Itthi Chatnuntawech¹, Borjan Gagoski², Berkin Bilgic³, Stephen Cauley³, Ellen Grant², Kawin Setsompop^3,4, and Elfar Adalsteinsson^1,5
1MIT, Cambridge, MA, United States, ²Fetal-Neonatal Neuroimaging & Developmental Science Center, MA, United States, ³A. A. Martinos Center for Biomedical Imaging, MA, United States, ⁴Harvard Medical School, MA, United States, ⁵Harvard-MIT Health Sciences and Technology, Institute of Medical Engineering & Science, MA, United States

In this work, an acquisition-reconstruction method (named random SENSE+TV) to accelerate MRSI acquisition through undersampling of spectral-spatial k-space data, while maintaining acceptable reconstruction quality as measured by a normalized root-mean-square error (RMSE) of the reconstructed metabolite maps is proposed. Random SENSE+TV uses spiral trajectories with different radii to randomly undersample the data in (kx, ky, kf) space, which leads to less-structured artifacts, and recovers the underlying data using the sensitivity encoding technique (SENSE) with a total variation (TV) regularization.

Yuqing Huang¹, Zhiyong Zhang¹, Shuhui Cai¹, and Zhong Chen^1
1Department of Electronic Science, Xiamen University, Xiamen, Fujian, China

Localized 2D J-resolved spectroscopy (JRES) enables the complete separation of chemical shift and J coupling information along two different dimensions, which provides a useful tool for assignment of overlapped resonances in metabolite detection of biological tissues. However, conventional 2D JRES approaches usually suffer from field inhomogeneous effects due to macroscopic magnetic susceptibility in biological tissues. In this report, a new pulse sequence based on intermolecular double-quantum coherences (iDQCs) is presented to achieve high-resolution localized 2D J-resolved information for studying metabolites in biological systems, even for in vivo applications.

Li An¹, Shizhe Li¹, James B Murdoch², Maria Ferraris Araneta¹, Christopher Johnson¹, and Jun Shen^1
1National Institute of Mental Health, National Institutes of Health, Bethesda, MD, United States, ²Toshiba Medical Research Institute USA, Mayfield Village, OH, United States

A PRESS pulse sequence inserted with a J-suppression RF pulse was optimized to resolve and measure glutamate, glutamine, and other metabolites such as glutathione at 7T. Phantom experiments were performed to validate results obtained from density matrix simulations. Metabolite concentration ratios were measured in the frontal lobe grey matter and white matter of eight healthy volunteers. Glutamate and glutamine concentrations were found to be significantly higher in the frontal lobe grey matter than in the frontal lobe white matter.

Weiqiang Dou¹, Joern Kaufmann², Meng Li³, Martin Walter³, and Oliver Speck^1
1Biomedical Magnetic Resonance, Otto-von-Guericke University Magdeburg, Magdeburg, Saxony-Anhalt, Germany, ²Department of Neurology, Otto-von-Guericke University Magdeburg, Magdeburg, Saxony-Anhalt, Germany, ³Clinical Affective Neuroimaging Laboratory, Otto-von-Guericke University Magdeburg, Magdeburg, Saxony-Anhalt, Germany

Trained technicians or medical doctors usually use visual determinations to place magnetic resonance spectroscopy (MRS) voxels over multiple scan sessions in longitudinal studies. However, manual voxel prescription extends the scan time and causes variability of voxel placement. In this study, a vendor-provided automatic voxel positioning technique was for the first time applied to prescribe MRS voxels for longitudinal studies at 7T. Through prescribing voxels on two regions of ten subjects, accurate voxel prescription (mean voxel overlap ratio 0.91¡À0.06 across scans and regions over subjects) and high reproducibility with intraclass-correlation-coefficient 0.88 between regions across scans and subjects validate this technique.

Radhouene Neji¹ and Christian Schuster^1
1Siemens Healthcare, Erlangen, Bayern, Germany

We propose a generic methold to build phase cycling scheme for the semi-laser single voxel spectroscopy sequence based on common PRESS phase-cycling schemens. We implement a 32-step phase cycling scheme and in-vivo brain semi-laser svs spectra show a reduction in spurious echoes and contamination from outside the voxel.

He Zhu¹ and John C. Gore^1
1VUIIS, Vanderbilt University, Nashville, TN, United States

Magnetic Resonance Spectroscopic Imaging (MRSI) should benefit from higher spectral resolution when translated from 3T to 7T. We recently developed a 7T MRSI method consisting of one pair of adiabatic full passage (AFP) pulses with dual band water and lipid suppression. However, earlier implementations suffered from B1 inhomogeneity effects associated with conventional quadrature RF transmission at 7T. Here, we report recently improved implementations of this MRSI method using 2-channel independent RF shimming. RF shimming with 2 independent channels based on B1-mapping achieved expected B1 compensation for 7T MRSI. This RF shimming approach may be implemented with more transmit channels to provide better MRSI measurements, but 2 channels improve performance over a single channel.

Richard Edden^1,2, Ashley D Harris^1,2, Nicolaas AJ Puts^1,2, C John Evans³, Laura M Rowland⁴, S Andrea Wijtenburg⁴, and Peter B Barker^1,2
1Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University, Baltimore, MD, United States, ²F.M. Kirby Research Centre, Kennedy Krieger Institute, Baltimore, MD, United States, ³CUBRIC, School of Psychology, Cardiff University, Cardiff, United Kingdom, ⁴Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland, Baltimore, MD, United States

Edited MRS of GABA, the main inhibitory neurotransmitter in the human brain, is increasingly applied in studies of normal brain function and disease. In vivo quantification of GABA is usually achieved either by a simple integral ratio to Creatine or in institutional units, neither of which allow the comparison of quantitative data from different studies. Herein, we quantify the editing efficiency of GABA and co-editing ratio of macromolecular signal for GABA-edited sequences on GE, Philips and Siemens scanners and demonstrate in vivo that correcting for these sequence-differences significantly improves agreement between concentration measures from each vendor.

KARIM SNOUSSI^1,2, JOSEPH S. GILLEN^1,2, ALENA HORSKA^1,2, NICOLAAS A.J. PUTS^1,2, SUBECHHYA PRADHAN^1,2, RICHARD A.E. EDDEN^1,2, and PETER B. BARKER^1,2
1Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, United States, ²F.M. Kirby Research Centre, Kennedy Krieger Institute, Baltimore, MD, United States

Macromolecule (MM) resonances in proton spectra of the brain are a complicating factor when determining metabolite concentrations, and also of interest in their own right in some pathological conditions. To date, there have been few studies of differences in MM resonances between gray (GM) and white matter (WM), or between different field strengths. This abstract presents results of MM concentrations in two GM and WM locations, and also compares results between 3 and 7T. No significant regional or field strength dependencies were found, however MM resonances (measured in Hz) were broader at 7T than 3T.

Jack Knight-Scott^1
1Radiology, Children's Healthcare of Atlanta, Atlanta, Georgia, United States

Exotic phase cycling provides a method for accessing the coherence suppression efficiency of phase rotation technique, but without its large memory demands. Here we implement and examine the fidelity of the technique in an ultra-short TE stimulated echo sequence.

Gilbert Hangel¹, Bernhard Strasser¹, Michal Považan¹, Stephan Gruber¹, Marek Chmelik¹, Siegfried Trattnig¹, and Wolfgang Bogner^1
1High Field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Vienna, Austria

This work presents high resolution metabolic maps of the brain at 7T acquired in four slices, using pulse-cascaded Hadamard Spectroscopic Imaging (HSI) and 2D-GRAPPA acceleration. HSI increases SNR compared to multi-slice acquisition, overcomes point-spread function problems and enables the measurement of few slices with high in-plane resolution (64×64) while short acquisition delays maximize SNR and avoids J-coupling effects. In plane GRAPPA acceleration by a factor of 6 (i.e., 3x2) allows a measurement time of 20 min while retaining enough SNR for metabolite quantification. Volunteer measurements show good comparability to the corresponding anatomical images.

Dinesh K Deelchand¹, Malgorzata Marjanska¹, and Melissa Terpstra^1
1Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, United States

We determined the accuracy and precision to measure GSH and Asc concentrations in ultra-short echo time spectra when injecting phantom measured GSH and Asc spectra into 5 in vivo human brain spectra acquired at 3 T and 7 T. We found that a change in GSH ≥ 40% is detectable at both fields while a change in Asc can only be quantified at 7 T.

