19 F VT NMR: Novel Tm3+ and Ce3+ Complexes Provide New Insight into Temperature Measurement Using Molecular Sensors.

The front cover artwork is provided by Dr. Markus Plaumann's group at the Otto-von-Guericke University Magdeburg. The image shows the investigated 19 F labeled molecules, which can be used as temperature MR-sensors in different solvents. The direction of the chemical shift change is strongly solvent dependent. Read the full text of the Research Article at 10.1002/cphc.202300057.

Organic Fluorine Compounds and Their Uses as Molecular MR-Based Temperature Sensors.

The interest in fluorinated substances has increased significantly in recent decades due to their diverse properties and possible uses. An important analytical method in this context is NMR spectroscopy, which provides information on the structure as well as on intermolecular interactions or generally on changes in the environment of the nucleus under consideration. A physical quantity that is of great importance in most studies is temperature. However, this is not always easy, e. g. in shielded systems or within an organism. However, the application potential in chemical reactors or in medical diagnosis and therapy is very high and for this reason 13 fluorinated organic compound were chosen for a first 19 F NMR signal temperature sensitivity examination for determination of local temperatures in solution. Polyfluorinated molecules with separate 19 F MR signals are particularly suitable for temperature determination. Those can be serve as internal error-correcting thermometers without the need of a reference substance. Under these conditions, a 19 F MR signal shift of up to 0.03 ppm/K was detectable. Fluorine position and chemical environment were very important for the temperature sensitivity.

Two fluorinated thulium complexes as molecular temperature sensors in MR applications.

19F-based magnetic resonance is a powerful tool to overcome several difficulties of standard 1H MR. We present the syntheses and characterization (including cell viability and stability tests) of two Tm3+ complexes. Both complexes allow the detection of temperature (ΔCT = -0.2319 ppm K-1 and -0.2122 ppm K-1) without a reference compound.

19 F VT NMR: Novel Tm3+ and Ce3+ Complexes Provide New Insight into Temperature Measurement Using Molecular Sensors.

In the past few decades, magnetic resonance spectroscopy (MRS) and MR imaging (MRI) have developed into a powerful non-invasive tool for medical diagnostic and therapy. Especially 19 F MR shows promising potential because of the properties of the fluorine atom and the negligible background signals in the MR spectra. The detection of temperature in a living organism is quite difficult, and usually external thermometers or fibers are used. Temperature determination via MRS needs temperature-sensitive contrast agents. This article reports first results of solvent and structural influences on the temperature sensitivity of 19 F NMR signals of chosen molecules. By using this chemical shift sensitivity, a local temperature can be determined with a high precision. Based on this preliminary study, we synthesized five metal complexes and compared the results of all variable temperature measurements. It is shown that the highest 19 F MR signal temperature dependence is detectable for a fluorine nucleus in a Tm3+ -complex.

Coherent Evolution of Signal Amplification by Reversible Exchange in Two Alternating Fields (alt-SABRE).

Parahydrogen (pH2 ) is a convenient and cost-efficient source of spin order to enhance the magnetic resonance signal. Previous work showed that transient interaction of pH2 with a metal organic complex in a signal amplification by reversible exchange (SABRE) experiment enabled more than 10 % polarization for some 15 N molecules. Here, we analyzed a variant of SABRE, consisting of a magnetic field alternating between a low field of ∼1 µT, where polarization transfer is expected to take place, and a higher field >50 µT (alt-SABRE). These magnetic fields affected the amplitude and frequency of polarization transfer. Deviation of a lower magnetic field from a "perfect" condition of level anti-crossing increases the frequency of polarization transfer that can be exploited for polarization of short-lived transient SABRE complexes. Moreover, the coherences responsible for polarization transfer at a lower field persisted during magnetic field variation and continued their spin evolution at higher field with a frequency of 2.5 kHz at 54 µT. The latter should be taken into consideration for an efficient alt-SABRE. Theoretical and experimental findings were exemplified with Iridium N-heterocyclic carbene SABRE complex and 15 N-acetonitrole, where a 30 % higher 15 N polarization with alt-SABRE compared to common SABRE was reached.

IT support in emergency remote teaching in response to COVID-19.

