15N MRI of SLIC-SABRE Hyperpolarized 15N-Labelled Pyridine and Nicotinamide

Article abstract of DOI:10.1002/chem.201900430

Magnetic Resonance Imaging (MRI) is a powerful non-invasive diagnostic method extensively used in biomedical studies. A significant limitation of MRI is its relatively low signal-to-noise ratio, which can be increased by hyperpolarizing nuclear spins. One promising method is Signal Amplification By Reversible Exchange (SABRE), which employs parahydrogen as a source of hyperpolarization. Recent studies demonstrated the feasibility to improve MRI sensitivity with this hyperpolarization technique. Hyperpolarized ¹⁵N nuclei in biomolecules can potentially retain their spin alignment for tens of minutes, providing an extended time window for the utilization of the hyperpolarized compounds. In this work, we demonstrate for the first time that radio-frequency-based SABRE hyperpolarization techniques can be used to obtain ¹⁵N MRI of biomolecule 1-¹⁵N-nicotinamide. Two image acquisition strategies were utilized and compared: Single Point Imaging (SPI) and Fast Low Angle SHot (FLASH). These methods demonstrated opportunities of high-field SABRE for biomedical applications.

Full text of DOI:10.1002/chem.201900430

A Journal of
Accepted Article
Title: 15N MRI of SLIC-SABRE hyperpolarized 15N-labelled pyridine
and nicotinamide
Authors: Kirill Viktorovich Kovtunov, Alexandra Svyatova, Ivan Skovpin,
Nikita Chukanov, Igor Koptyug, Eduard Chekmenev, Jan
Hoevener, and Andrey Pravdivtsev
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Chem. Eur. J. 10.1002/chem.201900430
Link to VoR: http://dx.doi.org/10.1002/chem.201900430
Supported by

Chemistry - A European Journal
10.1002/chem.201900430
COMMUNICATION
1
5
15
N MRI of SLIC-SABRE hyperpolarized N-labelled pyridine and
nicotinamide
[
a, b]
[a, b]
[a, b]
[a, b]
Alexandra Svyatova,
Ivan V. Skovpin,
Nikita V. Chukanov,
Kirill V. Kovtunov,*
Eduard Y.
[c, d]
[e]
[e]
[a, b]
Chekmenev,
Andrey N. Pravdivtsev, Jan-Bernd Hövener and Igor V. Koptyug
Abstract: Magnetic Resonance Imaging (MRI) is a powerful non-
invasive diagnostic method extensively used in biomedical studies. A
significant limitation of MRI is its relatively low signal-to-noise ratio,
which can be increased by hyperpolarizing nuclear spins. One
promising method is Signal Amplification By Reversible Exchange
At first, SABRE was demonstrated using pyridine and
[1]
nicotinamide as substrates.
magnetic fields of ≈10 mT simply by shaking a sample under
pH atmosphere while the signal was acquired later at the high
SABRE was performed at
2
magnetic field of an NMR spectrometer (9.4 T). These simple
“shake and run” experiments at low magnetic fields provided
(SABRE), which employs parahydrogen as
a
source of
1
hyperpolarization. Recent studies demonstrated the feasibility to
improve MRI sensitivity with this hyperpolarization technique.
high enhancements of the H signal by a factor of 550 and 345
1
for pyridine and nicotinamide, respectively. In addition, H MRI of
15
Hyperpolarized N nuclei in biomolecules can potentially retain their
spin alignment for tens of minutes, providing an extended time
window for the utilization of the hyperpolarized compounds. In this
work, we demonstrate for the first time that radio-frequency-based
pyridine was obtained with balanced steady-state free
[
8]
precession (b-SSFP) pulse sequence.
In another experiment, SABRE was used to continuously
[
9]
hyperpolarize substrates at a low magnetic field (6.5 mT). This
15
SABRE hyperpolarization techniques can be used to obtain N MRI
approach was used to enable MRI at Earth’s magnetic field.
15
[10]
of biomolecule 1- N-nicotinamide. Two image acquisition strategies
were utilized and compared: Single Point Imaging (SPI) and Fast
Low Angle SHot (FLASH). These methods demonstrated
opportunities of high-field SABRE for biomedical applications.
Continuous hyperpolarization
resolves the problem of short
hyperpolarization lifetimes (T
few seconds for protons).
