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In vivo MRI

Research group 8.12

In vivo MR spectroscopy

In vivo proton MR spectroscopy aims at the non-invasive, quantitative determination of metabolite concentrations in brain. Using PTB´s 3 tesla tomograph methods are being developed for measuring MR spectra with high spectral resolution, precise regional selectivity and large signal-to-noise ratio, that can be acquired in a short measuring time. Besides optimization of conventional procedures novel approaches are pursued permitting to unearth analytes hitherto hardly detectable, also by making use of the unprecedented signal-to-noise ratio and spectral resolution achievable at 7 Tesla.

3-T-PRESS spectra acquired at 30 ms and 80 ms echo time Metabolite determination using SPECIAL (SPin ECho full Intensity Acquired Localized): Spectrum (Orig) from the anterior cingulum and fit results for 13 metabolites


In close collaboration with the group for Data Analysis and Measurement Uncertainty (8.42) methods for the evaluation of in vivo MR spectra are developed that allow for the quantification of metabolite concentrations in mmol per liter or per kg of tissue with low uncertainty.

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  • Development and optimization of pulse sequences; novel sequences for the detection of coupled resonances; application of 8-channel transmit array for MRS in deliberately shaped voxels to improve anatomical selectivity

  • Application of phased array surface coils for sensitivity and localization enhancement; testing of novel coil arrays for other nuclei, eg 31P and 7Li

  • Development of novel fitting methods for in vivo MR spectra involving complex background treatment and uncertainty budgeting; quantification of metabolite concentrations

  • Testing, validation and application of novel methods for steady-state and functional MRS in approved studies of patients and healthy control subjects together with clinical partners

  • MRS on the 7 T whole-body human MR scanner at the Opens external link in new windowB.U.F.F. in Berlin-Buch

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  • Implementation of functional MRS at 7 Tesla: Quantification of metabolic changes in response to an alternating visual paradigm.

    Alternating stimulation of the visual hemifields decreases gamma-aminobutyric acid (GABA) and raises lactate in the activated voxel. Measurements were performed using a two-channel transmit-receive coil for the occipital cortex developed in-house.

  • Neurochemical profiling at 7 Tesla: MRS in cerebral orphan diseases. Glutamate und taurine in Mitochondrial Membrane Protein-Associated Neurodegeneration (MPAN) are significantly enhanced compared to heterozygotes and healthy volunteers.

    Example MR spectrum from white matter in MPAN using SPECIAL at 7 T and deduced concentrations of glutamate (Glu) and taurine (Tau).

  • Shaped voxel spectroscopy (SHAVE) using parallel excitation in human brain to minimize partial volume effects.

    In vivo MR spectrum acquired from an anatomically shaped, white-matter only voxel (insert) excited using SHAVE (8-channel transmit array). The insert shows the actually excited magnetization (left, with blue background) and the respective target voxel (right, superimposed on a localizer scan).

  • Time domain-frequency domain fitting procedure MRFit for evaluation of MR spectra considering background contributions and model spectra from tissue-mimicking metabolite phantoms; novel uncertainty concept including uncertainty of background fitting (8.42) 

    Relative uncertainties (means of 10 in vivo spectra) of spectra evaluation using MRFit with and without consideration of background fit uncertainty. Conventional methods like Cramér-Rao lower bounds underestimate measurement uncertainty.

  • Optimization of point resolved spectroscopy for detection of the neurotransmitter L-glutamate, implementation of a double quantum filter sequence for glutamate determination, quantification of glutamate and estimation of glutamine in cortical brain regions (cingulate gyrus, hippocampus, prefrontal cortex) of healthy controls for setting up a database for the study of psychiatric diseases (collaboration with Opens external link in new window Charité Universitätsmedizin Berlin, Opens external link in new windowMax Planck Institute for Human Development)

    Age dependence of glutamate concentration in anterior cingulate (ACC) and hippocampus (HC) (n = 118) and of glutamine concentration in ACC (n = 79)

  • Clinical study: MR spectroscopy in multiple sclerosis (MS), together with Jewish Hospital Berlin

    MR spectra from a lesion and from normal appearing white matter (NAWM) of an MS patient

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Selected references

F. Schubert, S. Kühn, J. Gallinat, R. Mekle, B. Ittermann
Towards a neurochemical profile of the amygdala using short-TE 1 H magnetic resonance spectroscopy at 3 T
Opens external link in new window NMR Biomed, 2017, [ahead of print].

R. Mekle, S. Kühn, H. Pfeiffer, S. Aydin, F. Schubert, B. Ittermann
Detection of metabolite changes in response to a varying visual stimulation paradigm using short-TE 1 H MRS at 7 T
Opens external link in new window NMR Biomed 30 (2017).

S. Wilke, J. List, R. Mekle, R. Lindenberg, M. Bukowski, S. Ott, F. Schubert, B. Ittermann, A.Flöel
No effect of anodal tDCS on GABA levels in patients with recurrent mild traumatic brain injury
Opens external link in new windowJournal of Neurotrauma 34, 281-90 (2017).

P. Waxmann, R. Mekle, F. Schubert, R. Brühl, A. Kuehne, T. D. Lindel, F. Seifert, O. Speck, B. Ittermann
A new sequence for shaped voxel spectroscopy in the human brain using 2D spatially selective excitation and parallel transmission
Opens external link in new windowNMR Biomed 29, 1028-37 (2016).

