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Magnetic Resonance Techniques to Investigate Human Brain Physiology: Acquisition and Postprocessing Tools to Advance Spectroscopy at Clinical and High Magnetic Fields

English title Magnetic Resonance Techniques to Investigate Human Brain Physiology: Acquisition and Postprocessing Tools to Advance Spectroscopy at Clinical and High Magnetic Fields
Applicant Kreis Roland
Number 135743
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 01.06.2011 - 30.11.2014
Approved amount 375'000.00
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All Disciplines (4)

Discipline
Neurophysiology and Brain Research
Biophysics
Pathophysiology
Biomedical Engineering

Keywords (6)

magnetic resonance spectroscopy; magnetic resonance imaging; methodology; quantitation; data processing; brain

Lay Summary (English)

Lead
Lay summary

Background:
Magnetic resonance imaging (MRI) and spectroscopy (MRS) on whole body MR scanners provide superb and extremely versatile tools to investigate human morphology, function and metabolism. MRS provides the only method to investigate the chemical composition of the human body non-invasively. MRS was delayed compared to MRI in its clinical impact, but higher field strengths (3T in the clinic and single 7T systems for research) are now available for MRS in humans, providing hardware that establishes a whole new basis for clinical MRS. Full exploitation of these technical ingredients will rely on dedicated re­search to enable de­tection and robust quantitation of metabolites that are of prime interest in the clinic and in neuroscience.

Overall Aims of this Project:

1) Data processing tools shall be developed to detect and quantify more brain metabolites than was possible before, in particular using dedicated multidimensional MR spectroscopy data arrays and extended simultanesous modelling of these datasets

2) Data acquisition methods shall be developed and tested that allow for easier detection of metabolite concentrations at high magnetic fields,  including metabolites with exchangeable protons using MRS methods without suppression of the water signal.

Methods:
H-MRS from previous work and mainly to be designed in this project.13 T and 7 T whole body MR systems (Siemens TIM TRIO, Philips Achieva), spectral simulation tools, data acquisition, processing and fitting schemes for quantitative clinical

Expected Value of the Proposed Project:

H-MRS in the clinical setting, as well as in dedicated neuroscience research performed with the highest field strengths currently available for humans in Switzerland. All main approaches, i.e. higher fields, MRS without water suppression, and data processing integrated with data acquisition, are expected to either enable non-invasive quantification of cerebral metabolites that had hitherto not been detectable in vivo, or - like in the case of GABA, glutamate, glutamine and GSH - to make them quantifiable simultaneously and in higher efficiency. We expect considerable impact on the potential of MRS for elucidation of the etiology of cerebral pathologies, for monitoring of treatment efficacy, but also in neuroscience research where neurotransmitter levels, in particular GABA, are connected more and more with psychiatric diseases, individuality and specific functional states. 1This proposal aims at substantially increasing the infor­ma­tion content of

Overall, improved data acquisition techniques and intricately connected data processing methods, as well as extended means of quantitation and quality control are expected to extend the range of routinely quantifiable metabolites and, hence, the scope of clinical applications in diagnosis and clinical research.

Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Clinical proton MR spectroscopy in central nervous system disorders.
Oz Gülin, Alger Jeffry R, Barker Peter B, Bartha Robert, Bizzi Alberto, Boesch Chris, Bolan Patrick J, Brindle Kevin M, Cudalbu Cristina, Dinçer Alp, Dydak Ulrike, Emir Uzay E, Frahm Jens, González Ramón Gilberto, Gruber Stephan, Gruetter Rolf, Gupta Rakesh K, Heerschap Arend, Henning Anke, Hetherington Hoby P, Howe Franklyn A, Hüppi Petra S, Hurd Ralph E, Kreis Roland, Kauppinen Risto A (2014), Clinical proton MR spectroscopy in central nervous system disorders., in Radiology, 270(3), 658-79.
Effects of beta-alanine supplementation and interval training on physiological determinants of severe exercise performance
Gross Micah A., Boesch Chris, Bolliger Christine Sandra, Norman Barbara, Gustafsson Thomas, Hoppeler Hans H., Vogt Michael (2014), Effects of beta-alanine supplementation and interval training on physiological determinants of severe exercise performance, in European Journal of Applied Physiology, 114(2), 221-234.
Magnetic resonance spectroscopy investigations of functionally defined language areas in schizophrenia patients with and without auditory hallucinations
Homan P, Vermathen P, van Swam C, Federspiel A, Boesch C, Strik W, Dierks T, Hubl D, Kreis R (2014), Magnetic resonance spectroscopy investigations of functionally defined language areas in schizophrenia patients with and without auditory hallucinations, in Neuroimage, 94, 23-32.
Magnetization exchange observed in human skeletal muscle by non-water-suppressed proton magnetic resonance spectroscopy.
Macmillan Erin L, Boesch Chris, Kreis Roland (2013), Magnetization exchange observed in human skeletal muscle by non-water-suppressed proton magnetic resonance spectroscopy., in Magnetic Resonance in Medicine, 70, 916-924.
Non-water-suppressed proton MR spectroscopy improves spectral quality in the human spinal cord.
Hock Andreas, MacMillan Erin L, Fuchs Alexander, Kreis Roland, Boesiger Peter, Kollias Spyros S, Henning Anke (2013), Non-water-suppressed proton MR spectroscopy improves spectral quality in the human spinal cord., in Magnetic Resonance in Medicine, 69(5), 1253-1260.
On the use of Cramér-Rao minimum variance bounds for the design of magnetic resonance spectroscopy experiments.
Bolliger Christine S, Boesch Chris, Kreis Roland (2013), On the use of Cramér-Rao minimum variance bounds for the design of magnetic resonance spectroscopy experiments., in NeuroImage, 83, 1031-1040.
Chaper 40, 1H-Magnetic Resonance Spectroscopy of cerebral phenylalanine content and its transport at the blood-brain barrier.
Kreis R (2012), Chaper 40, 1H-Magnetic Resonance Spectroscopy of cerebral phenylalanine content and its transport at the blood-brain barrier., in Choi I-Y (ed.), Springer, New York, 1117-1134.
The need for updates of spin system parameters, illustrated for the case of γ-aminobutyric acid.
Kreis Roland, Bolliger Christine Sandra (2012), The need for updates of spin system parameters, illustrated for the case of γ-aminobutyric acid., in NMR in Biomedicine, 25(12), 1401-1403.

