Abstract
In this study we set up and optimized a dynamic nuclear polarization (DNP) procedure for the hyperpolarization of a large dose suitable for cardiac metabolic imaging in vivo in swine models. The dose range proposed in this study allowed chemical shift imaging of cardiac metabolism with hyperpolarized [1-13C]pyruvate in pigs. We investigated the typical pattern of distribution of [1-13C]pyruvate and its downstream metabolites: we analysed the variation of the maximum value of the normalized [1-13C]pyruvate signal and the global pyruvate signal in left ventricle (LV). The study reports data obtained with a large dose increase compared to small animal studies: 20 ml of 230 mM [1-13C]pyruvate with 16 ± 3 % polarization (mean ± SD), using a DNP system operating at ~1.4 K with a magnetic field of 3.35 T. A significant correlation between the maximum value of the normalized [1-13C]pyruvate signal and the global pyruvate signal in the LV was found. The characterization of the dynamic range of the signal and the optimization of the standardized dose could be a starting point for designing pathophysiological studies in experimental large animal models. With this approach the hyperpolarization of metabolic substrates could be applied in biomedical magnetic resonance, which could become one of the most promising models for cardiovascular imaging.
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References
F.A. Gallagher, M.I. Kettunen, K.M. Brindle, Prog. Nucl. Magn. Reson. Spectrosc. 55, 285–295 (2009)
K. Golman, J.S. Petersson, Acad. Radiol. 13, 932–9422 (2006)
S. Aime, W. Dastrù, R. Gobetto, D. Santelia, A. Viale, Handbook of experimental pharmacology, vol. 185/1 (s.l.: SpringerLink) p. 247–272 (2008)
K. Golman, R. In’t Zandt, M. Lerche, R. Peherson, J.H. Ardenkjaer-Larsen, Cancer Res. 66(22), 10855–10860 (2006)
M.J. Albers, R. Bok, A.P. Chen, C.H. Cunningham, M.L. Zierhut, V.Y. Zhang, J. Tropp, R.E. Hurd, Y. Yen, S.J. Nelson, D.B. Vigneron, J. Kurhanewicz, Cancer Res. 68(20), 8607–8615 (2008)
M.L. Zierhut, Y.F. Yen, A.P. Chen, R. Bok, M.J. Albers, V. Zhang, J. Tropp, I. Park, D.B. Vigneron, J. Kurhanewicz, R.E. Hurd, S. Nelson, J. Magn. Reson. 202(1), 85–92 (2010)
I. Park, P.E.Z. Larson, M.L. Zierhut, S. Hu, R. Bok, T. Ozawa, J. Kurhanewicz, D.B. Vigneron, S.R. VandenBerg, C.D. James, S.J. Nelson, Neuro-Oncology. 12(2), 1–12 (2010)
T. Xu, D. Mayer, M. Gub, Y. Yen, S. Josan, J. Tropp, A. Pfefferbaum, R. Hurd, D. Spielman, NMR Biomed. 24, 997–1005 (2011)
M. Marjańska, I. Iltis, A.A. Shestov, D.K. Deelchand, C. Nelson, K. Uğurbil, P. Henry, J. Magn. Reson. 206, 210–218 (2010)
D.J. Tyler, M.A. Schroeder, L.E. Cochlin, K. Clarke, G. Radda, Appl. Magn. Reson. 34, 523–531 (2008)
A.Z. Lau, A.P. Chen, N.R. Ghugre, V. Ramanan, W.W. Lam, K.A. Connelly, G.A. Wright, C.H. Cunningham, Magn. Reson. Med. 64, 1323–1331 (2010)
A.P. Chen, R.E. Hurd, M.A. Schroeder, A.Z. Lau, Y. Gu, W.W. Lam, J. Barry, J. Tropp, C.H. Cunningham, NMR Biomed. 25(2), 305–311 (2012)
M.A. Schroeder, H.J. Atherton, L.C. Heather, J.L. Griffin, K. Clarke, G.K. Radda, D. Tyler, NMR Biomed. 24(8), 980–987 (2011)
H.J. Atherton, M.A. Schroeder, M.S. Dodd, L.C. Heather, E.E. Carter, L.E. Cochlin, S. Nagel, N.R. Sibson, G.K. Radda, K. Clarke, D.J. Tyler, NMR Biomed. 24(2), 201–208 (2011)
K. Golman, J.S. Petersson, P. Magnusson, E. Johansson, P. Ǻkeson, C.-M. Chai, G. Hansson, S. Månsson, Magn. Reson. Med. 59(5), 1005–1013 (2008)
R.T. Mallet, Proc. Soc. Exp. Biol. Med. 223, 136–148 (2000)
R.T. Mallet, J. Sun, E.M. Knott, A.B. Sharma, A.H. Olivencia-Yurvati, Exp. Biol. Med. 230(7), 435–443 (2005)
