Kim C.C. van de Ven¹, Marinette van der Graaf^1,2, Bastiaan E. de Galan³, Cees J.J. Tack³, and Arend Heerschap^1
1Radiology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands, ²Paediatrics, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands, ³General Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands

In this study human cerebral glucose content was determined during moderate hypoglycemia (~3 mM), in order to assess values of reversible MM kinetic parameters for glucose transport and compare this with previous data on glucose transport into the brain assessed during eu- and hyperglycemia. We found MM parameters Tmax/CMRglc = 2.93 and Kt = 3.27 mM, which is in agreement with previously published data in humans, and it is also in agreement with findings in rats under hypoglycemic conditions. We conclude that the reversible MM model is also valid at moderate hypoglycemic values.

Andrew Paul Prescot¹, Todd L Richards², Stephen R Dager², and Perry Franklin Renshaw^1
1Brain Institute, University of Utah, Salt Lake City, UT, United States, ²Radiology, University of Washington, Seattle, WA, United States

Proton (¹H) magnetic resonance spectroscopy (MRS) investigations have reported altered glutamatergic neurotransmission in a variety of psychiatric disorders. The unraveling of glutamate from glutamine resonances is crucial for interpreting these observations although this remains challenging at clinical static magnetic field strengths. Glu resolution can be improved through an approach known as echo-time (TE)-averaging, which involves the acquisition and averaging of multiple TE steps. However, that method strongly attenuates Gln resonances. We have developed a novel approach termed phase-adjusted TE (PATE)-averaging for retrieving Gln signals from a TE-averaged ¹H MRS dataset. Preliminary simulation and in vivo data are presented.

Richard Anthony Edward Edden ¹, Nick Adrianus Johannus Puts², Christopher John Evans³, and David John McGonigle^2,3
1Russell H Morgan Department of Radiology and Radiological Science, The Johns Hopkins University, Baltimore, MD, United States, ²School of Biosciences, Cardiff University, Cardiff, United Kingdom, ³CUBRIC, School of Psychology, Cardiff University, Cardiff, United Kingdom

Deficits in GABAergic transmission and perceptual processing have been implicated in a number of neuropsychiatric disorders. Here we use MEGA-PRESS MRS and tactile psychophysics to investigate the relationship between in vivo GABA concentration and individual vibrotactile thresholds in humans at 3T. GABA concentration correlated with individual vibrotactile frequency discrimination thresholds in sensorimotor cortex (R = 0.58; p < 0.02) but not in occipital cortex (n.s.). This study shows that MEGA-PRESS MRS can be used to link measures of perceptual ability to neurotransmitter concentration in the somatosensory domain.

Changho Choi¹, and Sandeep Ganji^1
1Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, United States

Glycine (Gly) in the healthy human brain has been measured at 3T using an optimized PRESS echo time, (TE1, TE2) = (60, 100) ms, which permitted detection of both Gly and myo-inositol (mI) with comparable selectivity. Metabolite concentrations were estimated with respect to the brain water concentration obtained from the GM and WM fractions within the voxel. From five normal subjects, the Gly and mI concentrations in the right parietal cortex were estimated to be 0.6¡¾0.1 mM and 4.3¡¾0.4 mM (mean¡¾SD, n=5), with mean CRLBs of 9¡¾1% and 5¡¾1%, respectively.

Maryam Vareth^1,2, Eugene Ozhinsky^1,2, and Sarah J. Nelson^1,3
1Surbeck Laboratory of Advanced Imaging, Department of Radiology and Biomedical Imaging, Univ. of California, San Francisco, San Francisco, CA, United States, ²UCSF/UCBerkeley Joint Graduate Group in Bioengineering, Univ. of California, San Francisco, San Francisco, CA, United States, ³Univ. of California, San Francisco, Department of Bioengineering and Therapeutic Sciences, San Francisco, CA, United States

In this study we have implemented the compressed sensing algorithm with an efficient reconstruction technique to obtain optimal phase estimation for 3D MRSI using non-water suppressed spectra. Compressed sensing was shown to reduce acquisition time for water referencing spectra by 5x without negatively affecting the quality of phase estimation.

Jannie Petra Wijnen¹, Mariska P. Luttje¹, Wybe J.M. van der Kemp¹, Peter R. Luijten¹, and Dennis W.J. Klomp^1
1Radiology, University Medical Centre Utrecht, Utrecht, Utrecht, Netherlands

In this study we quantified the metabolite levels of phosphocholine and phosphoethanolamine in the breast of healthy volunteers. We used a dedicated ³¹P breast coil at 7T and used outer volume suppression to eliminate contributions from the chest muscle. The phosphomonoester signals had good SNR and were artifact free. With routine proton imaging and phantom calibration measurements the PME content could be quantified to absolute concentrations. The concentration found for PE and PC are within physiological range and agree with literature that report on total choline levels in the breast.

Markus Sack¹, Gabriele Ende¹, and Wolgang Weber-Fahr^1
1Neuroimaging, Central Institute of Mental Health, Mannheim, Germany

The internal water signal is often used as an internal reference for metabolite quantification. We conducted two T₂ measurements for an anterior cingulate single voxel MRS location to determine the T₂ times for BM and CSF. Spectra and T2maps were obtained from 23 subjects and fitted by a bi-exponential and a mono-exponential function, respectively. Both obtained datasets showed a strong dependency of the evaluated T₂^CSF values on the CSF content calculated by SegSpec. A computational model could mimic this dependency by overestimating the CSF content. Nevertheless, further investigations are necessary to discover the underlying mechanism or unknown additional compartment(s).

Cristina Cudalbu¹, Bernard Lanz¹, Joao M Duarte¹, Nicolas Kunz¹, and Rolf Gruetter^1,2
1Laboratory for Functional and Metabolic Imaging (LIFMET), Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland, ²Departments of Radiology, Universities of Lausanne and Geneva, Geneva, Switzerland

In the present study we assess the impact of the prior knowledge on the quantification of in vivo 13C spectra using two different algorithms: LCModel and AMARES combined with 4 different approaches to handle the prior knowledge. The results obtained with AMARES were identical with those obtained with LCModel if improved prior knowledge is used. We can conclude that additional prior knowledge used in AMARES leads to a more accurate and reliable quantification of in vivo 13C spectra. In contrast, when limited prior knowledge is used the results obtained with AMARES are over/underestimated.

