therapy against vascular dysfunction in animal models.

Validation of NIRS in measuring tissue hemoglobin concentration and oxygen saturation on ex vivo and isolated limb models

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

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.

A model of hemodynamic responses of rat tumors to hyperoxic gas challenge

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.

Simultaneous Monitoring Tumor Vascular and Tissue Oxygen Tension Under Hyperbaric Oxygen Exposure

We demonstrate the ability to simultaneously investigate breast tumor oxygen dynamics by Steady-state diffuse reflectance spectroscopy and FOXY oxygen sensor in response to hyperbaric oxygen intervention.