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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).

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.

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 (V_MAX, K_T) 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 V_MAX=0.29µmol.g^-1.min^-1 and K_T=4.3µmol.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.

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.

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.

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.

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.

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.

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 (V_TCA) 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 V_TCA 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 V_TCA.

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.