Simon Konstandin¹, and Lothar R. Schad^1
1Computer Assisted Clinical Medicine, Heidelberg University, Mannheim, Germany

Sodium heart imaging is mainly used for research on myocardial infarction and viability purposes. The necessity of ECG-triggering for low resolutions was never examined. In this work, the reasonability of ECG-triggering is investigated at low resolutions needed for sodium MRI. Signal errors due to motion artifacts are below 5 % in myocardium and, therefore, the benefit of ECG-triggering is questionable. However, studies on patients with myocardial infarction (i.e., increased signal in the myocardium) must be performed to show the reasonability of ECG-triggering. Retrospective ECG-gating with Golden angle increments is shown for a time-efficient acquisition and, therefore, to increase signal-to-noise ratio.

Simon Konstandin¹, and Lothar R. Schad^1
1Computer Assisted Clinical Medicine, Heidelberg University, Mannheim, Germany

Minimal echo times are required for sodium MRI with a fast biexponential transversal decay. The RF pulse duration of slice-selective excitation is limited by gradient slew rate, amplitude, and RF peak power. The minimal necessary RF pulse duration was investigated, depending on flip angle and reference voltage of the coil using different VERSE approaches and Fermi-shaped RF pulses. Sodium heart measurements are shown to demonstrate SNR changes in myocardium due to different minimal echo times.

Joshua D Kaggie^1,2, John R Campbell³, James Badal³, Rock Hadley², Daniel J Park³, Glen Morrell², Dennis Parker², Rexford D Newbould⁴, and Neal Bangerter^2,3
1Physics, University of Utah, Salt Lake City, UT, United States, ²Utah Center for Advanced Imaging Research, University of Utah, Salt Lake City, UT, United States, ³Electrical and Computer Engineering, Brigham Young University, Provo, UT, United States, ⁴GSK Clinical Imaging Centre, London, United Kingdom

It is commonly accepted that phased array receive coils will improve SNR for 1H-MRI on typical clinical magnets (1.5T or 3T). This work presents a 5-channel 23Na/single-channel 1H coil configuration for 23Na-MRI of the breast at 3T, and demonstrates significant improvements in 23Na SNR in the breast with a 23Na phased-array when compared to a single 23Na loop.

Armin M. Nagel¹, Florian M. Meise¹, Marc-André Weber^2,3, Karin Jurkat-Rott⁴, Frank Lehmann-Horn⁴, Michael Bock¹, Wolfhard Semmler¹, and Reiner Umathum^1
1Dept. of Medical Physics in Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, ²University Hospital of Heidelberg, Heidelberg, Germany, ³Dept. of Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, ⁴Division of Neurophysiology, Ulm University, Ulm, Germany

Chlorine (Cl^-) is the most important anion in the human body and is involved in many physiological processes. In this work, for the first time ³⁵Cl-images of the human brain and the skeletal muscle were acquired on a whole body 7 T MRI system. ³⁵Cl exhibits short relaxation times of T_2f^* = 1.1 ms and T_2s^* = 6.2 ms in brain parenchyma and T_2f^* = 0.3 – 0.8 ms and T_2s^* = 2.5 – 4.5 ms in skeletal muscle. Spatial resolutions of (6 mm)³ (brain) and (11 mm)³ (muscle) could be achieved at an SNR of 15 (brain parenchyma) and 7-15 (muscle).

Sebastian Baier¹, Stefan Kirsch¹, Friedrich Wetterling¹, Laurent Tritschler², Patrick Heiler¹, and Lothar R Schad^1
1Computer Assisted Clinical Medicine, Heidelberg University, Mannheim, Germany, ²Department of Neurology, Heidelberg University, Mannheim, Germany

Here we present a method which enables non-invasive determination of the Cl^-/Na⁺ concentration ratio by means of MRI. The method employs a double resonant ³⁵Cl-²³Na surface coil which uses the same tunable loop element for measuring the ³⁵Cl and ²³Na signal. Since our sample dimensions are much smaller than /10, the ³⁵Cl and the ²³Na image exhibit approximately the same B₁ profile. Using a reference with known Cl^-/Na⁺ concentration enables calculation of a concentration ratio map by simply dividing the³⁵Cl image by the ²³Na image.

Rebecca E Feldman¹, and Christian Beaulieu^1
1Biomedical Engineering, University of Alberta, Edmonton, Alberta, Canada

Although sodium MRI is a promising technique for assessing knee cartilage health, the presence of fluid in the joint can confound the evaluation of cartilage. Fluid suppression can isolate cartilage signal, but a hard inversion pulse will drastically attenuate the SNR in the image, and make the received signal highly T1 dependant. This abstract shows that a long inversion pulse can improve signal intensity values in fluid suppressed sodium images. The soft inversion sequence produce better in-vivo cartilage SNR than a hard inversion sequence (SNR = 21 vs. 12) acquired in a similar time frame (~10 min).

Bhavana Shantilal Solanky¹, Frank Riemer¹, Claudia A. M. Wheeler-Kingshott¹, and Xavier Golay^2
1NMR Research Unit, Department of Neuroinflammation, UCL Institute of Neurology, London, United Kingdom, ²Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, London, United Kingdom

Partial volume effects and the high intensity of the CSF signal may lead to inaccuracies in the determination of 23Na concentrations in peri-ventricular regions (Peri-V). With this in mind we tested two methods of suppressing the CSF signal to enable a more accurate quantification of total 23Na in Peri-V tissue: An inversion recovery (IR) sequence to eliminate CSF based on exploiting T1 relaxation differences between CSF and tissue a dual echo sequence exploiting the difference in T2 relaxation. These methods were compared in terms of residual CSF signal and the resultant effect of CSF contamination in Peri-V regions was assessed

Mrignayani Kotecha¹, Sriram Ravindran², Aishwarya Vaidyanathan¹, Anne George², and Richard Magin^1
1Department of Bioengineering, University of Illinois at Chicago, Chicago, Illinois, United States, ²Department of Oral Biology, University of Illinois at Chicago, Chicago, Illinois, United States

Biomimetic scaffolds have been shown to be effective for bone regeneration and similar strategies are under active investigation for cartilage tissue regeneration. The principal components for cartilage tissue regeneration are proteoglycans and collagen, II. We have investigated application of triple quantum sodium spectroscopy for characterization of biomimetic scaffolds for cartilage tissue regeneration. We found that the motional parameter 0c increases during the first two weeks and then suddenly drops before increasing again towards the end of fourth week. This is assumed to be an indicator of proteoglycans production during the early growth stage and random collagen network during the later stage of the growth.

Marek Chmelik¹, Ivica Just Kukurova^1,2, Stephan Gruber¹, Martin Krššák³, Michal Povazan^1,4, Martin Tkacov^1,4, Ladislav Valkovic¹, Siegfried Trattnig¹, and Wolfgang Bogner^1
1MR Centre of Excellence, Dept. Radiology, Medical University of Vienna, Vienna, Austria, ²Department of NMR and MS, Institute of Analytical Chemistry, Slovak University of Technology, Bratislava, Austria, ³Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria, ⁴Department of Nuclear Physics and Biophysics, Faculty of Mathematics, Physics and Informatics, Commenius University, Bratislava, Slovakia

The purpose of this study was to measure T₁ relaxation times of hepatic ³¹P metabolites at 7T, which are necessary for further method optimizations and corrections during data quantifications. T₁ values of eight hepatic ³¹P metabolite resonances could be determined in our study. No significant differences in T1 were observed for hepatic ³¹P metabolites at 7 T compared to lower field strength (i.e. 2T and 3T). This absence of any significant changes in T₁ with increasing B₀ is consistent with previous observations in rat liver, where nearly identical T₁ relaxation times were reported for 4.7 T and 8.5 T.

Mihaela Rata¹, Nandita Desouza¹, Michael Germuska¹, Michael Partridge², Martin O Leach¹, and Geoffrey S Payne^1
1MRI Unit, CR-UK and EPSRC Cancer Imaging Centre, Institute of Cancer Research and Royal Marsden Hospital, Sutton, United Kingdom, ²Radiotherapy and Imaging, CR-UK and EPSRC Cancer Imaging Centre, Institute of Cancer Research and Royal Marsden Hospital, Sutton, United Kingdom

18FDG PET uptake represents the gold standard technique for staging aggressive non-Hodgkin’s lymphomas (NHL) but quantified SUVmax at outset is also predictive of treatment response. The phosphomonester peak normalized by the total amount of â-NTP (nucleoside triphosphates) on 31P-MRS has also demonstrated promise as a predictive biomarker: This study explores the relationship between the predictive biomarkers. The absence of significant correlation between the glucose uptake using 18FDG-PET and PME/bNTP using 31P MRS suggests that they may contain complementary information on response prediction

Jannie P Wijnen^1,2, Lu Jiang¹, Wybe J.M. van der Kemp², Dennis W.J. Klomp², and Kristine Glunde^1
1Johns Hopkins University In Vivo Cellular and Molecular Imaging Center,Russell H. Morgan Department, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States, ²Department of Radiology, University Medical Centre Utrecht, Utrecht, Netherlands

Here we have demonstrated that using polarization transfer (PT) methods such as refocused insensitive nuclei enhanced by polarization transfer (RINEPT) and its adiabatic version (BINEPT) at 7 and 9.4Tesla can improve the 31P magnetic resonance spectroscopy (MRS) detection of phosphomono- and –diesters in human breasts and breast tumor xenograft models in vivo. BINEPT ³¹P MRS was able to detect partially resolved phosphoethanolamine, phosphocholine, glycerophosphoethanolamine and glyerophosphocholine because it is insensitive to unwanted broad resonances from macromolecules that do not posses H-P J-coupling, without compromising SNR compared to direct ³¹P MRS.

Min-Hui Cui^1,2, Kamaiah Jayalakshmi^1,3, Wei Zhang³, Laibin Liu³, Chandan Guha³, and Craig A. Branch^1,2
1Gruss Magnetic Resonance Research Center, Albert Einstein College of Medicine, Bronx, New York, United States, ²Radiology, Albert Einstein College of Medicine, Bronx, New York, United States, ³Radiation Oncology, Albert Einstein College of Medicine

³¹P MRSI and ¹H MRS have been applied to measure hepatic phosphagens and creatine or cyclocreatine after they were administrated in CK-transgenic mouse expressing CK_BBin liver. Phosphocyclocreatine accumulated much more than phosphocreatine in liver. Creatine and cyclocreatine have been detected for the first time in hepatocytes of CK-Tg mouse by in vivo ¹H MRS. Hepatic cyclocreatine signal intensity from ¹H MRS was correlated strongly with hepatic phosphocyclocreatine concentration estimated by ³¹P MRSI. These combined ¹H MRS and ³¹P MRSI techniques may provide a noninvasive method to estimate creatine kinase activity in rodents with CK expressing hepatocytes.

Jonathan Goodwin¹, Shunichi Koda¹, Masashi Ohfuchi¹, Anna Pawlak¹, Hironobu Yasui², Valery Khramstov³, and Hiroshi Hirata^1
1Hokkaido University, Sapporo, Hokkaido, Japan, ²Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, Japan, ³Ohio State University

In this work we assess the viability of pH sensitive imidazoline nitroxide for in-vivo pH mapping of mouse tumour using continuous wave electron paramagnetic resonance imaging (CW-EPR) to perform four dimensional spectral-spatial imaging. Comparison of pH in tumour model mouse leg was found to be reduced compared control mouse leg. Co-registration with 7T MRI demonstrated anatomical distribution of acquired pH map obtained from tumour model mouse. Successful demonstration of the technique in a larger population will allow further exploration of the relationship between pHe in tumour, and how the relationship changes in response to radiotherapy with and without radio-sensitizing drugs.

Miho C Emoto¹, Hideo Sato-Akaba², Hiroshi Hirata³, and Hirotada G Fujii^1
1Center for Medical Education, Sapporo Medical University, Sapporo, Hokkaido, Japan, ²Graduate School of Engineering Science, Osaka University, ³Graduate School of Information Science and Technology, Hokkaido University

EPR imaging using nitroxides is a powerful non-invasive method for visualizing the quantification of redox status caused by free radicals in vivo. 3-hydroxymethyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (HMP) and 3-methoxycarbonyl-2,2,5,5-tetramethyl-pirrolidine-1-yloxy (MCP) are widely used as blood-brain barrier-permeable nitroxide probes. In this study, their distributions in a mouse brain and their time courses to enter the brain were compared using our newly developed EPR imaging system and by MRI. The EPR imaging results revealed that MCP was more concentrated in the brain than HMP and that MCP entered the brain more rapidly than HMP after their administration to mice.

Yun Xiang¹, and Jun Shen^2
1Department of Laboratory Medicine, Wuhan Medical and Health Center for Women and Children, Wuhan, Hubei, China, ²NIMH, Bethesda, MD, United States

Acetate is a useful substrate for studying astroglial metabolism. To spectrally separate glutamate C5 (182.0 ppm) and acetate C1 (182.15 ppm) a two-step J editing method was devised. Homonuclear ¹³C-¹³C couplings were introduced by infusing [1, 2-¹³C₂]acetate. In vivo and phantom experiments were performed to demonstrate complete spectral separation of glutamate C5 from acetate C1. ¹³C spectral editing allows for studying acetate transport and metabolism in brain using in vivo ¹³C MRS of carboxylic/amide carbons without spectral interference.

Leif Schröder¹, Jagoda Sloniec², Christopher Witte¹, Ute Resch-Genger², and Andreas Hennig^2
1Leibniz-Institut für Molekulare Pharmakologie (FMP), Berlin, Germany, ²Bundesanstalt für Materialforschung und -prüfung (BAM), Berlin, Germany

Hyperpolarized xenon is a powerful NMR probe with both high sensitivity and specificity. It has been applied recently to reveal different intracellular NMR signatures of various cell lines. Here, we present a complementary method to detect different NMR signatures of functionalized xenon that partitions into membranes with negligible translocation. Exposing such sensors to various well defined biomembrane models yield very different z-spectra acquired with the Hyper-CEST method. This approach is sensitive to xenon exchange dynamics reflected by the CEST response. It therefore provides access to the related differences in membrane fluidity and could be used to reveal cell identity.