1
-relaxation time is on the order of a
The hyperpolarization and imaging of substrates in situ, i.e.
[
11]
at the same, constant magnetic field, was shown as well. This
approach allowed to accelerate the imaging by shortening the
repetition time from 8 s to 0.2 s and to increase the spatial
[
1]
Signal Amplification By Reversible Exchange (SABRE) is a
rapidly developing parahydrogen-based hyperpolarization
resolution in a way that additional dynamic processes (e.g., pH
flow motion) became observable.
2
[
2]
approach. Although parahydrogen (pH
Nuclear magnetic Resonance (NMR)), simultaneous exchange
of pH and the substrate on an Ir-based organometallic complex
provides polarization transfer from pH –derived hydrides to the
substrate, and results in an enhancement of the nuclear spin
2
) itself is silent for
Hyperpolarized protons have a relatively short T
heteronuclei offer a significantly longer relaxation time. N T
1
, meanwhile,
2
15
1
2
[12–17]
relaxation values of three to twenty minutes were reported.
These comparatively long lifetimes significantly increase the
[
3–7]
polarization (P) by several orders of magnitude.
[18,19]
time available for sample purification,
in vivo administration,
1
5
distribution, metabolism and MRI. The first reports of
N
[
20]
polarization by dissolution DNP show a low efficiency of direct
[a]
A. Svyatova, Dr. I. V. Skovpin, Dr. N. A. Chukanov, Dr. K. V.
Kovtunov, Prof. I. V. Koptyug
15
N polarization (P~ 4%) with super long build-up times about 2
[13]
hours.
However, low temperature cross-polarization to
International Tomography Center, SB RAS
[
21]
nitrogen-15 during dissolution DNP conditions
allows to
3A Institutskaya st., Novosibirsk 630090, Russia
E-mail: kovtunov@tomo.nsc.ru
A. Svyatova, Dr. I. V. Skovpin, Dr. N. A. Chukanov, Dr. K. V.
Kovtunov, Prof. I. V. Koptyug
achieve about 20% polarization for urea molecule with moderate
[
b]
c]
[22]
build-up times (15 min).
the amount of polarized substance is extremely low (100µL,
.8M) that along with long build-up times and high cost of DNP
Despite the high polarization level,
Novosibirsk State University
0
2
Pirogova st., Novosibirsk 630090, Russia
[
Prof. E. Y. Chekmenev
Department of Chemistry
Wayne State University, Karmanos Cancer Institute (KCI),
Integrative Biosciences (Ibio)
Detroit, MI 48202, United States
Prof. E. Y. Chekmenev
instrument limit possible utilization of DNP polarized substances
for N MRI.
15
EXPERIMENTAL DESIGN
[
d]
e]
SABRE showed great potential for heteronuclear MRI:
Russian Academy of Sciences (RAS)
13
[1,7,23] 15
[24] 19 [25,26]
31 [27,28]
C,
polarized substrates were obtained. Here, we focused on
nucleus because it can be used in biomedical studies, for
N,
F
and
P
images of SABRE
14 Leninskiy Prospekt, Moscow 119991, Russia
15
N
[
Dr. A. N. Pravdivtsev, Prof. Jan-Bernd Hövener
Section Biomedical Imaging, Molecular Imaging North Competence
Center (MOIN CC), Department of Radiology and Neuroradiology
University Medical Center Schleswig-Holstein (UKSH), Kiel
University,
[
24,29]
[30–32]
example, in pH sensing
or metabolic imaging.
Many SABRE studies were based on polarization transfer at
microtesla magnetic fields. These fields are beneficial because
polarization transfer to heteronuclei occurs spontaneously in
strongly coupled spin systems. The approach based on the use
of low magnetic fields was termed SABRE - Shield Enables
Am Botanischen Garten 14, 24118 Kiel, Germany
Supporting information for this article is given via a link at the end of
the document.
[
33,34]
Alignment Transfer to Heteronuclei (SABRE-SHEATH)
and
This article is protected by copyright. All rights reserved.

Chemistry - A European Journal
10.1002/chem.201900430
COMMUNICATION
1
5
[18,34,35]
more than 30%
N-polarization was demonstrated.
used, but omitted in this paper. Introduction of such stage can
potentially increase the level of hyperpolarization.
