Abstract Parahydrogen-induced polarization of13C nuclei by side-arm hydrogenation (PHIP-SAH) for [1-13C]acetate and [1-13C]pyruvate esters with application of PH-INEPT-type pulse sequences for1H to13C polarization transfer is reported, and its efficiency is compared with that of polarization transfer based on magnetic field cycling (MFC). The pulse-sequence transfer approach may have its merits in some applications because the entire hyperpolarization procedure is implemented directly in an NMR or MRI instrument, whereas MFC requires a controlled field variation at low magnetic fields. Optimization of the PH-INEPT-type transfer sequences resulted in13C polarization values of 0.66 ± 0.04% and 0.19 ± 0.02% for allyl [1-13C]pyruvate and ethyl [1-13C]acetate, respectively, which is lower than the corresponding polarization levels obtained with MFC for1H to13C polarization transfer (3.95 ± 0.05% and 0.65 ± 0.05% for allyl [1-13C]pyruvate and ethyl [1-13C]acetate, respectively). Nevertheless, a significant13C NMR signal enhancement with respect to thermal polarization allowed us to perform13C MR imaging of both biologically relevant hyperpolarized molecules which can be used to produce useful contrast agents for the in vivo imaging applications.
more »
« less
High field para hydrogen induced polarization of succinate and phospholactate
The signal enhancement provided by the hyperpolarization of nuclear spins of metabolites is a promising technique for diagnostic magnetic resonance imaging (MRI). To date, most 13 C-contrast agents are hyperpolarized utilizing a complex or cost-intensive polarizer. Recently, the in situ para hydrogen-induced 13 C hyperpolarization was demonstrated. Hydrogenation, spin order transfer (SOT) by a pulsed NMR sequence, in vivo administration, and detection was achieved within the magnet bore of a 7 Tesla MRI system. So far, the hyperpolarization of the xenobiotic molecule 1- 13 C-hydroxyethylpropionate (HEP) and the biomolecule 1- 13 C-succinate (SUC) through the PH-INEPT+ sequence and a SOT scheme proposed by Goldman et al. , respectively, was shown. Here, we investigate further the hyperpolarization of SUC at 7 Tesla and study the performance of two additional SOT sequences. Moreover, we present first results of the hyperpolarization at high magnetic field of 1- 13 C-phospholactate (PLAC), a derivate to obtain the metabolite lactate, employing the PH-INEPT+ sequence. For SUC and PLAC, 13 C polarizations of about 1–2% were achieved within seconds and with minimal equipment. Effects that potentially may explain loss of 13 C polarization have been identified, i.e. low hydrogenation yield, fast T 1 / T 2 relaxation and the rarely considered 13 C isotope labeling effect.
more »
« less
- Award ID(s):
- 1904780
- PAR ID:
- 10274320
- Date Published:
- Journal Name:
- Physical Chemistry Chemical Physics
- Volume:
- 23
- Issue:
- 3
- ISSN:
- 1463-9076
- Page Range / eLocation ID:
- 2320 to 2330
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Abstract Hyperpolarized13C MRI visualizes real-time metabolic processes in vivo. In this study, we achieved high13C polarization in situ in the bore of an MRI system for precursor molecules of most widely employed hyperpolarized agents: [1-13C]acetate and [1-13C]pyruvate ethyl esters in their perdeuterated forms, enhancing hyperpolarization lifetimes, hyperpolarized toP13C ≈ 28% at 80 mM concentration andP13C ≈ 19% at 10 mM concentration, respectively. Using vinyl esters as unsaturated Parahydrogen-Induced Polarization via Side-Arm Hydrogenation (PHIP-SAH) precursors and our novel polarization setup, we achieved these hyperpolarization levels by fast side-arm hydrogenation in acetone-d6at elevated temperatures (up to 90°C) and hydrogenation pressures (up to 32 bar). We optimized the hyperpolarization process, reducing it to under 10 s, and employed advanced pulse sequences to enhance the polarization transfer efficiency. The hyperpolarization system has a small footprint, allowing it to be positioned in the same magnet, where13C MRI is performed. We exemplified the utility of the design with sub-second in situ13C MRI of ethyl [1-13C]pyruvate-d6. However, challenges remain in side-arm cleavage and purification in the MRI system to extract highly polarized aqueous agent solutions. Our results showcase efficient and rapid13C hyperpolarization of these metabolite precursors in an MRI system with minimal additional hardware, promising to enhance future throughput and access to hyperpolarized13C MRI.more » « less