James A. Rioux^1,2, Chris V. Bowen^2,3, and Valerij G. Kiselev^4
1Department of Physics, Dalhousie University, Halifax, Nova Scotia, Canada, ²Institute for Biodiagnostics (Atlantic), National Research Council, Halifax, Nova Scotia, Canada,³Departments of Physics, Radiology and Biomedical Engineering, Dalhousie University, Halifax, Nova Scotia, Canada, ⁴Department of Radiology and Medical Physics, University Medical Center Freiburg, Freiburg, Germany

Existing analytical models of the MRI signal response to spherical magnetic particles (including SPIO-labelled cells) describe the FID and the signal at the echo time TE of spin echo sequences. In this work, we present an extension of these models that also describes the complete signal evolution during the spin echo in regimes where diffusion cannot be neglected. This model shows good agreement with both experimental data and Monte Carlo simulations. Fitting experimental data to this model may allow extraction of additional physical parameters, providing improved quantification of labelled cells.

Navin Michael¹, Suresh Anand Sadananthan², Lei Zhongding³, Yevgen Marchenko¹, and S. Sendhil Velan^1
1Singapore Bioimaging Consortium, Biomedical Sciences Institutes, 11 Biopolis Way, Singapore, ²Singapore Institute for Clinical Sciences, ³Institute for Infoccomm Research, Singapore

2D pulse sequences like 2D JPRESS suffer from long acquisition times and can benefit from the acquisition acceleration provided by phase array coils. Prior time-domain signal combination techniques have focused on aligning the initial phase of the multichannel FID to an arbitrary reference. The first time point samples are prone to phase errors. The current work shows that eddy current correction in a maximum echo-sampled 2D JPRESS sequence, using the unsuppressed water signal, implicitly compensates the phase offsets in a phased array coil. This can be used for coherently combining the phased array signals in the time domain.

Xing Chen¹, Peter Boesiger¹, and Anke Henning^1
1Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Zurich, Switzerland

Localized natural abundance 13C MRS provides an investigative tool for studying metabolism. Polarization transfer methods like DEPT can be used to enhance sensitivity. The combination of DEPT with proton localized PRESS avoids the large chemical shift displacement and enables tissue specific investigation of lipid composition. However, the concurrent strong homonuclear proton scalar coupling in many metabolites modifies the proton spin coherence distribution and therefore leads to a substantial reduction in the 13C signal enhancement. In this work, J-refocused PRESS localized DEPT is introduced to suppress this effect and enable simultaneous and tissue specific DEPT enhancement of multiple fatty acid resonances.

Richard AE Edden^1,2, Nicolaas AJ Puts^1,2, and Peter B Barker^1,2
1Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University, Baltimore, MD, United States, ²FM Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States

In this abstract, we introduce a new experiment JAM-PRESS that combines the resolution benefits of J-resolved and Mega-edited PRESS measurements. This is achieved by adding editing pulses to alternate TE increments of a J-PRESS experiment. Essentially this modification separates edited and unedited peaks by half the F1 spectral width, improving the resolution of the editing target while retaining J-resolution for other maetabolite peaks. The method is demonstrated in phantom and in vivo as applied to GABA.

Martin A. Janich^1,2, Rolf F. Schulte², Steffen J. Glaser¹, and Dirk Mayer^3,4
1Department of Chemistry, Technische Universität München, Munich, Germany, ²GE Global Research, Munich, Germany, ³Neuroscience Program, SRI International, Menlo Park, CA, United States, ⁴Department of Radiology, Stanford University, United States

The combination of constant-time point-resolved spectroscopy (CT-PRESS) with optimized broad bandwidth refocusing pulses (S-BURBOP) improved the signal detection of homonuclear coupled spins by reducing the chemical-shift displacement error. The signals of Lactate, Glutamate, and Glutamine were significantly increased in evaluations in a phantom and in healthy volunteers.

Tangi Roussel¹, Patrick Giraudeau², Hélène Ratiney¹, Serge Akoka², and Sophie Cavassila^1
1CREATIS, UMR CNRS 5220, INSERM U1044, Université Claude Bernard Lyon1, University of Lyon, Lyon, Rhône-Alpes, France, ²CEISAM UMR CNRS 6230, Université de Nantes

2D Magnetic Resonance Spectroscopy (MRS) is a well known tool for the analysis of complicated and overlapped MR spectra. However, 2D MRS suffers from long acquisition times due to the necessary collection of numerous increments in the indirect dimension (t1). This paper presents the first 3D localized 2D ultrafast J-resolved MRS sequence, developed on a small animal imaging system, allowing the acquisition of a 3D localized 2D J-resolved MRS spectrum in a single scan. Sensitivity and spatial localization properties were characterized. This sequence offers an efficient signal localization and shows a great potential for in vivo dynamic spectroscopy.

Luke Yuan-Je Wang^1,2, Hui Jun Vicky Liao², Ana K. Cadena², Saadallah Ramadan³, Carolyn Mountford^2,3, and Alexander P. Lin^2
1Department of Anesthesiology, Children's Hospital Boston, Boston, MA, United States, ²Department of Radiology, Brigham and Women's Hospital, Boston, MA, United States,³Faculty of Health, The University of Newcastle, Newcastle, New South Wales, Australia

: Lysine and lysine-containing macromolecules have been hypothesized to co-resonate near GABA in 2D COSY. In this proof-of-concept study, we were able to separate the relevant cross-peaks at 3T in vitro and in vivo.

Woan-Chyi Wang¹, Yi-Ru Lin¹, David M. Niddam^2,3, and Shang-Yueh Tsai^4,5
1Department of Electronic Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan, ²Brain Research Center, National Yang-Ming University, Taipei, Taiwan, ³Laboratory of Integrated Brain Research, Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan, ⁴Graduate Institute of Applied Physics, National Chengchi University, Taipei, Taiwan, ⁵Reasearch Center for Mind, Brain and Learning, National Chengchi University, Taipei, Taiwan

Cingulate cortex (CC) is involved in many pathological conditions including psychiatric disorders and chronic pain. Quantification of Glu and Gln in CC may provide important information about pathological mechanisms and drug dynamics. We used PEPSI sequence with short-TE and TEavg protocols to detect Glu and Gln in CC. Although a better fit was obtained for Glu with TEavg there was no obvious difference in Glu COV between two protocols. In conclusion, PEPSI is suitable for assessment of short-term and long-term changes in brain metabolites. Compared to TEavg, short-TE protocol had similar performance on Glu but provides more accurate quantification of Gln and other metabolites.

Mary A McLean¹, Martin A Janich^2,3, Ralph Noeske⁴, John R Grififiths¹, Steffen J Glaser², and Rolf F Schulte^3
1Cambridge Research Institute, Cancer Research UK, Cambridge, Cambridgeshire, United Kingdom, ²Dept of Chemistry, Technische Universität München, Munich, Germany,³GE Global Research, Munich, Germany, ⁴Research and Collaboration, GE Healthcare, Berlin, Germany

We examined the effect on lactate yield at 3T of incorporating broadband universal rotation by optimized pulses (BURBOP) into PRESS, in comparison with Shinnar-Le Roux (SLR) refocusing pulses. Lactate yield relative to N-acetyl aspartate in a large uniform phantom was found to be up to 97% of the theoretical maximum when using BURBOP refocusing pulses in conjunction with the ‘overpress’ scheme for further reducing chemical shift misregistration. Without overpress, the yield was 87% for BURBOP pulses vs. 43% for SLR. Lactate signal using BURBOP pulses was also shown to be robust to B1 variation over a range of approximately ±20%.

Catalina S. Arteaga de Castro¹, Mariska P. Luttje¹, Marco van Vulpen¹, Uulke A. van der Heide², Peter R. Luijten¹, and Dennis W.J. Klomp^1
1University Medical Center Utrecht, Utrecht, Netherlands, ²Netherlands Cancer Institute, Amsterdam, Netherlands

A non-selective excitation semi-LASER sequence (nsLASER) is presented to use in combination with an endorectal coil (ERC) for prostate MRSI at 7 Tesla. The limited coverage of the ERC makes it possible to use non-localized RF pulses without having spurious artifacts and signals coming from the surrounding structures of the prostate at the cost of a slightly longer acquisition time due to the large FOV needed. Excellent in-vivo MRSI of the prostate is obtained. Even in the presence of water and lipid remaining signals no baseline corruption or artifacts appear. The nsLASER sequence is recommended for prostate MRSI when combined with the use of an ERC at high fields.

Mohamed Tachrount¹, Guillaume Duhamel¹, Patrick Cozzone¹, and Virginie Callot^1
1CNRS UMR 6612, Marseille, France

Short TE 1H MR Spectroscopy allows in vivo non-invasive assessment of central nervous system metabolism. It has however not been extensively applied in the spinal cord (SC) due to technical challenges. This work describes an optimized localized 1H MRS for examination of the mice cervical SC at very high magnetic field (11.75 T) using semi-LASER selection sequence. The optimized sequence was successfully validated on healthy mice. This work may open new perspectives to study various pathological conditions such as SC injury.

Lijing Xin¹, Vladimir Mlynarik², and Rolf Gruetter^1,2
1Department of Radiology, University of Lausanne, Lausanne, Switzerland, ²Laboratory of functional and metabolic imaging, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland

In this study, a short-TE MRSI sequence (TE=12ms) based on a semi-adiabatic spin-echo was implemented at 7T Siemens scanner, and we demonstrate that it is feasible to measure high quality spectra from multiple voxels in human brain simultaneously, with full signal intensity, no baseline distortion and minimal chemical shift displacement and signal loss due to T2 and J-modulation, thus allows regional maps of nine metabolites. The high SNR achieved in this study can allow the further improvement of spatial resolution.

Mélanie Craveiro¹, Cristina Cudalbu¹, Nicolas Kunz^1,2, Vladimir Mlynárik¹, and Rolf Gruetter^1,3
1Laboratory for Functional and Metabolic Imaging, Ecole polytechnique fédérale de Lausanne, Lausanne, Switzerland, ²Division of Child Growth & Development, University of Geneva, Geneva, Switzerland, ³Departments of Radiology, Universities of Lausanne and Geneva, Switzerland

SpRARE is a fast spectroscopic imaging sequence that allows a good spectral resolution due to effective homonuclear decoupling. However, requirements such as high B₁homogeneity and short echo spacing are mandatory to avoid signal loss of coupled metabolites. Moreover efficient water suppression (WS) is necessary to prevent from increased noise and artifacts in the spectra. In this study, MEGA water suppression was implemented in spRARE, which allowed the complete removal of the residual water signal, and the detection efficiency of the coupled metabolites by spRARE at 9.4T was demonstrated.

Sandeep K Ganji^1,2, Abhishek Banerjee¹, Elizabeth Maher^3,4, and Changho Choi^1,2
1Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, United States, ²Radiology, University of Texas Southwestern Medical Center, Dallas, Texas, United States, ³Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, United States, ⁴Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, Texas, United States

In vivo spectroscopic imaging of Gly is challenging due to its low concentrations and the spectral overlap, primarily with myo-inositol. By going to higher field strengths this situation can improve due to increased spectral resolution. We employed an optimized chemical shift imaging method for glycine imaging at 7T and present preliminary data from healthy volunteers and tumor patients.

Adil Bashir¹, Joseph J Ackerman², and Robert J Gropler^3
1Radiology, Washington University, St. Louis, MO, United States, ²Chemistry, Washington University, St. Louis, ³Radiology, Washington University, St. Louis

A 1D-CSI in combination with surface coil is widely used for 31P NMR spectroscopy of the heart. However, the discrete Fourier transform used to spatially construct low resolution phase encoded CSI data can lead to Fourier ringing. This contaminates the signal from the heart tissue with that from the chest muscles. In this work we demonstrate that using a superficial and highly non-linear field gradient the signal can be quickly and effectively localized to the deep lying heart tissue with little or no contamination. The applicability of the technique in phantom and animals is demonstrated.

Isabell K. Steinseifer¹, Patrícia M. Nunes¹, Marnix C. Maas¹, Tom W.J. Scheenen^1,2, Andor Veltien¹, Ralf Mekle³, Rolf Gruetter⁴, and Arend Heerschap^1
1Radiology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands, ²Erwin L. Hahn Institute for Mgnetic Resonance Imaging, Essen, Germany, ³Physikalisch-Technische Bundesanstalt, Berlin, Germany, ⁴EPFL, Lausanne, Switzerland

We present localized ³¹P MRS with a modified SPECIAL sequence of a 125µl voxel inside mouse skeletal muscle at 7T. By implementing a GOIA-WURST(16,4) pulse we overcome RF inhomogeneities and increased chemical-shift artefacts in slice selective localization caused by high-magnetic field. With a comparable time resolution we were able to obtain a similar SNR as with an FID measurement of the whole mouse leg. Artefacts caused by signal contamination from neighbouring bones were eliminated because of good localisation. The short echo time allowed acquisition of J-modulated ATP signals. We reached sufficient time resolution to follow ischemia in selected muscles.

Miriam W Lagemaat¹, Marnix C Maas¹, Thiele Kobus¹, Andreas K Bitz^2,3, Mark J van Uden¹, Stephan Orzada^2,3, Arend Heerschap¹, and Tom W J Scheenen^1
1Radiology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands, ²Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen, Germany, ³Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, Essen, Germany

In vivo ³¹P MRSI of the human prostate is potentially important in characterizing prostate cancer. We determined T₁ relaxation times of the ³¹P metabolites and evaluated the NOE effect in the healthy human prostate at 7T to optimize the protocol in terms of sensitivity and measurement time for clinical use. A ³¹P MRSI sequence with a TR of 1.5s, flip angle of 45° and nominal voxel size of 1.9cm³ produces well-resolved spectra with up to 38% signal increase by NOE.

Patrick Waxmann¹, Tomasz Dawid Lindel¹, Florian Schubert¹, Bernd Ittermann¹, and Ralf Mekle^1
1Physikalisch-Technische Bundesanstalt, Braunschweig & Berlin, Germany

Starting with a SPECIAL sequence for localized spectroscopy, we kept the initial plane inversion pulse and replaced the conventional excitation pulse with a 4-fold accelerated 2D spatially selective excitation (SSE) pulse. A refocusing pulse is no longer needed for voxel definition and was eliminated, thus reducing the minimum echo time to 1.5 ms. This sequence allows to excite voxels of uniform thickness but arbitrary shape in two dimensions. It was implemented on a 3 T scanner equipped with 8 Tx channels. In phantoms, good spatial selectivity was demonstrated in imaging and spectroscopy experiments.

