Monitoring of hemodynamic changes induced in the healthy breast through inspired gas stimuli with MR-guided diffuse optical imaging

Abstract

Purpose: The modulation of tissue hemodynamics has important clinical value in medicine for both tumor diagnosis and therapy. As an oncological tool, increasing tissue oxygenation via modulation of inspired gas has been proposed as a method to improve cancer therapy and determine radiation sensitivity. As a radiological tool, inducing changes in tissue total hemoglobin may provide a means to detect and characterize malignant tumors by providing information about tissue vascular function. The ability to change and measure tissue hemoglobin and oxygenation concentrations in the healthy breast during administration of three different types of modulated gas stimuli (oxygen/carbogen, air/carbogen, and air/oxygen) was investigated. Methods: Subjects breathed combinations of gases which were modulated in time. MR‐guided diffuse optical tomography measured total hemoglobin and oxygen saturation in the breast every 30 s during the 16 min breathing stimulus. Metrics of maximum correlation and phase lag were calculated by cross correlating the measured hemodynamics with the stimulus. These results were compared to an air/air control to determine the hemodynamic changes compared to the baseline physiology. Results: This study demonstrated that a gas stimulus consisting of alternating oxygen/carbogen induced the largest and most robust hemodynamic response in healthy breast parenchyma relative to the changes that occurred during the breathing of room air. This stimulus caused increases in total hemoglobin and oxygen saturation during the carbogen phase of gas inhalation, and decreases during the oxygen phase. These findings are consistent with the theory that oxygen acts as a vasoconstrictor, while carbogen acts as a vasodilator. However, difficulties in inducing a consistent change in tissue hemoglobin and oxygenation were observed because of variability in intersubject physiology, especially during the air/oxygen or air/carbogen modulated breathing protocols. Conclusions: MR‐guided diffuse optical imaging is a unique tool that can measure tissue hemodynamics in the breast during modulated breathing. This technique may have utility in determining the therapeutic potential of pretreatment tissue oxygenation or in investigating vascular function. Future gas modulation studies in the breast should use a combination of oxygen and carbogen as the functional stimulus. Additionally, control measures of subject physiology during air breathing are critical for robust measurements.

Pilot study assessment of dynamic vascular changes in breast cancer with near-infrared tomography from prospectively targeted manipulations of inspired end-tidal partial pressure of oxygen and carbon dioxide

“…6(b)] breasts. Considering the results we obtained in our previous study without feedback control of the inspired gas mixture based on end-tidal measurements, 11,14 this outcome may be due to StO 2 changes involving both Hb and HbO, but with some phase delay between the Hb and HbO alterations.…”

“…As opposed to otherwise administering inhaled gas mixtures (where a poor relationship exists between the exhaled gas concentrations and those in the blood), [11][12][13][14][15] end-tidal (i.e., exhaled gas) partial pressures were controlled, and these quantities have been shown to be surrogates for those in the arterial blood (allowing the arterial blood partial pressure to be monitored and controlled during NIRS imaging for the first time). The results in Figs.…”

Detecting gas‐induced vasomotor changes via blood oxygenation level‐dependent contrast in healthy breast parenchyma and breast carcinoma

“…We evaluated four stimulus paradigms, comprising carbogen and “carbogen‐light” interleaved with either medical air or oxygen relative to an all‐air control state. This investigation builds on previous work to optimize detection of vasomotor response in the breast via T 2 ‐based BOLD contrast,15 as it accounts for normal physiological variations in each subject, which is a confounding factor in these types of analyses 16. We also evaluated the efficacy of a lower (2%) CO 2 carbogen variant for inducing a vasomotor response, as previous studies have reported that subjects found this variant easier to breathe 24.…”

“…Carpenter et al similarly reported that 20% of volunteers breathing air vs. carbogen and 19% breathing oxygen vs. carbogen did not demonstrate a significant effect above natural background fluctuations, likely due to metabolic variations acting independently of the respiratory stimulus 16. The ability to detect a significant BOLD response appears to vary with menstrual cycle changes.…”

“…Immature tumor vessels were expected to exhibit a diminished response relative to surrounding parenchyma, but instead an inverse response to carbogen was observed in two out of three tumor regions they studied, illustrating the complexity of BOLD response in tumors. An optical imaging study measuring hemodynamic response to inspired gas stimuli in the breast has suggested these measurements may be confounded by the body's low‐frequency hemodynamic fluctuations, which may occur due to changes in heart rate, arterial blood pressure, and metabolism 16. Furthermore, the spectral amplitudes of background physiological fluctuations in this concurrent study were such that the authors suggested they could be mistakenly attributed to a modulated response to gas stimulus if not properly accounted for.…”