J. Balz, J. Keil, Y. Roa Romero, R. Mekle, F. Schubert, S. Aydin, B,Ittermann, J. Gallinat, D. Senkowski
GABA concentration in superior temporal sulcus predicts gamma power and perception in the sound-induced flash illusion
Opens external link in new windowNeuroimage 125, 724-30 (2016).

U. Lang, T.F. Ackermann, D. Wolfer, F. Schubert, R. Sohr, H. Hörtnagl, F. Lang, J. Gallinat
Phosphoinositide-Dependent Protein Kinase 1 (PDK1): Impact on Schizophrenia Risk and Endophenotype Profile
Opens external link in new windowZ Psychol 223, 165-72 (2015).

J. Gallinat, K. McMahon, S. Kühn, F. Schubert, M. Schaefer,
Cross-sectional Study of Glutamate in the Anterior Cingulate and Hippocampus in Schizophrenia
Opens external link in new windowSchizophr Bull 42, 425-33 (2016).

E. Ehrlich, F. Schubert, C. Pehrs, J. Gallinat
Alterations of cerebral glutamate in the euthymic state of patients with bipolar disorder
Opens external link in new windowJ Psychiatr Res 233, 73-80 (2015).

S. Kühn, F. Schubert, R. Mekle, E. Wenger, B. Ittermann, U. Lindenberger, J. Gallinat
Neurotransmitter changes during interference task in anterior cingulate cortex: Evidence from fMRI guided functional MRS at 3 T
Brain Struct Funct 221, 2541-51 (2016).

S. Hädel, C. Wirth, M. Rapp, J. Gallinat, F. Schubert
Effects of age and sex on the concentrations of glutamate and glutamine in the human brain
J Magn Reson Imaging 38, 1480-7 (2013).

S. Grimm, F. Schubert, M. Jaedke, J. Gallinat, M. Bajbouj
Prefrontal cortex glutamate and extraversion
Soc Cogn Affect Neurosci 7, 811-18 (2012).

S. Grimm, A. Luborzewski, F. Schubert, A. Merkl, G. Kronenberg, M. Colla, I. Heuser, M. Bajbouj
Region-specific glutamate changes in patients with unipolar depression
J Psychiatr Res 46, 1059-65 (2012).

C. Wirth, F. Schubert, M. Lautenschlager, R. Brühl, A. Klär, T. Majic, U. E. Lang, A. Ehrlich, G. Winterer, T. Sander, M. Schouler-Ocak, J. Gallinat
DTNBP1 (dysbindin) gene variants: in vivo evidence for effects on hippocampal glutamate status
Curr Pharm Biotechnol 13, 1513-21 (2012).

A. Merkl, F. Schubert, A. Quante, A. Luborzewski, E.L. Brakemeier, S. Grimm, I. Heuser, M. Bajbouj
Abnormal cingulate and prefrontal cortical neurochemistry in major depression after electroconvulsive therapy
Biol Psychatry 69, 772-9 (2011).

C.F. Pfueller, A.U. Brandt, F. Schubert, M. Bock, B. Walaszek, H. Waiczies, T. Schwenteck, J. Dörr, J. Bellmann-Strobl, C. Mohr, N. Weinges-Evers, B. Ittermann, J. T. Wuerfel, F. Paul
Metabolic Changes in the Visual Cortex Are Linked to Retinal Nerve Fiber Layer Thinning in Multiple Sclerosis
PLoS One 6, e18019 (2011).

T.H. Westhoff, F. Schubert, C. Wirth, M. Joppke, A.A. Klär, W. Zidek, J. Gallinat
The impact of blood pressure on hippocampal glutamate and mnestic function
Hum Hypertens 25, 256-61 (2010). 

J. Gallinat, F. Schubert, R. Brühl, R. Hellweg, A.A. Klär, C. Kehrer, C. Wirth, T. Sander, U.E. Lang
Met carriers of BDNF Val66Met genotype show increased N-acetylaspartate concentration in the anterior cingulate cortex
Neuroimage 49, 767-71 (2010). 

M. Colla, F. Schubert, M. Bubner, J.O. Heidenreich, M. Bajbouj, F. Seifert, A. Luborzewski, I. Heuser, G. Kronenberg
Glutamate as a spectroscopic marker of hippocampal structural plasticity is elevated in long-term euthymic bipolar patients on chronic lithium therapy and correlates inversely with diurnal cortisol
Mol. Psychiatry 14, 696-704 (2009).

C. Montag, F. Schubert, A. Heinz, J. Gallinat
Prefrontal cortex glutamate correlates with mental perspective-taking
PLoS One 12, e3890 (2008). 

J. Gallinat, U.E. Lang, LK. Jacobsen, M. Bajbouj, P. Kalus, D. von Haebler, F. Seifert, F. Schubert
Abnormal hippocampal neurochemistry in smokers: Evidence from proton magnetic resonance
spectroscopy at 3 T

Clin Psychopharmacol 27, 80-84 (2007).

J. Gallinat, F. Schubert
Regional cerebral glutamate concentrations and chronic tobacco consumption
Pharmacopsychiatry 40, 64-7 (2007).

C. Elster, F. Schubert, A. Link, M. Walzel,  F. Seifert,  H. Rinneberg
Quantitative MRS: Semi-parametric modelling and determination of uncertainties
Magn Reson Med 53, 1288-96 (2005).

F. Schubert, J. Gallinat, F. Seifert,  H. Rinneberg
Glutamate concentrations in human brain using single voxel proton magnetic resonance spectroscopy at 3 Tesla
Neuroimage 21, 1762-71 (2004).

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