In vivo paramagnetic resonance (EPR) requires optimal signal-to-noise (S/N) enhancement in the shortest possible time. To study radicals in deep tissues it is necessary to perform the EPR measurements at low radiofrequency (e.g., 250 MHz), as in MRI. This decreases the S/N relative to the more common 9 GHz EPR. Physiological motions and metabolism occurring within the time of the usual EPR measurements necessitate the development of special techniques for in vivo studies. It is proposed to establish a partnership of engineers, research scientists, clinicians, and industry to fully engineer an EPR system dedicated to in vivo spectroscopy and imaging. As a first step, it is proposed to engineer a CW 250 MHz EPR spectrometer system optimized for the best in vivo free radical sensitivity per unit time. The specific tasks include the design, construction, and testing of an air-core magnet for in vivo EPR optimized for rapid magnetic field scans, and a control system for scanning the magnetic field rapidly. We introduce the innovation that the magnet will be resonated, and magnetic field scans will be sinusoidal. Measurement of the noise spectral densities of the spectrometer system, and of a spectrometer with a mouse in the resonator, will provide the basis for a mathematical model of the spectrometer noise characteristics from which one can predict the S/N per unit time expected for various magnetic field scan rates. The S/N for various scan rates will be compared with the predicted values. Software will be written to linearize and deconvolute the spectral information recorded under rapid-scan conditions. In subsequent effort it is proposed to extend the scope of the bioengineering research partnership to tackle the problems of optimal compensation for physiological motion, acquisition of the full RF spectrum and post-processing to replace analog pre-processing, and design of open magnet structures to achieve better patient acceptance and decrease costs.
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