TY - JOUR
T1 - Rapid sequential injections of hyperpolarized [1-13C]pyruvate in vivo using a sub-kelvin, multi-sample DNP polarizer
AU - Hu, Simon
AU - Larson, Peder E.Z.
AU - VanCriekinge, Mark
AU - Leach, Andrew M.
AU - Park, Ilwoo
AU - Leon, Christine
AU - Zhou, Jenny
AU - Shin, Peter J.
AU - Reed, Galen
AU - Keselman, Paul
AU - Von Morze, Cornelius
AU - Yoshihara, Hikari
AU - Bok, Robert A.
AU - Nelson, Sarah J.
AU - Kurhanewicz, John
AU - Vigneron, Daniel B.
N1 - Funding Information:
The authors thank Dr. James Tropp for designing and building the coil used in this study. This study was supported by NIH grant P41EB013598 for the metabolic imaging studies and S10RR029570 for the multi-sample polarizer equipment.
PY - 2013/5
Y1 - 2013/5
N2 - The development of hyperpolarized technology utilizing dynamic nuclear polarization (DNP) has enabled the rapid measurement of 13C metabolism in vivo with very high SNR. However, with traditional DNP equipment, consecutive injections of a hyperpolarized compound in an animal have been subject to a practical minimum time between injections governed by the polarization build-up time, which is on the order of an hour for [1-13C]pyruvate. This has precluded the monitoring of metabolic changes occurring on a faster time scale. In this study, we demonstrated the ability to acquire in vivo dynamic magnetic resonance spectroscopy (MRS) and 3D magnetic resonance spectroscopic imaging (MRSI) data in normal rats with a 5min interval between injections of hyperpolarized [1-13C]pyruvate using a prototype, sub-Kelvin dynamic nuclear polarizer with the capability to simultaneously polarize up to 4 samples and dissolve them in rapid succession. There were minimal perturbations in the hyperpolarized spectra as a result of the multiple injections, suggesting that such an approach would not confound the investigation of metabolism occurring on this time scale. As an initial demonstration of the application of this technology and approach for monitoring rapid changes in metabolism as a result of a physiological intervention, we investigated the pharmacodynamics of the anti-cancer agent dichloroacetate (DCA), collecting hyperpolarized data before administration of DCA, 1min after administration, and 6min after administration. Dramatic increases in 13C-bicarbonate were detected just 1min (as well as 6min) after DCA administration.
AB - The development of hyperpolarized technology utilizing dynamic nuclear polarization (DNP) has enabled the rapid measurement of 13C metabolism in vivo with very high SNR. However, with traditional DNP equipment, consecutive injections of a hyperpolarized compound in an animal have been subject to a practical minimum time between injections governed by the polarization build-up time, which is on the order of an hour for [1-13C]pyruvate. This has precluded the monitoring of metabolic changes occurring on a faster time scale. In this study, we demonstrated the ability to acquire in vivo dynamic magnetic resonance spectroscopy (MRS) and 3D magnetic resonance spectroscopic imaging (MRSI) data in normal rats with a 5min interval between injections of hyperpolarized [1-13C]pyruvate using a prototype, sub-Kelvin dynamic nuclear polarizer with the capability to simultaneously polarize up to 4 samples and dissolve them in rapid succession. There were minimal perturbations in the hyperpolarized spectra as a result of the multiple injections, suggesting that such an approach would not confound the investigation of metabolism occurring on this time scale. As an initial demonstration of the application of this technology and approach for monitoring rapid changes in metabolism as a result of a physiological intervention, we investigated the pharmacodynamics of the anti-cancer agent dichloroacetate (DCA), collecting hyperpolarized data before administration of DCA, 1min after administration, and 6min after administration. Dramatic increases in 13C-bicarbonate were detected just 1min (as well as 6min) after DCA administration.
KW - Dichloroacetate (DCA)
KW - Dynamic nuclear polarization (DNP)
KW - Hyperpolarized carbon-13
KW - Pyruvate metabolism
KW - SpinLab™ prototype
UR - http://www.scopus.com/inward/record.url?scp=84876145959&partnerID=8YFLogxK
U2 - 10.1016/j.mri.2012.09.002
DO - 10.1016/j.mri.2012.09.002
M3 - Article
C2 - 23107275
AN - SCOPUS:84876145959
SN - 0730-725X
VL - 31
SP - 490
EP - 496
JO - Magnetic Resonance Imaging
JF - Magnetic Resonance Imaging
IS - 4
ER -