Thomas Kirchner¹, Anke Henning¹, and Peter Boesiger^1
1Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland

A striking manifestation of the voxel-bleeding effect in MRSI in vivo is subcranial fat signal falsely appearing in a voxel in the center of the brain. We developed a localized filtering technique for the suppression of fat artefacts. Unlike k-space apodization techniques, we achieve artifact suppression without incurring fat signal spread at the edge of the object.

Jürgen Finsterbusch^1,2
1Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg, Germany, ²Neuroimage Nord, University Medical Centers Hamburg-Kiel-Lübeck, Hamburg-Kiel-Lübeck, Germany

2D-selective RF excitations are a promising tool to minimize partial volume effects in single-voxel MRS. Segmentation is often applied to avoid excessive 2DRF pulse lengths. But for some trajectories like the blipped-planar trajectory, segmentation reduces the signal efficiency because many segments cover only outer k-space lines and yield low flip angles and signal amplitudes. Here, it is shown that the signal-to-noise ratio can be increased significantly by applying all segments with the full flip angle and scaling down the acquired signal accordingly. This does not alter the signal amplitude but can reduce the noise level considerably as is demonstrated experimentally.

Peter Ullmann¹, Johannes T. Schneider¹, Sarah R. Herrmann¹, and Wolfgang Ruhm^1
1Bruker BioSpin MRI GmbH, Ettlingen, Germany

Segmented parallel excitation (PEX) offers great potential for localized magnetic resonance spectroscopy (MRS) by allowing the excitation of arbitrarily shaped voxels which can be used to mitigate partial-volume effects and to increase SNR. In this study PEX-based spectroscopy was performed in a rat brain in vivo to assess the applicability of PEX for high-field small-animal MRS and to compare it to conventional selection methods. Results obtained at 9.4 T demonstrate that complex-shaped voxels adapted to the brain anatomy can be excited with good spatial selectivity and that spectra can be acquired thereof with improved SNR compared to cuboid-shaped spectroscopy voxels.

Ralph Noeske¹, Rolf Schulte², and Timo Schirmer^2
1Research and Collaboration, GE Healthcare, Berlin, Germany, ²GE Global Research, Munich, Germany

The SNR and excitation profile achievable by a localized MR spectroscopy experiment depends on the correct setting of the transmit gain (TG) to assure that the excitation pulses have correct flip angles across the prescribed ROI. Patient dependent spatial B₁⁺-inhomogeneities require a voxel based TG calibration method to achieve this. Automated slice based techniques can yield to B₁-miscalibration degrading excitation profile when B₁-sensitive pulses are used. This study presents a voxel based TG calibration based on the Bloch-Siegert shift method embedded into a standard spectroscopy sequence and determining TG for the same volume that is excited for the spectroscopy experiment.

Thomas Kirchner¹, Ariane Fillmer¹, Peter Boesiger¹, Klaas Paul Pruessmann¹, and Anke Henning^1
1Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland

We tailor the SENSE reconstruction algorithm towards accelerated parallel MRSI at ultra-high field strengths. Through calculation on an overdiscretized spatial grid and careful tuning of the spatial response function we achieve efficient suppression of signal contaminations caused by voxel bleeding without the increase of the effective voxel size that would be caused by conventional filtering techniques. We demonstrate up to 9-fold accelerated proton MRSI in vivo at 7T.

Trina Kok¹, and Elfar Adalsteinsson^1,2
1Massachusetts Institute of Technology, Cambridge, MA, United States, ²Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, United States

Metabolite spectra could be simulated and included as prior spectral information in the reconstruction of under-sampled 2D spectra via Multi-Task (MT) Bayesian CS. We previously showed that MT Bayesian CS successfully reconstructed peaks of Glu and Gln even with imperfect simulated metabolite spectra as priors. Spectroscopy data are intrinsically low SNR and here we extend previous work by incorporating noise modeling parameters for MT Bayesian CS and demonstrate improved reconstruction performance for under-sampled 2D spectra in CTPRESS compared to reconstruction without explicit noise modeling.

Guan Wang^1,2, AbdEl-Monem El-Sharkawy¹, William A. Edelstein¹, Michael Schär^1,3, and Paul A. Bottomley^1
1Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, United States, ²Electrical and Computer Engineering, Johns Hopkins University, Baltimore, MD, United States, ³Philips Healthcare, Cleveland, OH, United States

T1 and T2 are typically measured by separate partial saturation (PS) and spin-echo (SE) experiments. Here we present a new method to measure both T1 and T2 in just three acquisitions, without spin-echoes or varying the repetition period, TR. T2 is measured from two signals acquired with long- and short-duration adiabatic pulses. T1 is determined by varying the flip angle in two of the acquisitions. Thus, this 3-acquisition “Tri-tau” method employs a short α hard-pulse excitation, and short-and long-duration adiabatic β pulse excitations, all with TR≤T1. The method is validated with T1 and T2 SE and PS measurements on phantoms.

Vincent Oltman Boer¹, Peter R Luijten¹, and Dennis W.J. Klomp^1
1Radiology, UMC Utrecht, Utrecht, Utrecht, Netherlands

Double quantum filters suffer from severe signal loss if a long double quantum time is required. This is especially the case for applications in lipid rich environments such as fatty tumors or muscle tissue. Therefore a refocused double quantum filter was used that allows for the use of arbitrarily long dephasing gradients only at the cost of additional T2 loss. The lactate signal at rest and during exercise was detected in the human calf muscle after determination of the minimum required gradient area for complete lipid dephasing.

Deborah K. Hill¹, Erika Mariotti², Matthew R. Orton¹, Jessica K. R. Boult¹, Yann Jamin¹, Simon P. Robinson¹, Nada M. S. Al-Saffar¹, Martin O. Leach¹, Yuen-Li Chung¹, and Thomas R. Eykyn^1,2
1CRUK and EPSRC Cancer Imaging Centre, Division of Radiotherapy and Imaging, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, Surrey, United Kingdom, ²The Rayne Institute, Lambeth Wing, St Thomas Hospital, London, United Kingdom

While Dynamic Nuclear Polarisation is revolutionising the use of 13C MRS for real-time interrogation of metabolism, the complexity of the associated kinetic modelling used to extract rate constants for pyruvate-lactate exchange as a treatment biomarker lessens the immediate usefulness of the technique. We present a model-free approach to assessing treatment response in a range of cell lines, and show sensitivity to treatment response comparable to, yet much simpler in implementation than, kinetic modelling based on the modified Bloch equations.

Melissa Terpstra¹, Uzay E Emir¹, Lynn E Eberly¹, and Gulin Oz^1
1University of Minnesota, Minneapolis, MN, United States

Although increased precision of metabolite quantification at ultra-high field has been demonstrated, accompanying improvements in test-retest reproducibility have not been evaluated. Therefore, ¹H MR spectra were measured four times from each of four participants at both 3T and 7T. Outstanding spectral quality and reproducibility were achieved at 3T using commercially available hardware. While the Cramer-Rao lower bounds (CRLB) were universally lower at 7T than at 3T, the coefficients of variance (CV) were comparable at the two field strengths. Therefore, at the achieved spectral quality, factors other than quantification precision appear to limit inter-session reproducibility at 7T.

Catalina S. Arteaga de Castro¹, Alex Bhogal¹, Mariska P. Luttje¹, Marco van Vulpen¹, Juus Noteboom¹, Peter R. Luijten¹, Uulke A. van der Heide², and Dennis W.J. Klomp^1
1University Medical Center Utrecht, Utrecht, Netherlands, ²Netherlands Cancer Institute, Amsterdam, Netherlands

Variations of the main magnetic field can cause linewidth broadening and signal loss in long (8-10 min) MRSI experiments. In prostate MRSI a strongly coupled spin system (citrate) is observed. This spin system is sensitive to field variations, which can change the appearance of its peaks. Dynamic main field variations are observed in the prostate that exceed 15 Hz. These cause temporal susceptibility changes that explain the deteriorated spectrum. Second order B0 dynamic shimming simulations showed a gain of more than 10 Hz after correction of the B0 variations. Dynamic shimming can be implemented using localized navigators or field probes.

Céline Giraudeau¹, Odile Diou², Nicolas Tsapis², Philippe Robert³, Caroline Robic³, Marc Port³, Denis Le Bihan¹, Sébastien Mériaux¹, Fawzi Boumezbeur¹, Franck Lethimonnier¹, and Julien Valette^1,4
1NeuroSpin, I2BM, Commissariat à l'Energie Atomique, Gif-sur-Yvette, France, ²Univ Paris Sud, UMR CNRS 8612, Châtenay Malabry, France, ³Guerbet, Research Division, Roissy-Charles de Gaulle, France, ⁴MIRCen, I2BM, Commissariat à l'Energie Atomique, France

In the present work, an original spectroscopy sequence dedicated to PFOB and composed of a diffusion-weighted LASER module followed by an echo train is used to specifically detect angiogenesis in a carcinoma mouse model. We show that this sequence is more sensitive than a conventional LASER sequence and allows detection of sub-nanomolar concentrations of á_vâ₃-targeted PFOB nanoparticles. By selectively suppress signal coming from nanoparticles in the bloodstream, diffusion allows specific detection of angiogenesis on an individual animal. This method could be a novel concept to detect disease biomarkers by indicating the specificity of the signal provided by imaging.

Jyh-Miin Lin¹, Tzu-Chao Chuang², Wen-Chau Wu³, Hsiao-Wen Chung^4,5, and Shang-Yueh Tsai^6,7
1Department of Radiology, Duke University Medical Center, Durham, NC, United States, ²Department of Electrical Engineering, National Sun Yat-sen University, Kaohsiung, Taiwan, ³Graduate Institute of Oncology, National Taiwan University, Taipei, Taiwan, ⁴Department of Electrical Engineering, National Taiwan University, Taipei, Taiwan,⁵Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan, ⁶Graduate Institute of Applied Physics, National Chengchi University, Taipei, Taiwan, ⁷Research Center for Mind, Brain and Learning, National Chengchi University, Taipei, Taiwan

In vivo MR spectra without solvent suppression often incur poor spectral quality due to gradient-induced frequency modulation(FM). We invented an algorithmic method to identify and eliminate these artifacts. Advanced algebraic tool was introduced to separate symmetric peaks with opposite phases from metabolites and baseline. Based on time-domain methods, the amplitude contaminated by FM components are adjusted according to the diagonal elements of matrices which have been triangularized. Our result shows improvement of spectral quality and quantitatively lower biases. This method may be easily integrated into the processing programs, whereas the sequence and experimental design can remain similar.

Jeff Snyder¹, and Thomas Lange^1
1Dept. of Radiology, Medical Physics, University Medical Center Freiburg, Freiburg, Germany

A method to detect -aminobutyric acid (GABA) in vivo is presented based on subtraction spectroscopy. The method (JET) requires no special selective pulses and is based on flip angle variation in PRESS. The technique was tested in healthy subjects at 3 T with quantification analysis by LCModel and compared to the MEGA editing sequence. The Cramer-Rao lower bounds for GABA illustrated increased detection accuracy for JET (11%) as compared to MEGA (14%), signifying JET as a viable GABA detection method.

Changho Choi¹, Abhishek Banerjee¹, Sandeep Ganji¹, Ivan Dimitrov¹, Subroto Ghose¹, and Carol Tamminga^1
1University of Texas Southwestern Medical Center, Dallas, Texas, United States

A comparison study of GABA measurement by optimized PRESS and difference editing (MEGA) at 7 T is presented. The PRESS TE was optimized as 92 ms for detection of the GABA 2.28 ppm resonance. MEGA was used to edit the 3.0 ppm resonance with TE = 70 ms. Data were acquired from the medial occipital cortex in 5 healthy volunteers. The GABA levels estimated with PRESS and MEGA were 0.80±0.06 and 1.15±0.16 mM (mean±SD, n=5) with reference to creatine at 8 mM, respectively. The GABA measures by PRESS and MEGA are discussed, focusing on contaminations from macromolecules and homocarnosine.

Roland Kreis¹, Christine Sandra Bolliger¹, Erin Leigh MacMillan¹, Uwe Boettcher², and Chris Boesch^1
1Depts Clinical Research and Radiology, University Bern, Bern, Switzerland, ²Healthcare Sector, Customer Solutions Division, Siemens AG, Erlangen, Germany

MEGA PRESS editing is the most widely used technique for GABA measurements in human brain. Because it is an add/subtract method and measurement times are long, it is susceptible to small frequency, phase and amplitude drifts due to either patient related or technical instabilities. We have therefore combined it with non-water-suppressed MRS using the metabolite cycling technique to include the strong water signal in every acquisition as a reference signal. Editing parameters were optimized in vitro and in vivo for stability and sensitivity while retaining suppression efficiency for contaminating macromolecule signals.

Bernhard Strasser¹, Marek Chmelik¹, Siegfried Trattnig¹, Stephan Gruber¹, and Wolfgang Bogner^1
1Centre of Excellence, Department of Radiology, Medical University of Vienna, Vienna, Vienna, Austria

In this work the phase information obtained from a pair of gradient echo images is used for phasing CSI-data of 32 channels of a multi-channel-coil in order to sum up the signals of the coils and gain Signal to Noise Ratio compared to a Volume Coil. The additional 1.2 s measurement time is negligible. As a side benefit the resulting spectra are already correctly phased, leading to higher reproducibility, processing speed and accuracy of the fit. This method was tested in phantoms and healthy volunteers.

Ayse Sila Dokumaci¹, Niklaus Zölch¹, Michael Wyss¹, Alexander Fuchs¹, Peter Bösiger¹, and Anke Henning^1
1Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland

Neurotransmitters and antioxidants such as N-acetyl-aspartate (NAA), glutamate (Glu), glutamine (Gln), gamma-aminobutyric acid (GABA), and glutathione (GSH) play an important role in psychiatric pathophysiologies. Their detection in vivo can be performed by the dedicated 1H MRS methods such as PRESS using different echo times, MEGA-PRESS, and 2D JPRESS at 3T. However, the best method to be used is unknown. Therefore, in this work these methods were applied on 40 healthy volunteers and in 4 different brain regions for cross validation. PRESS sequence with the shortest echo time and JPRESS sequence were found to be the best candidates for this purpose.

