Direct and Repeated Measurement of Heart and Brain Oxygenation Using In Vivo EPR Oximetry

Low level of oxygen (hypoxia) is a critical factor that defines the pathological consequence of several pathophysiologies, particularly ischemia, that usually occur following the blockage of a blood vessel in vital organs, such as brain and heart, or abnormalities in the microvasculature, such as peripheral vascular disease. Therefore, methods that can directly and repeatedly quantify oxygen levels in the brain and heart will significantly improve our understanding of ischemic pathologies. Importantly, such oximetry capability will facilitate the development of strategies to counteract low levels of oxygen and thereby improve outcome following stroke or myocardial infarction. In vivo electron paramagnetic resonance (EPR) oximetry has the capability to monitor tissue oxygen levels in real time. The method has largely been tested and used in experimental animals, although some clinical measurements have been performed. In this chapter, a brief overview of the methodology to repeatedly quantify oxygen levels in the brain and heart of experimental animal models, ranging from mice to swine, is presented. EPR oximetry requires a one-time placement of an oxygen-sensitive probe in the tissue of interest, while the rest of the procedure for reliable, accurate, and repeated measurements of pO2 (partial pressure of oxygen) is noninvasive and can be repeated as often as desired. A multisite oximetry approach can be used to monitor pO2 at many sites simultaneously. Building on significant advances in the application of EPR oximetry in experimental animal models, spectrometers have been developed for use in human subjects. Initial feasibility of pO2 measurement in solid tumors of patients has been successfully demonstrated.