Rapid lung ventilation MRI using parahydrogen-induced polarization of propane gas.

Proton-hyperpolarized contrast agents are attractive because they can be imaged on virtually any clinical MRI scanner, which is typically equipped to scan only protons rather than heteronuclei (, anything besides protons, , C, N, Xe, Na, .). Even though the lifetime of the proton spin hyperpolarization is only a few seconds, it is sufficient for inhalation and scanning of proton-hyperpolarized gas media.

Developing Hyperpolarized Butane Gas for Ventilation Lung Imaging.

NMR hyperpolarization dramatically improves the detection sensitivity of magnetic resonance through the increase in nuclear spin polarization. Because of the sensitivity increase by several orders of magnitude, additional applications have been unlocked, including imaging of gases in physiologically relevant conditions. Hyperpolarized Xe gas recently received FDA approval as the first inhalable gaseous MRI contrast agent for clinical functional lung imaging of a wide range of pulmonary diseases.

Toward Lung Ventilation Imaging Using Hyperpolarized Diethyl Ether Gas Contrast Agent.

Hyperpolarized Xe gas was FDA-approved as an inhalable contrast agent for magnetic resonance imaging of a wide range of pulmonary diseases in December 2022. Despite the remarkable success in clinical research settings, the widespread clinical translation of HP Xe gas faces two critical challenges: the high cost of the relatively low-throughput hyperpolarization equipment and the lack of Xe imaging capability on clinical MRI scanners, which have narrow-bandwidth electronics designed only for proton (H) imaging. To solve this translational grand challenge of gaseous hyperpolarized MRI contrast agents, here we demonstrate the utility of batch-mode production of proton-hyperpolarized diethyl ether gas via heterogeneous pairwise addition of parahydrogen to ethyl vinyl ether.

Manipulating stereoselectivity of parahydrogen addition to acetylene to unravel interconversion of ethylene nuclear spin isomers.

Symmetric molecules exist as distinct nuclear spin isomers (NSIMs). A deeper understanding of their properties, including interconversion of different NSIMs, requires efficient techniques for NSIM enrichment. In this work, selective hydrogenation of acetylene with parahydrogen (p-H) was used to achieve the enrichment of ethylene NSIMs and to study their equilibration processes.

XPS and HR TEM Elucidation of the Diversity of Titania-Supported Single-Site Ir Catalyst Performance in Spin-Selective Propene Hydrogenation.

Immobilized [Ir(COD)Cl]-Linker/TiO catalysts with linkers containing Py, P(Ph) and N(CH) functional groups were prepared. The catalysts were tested via propene hydrogenation with parahydrogen in a temperature range from 40 °C to 120 °C which was monitored via NMR. The catalytic behavior of [Ir(COD)Cl]-Linker/TiO is explained on the basis of quantitative and qualitative XPS data analysis performed for the catalysts before and after the reaction at 120 °C.

Ultra-Low-Cost Disposable Hand-Held Clinical-Scale Propane Gas Hyperpolarizer for Pulmonary Magnetic Resonance Imaging Sensing.

Hyperpolarized magnetic resonance imaging (MRI) contrast agents are revolutionizing the field of biomedical imaging. Hyperpolarized Xe-129 was recently FDA approved as an inhalable MRI contrast agent for functional lung imaging sensing. Despite success in research settings, modern Xe-129 hyperpolarizers are expensive (up to $1M), large, and complex to site and operate.

Combined homogeneous and heterogeneous hydrogenation to yield catalyst-free solutions of parahydrogen-hyperpolarized [1-C]succinate.

We show that catalyst-free aqueous solutions of hyperpolarized [1-C]succinate can be produced using parahydrogen-induced polarization (PHIP) and a combination of homogeneous and heterogeneous catalytic hydrogenation reactions. We generate hyperpolarized [1-C]fumarate PHIP using para-enriched hydrogen gas with a homogeneous ruthenium catalyst, and subsequently remove the toxic catalyst and reaction side products a purification procedure. Following this, we perform a second hydrogenation reaction using normal hydrogen gas to convert the fumarate into succinate using a solid Pd/AlO catalyst.