Arabhi C Nagasunder^1,2, Ashok Panigrahy^1,3, Fawzi Boumezbeur⁴, Marvin D Nelson¹, and Stefan Bluml^1,2
1Radiology, Childrens Hospital Los Angeles, Los Angeles, CA, United States, ²Rudi Schulte Research Institute, Santa Barbara, CA, United States, ³Radiology, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States, ⁴Commissariat à l’Energie Atomique, Institute for Biomedical Imaging, Gif-sur-Yvette, Paris, France

Regular glucose (¹²C Glc) and ¹³C enriched (U-¹³C) glucose was administered orally to healthy controls. MR spectra, using a standard PRESS sequence on a clinical 3T scanner, were acquired before and after Glc administration. Increased brain glucose concentrations were readily detectable after ¹²C Glc administration. When U-¹³C Glc was used, ¹³C label replaced ¹²C and resulted in an apparent reduction of the ¹H MRS detectable breakdown products of glucose such as glutamate (Glu). This study demonstrates the feasibility of monitoring glucose metabolism in the human brain using widely available and FDA approved methods. Despite the limitations in specificity, this approach could be useful when the logistical challenges, posed by advanced approaches to study in vivo Glc metabolism, cannot be overcome.

YU ZHANG¹, Sanjeev Chawla¹, Sumei Wang¹, Sangeeta Chaudhary¹, Jaroslaw Krejza¹, E R Melhem¹, and Harish Poptani^1
1Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States

We investigated whether LC Model and linear discriminant analysis of the 1H MRS data from the contrast enhancing and peri-tumoral regions of the tumor can be used as an objective method for better classification of brain tumors. Linear discriminant analysis correctly classified 85% of 138 patients from six different brain tumor subtypes. Classification accuracies of glioblastomas versus metastases and astrocytomas versus oligodendrogliomas were 83% and 94% respectively. In comparison to previous 1H MRS studies, our study proposes a fully automated 1H MRS data analysis approach with minimum operator intervention and high diagnostic accuracy in brain tumor classification.

Niklaus Zoelch¹, Susanne Heinzer-Schweizer², Peter Boesiger¹, and Anke Henning^1
1Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland, ²Philips AG Healthcare, Zurich, Switzerland

A modified ERETIC method has been developed to enable quantification of metabolite concentrations in proton spectroscopic images (MRSI). Together with the acquisition of a B1 map, an accurate quantification of absolute metabolite concentrations is achieved in vivo.

Reggie Taylor^1,2, Peter Williamson^1,3, and Jean Théberge^1,2
1Medical Biophysics, University of Western Ontario, London, ON, Canada, ²Lawson Health Research Institute, London, ON, Canada, ³Psychiatry, University of Western Ontario, London, ON, Canada

Increasing the external magnetic field strength (B0) increases the SNR and spectral dispersion in a linear manner. Simulations were created to represent 4 B0 at 64 and 256 averages to examine how independent quantification of metabolites improves with B0. 200 noisy realizations were produced for each template and correlations between metabolites were extracted. Increasing B0 reduced the number of significantly correlated metabolites and in most cases reduced the magnitude of correlations. However, not all of the magnitudes of significantly correlated metabolites decreased as B0 increased. At equal SNR, precision increased by an average factor of 1.76 from 1.5T to 3T.

Hsiang Wei Ho¹, Shang Yueh Tsai¹, Yi Ru Lin², Stefan Posse^3,4, and Fa Hsuan Lin^5,6
1Electrical Engineering, Chang Gung University, Tao Yuan, Taiwan, ²Electronic Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan, ³Neurology, University of New Mexico School of Medicine, Albuquerque, NM, United States, ⁴Electrical and Computer Engineering, University of New Mexico, Albuquerque, NM, United States, ⁵Biomedical Engineering, National Taiwan University, Taipei, Taiwan, ⁶6 MGH-HST Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, United States

Regional metabolite T2 relaxation times are necessary for absolute quantification of metabolite concentration. Here, 3-diemensional Proton-Echo-Planar-Spectroscopic-Imaging (PEPSI) is proposed to obtain T2 maps of three major cerebral metabolites in four consecutive slices in less than 20 minutes. Our results show consistent T2 values between subject and regional difference of NAA between WM and GM which in agreement with previous studies. The estimation of T2 values is stable according to the high Pearson’s correlation coefficients between logarithmic MR signals and TE. In summary, PEPSI technique is a robust method to obtain fast maps of metabolite T2 values.

James B Murdoch¹, and Ulrike Dydak^2,3
1Toshiba Medical Research Institute USA, Mayfield Village, Ohio, United States, ²School of Health Sciences, Purdue University, West Lafayette, Indiana, United States, ³2Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, United States

GABA, a primary inhibitory neurotransmitter, is central to the understanding of many neurodegenerative and psychiatric disorders. The TE 68 MEGA-PRESS sequence has proven to be a reliable technique for measuring GABA at 3T, but subsequent analysis is frequently complicated by the presence of a co-edited macromolecule peak at 3.0 ppm (“MM30”). We have explored five different techniques for managing this macromolecular feature in LCModel. In particular, we have created and analyzed synthetic “metabolite-nulled” spectra to obtain a new set of MM functions appropriate for MEGA-PRESS difference spectra.

Donghoon Lee¹, Kenneth Marro¹, Mark Mathis¹, Eric Shankland¹, and Cecil Hayes^1
1University of Washington, Seattle, WA, United States

We obtained robust estimates of 31P metabolite content in mouse muscles using a synthetic signal injection method and an optimized, 1H/31P dual tuned probe. 31P metabolite concentrations obtained from normal mice were well within the expected range reported in the literature. Our 1H/31P dual tuned probe was composed of two separate solenoid coils and each solenoid included a second coil to allow injection of pseudo signals. In addition to in vivo 31P metabolite quantitation, 1H MR imaging was conducted for both legs to perform parametric MRI along with muscle volume measurements.