-
Hyperpolarization of 13 C-pyruvate via Signal Amplificaton By Reversibble Exchange (SABRE) is an important recent discovery because of both the relative simplicity of hyperpolarization and the central biological relevance of pyruvate as a biomolecular probe for in vitro or in vivo studies. Here, we analyze the [1,2- 13 C 2 ]pyruvate-SABRE spin system and its field dependence theoretically and experimentally. We provide first-principles analysis of the governing 4-spin dihydride- 13 C 2 Hamiltonian and numerical spin dynamics simulations of the 7-spin dihydride- 13 C 2 –CH 3 system. The analytical and the numerical results are compared to matching systematic experiments. With these methods we unravel the observed spin state mixing of singlet states and triplet states at microTesla fields and we also analyze the dynamics during transfer from micro-Tesla field to high field for detection to understand the resulting spectra from the [1,2- 13 C 2 ]pyruvate-SABRE system.more » « less
-
Abstract Magnetic resonance imaging of [1‐13C]hyperpolarized carboxylates (most notably, [1‐13C]pyruvate) allows one to visualize abnormal metabolism in tumors and other pathologies. Herein, we investigate the efficiency of1H and13C hyperpolarization of acetate and pyruvate esters with ethyl, propyl and allyl alcoholic moieties using heterogeneous hydrogenation of corresponding vinyl, allyl and propargyl precursors in isotopically unlabeled and 1‐13C‐enriched forms with parahydrogen over Rh/TiO2catalysts in methanol‐d4and in D2O. The maximum obtained1H polarization was 0.6±0.2 % (for propyl acetate in CD3OD), while the highest13C polarization was 0.10±0.03 % (for ethyl acetate in CD3OD). Hyperpolarization of acetate esters surpassed that of pyruvates, while esters with a triple carbon‐carbon bond in unsaturated alcoholic moiety were less efficient as parahydrogen‐induced polarization precursors than esters with a double bond. Among the compounds studied, the maximum1H and13C NMR signal intensities were observed for propyl acetate. Ethyl acetate yielded slightly less intense NMR signals which were dramatically greater than those of other esters under study.more » « less
-
Abstract Herein, we demonstrate “direct”13C hyperpolarization of13C‐acetate via signal amplification by reversible exchange (SABRE). The standard SABRE homogeneous catalyst [Ir‐IMes; [IrCl(COD)(IMes)], (IMes=1,3‐bis(2,4,6‐trimethylphenyl), imidazole‐2‐ylidene; COD=cyclooctadiene)] was first activated in the presence of an auxiliary substrate (pyridine) in alcohol. Following addition of sodium 1‐13C‐acetate, parahydrogen bubbling within a microtesla magnetic field (i.e. under conditions of SABRE in shield enables alignment transfer to heteronuclei, SABRE‐SHEATH) resulted in positive enhancements of up to ≈100‐fold in the13C NMR signal compared to thermal equilibrium at 9.4 T. The present results are consistent with a mechanism of “direct” transfer of spin order from parahydrogen to13C spins of acetate weakly bound to the catalyst, under conditions of fast exchange with respect to the13C acetate resonance, but we find that relaxation dynamics at microtesla fields alter the optimal matching from the traditional SABRE‐SHEATH picture. Further development of this approach could lead to new ways to rapidly, cheaply, and simply hyperpolarize a broad range of substrates (e.g. metabolites with carboxyl groups) for various applications, including biomedical NMR and MRI of cellular and in vivo metabolism.more » « less
An official website of the United States government

