Quality assurance of PASADENA hyperpolarization for 13C biomolecules



Define MR quality assurance procedures for maximal PASADENA hyperpolarization of a biological 13C molecular imaging reagent.

Materials and methods

An automated PASADENA polarizer and a parahydrogen generator were installed. 13C enriched hydroxyethyl acrylate, 1-13C, 2,3,3-d3 (HEA), was converted to hyperpolarized hydroxyethyl propionate, 1-13C, 2,3,3-d3 (HEP) and fumaric acid, 1-13C, 2,3-d2 (FUM) to hyperpolarized succinic acid, 1-13C, 2,3-d2 (SUC), by reaction with parahydrogen and norbornadiene rhodium catalyst. Incremental optimization of successive steps in PASADENA was implemented. MR spectra and in vivo images of hyperpolarized 13C imaging agents were acquired at 1.5 and 4.7 T.


Application of quality assurance (QA) criteria resulted in incremental optimization of the individual steps in PASADENA implementation. Optimal hyperpolarization of HEP of P = 20% was achieved by calibration of the NMR unit of the polarizer (B 0 field strength ± 0.002 mT). Mean hyperpolarization of SUC, P = [15.3 ± 1.9]% (N = 16) in D 2O, and P = [12.8 ± 3.1]% (N = 12) in H 2O, was achieved every 5–8 min (range 13–20%). An in vivo 13C succinate image of a rat was produced.


PASADENA spin hyperpolarization of SUC to 15.3% in average was demonstrated (37,400 fold signal enhancement at 4.7 T). The biological fate of 13C succinate, a normally occurring cellular intermediate, might be monitored with enhanced sensitivity.

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  1. 1

    Bowers CR, Weitekamp DP (1986) Transformation of symmetrization order to nuclear-spin magnetization by chemical-reaction and nuclear-magnetic-resonance. Phys Rev Lett 57: 2645–2648

    PubMed  Article  CAS  Google Scholar 

  2. 2

    Bowers CR, Weitekamp DP (1987) Para-hydrogen and synthesis allow dramatically enhanced nuclear alignment. J Am Chem Soc 109: 5541–5542

    Article  CAS  Google Scholar 

  3. 3

    Golman K, Axelsson O, Johannesson H, Mansson S, Olofsson C, Petersson JS (2001) Parahydrogen-induced polarization in imaging: subsecond C-13 angiography. Magn Reson Med 46: 1–5

    PubMed  Article  CAS  Google Scholar 

  4. 4

    Born M, Heisenberg W (1924) The quantum theory of molecules. Annalen Der Physik 74: 1–31

    Article  CAS  Google Scholar 

  5. 5

    Bonhoeffer KF, Harteck P (1929) Experiments on para-hydrogen and ortho-hydrogen. Naturwissenschaften 17: 182–182

    Article  CAS  Google Scholar 

  6. 6

    Goldman M, Johannesson H (2005) Conversion of a proton pair para order into C-13 polarization by rf irradiation, for use in MRI. C R Physique 6: 575–581

    Article  CAS  Google Scholar 

  7. 7

    Bhattacharya P, Harris K, Lin AP, Mansson M, Norton VA, Perman WH, Weitekamp DP, Ross BD (2005) Ultra-fast three dimensional imaging of hyperpolarized C-13 in vivo. Magn Reson Mater Phys 18: 245–256

    Article  CAS  Google Scholar 

  8. 8

    Mansson S, Johansson E, Magnusson P, Chai CM, Hansson G, Petersson JS, Stahlberg F, Golman K (2006) C-13 imaging—a new diagnostic platform. Eur Radiol 16: 57–67

    PubMed  Article  Google Scholar 

  9. 9

    Kuhn LT, Bargon J (2006) Transfer of parahydrogen-induced hyperpolarization to heteronuclei. Top Curr Chem 276: 25–68

    Article  Google Scholar 

  10. 10

    Bhattacharya P, Chekmenev EY, Perman WH, Harris KC, Lin AP, Norton VA, Tan CT, Ross BD, Weitekamp DP (2007) Towards hyperpolarized 13C-succinate imaging of brain cancer. J Magn Reson 186: 108–113

    Article  Google Scholar 

  11. 11

    Chekmenev EY, Hövener JB, Norton VA, Harris K, Batchelder LS, Bhattacharya P, Ross BD, Weitekamp D (2008) PASADENA hyperpolarization of succinic acid for MRI and MRS. J Am Chem Soc 130: 4212–4213

    PubMed  Article  CAS  Google Scholar 

  12. 12

    Esteban MA, Maxwell PH (2005) HIF, a missing link between metabolism and cancer. Nat Med 11: 1047–1048

    PubMed  Article  CAS  Google Scholar 

  13. 13

    Rustin P, Munnich A, Rotig A (2002) Succinate dehydrogenase and human diseases: new insights into a well-known enzyme. Eur J Hum Genet 10: 289–291

    PubMed  Article  CAS  Google Scholar 

  14. 14

    Hövener JB, Chekemenev EY, Norton VA, Weitekamp R, Harris K, Perman W, Robertson L, Weitekamp DP, Ross BD, Bhattacharya P (2008) Quality assurance for PASADENA hyperpolarization. Magn Reson Mater Phys (in press). doi:10.1007/s10334-008-0155-x

  15. 15

    Gridnev ID, Higashi N, Asakura K, Imamoto T (2000) Mechanism of asymmetric hydrogenation catalyzed by a rhodium complex of (S,S)-1,2-bis(tertbutylmethylphosphino)ethane. Dihydride mechanism of asymmetric hydrogenation. J Am Chem Soc 122(30): 7183–7194

    Article  CAS  Google Scholar 

  16. 16

    Gridnev ID, Imamoto T (2004) On the mechanism for predicting the sense of enantioselectivity. Acc Chem Res 37(9): 633–644

    PubMed  Article  CAS  Google Scholar 

  17. 17

    Natterer J, Bargon J (1997) Parahydrogen induced polarization. Prog Nucl Magn Reson Spectrosc 31: 293–315

    Article  Google Scholar 

  18. 18

    Goldman M, Johannesson H, Axelsson O, Karlsson M (2006) Design and implementation of C-13 hyperpolarization from para-hydrogen, for new MRI contrast agents. C R Chimie 9: 357–363

    CAS  Google Scholar 

  19. 19

    Association NEM (2001) Determination of signal-to-noise ratio (SNR) in diagnostic magnetic resonance imaging. NEMA Standards, Publication MS 1-2001

  20. 20

    Smith SA, Levante TO, Meier BH, Ernst RR (1994) Computer-simulations in magnetic-resonance—an object-oriented programming approach. J Magn Reson A 106: 75–105

    Article  CAS  Google Scholar 

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Correspondence to Brian D. Ross.

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Hövener, JB., Chekmenev, E.Y., Harris, K.C. et al. Quality assurance of PASADENA hyperpolarization for 13C biomolecules. Magn Reson Mater Phy 22, 123–134 (2009). https://doi.org/10.1007/s10334-008-0154-y

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  • Hyperpolarization
  • Fumarate
  • Succinate
  • Parahydrogen
  • 13C MRI