VERY LOW FREQUENCY EPR IMAGING FOR IN VIVO PHYSIOLOGY

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A novel technician has been developed which will image physiologic characteristics and toxic radicals in living tissues of animals and humans. This information has, heretofore, been unavailable. The technique has been slowly developing in a number of laboratories throughout the world despite widespread misconceptions about the possibility of obtaining good EPR signals at such low frequencies. However, recent advances in spectroscopic technique and spin probe development, as well as the understanding of the information that can be provided, poise this technique on the verge of breakthrough. The technique uses very low frequency electron paramagnetic resonance imaging, VLF-EPRI. Very low frequency (100 to 300 MHZ) is necessary to allow the electromagnetic energy, which stimulates resonant absorption, to penetrate deep into the tissue of animals. In many applications, the spectra are derived from a non-toxic spin probe, similar or identical to magnetic resonance imaging contrast material, which is infused into animal tissues. The spin probe, similar or identical to magnetic resonance imaging contrast material, which is infused into animal tissues. The spin probe can target various fluid compartment in tissues. Changes in the spectrum of the spin probe report local oxygen concentration with high accuracy. As a byproduct of the oxygen measurement, the spectrum can also report microviscosity, which may be important for cellular proliferation. Spin labeling of medicinal agents may allow in vivo images of their pharmacodynamics. These images deep in animal tissues have been recently reported with VLF-EPRI. Both signaling and toxic free radicals can be detected with VLF-EPRI in vivo. Nitric oxide and hydroxyl radical have been detected in animal tissues with VLF-EPRI. These early measurements have been relatively crude. However, there are clear paths to improvements in physiologic sensitivity and spatial resolution by orders of magnitude. We propose the development of center facilities with an array of VLF-EPRI spectroscopic imagers to achieve this improvement in sensitivity and resolution. It would exist within a major medical center. This would offer adjacent, coordinated animal care, access to MRI/Spiral CT scanning and advanced image correlation capability. The VLF-EPRI facilities would also coordinate with spin probe and spin trap synthesis investigators to improve the general technique and tailor it to the needs of an individual researcher. We envision the development of a unique center offering researchers the capability of generating new physiologic information from VLF-EPRI.