Alexandra Constantin¹, Adam Elkhaled², Trey Jalbert², Radhika Srinivasan², Soonmee Cha³, Susan M. Chang³, Ruzena Bajcsy¹, and Sarah J. Nelson^2
1Electrical Engineering and Computer Science, University of California, Berkeley, CA, United States, ²Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, United States, ³Department of Neurological Surgery, University of California, San Franisco, CA, United States

In this study, we applied multivariate pattern recognition methods to HRMAS spectra from image guided tissue samples in order to identify metabolites that are predictive of malignant transformations in gliomas and to accurately detect those patients exhibiting malignant transformations. Our method extracts a small subset of features in the HRMAS spectra and uses it to build a parsimonious model capable of discriminating between patients with different tumor grades with over 90% accuracy. The features used in our model are traced back to known metabolites in the corresponding chemical shift range, thus identifying a useful set of metabolites to acquire in-vivo.

Christoffer Laustsen^1,2, Steffen Ringaard¹, Mads Damkjær³, and Michael Pedersen^1
1Klinisk Institut, The MR Research Centre, Aarhus University, Aarhus, Denmark, ²Danish Research Centre for Magnetic Resonance, Hvidovre Hospital, Hvidovre, Denmark, ³Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark

Sodium is a pivotal metabolite in the equilibrium cell state, and is therefore an ideal candidate as a biomarker for macroscopic damage, which is directly linked to the cellular alterations in the sodium gradient across the cell membrane. We here show the use of a simple relaxometry method for gaining additional insight in ex vivo organs. We show that it is possible to differentiate the healthy kidney from the diseased by ²³Na-multi-component relaxation analysis.

Changho Choi¹, Sandeep Ganji¹, and Elizabeth Maher^2
1Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, United States, ²Internal Medicine and Neuro-oncology, University of Texas Southwestern Medical Center, Dallas, Texas, United States

Two-dimensional (2D) J-resolved spectroscopy may provide improved resolution for J-coupled resonances compared to conventional 1D data acquisitions. Single-voxel localized PRESS (point-resolved spectroscopy) data were acquired at 32 echo times from the tumor mass and contralateral normal-brain regions of three glimablastoma patients. The 2D NMR data were analyzed with spectral fitting (LCModel), using basis sets prepared with numerical calculation of model spectra that incorporated the actual parameters identical to those used in the data acquisition.

Zaiyang Long^1,2, James Brown Murdoch³, Jun Xu^1,2, and Ulrike Dydak^1,2
1School of Health Sciences, Purdue University, West Lafayette, IN, United States, ²Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, United States, ³Toshiba Medical Research Institute USA, Mayfield Village, OH, United States

In this study, we compare three LCModel fitting techniques for the original MEGA-PRESS sequence and a modified “MM-symmetric” version which has editing pulses alternating between 1.9 ppm and 1.5 ppm. Fitting technique A yields the highest GABA concentrations with small CRLB values, but the concentrations are probably overestimated. Technique B with an added MM30 peak yields the lowest GABA concentrations with largest CRLB. Fitting technique C with a soft constraint on MM30 seems to work best for the original MEGA-PRESS sequence and technique A for the MM-symmetric version. GABA levels may deviate considerably if an inappropriate fitting approach is chosen.

Donghoon Lee¹, Kenneth Marro¹, Eric Shankland¹, Mark Mathis¹, Timothy Wilbur¹, Gregory Wilson^1,2, Jeff Stevenson¹, Cecil Hayes¹, and Kenneth Maravilla^1
1University of Washington, Seattle, WA, United States, ²MR Clinical Science, Philips Healthcare, Cleveland, OH, United States

We report a simple way to implement an artificial signal injection method for absolute quantification on a clinical MR scanner. All injector RF components were placed in a shielded box that was isolated from the MR scanner circuitry so no hardware/software modifications were required for the implementation. We used the implemented injection device to acquire in vivo human muscle 31P MRS with a pseudo-signal acquired simultaneously. This approach is easy to implement with low cost hardware, making it attractive to a broad range of clinical and research MR sites.

Kenneth I Marro¹, Donghoon Lee¹, Eric G. Shankland¹, C. Mark Mathis¹, and Cecil E. Hayes^1
1Radiology, University of Washington, Seattle, WA, United States

Yan Zhang¹, Shizhe Li¹, Christine Rebsch¹, Stefano Marenco¹, and Jun Shen^1
1National Institute of Mental Health, Bethesda, MD, United States

This abstract introduces a method whereby TE-averaged PRESS spectroscopy is used in conjunction with regularized lineshape deconvolution to measure N-acetyl-aspartyl-glutamate (NAAG). Averaging different echo times suppressed the signals of strongly-coupled multiple resonance lines near 2 ppm, including the signals of glutamate and the macromolecule MM20. The signal distortions were corrected by using lineshape deconvolution, and Tikhonov regularization was introduced to reduce the noise amplification arising from the deconvolution; as a result, spectral resolution could be enhanced without significantly sacrificing signal-to-noise ratio (SNR). The acetyl proton signal of NAAG was directly quantified by fitting the deconvoluted spectra, from 1.8 to 2.2 ppm, with a model that consisted of two Voigt-type lineshape peaks, yielding the NAAG-NAA ratio.

Zenon Starcuk jr.¹, Jana Starcukova¹, and Danielle Graveron-Demilly^2
1Magnetic Resonance and Bioinformatics, Institute of Scientific Instruments, Academy of Sciences of the Czech Republic, Brno, Czech Republic, ²Creatis-LRMN, Université Claude Bernard Lyon 1, France

The new simulator, implemented as a jMRUI plugin, addresses the needs of a practical spectroscopist as well as a pulse sequence physicist. Pulse sequences, optionally controlled by protocols, may include arbitrarily modulated RF and gradient pulses, cycles, overlapping pulses. Homo- or heteronuclear spin systems are described by spatial position, chemical shifts, J-coupling, and the Redfield relaxation matrix, whose parameters can be derived from simplified models (Solomon, component relaxivities of coherences). It can be used for the study of the effects of spectrally or spatially selective excitation, steady-state formation, magnetization transfer, pulse sequence optimization.