Gaurav Verma¹, Michael Albert Thomas², and Harish Poptani^1
1Radiology, University of Pennsylvania, Philadelphia, PA, United States, ²Radiological Sciences, University of California Los Angeles, Los Angeles, CA, United States

The default post-processing methods implemented by magnetic resonance hardware manufacturers can often be proprietary closed-box algorithms, making it difficult to process data from unconventionally-acquired sequences. By reading and processing scan data from Siemens and Varian sequences directly into MATLAB, a robust and flexible post-processing utility has been created. The program can read, plot and quantify data from a variety of sequences and resolve issues associated with conventionally processing data from advanced sequences like parallel diagonals from phased-array coil combination. The new program can facilitate the development of new advanced or unconventional sequences.

Dinesh K Deelchand¹, Isaac M. Adanyeguh^2,3, Uzay E Emir^1,4, Tra-My Nguyen², Romain Valabregue^2,3, Pierre-Gilles Henry¹, Fanny Mochel^2,3, and Gülin Öz^1
1Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, United States, ²INSERM UMR S975, Brain and Spine Institute, Hospital La Salpêtrière, Paris, France, ³University Pierre and Marie Curie, Paris, France, ⁴FMRIB Centre, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom

In this work, we demonstrate that a wide range of metabolites (both singlet and J-coupled) can be quantified at two different sites with highly reproducible neurochemical profiles using an in-house developed and highly optimized semi-LASER sequence on clinical 3 T scanners. This will in turn allow pooling of data from multiple sites, which is particularly important for clinical research and clinical trials in rare diseases.

Ashley D Harris^1,2, Benjamin Glaubitz³, Jamie Near⁴, C John Evans⁵, Nicolaas AJ Puts^1,2, Tobias Schmidt-Wilcke³, Martin Tegenthoff³, Peter B Barker^1,2, and Richard AE Edden^1,2
1Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, United States, ²F.M. Kirby Research Centre, Kennedy Krieger Institute, Baltimore, MD, United States, ³Department of Neurology, BG-Klinikum Bergmannsheil, Ruhr - University, Bochum, Germany,⁴Douglas Mental Health University Institute and Department of Psychiatry, McGill University, Montreal, PQ, Canada, ⁵CUBRIC, School of Psychology, Cardiff University, Cardiff, United Kingdom

The impact of gradient-induced frequency drift on GABA-edited MRS that occurs after a typical fMRI was assessed. Gradient-induced frequency drift has a significant impact on measured GABA. The primary source of measured GABA underestimation appears to be subtraction artifacts, which can largely be corrected with retrospective frequency correction. Gradient-induced frequency drift causes reduced editing efficiency of GABA but increased editing of macromolecules; therefore, consideration of protocol order or developing prospective frequency correction should also be considered.

Antoine Hone-Blanchet^1,2, Rachel E Salas³, Nicolaas AJ Puts^4,5, Ashley D Harris^4,5, Michael Schär⁶, Aadi Kalloo⁷, Pablo Celnik^8,9, Peter B Barker^4,5, Christopher J Earley⁹, Shirley Fecteau^1,2, Richard P Allen⁹, and Richard AE Edden^4,5
1Centre Interdisciplinaire de recherche en réadaptation et intégration sociale, Laval University, Quebec City, PQ, Canada, ²Centre de Recherche de l’Institut Universitaire en Santé Mentale de Québec, Laval University, Quebec City, PQ, Canada, ³Department of Neurology, The Johns Hopkins University, Baltimore, MD, United States, ⁴Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, United States,⁵F.M. Kirby Research Centre, Kennedy Krieger Institute, Baltimore, MD, United States, ⁶Philips Healthcare, Cleveland, OH, United States, ⁷Johns Hopkins University, Baltimore, MD, United States, ⁸Department of Physical Medicine and Rehabilitation, Johns Hopkins University, Baltimore, MD, United States,⁹Department of Neurology, Johns Hopkins University, Baltimore, MD, United States

The increasing number of studies that combine MRS and TMS will benefit from a pipeline that enables co-localization of the MRS voxel with TMS. Here we present and validate such a pipeline in the primary motor cortex

Peter Adany¹, Phil Lee^1,2, Sarah Taylor³, Roukoz Chamoun⁴, and In-Young Choi^1,5
1Hoglund Brain Imaging Center, University of Kansas Medical Center, Kansas City, KS, United States, ²Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, United States, ³Department of Internal Medicine, University of Kansas Medical Center, Westwood, KS, United States, ⁴Department of Neurosurgery, University of Kansas Medical Center, Kansas City, KS, United States, ⁵Neurology, University of Kansas Medical Center, Kansas City, KS, United States

An improved 3D non-Fourier based spectral localization technique is proposed providing further advancement from our previous advanced SLIM technique with simultaneous corrections for both B0 inhomogeneity and inhomogeneous coil sensitivity: B0-Adjusted and Sensitivity-Encoded (BASE)-SLIM. 3D BASE-SLIM provides reliable localization and improved spectral quality in any non-rectangular, arbitrary-shaped lesions or anatomical boundaries. The performance of 3D BASE-SLIM is demonstrated in the brain of patients with gliomas in three compartments: gray and white matter and lesions.

Zhengchao Dong^1,2, Feng Liu^1,2, Yunsuo Duan^1,2, Alayar Kangarlu^1,2, and Yudong Zhang^3
1Columbia University, New York, NY, United States, ²New York State Psychiatric Institute, New York, NY, United States, ³Nanjing Normal University, Jiangsu, China

Proton MRSI has been applied for almost twenty years to the in vivo measurement of intramyocellular lipids (IMCL) in muscle. In the present study, we showed that the SPREAD (Spectral Resolution Amelioration by Deconvolution) technique can improve the spectral resolution of proton MRSI data and conducted Monte Carlo simulations to assess how SPREAD improves spectral resolution and the accuracy of spectral fitting.

C. John Evans¹, Nicolaas Puts^2,3, Richard Edden^2,3, and David McGonigle^1,4
1CUBRIC, School of Psychology, Cardiff University, Cardiff, Wales, United Kingdom, ²Russel H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, MD, United States, ³FM Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, MD, United States, ⁴School of Biosciences, Cardiff University, Cardiff, Wales, United Kingdom

Experiments relating GABA concentrations to individual differences in neuroimaging signals or behavioural measures are challenging due to the small variations in GABA concentration across healthy populations. The aim of this work is to quantify GABA-MRS measurement repeatability (within and between session) in three voxel locations, and to quantify the range of GABA values in a group of healthy controls. These measurements are used in simulations to estimate the required sample sizes for correctly-powered GABA-MRS experiments.

Jack Knight-Scott^1
1Radiology, Children's Healthcare of Atlanta, Atlanta, Georgia, United States

Relaxometry-based water compartmentalization is the most accurate and precise method for separating brain tissue and cerebral spinal fluid (CSF) water signals in proton MRI and MRS; however, its long acquisition times make the technique one of rare use in quantitative spectroscopy. Here we examine the use of one-minute RRAMSC (Rapid Relaxometry through Acquisition of Multiple Saturated T₂ Curves) for calculating brain metabolite concentrations in molal units.

Samira Kazan¹, Steven Reynolds², Gillian Tozer¹, Martyn Paley², and Michael Chappell^3,4
1CR-UK/YCR Sheffield Cancer Research Centre, University of Sheffield, Sheffield, South Yorkshire, United Kingdom, ²Academic Unit of Radiology, University of Sheffield, Sheffield, South Yorkshire, United Kingdom, ³Oxford Centre for Functional MRI of the Brain, University of Oxford, Oxfordshire, United Kingdom,⁴Department of Engineering Science, University of Oxford, Oxfordshire, United Kingdom

Dynamic nuclear polarization (DNP) is a novel technique for increasing the sensitivity of magnetic resonance spectroscopy and imaging. Intravenous administration of hyperpolarized pyruvate provides a means for quantifying pyruvate-lactate interconversion in living tissues via MRS/MRSIand in oncology, is a potential marker for the efficacy of anti-cancer drugs. The rate constant for pyruvate to lactate conversion, kpl, requires mathematical models to extract kinetic parameters, from the spectroscopy data and the quantification of such parameters depends on the mathematical model and the fitting approach used. In this study we determine whether a Bayesian fitting method (previously adopted in the quantification of perfusion from Arterial Spin Labeling) offers improvements in accuracy and robustness compared to common fitting methods such as Nelder-Mead when applied to the quantification of pyruvate to lactate rate constants. Additionally, we use the estimates of the uncertainty in kpl obtained from the Bayesian method to assess whether the variations kpl are the result of fitting error or inter-group variability.

