Hyperpolarized water as an MR imaging contrast agent: feasibility of in vivo imaging in a rat model.

PURPOSE: To assess the feasibility of a perfusion magnetic resonance (MR) imaging technique that uses Overhauser dynamic nuclear polarization (DNP) to provide contrast during the continuous delivery of hyperpolarized water in rats. MATERIALS AND METHODS: Protocols approved by the local institutional animal care and use committees were followed. Twelve male Wistar rats were anesthetized and prepared by placing injection tubing in the subcutaneous layer (n=3), peritoneum (n=3), aorta (n=3), or carotid artery (n=3). Water was hyperpolarized by means of Overhauser DNP in the 0.35-T fringe field of a 1.5-T MR imaging magnet by using a custom-built system to continuously deliver radical-free hyperpolarized water to the subject. Fast gradient-echo and spoiled gradient-recalled-echo MR imaging sequences were used. The signal-to-noise ratio (SNR) of the images was calculated and compared. RESULTS: Images showed greatly altered SNR and enhanced flow contrast at all injection locations. For subcutaneous and intraperitoneal injections, the water perfusion trajectory was observed for approximately 5 seconds after injection. Flow through a 4.2-cm length of artery was seen during intra-aortic injection. The right hemisphere of the brain was seen during injection into the right carotid artery. Images with hyperpolarized water had greatly altered SNR compared with images without injection or with the injection of nonhyperpolarized water, with a range of 13%-27% for the carotid and 444%-2900% for the other regions. CONCLUSION: Perfusion contrast for MR imaging can be obtained by continuously infusing hyperpolarized water, providing localized angiography or brain perfusion information in vivo for rat models.

Portable X-band system for solution state dynamic nuclear polarization.

This paper concerns instrumental approaches to obtain large dynamic nuclear polarization (DNP) enhancements in a completely portable system. We show that at fields of 0.35 T under ambient conditions and at X-band frequencies, 1H enhancements of >100-fold can be achieved using nitroxide radical systems, which is near the theoretical maximum for 1H polarization using the Overhauser effect at this field. These large enhancements were obtained using a custom built microwave transmitter and a commercial TE102 X-band resonant cavity. The custom built microwave transmitter is compact, so when combined with a permanent magnet it is readily transportable. Our commercial X-band resonator was modified to be tunable over a range of approximately 9.5-10 GHz, giving added versatility to our fixed field portable DNP system. In addition, a field adjustable Halbach permanent magnet has also been employed as another means for matching the electron spin resonance condition. Both portable setups provide large signal enhancements and with improvements in design and engineering, greater than 100-fold 1H enhancements are feasible.

Cation and anion transport in a dicationic imidazolium-based plastic crystal ion conductor.

Here we investigate the organic ionic plastic crystal 1,2-bis[N-(N'-hexylimidazolium-d2(4,5))]ethane 2PF6(-) in one of its solid plastic crystal phases by means of multinuclear solid-state (SS) NMR and pulsed-field-gradient NMR diffusometry. We quantify distinct cation and anion diffusion coefficients as well as the Arrhenius diffusion activation energies (Ea) in this dicationic imidazolium-based plastic crystal. Our studies suggest a change in transport mechanism for the cation upon varying thermal and magnetic treatment (9.4 T), evidenced by differences in cation and anion Ea. Moreover, variable temperature (2)H SSNMR line shapes support a change in local molecular environment upon slow cooling in B0. We quantify the percentage of mobile anions as a function of temperature with (19)F SSNMR, wherein two distinct spectral features are present. We also comment on the Arrhenius pre-exponential factor for diffusion (D0), giving insight into the number of degrees of freedom for transport for both cation and anion as a function of thermal treatment. Given the breadth and depth of our measurements, we propose that bulk ion transport is dominated by anion diffusion in ionic-liquid-like domain boundaries separating crystallites. This study elucidates fundamental properties of this plastic crystal, and allows for a more general and deeper understanding of ion transport within such materials.

Humidity-modulated phase control and nanoscopic transport in supramolecular assemblies.

