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      Hyperpolarized 13C Metabolic MRI of the Human Heart : Initial Experience

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          Abstract

          Rationale:

          Altered cardiac energetics is known to play an important role in the progression toward heart failure. A noninvasive method for imaging metabolic markers that could be used in longitudinal studies would be useful for understanding therapeutic approaches that target metabolism.

          Objective:

          To demonstrate the first hyperpolarized 13C metabolic magnetic resonance imaging of the human heart.

          Methods and Results:

          Four healthy subjects underwent conventional proton cardiac magnetic resonance imaging followed by 13C imaging and spectroscopic acquisition immediately after intravenous administration of a 0.1 mmol/kg dose of hyperpolarized [1- 13C]pyruvate. All subjects tolerated the procedure well with no adverse effects reported ≤1 month post procedure. The [1- 13C]pyruvate signal appeared within the chambers but not within the muscle. Imaging of the downstream metabolites showed 13C-bicarbonate signal mainly confined to the left ventricular myocardium, whereas the [1- 13C]lactate signal appeared both within the chambers and in the myocardium. The mean 13C image signal:noise ratio was 115 for [1- 13C]pyruvate, 56 for 13C-bicarbonate, and 53 for [1- 13C]lactate.

          Conclusions:

          These results represent the first 13C images of the human heart. The appearance of 13C-bicarbonate signal after administration of hyperpolarized [1- 13C]pyruvate was readily detected in this healthy cohort (n=4). This shows that assessment of pyruvate metabolism in vivo in humans is feasible using current technology.

          Clinical Trial Registration:

          URL: https://www.clinicaltrials.gov. Unique identifier: NCT02648009.

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          Most cited references17

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          Increase in signal-to-noise ratio of > 10,000 times in liquid-state NMR.

          A method for obtaining strongly polarized nuclear spins in solution has been developed. The method uses low temperature, high magnetic field, and dynamic nuclear polarization (DNP) to strongly polarize nuclear spins in the solid state. The solid sample is subsequently dissolved rapidly in a suitable solvent to create a solution of molecules with hyperpolarized nuclear spins. The polarization is performed in a DNP polarizer, consisting of a super-conducting magnet (3.35 T) and a liquid-helium cooled sample space. The sample is irradiated with microwaves at approximately 94 GHz. Subsequent to polarization, the sample is dissolved by an injection system inside the DNP magnet. The dissolution process effectively preserves the nuclear polarization. The resulting hyperpolarized liquid sample can be transferred to a high-resolution NMR spectrometer, where an enhanced NMR signal can be acquired, or it may be used as an agent for in vivo imaging or spectroscopy. In this article we describe the use of the method on aqueous solutions of [13C]urea. Polarizations of 37% for 13C and 7.8% for 15N, respectively, were obtained after the dissolution. These polarizations correspond to an enhancement of 44,400 for 13C and 23,500 for 15N, respectively, compared with thermal equilibrium at 9.4 T and room temperature. The method can be used generally for signal enhancement and reduction of measurement time in liquid-state NMR and opens up for a variety of in vitro and in vivo applications of DNP-enhanced NMR.
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            Adaptation and maladaptation of the heart in diabetes: Part I: general concepts.

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              Dynamic nuclear polarization polarizer for sterile use intent.

              A novel polarizer based on the dissolution-dynamic nuclear polarization (DNP) method has been designed, built and tested. The polarizer differs from those previously described by being designed with sterile use intent and being compatible with clinical use. The main features are: (1) an integral, disposable fluid path containing all pharmaceuticals constituting a sterile barrier, (2) a closed-cycle cryogenic system designed to eliminate consumption of liquid cryogens and (3) multi-sample polarization to increase throughput. The fluid path consists of a vial with the agent to be polarized, a pair of concentric inlet and outlet tubes connected to a syringe with dissolution medium and a receiver, respectively. The fluid path can operate at up to 400 K and 2.0 MPa and generates volumes as high as 100 mL. An inline filter removes the amount of electron paramagnetic agent in the final product by more than 100-fold in the case of [1-(13)C]pyruvate. The system uses a sorption pump in conjunction with a conventional cryocooler. The system operates through cycles of pumping to low temperature and regeneration of the sorption pump. The magnet accommodates four samples at the same time. A temperature of less than 1 K was achieved for 68 h (no sample heat loads) with a liquid helium volume of 2.4 L. The regeneration of the liquid helium could be achieved in less than 10 h, and the transition to cold (< 1.2 K) was achieved in less than 90 min. A solid state polarization of 36 ± 4% for [1-(13)C]pyruvic acid was obtained with only 10 mW of microwave power. The loading of a sample adds less than 50 J of heat to the helium bath by introducing the sample over 15 min. The heat load imposed on the helium bath during dissolution was less than 70 J. The measured liquid state polarization was 18 ± 2%. Copyright © 2011 John Wiley & Sons, Ltd.
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                Author and article information

                Journal
                Circ Res
                Circ. Res
                RES
                Circulation Research
                Lippincott Williams & Wilkins
                0009-7330
                1524-4571
                11 November 2016
                10 November 2016
                : 119
                : 11
                : 1177-1182
                Affiliations
                From the Physical Sciences, Sunnybrook Research Institute, Toronto, ON, Canada (C.H.C., J.Y.C.L., B.J.G., G.A.W.); Medical Biophysics, University of Toronto, ON, Canada (C.H.C., J.Y.C.L., B.J.G., G.A.W.); GE Healthcare, Toronto, ON, Canada (A.P.C.); Pharmacy (W.J.P.) and Schulich Heart Program (I.R., G.A.W.), Sunnybrook Health Sciences Centre, Toronto, ON, Canada; and Keenan Research Centre for Biomedical Science, St. Michael’s Hospital, Toronto, ON, Canada (K.A.C).
                Author notes
                Correspondence to Charles H. Cunningham, M7-613, 2075 Bayview Ave, Toronto, ON M4N 3M5, Canada. E-mail chuck@ 123456sri.utoronto.ca
                Article
                00013
                10.1161/CIRCRESAHA.116.309769
                5102279
                27635086
                aa79cd4f-f9df-416a-9e9c-c6d4191479a9
                © 2016 The Authors.

                Circulation Research is published on behalf of the American Heart Association, Inc., by Wolters Kluwer. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial-NoDervis License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited, the use is noncommercial, and no modifications or adaptations are made.

                History
                : 14 August 2016
                : 30 August 2016
                : 15 September 2016
                Categories
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                Brief UltraRapid Communication
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                heart failure,magnetic resonance imaging,metabolic imaging,metabolism,mitochondria

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