Dynamic changes in oxygenation of intracranial tumor and contralateral brain during tumor growth and carbogen breathing: A multisite EPR oximetry with implantable resonators

Abstract

Introduction Several techniques currently exist for measuring tissue oxygen; however technical difficulties have limited their usefulness and general application. We report a recently developed electron paramagnetic resonance (EPR) oximetry approach with multiple probe implantable resonators (IRs) that allow repeated measurements of oxygen in tissue at depths of greater than 10 mm. Methods The EPR signal to noise (S/N) ratio of two probe IRs was compared with that of LiPc deposits. The feasibility of intracranial tissue pO2 measurements by EPR oximetry using IRs was tested in normal rats and rats bearing intracerebral F98 tumors. The dynamic changes in the tissue pO2 were assessed during repeated hyperoxia with carbogen breathing. Results A 6–10 times increase in the S/N ratio was observed with IRs as compared to LiPc deposits. The mean brain pO2 of normal rats was stable and increased significantly during carbogen inhalation in experiments repeated for 3 months. The pO2 of F98 glioma declined gradually, while the pO2 of contralateral brain essentially remained the same. Although a significant increase in the glioma pO2 was observed during carbogen inhalation, this effect declined in experiments repeated over days. Conclusion EPR oximetry with IRs provides a significant increase in S/N ratio. The ability to repeatedly assess orthotopic glioma pO2 is likely to play a vital role in understanding the dynamics of tissue pO2 during tumor growth and therapies designed to modulate tumor hypoxia. This information could then be used to optimize chemoradiation by scheduling treatments at times of increased glioma oxygenation.

Monitoring oxygen levels in orthotopic human glioma xenograft following carbogen inhalation and chemotherapy by implantable resonator‐based oximetry

“…1A 12 . The sensory loops were loaded with 30–50 μg of LiPc crystals and then the entire implantable resonator was coated with a gas permeable and biocompatible Teflon AF2400 12, 24 .…”

“…The goal of this study was to demonstrate pO 2 measurements in both hemispheres of mouse brain by using implantable resonators with multi-site EPR oximetry. The multi-site oximetry approach involves the use of magnetic field gradients for simultaneous measurement of pO 2 at two or more sites in a tissue of interest 12, 14, 15 . The oximetry technique with implantable resonators was used to investigate temporal changes in the cerebral pO 2 of control mice and those inoculated with U251 glioma and the response to carbogen inhalation for hyperoxygenation.…”

Real-time monitoring of ischemic and contralateral brain pO2 during stroke by variable length multisite resonators

“…We have developed IRs to overcome the limited depth of tissue pO 2 measurement with direct implantation of particulate oximetry probes at L-band EPR (14,17,22). The IRs were constructed from enameled copper wires and can be used to measure pO 2 at any depth from the surface.…”

“…The coupling loop has a diameter of 10 mm and is used to couple inductively to the surface loop resonator of the L-band EPR spectrometer. The sensor loops (inner diameter of 0.2 – 0.3 mm) were loaded with LiPc crystals (50 – 80 μg) and the entire IR was coated by gas permeable Teflon AF2400 (14,17,18). The SLs were implanted in the site of interest, and the coupling loop was placed on the skull below the skin for coupling with the surface loop resonator of the EPR spectrometer (Figure 1a and 1b).…”

“…Consequently, we have developed IRs that can be used to assess pO 2 at depths greater than 10 mm from the surface (14). We report the application of IRs with four-probes to assess the dynamic changes in the regional oxygen levels at different depths (3 mm and 5 mm) during ischemia by MCAO in rats.…”