Supramolecular assembly allows for enhanced control of bulk material properties through the fine modulation of intermolecular interactions. We present a comprehensive study of a cross-linkable amphiphilic wedge molecule based on a sulfonated trialkoxybenzene with a sodium counterion that forms liquid crystalline (LC) phases with ionic nanochannel structures. This compound exhibits drastic structural changes as a function of relative humidity (RH). Our combined structural, dynamical, and transport studies reveal deep and novel information on the coupling of water and wedge molecule transport to structural motifs, including the significant influence of domain boundaries within the material. Over a range of RH values, we employ (23)Na solid-state NMR on the counterions to complement detailed structural studies by grazing-incidence small-angle X-ray scattering. RH-dependent pulsed-field-gradient (PFG) NMR diffusion studies on both water and the wedge amphiphiles show multiple components, corresponding to species diffusing within LC domains as well as in the domain boundaries that compose 10% of the material. The rich transport and dynamical behaviors described here represent an important window into the world of supramolecular soft materials, carrying implications for optimization of these materials in many venues. Cubic phases present at high RH show fast transport of water (2 × 10(-10) m(2)/s), competitive with that observed in benchmark polymeric ion conductors. Understanding the self-assembly of these supramolecular building blocks shows promise for generating cross-linked membranes with fast ion conduction for applications such as next-generation batteries.

Unraveling the local energetics of transport in a polymer ion conductor.

We compare diffusion activation energy measurements in a hydrated perfluorosulfonate ionomer and aqueous solutions of triflic acid. These measurements provide insight into water transport dynamics on sub-nm length scales, and gauge the contribution of the polymer sidechain terminal group. Future membrane materials design will hinge on detailed understanding of transport dynamics.

Overhauser dynamic nuclear polarization amplification of NMR flow imaging.

We describe the first study comparing the ability of phase shift velocity imaging and Overhauser dynamic nuclear polarization (DNP)-enhanced imaging to generate contrast for visualizing the flow of water. Prepolarization of water by the Overhauser DNP mechanism is performed in the 0.35T fringe field of an unshielded 2.0T non-clinical MRI magnet, followed by the rapid transfer of polarization-enhanced water to the 2.0T imaging location. This technique, previously named remotely enhanced liquids for image contrast (RELIC), produces a continuous flow of hyperpolarized water and gives up to an -8.2-fold enhanced signal within the image with respect to thermally polarized signal at 2.0T. Using flow through a cylindrical expansion phantom as a model system, spin-echo intensity images with DNP are compared to 3D phase shift velocity images to illustrate the complementary information available from the two techniques. The spin-echo intensity images enhanced with DNP show that the levels of enhancement provide an estimate of the transient propagation of flow, while the phase shift velocity images quantitatively measure the velocity of each imaging voxel. Phase shift velocity images acquired with and without DNP show that DNP weights velocity values towards those of the inflowing (DNP-enhanced) water, while velocity images without DNP more accurately reflect the average steady-state velocity of each voxel. We conclude that imaging with DNP prepolarized water better captures the transient path of water shortly after injection, while phase shift velocity imaging is best for quantifying the steady-state flow of water throughout the entire phantom.

Heisenberg spin exchange effects of nitroxide radicals on Overhauser dynamic nuclear polarization in the low field limit at 1.5mT.

Nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) at very low magnetic fields (0.05-20mT) have gained interest due to the simple and portable magnet design and newly emerging applications outside of the usual laboratory setting. A method to enhance the NMR signal is needed due to the low thermal polarization of nuclear spins at these fields; dynamic nuclear polarization (DNP) via the Overhauser effect from free radicals is an attractive option. In this report we describe a DNP-enhanced NMR system operating at a fixed field of 1.5mT and measure (1)H signal enhancements of up to -350 fold during the saturation of a selected electron spin resonance (ESR) transition of dissolved nitroxide radicals. This -350 fold enhanced polarization is equivalent to what would be obtained by prepolarization in a 0.53T field. The ESR spectra at varying radical concentrations are indirectly found through DNP-enhanced NMR detection. Here, ESR line broadening at higher radical concentrations due to Heisenberg electron spin exchange is observed. Enhancements in the limit of maximum power are reported as a function of concentration for three ESR transitions, and are found to increase with concentration. The >300 fold (1)H NMR signal amplifications achievable at 1.5mT will reduce experimental time by several orders of magnitude, permitting NMR relaxation, imaging or pulsed-field gradient diffusion experiments that are inaccessible without using the DNP effect at 1.5mT. We demonstrate the potential benefit of such large signal amplification schemes through T(1) and T(2) relaxation measurements carried out in a much shorter time when employing DNP. Finally, we compare our results to those obtained in the earth's magnetic field and find that the signal to noise ratio (SNR) of DNP-enhanced signal at 1.5mT is much greater than that obtained by previous studies utilizing DNP enhancement in the 0.05mT earth's magnetic field.