Background: The COVID-19 pandemic hit the German education system unexpectedly and forced its universities to shift to Emergency Remote Teaching (ERT). The Data Integration Center (DIC) of the University Hospital Magdeburg and the Institute of Biometry and Medical Informatics (IBMI) has developed a concept based on existing structures that can be quickly implemented and used by the Medical Faculty at Otto von Guericke University. This manuscript focuses on the IT support for lecturers, which allows them to concentrate on teaching their lessons, although the authors are aware that this is only a small part of the entire subject. Additionally, there is a great awareness that ERT can never replace well-structured in-person classes. Concept: The key feature of the concept uses the well-working management system for all physical rooms of the university by designing a virtual video conference room for every physical room. This allows high interactivity for lectures and seminars while applying proven teaching methods. Additionally, a collaboration software system to document all lessons learned and a technical support team have been available for the teaching staff. Courses with a hands-on approach require more personal interaction than lectures. Therefore, the issues of practical trainings have not been solved with this concept, but been tackled by using questionnaires and minimizing contacts during attestations. Applied IT tools: The concept's requirements were met by Zoom Meetings, Confluence, HIS/LSF and Moodle. Discussion and Conclusion: The concept helped the lecturers to provide high-quality teaching for students at universities. Additionally, it allows for a dynamic response to new needs and problems. The concept will be reviewed as part of a higher Universal Design for Learning concept and may support lecturers in the following semesters in hybrid meetings with real and virtual attendees.

Multiple Quantum Coherences Hyperpolarized at Ultra-Low Fields.

The development of hyperpolarization technologies enabled several yet exotic NMR applications at low and ultra-low fields (ULF), where without hyperpolarization even the detection of a signal from analytes is a challenge. Herein, we present a method for the simultaneous excitation and observation of homo- and heteronuclear multiple quantum coherences (from zero up to the third-order), which give an additional degree of freedom for ULF NMR experiments, where the chemical shift variation is negligible. The approach is based on heteronuclear correlated spectroscopy (COSY); its combination with a phase-cycling scheme allows the selective observation of multiple quantum coherences of different orders. The nonequilibrium spin state and multiple spin orders are generated by signal amplification by reversible exchange (SABRE) and detected at ULF with a superconducting quantum interference device (SQUID)-based NMR system.

Mapping fine-scale anatomy of gray matter, white matter, and trigeminal-root region applying spherical deconvolution to high-resolution 7-T diffusion MRI.

OBJECTIVES: We assessed the use of high-resolution ultra-high-field diffusion magnetic resonance imaging (dMRI) to determine neuronal fiber orientation density functions (fODFs) throughout the human brain, including gray matter (GM), white matter (WM), and small intertwined structures in the cerebellopontine region. MATERIALS AND METHODS: We acquired 7-T whole-brain dMRI data of 23 volunteers with 1.4-mm isotropic resolution; fODFs were estimated using constrained spherical deconvolution. RESULTS: High-resolution fODFs enabled a detailed view of the intravoxel distributions of fiber populations in the whole brain. In the brainstem region, the fODF of the extra- and intrapontine parts of the trigeminus could be resolved. Intrapontine trigeminal fiber populations were crossed in a network-like fashion by fiber populations of the surrounding cerebellopontine tracts. In cortical GM, additional evidence was found that in parts of primary somatosensory cortex, fODFs seem to be oriented less perpendicular to the cortical surface than in GM of motor, premotor, and secondary somatosensory cortices. CONCLUSION: With 7-T MRI being introduced into clinical routine, high-resolution dMRI and derived measures such as fODFs can serve to characterize fine-scale anatomic structures as a prerequisite to detecting pathologies in GM and small or intertwined WM tracts.

MIRACUM: Medical Informatics in Research and Care in University Medicine.

INTRODUCTION: This article is part of the Focus Theme of Methods of Information in Medicine on the German Medical Informatics Initiative. Similar to other large international data sharing networks (e.g. OHDSI, PCORnet, eMerge, RD-Connect) MIRACUM is a consortium of academic and hospital partners as well as one industrial partner in eight German cities which have joined forces to create interoperable data integration centres (DIC) and make data within those DIC available for innovative new IT solutions in patient care and medical research. OBJECTIVES: Sharing data shall be supported by common interoperable tools and services, in order to leverage the power of such data for biomedical discovery and moving towards a learning health system. This paper aims at illustrating the major building blocks and concepts which MIRACUM will apply to achieve this goal. GOVERNANCE AND POLICIES: Besides establishing an efficient governance structure within the MIRACUM consortium (based on the steering board, a central administrative office, the general MIRACUM assembly, six working groups and the international scientific advisory board), defining DIC governance rules and data sharing policies, as well as establishing (at each MIRACUM DIC site, but also for MIRACUM in total) use and access committees are major building blocks for the success of such an endeavor. ARCHITECTURAL FRAMEWORK AND METHODOLOGY: The MIRACUM DIC architecture builds on a comprehensive ecosystem of reusable open source tools (MIRACOLIX), which are linkable and interoperable amongst each other, but also with the existing software environment of the MIRACUM hospitals. Efficient data protection measures, considering patient consent, data harmonization and a MIRACUM metadata repository as well as a common data model are major pillars of this framework. The methodological approach for shared data usage relies on a federated querying and analysis concept. USE CASES: MIRACUM aims at proving the value of their DIC with three use cases: IT support for patient recruitment into clinical trials, the development and routine care implementation of a clinico-molecular predictive knowledge tool, and molecular-guided therapy recommendations in molecular tumor boards. RESULTS: Based on the MIRACUM DIC release in the nine months conceptual phase first large scale analysis for stroke and colorectal cancer cohorts have been pursued. DISCUSSION: Beyond all technological challenges successfully applying the MIRACUM tools for the enrichment of our knowledge about diagnostic and therapeutic concepts, thus supporting the concept of a Learning Health System will be crucial for the acceptance and sustainability in the medical community and the MIRACUM university hospitals.

