This project will combine for the first time the diverse and unique expertise of a number of national measurement institutes together with clinicians and academics to overcome specific metrological barriers in neurodegenerative disease (NDD) diagnosis and treatment with routes to implement this back into the clinic. The project outcomes will contribute to establishing the metrological infrastructure needed to a) facilitate NDD earlier stage diagnosis, b) track disease progression, c) monitor success of drug therapeutic clinical trials and d) monitor response to intervention to improve quality of life.

Together with Charité, PTB will contribute by quantifying imaging and molecular biomarkers in vivo using ultrahigh field MR technology.

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Cancer patients are treated with radiotherapy in which a high dose of ionizing radiation is used to target and kill cancerous cells. MR-guided radiotherapy, the simultaneous use of Magnetic Resonance (MR)-imaging and Megavolt (MV) photon irradiation allows to see what you treat, and will lead to a step change in radiotherapy the coming years. Improved metrology in dosimetry and imaging for the safe clinical implementation and to support future innovations in MR guided radiotherapy is of great importance.

A special problem of MR-guided radiotherapy in presence of intra-fractional anatomy changes consists of inner organ landmark tracking by real-time MR imaging. Before utilization in radiotherapy the robustness and reliability of such MR procedures must be independently assessed and verified. It was shown previously [24] that the synergetic use of multi-channel UWB radar and MRI is capable of gaining complementary information to reduce uncertainties and to improve reliability of inner organ landmark tracking. The project will go beyond state of the art by using the technique in MR-guided radiotherapy and will overcome the challenges to process the UWB radar data and to fuse them with the MRI information in real-time.

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Major surgery in elderly patients (> 65 years) often leads to major short-term cognitive disturbance (postoperative delirium, POD), with an associated tendency to increased vulnerability to late-life dementia. In the framework of a large study on 800 subjects, PTB will carry out MR spectroscopy and resting-state fMRI at 7 T in order to identify biomarkers for this vulnerability. A novel image-based technique will be established to quantify the Nucelus basalis Meynert, one of the cholinergic nuclei relevant to neurodegeneration.

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Subproject: Study of the age dependence of the effects of transcranial direct current stimulation on GABA concentration and resting-state brain connectivity

The effects of transcranial direct current stimulation (tDCS) on neurotransmitter concentrations and resting-state brain connectivity are studied. GABA and glutamate in healthy subjects from three age groups are determined using MR spectroscopy before and after intervention whilst during intervention resting-state fMRI data are acquired. MEGA-PRESS is used for MRS, wheras resting-state connectivity is measured using Eigenvector Centrality Mapping and FSL.

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Development of novel motion-compensated T₁-mapping approaches which utilise signal models during image reconstruction in order to provide accurate T₁ maps in the shortest possible scan time. The close collaboration with our clinical partners at the Charité Berlin allows for a quick translation of novel techniques into clinical practice to benefit patient care as soon and as effective as possible.

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The priority program aims to find answers to fundamental questions of modern particle physics and astrophysics by means of experiments with slow and ultra-cold neutrons. These questions encompass the understanding of natural forces and the associate symmetries and investigations on the gravitational force at very small intervals. In this context, PTB deals with the sub-project "Development of a procedure to optimize magnetic shielding for spin precession experiments like nEDM". Within the scope of this sub-project, a portable magnetically shielded room with a residual magnetic field of < 700 picoteslas and a field gradient of less than 300 pT/m was put into operation in 2015. In the magnetically shielded rooms of PTB in Berlin and of the Technical University of Munich (TU München), precision measurements of the free precession of highly polarized nuclear spins of rare gases are to be carried out in search of an electric dipole moment in the xenon nucleus. In addition to the work on the apparatus, data analysis is an important field of work to enable consistently stating the uncertainties of the upper limits to be determined from the measurements. Such experiments in the range of extremely low energies are expected to provide new insights into fundamental physics.

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A collaboration consisting of a specialist MRI enterprise, clinicians, physicists, and national metrology institutes was formed in order to develop a phantom-based quality assurance system for verification of T₁-measurement stability over time at individual sites. A phantom was designed and produced (by http://www.resonancehealth.com) covering clinically relevant ranges of T₁ and T₂ in blood and myocardium. At 16 sites the phantoms are regularly scanned using different T₁-mapping sequences and hardware, leading to a dataset for quality assessment and standardization.

