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Metabolic Fingerprints from Magnetic Resonance: Levels, Maps, and Microstructure

English title Metabolic Fingerprints from Magnetic Resonance: Levels, Maps, and Microstructure
Applicant Kreis Roland
Number 175984
Funding scheme Project funding (Div. I-III)
Research institution Abt. Magnetresonanz-Spektroskopie u. Method. Departement für Klinische Forschung Universität Bern
Institution of higher education University of Berne - BE
Main discipline Neurophysiology and Brain Research
Start/End 01.12.2017 - 30.11.2021
Approved amount 700'000.00
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All Disciplines (4)

Discipline
Neurophysiology and Brain Research
Endocrinology
Physiology : other topics
Biophysics

Keywords (14)

brain; lipids; magnetic resonance spectroscopy; metabolic imaging; magnetic resonance imaging; methodology; obesity; diffusion; neurotransmitters; depression; diurnal variation; microstructure; sleep; skeletal muscle

Lay Summary (German)

Lead
Magnet Resonanz (MR) ist die Basis für die vielseitigste Technik, um Eigenschaften von Molekülen und Geweben in verschiedensten Wissenschafts-Gebieten, wie der Chemie, Physik, Biologie und Medizin zu untersuchen. In der Form von MR Bildgebung (MRI oder MRT) bewährt sich diese Methodik als das vielseitigste Verfahren, das ganz ohne Eingriffe oder schädliche Strahlung auskommt, um Schnittbilder des Körpers, vor allem der Weichteile, anzufertigen. Die MR Spektroskopie (MRS) ist eine Technik, die es erlaubt mit den gleichen Instrumenten die chemische Zusammensetzung von Organen - wiederum eingriffsfrei - zu bestimmen. Diese chemische Information kann zur Untersuchung von grundlegenden Stoffwechselvorgängen oder zur Erforschung von Veränderungen bei verschiedenen Krankheiten verwendet werden. Auch im Einzelpatienten kann MRS zur Diagnose oder zur Beurteilung des Erfolgs einer Behandlung eingesetzt werden.
Lay summary

Inhalt und Ziele des Forschungsprojekts

Obwohl die MR Technik schon anfangs der 90er Jahre in der Medizin weitläufig Einzug gehalten hat, werden auch jetzt noch stetig grundlegende Weiterentwicklungen in den Apparaturen und in den Techniken, wie diese Methodik eingesetzt und verbessert werden können, erzielt.  Höhere Magnetfelder, stärkere Gradientenfelder und multiple Detektoren sind dabei einige der Hauptattraktionen der letzten Jahre, die es erlauben, Bilder immer schneller und mit höherer Auflösung, sowie mit ganz speziellen und anwendungs-spezialisierten Kontrasten aufzunehmen und auch weitere Eigenschaften von bestimmten Molekülen zuverlässiger zu bestimmen. Vor allem zum letzten Punkt soll dieses Forschungsprojekt beitragen.
Es befasst sich als erstes mit Verbesserungen in der Methodik von MR Spektroskopie, so wie sie heute in der Klinik angewendet wird. Damit sollen genauere und zuverlässigere Daten erhoben werden können und auch Gewebskonzentrationen von Molekülen erfasst werden können, die heute noch nicht messbar sind. Andererseits dreht sich das Projekt auch um Erweiterungen der MRS, die es erlauben die Moleküldiffusion, also die mikroskopische Bewegung von Molekülen in spezifischen Geweben, zu nutzen und zu beurteilen. Dazu werden in Zusammenarbeiten mit Forschungsinstitutionen in Zürich und Leipzig, neuste und einzigartige MR Scanner mit sehr starken Gradientenfeldern genutzt.  Auch MR Spektroskopie Methoden, die auf höheren Magnetfeldern beruhen als sie heute in der Klinik stehen, werden weiterentwickelt, um genauere chemische Analysen erlauben zu können. Des Weiteren zielt das Projekt auch auf einige konkrete Anwendungen im Bereich der Erforschung des Schlafs, psychischer Erkrankungen und des Diabetes.