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

Substrates containing 19 F 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 1 H 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 19 F 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 19 F 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 19 F MR images could be acquired, because photo-CIDNP enabled repetitive hyperpolarization without adding new substrates.

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.

Mutual benefit achieved by combining ultralow-field magnetic resonance and hyperpolarizing techniques.

Ultralow-field (ULF) nuclear magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) are promising spectroscopy and imaging methods allowing for, e.g., the simultaneous detection of multiple nuclei or imaging in the vicinity of metals. To overcome the inherently low signal-to-noise ratio that usually hampers a wider application, we present an alternative approach to prepolarized ULF MRS employing hyperpolarization techniques like signal amplification by reversible exchange (SABRE) or Overhauser dynamic nuclear polarization (ODNP). Both techniques allow continuous hyperpolarization of 1H as well as other MR-active nuclei. For the implementation, a superconducting quantum interference device (SQUID)-based ULF MRS/MRI detection scheme was constructed. Due to the very low intrinsic noise level, SQUIDs are superior to conventional Faraday detection coils at ULFs. Additionally, the broadband characteristics of SQUIDs enable them to simultaneously detect the MR signal of different nuclei such as 13C, 19F, or 1H. Since SQUIDs detect the MR signal directly, they are an ideal tool for a quantitative investigation of hyperpolarization techniques such as SABRE or ODNP.

Increasing the spatial resolution and sensitivity of magnetic resonance elastography by correcting for subject motion and susceptibility-induced image distortions.

PURPOSE: To improve the resolution of elasticity maps by adapting motion and distortion correction methods for phase-based magnetic resonance imaging (MRI) contrasts such as magnetic resonance elastography (MRE), a technique for measuring mechanical tissue properties in vivo. MATERIALS AND METHODS: MRE data of the brain were acquired with echo-planar imaging (EPI) at 3T (n = 14) and 7T (n = 18). Motion and distortion correction parameters were estimated using the magnitude images. The real and imaginary part of the complex MRE data were corrected separately and recombined. The width of the point-spread function (PSF) and the position variability were calculated. The images were normalized to the Montreal Neurological Institute (MNI) anatomical template. The gray-to-white matter separability of the elasticity maps was tested. RESULTS: Motion correction sharpened the |G*| maps as demonstrated by a narrowing of the PSF by 0.78 ± 0.51 mm at 7T and 0.52 ± 0.63 mm at 3T. The amount of individual head motion during MRE acquisition correlated with the decrease in the width of the PSF at 7T (r = 0.53, P = 0.025) and at 3T (r = 0.69, P = 0.006) and with the increase of gray-to-white matter separability after motion correction at 7T (r = 0.64, P = 0.0039) and at 3T (r = 0.57, P = 0.0319). Improved spatial accuracy after distortion correction results in a significant increase in separability of gray and white matter stiffness (P = 0.0067), especially in inferior parts of the brain suffering from strong B0 inhomogeneities. CONCLUSION: We demonstrate that our method leads to sharper images and higher spatial accuracy, raising the prospect of the investigation of smaller brain areas with increased sensitivity in studies using MRE. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:134-141.

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 ß-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.

Superior memorizers employ different neural networks for encoding and recall.