[
24,33,35–37]
However, this approach has two shortcomings:
a need
of fast magnetic field alteration and creation of polarizer with
precise ultralow magnetic field.
The MRI sequence with SABRE polarization consists of the
following steps: (i) preparation of hyperpolarization with SLIC-
SABRE (this stage can be repeated n times to gain the maximal
In another approach, termed HF-SABRE, the spontaneous
1
5
15
15
polarization transfer from pH
2
-derived hydrides to N nuclei and
signal enhancement); (ii) excitation of N signal with hard
N
1
5
MR observation are carryied out in situ at a constant, high
RF pulse; (iii) space encoding; (iv) acquisition of N signal. Two
different space encoding MRI approaches were used: Single
Point Imaging and Fast Low Angle SHot (compare Fig. 2, C and
Fig. 3, C).
[
38]
magnetic field (~10 T).
2
Here, pH is continuously bubbled
through the sample, which is placed in the magnet of NMR or
MRI, and spontaneous polarization transfer occurs while high-
frequency electro-magnetic fields are played out. Although some
shortcomings of SABRE-SHEATH were mitigated by HF-SABRE,
1
5
the
N-polarization enhancement factors were significantly
[
38,39]
lower than those provided by SABRE-SHEATH.
1
5
[40]
A previous report on MRI of N HF-SABRE revealed that
HF-SABRE generates (a relatively low) anti-phase polarization,
which is difficult to image due to partial signal cancelation.
Therefore, HF-SABRE will likely be limited to in vitro imaging
and the calibration of hardware or radio-frequency (RF) pulse
2
sequences. Moreover, continuous pH bubbling was required to
obtain 2D MRI with extensive signal averaging.
To improve the efficiency of SABRE polarization at high
magnetic fields, several polarization transfer techniques
employing RF irradiation were developed: Alternating Delays
[
41]
Achieve Polarization Transfer SABRE (ADAPT-SABRE),
SABRE Insensitive Nuclei Enhanced by Polarization Transfer
[
42]
(
SABRE-INEPT),
SABRE (LIGHT-SABRE),
Induced Crossing SABRE (SLIC-SABRE),
Low Irradiation Generation of High-Tesla
[
43]
[44]
adiabatic RF-SABRE,
Spin Lock
and Quasi-
Some of these
approaches may deliver N HP comparable with the one
[
45]
[
46]
resonance SABRE (QUASR-SABRE).
1
5
[
46]
achieved by SABRE-SHEATH,
SHEATH shortcomings.
and also mitigate SABRE-
1
5
15
15
In this work, we present a strategy for performing imaging of
SLIC-SABRE hyperpolarized compounds inside an MRI scanner
for potential biomedical applications. SLIC-SABRE sequence is
an improved version of LIGHT-SABRE where fast singlet –
triplet mixing on the Ir-complex is taken into account that makes
that variant more robust than LIGHT-SABRE. It was achieved by
Figure 1. N NMR spectra of N-Py (A) and N-NA (B) hyperpolarized by
SLIC-SABRE. Strongly enhanced signals of free and catalyst-bound substrate
15
15
were observed, enhanced by ε15N ~ 1,374 for N-Py and ε15N ~ 834 for N-NA
see Fig. S1, SI). A pH pressure of 3.4 bar and a flow rate of 80 sccm were
used. The experiments were carried out at room temperature. Two different
(
2
15
4
samples were used: 0.1 M N-Py and 5 mM Ir(IMes) methanol-d solution (A)
15
4
and 0.1 M N-NA and 5 mM Ir(IMes) methanol-d solution (B).
o
1
[45]
introduction of a 90 H-RF pulse before CW
(see Fig. 2, C
and Fig. 3, C). Note, that by repeating the SLIC-SABRE block
several times polarization is accumulated in the form of free
substrate (see SI, Fig. S2, B).