Michal Bittsansky^1,2, Petra Hnilicova¹, Hubert Polacek^1,2, and Dusan Dobrota^1
1Jessenius Faculty of Medicine, Comenius University, Martin, Slovakia, Slovakia, ²Radiodiagnostic Clinic, Martin University Hospital, Martin, Slovakia, Slovakia

Our aim was to create a robust method for water scaling of 3D 1H MRSI in the brain, easily implementable in clinical conditions. For water referencing, we evaluated the performance of a 3D FID sequence with low pulse angles, short TR, and voxels corresponding to the metabolic spin-echo 3D MRSI sequence, at 1.5 Tesla using a phased-array coil with inhomogeneous sensitivity profile. We have shown the usefulness of this scaling method in a phantom, healthy volunteers and tumor patients. We were able to compare scaled metabolite signals between patients and between different brain areas, including tumors.

Jamie Near¹, Yi-Ching Lynn Ho², Kristian Sandberg^3,4, Chathura Kumaragamage⁵, and Jakob Udby Blicher^6
1Department of Psychiatry, McGill University, Montréal, Québec, Canada, ²Department of Clinical Medicine - Diagnostic Radiology, Aarhus University, Aarhus, Aarhus, Denmark, ³Cognitive Neurosciences Research Unit, Aarhus University Hospital, Aarhus, Aarhus, Denmark, ⁴UCL Institute of Cognitive Neurosciences, University College London, London, London, United Kingdom, ⁵Biomedical Engineering, McGill University, Montréal, Québec, Canada, ⁶CFIN, Aarhus University Hospital, Aarhus, Aarhus, Denmark

In this study, we investigated the long-term reproducibility of MEGA-PRESS edited magnetic resonance spectroscopy measurements of GABA in the occipital cortex of 19 healthy male volunteers. Repeated measurements were performed over a period of seven months; a much longer interval than previous GABA reproducibility studies in the literature, which used intervals of eight days or less. Across all subjects, the average coefficient of variation for repeated measurements was 5.5%, which is similar to the findings of short-term reproducibility studies. These results suggest that GABA concentrations in the occipital cortex are stable over relatively long periods of time.

Alexander John Taylor¹, Josef Granwehr², James Lee Krupa³, Clémentine Lesbats⁴, Joseph S Six⁴, Galina Pavlovskaya⁴, Thomas Meersmann⁴, Neil R Thomas³, Dorothee P Auer¹, and Henryk M Faas^1
1Division of Clinical Neurosciences, School of Medicine, University of Nottingham, Nottingham, Nottinghamshire, United Kingdom, ²Sir Peter Mansfield Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, United Kingdom, ³Centre for Biomolecular Sciences, School of Chemistry, University of Nottingham, Nottingham, United Kingdom, ⁴Sir Peter Mansfield Magnetic Resonance Centre, University of Nottingham, Nottingham, United Kingdom

This work details a new theoretical method which aims to give a better understanding of the expected sensitivity achievable in a (19)F MR experiment.

Takeshi Yokoo^1,2, Qing Yuan¹, Hongyue Yu¹, and Robert E Lenkinski^1,2
1Radiology, UT Southwestern Medical Center, Dallas, TX, United States, ²Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, TX, United States

The importance of the fatty acid (FA) composition in triglycerides (TG) is increasingly recognized in many pathologic processes such as cancer. Proton spectra of TGs have multiple peaks of different frequencies, whose relative peak sizes reflect the FA composition. In this proof of concept study, we selected 6 different natural TGs of different FA composition, and compared the single-voxel proton MR spectroscopy acquired from a 3T clinical scanner (128 MHz) against 400 MHz high-resolution NMR and reported values by US Department of Agriculture (USDA). We showed that estimated TG composition at 3T is highly correlated to that by high-resolution NMR, and similar to reported values by USDA. We conclude that in vivo TG composition determination may be possible clinically using 3T MRS.

Guillaume Madelin¹, Ding Xia¹, Ronn Walvick¹, Jae-Seung Lee¹, and Ravinder R Regatte^1
1Radiology, New York University Langone Medical Center, New York, NY, United States

The FLORET sequence was implemented to acquire sodium MRI of articular cartilage with and without fluid suppression by inversion recovery in the knee joint at 7T. Sodium FLORET images were compared to conventional 3D radial acquisition and showed an average increase of SNR of 30% and 77%, without and with fluid suppression respectively, measured in different regions of cartilage and for the same acquisition time.

Eulalia Serés Roig¹, Lijing Xin², Daniel Gallichan³, Vladimir Mlynarik³, and Rolf Gruetter^1,4
1Laboratory of Functional and Metabolic Imaging (LIFMET), Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Vaud, Switzerland, ²Unit for Research in Schizophrenia, Center for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital (CHUV), Vaud, Switzerland,³Centre d'Imagerie Biomédicale - Animal and Imaging Technology (CIBM-AIT), Lausanne, Switzerland, ⁴Department of Radiology, Universities of Lausanne (UNIL) and Geneva (UNIGE), Vaud, Switzerland

One of the unique features of direct 13C-MRS is its large spectral width, allowing the detection of several resolved carbon signals. In vivo 13C MRS is currently performed using an adiabatic half passage (AHP) pulse for 13C excitation. However, the excitation bandwidth of AHP pulse is asymmetric relative to the carrier frequency, leading to an asymmetric excitation of the spectral lines off-resonance. In this study, we combine two phase-inverted AHP pulses in alternate scans for 13C excitation. We demonstrate a symmetric excitation bandwidth and a flatter phase-response to off-resonance by measuring 13C signals in vivo in human muscle at 7T.

Zhiliang Wei¹, Liangjie Lin¹, Jian Yang¹, Yanqin Lin¹, and Zhong Chen^1
1Department of Electronic Science, Xiamen University, Xiamen, Fujian, China

In spite of the importance of localized two-dimensional correlated spectroscopy, two aspects restrain its wider applications, namely long acquisition time and poor performances under inhomogeneous magnetic fields. Here, a scheme addressed as asymmetrical gradient based single-scan spatiotemporal localized correlated spectroscopy (AGE-SEL-COSY) is proposed for ultrafast high-resolution recording of 2D correlated spectra under inhomogeneous magnetic fields. Experiments have been carried out on chemical solution and biological tissue to prove the robustness of AGE-SEL-COSY against inhomogeneity. It offers important perspectives for fast in vivo analyses of metabolites and living inhomogeneous organisms.

Scott G Quadrelli¹, Saadallah Ramadan¹, Alexander Lin², Jordan D Dimitrikov³, and Carolyn Mountford^1,2
1Center for MR in Health, The University of Newcastle, Newcastle, NSW, Australia, ²Department of Radiology, Center for Clinical Spectroscopy - Harvard Medical School, Boston, MA, United States, ³Department of Nephrology, Children’s Hospital Boston and Harvard Medical School, Boston, MA, United States

Chronic Pelvic Pain (CPPS) is a common, troubling and poorly understood chronic pain condition affecting men. This study aimed to characterise changes in free and bound fucose in patients with CPPS using in vivo 2D L-COSY at 3T. We report a statsically significant increase in cross-peak volumes assigned to á-fucose of 68%between healthy controls and patients with inflammatory (type IIIB) CPPS. There is a concomitant 105% decrease in the assigned composite cross peak of Thr/Fuc I suggesting an altered pathway.

Ladislav Valkovic^1,2, Martin Gajdosík¹, Marek Chmelík¹, Wolfgang Bogner¹, Ivan Frollo², Stephan Gruber¹, Siegfried Trattnig¹, and Martin Krssák^1,3
1High Field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria, ²Department of Imaging Methods, Institute of Measurement Science, Slovak Academy of Sciences, Bratislava, Slovakia, ³Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria

Our aim was to test the reproducibility/reliability of the fast ³¹P saturation transfer (ST) in vivo at 7T for localized measurement of Pi-to-ATP reaction in the liver. Test-retest measurements of the hepatic ST experiment and a contamination check of the spectra from the surrounding muscles were performed. Our data show only negligible fraction of the abdominal muscle signal in the liver spectra and the test-retest variation was very low. Thus we can conclude that fast ST measurements in the liver at 7T are highly reproducible.

