Dissolution DNP

A dissolution-DNP experiment is a three step process: first, the sample is polarized via DNP by microwave irradiation at low temperature; second, the sample is dissolved in a hot solvent and transported into the spectrometer or imager magnet by blowing high-pressure gas through a plastic tube; third, the solution is injected into a NMR tube, an animal or a human and data acquisition is launched. Optimization of protocols that cover this sequence from the first to the last step is of great importance to obtain reliable, reproducible results. This is achieved through computer control of specifically designed hardware for each of the steps.

The original publication describing this technique is:

J.H. Ardenkjær-Larsen, B. Fridlund, A. Gram, G. Hansson, L. Hansson, M.H. Lerche, R. Servin, M. Thaning, K. Golman, Increase in signal-to-noise ratio of > 10000 times in liquid-state NMR. Proc. Natl. Acad. Sci. USA 100, 10158 (2003).

and their original instrumentation is described in:

J. Wolber, F. Ellner, B. Fridlund, A. Gram, H. Jóhannesson, G. Hansson, L.H. Hansson, M.H. Lerche, S. Månsson, R. Servin, M. Thaning, K. Golman, J.H. Ardenkjær-Larsen, Generating highly polarized nuclear spins in solution using dynamic nuclear polarization, Nucl. Instr. Methods A 526, 173 (2004).

In the meantime a highly engineered "white box" version of that instrument has been developed:

J.H. Ardenkjær-Larsen, A.M. Leach, N. Clarke, J. Urbahn, D. Anderson, T.W. Skloss, Dynamic Nuclear Polarization Polarizer for Sterile Use Intent. NMR Biomed. 24, 927 (2011),

which is now commercially available. Note that, very roughly, the first factor 100 in that "10'000 fold increase" just comes from the rapid dissolution: the sample goes from, say, 3 K to, say, 300 K, much in the way of the old "temperature jump" experiments:

E.M. Purcell, R.V. Pound, A Nuclear Spin System at Negative Temperature, Phys. Rev. 81, 279 (1951).

A. Abragam, W.G. Proctor, Spin Temperature, Phys. Rev. 109,1441 (1958).

Curie's law says that this factor goes as the ratio (B/T)solid/(B/T)liquid. It is the remaining factor 100 that is due to the DNP proper: the "nuclear spin temperature" Tspin is of the order of Tsolid/100. For large values of (B/T)solid Curie's law no longer holds, and the reasoning is somewhat more complex. For DNP by thermal mixing at values of (B/T)solid where Curie's law is valid; the DNP-enhancement proper is independent of nucleus and of temperature; and linear in Bsolid. The increase in liquid signal-to-noise ratio goes as Bsolid * (B/T)solid/(B/T)liquid.

Hyperpolarized substrates prepared via dissolution dynamic nuclear polarization (DNP) have been proposed as magnetic resonance imaging (MRI) contrast agents for cancer or cardiac failure diagnosis and therapy monitoring through the detection of metabolic impairments in vivo [1-3]. A clinical trial is under way in prostate cancer patients [4].

[1] S.E. Day, M.I. Kettunen, F.A. Gallagher, D.E. Hu, M. Lerche, J. Wolber, K. Golman, J.H. Ardenkjær-Larsen, K.M. Brindle, Detecting tumor response to treatment using hyperpolarized (13)C magnetic resonance imaging and spectroscopy, Nat. Med. 13, 1382 (2007).
[2] J. Kurhanewicz, D. B. Vigneron, K. Brindle, E. Y. Chekmenev, A. Comment, C. H. Cunningham, R. J. DeBerardinis, G. G. Green, M. O. Leach, S. S. Rajan, R. R. Rizi, B. D. Ross, W. S. Warren, C. R. Malloy, Analysis of Cancer Metabolism by Imaging Hyperpolarized Nuclei: Prospects for Translation to Clinical Research. Neoplasia 13, 81 (2011).
[3] C.R. Malloy, M.E. Merritt, A.D. Sherry, Could 13C MRI assist clinical decision-making for patients with heart disease? NMR Biomed. 24, 979 (2011).
[4] http://clinicaltrials.gov/ct2/show/study/NCT01229618