Mélanie Craveiro¹, Cristina Cudalbu¹, and Rolf Gruetter^1,2
1Laboratory for Functional and Metabolic Imaging, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, ²Departments of Radiology, Universities of Lausanne and Geneva, Switzerland

An accurate macromolecule (MM) knowledge is necessary to a reliable metabolite quantification. However, as MM signal acquisition is time-consuming and needs further pre-processing steps, a unique rodent MM signal is commonly used for quantifying mouse and rat brain spectra. We developed in this study a novel and accurate method to remove metabolite residuals from MM signals prior quantification. Moreover, we showed that potential regional alterations of the MM signal in the mouse brain and alterations between mouse and rat MM signals have no significant effects on metabolite quantification.

Jullie Pan¹, and Hoby Hetherington^1
1Neurosurgery, Yale University, New Haven, CT, United States

Potential improvements in SNR and spectral resolution are often cited as a primary advantage for MRSI in moving to higher field strength. However, the improvement in metabolite linewidth is governed by a number of factors including, macro and microscopic (óB0Macro, óB0Micro) inhomogeneity and the intrinsic T2. At 7T in superior brain locations after 4th order shimming the intrinsic susceptibility differences between gray and white matter represent a majority of the residual inhomogeneity. Metabolite resonances track the water resonance, leading to spectral broadening in voxels with both gray and white matter contributions.

Niklaus Zoelch¹, Alexander Fuchs¹, Peter Boesiger¹, and Anke Henning^1
1University and ETH Zurich, Institute for Biomedical Engineering, Zurich, Zurich, Switzerland

It is highly desirable to combine ERETIC with the Klose correction, which frees spectra from disturbing eddy current effects. So far this was only possible when drawbacks in the fitting procedure where accepted. In our work we increased the usability of ERETIC by implementing an automatic phase correction and eddy current correction compensation. Therefore for the first time the ERETIC peak and the metabolites peaks are simultaneously quantifiable using standardized freely or commercially available algorithms as LCModel.

Donghoon Lee¹, Kenneth Marro¹, Mark Mathis¹, Eric Shankland¹, Cecil Hayes¹, Stacey Hansen², and James Olson^2
1Department of Radiology, University of Washington, Seattle, WA, United States, ²Fred Hutchinson Cancer Research Center, Seattle, WA, United States

We obtained robust estimates of 31P metabolite content in mouse brain tumor using a synthetic signal injection method and an optimized, 1H/31P dual tuned probe. 31P metabolite concentrations were determined for brain tumors in a genetically engineered mouse model of medulloblastoma. The dual tuned 1H/31P probe was composed of a half volume coil and a second coil to allow injection of pseudo signals. In addition to in vivo 31P metabolite quantitation, 1H MR imaging was conducted to identify brain tumor and to determine tumor volume prior to 31P MRS.

Christine Sandra Bolliger¹, Chris Boesch¹, and Roland Kreis^1
1Depts Clinical Research and Radiology, University Bern, Bern, Switzerland

A method to optimize 2DJ experiments is presented. It is aimed at quantification of a set of metabolites and is based on searching acquisition parameters that yield minimal Cramer Rao Minimum Variance Bounds (CRBs). We present optimized experiments for GABA, glutamate, glutamine and glutathione quantification in human gray matter. Maxiumum-echo sampling was proven to provide a large benefit for all metabolites and careful selection of TEs can further lower the CRBs substantially. A further improvement can be achieved by optimizing what we call generalized 2DJ xperiments where arbitrary TEs and arbitrary number of scans per TE are used.

Caroline Rae¹, Guangqiang Geng¹, and Stephen R Williams^2
1NeuRA, UNSW, Randwick, NSW, Australia, ²The University of Manchester, United Kingdom

Glutamine measurement is problematic using single-shot methods at 3T. Here, we evaluate in vivo, recommended PRESS timings, optimized asymmetric PRESS (A-PRESS) timings and a variant A-PRESS designed to minimize overlap of glutamine with the aspartyl moiety of NAA. Standard deviations of estimates were determined using the QUEST algorithm from jMRUI and appropriate metabolite basis sets. A-PRESS was found to be significantly better than PRESS for Gln determination and comparable with standard PRESS for glu, NAA, Cho and Cre. Use of the variant A-PRESS may also help improve estimate precision for Gln.

Florian Schubert¹, Ralf Mekle¹, Simone Kühn², Jürgen Gallinat³, and Bernd Ittermann^1
1Physikalisch-Technische Bundesanstalt, Berlin, Germany, ²Psychology and Educational Sciences, Ghent University, Ghent, Belgium, ³Psychiatry and Psychotherapy, Charité University Medicine

MEGA editing has long been the method of choice for determination of the inhibitory neurotransmitter GABA. Novel spin echo based methods enabling ultrashort TE being potential competitors, we compared MEGA-PRESS and the SPECIAL technique that allows for very short TE. Spectra were acquired on 36 healthy subjects from 25x40x20mm3 comprising the anterior cingulate cortex using MEGA-PRESS at TE=68 ms and SPECIAL at TE=6.6 ms. GABA was fitted reliably (CRLB<20%) in all SPECIAL and 31 MEGA-PRESS spectra. Concentration estimates agreed reasonably well and were correlated. An added advantage of SPECIAL are good fit results for up to 12 more metabolites.

Xiaodan YAN¹, Ivan Kirov¹, and Oded Gonen^1
1Radiology, New York University, New York, NY, United States

Voxelwise analysis of 3D proton MR spectroscopic imaging: Absolute metabolic quantification in deep brain structures at 3 T Magnetic Resonance spectroscopy (MRS) and spectroscopic imaging (MRSI) in the human brain are both susceptible to: (i) repositioning error of the voxel (or grid) in cross-sectional and longitudinal studies; (ii) hypothesis error [inappropriate choice of region(s) of interest (ROI)]; and (iii) operator error in manual ROI outlining. These combine to increase the variance of localized metabolic quantification, i.e., reduce its sensitivity. To address these issues in order we (i) co-register the 3D MRSI data to the MRI and transform both into standard Talairach space; (ii) perform voxelwise statistical analysis on co-registered data from 10 healthy volunteers acquired annually over 3 years (40 data sets); and (iii) apply standard-space pre-defined deep brain structures (thalamus, putamen, globus pallidus, posterior cingulate cortex, corpus callosum, centrum semiovale and corona radiata) ROIs to preprocessed metabolic maps to extract their average metabolic concentrations. Voxelwise analysis reveals that most of the variance is at the volume-of-interest (VOI) edges due to positioning differences; within the VOI, CSF partial volume is the primary source of variance, followed by cross-subject fine scale differences at the level of gyri and sulci. The metabolic concentrations the and inter-and-intra- subject variance from each ROI were obtained, e.g., the concentrations for NAA, Cr, Cho, mI and Glu were 6.8±1.2, 5.2±0.9, 1.2±0.2, 3.9±0.7, 5.5±1.1 mM in the left thalamus and 6.8±1.5, 4.5±1.0, 1.2±0.3, 4.1±1.0, 4.7±1.1 mM in the left centrum semiovale. Finally, we also propose a protocol for voxelwise group comparisons for comparative studies.

Jun Xu^1,2, John D West¹, Andrew J Saykin¹, and Ulrike Dydak^1,2
1Department of Radiology and Imaging Sciences, Indiana University School of Medcine, Indianapolis, IN, United States, ²school of Health Sciences, Purdue University, West Lafayette, IN, United States

An automated analysis of 3D MRSI data is being presented, which takes into account contributions from specific brain structures to each MRSI spectrum and thus allows obtaining brain region specific metabolite values. We demonstrate on the example of hippocampus data extracted from a 3D MRSI dataset that this type of brain-region specific analysis if more sensitive to small neurochemical changes occurring only in one brain structure, but not in adjacent ones, than current analysis methods. The method has been developed for an easy and sensitive comparison of metabolite levels of specific brain structures across groups in clinical studies.

Alexander Fuchs¹, Anke Henning², and Peter Boesiger^2
1Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Zurich, Switzerland, ²University and ETH Zurich

MR acquired data is usually sampled at higher much higher frequencies than the Nyquist condition. Before further processing this data needs to be downsampled to reduce the burden on storage requirements and processing time. Two commonly used downsample strategies are applied to ideal spectroscopic data and different artifacts related to these methods are identified. Especially in spectroscopy, artifacts in the initial time points of FIDs or phase distortions can lead to problems in further quantitative evaluations. Therefore a method is proposed that avoids the described problems and gives more reliable downsampled data.

Alexander Fuchs¹, Peter Boesiger², and Anke Henning^2
1Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Zurich, Switzerland, ²University and ETH Zurich

ProFit, a previously developed fitting tool for 2D JRPRES spectra was revised and certain drawback of the original implementation were tackled. Measured 2D JPRESS macromolecular baseline signals, surface splines to handle residual baseline distortions and a 2D model-free lineshape based on regularized splines were incorporated into ProFit. The results were compared between the recent and the revised version and it is shown that the inclusion of the these additional features together with a fine-tuned handling of prior knowledge leads to significantly better fit results.

Chi-Cheng Wang¹, Chien-Yu Liao^2,3, Shin-Lin Shih¹, and Chi-Long Juang^3
1Department of Radiology, Mackay Memorial Hospital, Taipei, Taiwan, ²Medical Imaging, Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan, ³Department of Radiological Technology, Yuanpei University, Hsin Chu, Taiwan

Philips 3.0T Magnetic Resonace Imagers were used to scan 30 low back pain patients and 30 healthy volunteers. T2 relaxation time maps of sagittal lumbar spine were acquired to obtain the averaged T2 values of inter-vertebral disc nucleus. Chemical shift Images of mutifidus muscle next to L4-L5 inter-veterbral disc were also acquired, neither water signal nor fat single were suppressed in order to calculate the fat/water ratio. After statistical analysis, our results indicated disc T2 values were highly correlated with fat content of multifidus.

Lenka Minarikova¹, Wolfgang Bogner¹, Marek Chmelik¹, Katja Pinker-Domenig¹, Hubert Bickel¹, Thomas Helbich¹, Siegfried Trattnig¹, and Stephan Gruber^1
1Centre of Excellence HF MR, Department of Radiology, Medical University of Vienna, Vienna, Austria

In previous studies, using single-voxel MR-spectroscopy or mutlivoxel MR-spectroscopy imaging (MRSI), choline signal with higher SNR was defined as a marker of malignancy in breast lesions. We present that choline signal can be detected using MRSI with high SNR in a large fraction of normal breast tissue and the SNR demonstrates an exponential correlation with breast density and age of the subject. Therefore, breast MRS-data from younger subjects with breast lesions should be interpreted with caution.

Theodore F Towse^1,2, Amanda KW Buck¹, Jared A Godar³, and Bruce M Damon^1,4
1Radiology, Vanderbilt University, Nashville, TN, United States, ²Institute of Imaging Science, Nashville, TN, United States, ³Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, United States, ⁴Institute of Imaging Science

Interest in quantifying myocelluar lipid content including extramyocellular lipids (EMCL) and and intramyocellular lipids (IMCL) as well as the rate of turnover of these lipids has increased recently due to the finding of increased IMCL in insulin resistant subjects, suggesting a possible role in the pathogenesis of diabetes. However quantification of these lipid moieties is not trivial due to the overlap between the IMCL and EMCL peaks in the 1H spectrum. We propose using the fiber orientation, as determined by diffusion-tensor (DT-) MRI, as prior knowledge in fitting the EMCL and IMCL peaks, thereby improving overall quantification.

Xing Chen¹, Peter Boesiger¹, and Anke Henning^1
1Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Zurich, Switzerland

Adipose tissue is a major site of cholesterol storage. A variety of nutritional and metabolic alteration may influence the adipose tissue cholesterol level which has been studied in rats by chemical analysis. Localized natural abundance 13C MRS has been shown to be a powerful noninvasive technique for the study of lipids in vivo and has been applied to study the major classes of fatty acids. In this work, detection of cholesterol is reported for the first time noninvasively in human calf adipose tissue by 13C MRS at 7T, with J-refocused 1H PRESS localized DEPT sequence combined with broadband decoupling.

Mikael Fredrik Forsgren^1,2, Mattias Ekstedt³, Olof Dahlqvist Leinhard^1,2, Oscar Andregård⁴, Nils Dahlström^2,5, Johan Kihlberg^2,5, Stergios Kechagias^6,7, Sven Almer^7,8, Örjan Smedby^2,5, and Peter Lundberg^1,2
1Depts of Radiation Physics, Linköping University and Radiation Physics, UHL County Council of Ostergotland, Linköping, Sweden, ²Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden, ³Depts of Clinical and Experimental Medicine (IKE), Faculty of Health Sciences, Gastroenterology and Hepatology unit, Divison of Inlammation Medicine, Linköping University, Linköping, Sweden, ⁴Linköping University, Linköping, Sweden, ⁵Depts of Medical and Health Sciences (IMH), Division of Radiological Sciences, Linköping University, Linköping, Sweden, ⁶Depts of Medical and Health Sciences (IMH), Division of Cardiovascular Medicine, Linköping University, Linköping, Sweden, ⁷Depts of Endocrinology and Gastroenterology, UHL County Council of Ostergotland, Linköping, Sweden, ⁸Depts of Clinical and Experimental Medicine (IKE), Divison of Gastroenterology and Hepatology, Linköping University, Linköping, Sweden

Measuring the degree of liver steatosis is often important for treatment and prognosis in both a clinical and research context. The quantitative stereological point-counting analysis of biopsies has been shown to have high reproducibility, 1H MRS is a viable non-invasive method for liver fat content estimation. In this prospective study we have shown a good correlation between quantitative 1H MRS and stereological point-counting analysis of biopsies (Spearman rho = 0.90).

