Changes in oxygenation of intracranial tumors with carbogen: A BOLD MRI and EPR oximetry study

Abstract

Purpose: To examine, using blood oxygen level dependent (BOLD) MRI and EPR oximetry, the changes in oxygenation of intracranial tumors induced by carbogen breathing. Materials and Methods:The 9L and CNS-1 intracranial rat tumor models were imaged at 7T, before and during carbogen breathing, using a multi-echo gradient-echo (GE) sequence to map R 2 *. On a different group of 9L tumors, tissue pO 2 was measured using EPR oximetry with lithium phthalocyanine as the oxygen-sensitive material. Results:The average decline in R 2 * with carbogen breathing was 13 Ϯ 1 s -1 in the CNS-1 tumors and 29 Ϯ 4 s -1 in the 9L tumor. The SI vs. TE decay curves indicate the presence of multiple components in the tumor. Tissue pO 2 in the two 9L tumors measured was 8.6 Ϯ 0.5 and 3.6 Ϯ 0.6 mmHg during air breathing, and rose to 20 Ϯ 7 and 16 Ϯ 4 mmHg (mean Ϯ SE) with carbogen breathing. Significant changes were observed by 10 minutes, but changes in pO 2 and R 2 * continued in some subjects over the entire 40 minutes. Conclusion:EPR results indicate that glial sarcomas may be radiobiologically hypoxic. Both EPR and BOLD data indicate that carbogen breathing increases brain tumor oxygenation. These data support the use of BOLD imaging to monitor changes in oxygenation in brain tumors.

The chemistry and biology of nitroxide compounds

“…The advantages of MRI include the availability of MRI scanners, multi-slice imaging capability, enhanced spatial and temporal resolution, and co-registration of images of tissue redox status with anatomical information inherently available from MRI. Suitable contrast MRI agents provide important functional information such as blood flow and tissue perfusion [50]. Currently used agents used for T1-contrast enhancement contain paramagnetic entities such as the Gd 3+ or Mn 2+ complexes.…”

Magnetic resonance imaging of the migration of neuronal precursors generated in the adult rodent brain

“…Under 3% isoflurane anesthesia in 90% oxygen/10% medical air, animals were placed in a custom-built MR compatible stereotactic head frame. The high oxygen concentration lowers the amount of deoxygenated blood, lessening the appearance of dark veins in the MR images (Dunn et al, 2002). The surface coil was placed directly on the head of animals.…”

Assessment of tumor oxygenation by electron paramagnetic resonance: principles and applications

“…This feature permits the use of LiPc as an oximetry probe in brain. [168][169][170] The narrowness of the linewidth is also particularly suitable for multisite spectroscopy. One limitation of this material is the rapid saturation at low power.…”

“…In several studies, measurements of tumor oxygenation using EPR have been carried out as a proof of principle in order to show that a specific method or a newly developed paramagnetic material was applicable for this purpose. 119,183,160,214,221,222 In other studies, EPR oximetry was compared with other methods that provide direct or indirect measurements of tumor oxygenation: comparison with polarographic electrodes, 163,223 the distribution of nitroimidazoles, 83 the BOLD effect in MRI, 107,159,224 and pO 2 recordings using OxyLite 1 . [66][67][68] More interestingly, the power of EPR oximetry to measure oxygen from the same site over long periods of time offers the possibility of developing novel approaches to modifying tumor oxygenation, and thus optimizing anti-cancer treatments.…”

“…Breathing carbogen (possibly combined with nicotinamide administration) is now applied succesfully in the clinic together with irradiation. 102 The increase in pO 2 in tumors induced by breathing carbogen was shown in several tumor lines using EPR spectroscopy, 107,176,183,224 EPR imaging 146,160,159 or PEDRI. 163 Oxygen images were obtained in tumors before and after breathing carbogen by the group at the NCI using dynamic nuclear polarization and the extraction of T 2 of trityl radicals.…”