Atiyah Yahya^1,2 and Peter S. Allen^3
1Department of Medical Physics, Cross Cancer Institute, Edmonton, Alberta, Canada, ²Department of Oncology, University of Alberta, Edmonton, Alberta, Canada, ³Department of Biomedical Engineering, University of Alberta, Edmonton, Alberta, Canada

Two versions of a modified ¹³C INEPT sequence were considered at 3 T. The difference between the two versions is the location of the ¹³C inversion pulse, namely, 1/4J_CH after the first proton pulse or 1/4J_CH before the third proton pulse. Heteronuclear product operator calculations predict that the outcome should be the same. Our results show that the response of ¹³C₃-glutamate significantly differs depending on the ¹³C inversion pulse location. The signal is higher when the pulse is placed at the beginning of the sequence. The difference in response is due to strong homonuclear coupling between the glutamate protons.

Alessandra Bierwagen¹, Peter Nowotny¹, Jesper Lundbom¹, Jürgen Bunke², Julia Szendroedi¹, and Michael Roden^1,3
1Institute for Clinical Diabetology, German Diabetes Center, Duesseldorf, Germany, ²Philips Healthcare, Hamburg, Germany, ³Department of Endocrinology and Diabetology, Heinrich Heine University, Düsseldorf, Germany

The resonance at 2.06 ppm in the ³¹P human liver spectrum has been previously suggested to arise from biliary phosphatidylcholine rather than from phosphoenolpyruvate. Phantom measurements in the present study support this thesis. In a retrospective analysis the dependency of this peak from the distance to the gallbladder was evaluated. Significant differences were found between voxels i) with gall bladder infiltration, ii) without gall bladder infiltration and iii) of cholecystectomy subjects. Furthermore the Phosphatidylcholine concentration correlates with bile duct diameter (p = 0.03) and cholesterol blood levels (p = 0.01). Therefore we suggest that biliary phosphatidylcholine is detected in the liver.

Goldie R. E. Boone¹, Sunil K. Valaparla¹, Erika M. Ripley¹, and Geoffrey D. Clarke^1
1Radiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States

Use of the N-acetyl aspartate metabolite for temperature measurement in vitro has its disadvantages such as a spectral line overlap and peak inversion and its low viscosity can cause acquisition artifacts. This study demonstrates the novel use of polyethylene glycol as a proton nuclear magnetic resonance spectroscopy thermometry reference standard for phantom quantitative magnetic resonance imaging. The temperature dependent diffusion characteristics of polyethylene glycol can be adjusted by its inherent spectroscopic temperature reporting. Future work will develop polyethylene glycol for use in evaluating diffusion parameters and gradient performance in multicenter, longitudinal quantitative magnetic resonance imaging.

Somenath Ghatak¹, Prashant K Rai¹, Sakshi Sharma¹, Gaurav Sharma¹, and Rama Jayasundar^1
1Department of NMR, All India Institute of Medical Sciences, New Delhi, Delhi, India

In healthcare, nutrition now recognised to be as important as therapeutics is gaining attention as a scientific discipline. The objective of this study is to do multitechnique spectroscopic [NMR, FTIR (Fourier transform infrared spectroscopy) and LIBS (Laser induced breakdown spectroscopy)] profiling combined with multivariate analysis to assess nutritional and therapeutic properties of nutraceuticals. The nutraceutically important phytochemicals and elements (eg. carbohydrates, amino acids, polyphenol, flavonoids) observed using the three spectroscopic techniques correlated well with the antioxidant potential of these nutraceuticals. Spectroscopic profiling combined with multivariate analysis can provide reliable information on the nutritional and therapeutic properties of functional foods.

Gaëlle Diserens¹, Martina Vermathen², Christina Stahl³, Nicholas T. Broskey⁴, Chris Boesch¹, Francesca Amati^1,4, and Peter Vermathen^1
1Depts Clinical Research and Radiology, University Bern, Bern, Bern, Switzerland, ²Dept. of Chemistry & Biochemistry, University Bern, Bern, Switzerland, ³Dept. of Clinical Veterinary Medicine, Clinical Radiology, Vetsuisse-Faculty, University Bern, Bern, Switzerland, ⁴Dept. of Physiology, University of Lausanne, Lausanne, Switzerland

HR-MAS NMR diffusion measurements with strong and low diffusion weighting were used to obtain fat-free spectra: Pure lipid spectra obtained at strong diffusion weighting were subtracted from those obtained at low diffusion weighting, which include both, small metabolites and lipids. This operation results in a spectrum with low lipid contamination under specific metabolite peaks, allowing for a more accurate quantification. This technique has therefore potential to improve chemometric analysis for biomarkers detection. Moreover, the diffusion scans permit a separate lipid analysis and a regular diffusion analysis without expanding scan time.

Alan Wong¹, Beatriz Jiménez², Gérard Raffard³, Jean-Michel Franconi³, and Anne-Karine Bouzier-Sore^3
1SIS2M/LSDRM, CEA Saclay/UMR3299, Gif-sur-Yvette, France, ²Department of Surgery and Cancer, Clinical Phenotyping Centre, London, United Kingdom, ³CRMSB/UMR5536, CNRS/Université Bordeaux Segalen, Bordeaux, France

High-Resolution Magic-Angle sample Spinning (HR-MAS) NMR spectroscopy of biopsies combined with chemometric statistical tools has now emerged as a powerful methodology for metabolomics NMR and has led to many important disease diagnosis, therapeutic target discovery and environmental assessment. This technique is also a method of choice when studying metabolism. However, due to the intrinsically poor detection sensitivity, NMR analysis often requires large tissue mass (5 to 10 mg). Such mass could compromise the metabolic evaluation due to the high degree of tissue heterogeneity (in tumor for example). Unfortunately, today there are no practical means for NMR analysis of small quantity of tissue, or any soft-matter, where sample magic-angle spinning is essential for high quality data acquisition. For this reason, we are developing NMR-based analytical tools with good sensitivity and with good metabolic spectral quality for nanogram tissue biopsies1. Currently, one promising approach is the used of a simple micro-resonator (High-Resolution Magic-Angle Coil Spinning (MACS)), in which it can wirelessly coupled to a MAS probe. Here, we present the use of this micro-resonator High-Resolution (HR)MACS to explore rat brain metabolism, and to see if it was possible to detect and discriminate any differential biomarkers between rest and activated rat brain.

Nicolas Joudiou¹, Fanny Louat¹, Sandra Même¹, Martine Decoville¹, Vincent Sarou-Kanian², and Jean-Claude Beloeil^1
1CNRS CBM UPR4301, Orléans, France, ²CNRS CEMHTI UPR3079, Orléans, France

In addition to the models developed in monkeys and rodents, many human diseases have been successfully modeled in an insect, Drosophila. The aim of our work was to develop very effective non-invasive methods for in vivo study of Drosophila models of neurodegenerative diseases, at metabolome level, such as HR-MAS MRS. We have shown that it is possible to obtain semi-localized MRS spectra (head, thorax, abdomen) of alive drosophilae by using HR-MAS technique associated with rotating magnetic field gradients and very high magnetic field (17.6T). Applications to the study of mutants up101 will be shown. Studies on neurodegenerative flies models are ongoing.

Kaiyu Wang¹, Zhiyong Zhang¹, Hao Chen¹, Shuhui Cai¹, and Zhong Chen^1
1Department of Electronic Science, Xiamen University, Xiamen, Fujian, China

Two dimensional (2D) NMR fulfills a central role in the application of NMR on chemistry, biology and medicine High-resolution heteronuclear NMR spectroscopy is difficult to be obtained in inhomogeneous fields. Based on spatial encoding and spin-echo coherence transfer, we propose a new method to ultrafast achieve high-resolution HSQC spectra and J coupling information in inhomogeneous fields. The results reveal that the new sequence is an attractive way to eliminate the field inhomogeneous broadening with high time efficiency and provides a promising tool for in vivo and in situ high-resolution 2D NMR spectroscopy.

Poonam Rana¹, Mamta Gupta¹, Ahmad Raza Khan¹, B.S.Hemanth Kumar¹, Raja Roy², and Subash Khushu^3
1NMR Research Centre, Institute of Nuclear Medicine and Allied Sciences, Delhi, Delhi, India, ²Centre of Biomedical Magnetic Resonance, SGPGI Campus, Lucknow, India, ³Institute of Nuclear Medicine and Allied Sciences, Delhi, India

Recently, hippocampal neurogenesis is shown to be affected during acute phase of radiation exposure. To understand the primary changes in hippocampus metabolism during an acute phase of irradiation, proton NMR spectroscopy was exploited on a mouse model for single dose of 8 Gy cranial irradiation. In general, reduced metabolic activity was observed in irradiated animals compared with controls, typically evident in energy metabolism, glutamine/glutamate and ketone bodies metabolism. These changes provide strong evidence that hippocampus is metabolically responsive to radiation exposure. The changes observed in hippocampus metabolism during acute phase might have long lasting effects on cognitive development and function.

