This proposal requests continuation funding for applications of intermolecular multiple-quantum coherences (iMQCs) in nuclear magnetic resonance spectroscopy (NMR), in vivo magnetic resonance imaging (MRI) and magnetic resonance spectroscopy(MRS). iMQCs, which correspond to simultaneous spin flips on separated molecules in solution (separations of 10 um-l0 mm are typical), should be unobservable according to the conventional theoretical framework of NMR; yet over the last few years, Dr. Warren has experimentally generated iMQCs with signals nearly as large as the conventional magnetization, theoretically described this complex phenomenon, and developed useful applications. For example, Dr. Warren has shown that iMQC imaging gives tumor enhancement in rat brains and novel contrast in human brain imaging (including functional activation), with acceptable sensitivity at fields as low at 1.5 Tesla. Other demonstrated applications include elimination of inhomogeneous broadening without removal of chemical shift differences, spatially localized MRS (without susceptibility broadening and shimming artifacts which limit current applications of this technique for tumor detection and grading), and heteronuclear magnetization transfer between solute and solvent peaks. Clinical applications in the next grant period include refinement of iMQC imaging methods (contrast optimization, introduction of flow compensation and presaturation), functional MRI studies on the new 3 Tesla MRI at Princeton to validate the BOLD mechanism and determine sub-voxel activation structure, and a variety of applications of spatially localized in vivo iMQC imaging. Dr. Warren proposes to do high resolution 1066 MHz NMR of macromolecules using existing magnets which give inhomogeneous fields (and removing the inhomogeneity with iMQCs) to determine the potential value of ultrahigh field NMR for protein studies. Dr. Warren also proposes to extend his work on detection of magnetization fluctuations with dipolar fields, which could evolve into another unique contrast mechanism in imaging, and which could totally transform the way low-gamma or low-concentration species are detected in NMR.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
3R01EB002122-16S1
Application #
7018104
Study Section
Molecular and Cellular Biophysics Study Section (BBCA)
Program Officer
Mclaughlin, Alan Charles
Project Start
1985-07-01
Project End
2005-04-30
Budget Start
2005-02-15
Budget End
2005-04-30
Support Year
16
Fiscal Year
2005
Total Cost
$102,118
Indirect Cost
Name
Princeton University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
002484665
City
Princeton
State
NJ
Country
United States
Zip Code
08544
Davis, Ryan M; Zhou, Zijian; Chung, Hyunkoo et al. (2016) Multi-spin echo spatial encoding provides three-fold improvement of temperature precision during intermolecular zero quantum thermometry. Magn Reson Med 75:1958-66
Branca, Rosa T; Zhang, Le; Warren, Warren S et al. (2013) In vivo noninvasive detection of Brown Adipose Tissue through intermolecular zero-quantum MRI. PLoS One 8:e74206
Stokes, Ashley M; Feng, Yesu; Mitropoulos, Tanya et al. (2013) Enhanced refocusing of fat signals using optimized multipulse echo sequences. Magn Reson Med 69:1044-55
Feng, Yesu; Theis, Thomas; Liang, Xiaofei et al. (2013) Storage of hydrogen spin polarization in long-lived 13C2 singlet order and implications for hyperpolarized magnetic resonance imaging. J Am Chem Soc 135:9632-5
Cho, Jee-Hyun; Hong, Kwan Soo; Cho, Janggeun et al. (2012) Detection of iron-labeled single cells by MR imaging based on intermolecular double quantum coherences at 14 T. J Magn Reson 217:86-91
Khanna, Arjun; Branca, Rosa T (2012) Detecting brown adipose tissue activity with BOLD MRI in mice. Magn Reson Med 68:1285-90
Chen, Y Morris; Branca, R T; Warren, W S (2012) Revisiting the mean-field picture of dipolar effects in solution NMR. J Chem Phys 136:204509
Stokes, A M; Wilson, J W; Warren, W S (2012) Characterization of restricted diffusion in uni- and multi-lamellar vesicles using short distance iMQCs. J Magn Reson 223:31-40
Kurhanewicz, John; Vigneron, Daniel B; Brindle, Kevin et al. (2011) Analysis of cancer metabolism by imaging hyperpolarized nuclei: prospects for translation to clinical research. Neoplasia 13:81-97
Branca, Rosa T; Warren, Warren S (2011) In vivo NMR detection of diet-induced changes in adipose tissue composition. J Lipid Res 52:833-9

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