Using hyperpolarized ¹²⁹Xe gas in magnetic resonance imaging has enjoyed growing popularity in the past few years, both for use in animal models and in applications for humans. The natural occurrence of xenon in the atmosphere and the possibility of generating signals not only from the gas phase, but also dissolved in the body have contributed to this gain in popularity. The standard procedure to obtain hyperpolarization, however, requires the use of a gas mixture with a comparatively small xenon partial pressure. To date, the hyperpolarized xenon has mostly been separated from the process gases by cryogenic freezing. This procedure is complicated and makes it very difficult to obtain a continuous supply of hyperpolarized ¹²⁹Xe. By using semipermeable gas-separating membranes, we want to try and eliminate these disadvantages in order to provide a continuous gas flow of highly polarized xenon gas without active control elements and in a high concentration at the place of use.

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The first sub-project examined 14-year-olds and their family background within the scope of a European study. This study consisted in examining approx. 2000 young people at eight research centers (London, Nottingham, Dublin, Berlin, Hamburg, Mannheim, Paris, Dresden). The objective was to be able to make statements on the mental health and on the behavior in relation with risk factors (such as drugs, gambling, etc.) and to correlate these with independent measurement methods such as MRI and genetic analysis. This examination consisted of surveys, psychological tests, genetic investigations and a 2-hour MRI investigation program using fMRI, DTI and anatomic imaging. By repeating this examination on the same volunteers at the age of 18 and 21 years, valuable data on their development was obtained.

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The project is part of Research Group “Learning & habitization as predictors of the development & maintenance of alcoholism”. The impact of the dopamine x glutamate interaction on learning deficits and consecutive relapse probability is targeted with[18F]fallypride PET (Charité) and the measurement of absolute concentrations of glutamate with MRS (PTB).

Bei modernen Methoden der externen Strahlentherapie mit Beschleunigern müssen die Bestrahlungsparameter so gewählt werden, dass eine möglichst große Wirkung im Tumorgebiet erzielt und gleichzeitig umliegendes, gesundes Gewebe optimal geschont wird. Dies wird erst durch den Einsatz bildgebender Verfahren möglich, wobei Bildgebung und Bestrahlung bisher sequenziell mit getrennten Geräten erfolgen. Eine Steigerungsform dessen stellt die Kombination eines bildgebenden Verfahrens, wie z.B. der MRT, mit einem Linearbeschleuniger in einem Gerät dar. Solche MR-Linac-Geräte erlauben es, auf zeitliche Änderungen der Anatomie einzugehen, bis hin zu einer Anpassung der Bestrahlung in Echtzeit (4-D). Dieser neue Entwicklungsschritt in der Strahlentherapie kann nicht nur die Erfolgschancen der Therapie in bestehenden Anwendungsfeldern erhöhen, sondern auch neue Anwendungsgebiete erschließen, z.B. bei der Therapie von Tumoren, die sich aufgrund von Atmung oder Herzschlag stark bewegen. Andererseits stellt die Zusammenführung zweier hochkomplexer Methoden auch vor eine Reihe neuer Herausforderungen im Bereich der Medizinphysik und -technik. Ein Aspekt ist hierbei die qualitätsgesicherte Dosimetrie im Strahlungsfeld eines MR-Linac-Gerätes. Zentrale Idee des vorliegenden Projekts ist es, die Eignung der Alanin-Elektronenspinresonanz für die qualitätsgesicherte Dosimetrie im Strahlungsfeld von kombinierten MR-Linac-Geräten zu untersuchen. Parallel dazu wird die Entwicklung eines MR-kompatiblen Sekundärnormals auf Alaninbasis vorangetrieben.

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The goal of this research project is to promote the safe use of MRI by providing the metrological underpinning for future safety standards and regulations. Specific topics of interest are:

• The distribution of radio-frequency electromagnetic fields within the human body
• Induced effects due to movements in the stray magnetic field of an MRI scanner
• Emerging technologies 1: "Ultrahigh" magnetic field strengths and parallel transmission
• Emerging technologies 2: Photon dosimetry for an MRI-accelerator combination
• Metallic implants

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Using MR spectroscopy, it was tested whether GABA increases in the brain of patients who underwent recurrent traumatic brain injury. As GABAergic activity can be modulated by transcranial direct current stimulation (tDCS) in a polarization-dependent manner, a normalization of GABA was expected in these patients. In addition, transcranial magnetic stimulation was used to indirectly detect changed GABA levels, and correlational analyses served to detect an association of decreased GABA with learning success in behavioral paradigms, and cortical plasticity.