Ritu Tyagi¹, Poonam Rana¹, Mamta Gupta¹, Deepak Bhatnagar², Raja Roy³, and Subash Khushu^1
1NMR Research centre, Institute of Nuclear Medicine and Allied Sciences (INMAS), DELHI, DELHI, India, ²School of Biochemistry, Devi Ahilya Vishwavidayalaya, Indore, M.P., India, ³Centre of Biomedical Magnetic Resonance (CBMR), Sanjay Gandhi Post Graduate of Medical Science Campus (SGPGI), Lucknow, U.P., India

Tungsten(W) is a complex metal that has numerous applications due to its tensile strength and high melting point. 1H NMR spectroscopy based study has been conducted on urine, liver and kidney extracts samples for identification of metabolite markers for W toxicity. Urine samples were collected at 8, 16, 24, 72 and 120h whereas tissue extracts were prepared for 24, 72 and 120h post dose for low, moderate and high doses of Na2WO4.2H2O. Spectral analysis showed dose dependent alterations in various metabolites associated with renal and hepatic toxicity and could be been seen as early as 8h post dose.

Morteza Esmaeili¹, Tomas Stølen¹, Martin Wohlwend¹, Morten A. Høydal¹, Øivind Rognmo¹, Tone F. Bathen¹, and Øyvind Ellingsen^1
1Department of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), Trondheim, Norway

This study demonstrates the use of 31P NMR spectroscopy to investigate the changes in high energy metabolites of rat models with myocardial infarction under different exercise regimes.

Deepti Upadhyay¹, Naranamangalam R Jagannathan¹, Uma Sharma¹, Govind Makharia², Prasenjit Das³, and Siddhartha Datta Gupta^3
1Department of NMR & MRI Facility, All India Institute of Medical Sciences, New Delhi, Delhi, India, ²Department of Gastroeneterology, All India Institute of Medical Sciences, New Delhi, Delhi, India, ³Department of Pathology, All India Institute of Medical Sciences, New Delhi, Delhi, India

Celiac disease (CeD) is an autoimmune enteropathy caused by ingestion of gluten and related prolamines present in cereals like wheat, rye, and barley in genetically predisposed individuals. Proton NMR based metabonomics of blood plasma of CeD patients showed higher concentration of glucose, acetoacetate, alanine and glycine compared to controls which may be due to alteration in energy metabolism. Blood plasma of CeD patients were also characterized by higher level of glutamine suggesting its involvement in pathogenesis. Decreased concentration of creatinine is observed in blood plasma of CeD patients in comparison to controls. This may be due to protein malabsorption.

Vijayasarathi Nagarajan¹, Taehoon Shin¹, Chia Chu Chou², Sankaran Subramanian³, Murali Cherukuri³, Alan McMillan⁴, Rao Gullapalli¹, and Jiachen Zhuo^1
1Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, Maryland, United States, ²University of Maryland College Park, College Park, MD, United States, ³National Cancer Institute, Bethesda, MD, United States, ⁴University of Wisconsin Madison, Madison, WI, United States

In EPRI, single point imaging is typically adopted due to the very short T2's of the free radicals. This poses needs for acquisition schemes to shorten the total scan time, especially for dynamic imaging. Compressed sensing reconstruction with typical variable density under-samplings yielded unacceptable level of aliasing signals due to the low spatial resolution in EPRI images. We proposed a combined CS and partial Fourier reconstruction, which significantly improves the reconstruction accuracy by improving the reconstruction conditioning. Reasonable data quality were achieved with as little as 17% of data sampling (an acceleration factor of 6) in EPRI.

Rajakumar Nagarajan¹, Manoj K Sarma¹, and M.Albert Thomas^1
1Radiological Sciences, University of California Los Angeles, LOS ANGELES, CA, United States

Brain energy metabolism is believed to be disturbed in cirrhotic patients with hepatic encephalopathy (HE). Ammonia is a neurotoxin and causes increased conversion of glutamate to glutamine. Previous work has shown the important role of MRS in diagnosing and monitoring patients with metabolic disorders. In the one-dimensional (1D) proton MRS, it is very difficult to separate the resonances of glutamate from glutamine and quite often the two are reported together as Glx. In the two-dimensional (2D) localized correlated spectroscopy (L-COSY), additional spectral dimension will be used to separate the overlapping multiplets. The major goal of this study is to review the role of 2D-L-COSY combined with a prior knowledge fitting (ProFit) algorithm in separating glutamine from glutamate in HE patients.

Shizhe Li¹, Li An², Maria Ferraris Araneta², Christopher Johnson², and Jun Shen^1,2
1Magnetic Resonance Spectroscopy Core Facility, National Institutes of Health, Bethesda, Maryland, United States, ²Molecular Imaging Branch, National Institutes of Health, Maryland, United States

Feasibility of performing carboxylic/amide ¹³C MRS using low RF power stochastic proton decoupling at 7 Tesla is demonstrated. Significant improvement in spectral resolution was achieved as compared to previous 3 Tesla studies. As a result, The GABA C1 signal is clearly resolved from the nearby dominant glutamate C5 signal. Aspartate C1 and glutamine C1 are also resolved. These result warrants further optimization of this technique to improve spectral resolution and sensitivity for studying brain energy metabolism and neurotransmission.

Xiao-Hong Zhu¹, Xiao Liu¹, Ming Lu¹, Hannes M Wiesner¹, Kamil Ugurbil¹, and Wei Chen^1
1CMRR, Department of Radiology, University of Minnesota Medical School, Minneapolis, MN, United States

In vivo ¹⁷O MRS/I technique has unique ability for assessing oxygen metabolism via ¹⁷O-labeled oxygen gas inhalation. However, quantification of cerebral metabolic rate of oxygen (CMRO₂) in human is complicated by the large body size and slow gas exchange process, which becomes more problematic when a short inhalation is applied. In this study, a simple approach was proposed for measuring the gas exchange rate in the lung, which was incorporated into a comprehensive quantification model for simultaneous determination of three important physiology parameters of CMRO₂, CBF and OEF in the human brain. This new approach was tested in resting and stimulated human brain. The preliminary results showed similar resting state CMRO₂, CBF and OEF values as reported in literature; and a large CBF increase (>40%) in accompany with smaller increases in CMRO₂ and OEF (<20%) were observed in activated visual cortex, which support the notion of unmatched CMRO₂ and CBF changes in response to a physiological stimulation. The overall results validate the proposed model and provide a quantitative neuroimaging tool for noninvasive imaging CMRO₂, CBF and OEF in healthy and diseased human brains.

Donghan Yang¹, James E Huettner², Jeffrey J Neil^3,4, and Joseph J Ackerman^1,5
1Department of Chemistry, Washington University in St. Louis, St. Louis, Missouri, United States, ²Department of Cell Biology & Physiology, Washington University in St. Louis, St. Louis, Missouri, United States, ³Department of Neurology, Washington University in St. Louis, St. Louis, Missouri, United States, ⁴Department of Pediatrics, Washington University in St. Louis, St. Louis, Missouri, United States, ⁵Department of Radiology, Washington University in St. Louis, St. Louis, Missouri, United States

The intracellular water preexchange lifetime (_IN) determines in what exchange regime diffusion-weighted MR data should be interpreted. We have determined _IN for microbead-adherent cultures of rat cerebral cortical neurons and astrocytes: 0.88  0.24 s for neurons and 0.66  0.17 s for astrocytes. Upon oxygen-glucose-deprivation, a rapid _IN decrease was observed: 0.48  0.07 s and 0.18  0.04 s, respectively. Diffusion times used in clinical studies of normal subjects place them in the slow-exchange regime. The non-negligible difference between neuron and astrocyte _IN, especially in injured cells, should be taken into account in the analysis of time-scale-sensitive data.

