TY - JOUR

T1 - Subsecond Three-Dimensional Nitrogen-15 Magnetic Resonance Imaging Facilitated by Parahydrogen-Based Hyperpolarization

AU - Trepakova, Alexandra I.

AU - Skovpin, Ivan V.

AU - Chukanov, Nikita V.

AU - Salnikov, Oleg G.

AU - Chekmenev, Eduard Y.

AU - Pravdivtsev, Andrey N.

AU - Hövener, Jan Bernd

AU - Koptyug, Igor V.

N1 - Funding Information: A.I.T. and N.V.C. thank the Russian Science Foundation (Grant 21-73-10105) for supporting the SLIC-SABRE experiments and the synthesis of [N]fampridine. O.G.S. thanks the Council on Grants of the President of the Russian Federation (Grant MK-2826.2022.1.3) for supporting the optimization of the SABRE conditions. I.V.S., N.V.C., and I.V.K. thank the Russian Science Foundation (Grant 22-43-04426) for supporting SABRE simulations and MRI experiments. The ITC SB RAS team thanks the Russian Ministry of Science and Higher Education for access to NMR/MRI equipment. E.Y.C. is thankful for National Science Foundation Grant CHE-1904780 and National Institutes of Health NIBIB Grant R01EB029829. A.N.P. and J.-B.H. acknowledge funding from the German Federal Ministry of Education and Research (BMBF) within the framework of the e:Med research and funding concept (01ZX1915C), DFG (PR 1868/3-1, HO-4602/2-2, HO-4602/3, GRK2154-2019, EXC2167, FOR5042, and TRR287). MOIN CC was founded by a grant from the European Regional Development Fund (ERDF) and the Zukunftsprogramm Wirtschaft of Schleswig-Holstein (Project 122-09-053). 15 1 Publisher Copyright: © 2022 American Chemical Society.

PY - 2022/11/10

Y1 - 2022/11/10

N2 - Magnetic resonance imaging (MRI) provides unique information about the internal structure and function of living organisms in a non-invasive way. The use of conventional proton MRI for the observation of real-time metabolism is hampered by the dominant signals of water and fat, which are abundant in living organisms. Heteronuclear MRI in conjunction with the hyperpolarization methods does not encounter this issue. In this work, we polarized 15N nuclei of [15N1]fampridine (a drug used for the treatment of multiple sclerosis) to the level of 4% in nuclear magnetic resonance (NMR) experiments and 0.7% in MRI studies using spin-lock-induced crossing combined with signal amplification by reversible exchange. Consequently, three-dimensional 15N MRI of the hyperpolarized 15N-labeled drug was acquired in 0.1 s with a signal-to-noise ratio of 70. In addition, the NMR signal enhancements for 15N-enriched fampridine and fampridine with a natural abundance of 15N nuclei were compared and an explanation for their difference was proposed.

AB - Magnetic resonance imaging (MRI) provides unique information about the internal structure and function of living organisms in a non-invasive way. The use of conventional proton MRI for the observation of real-time metabolism is hampered by the dominant signals of water and fat, which are abundant in living organisms. Heteronuclear MRI in conjunction with the hyperpolarization methods does not encounter this issue. In this work, we polarized 15N nuclei of [15N1]fampridine (a drug used for the treatment of multiple sclerosis) to the level of 4% in nuclear magnetic resonance (NMR) experiments and 0.7% in MRI studies using spin-lock-induced crossing combined with signal amplification by reversible exchange. Consequently, three-dimensional 15N MRI of the hyperpolarized 15N-labeled drug was acquired in 0.1 s with a signal-to-noise ratio of 70. In addition, the NMR signal enhancements for 15N-enriched fampridine and fampridine with a natural abundance of 15N nuclei were compared and an explanation for their difference was proposed.

KW - Magnetic Resonance Spectroscopy/methods

KW - Magnetic Resonance Imaging/methods

KW - Nitrogen Isotopes/chemistry

KW - Protons

UR - http://www.scopus.com/inward/record.url?scp=85141480389&partnerID=8YFLogxK

U2 - 10.1021/acs.jpclett.2c02705

DO - 10.1021/acs.jpclett.2c02705

M3 - Article

C2 - 36301252

AN - SCOPUS:85141480389

VL - 13

SP - 10253

EP - 10260

JO - Journal of Physical Chemistry Letters

JF - Journal of Physical Chemistry Letters

SN - 1948-7185

IS - 44

ER -