Ssu-Ying Lu¹, Cheng-Wen Ko², Tzu-Chao Chuang², and Ping-Hong Lai^3,4
1National Sun Yat-sen University, Kaohsiung, Taiwan, ²National Sun Yat-sen University, ³Veterans General Hospital-Kaohsiung, ⁴School of Medicine, National Yang-Ming University, Taipei, Taiwan

The interest in using proton MRS to identify the bacteria in pyogenic brain abscesses has been arising. In this study, we propose an algorithm using principal component analysis (PCA) to differentiate anaerobic and aerobic abscesses by means of in vivo short TE proton MR spectra. Our preliminary result shows PCA can be one potentially useful tool to distinguish various types of brain abscesses without any complicated post-processing algorithm. Our processing scheme may provide more precise analysis for MRS especially when macromolecular or strong lipid play an important role of clinical diagnosis.

Bhaskaran David Prakash¹, Arunima Pola¹, Na Agarwal¹, and Sambasivam S Velan^1
1Laboratory of Molecular Imaging, Singapore Bioimaging Consortium, Singapore, Singapore, Singapore

ProFit based quantification has been demonstrated at 7T using localized max echo sampled J PRESS on the thalamus of rats on high fat vs placebo diets. Significant increase was detected in metabolic ratios with respect to creatine for NAA, alanine, glutamine, glutamate and lactate for the high fat group which could have implications for increased glucose metabolisms. None of the rats tested positive for insulin resistance. The results demonstrate ProFit’s ability to identify pre-diabetic markers. Creatine, alanine, aspartate, glycine, glucose, glutathione, lactate, myo-inositol and ascorbate shows lower Cramer-Rao lower bounds compared to 1D approach even at 16.1T.

Johannes Slotboom¹, Dirk van Ormondt², Olivier Scheidegger¹, Caspar Brekenfeld¹, Roland Wiest¹, Gerhard Schroth¹, and Danielle Graveron-Demilly^3
1DRNN-DIN/SCAN, University Hospital Berne, Berne, Switzerland, ²Applied Physics, Delft University of Technology, Delft, Netherlands, ³Laboratoire Creatis-LRMN, Université Claude Bernard LYON 1, Lyon, France

The Cramer-Rao minimum variance bounds (CR-MVB) are widely used as estimates of errors in spectral-parameters in localized MRS. Due to the macromolecular baseline, non-analytical line-shapes, and artefacts resulting from non-stationary signal acquisition conditions or RF-pulse imperfections, the parametric model is normally incomplete, and, strictly taken, the CR-MVBs estimates invalid. In general the CR-MVB under-estimates the variances in the estimated spectral-parameters. This work presents a novel method named “ER-ARSOS” to estimate the experimental errors of the parameters, as an alternative to the CR-MVBs in MRS.

Mariska Petra Luttje¹, Michael Wyss^1,2, Niklaus Zölch^1,2, Alexander Fuchs¹, Richard A.E. Edden^3,4, Susanne Heinzer⁵, Peter Bösiger¹, and Anke Henning^1
1Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Zurich, Switzerland, ²Contributed equally, ³Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States, ⁴F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland, United States, ⁵Philips AG, Zurich, Zurich, Switzerland

SV PRESS, MEGA-PRESS and localized 2D JPRESS are compared to investigate their ability of quantifying GABA, Glu, Gln and GSH accurately. ERETIC has been applied as a reliable reference. Next to this, for all sequences the metabolite ratios with the internal water reference were calculated. JPRESS shows to be the best method for simultaneous quantification of the selected metabolites, while MEGA-PRESS GABA-editing proofs to be a faster and reliable method for studies that target mainly GABA. The metabolite/ERETIC ratio shows to be a more stable and hence reliable quantification method compared to the metabolite/water reference ratio for all tested sequences.

Norbert W. Lutz¹, Yann LeFur¹, and Patrick J. Cozzone^1
1Dept. of Medicine La Timone, Marseille, France

Pathological processes are likely to induce variations in tissue pH. Thus, reliable measurement of intra and extracellullar pH (pHi, pHe) should be very useful for the characterization of tissue metabolism. ³¹P NMR-based methods exist for pH_i (chemical shift, δ, of endogenous P_i), and for pH_e (δ of exogenous APP). However, the consequences of pH heterogeneity within a measured tissue volume have not been considered in these pH calculations. We suggest here three ³¹P NMR-based pH calculation methods that take into account the characteristics of the pH distribution under consideration.

Kenneth I Marro¹, Donghoon Lee¹, Eric G. Shankland¹, C. Mark Mathis¹, Cecil E. Hayes¹, and Martin J. Kushmerick^1,2
1Radiology, University of Washington, Seattle, WA, United States, ²Physiology and Biophysics, University of Washington, Seattle, WA, United States

We have previously conducted in vitro measurements to demonstrate that conversion of MRS peaks to quantitative units of concentration can be efficiently achieved by using a second RF coil to inject a precalibrated, artificial reference signal into the data. In this work, we acquired ³¹P-MRS measurements from human tibialis anterior muscles and used pseudo-signal injection to determine PCr content. Our results demonstrate that pseudo-signal injection using inductive coupling provides a robust calibration factor that is immune to coil loading conditions and suitable for use in human measurements.

Brian J Soher¹, Philip Semanchuk¹, David Todd², Jeffrey Steinberg^1,3, and Karl Young^2
1Radiology, Duke University Medical Center, Durham, NC, United States, ²Radiology, Northern California Institute of Research and Education, San Francisco, CA, United States, ³Singapore Bioimaging Consortium, Agency for Science, Technology and Research

The VeSPA-Versatile Simulation, Pulses and Analysis package is an integrated set of open source applications written in Python that enable users to 1) synthesize RF pulses, 2) explore MRS data acquisition scenarios using multi-parametric spectral simulation and 3) improve processing/analysis of MRS data. VeSPA’s RFPulse, Simulation and Analysis applications are written in Python and integrated through a SQLite database. Applications are based on previous programs, MatPulse, GAVA and SITools. Scientific functionality was ported into a common infrastructure to ease access (no license fees), simplify extension (open source) and to create a consistent style across applications and platforms.

