Application of in vivo EPR in brain research: monitoring tissue oxygenation, blood flow, and oxidative stress.

Although oxygen levels are critical to tissue survival, monitoring tissue oxygen levels in vivo, in real time, remains a technical challenge. This is especially so for repetitive measurements in non-superficial tissue. There currently exist several techniques that can be utilized for tissue oxygen measurement, but technical difficulties have limited their usefulness and general application. Here we describe a relatively new method, electron paramagnetic resonance (EPR) oximetry, for in vivo measurement of brain tissue oxygen, as well as information on blood flow and oxidative stress. In this paper we report experiments designed to assess and illustrate the effectiveness of this new method. Using the unique capability of this approach, we have measured both absolute values and temporal changes of pO2 in ischemic penumbra and core during cerebral ischemia and reperfusion in a rat model. EPR oximetry with particulate probe sensitively reflected differential changes in oxygenation in the core and penumbra during ischemia, reperfusion and also hyperoxic conditions. Simultaneous two-site detection with particulate probes was also obtained with good spatial resolution. Additionally, EPR measurement of oxidative stress, EPR imaging of brain with nitroxide and triarylmethyl soluble probes are also described. These results demonstrate that EPR oximetry with particulate probe can provide accurate and reproducible measurements of localized pO2 in the brain, and it is a versatile and useful method in the measurement of tissue pO2 under a variety of physiological and pathophysiological conditions. Copyright 2004 John Wiley & Sons, Ltd.