In biological tissues, 19F magnetic resonance (MR) enables the non-invasive, background-free detection of 19F-containing biomarkers. However, the signal-to-noise ratio (SNR) is usually low because biomarkers are typically present at low concentrations. Measurements at low magnetic fields further reduce the SNR. In a proof-of-principal study we applied LED-based photo-chemically induced dynamic nuclear polarization (photo-CIDNP) to amplify the 19F signal at 0.6 T. For the first time, 19F MR imaging (MRI) and spectroscopy (MRS) of a fully biocompatible model system containing the antiviral drug favipiravir has been successfully performed. This fluorinated drug has been used to treat Ebola and COVID-19. Since the partially cyclic reaction scheme for photo-CIDNP allows for multiple data acquisitions, averaging further improved the SNR. The mean signal gain factor for 19F has been estimated to be in the order of 103. An in-plane resolution of 0.39 × 0.39 mm2 enabled the analysis of spatially varying degrees of hyperpolarization. The minimal detectable amount of favipiravir per voxel was estimated to about 500 pmol. The results show that 19F photo-CIDNP is a promising method for the non-invasive detection of suitable 19F-containing drugs and other compounds with very low levels of the substance.

Ultra-high-field MRI (UHF-MRI) at 7T is growing increasingly important for clinical diagnostics and research. However, UHF-MRI faces more challenges from susceptibility artifacts and B0-inhomogeneities, impacting segmentation procedures that are typically optimized for lower field strengths as UHF-MRI is not yet widely available across radiological sites. In this study, we assessed therefore, whether MONAI (The Medical Open Network for Artificial Intelligence), an open source framework for AI-based medical image segmentation, could be employed for accurately segmenting also UHF-MRI data as MONAI is trained on 3T datasets exhibiting different contrast behavior than 7T. For testing, we used a publicly accessible 7T-brain MRI dataset and compared the AI-based segmentations with segmentations yielded by the framework statistical parametric mapping (SPM). The segmentation accuracy was assessed through comparison of the mean balanced Hausdorff-Distance (bHD) with expert-level segmented ground truths. Statistical analysis (left-sided Wilcoxon signed-rank test) indicated that cortical and deep gray matter were more accurately segmented by MONAI than by SPM (mean bHD MONAI: 2.65x10-4 ; mean bHD SPM: 3.37x10-4). The findings demonstrate MONAI's ability to segment data more effectively than the standard functional MRI analysis tool SPM. This makes newest technology available for researchers not trained specifically in AI-based image segmentation.

The radio-frequency (RF) transmit power deposition in tissue during magnetic resonance imaging (MRI) at ultra-high fields, i.e. B-0 >= 7 T, is a major challenge for pulse sequences requesting large flip angles. The absorbed RF energy can pose safety risk to patients as it is rising temperature in the tissue. The temperature can be accessed using MRI itself via the proton-resonance frequency (PRF) shift technique, which at low B-0 has been shown a valid MR thermometry method. In this paper, we explore the applicability of the PRF method to the assessment of local temperature in 7 T MRI procedures. To this end, we built a phantom filled with a material presenting electrical conductivity and permittivity close to muscle tissue. Tubes filled with oil were placed nearby the phantom to observe the time dependent B(0 )drift. MRI phase images were acquired by gradient-echo (GRE) sequences at time points between spin-echo sequences with large flip angle allowing for a continuous assessment of the temperature during a 114 min RF-heating experiment. All acquired phase images were post-processed with attention to the time dependent instability of B-0, and, in addition, to potential spatial and temporal phase discontinuities, known as wraps. In this paper, we present a strategy to analyze and to unfold these phase wraps for large measurement fields and long acquisition times. It is shown that the PRF shift method is beneficial for the assessment of temperature at 7 T MRI. The temperature maps for axial and coronal planes display a temperature increase of approximately 3.5 degrees C during the time of the RF-heating experiment. Overall it is shown that B-0-drift correction and, importantly, the spatio-temporal unwrapping are an indispensable part of post-processing.