Lawrence Kenning¹, Martin Lowry¹, David John Manton¹, and Lindsay W Turnbull^1
1Centre for MR Investigations, University of Hull, Hull, United Kingdom

A repeatability study comparing the effects of field strength, pulse sequence and echo time was conducted. Data were acquired from ten volunteers on three occasions, using the mean of the differences between voxels to determine repeatability. An ANOVA model was used for statistical analysis (type IV). An interaction between field strength and echo time was found with shorter echo times being more repeatable at 3.0T, and longer echo times being more repeatable at 1.5T. Chemical shift dispersion is one possible cause. Robustness (no. good quality voxels/repeatability) was calculated and a relationship between theoretical SNR and robustness was found.

Erin Leigh MacMillan¹, Roland Kreis¹, Alex Fuchs², Maarten J Versluis³, Chris Boesch¹, Peter Boesiger², and Anke Henning^2
1Dept. of Clinical Research, University of Bern, Bern, Bern, Switzerland, ²Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Zurich, Switzerland, ³Dept. of Radiology, Leiden University Medical Center, Leiden, Netherlands

Non-water-suppressed MRS via metabolite cycling in the mixing period of STEAM was introduced to benefit from the ability to perform corrections on individual FIDs to increase SNR, and to provide a new tool to investigate exchangeable protons. At 7T, this technique successfully reduced the gradient sideband artifacts and water baseline tail to well below the prominent upfield peaks, and showed the same information as VAPOR water-suppressed spectroscopy. Furthermore, the 7.9ppm NAA peak was much better resolved with metabolite cycled non-water-suppressed MRS at 7T when compared to previous work at 3T.

Subechhya Pradhan^1,2, John C. Gore^2,3, and Kevin W. Waddell^3,4
1Vanderbilt University Institute of Imaging Science, Vanderbilt University, Nashville, 37232, United States, ²Department of Physics and Astronomy, Vanderbilt University, Nashville, TN, United States, ³Vanderbilt University Institute of Imaging Science, Vanderbilt University, Nashville, TN, United States, ⁴Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, United States

Increased resolution and higher sensitivity at high field require re-evaluation of protocols to optimize data quality. Inspection of signal information surfaces as a function of resolution and echo-time in PRESS show that precision optima for inositols and amino acids are mutually exclusive, and thus cannot be measured optimally at a single echo. Three cases to consider are: 1) methyl-bearing molecules should be acquired at short TE to avoid T2 loss, 2) amino acids (Glu/Gln) at 109 and mI/sI at 30/78 ms (mI), and 3) for amino acids and inositols, the optimum strategy is to combine 30 and 109 ms echoes.

Malgorzata Marjanska¹, Edward J Auerbach¹, Romain Valabregue², Pierre-Francois Van de Moortele¹, Gregor Adriany¹, and Michael Garwood^1
1Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, United States, ²Hôpital Pitié-Salpêtrière, Paris, France

To obtain absolute concentrations of metabolites from spectra obtained at longer echo times, the knowledge of both the J-modulation and T₂ relaxation times is required. The T₂ relaxation times at 7 T have been reported previously for the methyl protons of N-acetylaspartate (NAA) and the methyl protons of total creatine (creatine + phosphocreatine, tCr). The aim of this study was to measure T₂ relaxation times in different brain regions of the singlets and J-coupled metabolites.

Bernard Lanz¹, Lijing Xin¹, and Rolf Gruetter^1,2
1Laboratory for Functional and Metabolic Imaging, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, ²Department of Radiology, Universities of Lausanne and Geneva, Lausanne and Geneva, Switzerland

[2-¹³C]acetate infusion coupled with ¹³C MRS enables the separate assessment of glial and neuronal Krebs cycle fluxes and the determination of the apparent neurotransmission flux with higher accuracy than ¹³C labeled glucose, due to the glial specificity of acetate metabolism. Furthermore, these fluxes are determined with different precisions, which might strongly depend on the experimental conditions. In this study, we analyze the effect of the experiment duration, the time resolution and the noise level of the data on the standard deviation of the neuroglial fluxes, determined with Monte-Carlo simulation.

Shizhe S Li¹, Yan Zhang¹, Maria Ferraris Araneta¹, Christopher Johnson¹, Yun Xiang¹, Robert B Innis¹, and Jun Shen^1
1National Institutes of Health, Bethesda, Maryland, United States

Previously ¹³C isotopomers were observed in the human brain in the aliphatic spectral region using [1-¹³C]glucoseinfusion and long signal averaging time. Carboxylic/amide carbons can only form singlets and doublets even when uniformly labeled substrates are used, resulting in spectral simplification. To investigate the feasibility of simultaneously detecting two different isotopomers on the same carbon in the carboxylic/amide region in the human brain, we infused [U-¹³C]glucose and [2-¹³C]glucose because [U-¹³C]glucose produces doublets in the carboxylic/amide region while [2-¹³C]glucose only produces singlets. Dynamic turnover of these isotopomers were detected for the first time in the human brain.

Saadallah Ramadan¹, Ovidiu C Andronesi², Peter Stanwell¹, Alexander Lin¹, Gregory A Sorensen², and Carolyn Mountford^1
1Radiology, Brigham and Women's Hospital, Boston, MA, United States, ²Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, MA, United States

Acquisition and post processing parameters have been developed to allow, at 3T with a 32 channel head coil, an L-COSY to be acquired from the brain in 11 minutes. Cross peak assignments and relative ratios of metabolites in the healthy brain were recorded and statistically significant differences were recorded between healthy brain and glioblastoma. Good spectral resolution of the in vivo L-COSY allowed comparison with COSY from cultured cell lines.

