title: 15N Hyperpolarization by Reversible Exchange Using SABRE-SHEATH.
abstract: NMR signal amplification by reversible exchange (SABRE) is a NMR hyperpolarization technique that enables nuclear spin polarization enhancement of molecules via concurrent chemical exchange of a target substrate and parahydrogen (the source of spin order) on an iridium catalyst. Recently, we demonstrated that conducting SABRE in microtesla fields provided by a magnetic shield enables up to 10%15N-polarization (Theis, T.; et al.J. Am. Chem. Soc.2015,137, 1404). Hyperpolarization on15N (and heteronuclei in general) may be advantageous because of the long-lived nature of the hyperpolarization on15N relative to the short-lived hyperpolarization of protons conventionally hyperpolarized by SABRE, in addition to wider chemical shift dispersion and absence of background signal. Here we show that these unprecedented polarization levels enable15N magnetic resonance imaging. We also present a theoretical model for the hyperpolarization transfer to heteronuclei, and detail key parameters that should be optimized for efficient15N-hyperpolarization. The effects of parahydrogen pressure, flow rate, sample temperature, catalyst-to-substrate ratio, relaxation time (T1), and reversible oxygen quenching are studied on a test system of15N-pyridine in methanol-d4. Moreover, we demonstrate the first proof-of-principle13C-hyperpolarization using this method. This simple hyperpolarization scheme only requires access to parahydrogen and a magnetic shield, and it provides large enough signal gains to enable one of the first15N images (2 × 2 mm2resolution). Importantly, this method enables hyperpolarization of molecular sites with NMRT1relaxation times suitable for biomedical imaging and spectroscopy.
authors.affiliation: Institute of Imaging Science, Department of Radiology, Department of Biomedical Engineering, Department of Physics and Astronomy, Department of Biochemistry, and Vanderbilt-Ingram Cancer Center (VICC), Vanderbilt University , Nashville, Tennessee 37232-2310, United States.
authors.forename: Milton L
authors.initials: ML
authors.lastname: Truong
authors.affiliation: Department of Chemistry, Duke University , Durham, North Carolina 27708, United States.
authors.forename: Thomas
authors.initials: T
authors.lastname: Theis
authors.affiliation: Institute of Imaging Science, Department of Radiology, Department of Biomedical Engineering, Department of Physics and Astronomy, Department of Biochemistry, and Vanderbilt-Ingram Cancer Center (VICC), Vanderbilt University , Nashville, Tennessee 37232-2310, United States.
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Coffey
authors.affiliation: Institute of Imaging Science, Department of Radiology, Department of Biomedical Engineering, Department of Physics and Astronomy, Department of Biochemistry, and Vanderbilt-Ingram Cancer Center (VICC), Vanderbilt University , Nashville, Tennessee 37232-2310, United States.
authors.forename: Roman V
authors.initials: RV
authors.lastname: Shchepin
authors.affiliation: Institute of Imaging Science, Department of Radiology, Department of Biomedical Engineering, Department of Physics and Astronomy, Department of Biochemistry, and Vanderbilt-Ingram Cancer Center (VICC), Vanderbilt University , Nashville, Tennessee 37232-2310, United States ; Institute of Imaging Science, Department of Radiology, Department of Biomedical Engineering, Department of Physics and Astronomy, Department of Biochemistry, and Vanderbilt-Ingram Cancer Center (VICC), Vanderbilt University , Nashville, Tennessee 37232-2310, United States.
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Waddell
authors.affiliation: Department of Chemistry and Biochemistry and Materials Technology Center, Southern Illinois University , Carbondale, Illinois 62901, United States.
authors.forename: Fan
authors.initials: F
authors.lastname: Shi
authors.affiliation: Department of Chemistry and Biochemistry and Materials Technology Center, Southern Illinois University , Carbondale, Illinois 62901, United States ; Department of Chemistry and Biochemistry and Materials Technology Center, Southern Illinois University , Carbondale, Illinois 62901, United States.
authors.forename: Boyd M
authors.initials: BM
authors.lastname: Goodson
authors.affiliation: Department of Chemistry, Duke University , Durham, North Carolina 27708, United States.
authors.forename: Warren S
authors.initials: WS
authors.lastname: Warren
authors.affiliation: Institute of Imaging Science, Department of Radiology, Department of Biomedical Engineering, Department of Physics and Astronomy, Department of Biochemistry, and Vanderbilt-Ingram Cancer Center (VICC), Vanderbilt University , Nashville, Tennessee 37232-2310, United States ; Institute of Imaging Science, Department of Radiology, Department of Biomedical Engineering, Department of Physics and Astronomy, Department of Biochemistry, and Vanderbilt-Ingram Cancer Center (VICC), Vanderbilt University , Nashville, Tennessee 37232-2310, United States ; Institute of Imaging Science, Department of Radiology, Department of Biomedical Engineering, Department of Physics and Astronomy, Department of Biochemistry, and Vanderbilt-Ingram Cancer Center (VICC), Vanderbilt University , Nashville, Tennessee 37232-2310, United States ; Institute of Imaging Science, Department of Radiology, Department of Biomedical Engineering, Department of Physics and Astronomy, Department of Biochemistry, and Vanderbilt-Ingram Cancer Center (VICC), Vanderbilt University , Nashville, Tennessee 37232-2310, United States.
authors.forename: Eduard Y
authors.initials: EY
authors.lastname: Chekmenev