Qiong Ye¹, Alexander Fuchs¹, and Markus Rudin^1,2
1Institute for Biomedical Engineering, Zürich, Switzerland, ²Institute of Pharmacology and Toxicology, Zürich, Switzerland

Both fat content and their composition in adipose tissues and liver were accessed non-invasively with proton magnetic resonance spectroscopy in 34 weeks old ob/ob mice, a well-established murine model of obesity, using 9.4T system. In this work, spectra from different adipose tissues (subcutaneous fat pads at neck and belly as well as visceral fat) and from liver were compared. Liver showed a significant lower amount of lipids amount than three adipose tissues compartments. Lipids from lower belly displayed a higher degree of saturation. Furthermore, the fraction of polyunsaturated and monounsaturated lipids was found different among adipose tissues and liver.

Michael D Nelson¹, Vinaya Simha², Edward Szczepaniak¹, Ronald G Victor¹, Abhimanyu Garg², and Lidia S Szczepaniak^1
1Cedars-Sinai Medical Center, Los Angeles, California, United States, ²UT Southwestern Medical Center, Dallas, Texas, United States

Obesity is associated with ectopic accumulation of fat in organs such as the heart, skeletal muscle and the liver. Seminal basic research suggests that excessive accumulation of fat in non-adipocytes triggers adverse signaling pathways ultimately leading to organ dysfunction. Patients with generalized lipodystrophies, have near total lack of body fat and provide the unique opportunity to study the effects of ectopic myocardial fat deposition in the absence of obesity. We propose that myocardial steatosis and associated lipotoxicity may be one of the mechanisms contributing to cardiomyopathy in patients with generalized lipodystrophy.

Åsa Carlsson^1,2, Maja Sohlin², Maria Ljungberg^1,2, and Eva Forssell-Aronsson^1,2
1Department of Medical physics and Biomedical Engineering, Sahlgrenska University Hospital, Gothenburg, Sweden, ²Department of Radiation Physics, University of Gothenburg, Gothenburg, Sweden

Proton MR-spectroscopy is an increasingly popular tool for studying the heart metabolism. For quantification, the triglyceride signal is often related to an internal reference. However, if the volume of interest (VOI) includes any of the ventricular blood those ratios might be affected. In this work, we investigated how the lipid quantification is affected by blood contamination by comparing spectra from VOIs fitted within the ventricular septum with spectra from VOIs enclosing the septum. It is shown that the lipid, water and creatin signal are differently affected by blood contaminations and hence, blood contamination will affect lipid quantification.

Anant Bahadur Patel¹, Vivek Tiwari¹, and Dev Ketan Thacker^1
1NMR Microimaging and Spectroscopy, Centre for Cellular and Molecular Biology, Hyderabad, Andhra Pradesh, India

Brain development continues throughout gestation and postnatal period. As alcohol binds to glutamate and GABA receptors, exposure of alcohol during prenatal and postnatal period might affect the development of neurons and associated functions. Current study investigates the glutamatergic and GABAergic metabolism in the pups at P25 age obtained from dams exposed with alcohol during prenatal or postnatal period by using ¹H-[¹³C]-NMR spectroscopy in conjunction with infusion of [1,6-¹³C₂]glucose. Both, prenatal and postnatal exposure of alcohol to pups led to a reduction in glucose oxidation and neurotransmission associated with glutamatergic and GABAergic neurons.

Anant Bahadur Patel¹, Vivek Tiwari¹, and Vaidyanathan Subramanian^1
1NMR Microimaging and Spectroscopy, Centre for Cellular and Molecular Biology, Hyderabad, Andhra Pradesh, India

Alcohol is known to cause impairment of cognitive, psychological functions and neural activities. Ethanol modulates synaptic transmission in central nervous system upon its binding to NMDA, AMPA and GABAA receptors. The objective of current study was to evaluate the effect of acute alcohol on cerebral metabolism associated with glutamatergic and GABAergic neurons using ¹³C NMR spectroscopy in conjunction with infusion of [1,6-¹³C₂]glucose in mice. Our findings indicate that acute alcohol treatment selectively impaired glutamatergic TCA cycle and neurotransmitter cycling without any significant change in GABAergic activity.

Anant Bahadur Patel¹, and Pandichelvam Veeraiah^1
1NMR Microimaging and Spectroscopy, Centre for Cellular and Molecular Biology, Hyderabad, Andhra Pradesh, India

Effects of alcohol exposure via oral route on cerebral metabolism is not fully understood. In this study, we have investigated glutamatergic and GABAergic metabolism in cerebral cortex in mice exposed with different dose of alcohol via intra-gastric route. Acute treatment with alcohol at higher dose increased level of cortical GABA. Alcohol exposure selectively attenuates the excitatory activity without much changes in inhibitory function.

Anant Bahadur Patel¹, Henk De Feyter², Douglas L Rothman², Kevin L Behar³, and Puneet Bagga^1
1NMR Microimaging and Spectroscopy, Centre for Cellular and Molecular Biology, Hyderabad, Andhra Pradesh, India, ²Diagnostic Radiolgy, Magnetic Resonance Research Center, Yale University, New Haven, CT, United States, ³Psychiatry, Magnetic Resonance Research Center, Yale University, New Haven, CT, United States

The steady state ¹³C enrichment of cortical glutamine (Gln) during intravenous infusion of [1-¹³C]/[1,6-¹³C₂]glucose is ~25-30% lower than the corresponding glutamate enrichment. The source of this Gln ‘dilution’ is unknown. The contribution of plasma Gln to the cortical Gln dilution was assessed in anesthetized mice after intravenous [U-¹³C₅]glutamine infusion. Cortical Gln ¹³C enrichment increased with time while total cortical metabolite levels were unaltered over a range of plasma Gln. The steady state labeling of cortical Gln-C4 appeared to be independent of plasma glutamine level. Basal plasma Gln could account for ~30-35% of glutamine dilution.

Silvia Mangia¹, Anjali Kumar², Amir Moheet², Lynn Eberly³, Rachel Roberts³, Elizabeth Seaquist², and Ivan Tkac^1
1CMRR - Dept. of Radiology, University of Minnesota, Minneapolis, Minnesota, United States, ²Dept. of Medicine, University of Minnesota, Minneapolis, Minnesota, United States, ³Div. of Biostatistics, University of Minnesota, Minneapolis, Minnesota, United States

In this work we investigated differences in the neurochemical profiles of subjects with Type 1 Diabetes Mellitus (T1DM) relative to similarly aged healthy controls at the same level of plasma glucose using the increased sensitivity and spectral resolution of 1H-MRS at 4T. Data were analyzed from a group of 14 patients with long-standing T1DM (>10 years) and a group of 32 healthy controls. Levels of NAA and glutamate were lower by 6% in the grey matter of T1DM as compared to controls (p<0.005 and p<0.05, respectively), supporting the hypothesis that T1DM is associated with neuronal loss or dysfunction.

Susann Boretius^1,2, Roland Tammer^1,3, Thomas Michaelis¹, and Jens Frahm^1,3
1Biomedizinische NMR Forschungs GmbH, Max-Planck-Institut für biophysikalische Chemie, Göttingen, Germany, ²Klinik für Diagnostische Radiologie, Universitätsklinikum Schleswig-Holstein, Kiel, Germany, ³DFG Center of Molecular Physiology of the Brain (CMPB), Göttingen, Germany

It is largely unknown how the brain metabolism is modified by volatile anesthetic agents like isoflurane in intact living organisms. Localized proton MRS in mice revealed a major increase of lactate and alanine by isoflurane. Further analysis of this phenomenon also revealed significantly increased GABA, choline containing compounds, and myo-Inositol. Glutamate initially increased but then decreased under constant isoflurane. Isoflurane effects were attenuated by suppression of the adrenergic nervous system and amplified by adrenergic stimulators. Apparently, MRS has a great potential of new insights into anesthesia. Brain studies using isoflurane anesthesia must take these metabolic changes into consideration.

Puneet Bagga¹, Suresh Kumar M¹, and Anant Bahadur Patel^1
1NMR Microimaging and Spectroscopy, Centre for Cellular and Molecular Biology, Hyderabad, Andhra Pradesh, India

MPTP is a well established neurotoxin which causes selective degeneration of dopaminergic neurons in substantia nigra leading to dopamine loss and hence PD. Neuroprotective effects of caffeine, a MAO-B inhibitor against MPTP were investigated using infusion of [1,6-13C2]glucose and 1H-[13C]-NMR spectroscopy in adult male C57BL6 mice. Treatment with MPTP led to loss of glutamatergic and GABAergic activity in cortex, striatum, thalamus-hypothalamus and olfactory bulb. Pretreatment with caffeine led to recovery of glutamatergic and GABAergic activity in cortex and olfactory bulb, but the same in striatum and thalamus-hypothalamus was only partially recovered, suggesting partial neuroprotection conferred by caffeine against MPTP neurotoxicity.

Benoit Schaller¹, Lijing Xin², and Rolf Gruetter^3
1Laboratory of Functional and Metabolic Imaging, Ecole Polytechnique Federale de Lausanne, Lausanne, Vaud, Switzerland, ²Department of Radiology, University of Lausanne, Lausanne, Switzerland, ³Laboratory of Functional and Metabolic Imaging, Ecole Polytechnique Federale de Lausanne, Lausanne, Switzerland

The accuracy of the metabolite quantification of short echo time is challenged by the broad baseline resonances underlying the whole ¹H spectrum, identified as macromolecules (MM) and characterized by short T₁ and T₂. Macromolecule signal was acquired with a semi adiabatic IR SPECIAL sequence in two different tissues (white matter and grey matter, n=5 for each). Small but significant changes were found in the quantification Gln, Glu and NAA which are directly link the macromolecules signal differences in the region around 2.3-2.6ppm. A general in vivo measured MM baseline seems sufficient to ensure a reliable quantification of the metabolites.

Francesca Branzoli¹, Aranee Techawiboonwong², Sebastian Aussenhofer¹, Andrew Webb¹, and Itamar Ronen^1
1C. J. Gorter Center for High Field MRI, Department of Radiology, Leiden University Medical Center, Leiden, Netherlands, ²Department of Electrical Engineering, Mahidol University, Bangkok, Thailand

Here we propose functional Diffusion-Weighted Spectroscopy (fDWS) as a new method to investigate compartment-specific microstructural and metabolic changes related to neuronal activation. In this method a time series of alternating diffusion and non-diffusion weighted spectra is acquired, yielding a time-resolved series of apparent diffusion coefficient (ADC) values of metabolites correlated with neuronal activation. Especially, the detected changes in tCr and tCho ADCs can be exploited as a viable probe for brain activity, providing a tool for direct measurement of metabolic and microstructural changes during neuronal activation.

Markus Sack^1,2, Gabriele Ende¹, Alexander Sartorius^2,3, and Wolfgang Weber-Fahr^1,2
1Neuroimaging, Central Institute of Mental Health, Mannheim, Germany, ²Translational Imaging, Central Institute of Mental Health, Mannheim, Germany, ³Psychiatry and Psychotherapy, Central Institute of Mental Health, Mannheim, Germany

¹³C MRS suffers from an extremely low signal-to-noise ratio (SNR) compared to ¹H MRI/MRS due to the low Larmor frequency and low natural abundance. Because of the small brain size the approach of dynamic ¹³C MRS in mice is even more challenging but provides the advantage of investigating mouse models. We present in vivo data from one of the first ¹³C-cryo-coils for mouse brain imaging using an ISISDEPT sequence and [1-¹³C]-enriched glucose on a 9.4T scanner. The obtained spectra show a good SNR and proof that the use of a cryo-coil is feasible for ¹³C MRS in the mouse brain.

Ida Ashoori^1,2, Ashok Panigrahy^1,3, Arabhi Nagasunder^1,4, Girish Dhall⁵, Marvin D. Nelson¹, and Stefan Blüml^1,2
1Radiology, Childrens Hospital Los Angeles, Los Angeles, CA, United States, ²Rudi Schulte Research Institute, Santa Barbara, CA, United States, ³Pediatric Radiology, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States, ⁴Radiology, Children's Medical Center, Dallas, Dallas, TX, United States, ⁵Hematology/Oncology, Childrens Hospital Los Angeles, Los Angeles, CA, United States

13C enriched (U-13C) glucose was administered orally to three pediatric brain tumor patients with prominent citrate and to four healthy controls. MR spectra, using a standard PRESS sequence were acquired before and after Glc administration. 13C label replaced 12C and resulted in an apparent reduction of the 1H MRS detectable breakdown products of glucose such as glutamate (Glu) in controls. In patients, citrate, an intermediate of the TCA-cycle, did not accumulate significant label. This is consistent with citrate being not actively involved in glucose metabolism.

Brian Andrews-Shigaki^1,2, Yifan Chen¹, Asamoah Bosomtwi², Reed Selwyn², and Haiying Tang^2
1Military & Emergency Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, United States, ²Radiology & Radiological Sciences, Uniformed Services University of the Health Sciences, Bethesda, MD, United States

The effects of heat stress on the brain remain undetermined. Ee analyzed changes in metabolites from selected brain regions in mice following heat exposure using proton Magnetic Resonance Spectroscopy (1H-MRS). In the hypothalamus, significant decreases in NAA and Cr were shown 24 hours after heat exposure. In addition, significant increases in Glx were also demonstrated in the cerebellum. Results show no changes in metabolites in the hippocampus. Neuronal injury from heat stress is not homogeneously distributed in the brain and is localized hypothalamus. Increase of Glx in the cerebellum is unexpected and should be investigated further.

Saadallah Ramadan¹, Hui Jun Liao Liao², Alexander Lin², and Carolyn Mountford^2,3
1Centre for MR in Health, School of Health Sciences, University of Newcastle, Callaghan, New South Wales, Australia, ²Center for Clinical Spectroscopy, Brigham and Women's Hospital, Boston, MA, United States, ³Centre for MR in Healt, University of Newcastle, Callaghan, NSW, Australia

: Different types of COSY spectroscopy (adiabatic COSY, constant-time COSY, and localized COSY) are evaluated with a series of phantoms with variable concentrations of glutamate (Glu)/glutamine (Gln), to find out which sequence is the most optimal in determining relative amounts of Glu and Gln. While cross peaks obtained in the three types of COSY correlated well with total pool of Glu/Gln, they did not correlate with ratio of Glu to Gln.