Yoshichika Yoshioka^1,2, Hiroshi Oikawa³, Yoshiyuki Kanbara⁴, Yutaka Matsumura⁴, Takashi Inoue⁵, Tsuyoshi Matsuda⁶, Akira Nabetani⁶, and Junji Seki^7
1Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan, ²CREST, JST, Kawaguchi, Saitama, Japan, ³Radiology, Ninohe Haspital, Iwate, Japan, ⁴High Field MRI Research Institute, Iwate Medical University, Iwate, Japan, ⁵Neurosurgery, Kohnan Hospital, Sendai, Japan, ⁶GE Healthcare Japan Corp., Tokyo, Japan, ⁷National Cerebral and Cardiovascular Center Research Institute, Suita, Japan

We could detect the dynamic change of human brain temperature noninvasively using 1H-NMR spectroscopy. Our results show that the human brain temperature changes dynamically even at physiological conditions and by physiological tasks. Moreover the temperature change of human brain was larger than that of esophagus and axilla. This indicates that the brain temperature is affected easily by the blood flowing into the brain and also that the temperature of this blood is easily affected by foods and drinks. We can easily change the brain temperature of about 0.5 oC by drinking or light exercise.

Aranee Techawiboonwong¹, Hermien Kan², Maarten Versluis², Andrew Webb², and Itamar Ronen^2
1Electrical Engineering, Mahidol University, Puttamonton, Nakornpathom, Thailand, ²C.J. Gorter Center for High Field MRI, Radiology, Leiden University Medical Center, Netherlands

Diffusion-weighted spectroscopy of brain metabolites provides microstructural information specific to compartmental geometry in which they reside. So far, all DWS studies have been performed as single volume scans where accurate calculations of metabolite diffusion properties requires proper phasing of individual spectra prior to averaging to avoid destructive signal summation. Here, we present for the first time a complete 2D-DW-CSI experiment of human brain metabolites which yield sensible maps of their diffusion properties. The technique’s reliability is crucially enhanced using a navigator, which helps remove severe phase fluctuations induced by the diffusion gradients and correctly evaluate metabolite diffusion properties.

Lisa Angelos¹, Brendon M Nacewicz¹, Andrew L Alexander^1,2, and Richard J Davidson^1,3
1Waisman Brain Imaging Laboratory, University of Wisconsin -- Madison, Madison, WI, United States, ²Department of Medical Physics, University of Wisconsin -- Madison, Madison, WI, United States, ³Department of Psychology, University of Wisconsin -- Madison, Madison, WI, United States

We have developed a single-voxel amygdala spectroscopy protocol that maximizes voxel volume by adapting the prescription to each individual’s anatomy, and minimizes contamination and artifacts from surrounding tissue, especially hippocampus, with outer volume saturation bands. Compared to an occipital cortex voxel with similar data quality, amygdala NAA was 34% lower and Cho was 2.6 times higher, while Cre concentrations were similar. Amygdala NAA/(Cre+Cho) was higher than results from the hippocampus literature, suggesting an amygdala partial volume contribution to metabolite gradients observed in CSI measurements of the hippocampus.

Napapon Sailasuta¹, Kent C Harris¹, Thao Tran¹, and Brian D Ross^1
1Magnetic Resonance Spectroscopy Unit, Huntington Medical Research Institute, Pasadena, California, United States

Natural abundance 13C MRS and proton decoupled 31P MRS were utilized to explore the impact of fasting on Intracerebral pH and acid-base homeostasis. There were no findings of altered pH when a significant reduction of HCO3 was found. This unexpected finding suggests unknown factors may be at play and relevant for outcome predictions in bicarbonate replacement therapy.

Nikita Agarwal¹, Loyola D'Silva¹, and Sambasivam S Velan^1
1Laboratory of Molecular Imaging, Singapore Bioimaging Consortium, Singapore, Singapore, Singapore

In this work we have analyzed the residual dipolar couplings on Creatine (Cr) and Phosphocreatine (PCr) in the skeletal muscle spectra of the Tibialis Anterior muscle compartment in rats. The chemical shift separation of Cr, PCr, Taurine and carnitine is dependent on the foot angle which alters the orientation of the muscle fibers with respect to the main magnetic field. We have also measured the separation of Cr and PCr by changing the angle of the foot with respect to the main magnetic field.

Trina Kok¹, Berkin Bilgic¹, and Elfar Adalsteinsson^1,2
1Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, United States, ²Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, United States

This work is an investigation of the application of compressed sensing reconstruction methods to 2D spectroscopy methods, specifically CTPRESS. The investigated reconstructed methods are conjugate gradient, single bayesian reconstruction and joint bayesian reconstruction.

Johannes Slotboom¹, Dirk van Ormondt², Danielle Graveron-Demilly³, Dan Stefan⁴, Caspar Brekenfeld¹, Roland Wiest¹, Gerhard Schroth¹, and Olivier Scheidegger^1
1DRNN-DIN/SCAN, University Hospital Berne, Berne, Switzerland, ²Applied Physics, Delft University of Technology, Delft, Netherlands, ³Laboratoire Creatis-LRMN, Université Claude Bernard LYON 1, Lyon, France, ⁴Alter Systems

Most advanced applications for quantitative MRS can poorly be integrated in clinical routine workflow. The reasons are: (1.) they have very rudimentary image display/analysis possibilities; (2.) they have no DICOM-network capabilities for receiving/sending spectroscopy/image report files using the DICOM network protocol (data must manually be exported to off-line files (time consuming)), and (3.) they are file oriented, i.e. the user has to open files. Clinical users however do not work file-oriented, but patient/study/series-oriented. This paper reports on developed plug-ins for jMRUI to make quantitative MRS attractive for clinical routine-use.

Hidehiro Watanabe¹, Nobuhiro Takaya¹, and Fumiyuki Mitsumori^1
1Environmental Chemistry Division, National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan

Shifted echo center causes overlapped tilted peaks in the 2D CT-PRESS spectra. To achieve highly resolved 2D CT-PRESS spectra in human brain, a resolution enhancement window function was proposed. This window function consists of an enhancement part for shifting echoes and a conventional window part, such as Lorentzian, Gaussian or sine-bell. 2D CT-PRESS spectra were obtained from human brains at 4.7 T. While three peaks of GABA C2H (2.28 ppm), Glu C4H (2.35 ppm) and Gln C4H (2.44 ppm) were overlapped on the spectra applied with the conventional window, these peaks were resolved on the spectra with the enhancement window.

