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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB000557-05
Application #
7057827
Study Section
Special Emphasis Panel (ZRG1-BBCB (01))
Program Officer
Mclaughlin, Alan Charles
Project Start
2002-05-06
Project End
2007-06-30
Budget Start
2006-05-01
Budget End
2007-06-30
Support Year
5
Fiscal Year
2006
Total Cost
$293,195
Indirect Cost
Name
University of Denver
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
007431760
City
Denver
State
CO
Country
United States
Zip Code
80208
Elajaili, Hanan; Biller, Joshua R; Rosen, Gerald M et al. (2015) Imaging disulfide dinitroxides at 250 MHz to monitor thiol redox status. J Magn Reson 260:77-82
Elajaili, Hanan B; Biller, Joshua R; Tseitlin, Mark et al. (2015) Electron spin relaxation times and rapid scan EPR imaging of pH-sensitive amino-substituted trityl radicals. Magn Reson Chem 53:280-4
Biller, Joshua R; Tseitlin, Mark; Mitchell, Deborah G et al. (2015) Improved sensitivity for imaging spin trapped hydroxyl radical at 250 MHz. Chemphyschem 16:528-31
Eaton, Sandra S; Eaton, Gareth R (2015) Rapid-Scan EPR of Nitroxide Spin Labels and Semiquinones. Methods Enzymol 563:3-21
Tseitlin, Mark; Yu, Zhelin; Quine, Richard W et al. (2014) Digitally generated excitation and near-baseband quadrature detection of rapid scan EPR signals. J Magn Reson 249:126-134
Biller, Joshua R; Tseitlin, Mark; Quine, Richard W et al. (2014) Imaging of nitroxides at 250MHz using rapid-scan electron paramagnetic resonance. J Magn Reson 242:162-8
Yu, Zhelin; Quine, Richard W; Rinard, George A et al. (2014) Rapid-scan EPR of immobilized nitroxides. J Magn Reson 247:67-71
Tseitlin, Mark; Biller, Joshua R; Elajaili, Hanan et al. (2014) New spectral-spatial imaging algorithm for full EPR spectra of multiline nitroxides and pH sensitive trityl radicals. J Magn Reson 245:150-5
Mitchell, Deborah G; Rosen, Gerald M; Tseitlin, Mark et al. (2013) Use of rapid-scan EPR to improve detection sensitivity for spin-trapped radicals. Biophys J 105:338-42
Tseitlin, Mark; Eaton, Gareth R; Eaton, Sandra S (2013) Computationally Efficient Steady-State Solution of the Bloch Equations for Rapid Sinusoidal Scans Based on Fourier Expansion in Harmonics of the Scan Frequency. Appl Magn Reson 44:1373-1379

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