Continuous flow Overhauser dynamic nuclear polarization of water in the fringe field of a clinical magnetic resonance imaging system for authentic image contrast.

We describe and demonstrate a system to generate hyperpolarized water in the 0.35 T fringe field of a clinical 1.5 T whole-body magnetic resonance imaging (MRI) magnet. Once generated, the hyperpolarized water is quickly and continuously transferred from the 0.35 T fringe to the 1.5 T center field of the same magnet for image acquisition using standard MRI equipment. The hyperpolarization is based on Overhauser dynamic nuclear polarization (DNP), which effectively and quickly transfers the higher spin polarization of free radicals to nuclear spins at ambient temperatures. We visualize the dispersion of hyperpolarized water as it flows through water-saturated systems by utilizing an observed -15-fold DNP signal enhancement with respect to the unenhanced (1)H MRI signal of water at 1.5 T. The experimental DNP apparatus presented here is readily portable and can be brought to and used with any conventional unshielded MRI system. A new method of immobilizing radicals to gel beads via polyelectrolyte linker arms is described, which led to superior flow Overhauser DNP performance compared to previously presented gels. We discuss the general applicability of Overhauser DNP of water and aqueous solutions in the fringe field of commercially available magnets with central fields up to 4.7 T.

Dynamic nuclear polarization of 13C in aqueous solutions under ambient conditions.

The direct enhancement of the (13)C NMR signal of small molecules in solution through Overhauser-mediated dynamic nuclear polarization (DNP) has the potential to enable studies of systems where enhanced signal is needed but the current dissolution DNP approach is not suitable, for instance if the sample does not tolerate a freeze-thaw process or if continuous flow or rapid re-polarization of the molecules is desired. We present systematic studies of the (13)C DNP enhancement of (13)C-labeled small molecules in aqueous solution under ambient conditions, where we observe both dipolar and scalar-mediated enhancement. We show the role of the three-spin effects from enhanced protons on (13)C DNP through DNP experiments with and without broadband (1)H decoupling and by comparing DNP results with H(2)O and D(2)O. We conclude that the efficiency of (13)C Overhauser DNP in small molecules strongly depends on the distance of closest approach between the electron and (13)C nucleus, the presence of a scalar contribution to the coupling factor, and the magnitude of the three-spin effect due to adjacent polarized protons. The enhancement appears to depend less on the translational dynamics of the (13)C-labeled small molecules and radicals.

Hyperpolarized water as an authentic magnetic resonance imaging contrast agent.

Pure water in a highly (1)H spin-polarized state is proposed as a contrast-agent-free contrast agent to visualize its macroscopic evolution in aqueous media by MRI. Remotely enhanced liquids for image contrast (RELIC) utilizes a (1)H signal of water that is enhanced outside the sample in continuous-flow mode and immediately delivered to the sample to obtain maximum contrast between entering and bulk fluids. Hyperpolarization suggests an ideal contrast mechanism to highlight the ubiquitous and specific function of water in physiology, biology, and materials because the physiological, chemical, and macroscopic function of water is not altered by the degree of magnetization. We present an approach that is capable of instantaneously enhancing the (1)H MRI signal by up to 2 orders of magnitude through the Overhauser effect under ambient conditions at 0.35 tesla by using highly spin-polarized unpaired electrons that are covalently immobilized onto a porous, water-saturated gel matrix. The continuous polarization of radical-free flowing water allowed us to distinctively visualize vortices in model reactors and dispersion patterns through porous media. A (1)H signal enhancement of water by a factor of -10 and -100 provides for an observation time of >4 and 7 s, respectively, upon its injection into fluids with a T(1) relaxation time of >1.5 s. The implications for chemical engineering or biomedical applications of using hyperpolarized solvents or physiological fluids to visualize mass transport and perfusion with high and authentic MRI contrast originating from water itself, and not from foreign contrast agents, are immediate.