Sun Kim¹, and Glen Morrell^2
1School of Medicine, University of Utah, Salt Lake City, Utah, United States, ²Radiology, University of Utah, Salt Lake City, Utah, United States

The fast Padé transform can be used to create NMR spectra from truncated free induction decay (FID) signals at high spectral resolution that would require long readout times for conventional Fourier transform reconstruction. The capability to create high resolution spectra from short truncated FIDs with the Padé transform enables spectroscopy with short TR, low flip angle, and rapid acquisition, potentially yielding SNR improvements by optimization of SNR efficiency. We investigate the SNR gains that are possible using the fast Padé transform to shorten the required readout time for high resolution spectra, within the parameters of a typical brain spectroscopy experiment.

Zhong Chen¹, Yulan Lin¹, Zhiyong Zhang¹, and Shuhui Cai^1
1Department of Physics, Fujian Key Laboratory of Plasma and Magnetic Resonance, Xiamen University, Xiamen, Fujian, China, People's Republic of

The 2D NMR J-resolved spectroscopy can effectively simplify the spectra and improve the spectral resolution. In this abstract, a new pulse sequence based on spatially encoded intermolecular zero-quantum coherences (iZQCs) was presented to ultrafast obtain high-resolution NMR spectra in inhomogeneous fields. Eexperimental results indicate that the chemical shift and J-coupling information are well retained in severely inhomogeneous fields.

Judd M Storrs^1,2, Mohan Jayatilake^1,3, Wen-Jang Chu^1,2, and Jing-Huei Lee^1,4
1Center for Imaging Research, University of Cincinnati, Cincinnati, Ohio, United States, ²Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, Cincinnati, Ohio, United States, ³Department of Physics, University of Cincinnati, Cincinnati, Ohio, United States, ⁴School of Energy, Environmental, Biological and Medical Engineering, University of Cincinnati, Cincinnati, Ohio, United States

B₀ inhomogeneity within a single-voxel MRS volume-of-interest (VOI) is measured using a 333 grid of smaller MRS voxels distributed within the VOI. A specific sequence for acqisition of the grid allows repetition time to be halved without decreasing the effective relaxation time of each grid voxel. The acquired spectra is analyzed to produce first- and second-order shim updates to improve B₀ homogeneity within the VOI.

Jack Knight-Scott^1
1Radiology, CHOA, Atlanta, Georgia, United States

The Rapid Relaxometry through Acquisition of Multiple Saturated T₂ Curves (RRAMSC) technique is, in theory, limited to STEAM localization, where the recovery period allows specific control of the degree of longitudinal magnetization that recovers. Because PRESS lacks a well-defined recovery period, RRAMSC trade-off between changes in the TE and TR, to keep saturation effects constant, cannot be calculated over a generic range of different T₁ values. Here we examine the effects of approximating the recovery when employing RRAMSC with PRESS localization.

Kayvan R. Keshari¹, Mark Van Criekinge², Daniel Vigneron², and John Kurhanewicz^2
1UCSF, San Francisco, CA, United States, ²UCSF

Current NMR-compatible bioreactor systems have utilized standard 10–25mm designs to study cellular metabolism inside of a magnet. Though these systems are applicable to large volumes of immortalized cells (108 cells), obtaining the required volumes of primary cells and/or tissues is prohibitive. The use of primary cell and tissue cultures provides a more clinically relevant platform for testing new hyperpolarized MR probes and therapies. This preliminary study demonstrates the feasibility of using this 5mm bioreactor design in combination with hyperpolarized MR to explore both in cell steady-state and dynamic metabolism using dramatically reduced cell and perfusate volumes.

Anika Gallinger¹, Mailin Doepkens¹, Thorsten Biet¹, Luc Pellerin², and Thomas Peters^1
1Institute of Chemistry, University of Luebeck, Luebeck, Germany, ²Department of Physiology, University of Lausanne, Lausanne, Switzerland

UDP-N-acetylglucosamine (UDP-GlcNAc) is an activated sugar, produced via the hexosamine biosynthetic pathway (HBP). This activated sugar is the key substrate for O-GlcNAcylation, a dynamic posttranslational modification of nuclear and cytosolic proteins. Changes in flux through the HBP either increase or decrease UDP-GlcNAc levels, affecting the O-GlcNAcylation of many proteins. Aberrant O-GlcNAcylation can be associated with human diseases such as diabetes, Alzheimer’s disease and cancer. Alterations of UDP-GlcNAc levels may provide an indication of the development of metabolic disorders. Therefore, we are currently exploring the potential of UDP-GlcNAc as a NMR detectable metabolic marker in neuronal cells.

Jean-Philippe Galons^1,2, Logan Robinson³, Mike Bower⁴, Joseph Divijak⁴, Greg Russell⁵, and Ted Trouard^1,4
1Radiology, University of Arizona, Tucson, AZ, United States, ²Cancer Center, University of Arizona, Tucson, AZ, United States, ³Chemical Engineering, University of Arizona, Tucson, AZ, United States, ⁴Biomedical Engineering, University of Arizona, Tucson, AZ, United States, ⁵Physics, University of Arizona, Tucson, AZ, United States

Currently there is no commercially available perfused cell culture bioreactor system that is compatible with conventional NMR/MRI hardware. Taking advantage of new capabilities in 3D polymer printing technology we have generated a new small-volume hollow-fiber bioreactor device that is compatible with conventional vertical-bore MR magnets (top loading) and that fits within commercial 5 mm diameter RF probes. This bioreactor provides an inexpensive new tool for studying cell cultures with MR and utilizes the high sensitivity of commercial 5mm diameter RF hardware to generate high SNR.

