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Functional Magnetic Resonance Spectroscopic Imaging of the Mouse Brain: Overcoming Current Sensitivity Limitations

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Functional Magnetic Resonance Spectroscopic Imaging of the Mouse Brain: Overcoming Current Sensitivity Limitations Research Collection Doctoral Thesis Functional magnetic resonance spectroscopic imaging of the mouse brain: overcoming current sensitivity limitations Author(s): Seuwen, Aline Publication Date: 2015 Permanent Link: https://doi.org/10.3929/ethz-a-010579480 Rights / License: In Copyright - Non-Commercial Use Permitted This page was generated automatically upon download from the ETH Zurich Research Collection. For more information please consult the Terms of use. ETH Library DISS. ETH NO. 23040 Functional magnetic resonance spectroscopic imaging of the mouse brain: overcoming current sensitivity limitations. A thesis submitted to attain the degree of DOCTOR OF SCIENCES of ETH ZURICH (Dr. sc. ETH Zurich) presented by ALINE SEUWEN Master of Science in physics (M Sc), University of Basel born on 22.04.1985 citizen of France accepted on the recommendation of Prof. Dr. Markus Rudin, examiner Prof. Dr. Rolf Gruetter, co-examiner Dr. Anke Henning, co-examiner 2015 1 Contents: List of abbreviations-----------------------------------------------------------------------------------------------4 Summary-------------------------------------------------------------------------------------------------------------6 Zusammenfassung--------------------------------------------------------------------------------------------------8 1 Introduction ---------------------------------------------------------------------------------------------------------- 12 Noninvasive imaging in mice: high demands on spatial resolution and sensitivity --------------------- 13 In vivo proton magnetic resonance spectroscopy: the sensitivity challenge ----------------------------- 13 Hardware optimization to improve signal-to-noise ratio in MR spectroscopy --------------------------- 14 Data acquisition strategies to increase sensitivity in 1H-MRS ------------------------------------------------ 17 Potential and issues of MRS at high magnetic field strength ------------------------------------------------- 22 The neurochemical profile as indicator of brain function ----------------------------------------------------- 23 2 Objectives and outlines -------------------------------------------------------------------------------------------- 28 3 A four-element cryogenic phased array receive only RF probe for mouse MR imaging and spectroscopy ------------------------------------------------------------------------------------------------------------- 32 Introduction--------------------------------------------------------------------------------------------------------------- 33 Theoretical Background ------------------------------------------------------------------------------------------------ 34 Materials and Methods ------------------------------------------------------------------------------------------------ 38 Results ---------------------------------------------------------------------------------------------------------------------- 39 Discussion ----------------------------------------------------------------------------------------------------------------- 45 Outlook -------------------------------------------------------------------------------------------------------------------- 47 4 High resolution spectroscopic imaging in mice using a cryogenic receive-only phased array coil ------------------------------------------------------------------------------------------------------------------------- 50 Introduction--------------------------------------------------------------------------------------------------------------- 51 Materials and methods ------------------------------------------------------------------------------------------------ 52 Results ---------------------------------------------------------------------------------------------------------------------- 54 Discussion ----------------------------------------------------------------------------------------------------------------- 56 2 5 Metabolic changes assessed by MRS accurately reflect brain function during drug-induced epilepsy in mice in contrast to fMRI-based hemodynamic readouts. ------------------------------------ 60 Introduction--------------------------------------------------------------------------------------------------------------- 61 Material and methods -------------------------------------------------------------------------------------------------- 62 Results ---------------------------------------------------------------------------------------------------------------------- 65 Discussion ----------------------------------------------------------------------------------------------------------------- 72 6 Functional SI: mapping glutamate and lactate levels in the mouse brain during electrical stimulation of the hind paw ----------------------------------------------------------------------------------------- 80 Introduction--------------------------------------------------------------------------------------------------------------- 81 Materials and methods ------------------------------------------------------------------------------------------------ 82 Results ---------------------------------------------------------------------------------------------------------------------- 84 Discussion ----------------------------------------------------------------------------------------------------------------- 90 Discussion ---------------------------------------------------------------------------------------------------------------- 96 Conclusion and outlook -------------------------------------------------------------------------------------------- 104 Appendix: Standard Operating Procedure for Animal Preparation ---------------------------------- 108 Introduction------------------------------------------------------------------------------------------------------------- 109 Animal preparation protocol --------------------------------------------------------------------------------------- 110 Evaluation of quality and criteria for abortion of an experiment ------------------------------------------ 113 Animal recovery-------------------------------------------------------------------------------------------------------- 115 Discussion and conclusion ------------------------------------------------------------------------------------------- 116 Acknowledgments-----------------------------------------------------------------------------------------------120 CV------------------------------------------------------------------------------------------------------------------122 3 List of abbreviations 1H MRS Proton magnetic resonance spectroscopy Ala Alanine Asp Aspartate B0 Static (main) magnetic field B1 Transmit/receive filed BOLD Blood oxygenation level dependent (contrast) CBV Cerebral blood volume Cho Choline CNR Contrast to noise ratio Cr Creatine CRLB Cramer-Rao lower Bounds CRP Cryogenic coil CSDE Chemical shift displacement error FID Free induction decay FMRI Functional magnetic resonance imaging FMRS Functional magnetic resonance spectrscopy FMRSI Functional magnetic resonance spectrscopic imaging GABA ɣ-Aminobutyric acid Glc Glucose Gln Glutamine Glu Glutamate Glx Glutamate and Glutamine Ins Myo-Inositol Lac Lactate MRS Magnetic resonance spectroscopy NAA N-acetyl-aspartate OVS Outer volume suppression paCRP phased array receive only cryogenic coil PCh Phosphocholine PCr Phosphocreatine quadCRP qudrature transmit/receive cryogenic coil RF Radio Frequency ROI Region of interest SI Spectroscopic imaging SNR Signal to noise ratio SVS Single Voxel Spectroscopy Tau Taurine TE Echo Time totCre total Creatine (Cr+PCr) TR Repetition time VOI Volume of interest WS Water suppression ω0 Larmor frequency 4 5 Summary Proton Magnetic Resonance Spectroscopy (1H-MRS) serves to detect quantitative information about several neurotransmitters, general indicators of brain metabolism, and also certain antioxidants and osmolytes non-invasively. This technique is becoming increasingly important as a diagnostic tool in clinical routine, but also as a research tool for biomedical, pre-clinical research. Particularly when applied to mice, MRS represents a unique technique able to deliver spatially resolved information about brain biochemistry and function in various genetic models of neurological disorders available only in this species. However, MRS faces several technical challenges, mainly due to intrinsically low signal to noise ratio (SNR) and long measurement times. For measurements on mice, ultra-high field systems together with dedicated hardware and measurement techniques are required to overcome these difficulties. As a consequence, and despite the attractive possibilities of the technique, MRS and particularly Spectroscopic Imaging (SI) is not yet routinely applied in mice. In this thesis, we developed protocols for fast and reliable acquisition of highly resolved metabolite maps of the mouse brain. We used the first existing prototype of receive-only cryogenic coil array designed for the mouse brain. For very small objects, such as mice, the system noise is the dominant noise source in an MR experiment. Cooling down the receive coil to 30K using liquid Helium leads to significant noise reduction and therefore to an increased SNR by a factor of 2 to 3. This gain in SNR can generally be reinvested in higher temporal or spatial resolution for all kinds of MR experiments, and also for SI. In a second step, optimized experimental procedures and measurement techniques dedicated to SI on the mouse brain were implemented. Conventionally, an MRS measurement involves the formation of
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