Methods for Spectroscopic Quantitation
Tuesday 21 April 2009
Room 315 10:30-12:30


Sarah J. Nelson and Geoffrey S. Payne

10:30  232. In-Vivo Measurement of Absolute Metabolite Concentrations Using the ERETIC Method
    Susanne Heinzer-Schweizer1, Nicola De Zanche1,2, Matteo Pavan1, Giel Mens3, Urs Sturzenegger4, Anke Henning1, Peter Boesiger1
Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland; 2Department of Medical Physics , Cross Cancer Institute and University of Alberta, Edmonton, Canada; 3Philips Healthcare, Best, Netherlands; 4Philips AG Healthcare, Zurich, Switzerland
    Absolute quantification is an indispensable tool to precisely determine metabolite changes. Calibration with ERETIC (Electric REference To access In vivo Concentrations), whereby a synthetic reference signal is injected during the acquisition of spectra, was used to determine quantitative in-vivo metabolite concentrations in volunteers. Brain 1H MRS spectra were acquired and cross-validated against the internal water reference method. The results of both calibration techniques were in good agreement in healthy tissue. In addition, the ERETIC setup was perfected by substitution of the electrical by an optical signal transmission line to eliminate fluctuations of the ERETIC signal intensity due to parasitic coupling.
10:42 233. Simultaneous Localized in Vivo 1H and 15N MRS of Glutamine Synthesis in the Hyperammonaemic Rat Brain
    Cristina Cudalbu1, Bernard Lanz1, Florence D. Morgenthaler1, Yves Pilloud1, Vladimir Mlynárik1, Rolf Gruetter1,2
Laboratory for Functional and Metabolic Imaging (LIFMET), Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland; 2Departments of Radiology, Universities of Lausanne and Geneva, Switzerland
    A complementary approach to 13C MRS for studying glutamate and glutamine metabolism is 15N MRS during infusion of 15N labeled ammonia. The goal of this study was to use in vivo localized 15N MRS interleaved with in vivo 1H MRS to measure the glutamine synthesis rate under ammonia infusion in the rat brain. We obtained a net synthesis flux of 0.021±0.006µmol/min/g. By fitting the in vivo 5-15N Gln time course the apparent glutamine synthesis rate and the plasma FE of NH3 were 0.29±0.1µmol/min/g and 71±6%, respectively. Finally, the apparent neurotransmission rate was 0.26±0.1µmol/min/g.


10:54 234. Measurement of Glutathione (GSH) Using a Standard STEAM Sequence with Optimized (TE, TM) Parameters: Spectral Simulation, Phantom, and Human Experiments at 3T
    Shaolin Yang1, Yihong Yang1
Neuroimaging Research Branch, National Institute on Drug Abuse, NIH, Baltimore, MD, USA
    Glutathione (GSH) is a major intracellular antioxidant. Due to spectral overlap with other metabolites, spectral editing has been primarily employed to measure GSH. A recent report suggested resolving the GSH resonance at 2.54 ppm using a standard STEAM sequence with optimized (TE, TM) parameters. However, N-acetylaspartylglutamate (NAAG), which also yields proton resonances around 2.54 ppm, was ignored. In this study, we extended the (TE, TM) optimization originally proposed in that report by adding NAAG as another overlapping metabolites, and found optimized (TE, TM) parameters for resolved GSH measurement at 3T. Phantom and human experiments were conducted for verification.
11:06 235.

Simultaneous Quantitation of T2 and Concentration of Vitamin C and GSH in the Human Brain in Vivo Using Multiple Echo Time Double Editing with MEGA-PRESS  at 4 and 7 T

    Uzay Emir1, Malgorzata Marjanska1, Dinesh Deelchand1, Pierre-Gilles Henry1, Ivan Tkac1, Melissa Terpstra1
University of Minnesota, Minneapolis, MN, USA
    Double Edited MEGA-PRESS spectra were detected at multiple TE in the human brain to measure T2 of Asc and GSH. Data from 22 subjects studied at 4 T were pooled to measure a 50 ms T2 for GSH (95% CI 41-62). The Asc T2 was not determined due to contamination by co-edited resonances. To our knowledge, this is the first time the T2 of GSH has been reported. Spectra measured at several TE in the human brain at 7 T suggest that this methodology can be utilized to measure the Asc and GSH T2 at 7 T.
11:18 236. Measurement of N-Acetylaspartylglutamate in Human Brain by Difference Editing at 7.0 Tesla
    Changho Choi1, Subroto Ghose2, Ivan Dimitrov1,3, Deborah Douglas1, Perry Mihalakos2
Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, USA; 2Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA; 3Philips Medical Systems, Cleveland, OH, USA
    N-acetylaspartylglutamate (NAAG) in human brain has been measured with difference editing at 7T. The C3 proton resonances (~2.5 ppm) of the aspartyl groups of NAAG and N-acetylaspartate (NAA) were differentiated using a 20 ms Gaussian radio-frequency (RF) pulse (bandwidth = 57 Hz) for selective excitation of the their coupling partners at 4.61 and 4.38 ppm, respectively. Symmetric carriers of the editing 180° pulse were applied to separate NAAG and NAA completely. In vivo measurement was conducted on the medial prefrontal and the left frontal lobes of a healthy volunteer. Assuming identical relaxation times between NAAG and NAA, the concentration of NAAG was estimated to be 1 and 2.3 mM for prefrontal and left frontal, respectively, with reference to NAA at 9 mM.


