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C in solution at T?300K and B0=7.05T. (e) Signals of sodium pyruvate-1-13C immediately after dissolution (red) and at thermal equilibrium (blue, x2048). Discussion/Conclusion: We have demonstrated that Dissolution-DNP with TEMPO at B0=6.7T and T=1.2K in combination with cross polarization is an efficient method for maximizing 13C polarization in record build-up rates. Currently, we are performing DNP at even higher magnetic fields, B0=9.4T and T=4.2K and we already obtained improved efficiency. We are also working on other nuclei such as 15N and 6Li. Most recent results will be presented. References: [1] J. H..Ardenkjaer-Larsen et al. NMR Biomed. 2011, 24, 927. [2] S. Jannin et al. Chem.Phys.Lett. 2011, 517, 234. [3] S. Jannin et al. Chem.Phys.Lett. 2012, 549, 99. [4] J. H. Ardenkjaer-Larsen et al. Proc.Natl.Acad.Sci.U.S.A. 2003, 100, 10158. [5] P. Miéville et al. Angew.Chem.Intern.Ed. 2010, 49, 6182. [6] A. Bornet et al. J.Phys.Chem.Lett. 2013, 4, 111.

74 Scientific Session - Preclinical Studies & Basic Science 15:40 - 17:10

Concorde 2

Improving MR sensitivity 468 Dissolution Dynamic Nuclear Polarization Revisited S. Jannin1,2, A. Bornet1, J. Milani1, R. Melzi3, A.J. Perez Linde1, P. Hautle4, B. Van Den Brandt4, J. Lohman5, G. Bodenhausen1,6,7,8 1 Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne, Lausanne/SWITZERLAND, 2R&D, Bruker BioSpin AG, Fällanden/SWITZERLAND, 3Bruker, Bruker Italia S.r.l., Milano/ITALY, 4 SEPT, PSI, Villigen/SWITZERLAND, 5R&D, Bruker UK Limited, Coventry/ UNITED KINGDOM, 6Département de Chimie, Ecole Normale Supérieure, Paris Cedex/FRANCE, 7Chemistry, Université Pierre-et-Marie Curie, Paris Cedex/FRANCE, 8UMR 7203, CNRS, Paris Cedex /FRANCE

469 [1-13C] Glutamate hyperpolarisation for metabolism study in the rodent brain using Magnetic Resonance Spectroscopy (MRS)

Purpose/Introduction: Direct polarization of long T1 low gamma nuclei by dissolution DNP usually works better with polarizing agents with narrow ESR lines such as trityl radical than with nitroxides with broad lines such as TEMPO. In fact trityl very efficiently polarizes 13C, at B0=3.35T and T=1.0K, up to polarization levels P(13C)~35%, although the build-up times tDNP(13C)>2000 s are quite long[1]. However, while DNP with trityl leaves the 1 H spins largely unpolarized, TEMPO turns out to be an efficient 1H polarizer. We have demonstrated that polarization levels P(1H)>95% could be obtained in tDNP(1H)=150s at B0=6.7T and T=1.2K. This achievement, in combination with 1H → 13C cross polarization at 1.2K opens the way to unprecedented 13C polarizations P(13C)>70% in less than 20 minutes[2-3]. Subjects and Methods: We describe how CP-DNP was made compatible with dissolution experiment[4] where samples containing highly polarized 13C spins are rapidly dissolved to room temperature and transferred to a liquid-state spectrometer or MRI system. Results: In figure 1, P(13C)?50% was obtained in sodium pyruvate-1-13C with CP (see 1a and 1b) using a dedicated triple resonance CP-DNP probe. After only 25 minutes, rapid dissolution of the DNP sample resulted in P(13C)=40% in the liquid state (see 1d). [6]

Figure 1. (a) Signals of 13C of 50 μL of a 3 M frozen solution of 1-13C enriched sodium pyruvate measured without CP (blue) at thermal equilibrium (T=4.2K and B0=6.7T, x100) and with CP-DNP (red). (b) 13C DNP build-up with (red) and without (gray) CP. (c) Dissolution and transfer (10s). (d) Relaxation of