Wissenschaftlicher und gesellschaftlicher Kontext des Forschungsprojekts

MR Untersuchungen sind zwar teuer, aber erlauben häufig auch sehr genaue Diagnosen und die nicht-invasive Beurteilung der Wirksamkeit diverser Therapien, was dann sehr wohl kostensparend wirkt.  Der Grossteil der beabsichtigten Forschung ist zwar Grundlagenforschung und kann deshalb nicht direkt mit einem konkreten sicheren gesellschaftlichen Gewinn verbunden werden. Basierend auf den Erfahrungen in den letzten 20 bis 30 Jahren im Gebiet der medizinischen MR Technologie kann aber klar behauptet werden, dass auch dieses Projekt grosse Chancen hat, diagnostische und basiswissenschaftliche Fortschritte für die Behandlung von Patienten zu liefern. Diese werden das Verständnis von Stoffwechselvorgängen im Allgemeinen und im einzelnen Patienten fördern und so zu verbesserter Diagnostik und Behandlungsmöglichkeiten beitragen.

Direct link to Lay Summary Last update: 10.11.2017

Responsible applicant and co-applicants

Employees

Project partner

Publications

Publication
Non‐water‐excitation MR spectroscopy techniques to explore exchanging protons in human brain at 3 T
Dziadosz Martyna, Bogner Wolfgang, Kreis Roland (2020), Non‐water‐excitation MR spectroscopy techniques to explore exchanging protons in human brain at 3 T, in Magnetic Resonance in Medicine, 84, 2352-2363.
Parameterization of metabolite and macromolecule contributions in interrelated MR spectra of human brain using multidimensional modeling
Hoefemann Maike, Bolliger Christine Sandra, Chong Daniel G.Q., Veen Jan Willem, Kreis Roland (2020), Parameterization of metabolite and macromolecule contributions in interrelated MR spectra of human brain using multidimensional modeling, in {NMR} in Biomedicine, 33(9), e4328.
Preprocessing, analysis and quantification in single‐voxel magnetic resonance spectroscopy: experts' consensus recommendations
Near Jamie, Harris Ashley D., Juchem Christoph, Kreis Roland, Marjańska Małgorzata, Öz Gülin, Slotboom Johannes, Wilson Martin, Gasparovic Charles (2020), Preprocessing, analysis and quantification in single‐voxel magnetic resonance spectroscopy: experts' consensus recommendations, in {NMR} in Biomedicine, e4257.
Proton magnetic resonance spectroscopy in skeletal muscle: Experts' consensus recommendations
Krššák Martin, Lindeboom Lucas, Schrauwen-Hinderling Vera, Szczepaniak Lidia S., Derave Wim, Lundbom Jesper, Befroy Douglas, Schick Fritz, Machann Jürgen, Kreis Roland, Boesch Chris (2020), Proton magnetic resonance spectroscopy in skeletal muscle: Experts' consensus recommendations, in {NMR} in Biomedicine, e4266.
Terminology and concepts for the characterization of in vivo MR spectroscopy methods and MR spectra: Background and experts' consensus recommendations
Kreis Roland, Boer Vincent, Choi In-Young, Cudalbu Cristina, Graaf Robin A., Gasparovic Charles, Heerschap Arend, Krššák Martin, Lanz Bernard, Maudsley Andrew A., Meyerspeer Martin, Near Jamie, Öz Gülin, Posse Stefan, Slotboom Johannes, Terpstra Melissa, Tkáč Ivan, Wilson Martin, Bogner Wolfgang (2020), Terminology and concepts for the characterization of in vivo MR spectroscopy methods and MR spectra: Background and experts' consensus recommendations, in {NMR} in Biomedicine, e4347.
Magnetic resonance spectroscopy extended by oscillating diffusion gradients: Cell-specific anomalous diffusion as a probe for tissue microstructure in human brain.
DöringAndré, KreisRoland (2019), Magnetic resonance spectroscopy extended by oscillating diffusion gradients: Cell-specific anomalous diffusion as a probe for tissue microstructure in human brain., in Neuroimage, 202, 116075.
Optimizing acquisition and fitting conditions for 1 H MR spectroscopy investigations in global brain pathology
Hoefemann Maike, Adalid Victor, Kreis Roland (2019), Optimizing acquisition and fitting conditions for 1 H MR spectroscopy investigations in global brain pathology, in {NMR} in Biomedicine, 32(11), e4161.
Deep learning approaches for detection and removal of ghosting artifacts in MR spectroscopy.
SP Kyathanahally, A Döring, R Kreis (2018), Deep learning approaches for detection and removal of ghosting artifacts in MR spectroscopy., in Magnetic resonance in medicine, 80, 851-863.
Diffusion-weighted magnetic resonance spectroscopy boosted by simultaneously acquired water reference signals.
A Döring, V Adalid, C Boesch, R Kreis (2018), Diffusion-weighted magnetic resonance spectroscopy boosted by simultaneously acquired water reference signals., in Magnetic resonance in medicine, 80(6), 2326-2338.