11:30 237.

GABA Concentration in Visual Cortex Correlates with Individual Differences in γ-Band Oscillation Frequency

    Richard A. Edden1, Suresh Daniel Muthukumaraswarmy2, Derek K. Jones2, Jennifer B. Swettenham2, Krish D. Singh2
Schools of Chemistry and Biosciences, Cardiff University, Cardiff, Wales, UK; 2CUBRIC, School of Psychology, Cardiff University, Cardiff, Wales, UK
    GABA, the principle inhibitory neurotransmitter in the human CNS, plays an important role in the neuronal processes of the healthy brain, and altered GABAergic neurotransmission has been implicated in pathologies from epilepsy to bipolar disorder. This study presents a novel combination of edited MRS measurements of GABA with functional measurements of brain activity by magnetoencephalography and shows a strong correlation between GABA and γ-band oscillation frequency.
11:42 238. Simplified 13C Metabolic Modeling for Simplified Measurements of Cerebral TCA Cycle Rate in Vivo
    Julien Valette1, Fawzi Boumezbeur1, Vincent Lebon1,2
CEA-NeuroSpin, Gif-sur-Yvette, France; 2CEA-MIRCen, Fontenay-aux-Roses, France
    13C NMR spectroscopy is a unique tool to measure cerebral TCA cycle rate in vivo. The measurement relies on metabolic modeling of glutamate C3 and C4 enrichment time-courses during a 13C-glucose i.v. infusion. Classical metabolic models require as additional input functions the plasma glucose and 13C-glucose time-courses, as well as the knowledge of Michaelis-Menten kinetics parameters governing passage through the blood brain barrier. It is shown in the present work that metabolic modeling can be simplified in a manner that these additional inputs are not required anymore, significantly simplifying the measurement of cerebral TCA cycle rate in vivo.


11:54 239.

Phase Navigators for Localized MR Spectroscopy Using Water Suppression Cycling

    Thomas Ernst1, Jikun Li2
Medicine, University of Hawaii, Honolulu, HI, USA; 2Electrical Engineering, University of Hawaii
    Magnetic resonance spectroscopy (MRS) is sensitive to subject motion, in part due to phase and frequency variations during movements. A novel water-suppression cycling scheme was developed that alternates between under-suppressed and over-suppressed residual water, and allows 1) phase and frequency correction of individual FIDs using the residual water signal, 2) restoration of signal losses due to incoherent averaging, and 3) near-complete attenuation of residual water. It is demonstrated that phase-correction, using the residual (cycled) water signal, can restore spectra with very poor signal-to-noise ratio (SNR) and line-width induced by subject motion.
12:06 240. Versatile Fitting Tool for Simultaneous Modeling of Spectral Arrays Using Prior Knowledge Restrictions in Two Dimensions
    Daniel Guo Quae Chong1, Johannes Slotboom2, Chris Boesch1, Roland Kreis1
Department of Clinical Research, University of Be rn, Bern, Switzerland; 2Neuroradiology, Inselspital, Bern, Switzerland

A versatile fitting tool for 1D and 2D MRS data is introduced. It uses a hierarchical spectral model that allows for complex prior knowledge implementation. In the second dimension, constraints for common frequencies, widths or phases can be enforced, while predefined amplitude relations allow to fit further parameters, like T2 or T1. It was successfully used for a time series of spectra with varying concentration of a single metabolite, determination of T1 ‘s in a simulated saturation-recovery spectra, and 2DJ data.

12:18 241.

31P Spectroscopic Imaging of Human Brain at 7T

    Jullie W. Pan1,2, Nikolai Avdievich1, Jonathan Knisely3, Hoby P. Hetherington1
Neurosurgery, Yale University School of Medicine, New Haven, CT, USA; 2BME, Yale University School of Medicine, New Haven, CT, USA; 3Therapeutic Radiology, Yale University School of Medicine, New Haven, CT, USA

Because of reduced spectral overlap and sensitivity to B0 inhomogeneity, 31P MRSI is advantageous for whole brain studies. 31P MRS is also sensitive to chemical exchange, this aspect not widely utilized for human brain studies. The SNR limitation of 31P MRSI can be offset by acquiring data at 7T. We measured the T1s of PCr, ATP and Pi at 7T using a multi-tip IR sequence and a 3site exchange model. In brain tumor patients, 31P SI show dramatic reductions in PCr with normal ATP levels, arguing that the reduced PCr signal results from lower concentrations, not only chemical exchange differences.