Saturday, October 5

C. Chassain1, L. Mazuel2, A. Cladière1, C. Speziale1, R. Schulte3, C. Rabrait4, B. Jean1, F. Durif2,5 1 MRI service, CHU Gabriel Montpied, Clermont-Ferrand/FRANCE, 2EA 7280, Université d’Auvergne, Clermont-Ferrand/FRANCE, 3NMR, GE Global Research, Munich/GERMANY, 4Clinical Science Development Group, General Electric Healthcare, Buc/FRANCE, 5Neurology, CHU Gabriel Montpied, Clermont-Ferrand/FRANCE Purpose/Introduction: Previous studies using MRS showed a change in neurotransmitters levels in the striatum in Parkinson’s disease models (Chassain et al, 2005;2010). Experimental times are on the order of several tens of minutes. In the aim to reduce this time, we want to use the highly amplified signal generated by hyperpolarization to achieve both spatial and temporal resolution adequate for in vivo metabolism studies. The aim of this study was to hyperpolarize the [1-13C] glutamate, inject it in vivo and visualise its biodistribution inside the rat brain overcoming the challenge of crossing the blood-brain-barrier (BBB). Subjects and Methods: All experiments were performed on a 3T MR750 scanner (GEHC Milwaukee, WI, USA), using a dual-tuned birdcage coil (1H/13C). Rats were anaesthetized with isoflurane. L-[1-13C]-glutamic acid was hyperpolarized (Gallagher et al, 2011) using the Hypersense (Oxford Instruments). The frozen sample was dissolved with phosphate buffer and 0.2mL of 9mM hyperpolarized [1-13C] Glutamate solution was quickly (10s) administered via the carotid artery. To obtain an osmotic BBB disruption, 10 minutes before injection of the hyperpolarized solution, rats were infused with a hypertonic solution of 25% mannitol into the carotid. A control was performed after infusion of NaCl. The brain was localized using T1-weighting axial images. A lactate syringe was used for pulses calibration. 13C CSI was performed using Spectral-Spatial (SPSP) excitation combined with a single shot spiral readout (Schulte et al, 2012). Data were acquired from a single transversal slice (thickness=20mm) through the brain with FOV=50mm; repetition time=1s; flip angle=15° and excitation frequency centered on Glu. This acquisition was repeated 64 times and started simultaneously with intra-arterial injection. Data reconstruction was performed using MATLAB (Wiesinger et al, 2012). Results: L-[1-13C]-glutamic acid was polarized by up to 15.8% in the liquid state and the T1 was 19.75s. Spectra acquired following injection of hyperpolarized glutamate showed the hyperpolarized 13C-labeled carboxyl bolus, which typically occurred in the carotid after 4s (figure 1). After NaCl infusion, signal was concentrated around the injection site for all the experimental time. With 25% mannitol infusion, the signal was detected in the rat brain after 8s (figures 1 and 2).

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Discussion/Conclusion: In conclusion, the hyperpolarized [1-13C] Glutamate is imaged in vivo in the rat brain. Thus it may be a promising substrate for evaluation of cerebral glutamate activity in conjunction with neurodegenerative disease. References: Chassain et al.2005.Exp Neurol;191:276-84. Chassain et al.2010.NMR Biomed;23:547-53. Gallagher et al.2011.MRM;66:18-23. Schulte et al.2012.MRM;69:1209-16. Wiesinger et al.2012.MRM;68:8-16.

470  Using Inversion Recovery to Optimize the performance of 1.5T in-bore Continuous Flow Overhauser DNP MRI M. Terekhov1, V. Denisenkov2, T. Prisner2, L.M. Schreiber1 1 Department of Radiology, Section of Medical Physics, Johannes Gutenberg University Medical Center Mainz, Mainz/GERMANY, 2Institute of Physical and Theoretical Chemistry, Center for Bimolecular Magnetic Resonance, Goethe-University, Frankfurt-am-Main/GERMANY Purpose/Introduction: Dynamic Nuclear Polarization (DNP) is a technique to achieve hyperpolarization by microwave irradiation of electron spins in radicals, coupled to the nuclear spins. Recently, the first in-bore liquid-state “Overhauser DNP” (ODNP) at 1.5 T was reported with placing the polarizer core inside MRI magnet and delivery of hyperpolarized (HP-) agent in continuous flow [1][2]. The amount of polarization depends both on the sample flow-rate and T1. We performed the study in order to establish the method of quantification and optimization of the images obtained with ODNP. The equation for magnetization: dMz/dt= -R*Mz(t)+V describing balance between losses due to relaxation and rf-pulses (R*) and magnetization income by inflow of HP-sample with rate V was used to fit experimental data. However, in the 1 H-MRI the HP-substrate mixes with the thermally polarized one distorting quantification. The Inversion Recovery (IR) preparation was employed to solve the problem using negative enhancement of polarization by ODNP. By adjusting inversion period to TI=2×log(T1) the signal of “thermal background” was suppressed while preserving the ODNP-magnetization signal. Subjects and Methods: The hyperpolarized agent in resonator streams through the ID=0.4mm quartz capillary. The outlet capillary (ID=0.15 mm) transfers it to 0.4mm phantom flat-cell. Images were acquired by 1.5T Scanner (Sonata, Siemens, Germany). The 20 mmol/l solution of TEMPOL streamed with flow rate of 10-30 ml/hours. SE and SGRE sequences with IR-preparation have been used. Results: Figure 1 shows that the background thermal magnetization signal can be suppressed by the IR-preparation. The pure DNP-magnetization volume was measured. The acquired data demonstrates the expected plateau indicating approaching a balance between inflow and losses (Fig 2a). The flip-angle dependence S(α) (Fig. 2b) shows profile with maximum characteristic for sequences with using steady-state and transient state magnetization.

Saturday, October 5

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