Jordan A. Lovis^1,2, Matthew S. Fox², Iain K. Ball², Tao Li², Marcus J. Couch^1,2, and Mitchell S. Albert^1,2
1Lakehead University, Thunder Bay, Ontario, Canada, ²Thunder Bay Regional Research Institute, Thunder Bay, Ontario, Canada

After several decades of use, 5-Fluorouracil (5-FU) remains one of the most heavily used cytotoxic drugs for treatment of cancer. Over the last 20 years, an increased understanding of 5-FU’s mechanism of action has led to an increase in its anticancer activity. Despite these advances, drug resistance remains a significant limitation in clinical use. The purpose of this study was to map 5-FU and its metabolite’s distribution in healthy rats using 19F CSI in a 3T clinical whole-body scanner. These studies may yield information with respect to drug resistance, thereby facilitating personalized treatment.

Tessa N van de Lindt¹, Ronald Mooiweer², Peter R Luijten², Dennis W J Klomp², and Vincent O Boer^2
17 Tesla, UMC Utrecht, Amsterdam, Noord-Holland, Netherlands, ²UMC Utrecht, Utrecht, Utrecht, Netherlands

In brain MRSI, spatial resolution is limited by a relatively low SNR because localization methods generally require a long TR. With recent developments in more efficient localization methods the duration of the WS sequence has become a limiting factor in MRSI. In this work, an ultra short WS method, by using frequency selective spokes pulses to correct for B1-inhomogenieties, is presented. Sufficient water suppression over a whole slice was obtained and very high resolution 2D MRSI spectra were acquired.

Li An¹, Shizhe Li¹, Maria Ferraris Araneta¹, Christopher Johnson¹, James B Murdoch², and Jun Shen^1
1National Institute of Mental Health, National Institutes of Health, Bethesda, MD, United States, ²Toshiba Medical Research Institute USA, Mayfield Village, OH, United States

The feasibility of using a proton-only pulse sequence to measure dynamic glutamate and glutamine labeling process during infusion of ¹³C labeled glucose at 7T was demonstrated by numerical simulations and in vivo experiments on two healthy volunteers. Compared to conventional proton-observed ¹³C-edited experiments, the proton-only pulse sequence is much simpler in hardware and software requirements since it is a pure ¹H pulse sequence with no RF pulses at ¹³C resonances.

Yohan van de Looij^1,2, Vanessa Ginet-Puyal¹, Rolf Gruetter^2,3, Petra S Hüppi¹, and Stéphane V Sizonenko^1
1Division of Child Growth and Development, University of Geneva, Geneva, GE, Switzerland, ²Laboratory for Functional and Metabolic Imaging, Ecole Polytechnique Fédérale de Lausanne, Lausanne, VD, Switzerland, ³Department of Radiology, University of Geneva and Lausanne, Geneva and Lausanne, GE and VD, Switzerland

Lactoferrin (Lf) is an iron-binding glycoprotein secreted in milk known as antioxydant, anti-inflammatory and antimicrobial. The aim of this work was to assess by 1H-MRS neuroprotective effects of Lf during lactation on 3 days-old pup rats (corresponding to human preterm born at 24-28 weeks of gestation) injected with Lipopolysaccharide (LPS) in the corpus callosum. Results show a partial neuroprotection of Lf supplemented in food during lactation following LPS exposure with less compromised metabolism and reduced ventriculomegaly.

Sandra Même¹, Frederic Szeremeta¹, Patricia Lopes-Pereira², Jean-Claude Beloeil¹, William Même¹, and Yan Hérault^3
1CNRS CBM UPR4301, Orléans, France, ²CNRS TAAM UPS44, Orléans, France, ³CNRS UMR7104, UMR964, Strasbourg, France

Down Syndrom (human trisomy 21) is a chromosomal abnormality characterized by the presence of an additional copy of some genes on chrosome 21. This pathology is characterized by a set of behavioural, morpholical and metabolic alterations. Ts65Dn model is the most widely studied mice model for DS.. Some studies have been performed on Ts65Dn mice on the hippocampus and the on the cerebellum but never in vivo. The aim of this study was to quantify changes in brain metabolites concentrations for TS65Dn mice compared to control mice with 9.4T Magnetic Resonance Spectroscopy (MRS).

Ana Francisca Soares¹, Hongxia Lei^2,3, Frédéric Preitner⁴, Bernard Thorens⁴, and Rolf Gruetter^1,5
1LIFMET, EPFL, Lausanne, Vaud, Switzerland, ²CIBM-AIT, EPFL, Vaud, Switzerland, ³University of Geneva, Geneva, Switzerland, ⁴Institute of Pharmacology and Toxicology, University of Lausanne, Vaud, Switzerland, ⁵University of Lausanne, Vaud, Switzerland

We performed ¹H MRS at 14.1T in the liver of GLUT2^-/- and wild-type (WT) mice. Improved spectral resolution allowed identifying peaks from the lipid resonances, choline containing compounds, taurine and glycogen in WT mice. Performing the same measurements in GLUT2^-/- mice revealed a strong contribution from carbohydrates, notably glucose, to the ¹H MR liver spectrum. Also a reduced lipid content was detected by ¹H MRS in those mice. The characterization of the hepatic profile by ¹H MRS in GLUT2^-/- mice is of great value to address changes in the main energy fuels in the liver longitudinally.

Honghao Cai¹, Yushan Chen¹, Xiaohong Cui¹, Shuhui Cai¹, and Zhong Chen^1
1Department of Electronic Science, Xiamen University, Xiamen, Fujian, China

Extraction and high-resolution magic angle spinning (HR MAS) are widely applied for HR NMR spectra of tissues. However, both of the methods are subject to limitations. In this study, the feasibility of ¹H ex vivo and in vivo NMR spectroscopy based on Hadamard-encoded intermolecular multiple-quantum coherence (iMQC) technique is explored using fish muscle, fish eggs and a whole fish as examples. Experimental results indicate that HR in vivo NMR spectra of these samples can be obtained by the iMQC technique. Hadamard encoding improves acquisition efficiency. Compared to MAS, it is non-invasive and suitable for in vivo and in situ applications.

Manoj Kumar¹, Jessica Bagel², Patricia O’Donnell³, Katherine P Ponder⁴, James M Wilson⁵, Mark Haskins³, Charles H Vite², and Harish Poptani^1
1Radiology, University of Pennsylvania, Philadelphia, PA, United States, ²Clinical Studies, University of Pennsylvania, Philadelphia, PA, United States,³Pathobiology, University of Pennsylvania, Philadelphia, PA, United States, ⁴Internal Medicine, Washington University School of Medicine, St. Louis MO, United States, ⁵Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, United States

In vivo 1H MRS was performed on MPS I (n=8) and normal dogs (n=4) from the cerebellar regions of the brain to assess metabolic changes. LC-model was used to measure concentration of the major brain metabolites [N-acetylaspartate (NAA), creatine (Cr), choline (Cho), and myo-inositol (mI)]. NAA, Cho, and mI peaks values were normalized to Cr peak values. We observed significantly reduced NAA/Cr and significantly increased Cho/Cr in MPS I along with slightly elevated mI/Cr reflecting increased demyelination, gliosis, and axonal injury. Our studies indicate that 1H MRS might be a sensitive technique for detecting and quantifying the neuroaxonal injury status in this model.

William E. Wu¹, Assaf Tal¹, James S. Babb¹, Eva-Maria Ratai², R. Gilberto Gonzalez², and Oded Gonen^1
1Radiology, New York University School of Medicine, New York, New York, United States, ²Neuroradiology, Massachusetts General Hospital, Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, Massachusetts, United States

As ~40% of HIV-infected persons experience neurocognitive decline, we test whether proton MR spectroscopic imaging can detect early metabolic abnormalities in the cerebral cortex of an accelerated (CD8+ T-lymphocyte depleted) simian immunodeficiency virus-infected macaque model of neuroAIDS. Mean pre infection concentrations of glial markers, myo-inositol, creatine and choline: 5.8±0.9, 7.2±0.4 and 0.9±0.1mM increased 28% (p=0.06), 15% and 10% (both p’s‹0.05) four to six weeks post-infection, while neuronal marker, N-acetylaspartate, remained unchanged (7.0±0.6 to 7.3±0.8mM). Taken together with previous studies, these findings suggest treatment regimens aimed at reducing cortical gliosis may reduce the risk of neurodegeneration and its associated neurocognitive impairments.