Collaboration

Group / person Country
Types of collaboration
Dr. Jan Willem van der Veen / NIH United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Prof Everts/ Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Prof. Klaas Prüssmann/ETH Zürich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Prof. Claudio Bassetti / Neurologische Klinik, Universitätsspital Bern Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Prof Anke Henning/Max-Planck-Institute für biologische Kybernetik Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
Prof. Harald Möller/Max-Planck-Institut für Kognitions- und Neurowissenschaften Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Prof. Emanuel Christ/Universitätsklinik Basel Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
28th Meeting of the ISMRM Talk given at a conference Investigation of potential effects of sleep on diffusion characteristics of metabolites and water: initial results 08.08.2020 Virtual Meeting, United States of America Kreis Roland; Döring André; Bassetti Claudio L.;
28th Meeting of the ISMRM Talk given at a conference Diffusion-weighted MRS at short TE using a Connectom system: non-Gaussian metabolite diffusion and macromolecular signals in human brain. 08.08.2020 Virtual Meeting, United States of America Döring André; Simsek Kadir; Moeller Harald; Kreis Roland;
28th Meeting of the ISMRM Poster A non-water-excitation MRS sequence with zero-echo time to investigate exchangeable moieties in the human brain at 3T. 08.08.2020 Virtual Meeting, United States of America Kreis Roland; Dziadosz Martyna;
28th Meeting of the ISMRM Talk given at a conference Quantification of phenylalanine with 1H MRS using optimized acquisition conditions and downfield background modelling 08.08.2020 Virtual Meeting, United States of America Höfemann Maike; Kreis Roland; Slotboom Johannes;
28th Meeting of the ISMRM Talk given at a conference Combining CEST and 1H MR Spectroscopy for simultaneous determination of metabolite concentrations and effects of magnetization exchange. 08.08.2020 Virtual Meeting, United States of America Höfemann Maike; Döring André; Kreis Roland;
23rd Swiss Symposium on NMR Spectroscopy Talk given at a conference Diffusion-Weighting for in vivo Spectroscopy. 14.01.2020 Geneva, Switzerland Kreis Roland;
27th Meeting of the ISMRM Poster Towards probing diffusion barriers for water and metabolites in skeletal muscle by MR spectroscopy using oscillating and pulsed diffusion gradients with a large range of diffusion times. 11.05.2019 Montreal, Canada Kreis Roland; Simsek Kadir; Döring André;
27th Meeting of the ISMRM Talk given at a conference Novel methods to record MR spectra in human brain without suppressing or exciting the water signal to investigate exchange-sensitive protons. 11.05.2019 Montreal, Canada Kreis Roland; Dziadosz Martyna; Döring André;
27th Meeting of the ISMRM Talk given at a conference MRS extended by oscillating diffusion gradients as a probe for investigation of human brain tissue microstructure. 11.05.2019 Montreal, Canada Kreis Roland; Döring André;
27th Meeting of the ISMRM Poster Detection of NAD+ in human brain is possible even at 3T and in spite of water pre-saturation when using a large voxel size 11.05.2019 Montreal, Canada Kreis Roland; Höfemann Maike;
27th Meeting of the ISMRM Talk given at a conference About the need for a comprehensive description of the macromolecular baseline signal for MR fingerprinting and multidimensional fitting of MR spectra. 11.05.2019 Montreal, Canada Kreis Roland; Höfemann Maike;
Minerva-Gentner Symposium on MR Spectroscopy & Molecular Imaging Talk given at a conference Quality assessments in clinical MRS: of men and machine. 18.02.2019 Rehovot, Israel Kreis Roland;
MRS Workshop 2018: Metabolic Imaging, Talk given at a conference Simultaneous fitting of the individual spectra recorded by multichannel receive arrays in 1H MRS investigations of global brain pathology. 03.10.2018 Utrecht, Netherlands Höfemann Maike; Kreis Roland;
Joint 26th Meeting of ISMRM and 35th Meeting of the ESMRMB Talk given at a conference Automatic removal of ghosting artifacts from mr spectra using deep learning 16.06.2018 Paris, France Kreis Roland; Döring André;
Joint 26th Meeting of ISMRM and 35th Meeting of the ESMRMB Poster Estimation of T2 Relaxation Times of Downfield Peaks in Human Brain at 9.4 T 16.06.2018 Paris, France Kreis Roland; Henning Anke;
Joint 26th Meeting of ISMRM and 35th Meeting of the ESMRMB Poster On the exploitation of slow macromolecular diffusion for baseline estimation in MR spectroscopy using 2D simultaneous fitting. 16.06.2018 Paris, France Kreis Roland; Döring André;
Joint 26th Meeting of ISMRM and 35th Meeting of the ESMRMB Poster What is the optimal ROI size for single voxel MRS in global brain pathology? 16.06.2018 Paris, France Höfemann Maike; Kreis Roland;