Collaboration

Group / person Country
Types of collaboration
Institut Biomedizinische Technik, ETH & University Zurich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Max-Planck-Institut für biologische Kybernetik, Tübingen Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
2nd TRANSACT Workshop on “Quality Issues in Clinical MR Spectroscopy” Talk given at a conference Potential effects of superficial fat on metabolite concentrations determined by water referencing 16.06.2014 Bern, Switzerland Adalid Lopez Victor; Fichtner Nicole Damara; Kreis Roland;
2nd TRANSACT Workshop on “Quality Issues in Clinical MR Spectroscopy” Talk given at a conference Quality criteria, artefacts and variabilities in clinical MRS 16.06.2014 Bern, Switzerland Kreis Roland;
2nd TRANSACT Workshop on “Quality Issues in Clinical MR Spectroscopy” Poster Pitfalls with quantification references 16.06.2014 Bern, Switzerland Kreis Roland;
22nd Annual Meeting of the International Society of Magnetic Resonance in Medicine & 30th Annual Meeting of ESMRMB Poster Optimisation of asymmetric adiabatic pulses for single voxel metabolite cycled 1H-MRS in the human brain at 9.4 Tesla 10.05.2014 Milan, Italy Kreis Roland;
GCB Students' Symposium 2014 Poster Tikhonov Regularized Lineshape Deconvolution for 2DJ Maximum-Echo-Sampled Magnetic Resonance Spectra 29.01.2014 Bern, Switzerland Adalid Lopez Victor;
Joint Meeting of the Swiss Society for Neuroscience and the Clinical Neuroscience Bern Poster Magnetic resonance spectroscopy investigations of functionally defined language areas in schizophrenia 24.01.2014 Bern, Switzerland Kreis Roland;
Joint Meeting of the Swiss Society for Neuroscience and the Clinical Neuroscience Bern Poster Improving robustness of brain GABA measurements in human brain 24.01.2014 Bern, Switzerland Kreis Roland;
21st Annual Meeting of the International Society of Magnetic Resonance in Medicine Poster Extended metabolite profile of the human spinal cord 20.04.2013 Salt Lake City, United States of America Kreis Roland; MacMillan Erin Leigh;
21st Annual Meeting of the International Society of Magnetic Resonance in Medicine Poster Water proton relaxation times exhibit muscle fibre orientation dependence, while water to creatine magnetization transfer rates do not 20.04.2013 Salt Lake City, United States of America Kreis Roland; Bolliger Christine; MacMillan Erin Leigh;
GCB Students' Symposium 2013 Poster Experimental Verification of Improved Acquisition Strategies for 2D MR Spectroscopy Using Bootstrapping 30.01.2013 Bern, Switzerland Bolliger Christine;
29th Annual Meeting of the European Society of Magnetic Resonance in Medicine and Biology Talk given at a conference High spectral quality for a reliable detection of an extended metabolite profile in the human spinal cord 04.10.2012 Lissabon, Portugal MacMillan Erin Leigh; Kreis Roland;
20th Annual Meeting of the International Society of Magnetic Resonance in Medicine Poster GABA editing without water suppression 05.05.2012 Melbourne, Australia Boesch Chris; MacMillan Erin Leigh; Kreis Roland; Bolliger Christine;
20th Annual Meeting of the International Society of Magnetic Resonance in Medicine Poster Optimizing 2DJ experiments using Cramer Rao minimum variance bounds. 05.05.2012 Melbourne, Australia Boesch Chris; Bolliger Christine; Kreis Roland;
20th Annual Meeting of the International Society of Magnetic Resonance in Medicine Talk given at a conference 1H MRS in the human spinal cord at 7T using a combined RF shimming and travelling wave transmit approach 05.05.2012 Melbourne, Australia MacMillan Erin Leigh;
20th Annual Meeting of the International Society of Magnetic Resonance in Medicine Talk given at a conference Scyllo-Inositol Detection in the Human Spinal Cord 05.05.2012 Melbourne, Australia Kreis Roland; MacMillan Erin Leigh;
20th Annual Meeting of the International Society of Magnetic Resonance in Medicine Talk given at a conference Clinical MRS: Promise, Potential, Power and Pitfalls 05.05.2012 Melbourne, Australia, Australia Kreis Roland;
20th Annual Meeting of the International Society of Magnetic Resonance in Medicine Poster MR spectroscopy in the spinal cord of patients with traumatic injuries. 05.05.2012 Melbourne, Australia Boesch Chris; Kreis Roland; MacMillan Erin Leigh;
20th Annual Meeting of the International Society of Magnetic Resonance in Medicine Poster Magnetization transfer effects from water to metabolites in human skeletal muscle observed by non-water-suppressed MR spectroscopy 05.05.2012 Melbourne, Australia Boesch Chris; Kreis Roland; MacMillan Erin Leigh;
GCB Students' Symposium 2012 Poster Magnetization Transfer Effects from Water to Metabolites in Human Skeletal Muscle Observed by Non-Water-Suppressed Magnetic Resonance Spectroscopy 01.02.2012 Bern, Switzerland MacMillan Erin Leigh;
7th Annual Meeting of the Clinical Neuroscience Bern Talk given at a conference Optimizing two-dimensional magnetic resonance spectroscopy experiments for the quantification of GABA and other metabolites in human brain 22.11.2011 Bern, Switzerland Bolliger Christine; Kreis Roland;
28th Annual Meeting of the European Society of Magnetic Resonance in Medicine and Biology Talk given at a conference Generalizing the 2DJ experiment for optimal simultaneous detection of a set of metabolites 06.10.2011 Leipzig, Germany Boesch Chris; Bolliger Christine; Kreis Roland;
28th Annual Meeting of the European Society of Magnetic Resonance in Medicine and Biology Poster Metabolite cycled proton MR spectroscopy enables coherent signal averaging in the human spinal cord at 3T 06.10.2011 Leipzig, Germany Kreis Roland; MacMillan Erin Leigh;
28th Annual Meeting of the European Society of Magnetic Resonance in Medicine and Biology Talk given at a conference Simultaneous up- and downfield spectroscopy using SPECIAL at 7T 06.10.2011 Leipzig, Germany Kreis Roland;


Self-organised

Title Date Place

Knowledge transfer events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
School of MRI, Course on Advanced Neuro Imaging: Diffusion, Perfusion, Spectroscopy Talk 17.10.2013 Split, Croatia
School of MRI, Course on Advanced Neuro Imaging: Diffusion, Perfusion, Spectroscopy Talk 25.10.2012 Antwerpen, Belgium
School of MRI, Course on Advanced Neuro Imaging: Diffusion, Perfusion, Spectroscopy Talk 08.09.2011 Cambridge, Great Britain and Northern Ireland


Communication with the public

Communication Title Media Place Year
Talks/events/exhibitions Nacht der Forschung German-speaking Switzerland 2014

Awards

Title Year
Trainee Stipend, ISMRM, 2012 2012
Fellow of the European Society for Magnetic Resonance in Medicine and Biology 2012

