Markus Plaumann

Parahydrogen-induced polarization transfer to 19F in perfluorocarbons for 19F 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 (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.

SQUID-based detection of ultra-low-field multinuclear NMR of substances hyperpolarized using signal amplification by reversible exchange

Ultra-low-field (ULF) nuclear magnetic resonance (NMR) is a promising spectroscopy method allowing for, e.g., the simultaneous detection of multiple nuclei. To overcome the low signal-to-noise ratio that usually hampers a wider application, we present here an alternative approach to ULF NMR, which makes use of the hyperpolarizing technique signal amplification by reversible exchange (SABRE). In contrast to standard parahydrogen hyperpolarization, SABRE can continuously hyperpolarize 1 H as well as other MR-active nuclei. For simultaneous measurements of 1 H and 19 F under SABRE conditions a superconducting quantum interference device (SQUID)-based NMR detection unit was adapted. We successfully hyperpolarized fluorinated pyridine derivatives with an up to 2000-fold signal enhancement in 19 F. The detected signals may be explained by two alternative reaction mechanisms. SABRE combined with simultaneous SQUID-based broadband multinuclear detection may enable the quantitative analysis of multinuclear processes.

Evidence for an intrinsic binding force between dodecaborate dianions and receptors with hydrophobic binding pockets

A gas phase binding study revealed strong intrinsic intermolecular interactions between dianionic halogenated closo-dodecaborates [B12X12](2-) and several neutral organic receptors. Oxidation of a tetrathiafulvalene host allowed switching between two host-guest binding modes in a supramolecular complex. Complexes of β-cyclodextrin with [B12F12](2-) show remarkable stability in the gas phase and were successfully tested as carriers for the delivery of boron clusters into cancer cells.

The Travelling-Wave Primate System: A New Solution for Magnetic Resonance Imaging of Macaque Monkeys at 7 Tesla Ultra-High Field.

Introduction Neuroimaging of macaques at ultra-high field (UHF) is usually conducted by combining a volume coil for transmit (Tx) and a phased array coil for receive (Rx) tightly enclosing the monkey’s head. Good results have been achieved using vertical or horizontal magnets with implanted or near-surface coils. An alternative and less costly approach, the travelling-wave (TW) excitation concept, may offer more flexible experimental setups on human whole-body UHF magnetic resonance imaging (MRI) systems, which are now more widely available. Goal of the study was developing and validating the TW concept for in vivo primate MRI. Methods The TW Primate System (TWPS) uses the radio frequency shield of the gradient system of a human whole-body 7 T MRI system as a waveguide to propagate a circularly polarized B1 field represented by the TE11 mode. This mode is excited by a specifically designed 2-port patch antenna. For receive, a customized neuroimaging monkey head receive-only coil was designed. Field simulation was used for development and evaluation. Signal-to-noise ratio (SNR) was compared with data acquired with a conventional monkey volume head coil consisting of a homogeneous transmit coil and a 12-element receive coil. Results The TWPS offered good image homogeneity in the volume-of-interest Turbo spin echo images exhibited a high contrast, allowing a clear depiction of the cerebral anatomy. As a prerequisite for functional MRI, whole brain ultrafast echo planar images were successfully acquired. Conclusion The TWPS presents a promising new approach to fMRI of macaques for research groups with access to a horizontal UHF MRI system.

Non-invasive high-resolution tracking of human neuronal pathways: diffusion tensor imaging at 7T with 1.2 mm isotropic voxel size

Diffusion tensor imaging (DTI) allows characterizing and exploiting diffusion anisotropy effects, thereby providing important details about tissue microstructure. A major application in neuroimaging is the so-called fiber tracking where neuronal connections between brain regions are determined non-invasively by DTI. Combining these neural pathways within the human brain with the localization of activated brain areas provided by functional MRI offers important information about functional connectivity of brain regions. However, DTI suffers from severe signal reduction due to the diffusion-weighting. Ultra-high field (UHF) magnetic resonance imaging (MRI) should therefore be advantageous to increase the intrinsic signal-to-noise ratio (SNR). This in turn enables to acquire high quality data with increased resolution, which is beneficial for tracking more complex fiber structures. However, UHF MRI imposes some difficulties mainly due to the larger B1 inhomogeneity compared to 3T MRI. We therefore optimized the parameters to perform DTI at a 7 Tesla whole body MR scanner equipped with a high performance gradient system and a 32-channel head receive coil. A Stesjkal Tanner spin-echo EPI sequence was used, to acquire 110 slices with an isotropic voxel-size of 1.2 mm covering the whole brain. 60 diffusion directions were scanned which allows calculating the principal direction components of the diffusion vector in each voxel. The results prove that DTI can be performed with high quality at UHF and that it is possible to explore the SNT benefit of the higher field strength. Combining UHF fMRI data with UHF DTI results will therefore be a major step towards better neuroimaging methods.

Dipolar induced para-hydrogen-induced polarization.