Mechanisms of Methylenecyclobutane Hydrogenation over Supported Metal Catalysts Studied by Parahydrogen-Induced Polarization Technique.

In this work the mechanism of methylenecyclobutane hydrogenation over titania-supported Rh, Pt and Pd catalysts was investigated using parahydrogen-induced polarization (PHIP) technique. It was found that methylenecyclobutane hydrogenation leads to formation of a mixture of reaction products including cyclic (1-methylcyclobutene, methylcyclobutane), linear (1-pentene, cis-2-pentene, trans-2-pentene, pentane) and branched (isoprene, 2-methyl-1-butene, 2-methyl-2-butene, isopentane) compounds. Generally, at lower temperatures (150-350 °C) the major reaction product was methylcyclobutane while higher temperature of 450 °C favors the formation of branched products isoprene, 2-methyl-1-butene and 2-methyl-2-butene.

Heterogeneous H and C Parahydrogen-Induced Polarization of Acetate and Pyruvate Esters.

Magnetic resonance imaging of [1- C]hyperpolarized carboxylates (most notably, [1- C]pyruvate) allows one to visualize abnormal metabolism in tumors and other pathologies. Herein, we investigate the efficiency of H and C 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- C-enriched forms with parahydrogen over Rh/TiO catalysts in methanol-d and in D O. The maximum obtained H polarization was 0.

Mechanistic in situ investigation of heterogeneous hydrogenation over Rh/TiO catalysts: selectivity, pairwise route and catalyst nature.

The selectivity of product formation is strongly correlated with the nature of the catalyst active centers. Therefore, the selective synthesis of active sites with certain structure is a big challenge in modern catalysis. Here synthetic procedures are adopted for the formation of 1% Rh/TiO catalysts with different properties.

Heterogeneous Parahydrogen-Induced Polarization of Diethyl Ether for Magnetic Resonance Imaging Applications.

Magnetic resonance imaging (MRI) with the use of hyperpolarized gases as contrast agents provides valuable information on lungs structure and function. While the technology of Xe hyperpolarization for clinical MRI research is well developed, it requires the expensive equipment for production and detection of hyperpolarized Xe. Herein we present the H hyperpolarization of diethyl ether vapor that can be imaged on any clinical MRI scanner.

Parahydrogen-Induced Polarization of Diethyl Ether Anesthetic.

The growing interest in magnetic resonance imaging (MRI) for assessing regional lung function relies on the use of nuclear spin hyperpolarized gas as a contrast agent. The long gas-phase lifetimes of hyperpolarized Xe make this inhalable contrast agent acceptable for clinical research today despite limitations such as high cost, low throughput of production and challenges of Xe imaging on clinical MRI scanners, which are normally equipped with proton detection only. We report on low-cost and high-throughput preparation of proton-hyperpolarized diethyl ether, which can be potentially employed for pulmonary imaging with a nontoxic, simple, and sensitive overall strategy using proton detection commonly available on all clinical MRI scanners.

Relaxation Dynamics of Nuclear Long-Lived Spin States in Propane and Propane-d Hyperpolarized by Parahydrogen.

We report a systematic study of relaxation dynamics of hyperpolarized (HP) propane and HP propane-d prepared by heterogeneous pairwise parahydrogen addition to propylene and propylene-d respectively. Long-lived spin states (LLS) created for these molecules at the low magnetic field of 0.0475 T were employed for this study.

Heterogeneous hydrogenation of phenylalkynes with parahydrogen: hyperpolarization, reaction selectivity, and kinetics.

Parahydrogen-induced polarization (PHIP) is a powerful technique for studying hydrogenation reactions in gas and liquid phases. Pairwise addition of parahydrogen to the hydrogenation substrate imparts nuclear spin order to reaction products, manifested as enhanced 1H NMR signals from the nascent proton sites. Nanoscale metal catalysts immobilized on supports comprise a promising class of catalysts for producing PHIP effects; however, on such catalysts the percentage of substrates undergoing the pairwise addition route-a necessary condition for observing PHIP-is usually low.