Benoit Schaller¹, Lijing Xin², and Rolf Gruetter^1,3
1Laboratory of Functional and Metabolic Imaging, Ecole Polytechnique Federale de Lausanne, Lausanne, Vaud, Switzerland, ²Department of Radiology, University of Lausanne, Lausanne, Switzerland, ³Department of Radiology, Univerisities of Lausanne and Geneva, Switzerland

Macromolecules exhibit a broad signal underlying the entire ¹H spectrum and inaccuracy in the measurement of the macromolecules might lead to systematic errors preventing an accurate and reliable quantification of the metabolites. Macromolecule signal was acquired with an IR SPECIAL sequence and then inserted into the LCModel basis sets. The choice of the built-in LCModel spline baseline and acquired in vivo macromolecules (n=3) yielded either minor (Ins, Cr, PCr, Glu around 8-25%) or major (GABA, PE, GPC around 36-68%) differences in the metabolites quantification. These substantial differences are mainly due to an underestimation of the macromolecule signal around 2-3.5ppm.

Xiao-Hong Zhu¹, and Wei Chen^1
1CMRR, Department of Radiology, University of Minnesota Medical School, Minneapolis, MN, United States

In vivo ³¹P MRS is useful for studying the brain high-energy phosphate metabolism and ATP energy, and its low intrinsic sensitivity can be partially overcome at high/ultrahigh field. One key benefit of the high field in addition to the sensitivity gain is the improvement in spectral resolution. However, the field dependence of ³¹P resonance linewidth or T₂* is determined by two relaxation mechanisms: dipole-dipole and chemical shift anisotropy (CSA). The later will accelerate the linewidth broadening at higher field following B₀² relation. To address this concern, we quantitatively investigated the field dependence of PCr, -ATP and -ATP linewidths based on the ³¹P MRS data of human and cat brains covering B₀ from 1.5T to 16.4T. The overall results indicate large improvements in spectral resolution towards higher fields; they don’t support the notion that CSA could become the dominate T₂* relaxation mechanism at high/ultrahigh field.

Jin Seo¹, Hyun Jin Park¹, Youn-Ki Nam², Young Han Lee¹, Ho-Taek Song¹, and Jin-Suck Suh^1
1College of Medicine, Yonsei University, Seoul, Korea, ²Agilent Technologies Korea Ltd., Seoul, Korea

Among the various metabolites involved in the glucose metabolism of the tumor, pyruvate and lactate are the highlighted metabolites in the up-regulated glucose metabolism of malignant neoplasm. The purpose of this study is to determine the enzymatic conversion of [1-13C]pyruvate to [1-13C]lactate with exclusion of magnetization transfer effect from the hyperpolarized ¹³C. Enzymatic conversion ratio of [1-13C]lactate/pyruvate in glioma and normal brain were evaluated ex-vivo by using 11.7T NMR. DCE-MRI elucidated the vascular permeability characteristics of highly metabolic glioma. In-vitro cellular LDH assay of C6 glioma cells proved enzyme activity. The conversion ratio and quantitative DEC-MRI parameter K_ep were correlated.

Vasile Stupar^1,2, Coquery Nicolas^2,3, Farion Régine^1,2, Emmanuel Luc Barbier^2,3, Chantal Rémy^2,3, and Florence Fauvelle^4
1Precilinical MRI Facility, Grenoble, France, ²U836, INSERM, Grenoble, France, ³Université Joseph Fourier, Grenoble, France, ⁴IRBA antenne CRSSA, La Tronche, France

In vivo 1H MRS can provide information regarding glioma growth and response to treatment. A wider range of metabolites can be obtained ex vivo in biopsies using HRMAS 1H MRS. The metabolic data can be interpreted and classified using multivariate pattern recognition methods, such as Projection to Latent Structure-Discriminant Analysis (PLS-DA). Comparison of metabolic profiles between 1H MRS and HRMAS 1H MRS is essential and the ability of both approaches to discriminate tumoral from normal tissue with statistical tools such as PLS-DA might help for diagnosis. We have used this approach in the rat RG2 model of glioma.

Noriko Mori¹, Flonne Wildes¹, Kristine Glunde^1,2, Catherine Hudson³, and Zaver M Bhujwalla^1,2
1JHU ICMIC Program, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States, ²The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, ³Vertex Pharmaceuticals (Europe) Ltd, Abingdon, Abingdon, Oxfordshire, United Kingdom

High choline kinase (Chk) expression and increased phosphocholine (PC) levels are frequently observed in aggressive cancers. Unraveling the role of Chk and PC will provide new insights in the malignant phenotype and lead to the development of treatments targeting this enzyme and choline metabolism. We previously observed that downregulating Chk expression with siRNA resulted in a significant reduction of PC and proliferation in breast cancer cells. Here we have found that a potent inhibitor of Chk activity reduced PC without altering cell proliferation, pointing to the importance of the enzyme, but not necessarily its activity, in breast cancer cell survival.

Thiele Kobus¹, Jack Van Asten¹, Alan Wright¹, Arend Heerschap¹, and Tom Scheenen^1
1Radiology, Radboud University Nijmegen Medical Centre, Nijmegen, Gelderland, Netherlands

PRESS and semi-LASER based ¹H MRSI was performed in 17 patients with highly aggressive prostate cancer. The maximum choline plus creatine over citrate ratio and the maximum choline over creatine ratio were determined. Both metabolite ratios were very abnormal in all patients. The absence of frequency-selective lipid suppression in the semi-LASER sequence enables detection of metabolites in a broader frequency range. This enabled detection of an unassigned peak at 2.05 ppm. Although the identity of this resonance remains unknown, it was excluded that this resonance belonged to either spermine, glutamate or glutamine.

Alexandra Constantin¹, Adam Elkhaled², Llewellyn Jalbert¹, Kenneth Smith², Tracy McKnight², Annette Molinaro², Joanna Phillips², Susan M. Chang², and Sarah J. Nelson^2
1University of California, Berkeley, Berkeley, CA, United States, ²University of California, San Francisco

The HRMAS metabolic profiles of recurrent and newly diagnosed grade 2 and 3 gliomas were compared in order to examine the changes that occur after treatment. Lower levels of myo-inositol/total choline (MCI) were found in recurrent gliomas. Higher levels of glutathione and MCI were detected in the recurrent grade 2 gliomas. Higher levels of taurine and aspartate and lower MCI levels were recorded in recurrent grade 3 gliomas compared to their newly diagnosed counterparts. Multivariate models were able to distinguishing between the recurrent and newly diagnosed tumors with more than 90% accuracy, suggesting that these lesions are metabolically distinct.

Kamaiah Jayalakshmi^1,2, Min-Hui Cui^1,3, Wei Zhang², Laibin Liu², Craig A. Branch^1,3, and Chandan Guha^2
1Gruss Magnetic Resonance Research Center, Albert Einstein College of Medicine, Bronx, New York, United States, ²Radiation Oncology, Albert Einstein College of Medicine,³Radiology, Albert Einstein College of Medicine, Bronx, New York, United States

³¹P MRSI has been employed to estimate hepatic phosphagen and ATP concentrations in transgenic mice expressing creatine kinase (CK-Tg) in liver with administration of cyclocreatine. A marked amount of phosphocyclocreatine was stored in liver of CK-Tg mouse with administration of cyclocreatine. In contrast, hepatic ATP concentrations decreased. These were accompanied by decreased serum creatine levels and increased urinary creatine levels. The significant amount of phosphocyclocreatine stored in CK-Tg mouse liver may serve as a false feedback corepressor of creatine biosynthesis since liver is usually lack of phosphagen. Abundant phosphocyclocreatine, a poor creatine kinase substrate, may also impede ATP production.

John James Walsh^1,2, and Samuel Colles Grant^1,2
1Center for Interdisciplinary Magnetic Resonance, The National High Magnetic Field Laboratory, Tallahassee, Florida, United States, ²Chemical & Biomedical Engineering, The Florida State University, Tallahassee, Florida, United States

The abdominal ganglia of the sea hare Aplysia californica was utilized to study the relaxation and diffusion properties of neurons in a tissue model under different osmotic states. Both ¹H and ²³Na MRI at 11.75 T were performed to quantify relaxation as a function of tonicity. The relationship of these parameters to cell volume changes can be used as a basis for understanding cell swelling, osmotic regulation and ionic redistributions in a neural tissue model and provide insight into the origins of sodium hyperintensities seen in ischemia and neurodegeneration.

Jianghua Feng^1
1Department of Electronic Science, Fujian Key Laboratory of Plasma and Magnetic Resonance, Xiamen University, Xiamen, Fujian, China

NMR-based metabonomic strategy was used to investigate the metabolic responses to nicotine-induced dose- and time-dependent effects. Multivariate analysis of NMR data from respective pathophysiological regime including materal and fetal plasma and rat amniotic fluids revealed that nicotine ingestion caused the abnormal changes of glucose, lipid and protein metabolisms. Furthermore, under the defined screening principles, a set of small molecular metabolites in maternal plasma were selected out as the candidate biomarker served the diagnosis of IUGR. Although the specificity and universality of these biomarkers need a further investigation, the present study gives a new clue for the diagnosis and prevention of IUGR.

Mikael Fredrik Forsgren^1,2, Ann Bengtsson³, Olof Dahlqvist Leinhard^1,2, Birgitta Sören³, Vaclav Brandejsky^4,5, Eva Lund^1,5, and Peter Lundberg^1,2
1Depts of Radiation Physics, Linköping University and Radiation Physics, UHL County Council of Ostergotland, Linköping, Sweden, ²Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden, ³Depts of Rheumatology, University Hospital and Faculty of Health Sciences, Linköping, Sweden, ⁴Depts Clinical Research and Radiology, University Bern, Bern, Switzerland, ⁵Depts of Medical and Health Sciences (IMH), Division of Radiological Sciences, Linköping University, Linköping, Sweden

An impaired muscle energy metabolism in fibromyalgia (FM) patients has been suggested. The purpose of this study was to non-invasively analyze the content of phsophogens in the resting quadriceps muscle in FM patents compared to healthy controls using quantitative 31P MRS. Using an external reference for normalization we found significant group differences in PCr and NTP-Mg, suggesting that quantitative 31P MRS might be used as a biomarker for FM.

Ligong Wang¹, Nouha Salibi², Gregory Chang¹, Jenny T. Bencardino¹, James S. Babb¹, Andrew Rokito³, Laith Jazrawi³, Orrin Sherman³, and Ravinder R. Regatte^1
1Radiology, New York University Langone Medical Center, New York, New York, United States, ²Siemens HealthCare, Malvern, PA, United States, ³Orthopaedic Surgery, NYU Langone Medical Center, New York, New York, United States

This study evaluated saturated lipids and unsaturated indices in different compartments of femoral-tibial bone marrow of acute anterior cruciate ligament (ACL) injured patients and compared to healthy controls and osteoarthritic (OA) patents at 3T. There were statistically significant differences (P<0.05) of unsaturation index between LT except LF in OA patients and LT, MF, MT in ACL injured patients; statistically significant differences also existed among different compartments of femoral-tibial bone marrow at 2.03ppm for saturated lipids (P < 0.02) between these two groups. OA patients have the highest saturated lipids at 2.03ppm compared to healthy controls and ACL injured patients.

Jimin Ren¹, Ivan Dimitrov¹, A. Dean Sherry^1,2, and Craig R Malloy^1,3
1Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, United States, ²Department of Chemistry, University of Texas at Dallas, Dallas, Texas, United States, ³VA North Texas Health Care System, Dallas, Texas, United States

Proton MR detection of low level of acetyl-carnitine (AcCtn) in skeletal muscle is limited by the contamination of dominant lipid signals. Lipid interference also makes spectral fitting difficult due to the irregular EMCL lineshape. In the current study, we utilize inversion-recovery technique to optimize the detection of AcCtn acetyl signal by eliminating the lipid contamination. The method is based on the T1 difference between acetyl signal (long T1) and the lipid signals (short T1) to null the lipid signals in the early phase of recovery process post-inversion, allowing a contamination-free acetyl signal to be obtained with a few minutes.

Åsa Carlsson^1,2, Maja Sohlin², Maria Ljungberg^1,2, and Eva Forssell-Aronsson^1,2
1Department of Medical physics and Biomedical Engineering, Sahlgrenska University Hospital, Gothenburg, Sweden, ²Department of Radiation Physics, University of Gothenburg, Gothenburg, Sweden

Localized cardiac MR-spectroscopy (CMRS) is an increasingly popular tool for evaluation of the heart metabolism. To receive good spectrum quality in the human myocardium the scanning needs to be cardiac triggered. In this work, the spectrum quality related to the choice of cardiac triggering time delay was investigated by comparing several spectrum quality parameters for different cardiac triggering time delays. It was shown that cardiac triggering in systole resulted in better spectrum compared to diastole. Each subject had an individual optimal cardiac triggering delay time that could be found approximately at 25 % of a full cardiac cycle.

Juyeun Park¹, YoonSeok Choi¹, Yunjung Lee², Jisu Woo³, In-Chan Song³, Ji-Hoon Kim³, and Hyeonjin Kim^3
1Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea, ²Lee Gil Ya Cancer and Diabetes Institute, Incheon, Korea, ³Department of Radiology, Seoul National University Hospital, Seoul, Korea

Hepatic encephalopathy (HE) is a serious neuro-psychiatric complication of liver disease. To elucidate the pathogenesis of HE, 31P-MRS has been used. However, previous findings remain controversial due, at least in part, to relatively low sensitivity of the nucleus and limited spectral dispersion at low field. To this end, we have characterized HE in animal using 31P-MRS with substantially improved spectral dispersion and SNR at 9.4 T. Our results demonstrate that 31P-MRS at high field allows for highly resolved spectra in vivo, and thus can provide more vivid picture of the altered brain metabolism in the progression of HE.

