2D-resolved MRS

Metabolites of particular interest are neurotransmitters and their precursors such as glutamine (Gln), glutamate (Glu), and gamma amino butyric acid (GABA), as well as antioxidants such as glutathion (GSH) and ascorbic acid (Asc), whose important roles in the pathophysiology of neurological and psychiatric disorders like epilepsy, migraine, schizophrenia, depression or panic disorders is still not fully understood.

These metabolites are only present at low concentrations and hence give rise to small signal intensities and exhibit complex multiplet structures due to the effect of J-coupling. Their quantification is complicated or even impossible by conventional 1D magnetic resonance spectroscopy due to strong spectral overlap of the individual signal contributions that partly stem from much more intense resonance lines.

A possible way to approach this problem is the use of 2-dimensional MR spectroscopy. In these types of experiments different physical phenomena like J-coupling induced phase evolution differences or coherence transfer between J-coupled spins can be utilized to transfer some of the previously overlapped and hidden information into a second frequency dimension. While these techniques are well established within the in vitro NMR world, their application for in-vivo measurements is still quite rare.

This project aims at combination of in vivo 2D spectroscopy techniques such as JPRESS and COSY with high (3T) and ultra high field (7T) strength to establish useful scanner protocols for more accurate detection and quantification of neurotransmitters and antioxidants. To that sequences are developed that suppress unwanted coherence transfer pathways and artifacts sources and enable precise localization and high SNR.

In addition, a 2D prior-knowledge fitting (ProFit) routine has been recently developed in our institute that enables direct quantification of 2D J-resolved spectra. To that a linear combination of simulated 2D basis spectra is fitted to the original spectrum. This routine is currently extended to different 2D MRS sequences, regularization is optimized and macromolecules are considered. 2D JPRESS and COSY is finally combined with internal water referencing or ERETIC to enable absolute quantification.

Enlarged view: In vivo 2D-resolved MRS
In vivo 2D-resolved MRS: JPRESS spectrum from the human brain acquired at 3T (top left); metabolite basis for fitting COSY spectra with ProFit (top right). Covariance coefficients indicate orthogonality of basis spectra for different brain metabolites and hence their discriminibility for in vico line width. At 3T JPRESS and COSY largely extend the number of metabolites that can be quantified reliably and simultaneously (bottom).

Publications:

  • Lange T, Schulte RF, Boesiger P. Quantitative J-resolved prostate spectroscopy using two-dimensional prior-knowledge fitting. Magn Reson Med 59(5), 966-972, 2008
  • Thomas MA, Lange T, Velan SS, Nagarajan R, Raman S, Gomez A, Margolis D, Swart S, Raylman RR, Schulte RF, Boesiger P. Two-dimensional MR spectroscopy of healthy and cancerous prostates in vivo.MAGMA 21, 443-458, 2008
  • Lange T, Trabesinger AH, Schulte RF, Dydak U, Boesiger P. Prostate spectroscopy at 3 Tesla using two-dimensional S-PRESS. Magn Reson Med 56(6), 1220-1228, 2006
  • Schulte RF, Boesiger P. ProFit: two-dimensional prior-knowledge fitting of J-resolved spectra. NMR Biomed 19(2), 255-263, 2006
  • Schulte RF, Lange T, Beck J, Meier D, Boesiger P. Improved two-dimensional J-resolved spectroscopy. NMR Biomed 19(2), 264-270, 2006
  • Schulte RF, Trabesinger AH, Boesiger P Chemical-shift-selective filter for the in vivo detection of J-coupled metabolites at 3T. Magn Reson Med 53(2), 275-281, 2005

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