A versatile synthetic route to the preparation of N heterocycles.

A robust medium-scale (approximately 3 g) synthetic method for N labeling of pyridine ( N-Py) is reported based on the Zincke reaction. N enrichment in excess of 81% was achieved with approximately 33% yield. N-Py serves as a standard substrate in a wide range of studies employing a hyperpolarization technique for efficient polarization transfer from parahydrogen to heteronuclei; this technique, called SABRE (signal amplification by reversible exchange), employs a simultaneous chemical exchange of parahydrogen and a to-be-hyperpolarized substrate (e.

Chemical Exchange Reaction Effect on Polarization Transfer Efficiency in SLIC-SABRE.

Signal Amplification By Reversible Exchange (SABRE) is a new and rapidly developing hyperpolarization technique. The recent discovery of Spin-Lock Induced Crossing SABRE (SLIC-SABRE) showed that high field hyperpolarization transfer techniques developed so far were optimized for singlet spin order that does not coincide with the experimentally produced spin state. Here, we investigated the SLIC-SABRE approach and the most advanced quantitative theoretical SABRE model to date.

Single-Site Heterogeneous Catalysts: From Synthesis to NMR Signal Enhancement.

Catalysts with well-defined, single, active centers are of great importance and their utilization allows the gap between homo- and heterogeneous catalysis to be bridged and, importantly, the main selectivity problem of heterogeneous catalysis and the main separation challenge of homogeneous catalysis to be overcome. Moreover, the use of single-site catalysts allows the NMR signal to be significantly enhanced through the pairwise addition of two hydrogen atoms from a parahydrogen molecule to an unsaturated substrate. This review covers the fundamentals of the synthesis of single-site catalysts and shows the new aspects of their applications in both modern catalysis and the field of parahydrogen-based hyperpolarization.

Heterogeneous Parahydrogen Pairwise Addition to Cyclopropane.

Hyperpolarized gases revolutionize functional pulmonary imaging. Hyperpolarized propane is a promising emerging contrast agent for pulmonary MRI. Unlike hyperpolarized noble gases, proton-hyperpolarized propane gas can be imaged using conventional MRI scanners with proton imaging capability.

Aqueous, Heterogeneous Parahydrogen-Induced N Polarization.

The successful transfer of parahydrogen-induced polarization to N spins using heterogeneous catalysts in aqueous solutions was demonstrated. Hydrogenation of a synthesized unsaturated N-labeled precursor (neurine) with parahydrogen (p-H) over Rh/TiO heterogeneous catalysts yielded a hyperpolarized structural analog of choline. As a result, N polarization enhancements of over two orders of magnitude were achieved for the N-ethyl trimethyl ammonium ion product in deuterated water at elevated temperatures.

Heterogeneous Microtesla SABRE Enhancement of N NMR Signals.

The hyperpolarization of heteronuclei via signal amplification by reversible exchange (SABRE) was investigated under conditions of heterogeneous catalysis and microtesla magnetic fields. Immobilization of [IrCl(COD)(IMes)], [IMes=1,3-bis(2,4,6-trimethylphenyl), imidazole-2-ylidene; COD=cyclooctadiene] catalyst onto silica particles modified with amine linkers engenders an effective heterogeneous SABRE (HET-SABRE) catalyst that was used to demonstrate a circa 100-fold enhancement of N NMR signals in N-pyridine at 9.4 T following parahydrogen bubbling within a magnetic shield.

Production of Pure Aqueous C-Hyperpolarized Acetate by Heterogeneous Parahydrogen-Induced Polarization.

A supported metal catalyst was designed, characterized, and tested for aqueous phase heterogeneous hydrogenation of vinyl acetate with parahydrogen to produce C-hyperpolarized ethyl acetate for potential biomedical applications. The Rh/TiO catalyst with a metal loading of 23.2 wt % produced strongly hyperpolarized C-enriched ethyl acetate-1- C detected at 9.