This proposal is for development of novel instrumentation to enable rapid measurement and imaging of free radicals in biomedical applications using Dynamic Nuclear Polarization (DNP) and Proton Electron Double Resonance Imaging (PEDRI). A unique variable field, rapid field cycling (FC) PEDRI instrument will be built capable of performing measurements from fields of 0 to 0.2 T. DNP/PEDRI can provide rapid high quality measurements of free radicals in living animals and these novel dual resonance techniques overcome a number of the fundamental limitations of EPR imaging that requires relatively long times for image data collection, provides limited image resolution due to the inherently broad linewidths of paramagnetic labels, and needs very large gradients as well as independent techniques for anatomic registration. Therefore, DNP and PEDRI have great potential to advance this field providing: sensitive, rapid and high quality measurements and imaging of paramagnetic molecules in biomedical systems. There are 5 aims: 1) Development of a magnet, gradient, field control, and system control interface optimized for PEDRI of free radicals in small animal models of disease; 2) Development of DNP spectroscopy and PEDRI with variable field EPR preexcitation for NMR based detection and imaging of the EPR spectra of free radicals; 3) Development of Field Cycled DNP and Spectral-Spatial PEDRI to enhance measurement sensitivity and minimize problems with power deposition and sample heating; 4) Development of innovative resonator and RF design optimized for DNP and PEDRI of in vivo and ex vivo biomedical applications; 5) Development of optimized software and algorithms enabling rapid acquisition and analysis of DNP and PEDRI spectral and image data. Together these aims will overcome existing limitations of RF power deposition and result in the development of a unique variable field rapid field cycling PEDRI/DNP instrument capable of rapid, high quality measurement and imaging of free radicals in small animal models of disease. This new instrumentation and related innovations in rapid field cycling, resonator technology and ultra fast image acquisition, have the potential to provide 100-fold enhanced sensitivity in radical detection, with 10-fold higher image resolution and over 10-fold faster image acquisition than prior fixed field PEDRI instrumentation, while reducing RF power deposition by over two orders of magnitude.
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