Knowledge transfer events

Active participation

Title Type of contribution Date Place Persons involved
Proton MR Spectroscopy in Neuroradiological Diagnostics Talk 23.02.2018 Tübingen, Germany Kreis Roland;


Associated projects

Number Title Start Funding scheme
156952 Magnetic resonance techniques to determine metabolite levels: extending scope and clinical robustness 01.12.2014 Project funding (Div. I-III)
170062 The aging mitochondria, dynamic and protective adaptations of exercise 01.12.2016 Project funding (Div. I-III)
188142 Accessing living human brain microstructure by diffusion-weighted MR spectroscopy with ultra-strong gradients 01.10.2019 Early Postdoc.Mobility

Abstract

BackgroundMagnetic resonance imaging (MRI) and spectroscopy (MRS) provide non-invasive modalities to explore human morphology, function and metabolism. MRS is widespread as biomedical research tool to investigate chemical fingerprints of human physiology in health and disease. Clinical applications still lag behind for lack of a simple push-button tool and limited robustness. In research on the other hand, applications abound while progress is far from complete. It relies on dedicated explorations using the latest technological advances in MR hardware and methodology, but also on specific step-by-step optimization of existing methods under the aspect of specific metabolic imaging targets. Ultra-high magnetic fields (UHF, 7-9.4T) provide the arena to overcome previous limitations in signal-to-noise, while ultra-strong gradient (USG) systems are now available to obliterate previous limits in diffusion-related techniques. In addition, techniques like exchange saturation transfer (CEST) MRI and relaxation enhancement MRS extend the range of metabolites of high clinical interest, while using an interplay of optimized acquisition and processing algorithms promises pushing into the micromolar range. The novel methods will immediately be applied to address diverse crucial open issues in human physiology: 1) Neurotransmitter levels, like GABA, glutamate come into focus for non-invasive mapping by MR in humans. 2) Accumulation of ectopic lipids in diabetes and obesity, where it is of prime interest to distinguish between beneficial and detrimental lipid accrual. 3) Physiology of sleep and diurnal homeostasis, where invasive animal data suggests a major role for sleep in detoxification and initial cardiac studies show changes in ectopic lipd levels.Working HypothesesA) “Use of forefront technology and methods” and B) “Optimization of all steps in state-of-the-art methodology” are two paths that lead in this project to substantial lowering of the detection thresholds for metabolite levels in humans.C) Seminal findings with wide-ranging consequences will emerge from application of the developed techniques for distinct applications in the context of neurophysiology and ectopic lipids. Methods & Expected ResultsForefront technology and a collaboration network at five prime MR research sites allow the use and combination of pioneering UHF and USG systems with sophisticated acquisition and processing methods, as well as a unique constellation of know-how, including field probes and optical devices for measurement stabilization, non-water-suppressed sequences for signal enhancement, as well as specialized expertise on MR technology, spectral fitting, as well as sleep physiology, ectopic lipids and serotonin disorders.Expected Value of the Proposed ProjectThe proposal aims at extending methodology towards more sensitive and robust MRS and metabolic imaging on one side and at novel uses in physiology and medicine on the other. The use of forefront methodology will pave the way for further technical innovation, but also provides results that can be used on clinical systems. The specific applications promise to provide groundbreaking new findings themselves. In particular, any means to further characterize diurnal homeostasis and sleep physiology may have substantial impact in neurodegeneration research. In addition,lipid droplet size may become a crucial parameter to judge the interplay of ectopic fat deposition, insulin resistance and benefits from exercise training and specific diets.
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