|Exploring the Frontiers of MRS Methodology|
Enhanced Sensitivity for Multidimensional
High-Resolution Magic-Angle-Spinning 1H-MR Spectroscopy
Ovidiu Cristian Andronesi1, 2, Dionyssios Mintzopoulos1, 2, Jochem Struppe3, Peter McLaren Black4, Aria A. Tzika1, 2
1Massachusetts General Hospital and Shriners Burn Hospital, Harvard Medical School, Boston, Massachusetts, USA; 2Athinoula A. Martinos Center for Biomedical Imaging, Boston, Massachusetts, USA; 3Bruker BioSpin Corp, Billerica, Massachusetts, USA; 4Brigham and Women's Hospital, Boston, Massachusetts, USA
We present a solid-state NMR method that maximizes the advantages of HRMAS 1H-MRS applied to intact tissue biopsies. Liquid-state NMR sequences, currently employed, may reintroduce, unintentionally, residual anisotropic interactions. Simulations and experiments on brain biopsies of an adiabatic TOBSY (TOtal through Bond correlation SpectroscopY) solid-state sequence for two-dimensional 1H-1H scalar-coupling mixing indicate a significant SNR gain (>100% theoretically and 20-50% experimentally) relative to its liquid-state analogue TOCSY (TOtal Correlation SpectroscopY). This is the first demonstration of such a concept for HRMAS metabolic profiling that can help in detecting new macromolecular biomarkers (proteins) and reducing sample degradation for further analysis (genomics).
Downfield Spectra at Ultrahigh Field
Anke Henning1, Alex Fuchs1, Chris Boesch2, Peter Boesiger1, Roland Kreis2
1University and ETH Zurich, Zurich, Switzerland; 2University Berne, Berne, Switzerland
The advantages of very high fields for MRS in humans (increased SNR and chemical shift dispersion) have been exploited for the upfield part of the human cerebral 1H spectrum but not for the downfield part, which is still poorly characterized. In this work, 7T downfield spectra from human periventricular white matter are presented, compared to corresponding spectra recorded at lower field strength and characterized regarding contributing metabolites and relaxation behaviour as well as in view of chemical exchange with (suppressed) water. Communalities, but also substantial differences were found when compared to equivalent spectra obtained at lower fields.
Lactate Metabolism in Human Brain
Measured by Dynamic 13C MRS
Fawzi Boumezbeur1, 2, Kitt Falk Petersen2, Graeme F. Mason1, Robin A. de Graaf1, Gary W. Cline2, Kevin L. Behar1, Gerald I. Shulman, 23, Douglas L. Rothman1
1Magnetic Resonance Research Center, Yale University, New Haven, USA; 2Yale School of Medicine, New Haven, USA; 3Howard Hughes Medical Institute, Yale School of Medicine, New Haven, USA
Previous studies have shown that lactate is a potential fuel for brain energy metabolism. To elucidate lactate transport kinetics (VMAX, KT) and estimate its net contribution to human brain energy metabolism in vivo (CMRlac), we used localized 13C MRS and infusions of [3-13C]lactate. With a plasma concentration being in the 0.8-2.8 mmol.L-1 range, we have estimated VMAX=0.29Ámol.g-1.min-1 and KT=4.3Ámol.g-1, CMRlac being found to be modest in normal condition. The same approach could be used to investigate in vivo the role of lactate metabolism in sustaining brain function in conditions such as fasting, hypoglycemia, hypoxia/ischemia or neurodegenerative processes.
Measuring NAA Synthesis in Vivo Using Proton
Su Xu1, Jun Yang1, Jun Shen1
1NIMH, Bethesda, Maryland, USA
Here we demonstrate that NAA synthesis can be measured using proton MRS during infusion of uniformly 13C-labeled glucose without using the 13C channel. The rate of 13C-label incorporation into the acetyl group of NAA was measured in the rat brains in vivo using localized long echo-time proton MRS by detecting the 13C satellites of the main NAA methyl proton signal at 2.02 ppm. The NAA synthesis rate measured by this method is ~19 μmol/g h.
Efficient 1H to 31P Polarization Transfer in the
Human Brain on a Clinical 3T MR System with a Single RF Transmit Channel
Dennis Klomp1, Jannie Wijnen1, Tom Scheenen1, Arend Heerschap1
1Radboud University Nijmegen, Medical Center, Nijmegen, Netherlands
(Glycerol)phosphocholine and (glycerol)phosphoetanolamine can be used as early markers for response to treatment, detectable by 31P MRS. A potential sensitivity enhancement of γ 1H/γ 31P can be obtained using 1H to 31P polarization transfer techniques. However, due to J couplings between 31P and 1H that have similar magnitudes for homonuclear J couplings in these metabolites, the enhancement is conventionally less than 50%. We applied chemical shift selective refocusing pulses for full 1H to 31P polarization transfer for these metabolites, have integrated the method in a clinical broadband MR system, and quantified the sensitivity gain using measured T1 and T2 values.
