Hyperpolarized F-19-MRI: parahydrogen-induced polarization and field variation enable F-19-MRI at low spin density

The use of parahydrogen-induced polarization (PHIP) for signal enhancement in nuclear magnetic resonance spectroscopy (NMR) is well established. Recently, this method has been adopted to increase the sensitivity of magnetic resonance imaging (MRI). The transfer of non-thermal spin hyperpolarization-from parahydrogen to a heteronucleus-provides better contrast, thus enabling new imaging agents. The unique advantage of F-19-MRI is that it provides non-invasive and background-free active marker signals in biomedical applications, such as monitoring drugs that contain F-19. In former NMR spectroscopic experiments, hyperpolarized F-19 nuclei were efficiently generated by using low magnetic field (Earth's field) conditions. In order to apply the method to F-19-hyperpolarized MRI, we chose an exploratory target molecule, for which a successful transfer of PHIP had already been attested. The transfer of hyperpolarization to F-19 was further optimized by adequate field manipulations below Earth's magnetic field. This technique, called field cycling, led to a signal enhancement of about 60. For the first time, hyperpolarized F-19-MR images were received. Despite the low spin density of the sample (0.045 of the H-1 density in H2O), a sufficient signal-to-noise was obtained within a short acquisition time of 3.2 s

Understanding the leaching properties of heterogenized catalysts: A combined solid-state and PHIP NMR study

Para-hydrogen induced polarization (PHIP) NMR in solution, combined with solid-state NMR, can be efficiently employed for the highly sensitive in-situ detection of the leaching properties of immobilized catalysts. The knowledge of this property is important for possible applications of PHIP experiments in medicine, biology or industry, where leached catalysts poison the solution of hyperpolarized products. As experimental example Wilkinson's catalyst RhCl(PPh3)(3) (1) immobilized on mesoporous silica is chosen. As model reaction the hydrogenation of styrene in solvents with different polarities (methanol-d(4), acetone-d(6) and benzene-d(6)) is used. A P-31 solid-state MAS-NMR study reveals that there are two different species of catalysts on the silica, namely coordinatively bound catalysts and physisorbed catalyst. Only the second species exhibits substantial leaching, which is visible in a strong PHIP enhancement of the reaction product. (C) 2011 Elsevier Inc. All rights reserved

Parahydrogen induced polarization in face of keto-enol tautomerism: proof of concept with hyperpolarized ethanol

Hyperpolarization (HP) techniques are increasingly important in magnetic resonance imaging (MRI) and spectroscopy (MRS). HP methods have the potential to overcome the fundamentally low sensitivity of magnetic resonance (MR). A breakthrough of HP-MR in life sciences and medical applications is still limited by the small number of accessible, physiologically relevant substrates. Our study presents a new approach to extend PHIP to substrates that primarily cannot be hyperpolarized due to a steady intramolecular re-arrangement, the so-called keto-enol tautomerism. To overcome this obstacle we exploited the fact that instead of the instable enol form the corresponding stable ester can be used as a precursor molecule. This strategy now enables the hydrogenation which is required to apply the standard PHIP procedure. As the final step a hydrolysis is necessary to release the hyperpolarized target molecule. Using this new approach ethanol was successfully hyperpolarized for the first time. It may therefore be assumed that the outlined multi-step procedure can be used for other keto-enol tautomerized substances thereby opening the application of PHIP to a multitude of molecules relevant to analyzing metabolic pathways

Application of Parahydrogen-Induced Polarization to Unprotected Dehydroamino Carboxylic Acids

One focus of current nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) investigation is the hyperpolarization of biologically relevant substrates. In this study, the application of parahydrogen-induced polarization (PHIP) to amino carboxylic acids was enabled by protonation of the amino group as well as of the carboxylic acid. Due to the donor character of these functional groups, they usually act as ligands at the active catalytic sites. To enable parahydrogenation, blocking of the catalytic sites by the functional groups has to be avoided. In a new approach, this was realized via protonation of the starting material. For the first time PHIP spectra of allylglycine, vigabatrin and gamma-amino-butyric acid (GABA) were generated. The feasibility of the hydrogenation of amino carboxylic acids without using a protection group supersedes the deprotection reaction usually required. Hence, hydrogenation after protonation of the substrate opens the class of free dehydroamino carboxylic acids to PHIP

Time domain para hydrogen induced polarization

Para hydrogen induced polarization (PHIP) is a powerful hyperpolarization technique, which increases the NMR sensitivity by several orders of magnitude. However the hyperpolarized signal is created as an anti-phase signal, which necessitates high magnetic field homogeneity and spectral resolution in the conventional PHIP schemes. This hampers the application of PHIP enhancement in many fields, as for example in food science, materials science or MRI, where low B0-fields or low B0-homogeneity do decrease spectral resolution, leading to potential extinction if in-phase and anti-phase hyperpolarization signals cannot be resolved. Herein, we demonstrate that the echo sequence (45°-t-180°-t) enables the acquisition of low resolution PHIP enhanced liquid state NMR signals of phenylpropiolic acid derivatives and phenylacetylene at a low cost low-resolution 0.54 T spectrometer. As low field TD-spectrometers are commonly used in industry or biomedicine for the relaxometry of oil–water mixtures, food, nano-particles, or other systems, we compare two variants of para-hydrogen induced polarization with data-evaluation in the time domain (TD-PHIP). In both TD-ALTADENA and the TD-PASADENA strong spin echoes could be detected under conditions when usually no anti-phase signals can be measured due to the lack of resolution. The results suggest that the time-domain detection of PHIP-enhanced signals opens up new application areas for low-field PHIP-hyperpolarization, such as non-invasive compound detection or new contrast agents and biomarkers in low-field Magnetic Resonance Imaging (MRI). Finally, solid-state NMR calculations are presented, which show that the solid echo (90y-t-90x-t) version of the TD-ALTADENA experiment is able to convert up to 10% of the PHIP signal into visible magnetization

New investigations of technical rhodium and iridium catalysts in homogeneous phase employing para-hydrogen induced polarization

It is shown that the para-hydrogen induced polarization (PHIP) phenomenon in homogenous solution containing the substrate styrene is also observable employing simple inorganic systems of the form MCl(3)center dot xH(2)O (M= Rh, Ir) as catalyst. Such observation confirms that already very simple metal complexes enable the creation of PHIP signal enhancement in solution. This opens up new pathways to increase the sensitivity of NMR and MRT by PHIP enhancement using cost-effective catalysts and will be essential for further mechanistic studies of simple transition metal systems. (C) 2011 Elsevier Inc. All rights reserved

Parahydrogen-Induced Polarization Transfer to F-19 in Perfluorocarbons for F-19 NMR Spectroscopy and MRI

Fluorinated substances are important in chemistry, industry, and the life sciences. In a new approach, parahydrogen-induced polarization (PHIP) is applied to enhance 19FMR signals of (perfluoro-n-hexyl)ethene and (perfluoro-n-hexyl)ethane. Unexpectedly, the end-standing CF3 group exhibits the highest amount of polarization despite the negligible coupling to the added protons. To clarify this non-intuitive distribution of polarization, signal enhancements in deuterated chloroform and acetone were compared and 19F19FNOESY spectra, as well as 19F T1 values were measured by NMR spectroscopy. By using the well separated and enhanced signal of the CF3 group, first 19FMR images of hyperpolarized linear semifluorinated alkenes were recorded