Analytical expressions for the signal enhancement in solid-state PHIP NMR spectroscopy mediated by homonuclear dipolar interactions and single pulse or spin-echo excitation are developed and simulated numerically. It is shown that an efficient enhancement of the proton NMR signal in solid-state NMR studies of chemisorbed hydrogen on surfaces is possible. Employing typical reaction efficacy, enhancement-factors of ca. 30-40 can be expected both under ALTADENA and under PASADENA conditions. This result has important consequences for the practical application of the method, since it potentially allows the design of an in-situ flow setup, where the para-hydrogen is adsorbed and desorbed from catalyst surfaces inside the NMR magnet.

Metamaterial-based transmit and receive system for whole-body magnetic resonance imaging at ultra-high magnetic fields

Magnetic resonance imaging (MRI) at ultra-high fields (UHF), such as 7 T, provides an enhanced signal-to-noise ratio and has led to unprecedented high-resolution anatomic images and brain activation maps. Although a variety of radio frequency (RF) coil architectures have been developed for imaging at UHF conditions, they usually are specialized for small volumes of interests (VoI). So far, whole-body coil resonators are not available for commercial UHF human whole-body MRI systems. The goal of the present study was the development and validation of a transmit and receive system for large VoIs that operates at a 7 T human whole-body MRI system. A Metamaterial Ring Antenna System (MRAS) consisting of several ring antennas was developed, since it allows for the imaging of extended VoIs. Furthermore, the MRAS not only requires lower intensities of the irradiated RF energy, but also provides a more confined and focused injection of excitation energy on selected body parts. The MRAS consisted of several antennas with 50 cm inner diameter, 10 cm width and 0.5 cm depth. The position of the rings was freely adjustable. Conformal resonant right-/left-handed metamaterial was used for each ring antenna with two quadrature feeding ports for RF power. The system was successfully implemented and demonstrated with both a silicone oil and a water-NaCl-isopropanol phantom as well as in vivo by acquiring whole-body images of a crab-eating macaque. The potential for future neuroimaging applications was demonstrated by the acquired high-resolution anatomic images of the macaque’s head. Phantom and in vivo measurements of crab-eating macaques provided high-resolution images with large VoIs up to 40 cm in xy-direction and 45 cm in z-direction. The results of this work demonstrate the feasibility of the MRAS system for UHF MRI as proof of principle. The MRAS shows a substantial potential for MR imaging of larger volumes at 7 T UHF. This new technique may provide new diagnostic potential in spatially extended pathologies such as searching for spread-out tumor metastases or monitoring systemic inflammatory processes.

Metabolic and Molecular Imaging with Hyperpolarised Tracers

Since reaching the clinic, magnetic resonance imaging (MRI) has become an irreplaceable radiological tool because of the macroscopic information it provides across almost all organs and soft tissues within the human body, all without the need for ionising radiation. The sensitivity of MR, however, is too low to take full advantage of the rich chemical information contained in the MR signal. Hyperpolarisation techniques have recently emerged as methods to overcome the sensitivity limitations by enhancing the MR signal by many orders of magnitude compared to the thermal equilibrium, enabling a new class of metabolic and molecular X-nuclei based MR tracers capable of reporting on metabolic processes at the cellular level. These hyperpolarised (HP) tracers have the potential to elucidate the complex metabolic processes of many organs and pathologies, with studies so far focusing on the fields of oncology and cardiology. This review presents an overview of hyperpolarisation techniques that appear most promising for clinical use today, such as dissolution dynamic nuclear polarisation (d-DNP), parahydrogen-induced hyperpolarisation (PHIP), Brute force hyperpolarisation and spin-exchange optical pumping (SEOP), before discussing methods for tracer detection, emerging metabolic tracers and applications and progress in preclinical and clinical application.

Low-cost LED-based Photo-CIDNP Enables Biocompatible Hyperpolarization of 19F for NMR and MRI at 7 T and 4.7 T

Abstract 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.

Parahydrogen-induced polarization of carboxylic acids: a pilot study of valproic acid and related structures

Parahydrogen‐induced polarization (PHIP) is a promising new tool for medical applications of MR, including MRI. The PHIP technique can be used to transfer high non‐Boltzmann polarization, derived from parahydrogen, to isotopes with a low natural abundance or low gyromagnetic ratio (e.g. 13C), thus improving the signal‐to‐noise ratio by several orders of magnitude. A few molecules acting as metabolic sensors have already been hyperpolarized with PHIP, but the direct hyperpolarization of drugs used to treat neurological disorders has not been accomplished until now. Here, we report on the first successful hyperpolarization of valproate (valproic acid, VPA), an important and commonly used antiepileptic drug. Hyperpolarization was confirmed by detecting the corresponding signal patterns in the 1H NMR spectrum. To identify the optimal experimental conditions for the conversion of an appropriate VPA precursor, structurally related molecules with different side chains were analyzed in different solvents using various catalytic systems. The presented results include hyperpolarized 13C NMR spectra and proton images of related systems, confirming their applicability for MR studies. PHIP‐based polarization enhancement may provide a new MR technique to monitor the spatial distribution of valproate in brain tissue and to analyze metabolic pathways after valproate administration. Copyright