M.A. Janich, M.I. Menzel, F. Wiesinger, E. Weidl, O. Khegai, J.H. Ardenkjaer‐Larsen, S.J. Glaser, A. Haase, R.F. Schulte, M. Schwaiger, NMR Biomed. 25(1), 142–151 (2012)
Schroeder M. A., Atherton H. J., Cochlin L. E., Clarke K., Radda G. K. and Tyler D. J., Magn. Reson. Med. 61, p. 1007–1014 (2009)
K. Golman, R. in’t Zandt, M. Thaning, Proc. Natl. Acad. Sci. USA 103(30), 11270–11275 (2006)
T. Harris, G. Eliyahu, L. Frydman, H. Degani, Proc. Natl. Acad. Sci. USA 106(43), 18131–18136 (2009)
M.H. Lerche, S. Meier, P.R. Jensen, S. Hustvedt, M. Karlsson, J.O. Duus, J.H. Ardenkjaer-Larsen, NMR Biomed. 24, 96–103 (2011)
M.A. Schroeder, H.J. Aterthon, D.R. Ball, M.A. Cole, L.C. Heather, J.L. Griffin, K. Clarke, G.K. Radda, D.J. Tyler, FASEB J. 23, 2529–2538 (2009)
M.E. Merritt, C. Harrison, C. Storey, A.D. Sherry, C.R. Malloy, Magn. Reson. Med. 60(5), 1029–1036 (2008)
M.A. Schroeder, P. Swietach, H.J. Atherton, F.A. Gallagher, P. Lee, G.K. Radda, K. Clarke, D.J. Tyler, Cardiovasc. Res. 86, 82–91 (2010)
S.E. Day, M.I. Kettunen, F.A. Gallagher, D.E. Hu, M. Lerche, J. Wolber, K. Golman, J.H. Ardenkjaer-Larsen, K.M. Brindle, Nat. Med. 13(11), 1382–1387 (2007)
S. Hu, A.P. Chen, M.L. Zierhut, R. Bok, Y. Yen, M.A. Schroeder, R.E. Hurd, S.J. Nelson, J. Kurhanewicz, D.B. Vigneron, Mol. Imaging Biol. 11, 399–407 (2009)
H.L. Atherton, M.S. Dodd, L.C. Heather, M.A. Schroeder, J.L. Griffin, G.K. Radda, K. Clarke, D.J. Tyler, Circulation pp. 2552–2561 (2011)
L. Menichetti, F. Frijia, A. Flori, F. Wiesinger, V. Lionetti, G. Giovannetti, G.D. Aquaro, F.A. Recchia, J.H. Ardenkjaer-Larsen, M.F. Santarelli, M. Lombardi, Contrast Media Mol. Imaging. 7, 85–94 (2012)
L. Menichetti, F. Frijia, V. Lionetti, M.F. Santarelli, J.H. Ardenkjaer Larsen, G. Giovannetti, V. Positano, D. De Marchi, G. Aquaro, M. Campan, V. Hartwig, M. Milanesi, F.A. Recchia, L. Landini, M. Lombardi, J. Cardiovasc. Magn. Reson. 12(1), 323–324 (2010)
F. Wiesinger, E. Weidl, M.I. Menzel, M. Janich, P. Sipilae, M. Schwaiger, R. Schulte, Stockholm: s.n., 2010. Proc 18th Annual Meeting ISMRM. p. 3290.
F. Wiesinger, E. Weidl, M.I. Menzel, M.A. Janich, O. Khegai, S.J. Glaser, A. Haase, M. Schwaiger, R.F. Schulte, Magn. Reson. Med. (2011), doi:10.1002/mrm.23212 (Article first published online: 29 Nov 2011)
F. Wiesinger, I. Miederer, M.I. Menzel, E. Weidl, M. Janich, J.-H. Ardenkjaer-Larsen, M. Schwaiger, R.F. Schulte, in Proc. of 18th Annual Meeting ISMRM (Stockholm, 2010), p. 3282
V. Positano, M.F. Santarelli, F. Frijia, G. Aquaro, L. Menichetti, V. Lionetti, G. Bianchi, A. Flori, J.H. Ardenkjaer-Larsen, F. Wiesinger, R.F. Schulte, G. Giovannetti, F.A. Recchia, L. Landini, M. Lombardi, J. Cardiovasc. Magn. Reson. 14(1), 139–140 (2012)
V. Gemignani, E. Bianchini, F. Faita, V. Lionetti, M. Campan, F.A. Recchia, E. Picano, T. Bombardini, Pacing Clin. Electrophysiol. 33(7), 795–803 (2010)
A. Comment, J. Rentsch, F. Kurdzesau, S. Jannin, K. Uffmann, R.B. van Heeswijk, P. Hautle, J.A. Konter, B. van de Brandt, J.J. van der Klink, J. Magn. Reson. 194, 152–155 (2008)
Acknowledgments
Our work is supported by the Fund of the Fondazione CNR/Regione Toscana G.Monasterio, Pisa, Italy. We thank Mr. William Mander (Oxford Instruments plc) for his expertise and support in the Hypersense® modification and Mr. Matteo Liserani for data analysis.
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Flori, A., Frijia, F., Lionetti, V. et al. DNP Methods for Cardiac Metabolic Imaging with Hyperpolarized [1-13C]pyruvate Large Dose Injection in Pigs. Appl Magn Reson 43, 299–310 (2012). https://doi.org/10.1007/s00723-012-0350-9
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DOI: https://doi.org/10.1007/s00723-012-0350-9