Ultrafast 2D Spectroscopy for in Vivo Applications on
a 7T Whole Body Scanner
Rafal Panek1, Walter Kockenberger1
1University of Nottingham, Nottingham, UK
In vivo 1H NMR spectroscopy is made difficult owing to complex and overcrowded spectra and signal overlap of broadened resonance lines. A powerful strategy to facilitate the assignment of crowded spectra is the use of 2-dimensional spectroscopy. However, these methods suffer from long data acquisition times that makes their use for in vivo applications difficult. Ultrafast gradient assisted single-scan 2D MRS schemes proposed recently have the potential to overcome these limitations but their implementation on whole body scanners is technically challenging. This work demonstrates the first implementation of an ultrafast single-scan approach on a 7T whole body scanner.
Age Dependence of the Downfield Region of
Cerebral 1H MR Spectra
Roland Kreis1, Karin Zwygart1, Verena Beutler1, Daniela Trapp2, Chris Boesch1, Jean-Marc Nuoffer2
1University Berne, Berne, Switzerland; 2Childrens University Hospital, Berne, Switzerland
The downfield part of the 1H-MR spectrum is still ill-defined, and there is no information on its age-dependence. Thirtyseven healthy subjects (newborn to 48 y) were investigated by 1H-MRS using a protocol focused on the downfield spectrum. Major metabolic differences were found for neonates. Additionally, the NH peak of NAA is shown to still increase up to age 15, while no significant changes were detected for any part of the downfield spectrum from 15 to 50 years. The averaged spectra can now serve as age-dependent norm for determination of phenylalanine in phenylketonuria or for diagnostic MRS in children and neonates.
Safety Evaluation for 1H Decoupled 13C Spectroscopy
at 3T in Human Frontal Lobe: SAR Analysis Using Numerical Simulations
Shizhe Li1, Shumin Wang1, Jun Shen1
1NIH, Bethesda, Maryland, USA
Past human brain 13C spectroscopy studies were limited to the occipital lobe partially because strong proton decoupling power is required. A recent new strategy has shown that the proton decoupling power can be significantly reduced when [2-13C]glucose was used. This approach provides an opportunity to acquire proton decoupled 13C spectrum from human's frontal lobe. To evaluate the safety of frontal lobe decoupling, we have performed SAR analysis for two coil designs using computer simulations with a human head model. The results show that, using the new strategy approach, one can safely acquire proton decoupled 13C spectroscopy in human's frontal lobe within current safety guidelines.
|17:36||784.||NMR Measurement of VTCA Correlates with Enzymatic
Activity Along the TCA Cycle as Measured by Histochemistry in the
Fawzi Boumezbeur1, Laurent Besret2, Julien Valette1, Emmanuel Brouillet2, 3, Martine Guillermier2, 3, Caroline Jan2, 3, Philippe Hantraye2, 3, Gilles Bloch4, Vincent Lebon1, 3
1NeuroSpin, Gif-sur-Yvette, France; 2CNRS URA 2210, Orsay, France; 3MIRCen, Fontenay-aux-Roses, France; 4SHFJ, Orsay, France
For the past years, 13C MRS has been used to explore brain metabolism. Yet, NMR-measured TCA cycle flux (VTCA) remains somewhat controversial. To estimate the ability of MRS to detect changes in enzymatic activity, we have induced a stable inhibition of the succinate dehydrogenase. This inhibition has led to a major decrease of VTCA as measured in vivo (mean -44%, -52% for the sacrificed monkey). Post-mortem measurement of SDH inhibition using in situ histochemistry has led to a remarkably similar estimation (putamen: 48%; caudate: 42%). This comparison supports strongly the validity of in vivo MRS measurement of VTCA.
|Two-Echo Multiple Quantum Chemical Shift Imaging of
Ascorbic Acid (Vitamin C) in the Human Brain in Vivo at 3 T
In-Young Choi1, 2, Sang-Pil Lee1
1University of Kansas Medical Center, Kansas City, Kansas, USA
A spectral editing method is proposed for measuring ascorbic acid in the human brain in vivo at 3 T. It utilizes the selective multiple quantum filtering method to suppress all overlapping resonances with ascorbic acid in a single scan. A combination of the multiple quantum filtering method and two-echo approach provides a simultaneous measurement of ascorbic acid and singlet signals without increase of scan time. Singlet signals of creatine, choline and NAA are used for reliable quantification of ascorbic acid. This method allows assessment of the distribution of ascorbic acid in the human brain at clinical field strength, 3 T.