Magnetic resonance elastography (MRE) and diffusion-weighted imaging (DWI) are complementary imaging techniques that detect disease based on viscoelasticity and water mobility, respectively. However, the relationship between viscoelasticity and water diffusion is still poorly understood, hindering the clinical translation of combined DWI-MRE markers.We used DWI-MRE to study 129 biomaterial samples including native and cross-linked collagen, glycosaminoglycans (GAGs) with different sulfation levels, and decellularized specimens of pancreas and liver, all with different proportions of solid tissue, or solid fractions. We developed a theoretical framework of the relationship between mechanical loss and tissue-water mobility based on two parameters, solid and fluid viscosity. These parameters revealed distinct DWI-MRE property clusters characterizing weak, moderate, and strong water-network interactions. Sparse networks interacting weakly with water, such as collagen or diluted decellularized tissue, resulted in marginal changes in water diffusion over increasing solid viscosity. In contrast, dense networks with larger solid fractions exhibited both free and hindered water diffusion depending on the polarity of the solid components. For example, polar and highly sulfated GAGs as well as native soft tissues hindered water diffusion despite relatively low solid viscosity.Our results suggest that two fundamental properties of tissue networks, solid fraction and network polarity, critically influence solid and fluid viscosity in biological tissues. Since clinical DWI and MRE are sensitive to these viscosity parameters, the framework we present here can be used to detect tissue remodeling and architectural changes in the setting of diagnostic imaging.Statement of SignificanceThe viscoelastic properties of biological tissues provide a wealth of information on the vital state of cells and host matrix. Combined measurement of viscoelasticity and water diffusion by medical imaging is sensitive to tissue microarchitecture. However, the relationship between viscoelasticity and water diffusion is still poorly understood, hindering full exploitation of these properties as a combined clinical biomarker. Therefore, we analyzed the parameter space accessible by diffusion-weighted imaging (DWI) and magnetic resonance elastography (MRE) and developed a theoretical framework for the relationship between water mobility and mechanical parameters in biomaterials. Our theory of solid material properties related to particle motion can be translated to clinical radiology using clinically established MRE and DWI.

Abstract At ultra-high field MRI (Bo>7T) it is crucial to predict and control the patient safety. Commonly patient safety is controlled by the power deposited in the tissue (specific absorption rate - SAR). However, temperature distributions do not always correlate directly with SAR distributions, which makes temperature control also a crucial parameter to guarantee patient safety. In this work, temperature changes were accessed by MR thermometry, specifically by the proton resonance frequency shift technique (PRF). A phantom mimicking muscle tissue was used to evaluate the temperature rise caused by the radiofrequency (RF) absorption during 7T MRI, applied through a commercial birdcage head coil. A pulse-sequence protocol was implemented for both, the generation of temperature increase and the MR thermometry. To control the temperature, a digital thermometer was used, and oil tubes were utilized to dismiss the drift effects for PRF. Measurements of the phantom’s dielectric characteristics, i.e. conductivity and permittivity, were in good agreement with the literature values for muscle. Spatio-temporal evaluations showed a temperature increase in time via RF exposure and the feasibility of measuring temperature maps using the PRF shift method. The accuracy of the PRF shift method increased when the drift effects were quantified and dismissed, indicating a PRF reading accuracy differing less than 0.5 °C from the thermometer. Results also validate our heating and temperature imaging protocol. This study is a valuable contribution to the evaluation of heating effects caused by RF absorption and demonstrates potential impact on future thermal investigations, which may use different heating sources, as well validate thermal simulations.

Temperature is an important factor for various physiological phenomena. Hyperthermia and hypothermia are only two examples in clinical application. As the resolution of MR data increases, so does interest in the exact determination of the temperature. Molecular sensors offer the opportunity to determine temperature in living organisms. Based on the preliminary investigations of our working group using Ce 3+ complexes, the more detailed characterization of Tm 3+ complexes was carried out with regard to the temperature sensitivity of the 19 F MR signals and, for the first time, also to the toxicity using the example of fibroblasts.

Ziel/Aim Die Medizininformatik-Initiative (MII) ist ein vom BMBF gefördertes Projekt, mit dem Ziel, Daten standortübergreifend verfügbar zu machen.