The effect of atDCS on GABA concentration and functional connectivity is studied in two seperate sessions (atDCS vs. sham). T1 = T1-weighted MRI sequence, MRS = MR spectroscopy, atDCS = anodal transcranial direct current stimulation, fMRT = functional MRI („resting state“ fMRI)

A key objective of this project is to examine the relationships of resting GABA concentration in a cortical network comprising primary sensory areas and traditional multisensory regions (e. g. the superior temporal gyrus) to multisensory integration through neural synchronization. To this end localized cortical GABA concentration will be measured in a cortical network using MRS, and correlated to synchronized EEG activity during multisensory processing.

This project aimed to systematically investigate the structure/function relation for peptides in their interaction with membranes of microbes or corresponding model systems. The investigations focused on the metrological characterization of antimicrobial substances for medicine. As a result, procedures for the quantification of relevant quantities for the interaction of peptides both with liposomes and with living cells and also strategies for their imaging were developed and established.

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State of the art in quantitative brain MRS is to acquire the signal from a cuboid voxel placed in or around the brain structure of interest. Adaptation of a voxel to the anatomical structure of interest is highly desirable in order to avoid either prohobitively small voxels or large amounts of contaminating tissue. The novel sequence SHAVE (SHAped Voxel Excitation) allows for a two-dimensional anatomically adapted excitation. An added two-shot approach permits localization in the third dimension, including readout at very short echo times, which enables the detection of metabolites having short T₂ relaxation.

The project EARS addresses the human perception of non-audible sound. Although the applied frequencies of 8 to 20 Hz and 20 to 24 kHz are considered to be outside the human spectrum they can be sensed at high sound pressure. The brain activity and cognitive performance of 20 volunteers were recorded at different frequencies and sound pressure levels. Standardized use of the measurement modalities MEG and fMRI were made possible due to the collaboration of 4 working groups.

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A method for in vivo quantification of brain glutamate developed at PTB was applied in this project. Chronic intake of ethanol is associated with a compensatory up-regulation of glutamatergic neurotransmission. Polymorphisms within the glutamate-associated genes modulate the risk of alcohol intake, dependence, craving and relapse. The goal of the project SP14 of the Integrated Genome Research Network „Genetics of Alcohol Addiction“ in NGFN Plus was to investigate (i) the association of genetic variants with cerebral glutamate concentration measured by MRS, (ii) whether increased glutamate brain levels are predictive for treatment response and (iii) if glutamate concentrations are related to alcohol risk factors for alcohol use in non-dependent probands.

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Das interdisziplinäre Forschungsvorhaben ultraMEDIS, das innerhalb des DFG-Schwerpunktprogramms 1202 "Ultrabreitband-Funktechniken für Kommunikation, Lokalisierung und Sensorik" (UKoLoS) angesiedelt war, zielte auf die Nutzung der Ultrabreitband-Radartechnik (UWB-Radar, Bandbreite 1-10 GHz) für biomedizinische Anwendungen. Dabei nutzt man die hohe zeitliche und räumliche Auflösung der Radarsensoren, deren Kompatibilität zu Schmalbandsystemen sowie die geringe Leistung der Sondierungssignale einschließlich deren Fähigkeit zur Objektdurchdringung. Gerade letztere Eigenschaft macht das UWB-Radar sehr attraktiv für Anwendungen in der Medizin.

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Ziel des INUMAC-Konsortiums war die Erforschung von Hochfeld-Magnetresonanztomographie-Verfahren und neuen zielgerichteten Kontrastmitteln, die für die Diagnostik neurologischer Erkrankungen geeignet sind. Das Projekt war in drei Arbeitspakete gegliedert:

