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.

Fluorinated substances are important in chemistry, industry, and the life sciences. In a new approach, parahydrogen-induced polarization (PHIP) is applied to enhance (19)F MR 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 (19)F-(19)F NOESY spectra, as well as (19)F T1 values were measured by NMR spectroscopy. By using the well separated and enhanced signal of the CF3 group, first (19)F MR images of hyperpolarized linear semifluorinated alkenes were recorded.

Substrates containing 19F can serve as background‐free reporter molecules for NMR and MRI. However, in vivo applications are still limited due to the lower signal‐to‐noise ratio (SNR) when compared with 1H NMR. Although hyperpolarization can increase the SNR, to date, only photo‐chemically induced dynamic nuclear polarization (photo‐CIDNP) allows for hyperpolarization without harmful metal catalysts. Photo‐CIDNP was shown to significantly enhance 19F NMR signals of 3‐fluoro‐DL‐tyrosine in aqueous solution using flavins as photosensitizers. However, lasers were used for photoexcitation, which is expensive and requires appropriate protection procedures in a medical or lab environment. Herein, we report 19F MR hyperpolarization at 4.7 T and 7 T with a biocompatible system using a low‐cost and easy‐to‐handle LED‐based set‐up. First hyperpolarized 19F MR images could be acquired, because photo‐CIDNP enabled repetitive hyperpolarization without adding new substrates.

No abstract

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 (19)F-MRI is that it provides non-invasive and background-free active marker signals in biomedical applications, such as monitoring drugs that contain (19)F. In former NMR spectroscopic experiments, hyperpolarized (19)F nuclei were efficiently generated by using low magnetic field (Earth's field) conditions. In order to apply the method to (19)F-hyperpolarized MRI, we chose an exploratory target molecule, for which a successful transfer of PHIP had already been attested. The transfer of hyperpolarization to (19)F 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 (19)F-MR images were received. Despite the low spin density of the sample (0.045 per thousand of the (1)H density in H(2)O), a sufficient signal-to-noise was obtained within a short acquisition time of 3.2 s.