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)
149779 Multi-nuclear magnetic resonance spectroscopy (MRS) and imaging (MRI) on a clinical whole-body MR-system: Lipid organelles and mitochondria 01.12.2013 Project funding (Div. I-III)
116400 Computational analysis and design of RF arrays for human high-field MRI 01.09.2007 Project funding (Div. I-III)
132935 Multi-nuclear magnetic resonance spectroscopy (MRS) and imaging (MRI) on a clinical whole-body MR-system: insulin resistance, ageing, and physical activity 01.12.2010 Project funding (Div. I-III)
127359 Formal thought disorder: Pathophysiology and its implication for specific treatment 01.05.2010 Project funding (Div. I-III)
120324 Magnetic Resonance Techniques to Investigate Human Brain Physiology: Novel Acquisition and Processing Methods to Extend the Scope and Robustness of Clinical Spectroscopy at High Magnetic Fields 01.04.2008 Project funding (Div. I-III)

Abstract

Background: Magnetic resonance imaging (MRI) and spectroscopy (MRS) on whole body MR scanners provide superb and extremely versatile tools to investigate human morphology, function and metabolism. MRS provides the only method to investigate the chemical composition of the human body non-invasively. MRS was delayed compared to MRI in its clinical impact. But higher field strengths (3T in the clinic and single 7T systems for research) are now available for MRS in humans. Together with multiple coil technology and rapid gradients, this now provides a whole new basis for clinical MRS. Full exploitation of these technical ingredients will rely on dedicated research to enable detection and robust quantitation of metabolites that are of prime interest in the clinic and in neuroscience. Working Hypothesis: New MR hardware (in particular 3 and 7 T whole body magnets) in combination with novel methodology, in particular dedicated acquisition strategies and integrated data processing of arrays of interrelated datasets, as well as MRS without water suppression boosts the potential for MRS to accurately quantify many brain metabolites simultaneously that are relevant in health and disease, e.g neurotransmitters (GABA, glutamate) and antioxidants (GSH, ascorbate). Specific Aims:A1.Integrated acquisition and postprocessing: Develop postprocessing and fitting tools that allow simultaneous modeling of complementary data obtained from different MR methods and design improved methods based on modeling results. A2.Extended set of observable metabolites at 3 and 7 T: Design and improve methods for detection of more biochemically and clinically relevant metabolites beyond the current routine observables, including metabolites with exchangeable protons.In A1, we aim at improving the effective sensitivity of MRS by combining complementary information in data processing and thereby at increasing the information yield per acquisition time period, e.g spectra manipulated with editing pulses or obtained with different echo times combined with lineshape or stability information. Secondly, the use of integrated processing allows for innovative new acquisition strategies. In A2, we strive at obtaining unprecedented metabolic information based on novel acquisition schemes, inclusion of the water signal and of exchangeable protons as source of information, and based on benefits from highest magnetic fields and RF technology.Methods: Existing hardware:state of the art 3 T and 7 T whole body MR systems and newly developed field probes.Existing software: MR spectral simulation tool GAVA; FiTAID, a general model fitting tool for arrays of interdependent datasets, as initiated in the precursor project; initial schemes for MRS without water saturation. Target methods: novel MR acquisition techniques and processing methods to detect and quantify relevant brain metabolites in a sensitive and robust way are being developed in this proposal.Expected Value of the Proposed Project: This proposal aims at substantially increasing the information content of 1H-MRS in the clinical setting, as well as in dedicated neuroscience research performed with the highest field strengths currently available for humans in Switzerland. All main approaches, i.e. higher fields, MRS without water suppression, and data processing integrated with data acquisition, are expected to either enable non-invasive quantification of cerebral metabolites that had hitherto not been detectable in vivo, or - like in the case of GABA, glutamate, glutamine and GSH - to make them quantifiable simultaneously and in higher efficiency. We expect considerable impact on the potential of MRS for elucidation of the etiology of cerebral pathologies, for monitoring of treatment efficacy, but also in neuroscience research where neurotransmitter levels, in particular GABA, are connected more and more with psychiatric diseases, individuality and functional states including the resting state network. GABA has also been implicated as essential mediator for the effects of transcranial magnetic stimulation and hence the potential to induce cortical plasticity. The novel tools aim at general quantification of metabolites of prime physiologic interest, while retaining information on routinely observable surrogate markers of glial and neuronal metabolism with best MR detectability. In addition, determination of cell-specific pH or water exchange rates can be of cardinal importance in patient treatment (e.g. stroke, radiation therapy of tumors). Overall, improved data acquisition techniques and intricately connected data processing methods, as well as extended means of quantitation and quality control are expected to extend the range of routinely quantifiable metabolites and, hence, the scope of clinical applications in diagnosis and clinical research. Independently, the use of MR scanners of high fields will pave the way for further extension of the use of MRS in specific neuroscience research applications and subsequently for resolution of specific clinical questions.
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