1
5
N-Single-point MRI enhanced by SLIC-SABRE. High-
resolution, 2D Single Point Imaging (SPI) was realized by using
two spatial encoding gradients G and G without slice selection
1
5
15
Specifically, we hyperpolarized N-pyridine ( N-Py) and 1-
x
y
1
5
15
N-nicotinamide ( N-NA) via SLIC-SABRE at the high field of
(Fig. 2, С). Each point of k-space was acquired consequently
after the SLIC-SABRE pulse sequence, a 90° excitation pulse
and two spatial encoding gradients. In total, 16x16=256 points
were acquired, resulting in a high native spatial resolution of
15
an MRI scanner. The parameters for the SLIC-SABRE of N-Py
were similar to those optimized and reported before: amplitude
1
5
of RF-pulse, ν
1
= 5 Hz, offset from the center of bound N-Py
2
resonance, Δrf ≅ 17 Hz and duration of continuous wave (CW)
565×565 μm /pixel. It means that the experiments were repeated
[
47]
15
RF-pulse, tcw = 1.17 s.
parameters of SLIC-SABRE (ν
to active SABRE-complex it has similar J-coupling constants
with hydride protons coming from pH Additionally, we
optimized the number of pumping cycles and pH flow rate, as
(see Fig. S2, SI). All necessary
For N-NA, we used the same
256 times with constant hyperpolarization production. Here we
took advantage of SABRE method that allows, unlike DNP, fast
and continuous production of hyperpolarization. The gained
resolution was sufficient to image the thin, 1/16 inches ≅ 1.6 mm
capillary supplying pH
fine details were resolved despite the fact that pH
1
, Δrf, tcw) because when attached
2
.
2
2
to the NMR tube (Fig. 2). Note that the
was
[
47]
described previously
2
parameters of the experiments are listed in the Tab. S4 (SI).
continuously supplied, which induces convection in the liquid
sample. In the context of biomedical applications, however, the
scan times of 5.5 minutes (Py) or 27 minutes (NA) are
The resulting polarization enhancement factors for free
15
substrate were: ε15N ~ 1,374 for N-Py (P ≈ 0.3 %) and ε15N
~
1
5
15
8
34 (P ≈ 0.2 %) for N-NA at 7 T (Fig. 1). Optimization of the
impractical. Moreover, N polarization had to be re-created for
SLIC-SABRE pulse sequence parameters and the calculation of
each point of k-space, which makes the method inherently slow.
[
45]
the signal enhancement are given in SI. In the Ref.
the time
was
period free from RF excitation to refresh system with pH
2
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Chemistry - A European Journal
10.1002/chem.201900430
COMMUNICATION
1
5
15
Figure 3. N FLASH-MRI of 1 M N-Py with 50 mM of Ir(COD)(IMes)Cl (A)
15
and 0.1 M
N-NA with 5 mM Ir(COD)(IMes)Cl (B) in methanol-d
4
1
5
15
15
hyperpolarized by SLIC-SABRE with 35 sccm pH2 flow rate at 9.4 T. 2D
images were acquired using SLIC-SABRE hyperpolarization and FLASH
spatial encoding and acquisition elements (C). Repetition time (TR) was 3.1
ms, echo time time (TE) was 1 ms. Experiments were carried out at room
temperature. The number of SLIC-SABRE pumping cycles, n, was 10 and no
signal averaging was employed. Acquisition spectral width (SW) was 10 kHz,
Figure 2. N single-point MRI of 0.1 M N-Py (A) and 0.1 M N-NA (B) in
methanol-d with 5 mM Ir(COD)(IMes)Cl hyperpolarized by means of SLIC-
SABRE with a 7 sccm pH flow rate at 9.4 T. 2D images were acquired using
4
2
SLIC-SABRE hyperpolarization and SPI spatial encoding and acquisition
elements (C). Total scan time was 5.5 min (A) and 27 min (B). The signal void
circle) corresponds to the pH
(
2
supply capillary. Experiments were carried out
2
2
15
spatial resolution was 0.15×2.4 mm /pixel (A) and 0.3×4.8 mm /pixel (B). Field
2 2
at room temperature. The number of SLIC-SABRE cycles, n, was 1 for N-Py
1
5
of view was 1.9×1.9 cm (A) and 3.8×3.8 cm (B), Acquisition matrix was
128×8, it was were zero-filled to matrix size of 128×128 (A) and 256×256 (B)
before image reconstruction.
and 5 for N-NA. In both cases, k-space was acquired once, acquisition
2
spectral width (SW) was 12 kHz, spatial resolution was 565×565 μm /pixel.
Field of view was 0.9×0.9 cm , acquisition matrix was 16×16, It was zero-filled
2
to 128×128 before the image reconstruction.