Omkar B Ijare¹, Tedros Bezabeh¹, Nils Albiin², Annika Bergquist², Urban Arnelo², Matthias Lohr², and Ian C.P. Smith^1
1National Research Council Institute for Biodiagnostics, Winnipeg, Manitoba, Canada, ²Karolinska University Hospital, Karolinska Institutet, Huddinge, Stockholm, Sweden

Bile acids are major components of bile and are present mostly in conjugated forms with glycine and/or taurine. Amide bonds formed as a result of this conjugation provide well resolved ‘NH’ signals in the down-field region of ¹H MR spectrum of bile. However, at physiologic pH, these amide protons are in dynamic exchange with biliary water and show decreased signal intensity. Lowering the pH of bile below physiologic value (~ 6.0) has been helpful in recovering such signal loss. In this study, we propose the use of excitation sculpting sequence for the quantification of conjugated bile acids using their ‘NH’ signals without the need for pH adjustment.

abhinav arun sonkar¹, shatakshi shrivastav², raghuvendra kumar³, amita jain⁴, and Raja Roy^5
1surgery, csm medical university, lucknow, uttar pradesh, India, ²center for bio magnaetic resonance, SGPGI, Lucknow, Uttar Pradesh, India, ³surgery, CSM Medical University( King Georges Medical University), Lucknow, uttar pradesh, India, ⁴Microbiology, CSM Medical University, Lucknow, Uttar Pradesh, India, ⁵Center for Bio magnetic Resonance, SGPGI, Lucknow, Uttar Pradeshi, India

Abdominal TB involves the gastrointestinal tract, peritoneum, lymph node or solid viscera, constituting up to 12% of extra pulmonary TB and 1-3% of the total cases of tuberculosis. The disease involves different site/s within the abdomen with different morphologies, making the signs and symptoms of disease, very non-specific. This results in poor prognosis and diagnosis and opens an avenue for investigative research. In the present study, the ascitic fluid obtained from different groups of patients suffering with TB or other benign diseases were studied by 1H NMR spectroscopy to identify the fingerprint biomarker in tubercular ascitis for its differential diagnosis.

Valeria Righi^1,2, Georgios Apidianakis ³, Nikos Psychogios^1,2, Laurence G. Rahme³, Ronald G. Tompkins⁴, and Aria A. Tzika^1,2
1Department of Surgery, NMR Surgical Laboratory, MGH and Shriners Burn Institute, Harvard Medical School, Boston, MA, United States, ²Department of Radiology, Athinoula A. Martinos Center of Biomedical Imaging, Boston, MA, United States, ³Department of Surgery, Molecular Surgery Laboratory, MGH and Shriners Burn Institute, Harvard Medical School, Boston, MA, United States,⁴Department of Surgery, MGH and Shriners Burn Institute, Harvard Medical School, Boston, MA, United States

Using high-resolution magic angle spinning proton NMR spectroscopy in vivo, we evaluated in a Drosophila melanogaster. The main finding of this study was an increase in (CH₂)n lipids at 1.33 ppm which is an insulin resistance biomarker in skeletal muscle of Drosophila. We thus provide evidence for the hypothesis that GST2 mutation is linked to insulin signaling. Our approach advances the development of novel in vivo non-destructive research approaches in the model host D. melanogaster, and suggests biomarkers for investigation of biomedical paradigms that may contribute to the development of novel therapeutics.

Song I Chun¹, Dong Hwa Kim¹, Jee Hyun Cho², Kwan Soo Hong², Jung Woog Shin¹, and Chi Woong Mun^1,3
1Biomedical Engineering, Inje University, Gimhae, Korea, Republic of, ²Korea Basic Science Institute, Cheongwon-Gun, Chungcheongbuk-Do, Korea, Republic of, ³First Research Group, Inje University, Korea, Republic of

Stem cells have the unique properties of pluripotency/multipotency and they are able to differentiate into a diverse range of specialized cell types. Unknown materials generated during the differentiation of the stem cells were presumed to be another cell. The purpose of this study is to compare the metabolite changes between the pellet samples and the hydrogelation lysed samples of the human mesenchymal stem cells (hMSC) which are differentiated to adipose using magnetic resonance spectroscopy (MRS) along the passing time. Adipogenic differentiation of hMSCs was processed for 4 cycles using adipogenic induction medium and adipogenic maintenance medium (1cycle: adipogenic induction medium - 3 days + adipogenic maintenance medium - 1 day). The adipogenic differentiation rate of hMSCs was confirmed by Oil Red O staining as shown in Figure 1. Two type samples, one was hydrogelation lysed cell samples prepared by using 2.5% viscosity alginic acid and solubilization solution (55mM sodium citrate, 150mM NaCl). The other was cell pellet washed by D2O saline (99% D2O+0.9% NaCl) and minimized H2O signal. All samples were filled in 5mm NMR tube with external reference, 45.8mM 3-(trimethylsilyl)-1-propanesulfonic acid, sodium salt (DSS, Sigma).14.1T NMR micro-imaging machine (Bruker, Germany) was used to obtain the spectrum from the samples with Point Resolved Spectroscopy (PRESS; volume selected) pulse sequence and zqpr pulse (total volume) sequence.The acquired data were analyzed by the NMR spectrum processing software (TopSpin 2.1, Bruker, Germany) after the phase/baseline correction, peaks picking and integration.The adipose MR peaks were increased at both hydrogelation lysed sample and cell pellet sample. Especially, lipid signals of methyl group (-CH3) and methylene group (-CH2) were noticeably increased. For the samples of lysis cells no signal increment was found except lipids.On the other hand, the other metabolite variations in the cell pellet samples were observed such as isoleucine, alanine, leucine, lysine, methionine, glutamate, glutamine, choline, phosphocholine, myo-inositol and creatine etc. In case of methionine signal, peak 16, it was not observed during 1~3 cycles, but we could find it at 4 cycle when completed adipogenic differentiation.In this study, we confirmed that MR spectral peaks related to various lipid metabolites were increased when hMSCs were differentiated to adipose. During adipogenic differentiation process, authors also observed that lipid and other amino-acids related to energy metabolism were increased from the pellet of the cell samples. On the basis of this results, confirming the cell metabolites in the pellet will be helpful to find the basis standard of in-vivo cell metabolite measurements