Sunitha Thakur¹, Sanjay Annarao², Louisa Bokacheva³, and Junh Hun Oh^4
1Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY, United States, ²Memorial Sloan-Kettering Cancer Center, New York, NY, United States, ³Medical Physics, Memorial Sloan-Kettering Cancer Center, NY, United States, ⁴Memorial Sloan-Kettering Cancer Center, NY, United States

The purpose of this study is to measure lactate concentrations, [Lac] in breast mammary tumors (MCF7, BT474, MDA231, and MDA435) with contrasting growth rates, tumor aggressiveness, and metastatic risk. In this work, we implemented the SS-SelMQC using higher order binomial pulses (SS1-SelMQC) for lactate detection as well as T1- and T2- versions of SS1-SelMQC. The [Lac] in tumors were measured at different tumor volumes. In all four tumor types, the [Lac] was found to be higher at tumor volume (100-200 mm³), and as tumor volume increases, [Lac] tend to decrease. No significant differences in [Lac] were found among different models.

Jannie P Wijnen^1,2, Ronald Zielman³, Andrew Webb², Gisela M Terwindt³, Michel Ferrari³, Hermien E Kan², and Mark C Kruit^2
1Radiology, University Medical Centre Utrecht, Utrecht, Utrecht, Netherlands, ²Radiology, Leiden University Medical Centre, Leiden, Netherlands,³Neurology, Leiden University Medical Centre, Leiden, Netherlands

In this study we assessed the interictal (between attacks) glutamate levels of migraine patients and compared the levels to age and gender matched healthy controls. Ultra high field Magnetic Resonance Spectroscopy (7 Tesla) of the visual cortex was performed in 20 patients and 20 controls. Linear regression of between subject effects was performed on the glutamate concentration with the fraction of gray matter (GM) in the voxel as covariate. This analysis revealed elevated interictal glutamate levels in patients with migraine. At ultra high field, glutamate can be robustly detected, which opens opportunities to study the role of glutamate in migraine in more detail.

Shalmali Dharmadhikari^1,2, Swaantje Casjens³, Benjamin Glaubitz⁴, Martin Lehnert³, Clara Quetscher³, Anne Lotz³, Thomas Brüning³, Tobias Schmidt-Wilcke⁴, Christian Beste⁵, Beate Pesch³, Dirk Woitalla⁶, and Ulrike Dydak^1,2
1School of Health Sciences, Purdue University, W Lafayette, Indiana, United States, ²Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana, United States, ³Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-Universität Bochum (IPA), Bochum, Germany, ⁴Department of Neurology, BG-Klinikum Bergmannsheil, Ruhr-University, Bochum, Germany, ⁵Cognitive Neurophysiology, Department of Child and Adolescent Psychiatry, University of Dresden, Germany, ⁶Neurological Clinic, St. Josef-Hospital, Ruhr-Universität Bochum, Bochum, Germany

Parkinson’s disease (PD) is caused by loss of dopamine in the basal ganglia which in turn affects the gamma-aminobutyric acid (GABA) and glutamate metabolism in the motor pathways. This study investigated the association of GABA and glutamate levels measured by MRS in the basal ganglia with motor scores obtained in PD patients in order to understand the implications of such disruptions on motor performance. Higher thalamic GABA levels were found to be associated with increasing tremor and worse motor performance.

Zaiyang Long^1,2, Yue-Ming Jiang³, Xiang-Rong Li⁴, Jun Xu², Chien-Lin Yeh^1,2, Li-Ling Long⁴, Wei Zheng¹, James B Murdoch⁵, and Ulrike Dydak^1,2
1School of Health Sciences, Purdue University, West Lafayette, IN, United States, ²Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, United States, ³Department of Health Toxicology, Guangxi Medical University, Nanning, Guangxi, China, ⁴Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China, ⁵Toshiba Medical Research Institute USA, Mayfield Village, OH, United States

Metal workers chronically exposed to manganese (Mn) may suffer from its neurotoxic effects, which may lead to Parkinson-type symptoms. In a search for early signs of Mn neurotoxicity, we investigated Mn accumulation in the brain as well as changes in thalamic γ-aminobutyric acid (GABA) and cortical glutamate levels in 39 metal workers, 37 controls and 7 manganism patients. Significantly decreased T1 values indicate Mn accumulation in the workers’ brains. Significantly elevated thalamic GABA levels in all, and decreased glutamate levels in several of the groups may help further elucidate the underlying mechanisms and serve as early biomarkers of Mn neurotoxicity.

Ming Lu¹, Xiao-Hong Zhu¹, Yi Zhang¹, and Wei Chen^1
1Center for Magnetic Resonance Research, University of Minnesota Medical School, Minneapolis, Minnesota, United States

Nicotinamide adenine dinucleotide (NAD) participates in various redox reactions in living organisms for supporting normal cellular functions and activities. The reduced (NADH) and oxidized (NAD⁺) forms of NAD play key roles in cellular metabolism and regulation. The intracellular NAD⁺/NADH ratio, defined as intracellular redox state, reflects metabolic status and has been found to be associated with alterations in physiology and pathology. However, direct quantification of NAD and redox state in vivo is challenging. In this study, using our newly developed in vivo ³¹P MRS approach for imaging NAD and its redox state in animal brains at 16.4 T, alterations of the NAD concentrations and redox state in rat brains from normoxia to hypoxia were studied. When reducing the oxygen supply from 30~40% (of O₂ and N₂O mixture) to 5~6% level, the results indicated an increase of NADH contents (+25%), and decreases of [NAD⁺] (-26%), NAD⁺/NADH ratio (-43%) and total [NAD] (-13%). Also, there were further increase of [NADH] and decreases of [NAD⁺], NAD⁺/NADH ratio and total [NAD] in the postmortem brains. In summary, by using the novel ³¹P MRS method, changes of cerebral redox state and the intracellular NAD contents can be robustly and non-invasively quantified under normal and hypoxic conditions. This simple and highly applicable MR imaging approach has a great potential for studying metabolic disorders in different organs of patients with hypoxic or ischemic syndrome.

Gaurav Verma¹, David Roalf², Ruben Gur², Raquel Gur², and Harish Poptani^1
1Radiology, University of Pennsylvania, Philadelphia, PA, United States, ²Psychiatry, University of Pennsylvania, Philadelphia, PA, United States

Irregularities in cortical glutamate, glutamine, glutathione and gamma-aminobutyric acid (GABA) have been correlated with symptoms of schizophrenia, yet these spectral overlap with nearby resonances makes these metabolites difficult to resolve. Two-dimensional (2D) localized correlated spectroscopy (L-COSY) at 7T facilitates the unambiguous detection of these metabolites. Twelve subjects (six patients, six controls) were scanned with L-COSY at 7T. Glutamate, glutamine, glutathione and GABA were reliably detected using L-COSY – with coefficients of variation of 20% or below – and Glutathione was found to be significantly higher in the patient group. L-COSY could have potential application in monitoring treatment response in schizophrenia patients.

Reggie Taylor^1,2, Betsy Schaefer³, Richard Neufeld³, Peter Williamson^1,3, and Jean Theberge^1,2
1Medical Biophysics, Western University, London, ON, Canada, ²Lawson Health Research Institute, London, ON, Canada, ³Psychiatry, Western University, London, ON, Canada

The glutamatergic response to functional activation in the anterior cingulate cortex (ACC) was examined in 14 healthy controls (HC), 14 subjects with schizophrenia (SZ), and 10 subjects with mood disorder. The ACC was activated using a Stroop task, which is known to activate the area, and the glutamatergic response was monitored using 1H-MRS. Significant (p<0.05) increases were observed in both HC and SZ groups, but not the mood group. This ongoing study is the first to report on the ability of patients with SZ to dynamically regulate their levels of ACC Glu.

Li Wei^1,2, xiaoping Hu^1,2, Andrew H Miller^2,3, and Ebrahim Haroon^2,3
1Biomedical Imaging Technology Center, Emory University, Atlanta, GA, United States, ²School of Medicine, Emory University, Atlanta, GA, United States,³Winship Cancer Institute, Atlanta, GA, United States

Chronic immune activation forms the basis of many medical and behavioral disorders. The mechanism of the association between immune changes and behavior disorder is not clear. We hypothesize that the link might reside in the metabolism of glutamate, an excitatory amino acide neurotransmitter. Interestingly unbridled increase in glutamate concentration might result in neurodegenwerative and behavioral changes. We studied 9 depressed patients with high inflammation and compared them to 15 patients who had depression with low inflammation. We measured glutamate concentrations in the bilateral basal ganglia using chemical shift imaging (MRS). Depressed patients with high inflammation had significantly increased concentrtion of glutamate/creatine, choline/creatine and inositol/creatine that supporting our intial hypothesis.