Conclusion. The presented approach allowed us to
1
5
15
N-FLASH MRI enhanced by SLIC-SABRE. Using a
gradient echo pulse sequence such as Fast Low Angle Shot
FLASH) allows one to decrease the scan time by orders of
hyperpolarize and image
N biomolecules inside an MRI
instrument, in situ, by SLIC-SABRE in less than a minute. The
HP was continuously renewed inside the MRI scanner, which
provides certain advantages in the context of biomedical
(
magnitude. Here, an entire k-space was read out after one
SLIC-SABRE block (Fig. 3, C). This is advantageous, because
in biomedical conditions, it would be impossible to re-
hyperpolarize an injected HP bolus for every excitation, as was
done for SPI.
[
48]
applications. The HP was strong enough to allow subsecond
1
5
15
15
15
N MRI of two N-labeled biomolecules: N-Py and N-NA
(vitamin B ). No external polarizer or sample transfer to an MRI
3
scanner are required.
In this setting, the hyperpolarization by SLIC-SABRE took
3 s and the FLASH MRI less than 1 s (repetition time 3.1 ms,
SLIC-SABRE was introduced as an efficient way to transfer
1
5
1
2
polarization from pH to a N substrate. Here, we obtained
15
15
echo time 1 ms, 8 phase encoding steps, 128 readout points,
Cartesian encoding). There was a delay of approximately 2-4 s
between SLIC-SABRE and MRI due to hardware limitations
while switching between two pulse sequences. We do not
expect significant polarization losses during this delay (see HP
decay kinetics in Fig. S3, SI). Note that the whole k-space was
acquired after only one implementation of SLIC-SABRE.
1,374- and 834-fold signal enhancements for N-Py and N-NA,
respectively. Although the polarizations are moderate the
enhancements are quite significant and sufficient for fast MRI.
We expect that future advances in SLIC-SABRE or related
methods will increase the polarization further.
While in these studies organic solvents were used and the
catalyst was not removed before imaging, recent advances in
15
[7,18]
[49]
15
As a result, N images (Fig. 3) were obtained using a 128×8
filtering,
heterogeneous catalysis
and
N SABRE-
2
[36]
matrix that provide a spatial resolution of 0.15×2.4 mm /pixel
SHEATH in aqueous medium
bode well for a future in vivo
1
5
2
15
15
(
N-Py) and 0.3×4.8 mm /pixel ( N-NA). For representation, the
translation of the presented approach. The N sites can retain
HP state for tens of minutes, but their detection sensitivity is
approximately two orders of magnitude lower than that of
protons. This shortcoming can be mitigated by transferring
k-space data sets were zero-filled to 128×128 and 256×256 for
1
5
15
N-Py and N-NA, respectively.
15
1
1
polarization from N to J-coupled H nuclei and subsequent H
imaging. Various schemes have been designed for this indirect
[
50–53]
readout and have already been demonstrated in vivo.
This work is the first demonstration of hyperpolarized,
heteronuclear MRI that was enhanced by SLIC-SABRE rather
than by spontaneous polarization transfer. This method can be
1
3
19
31
extended to other heteronuclei such as C, F, P, etc. for
biomedical and other applications.
This article is protected by copyright. All rights reserved.

Chemistry - A European Journal
10.1002/chem.201900430
COMMUNICATION
of SLIC) to reduce magnetic field inhomogeneities and fast convection
caused by the bubbles. There was a delay of approximately 2-4 s
between SLIC-SABRE and MRI due to hardware limitations. Duration of
the FLASH was less than a second, TR was 3.1 ms, TE was 1 ms.
Phase encoding gradient had 8% strength of maximal value and 400 μs
duration, readout gradient had 4% strength and 2.1 ms duration. The flip
Experimental Section
Iridium N-heterocyclic carbene complexes, Ir(COD)(IMes)Cl (IMes = 1,3-
bis(2,4,6-trimethylphenyl)imidazole-2-ylidene, COD
was used as a pre-catalyst to provide SABRE. This complex was
prepared from commercially available precursors ([It(COD)Cl] , abcr
] , Sigma Aldrich, CAS: 245679-18-
= cyclooctadiene)
2
o
+
-
angle was 30 . No k-space filter was applied.
GmbH, CAS: 12112-67-3; [IMes] [BF
4
[
54,55]
9
) according to the previously described method.