Do-Wan Lee¹, Sang-Young Kim¹, Hyunseung Lee², Taehyeong Lee³, Changbum Yoo³, Jae-Hwa Kim⁴, Chi-Bong Choi⁵, Hwi-Yool Kim³, Dai-Jin Kim^4,6, Kwan-Soo Hong², and Bo-Young Choe^1
1Department of Biomedical Engineering and Research Institute of Biomedical Engineering, College of Medicine, The Catholic University of Korea, Seoul, Seoul, Korea, ²MRI Team, Korea Basic Science Institute, ³Department of Veterinary Surgery, Konkuk University of Korea, ⁴Department of Biomedical Science, College of Medicine, The Catholic University of Korea, ⁵Department of Veterinary Diagnostic Radiology, Dr. PET Animal Medical Center, ⁶Department of Psychiatry, Seoul St. Mary¡¯s Hospital, College of Medicine, The Catholic University of Korea

This study was aimed to investigate the cerebral neurochemical effects of long-term alcohol exposure on the adolescent rat frontal cortex. Our results show that GPC+PCh, Ins, Glx concentrations and (GPC+PCh)/NAA levels were significantly differed in frontal cortex of ethanol group. In particular, GPC+PCh concentrations and (GPC+PCh)/NAA levels showed most significant differences in ethanol group. Increased GPC+PCh concentrations and (GPC+PCh)/NAA levels may indicate that increased turnover of phosphatidylcholine and/or changed adaptive mechanism in frontal cortex of rat brain. Therefore, increased GPC+PCh concentrations and (GPC+PCh)/NAA ratio levels of frontal cortex might be utilized as key marker in long-term adolescent alcohol intoxication.

Chunxia Li¹, Xiaodong Zhang^1,2, Amelia Komery², Yingxia Li¹, Hui Mao³, Francis J Novembre⁴, and James G Herndon^2
1Yerkes Imaging Center,Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, United States, ²Division of Neuropharmacology and Neurologic Diseases, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, United States, ³Department of Radiology, Emory University, Atlanta, Georgia, United States, ⁴Divisions of Neuroscience, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, United States

In this study, a novel macaque model of neuro-AIDS was employed to investigate the longitudinal cerebral metabolite alternation in asymptomatic patients with in vivo MRS at 3T. The results demonstrated that NAA was reduced significantly in the acute phase and Glx was reduced significantly in both acute and chronic phases after the SIV inoculation. The progressive alternations in NAA and Glx correlated significantly with the CD8 T cell %.

Malgorzata Marjanska¹, Stephen D Weigand², Geoffry L Curran², Thomas M Wengenack², Joseph F Poduslo², Michael Garwood¹, and Clifford R Jack, Jr.^2
1Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, United States, ²Mayo Clinic College of Medicine, Rochester, MN, United States

Previously, reduced levels of N-acetylaspartate (NAA) and glutamate (Glu) were observed in various mouse models of Alzheimer’s disease (AD). Dramatic increase in the concentration of myo-inositol (mIns) with age was observed for APP-PS1 mouse model of AD. Additionally, the treatment of transgenic AD mice with anti-Aβ antibody regimes appeared to slow the rate at which mIns normally increases in AD mice. In this project, we looked at the correlation between concentrations of metabolites obtained in vivousing ¹H MRS just prior to sacrifice and the plaque counts obtained from histological Thio-S stained brain sections. Higher plaque counts were associated with lower NAA values and higher mIns values.

Abhishek Banerjee¹, Tomoyuki Mashimo¹, Sandeep K Ganji¹, Kim Kangasniemi¹, Todd Soesbe¹, Elizabeth Maher¹, Robert Bachoo¹, and Changho Choi^1
1University of Texas Southwestern Medical Center, Dallas, Texas, United States

Abnormal metabolisms in tumors have been reported in several studies. Here we present preliminary in vivo data of high field MRS of human glioblastoma implanted in NOD-SCID mouse brain using short echo time (TE = 19 ms) PRESS at 9.4T. Comparison between normal mice and mice with GBM is presented in terms of changes in concentration of metabolites and their ratios.

Roger J. Mullins^1,2, Su Xu^1,3, Jacek A. Mamczarz⁴, Edna F. R. Pereira⁴, Edson X. Albuquerque⁴, and Rao P. Gullapalli^1
1Core for Translational Research in Imaging, University of Maryland, Baltimore, Baltimore, Maryland, United States, ²Program in Neuroscience, University of Maryland, Baltimore, Baltimore, MD, United States, ³Department of Diagnostic Radiology & Nuclear Medicine, University of Maryland, Baltimore, Baltimore, MD, United States, ⁴Division in Translational Toxicology, Department of Epidemiology and Public Health, University of Maryland, Baltimore, Baltimore, MD, United States

Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS) methods were evaluated for their ability to detect CNS changes following acute prepubertal exposure of guinea pigs to chlorpyrifos, an organophosphorus pesticide. Guinea pigs received a subcutaneous injection of either chlorpyrifos or peanut oil . One year later, imaging and spectroscopic changes were correlated with changes in spatial learning behavior in the Morris water maze (MWM). Chlorpyrifos-injected guinea pigs showed significant decreases in performance in the MWM that were associated with a reduction in hippocampal myo-inositol concentration. Results indicate that 1H MR spectroscopy may reveal subtle metabolic changes associated with detrimental organophosphorus exposure.

Janna L Harris¹, William M Brooks¹, In-Young Choi^1,2, Hung-Wen Yeh³, and John A Stanford^4
1Hoglund Brain Imaging Center, University of Kansas Medical Center, Kansas City, KS, United States, ²Department of Neurology, University of Kansas Medical Center,³Department of Biostatistics, University of Kansas Medical Center, ⁴Department of Molecular and Integrative Physiology, University of Kansas Medical Center

Recent evidence suggests a link between consumption of a high fat (HF) diet and cognitive decline. In order to better understand the effects of excess fat consumption on brain function, we maintained rats on a HF diet or standard low fat chow for 16 weeks before acquiring 1H-MRS in the hippocampus and striatum at 9.4T. In animals on the HF diet we observed changes in several metabolites including total creatine, total choline, glutamine, inositol, and glutathione. Collectively these data suggest that a HF diet produces disturbances in brain energy metabolism, cell membrane biodynamics, astroglial populations, and oxidative stress

Brian Andrews-Shigaki^1,2, Aryan M.A. Namboodiri³, Asamoah Bosomtwi², Prasanth Ariyannur³, John Moffett³, Xianling Mao⁴, Dikoma Shungu⁴, Reed Selwyn², and Haiying Tang^2
1Military & Emergency Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, United States, ²Radiology & Radiological Sciences, Uniformed Services University of the Health Sciences, Bethesda, MD, United States, ³Anatomy, Phyisiology & Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, United States, ⁴Department of Radiology, Weill Cornell Medical College, New York, NY, United States

We characterized NAA concentrations in localized brain regions of the NAT8l knockout mouse by using proton magnetic resonance spectroscopy (1H-MRS). Four control and NAT8l knockout mice were scanned on a 7T Bruker scanner using a PRESS sequence. NAA concentrations were significantly decreased in the Cortex and Hypothalamus, with a less significant decrease in the Cerebellum. NAT8l knockout heterozygote mice have significantly decreased NAA levels in the brain. Further studies using these animals will be important for understanding the functional roles of NAA in the brain and its involvement in neurological and mental disorders.

Uzay E Emir¹, Diane Hutter¹, Khalaf O Bushara¹, Christopher M Gomez², Lynn E Eberly¹, and Gulin Oz^1
1University of Minnesota, Minneapolis, MN, United States, ²University of Chicago, Chicago, IL, United States

A prior MRS study demonstrated neurochemical alterations in SCA1 using a 4T research scanner, however the feasibility of reliably detecting neurochemical alterations on clinical platforms remains to be investigated. We measured neurochemical profiles in the cerebellum and brainstem of patients with SCA1 and controls by 3T and 7T 1H MRS. Concentrations of major metabolites obtained at 3T and 7T were strongly correlated. Prior findings at 4T were reproduced at both 3T and 7T. In addition, the increased sensitivity at 7T enabled the reliable quantification of a higher number of neurochemicals than at 3T and the detection of additional neurochemical alterations.

Ravi Prakash Reddy Nanga¹, David R Roalf², Kejia Cai¹, Mark Elliott¹, Hari Hariharan¹, James Loughead², Harish Poptani¹, Ravinder Reddy¹, and Ruben C Gur^2
1Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States, ²Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania, United States

Ultra-high field neuroimaging provides enhanced sensitivity and spectroscopic resolution. However, the increased field strength has several limitations, especially in deep brain regions which are prone to severe field inhomogeneities. Here, we show accurate and reliable quantification of glutamate/glutamine in deep brain structures (amygdala and hippocampus) at 7.0T. Given the importance of these deep brain structures in memory, emotion and other cognitive processes, accurate quantification could provide insight into the well-documented volumetric and functional differences in a variety of neuropsychological disorders.

Daniel Polders¹, Esther Verstraete², Vincent Boer¹, Leonard H van den Berg², Peter Luijten¹, and Dennis Klomp^1
1Radiology, UMC Utrecht, Utrecht, Netherlands, ²Neurology, UMC Utrecht, Utrecht, Netherlands

In this study, we utilized the increased SNR and chemical shift dispersion available with MRS at 7T to investigate selected metabolites in ALS patients and healthy controls. A single voxel (STEAM) measurement was performed, located in the sub-cortical white matter and covering the left motor tract. Fitting to a simulated basis set of nine metabolites and a separately collected macromolecular baseline showed significantly decreased levels of glutamate and N-acetylaspartylglutamate.

Manoj K Sammi¹, Yosef A Berlow^1,2, Thomas M Barbara¹, Audrey H Selzer¹, John W Grinstead³, Edward Kim⁴, Dennis Bourdette⁴, and William D Rooney^1,2
1Advanced Imaging Research Center, Oregon Health & Science University, Portland, OR, United States, ²Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, United States, ³Siemens Medical Solutions, Portland, OR, United States, ⁴Department of Neurology, Oregon Health & Science University, Portland, OR, United States

Mitochondrial dysfunction has been hypothesized to be a risk factor for neurodegeneration that leads to Multiple Sclerosis symptoms. Current work investigates and compares the normalized phosphorus metabolite signals in the brain over the same volume of interest in MS and healthy control subjects using phosphorus spectroscopic imaging at 7T while correcting for the signal contributions of gray matter, white matter, cerebrospinal and skeletal muscle tissue.

Anouk Marsman¹, Vincent Boer², Martijn Van den Heuvel³, Peter Luijten², Hilleke Hulshoff Pol³, Dennis Klomp², and René Mandl^3
1Psychiatry, UMC Utrecht, Utrecht, Utrecht, Netherlands, ²Radiology, UMC Utrecht, Netherlands, ³Psychiatry, UMC Utrecht, Netherlands

1H-MRS at 7T can be used to accurately determine glutamate in the human brain. A sLASER sequence has been developed, using field focusing at short TE resulting in twice as much signal as can be obtained by using STEAM. To assess reliability and reproducibility of sLASER compared to STEAM, eight subjects were scanned twice with both sequences, in the frontal and occipital lobe. sLASER has significant intraclass correlations for glutamate in both locations, STEAM did not show any significant correlations. Thus, sLASER is a reliable method to obtain glutamate in the human brain at higher accuracy than physiological variability.

Yan Li¹, Peder Larson¹, Albert Chen², Douglas Kelley^1,3, Susan Chang⁴, and Sarah J Nelson^1,5
1Department of Radiology and Biomedical Imaging, University of California, San Francisco, California, United States, ²GE Healthcare, Toronto, Ontario, Canada, ³GE Healthcare, San Francisco, California, United States, ⁴Department of Neurosurgery, University of California, San Francisco, California, United States, ⁵Department of Bioengineering and Therapeutic sciences, University of California, San Francisco, California, United States

The purpose of this study was to compare metabolite ratios in the T2 lesion for 5 patients with glioma relative to ratios in 3 normal volunteers using H-1 MRSI. The use of 7 Tesla provided high SNR and spectral resolution. The presence of low Cho/Cr, NAA/Cr, Cho/Cr and mI/Cr were suggestive of edema, while high Cho/Cr and low NAA/Cr were interpreted as active tumor and low NAA/Cr and high mI/Cho as being suggestive of treatment effects. Our results suggest that using a combination of metabolite ratios would be helpful in the interpretation of treatment response.

Neva M Corrigan¹, Mindy Olson², Todd Richards¹, Dennis WW Shaw^1,2, Annette Estes^3,4, Stefan Posse⁵, and Stephen R Dager^1,3
1Radiology, University of Washington, Seattle, WA, United States, ²Seattle Children's Hospital, Seattle, WA, United States, ³Autism Center, University of Washington, Seattle, WA, United States, ⁴Speech and Hearing Sciences, University of Washington, Seattle, WA, United States, ⁵University of New Mexico, Albuquerque, NM, United States

Brain imaging research has demonstrated alterations in brain volume and chemistry in children with autism spectrum disorder (ASD) at 2-5 years of age. The mechanisms and time of onset of these abnormalities are unknown. Magnetic spectroscopy provides chemical information that may help elucidate the cellular mechanisms that lead to the observed structural alterations as well as abnormal behavioral features characteristic of this disorder. We present findings from 3D MR spectroscopic imaging of children at higher risk for developing of ASD at 6, 12 and 24 months of age and compare them to findings for children at lower risk for developing ASD.

Brenda Bartnik Olson¹, Harrison Wang¹, Sarah Uffindell², Stephen Ashwal³, Valarie Wong⁴, Karen Tong¹, and Barbara Holshouser^1
1Radiology, Loma Linda University, Loma Linda, CA, United States, ²Neurology, Loma Linda University, Loma Linda, CA, ³Pediatric Neurology, Loma Linda University, Loma Linda, CA, ⁴Redlands Pediatric and Adult Medicine, Redlands, CA

Approximately 80% of traumatic brain injuries (TBI) are classified as mild with persistent deficits occurring in ~50-80%. Using 3D magnetic resonance spectroscopic imaging and DSC-perfusion weighted imaging we demonstrate decreased NAA/Cr and cerebral blood flow in multiple brain regions in a population of mild TBI patients with persistent symptoms. In the basal ganglia, the percentage of voxels with decreased NAA strongly correlate to the decrease in CBF. These findings may reflect decreased neuronal activity or a reduction in neuronal volume and could suggest a role for basal ganglia dysfunction in the pathophysiology of persistent deficits following a mild TBI.