Superior memorizers often employ the method of loci (MoL) to memorize large amounts of information. The MoL, known since ancient times, relies on a complex process where information to be memorized is bound to landmarks along mental routes in a previously memorized environment. However, functional magnetic resonance imaging data on groups of trained superior memorizer are rare. Based on the memorizing strategy reported by superior memorizers, we developed a scheme of the processes successively employed during memorizing and recalling digits and relate these to brain activation that is specific for the encoding and recall period. In the examined superior memorizers several regions, suggested to be involved in mental navigation and digit-to-word processing, were specifically activated during encoding: bilateral early visual cortex, retrosplenial cortex, left parahippocampus, left visual cortex, and left superior parietal cortex. Although the scheme suggests that some steps during encoding and recall seem to be analog, none of the encoding areas were specifically activated during the recall. Instead, we found strong activation in left anterior superior temporal gyrus, which we relate to recalling the sequential order of the digits, and right motor cortex that may be related to reciting the digits.

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.

Changes in gray matter volume after microsurgical lumbar discectomy: a longitudinal analysis.

People around the world suffer chronic lower back pain. Because spine imaging often does not explain the degree of perceived pain reported by patients, the role of the processing of nociceptor signals in the brain as the basis of pain perception is gaining increased attention. Modern neuroimaging techniques (including functional and morphometric methods) have produced results that suggest which brain areas may play a crucial role in the perception of acute and chronic pain. In this study, we examined 12 patients with chronic low back pain and sciatica, both resulting from lumbar disc herniation. Structural magnetic resonance imaging (MRI) of the brain was performed 1 day prior to and about 4 weeks after microsurgical lumbar discectomy. The subsequent MRI revealed an increase in gray matter volume in the basal ganglia but a decrease in volume in the hippocampus, which suggests the complexity of the network that involves movement, pain processing, and aspects of memory. Interestingly, volume changes in the hippocampus were significantly correlated to preoperative pain intensity but not to the duration of chronic pain. Mapping structural changes of the brain that result from lumbar disc herniation has the potential to enhance our understanding of the neuropathology of chronic low back pain and sciatica and therefore may help to optimize the decisions we make about conservative and surgical treatments in the future. The possibility of illuminating more of the details of central pain processing in lumbar disc herniation, as well as the accompanying personal and economic impact of pain relief worldwide, calls for future large-scale clinical studies.

A proof-of-principle study of multi-site real-time functional imaging at 3T and 7T: Implementation and validation.

Real-time functional Magnetic Resonance Imaging (rtfMRI) is used mainly for neurofeedback or for brain-computer interfaces (BCI). But multi-site rtfMRI could in fact help in the application of new interactive paradigms such as the monitoring of mutual information flow or the controlling of objects in shared virtual environments. For that reason, a previously developed framework that provided an integrated control and data analysis of rtfMRI experiments was extended to enable multi-site rtfMRI. Important new components included a data exchange platform for analyzing the data of both MR scanners independently and/or jointly. Information related to brain activation can be displayed separately or in a shared view. However, a signal calibration procedure had to be developed and integrated in order to permit the connecting of sites that had different hardware and to account for different inter-individual brain activation levels. The framework was successfully validated in a proof-of-principle study with twelve volunteers. Thus the overall concept, the calibration of grossly differing signals, and BCI functionality on each site proved to work as required. To model interactions between brains in real-time, more complex rules utilizing mutual activation patterns could easily be implemented to allow for new kinds of social fMRI experiments.

A form-fitted three channel (31) P, two channel (1) H transceiver coil array for calf muscle studies at 7 T.

PURPOSE: To enhance sensitivity and coverage for calf muscle studies, a novel, form-fitted, three-channel phosphorus-31 ((31) P), two-channel proton ((1) H) transceiver coil array for 7 T MR imaging and spectroscopy is presented. METHODS: Electromagnetic simulations employing individually generated voxel models were performed to design a coil array for studying nonpathological muscle metabolism. Static phase combinations of the coil elements' transmit fields were optimized based on homogeneity and efficiency for several voxel models. The best-performing design was built and tested both on phantoms and in vivo. RESULTS: Simulations revealed that a shared conductor array for (31) P provides more robust interelement decoupling and better homogeneity than an overlap array in this configuration. A static B1 (+) shim setting that suited various calf anatomies was identified and implemented. Simulations showed that the (31) P array provides signal-to-noise ratio (SNR) benefits over a single loop and a birdcage coil of equal radius by factors of 3.2 and 2.6 in the gastrocnemius and by 2.5 and 2.0 in the soleus muscle. CONCLUSION: The performance of the coil in terms of B1 (+) and achievable SNR allows for spatially localized dynamic (31) P spectroscopy studies in the human calf. The associated higher specificity with respect to nonlocalized measurements permits distinguishing the functional responses of different muscles.

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.