Pre-catalyst was
through the reagent solution in the presence of
flow rate of 20 sccm and 1.7 bar
activated by bubbling pH
a substrate during 20 minutes with pH
2
2
Acknowledgements
overpressure. Activation was required to convert the pre-catalyst to the
active SABRE-complex.
A.S., N.V.C., and K.V.K. thank the Russian Science Foundation
1
5
15
15
(grant #17-73-20030) for the support
N
MR imaging
N-pyridine and 1- N-nicotinamide used as SABRE substrates were
synthesized according to the procedures described in the literature (for
experiments of pyridine and nicotinamide. I.V.S and I.V.K thank
15
[56,57]
15
details of synthesis of N-pyridine see SI).
600 μl methanol-d
4
RFBR (grant # 19-53-12013) for the support of synthesis of N-
labeled compounds and Ministry of Science and Higher
Education of the RF (АААА-А16-116121510087-5) for
access to NMR equipment. E.Y.C thanks the following funding
support: NSF under grant CHE-1836308, NIH 1R21EB020323
15
mixtures: 1 M solution of N-Py and 50 mM of Ir(COD)(IMes)Cl, 0.1 M
15
15
solution of N-Py and 5 mM of Ir(COD)(IMes)Cl or 0.1 M solution of N-
NA and 5 mM Ir(COD)(IMes)Cl, were used for MRI experiments. All
experiments were carried out using standard 5 mm NMR tubes. pH
supplied to the solution through the capillary system equipped with a
mass flow controller and back pressure valves (Fig. 4). pH was prepared
using commercially available pH generator with conversion
temperature of 38 K that provides ∼90% enrichment of the para fraction
Bruker, BPHG90).
2
was
2
and
R21CA220137,
DOD
CDMRP
W81XWH-12-1-
a
2
a
0159/BC112431. A. N. P. and J.-B. H. acknowledge support by
(
the DFG in the Emmy Noether Program (HO 4604/2-1), the
Research Training Circle Materials for Brain (GRK 2154), a
research grant (HO 4604/3-1), the cluster of excellence
“
Inflammation at Interfaces” (EXC 306) and precision medicine
in inflammation (PMI 1267). Kiel University and the Medical
Faculty are acknowledged for supporting the Molecular Imaging
North Competence Center (MOIN CC) as a core facility for
imaging in vivo. MOIN CC was founded by a grant of the
European Regional Development Fund (ERDF) and the
Zukunftsprogramm Wirtschaft of Schleswig-Holstein (Project no.
122-09-053).
1
5
Keywords: SABRE • N MRI • parahydrogen •
hyperpolarization • molecular imaging
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Figure 4. Scheme of the HF-SABRE MR setup. pH was supplied to the
sample solution placed inside the spectrometer trough the capillary system.
The gas system contained mass flow controller and back pressure valves
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1
instrument (Bruker, Avance III) equipped with a two-channel probe ( H,
1
5
N) and maximal gradient strength of 150 G/cm. The SLIC pulse
[
58]
15
sequence was used to transfer nuclear spin order from pH
2
to N in
NMR spectra were obtained on a 300 MHz
0
(B = 7 T) NMR spectrometer (Bruker, Avance).
[
45,58]
[5]
the strong magnetic field.
[6]
15
[7]
N-Single-point MRI enhanced by SLIC-SABRE. Parahydrogen was
delivered to the solution at 1.7 bar and 7 sccm flow rate during SLIC-
SABRE and MRI. For SPI, two phase encoding gradients (Fig. 2, C) were
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Chemistry - A European Journal
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COMMUNICATION
Entry for the Table of Contents
COMMUNICATION
1
5
N Signal Amplification By Reversible
Alexandra Svyatova, Ivan V. Skovpin,
Nikita V. Chukanov, Kirill V. Kovtunov,*
Eduard Y. Chekmenev, Andrey N.
Pravdivtsev, Jan-Bernd Hövener, Igor V.
Koptyug
Exchange hyperpolarization of
biomolecules were carried out in situ
in a MRI scanner. This allowed us to
1
5
15
perform N MRI of N-pyridine and 1-
1
5
N-nicotinamide using two different
Page No. – Page No.
pulse sequences: Single Point
Imaging and Fast Low Angle SHot
15
N MRI of SLIC-SABRE
(
FLASH). The demonstrated method
15
hyperpolarized N-labelled pyridine
and nicotinamide
is a promising approach for
biomedical applications.
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