Xiangchuan Chen¹, Xiaoping Hu¹, Andrew H. Miller^2,3, and Ebrahim Haroon^2,3
1Biomedical Imaging Technology Center, Emory University, Atlanta, GA, United States, ²School of Medicine, Emory University, Atlanta, GA, United States,³Winship Cancer Institute, Atlanta, GA, United States

Increased neural and glial activity in several brain regions including dorsal anterior cingulate cortical (dACC) regions has been reported to occur in response to inflammatory activation by infections, cancer and chronic psychological stress. We designed a study to test the hypothesis that depressed patients with CRP > 3mg / L (high inflammation) will show an increase in the dACC glutamate and inositol levels indicating high levels of neuronal and glial activation and further that the neural metabolite changes will be directly and positively correlated with inflammatory biomarkers seen in plasma.

Ulrich Pilatus¹, Christian Lückerath¹, Stefanie Pellikan¹, Dmitri Vronski¹, Susanne Knake², Matthias Kieslich³, and Elke Hattingen^1
1Institute of Neuroradiology, Goethe-University Frankfurt, Frankfurt, Germany, ²Centrum of Epilepsy Hessen, Philipps-University Marburg, Marburg, Germany, ³Department of Pediatric Neurology, Goethe-University Frankfurt, Frankfurt, Germany

In juvenile myoclonic epilepsy (JME) dysfunction of thalamocortical circuits is considered to trigger myoclonic seizures and frontal lobe dysfunction is a common pathology. Here we present data on metabolite concentrations in brain structures relevant for JME (thalamus, frontal lobe, motor cortex) focusing on changes of GABA, glutamate, glutamine and NAA. In addition to short-TE MR spectroscopy a specific MR spectroscopic GABA editing sequences was employed. The study was designed to obtain information of drug effects, hemispheric and tissue differences, too.

Rajesh Kumar¹, Santosh K Yadav¹, Paul M Macey², Mary A Woo², Frisca L Yan-Go³, and Ronald M Harper^4
1Anesthesiology, University of California at Los Angeles, Los Angeles, CA, United States, ²UCLA School of Nursing, University of California at Los Angeles, Los Angeles, CA, United States, ³Neurology, University of California at Los Angeles, Los Angeles, CA, United States, ⁴Neurobiology, University of California at Los Angeles, Los Angeles, CA, United States

Obstructive sleep apnea (OSA) subjects show both structural injury and functional deficits in multiple brain sites, and these deficits are especially prominent in the anterior insular cortices that assist regulation of autonomic and neuropsychologic functions. We examined anterior insular metabolites using PMRS to determine the nature of tissue changes in OSA, and observed bilaterally reduced NAA, and increased MI on the left side, indicating neuronal damage/loss of function, and glial activation, respectively. The presence of abnormal metabolites in OSA may result from intermittent hypoxia, impaired perfusion, or deficient micronutrient support accompanying the condition.

Caterina Tonon¹, Laura Ludovica Gramegna¹, Ilaria Naldi², Claudia Testa¹, David Neil Manners¹, Giovanni Rizzo¹, Lorenzo Ferri², Claudio Bianchini¹, Francesca Bisulli^2,3, Paolo Tinuper^2,3, and Raffaele Lodi^1
1Functional MR Unit, Department of Biomedical and NeuroMotor Sciences (DiBiNeM), University of Bologna, Bologna, Italy, ²Department of Biomedical and NeuroMotor Sciences (DiBiNeM), University of Bologna, Bologna, Italy, ³Institute of Neurological Sciences of Bologna, Bologna, Italy

Nocturnal frontal lobe epilepsy (NFLE) is a syndromic entity that includes paroxysmal episodes appearing almost exclusively during sleep. The study used 1H-MRS to evaluate the possible involvement in NFLE of the anterior cingulated cortex, which is considered to have inhibitory function on spontaneous motor activity. Spectra were acquired in the anterior cingulated cortex using single voxel PRESS (TR/TE=4000/35). In the anterior cingulated cortex of patients NAA/Cr was lower than in healthy controls (p<0.01). NAA/Cr values correlated negatively with clinical severity of NFLE (beta: -0,473, p<0.05). Our results point to a role of anterior cingulated cortex dysfunction in the NFLE pathophysiology

Luke Y.-J. Wang^1,2, Sai K. Merugumala², Huijun Liao², and Alexander P. Lin^2
1Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital and Harvard Medical School, Boston, MA, United States,²Department of Radiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States

Sleep and wakefulness are a complex yet distinct physiological states. However, they are not generally controlled for during brain spectroscopy. We report higher detected levels of GABA during sleep, compared to a controlled wakeful state.

Alexander Gussew¹, Stefan Smesny², Reinhard Rzanny¹, Patrick Hiepe¹, and Jürgen R. Reichenbach^1
1Medical Physics Group, Department of Diagnostic and Interventional Radiology I, Jena University Hospital, Jena, Thuringia, Germany, ²Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Thuringia, Germany

This study combined ¹H- and ³¹P-MR brain spectroscopy to assess the associations between the neurotransmitter glutamate, the membrane phospholipid precursors (PME) and breakdown products (PDE) and the energy turnover markers (PCr) in healthy subjects. Significant positive correlations were observed between glutamate and PDE (rho>0.3), indicating for the glutamatergic modulation of membrane phospholipid breakdown. Furthermore, PDE increased with decreasing PCr (rho < -0.25), indicating increased energy demand to compensate the increased membrane turnover.

Ivica Just Kukurova^1,2, Martin Krššák^1,3, Marek Chmelik¹, Martin Gajdošík¹, Siegfried Trattnig¹, and Ladislav Valkovič^1,4
1High-field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria, ²Slovak University of Technology, Bratislava, Slovakia, ³Division of Endocrinology and Metabolism, Department of Internal Medicine III, Vienna, Austria, ⁴Department of Imaging Methods, Institute of Measurement Science, Slovak Academy of Sciences, Bratislava, Slovakia

Carnosine in skeletal muscle plays an important role as a buffer for intracellular pH. Its concentration can be measured by proton MRS. Aim of this study was to measure relaxation times of carnosine in m. gastrocnemius in vivo at 7T which was achieved and succesfully applied for quantification of concentration of carnosine. Results will be used for further metabolic studies.

Joshua D Kaggie^1,2, Nabraj Sapkota^1,2, Kyle Jeong², Xianfeng Shi³, Glen R Morrell¹, Neal K Bangerter^1,4, and Eun-Kee Jeong^1
1Utah Center for Advanced Imaging Research, Radiology, University of Utah, Salt Lake City, UT, United States, ²Physics, University of Utah, Salt Lake City, UT, United States, ³The Brain Institute and Department of Psychiatry, University of Utah, UT, United States, ⁴Electrical and Computer Engineering, Brigham Young University, UT, United States

This study acquires proton and sodium images within the same sequence at 3T, without internal modification of the clinical hardware. Proton GRE and SE MR images were separately acquired, synchronously with 23Na GRE images. To overcome scanner limitations: the 1H/23Na transmit pulses were interleaved; additional hardware was added to the scanner to down-convert the 1H signal, so that both the 23Na and 1H signal were acquired at 23Na frequency through the scanner; the sequence allowed multiple 23Na acquisitions to occur between 1H acquisitions for 1H SE imaging. Both phantom and in vivo 1H/23Na synchronous images were obtained.

Guillaume Madelin¹, Richard Kline², Ronn Walvick¹, Christopher Glielmi³, Dominik Paul⁴, Heiko Meyer⁴, Mony de Leon⁵, Henry Rusinek^1,5, and Ravinder R Regatte^1
1Radiology, New York University Langone Medical Center, New York, NY, United States, ²Anesthesiology, New York University Langone Medical Center, New York, NY, United States, ³Siemens Medical Solutions USA, Inc, New York, NY, United States, ⁴Siemens AG, Erlangen, Germany, ⁵Psychiatry, New York University Langone Medical Center, New York, NY, United States

A combined 1H-23Na MRI method was implemented at 3T for measuring apparent total and intracellular sodium concentrations (aTSC, aISC) in gray and white matter (GM, WM) in brain in vivo. Sodium images were acquired with and without fluid suppression by inversion recovery. A double inversion recovery (DIR) sequence (1H) was used to create masks of GM and WM which were applied to the sodium data. Statistical parameters of distributions of aTSC and aISC values are measured in GM and WM and revealed non-Gaussian shape. This MRI method has potential for assessing early metabolic information in neurodegenerative pathologies non-invasively.