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.

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.

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.

The Front Cover shows 19F-labeled molecules studied in two different liquids. By using 19F-MR signals (here the mountain), determination of the local temperature is possible. Signal intensities decrease with increasing temperature. The chemical shifts vary strongly depending on 19F position and solvent (here DMSO or D2O). Cover design by Mona Borggrefe and Felix Mysegaes and Dr. Markus Plaumann. More information can be found in the Research Article by Felix Mysegaes, Markus Plaumann and co-workers.

Although 19 F has high potential to serve as a background-free molecular marker in bioimaging, the molar amount of marker substance is often too small to enable 19 F MR imaging or 19 F NMR spectroscopy with a sufficiently high signal-to-noise ratio (SNR). Hyperpolarization methods such as parahydrogen-based hyperpolarization or dynamic nuclear polarization (DNP) can significantly improve the SNR, but require expensive and complex sample preparation and the removal of toxic catalysts and solvents. Therefore, we used the biologically compatible model of the fluorinated amino acid 3-Fluoro-DL-tyrosine with riboflavin 5ʹ-monophosphate (FMN) as a chromophore dissolved in D 2 O with 3.4% H 2 O dest. , allowing to transform light energy into hyperpolarization of the 19 F nucleus via photo-chemically induced dynamic nuclear polarization (photo-CIDNP). We used a low-cost high-power blue LED to illuminate the sample replacing traditionally used laser excitation, which is both potentially harmful and costly. For the first time, we present results of hyperpolarized 19 F MRI and 19 F NMR performed with a low-cost 0.6 T benchtop MRI system. The device allowed simultaneous dual-channel 1 H/ 19 F NMR. 19 F imaging was performed with a (0.94 mm) 2 in-plane resolution. This enabled the spatial resolution of different degrees of hyperpolarization within the sample. We estimated the photo-CIDNP-based 19 F signal enhancement at 0.6 T to be approximately 465. FMN did not bleach out even after multiple excitations, so that the signal-to-noise ratio could be further improved by averaging hyperpolarized signals. The results show that the easy-to-use experimental setup has a high potential to serve as an efficient preclinical tool for hyperpolarization studies in bioimaging.

Abstract 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 15N 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 15N‐acetonitrole, where a 30 % higher 15N polarization with alt‐SABRE compared to common SABRE was reached.

The Cover Feature illustrates the quest for efficient Signal Amplification By Reversible Exchange (SABRE). It shows conventional SABRE on the left side and the method alt-SABRE on the right side, where the polarization evolution switches back and forth between the strong coupling regime at ∼1 mT and the weak coupling regime at ∼50 mT. With this effect the polarization of 15N can be boosted by at least 30%. The authors thank the DEAL project for promoting open access to research publications. More information can be found in the Communication by Andrey N. Pravdivtsev, Kai Buckenmaier and co-workers.

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.

A number of Ir–N-heterocyclic carbene (Ir–NHC) complexes with asymmetric N-heterocyclic carbene (NHC) ligands have been prepared and examined for signal amplification by reversible exchange (SABRE). Pyridine was chosen as model compound for hyperpolarization experiments. This substrate was examined in a solvent mixture using several Ir–NHC complexes, which differ in their NHC ligands. The SABRE polarization was created at 6 mT and the 1H nuclear magnetic resonance signals were detected at 7 T. We show that asymmetric NHC ligands, because of their favorable chemistry, can adapt the SABRE active complexes to different chemical scenarios.

We present a method for the simultaneous observation of heteronuclear multi-quantum coherences (up to the 3rd order), which give an additional degree of freedom for ultralow magnetic field (ULF) MR experiments, where the chemical shift is negligible. The nonequilibrium spin state is generated by Signal Amplification By Reversible Exchange (SABRE) and detected at ULF with SQUID-based NMR. We compare the results obtained by the heteronuclei Correlated SpectroscopY (COSY) with a Flip Angle FOurier Series (FAFOS) method. COSY allows a quantitative analysis of homo- and heteronuclei quantum coherences.

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.

Summary 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.