Project

Discipline

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

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.

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Last update: 21.02.2013

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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.