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Ziel des Projektes war es, bei der Fa. Rapid Biomedical ("Rapid") ein Verfahren zu implementieren, das einen sicheren Betrieb der dort entwickelten Hochfrequenz(HF)-Spulen an MR-Systemen mit hohen Feldstärken (überwiegend 3 T und 7 T) gewährleistet. Diese Sicherheit betrifft insbesondere die SAR-Belastung von Patienten, die in MR-Untersuchungen nicht vermeidbar, aber minimierbar ist. Die gesetzlichen Grenzwerte sind zwar klar definiert, aber nur schwer genau bestimmbar. Hierfür sollte die Kooperation mit der PTB weiterhelfen. Grundsätzliche Konzepte zu dieser Fragestellung existierten an der PTB bereits vor Projektbeginn, waren jedoch nicht unmittelbar in das KMU übertragbar, da sie Zugang zu teuren MRT-Scannern und weiterem High-End-Equipment voraussetzten. Die Erarbeitung einer kostengünstigen und aufgabenangepassten Implementierung dieser Verfahren bei Rapid war eine zentrale Aufgabenstellung des Projekts.

Due to the very long coherence times, the simultaneous and free precession of highly polarized nuclear spins of rare gases in ultra-low, highly homogeneous magnetic fields allows very long measurement times (from several hours to several days) and, thus, an extremely high frequency resolution. By using two sorts of atoms, this procedure represents a kind of clock comparison which allows influences due to magnetic field variations to be eliminated and, thus, enables the search for hypothetical effects which are postulated by theories beyond the standard model of particle physics. In this project, the existing upper limits were lowered for both interactions which lead to Lorentz invariance violation and which would generate the short-range spin/mass interaction (mediated by pseudo-scalar bosons).

The joint research project directed by PTB aimed to develop a technology of molecular imaging of immunologically relevant systems by using hyperpolarized ¹²⁹Xe in MRI. For this purpose, a mobile polarizer for use in animal imaging (external lab) and an animal ventilator for mice or rats were developed and manufactured, and the fundamental mechanisms of the interaction of hyperpolarized ¹²⁹Xe with binding substances (contrast agents) relevant to molecular imaging were elucidated.

Die Berliner Ultrahochfeld Facility (BUFF) wurde von einem Konsortium Berliner Forschungseinrichtungen unter Führung des Max-Delbrück-Centrum für Molekulare Medizin (MDC) Berlin-Buch auf dem MDC-Campus errichtet. Kernstücke der neuen Einrichtung waren zunächst ein 7-Tesla-Ganzkörper-MRT für die klinische Forschung und ein 9,4-Tesla-MRT für Untersuchungen an Kleintieren.

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Nuclear magnetic resonance (NMR) spectroscopy, microscopy and imaging techniques (MRI) play a crucial role in numerous fields of science ranging from physics, chemistry, and material sciences to biology and medicine. However, despite all their versatility, a common key issue is sensitivity, which limits the applicability of NMR spectroscopy and imaging techniques in the case of fast dynamic processes and detection of low concentrated molecules in both in vitro and in vivo applications. The action aims to stimulate and accelerate collaborations and joint research efforts between European groups into hyperpolarization physics and methodology with the goal to develop robust strategies for sensitivity enhancement in NMR and MRI.

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Das Imaging Netzwerk Berlin (INB) hat das Ziel, die Zusammenführung und Koordination der verteilten Aktivitäten im Bereich der medizinischen Bildgebung voranzutreiben und mögliche Lücken im Wertschöpfungsprozess zu schließen. Das Imaging Netzwerk Berlin (INB) ist als offenes Netzwerk konzipiert, in dem neue Partner willkommen sind. Seit 2012 ist es bundesweit für neue Mitglieder geöffnet.

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Innerhalb der vergangenen Jahre wurden in Deutschland sieben Zentren für humane Ultrahochfeld(UHF)-MR-Bildgebung eingerichtet. Um diese hochkomplexe Technologie einer größeren Anzahl von Forschern zugänglich zu machen, bedarf es einer Zusammenarbeit der UHF-MR-Zentren. Zur Erlangung dieses Ziels haben alle deutschen UHF-Zentren beschlossen, ein nationales Netzwerk mit dem Namen German Ultrahigh Field Imaging (GUFI) zu etablieren. Dreizehn Standorte gehören derzeit zu GUFI. Weitere UHF-Einrichtungen sind herzlich eingeladen, sich dem GUFI-Netzwerk anzuschließen. Dieses Projekt wird im Rahmen der Förderung „Gerätezentren – Core Facilities“ von der Deutschen Forschungsgemeinschaft (DFG), Fördernummer: LA 1325/5-1, gefördert.

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