"I have not yet lost a feeling of wonder, and of delight, that this delicate motion should reside in all the things around us, revealing itself only to him who looks for it. I remember, in the winter of our first experiments, just seven years ago, looking on snow with new eyes. There the snow lay around my doorstep — great heaps of protons quietly precessing in the earth's magnetic field. To see the world for a moment as something rich and strange is the private reward of many a discovery."
-Edward M. Purcell (1952 Nobel Prize in Physics) on the discovery of NMR.
Dynamic nuclear polarization
DNP can be traced in 1953 when Albert Overhauser postulated that the saturation of the ESR line of the conduction electrons leads to an enhancement of the NMR signal. Subsequent experiments by Carver and Slichter in 1956 confirmed the existence of Overhauser effect in metals. The Overhauser effect was extended to non-metals in the works of Abragam et. al. and subsequently the solid effect and thermal mixing DNP mechanisms were discovered. Since the mechanism of DNP is mostly expressed in thermodynamic language, it is important to introduce the concepts of (i) lattice temperature TL and (ii) spin temperature Ts. TL is the thermodynamic temperature of the sample as measured by a sensor, while Ts is the temperature of the spin system calculated using the NMR intensity as the thermometer. Thus Ts is an "artificial" temperature that describes distribution of spin populations in Zeeman energy levels. The time it takes for the spin temperature of the spin system to equalize with the lattice temperature, that is, for the spin system to return to thermal equilibrium, is given by the spin-lattice relaxation time T1. Typically for dissolution DNP, the liquid-state T1 of hyperpolarized substrates need to be at least 10 s so that MRS and MRI experiments could be performed.
In DNP, the spin temperature of the nuclear spin system is lowered by microwave irradiation. It is important to realize the interplay of three heat reservoirs in DNP: (i) electron Zeeman system (ii) electron spin-spin interaction reservoir and (iii) nuclear Zeeman system. The nuclear spin-spin/dipole-dipole system here was neglected because of its weaker contribution.
Calculating the polarization
How to achieve the maximum DNP-NMR signal via thermal mixing
Impact of Gd3+ on 13C dynamic nuclear polarization
Influence of deuteration in the glassing matrix on 13C dynamic nuclear polarization
It was reported in a previous study that deuteration of the glassing solvents of 13C samples doped with TEMPO free radical approximately doubled the nuclear polarization. Based on this paper, it is becoming customary to use deuterated glassing matrices regardless of the type of free radical polarizing agent. Here we investigate the influence of deuteration of the glassing matrix on 13C DNP samples doped with different free radical polarizing agents commonly used for dissolution DNP: BDPA, trityl OX063, galvinoxyl, DPPH, and 4-oxo-TEMPO.
Results: Deuteration of the glassing matrix increases the 13C polarization of samples doped with free radicals that have ESR D comparable to or larger than the 1H Larmor frequency such as galvinoxyl, DPPH, and 4-oxo-TEMPO. This is attributed to the lower heat capacity of the deuteron Zeeman system compared to protons. However, glassing solvent deuteration is not recommended for DNP with free radicals that have narrow ESR linewidth such as BDPA and trityl OX063 where the proton Zeeman system has little or no contact with EDS. In this case, deuteration would only add more heat load to the nuclear Zeeman system, resulting in lower 13C polarization.
ESR studies of trityl OX063 at multiple magnetic fields
It is interesting to note that although there is a significant ESR linewidth broadening from
0.35 T (X-band) to 3.35 T (W-band), the temperature dependence of their electron relaxation rates are very similar. The similarity of the relaxation rate values of trityl OX063 (15 mM) at X- and W-bands was also previously observed in an earlier work on a more dilute trityl radical concentration (0.2 mM). This relaxation behavior was ascribed to the field-independent Raman process and local mode being the dominant relaxation processes at a wide temperature range for trityl radical. On the other hand, increasing the magnetic field to 8.5 T (240 GHz) and 12 T (336 GHz) shortens the electron relaxation time. This is in line with the expected frequency dependence of the direct process. Nevertheless, the log–log plot of electron relaxation rate vs. temperature shown in the Figure shows a monotonic decrease in slope in the high temperature region (T > 15 K) as the field is increased from X or W-band, suggesting deviation from the Raman process. As DNP is pushed to higher fields, the ESR properties of the free radical polarizing agent (e.g. linewidth D and spin–lattice T1e relaxation) play an important role in the performance of DNP. The current results seem to suggest that higher field and lower temperatures will continue to provide increases in nuclear polarization which will approach the theoretical limit without serious hindrance from the free radical relaxation properties.