Xiaodan YAN¹, Ivan Kirov¹, and Oded Gonen^1
1Radiology, New York University, New York, NY, United States

Traumatic brain injury (TBI) and related disabilities affect nearly 5.3 million people in the U.S, imposing a costly economic burden of about $56 billion. Diagnosis based on the Glassgow Coma Scale (GCS) indicates that 85% of TBI cases are mild (GCS:13-15). Mild-TBI (mTBI) pathology was previously believed to be “microscopic” and “diffuse” diseases. 1H MR spectroscopy imaging (MRSI) is a noninvasive technique for detecting microscopic and metabolic changes in the brain. In order to investigate whether there are focal metabolic changes associated with mTBI, a data-driven voxelwise analysis was adapted after MRSI data was co-registered to a standard space. This rigorous statistical approach avoids the bias and errors from manually outlining regions of interest (ROI-s).Significant group difference is found for NAA, Cr, Cho and mI in left thalamus (p < 0.01), and significant difference for Cho and NAA (p < 0.05) in right putamen, with mTBI patients showing decreased concentrations. Hypoactivity at thalamus, as well as decreased thickness of thalamus and putamen was also reported in previous studies. The hypometabolism in the present study together with hypoactivity in previous relevant studies, indicate dysfunction of thalamus and putamen may contribute to mTBI pathology.

Janna L Harris¹, In-Young Choi^1,2, Phil Lee^1,3, Hung-Wen Yeh⁴, and William M Brooks^1
1Hoglund Brain Imaging Center, University of Kansas Medical Center, Kansas City, KS, United States, ²Department of Neurology, University of Kansas Medical Center,³Department of Molecular and Integrative Physiology, University of Kansas Medical Center, ⁴Department of Biostatistics, University of Kansas Medical Center

A traumatic brain injury (TBI) initiates a progressive neurodegeneration that develops over days to weeks following the initial physical impact. We used 1H-MRS one hour after experimental TBI in rats to examine two brain regions: a proximal VOI containing tissue destined to degenerate into a lesion cyst, and a more distal VOI that would not develop any overt MR-visible lesion. Our results demonstrate a different early spectroscopic profile in tissue destined to degenerate vs. tissue destined to survive. We propose that 1H-MRS early after TBI could be useful for predicting the extent and location of ultimate tissue damage in TBI patients.

Carmen M Cirstea^1,2, Hung-Wen Yeh^1,3, Anda E Popescu¹, Ali Bani-Ahmed^1,2, In-Young Choi^1,4, Phil Lee^1,5, Sorin Craciunas⁶, and William M Brooks^1,4
1Hoglund Brain Imaging Center, University of Kansas, Kansas City, KS, United States, ²Departments of Physical Therapy, ³Biostatistics, ⁴Neurology, ⁵Molecular & Integrative Physiology, University of Kansas, Kansas City, KS, ⁶Neurosurgery Unit IV, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania

Although metabolite abnormalities have been documented in survivors of stroke by magnetic resonance spectroscopy, the relationship between metabolites in discrete anatomic areas that form cognitive networks is less well understood. Our goals were to establish evidence of "metabolic connectivity" in normal brain and to determine whether such connectivity was altered in radiologically normal appearing cortex following a sub-cortical stroke.

Changho Choi¹, Sandeep Ganji¹, Abhishek Banerjee¹, Ivan Dimitrov¹, Ralph DeBerardinis¹, Craig Malloy¹, Bruce Mickey¹, Robert Bachoo¹, and Elizabeth Maher^1
1University of Texas Southwestern Medical Center, Dallas, Texas, United States

Mutations in isocitrate dehydrogenase (IDH) 1 and 2 in the majority of WHO grade-2 and -3 gliomas and secondary glioblastomas lead to production of 2-hydroxyglutarate (2HG) and are associated with longer overall survival compared to IDH wild-type gliomas. Here we report preliminary in-vivo 2HG measures by 1H-MR spectroscopy at 7 T. The echo time of PRESS was optimized as 92 ms for detection of the 2HG multiplet at 2.25 ppm. The performance of this optimized TE PRESS is discussed together with short TE PRESS (34 ms).

In-Young Choi^1,2, Ping-Chang Lin¹, Wen-Tung Wang¹, and Phil Lee^1,3
1Hoglund Brain Imaging Center, University of Kansas Medical Center, Kansas City, Kansas, United States, ²Neurology, University of Kansas Medical Center, Kansas City, Kansas, United States, ³Molecular & Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas, United States

Diabetic ketoacidosis is a serious condition characterized by elevated levels of ketone bodies that may lead to diabetic coma or even death in patients, particularly, with type-1 diabetes. Detection of changes in ketone body levels in the brain should help to detect ketoacidosis in hyperglycemic state. In this study, we identified a cerebral acetone signal at 2.22 ppm and significantly elevated levels of both acetone and beta-hydroxybutyrate (bHB) along with the elevation of glucose concentration in a rat model of streptozotocin-induced diabetes using 1H MRS at 9.4T. A moderate correlation between bHB and acetone was also observed.

Andreas Hock¹, Fuchs Alexander¹, Erin L. MacMillan², Roland Kreis², Spyros S. Kollias³, Peter Boesiger¹, and Anke Henning^1
1University and ETH Zurich, Institute for Biomedical Engineering, Zurich, Switzerland, ²University of Bern, Dept. of Clinical Research, Bern, Switzerland, ³Institute of Neuroradiology, University Hospital of Zurich, Zurich, Switzerland

Scyllo-Inositol (sI) is one of the stereoisomers of inositol yielding to a singlet resonance at a chemical shift of 3.35 ppm in 1H MR spectroscopy (MRS). This work represents the first report of sI detection in the human spinal cord, which was enabled by non-water suppressed metabolite cycled 1H MRS at 3T. The results show an increased mI/Creatine and sI/Creatine ratio compared to the brain which might be an indicator of a different metabolism in the spinal cord.

Anders Tisell^1,2, Olof Dahlqvist Leinhard^1,2, Jan Bertus Marcel Warntjes^1,2, Anne-Marie Landtblom^3,4, and Peter Lundberg^2,5
1Division of Radiological Sciences, Department of Medicine and Health Sciences, Linköping University, Linköping, Sweden, ²Center for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden, ³Neurology, Department of Clinical and Experimental Medicine, Division of Neuroscience, Linköping University, Linköping, Sweden, ⁴Neurology Clinic, UHL, County Council of Östergötland, Linköping, Sweden, ⁵Depts of Radiation Physics, Linkoping University and Radiation Physics, UHL County Council of Östergötland, Linköping, Sweden

Absolute quantitative MRS and quantitative MRI was used to assess the difference of NAWM between MS patients with non or a low number of MS lesions, MS patient with MS lesions, and healthy controls. Elevated levels of total glutamine + glutamate was observed in both investigate phenotypes of MS compered to healthy controls. In contrast elevated myo-Inositol, Choline containing compounds and lower levels of N-acetyl aspartate glutamate was only observed in NAWM of MS patients with several lesions. Furthermore a correlation between atrophy and increased total creatine + phosphocreatine was also observed in NAWM of MS patients.

Lijing Xin¹, Benoit Schaller², Vladimir Mlynarik², Huanxiang Lu³, and Rolf Gruetter^1,2
1Department of Radiology, University of Lausanne, Lausanne, Switzerland, ²Laboratory of functional and metabolic imaging, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, ³Institute of Surgical Technologies and Biomechanics, University of Bern, Switzerland

In this study, T₁ relaxations of ¹H resonances (singlets and J-coupled peaks) of brain metabolites in occipital white matter and grey matter were measured at 7T using an inversion recovery semi-adiabatic SPECIAL sequence. T₁ values of metabolites ranged from 900-2100ms and those of GSH, scyllo-Ins, Tau and NAAG were determined for the first time. T₁ of NAA, tCho, Glu and NAAG were significantly different in WM and GM. The reported values will be useful for the quantification of metabolites by MR spectroscopy at 7T.

Ece Ercan¹, Andrew Webb¹, and Itamar Ronen^1
1C. J. Gorter Center for High Field MRI, Department of Radiology, Leiden University Medical Center, Leiden, Netherlands

We present a rapid method for the robust and accurate estimation of brain metabolite relaxation rates based on a single-shot CPMG sequence with multiple echoes. Each echo consists of a small number of acquired time-domain points. These truncated data sets are subsequently extended with additional data points calculated via solving a set of linear equations for the peak amplitudes using previously estimated frequencies and linewidths as priors. These priors are obtained from a short single volume MRS experiment with subsequent linear prediction using singular value decomposition (LPSVD) processing.

Bernadeta Walaszek¹, Florian Schubert¹, Ralf Mekle¹, and Bernd Ittermann^1
1Physikalisch-Technische Bundesanstalt (PTB), Berlin, Germany

In absolute metabolite quantification at moderate to long echo times, most often for T2 correction the global transverse relaxation times are used. However, it has been shown that the metabolite T2s may differ individually and depend on the brain region. Additionally, the process of ageing of the human brain, may affect the metabolite transverse relaxation times. Given the increasing importance of metabolite quantification in the hippocampus as well as in cortical areas of the brain, we determined T2 values of relevant brain metabolites in these brain regions using PRESS, and studied their age dependence.

Uzay E Emir¹, Malgorzata Marjanska¹, Dinesh Deelchand¹, and Melissa Terpstra^1
1University of Minnesota, Minneapolis, MN, United States

Differences in T₂ among experimental groups can confound quantification of metabolite concentrations. Existence of such differences in young versus elderly human subjects is controversial. This study used STEAM spectroscopy at several echo times to measure T₂ at ultra high magnetic field (4 T) in 29 young (age 18-22) and 32 elderly (age 70+) subjects. Artifact free spectra allowed for reliable determination of signal strengths via LCModel, which led to good fitting of the data to the T₂ relaxation curve for each metabolite. The T₂'s were faster in the elder than in the young subjects (p<0.01) for all metabolites.

Xiao-Hong Zhu¹, and Wei Chen^1
1CMRR, Department of Radiology, University of Minnesota Medical School, Minneapolis, MN, United States

This study aims to exploit new MR approaches for noninvasively measuring the rotational correlation time (_c) and hydrodynamic radius (R_h) of the brain tissue water. In vivo¹⁷O MRS was used to measure T₁ of the quadrupolar ¹⁷O spin of water in the rat brain at 9.4T, and to calculate _c according to a simple, field-independent relation. ¹H MRI was applied to image the brain translational diffusion coefficient (D_t); and the value of R_h was derived from the D_t/T₁ ratio. It was found that i) the brain water _c was in a range of several picoseconds and sensitive to brain temperature change, ii) R_h was about 1 Å that is in line with the water molecular size. This work indicates excellent utilities of in vivo ¹⁷O MRS for potentially imaging the microscopic matrix of brain tissue water properties in vivo.

Saadallah Ramadan¹, Tapan Biswas², Keith Heberlein³, Mark Brown⁴, and Alexander Lin^5
1School of Health Sciences, University of Newcastle, Callaghan, New South Wales, Australia, ²Biswas X Ray & Scan Center, West Apcar gardens, Asansol, India, ³Siemens Medical Solutions, Charlestown, MA, United States, ⁴Training and Development Center, Siemens Healthcare, Cary, NC, United States, ⁵5Center for Clinical Spectroscopy, Brigham and Women's Hospital, Boston, MA, United States

: Glx and GABA were measured in cerebellum and occipital lobe of human brain (n=24). Ratio of Glx peaks at 3.8 and 2.3 ppm, as well as GABA peak at 3.0ppm to NAA was calculated. Higher levels of GABA and Glx were found in cerebellum. This is in accordance with known function of cerebellum in

Anant Bahadur Patel¹, Pandichelvam Veeraiah¹, Mohammad Shameem¹, and Vivek Tiwari^1
1NMR Microimaging and Spectroscopy, Centre for Cellular and Molecular Biology, Hyderabad, Andhra Pradesh, India

Changes in mitochondrial function at the cellular level is not fully understood under normal aging. Present study investigates glucose oxidation by glutamatergic and GABAergic neurons, and neurotransmitter cycling in adult and aged mice. Cortical glutamate level was found to be reduced in aged mice. The glucose oxidation by glutamatergic neurons was decreased in aged mice while GABAergic functions seems to be unperturbed.

Nicolaas AJ Puts^1,2, C John Evans³, David J McGonigle³, and Richard AE Edden^1,2
1Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University, Baltimore, MD, United States, ²FM Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, ³CUBRIC, School of Psychology, Cardiff University, Cardiff, United Kingdom

Inter-individual differences in GABA concentration can shed light on the role of inhibition in cognitive processes. To date, several studies have shown that GABA concentration in functionally unrelated regions does not correlate between individuals. In this study we test the hypothesis that GABA concentration in two functionally related regions, right and left sensorimotor cortex, correlates across individuals.

Saadallah Ramadan¹, Tracy Burrows¹, Kirrilly Pursey¹, and Peter Stanwell^1
1School of Health Sciences, University of Newcastle, Callaghan, New South Wales, Australia

1H One-dimensional (1D) spectroscopic data from a single voxel in the bi-occipital lobe were acquired from a group of Red Bull drinkers (n=4) and another control group(n=5). Each subject was monitored for more than 45 minutes with a 1D spectrum acquired every 5 minutes on a 1.5 T Achieva XR MR scanner (Phillips, The Netherlands). Data was processed and analyzed using LcModel. Data revealed a decrease in PCr, Ins, and MM20, and an increase in GSH and Glx as a result of drinking Red Bull.

Serguei Liachenko¹, and Jaivijay Ramu^1
1NCTR / FDA, Jefferson, AR, United States

Circadian clocks regulate many physiological processes in biological systems. The diurnal changes in these processes may result in different sensitivity to pharmacological intervention as well as to the toxicity. Current study investigated the diurnal differences in neurometabolic profiles of naïve adult rats using proton MRS

Aline Seuwen¹, Sandra Bürgi¹, Aileen Schröter¹, and Markus Rudin^1,2
1Institute for Biomedical Engineering, University and ETH, Zürich, Switzerland, ²institute of pharmacology and toxicology, University Zürich, Switzerland

Spectroscopic imaging (SI) on the mouse brain is an attractive tool to quantitatively determine brain metabolite concentrations on different models of human diseases. However, SI suffers from low signal-to-noise ratio and long acquisition times, which restrain the practically achievable spatial resolution. In this work, a novel receive-only cryogenic phased array coil was used to overcome those issues. Using this setup, we could acquire spectra of excellent quality on a mouse model of glioblastoma at resolutions of 0.32 µl per voxel in less than 2h.