Galvinoxyl as a polarizing agent for dissolution DNP-NMR spectroscopy
The efficiency of DPPH as a polarizing agent for DNP-NMR spectroscopy
BDPA: teaching an old free radical new tricks
The two lives of hyperpolarized Silver
Physics of Hyperpolarized [13C]-89YDOTA
13C spin diffusion: domino effect expedites DNP process
"Dynamic nuclear polarization has recently been used to produce highly polarized solutions of 13C nuclei suitable for MRI studies. In this report, we detail the use of 13C DMSO in the glassing matrix used to polarize [1-13C]pyruvate. Inclusion of the labeled DMSO results in a faster build up rate for the pyruvate, which can be attributed to increased 13C–13C spin diffusion in the sample."
Thermal mixing occurs when the electronic linewidth δωe is greater than the nuclear Larmor frequency νn. In this case, the nuclear Zeeman system (nZS) is in thermal contact with the electron spin-spin interaction system (eSSIS). In other words, both nZS and eSSIS are "on resonance" and have comparable energies thus they can exchange energies. This leads to the equalization of the spin temperature of both systems under microwave irradiation.
The Solid Effect
DNP: application of physics to chemistry and biology
Production of pyruvate from glucose.
Glycolysis is a series of 10 enzyme-catalyzed reactions that converts glucose into pyruvate. Glycolysis occurs in the cytosol of the cell. Note that enzymes involved in the reaction steps are currently not shown in this figure. Click here for a detailed schematic of glycolytic pathways. An excellent animation of glycolysis is provided by the International Union of Biochemistry and Molecular Biology (IUBMB, click here for the link to the animation). Aberrant glycolytic activity of cells in diseases such as diabetes and cancer are important to understand and carbon-13 NMR is an excellent tool to elucidate the abnormal glycolytic activities. The problem with carbon-13 NMR is the insensitivity but this has recently been addressed by dissolution DNP-NMR technology with allows real time monitoring of metabolic activities via 13C NMR with superb sensitivity.
Normal and Aberrant Cell Metabolism
A simplified version of the TCA cycle.
The tricarboxylic acid (TCA) cycle, also known as citric acid or Krebs cycle, is a series of enzyme-catalyzed reactions that oxidizes acetyl-CoA from pyruvate (the end product of glycolysis), reduces NAD+ into NADH and produces carbon dioxide. NADH is prerequisite to the production of ATP, the energy currency of cells. The TCA cycle occurs in the mitochondria for eukaryotic cells and in the cytosol for bacteria. Note: the backward reaction of the most of the steps in the TCA cycle are not shown. Click here for a more detailed TCA cycle diagram. The TCA cycle is a central series of biochemical reactions for all aerobic organisms, thus an important target of the hyperpolarized carbon-13 NMR technology which is being utilized to understand normal and aberrant cellular metabolism.
 A. Abragam and M. Goldman, Rep. Prog. Phys. 41, 395-467 (1978).
 W. de Boer, J. Low Temp. Phys. 22, 185-212 (1976).
 D. G. Crabb and W. Meyer, Annu. Rev. Nucl. Part. Sci. 47, 67-109 (1997).
 J. H. Ardenkjaer-Larsen et al., Proc. Natl. Acad. Sci. U.S.A. 100, 10158-10163 (2003).
 J. Kurhanewicz et al., Neoplasia 13, 81-97 (2011).
 K. Brindle, Nat. Rev. Cancer 8, 94-107 (2008).
 K. M. Brindle et al., Magn. Reson. Med. 66, 505-519 (2011).
 L. Lumata et. al., Angew. Chem. Intl. Ed. 51, 525-527 (2012).
 M. G. Vander Heiden, L. C. Cantley, and C. B. Thompson, "Understanding the Warburg effect: the metabolic requirements of cell proliferation" Science 324, 1029-1033 (2009).