Electronic Poster Session - MRS, non-H1 & ESR
  MRS Quantification 4382-4405
  MRS of Metabolism Plus 4406-4429
  MRS & Profiling 4430-4453
  MRS: Methods, Tactics, Strategies 4454-4477

MRS Quantification
Click on to view the abstract pdf and click on to view the video presentation. (Not all presentations are available.)
Thursday 10 May 2012
Exhibition Hall  13:30 - 14:30

  Computer #  
49 Transport mechanisms of intracellular metabolites in the brain: new insights by diffusion-weighted NMR spectroscopy with oscillating gradients
Charlotte Marchadour1,2, Vincent Lebon1,2, and Julien Valette1,2
1CEA-MIRCen, Fontenay-aux-Roses, France, 2CEA-CNRS URA 2210, Fontenay-aux-Roses, France

Transport of molecules within cells is a key process that can be achieved either passively by random diffusion, or by active transport (e.g. cytoplasmic streaming). The relative contribution of passive and active transport mechanisms to the ADC of intracellular metabolites and intracellular water is still debated. We investigate metabolite motion in the rat brain using diffusion-weighted spectroscopy with oscillating gradients. The dependence of metabolite ADC on the diffusion frequency is observed for the first time, making random diffusion emerge as the dominant transport mechanism. Subsequent data modeling further rules out the plausibility of significant active transport.

4383.   50 Using Short TE 1H MRS Methodology for the Reliable Detection of GABA in the Human Amygdala
Ralf Mekle1, Simone Kuehn2, Tomasz Dawid Lindel1, Florian Schubert1, Juergen Gallinat3, and Bernd Ittermann1
1Medical Metrology, Physikalisch-Technische Bundesanstalt, Berlin, Germany, 2Department of Experimental Psychology and Ghent Institute for Functional and Metabolic Imaging, Ghent University, Ghent, Belgium, 3Clinic for Psychiatry and Psychotherapy, Charité University Medicine, Berlin, Germany

The tiny amygdala is believed to a play central role in conditioning, i.e. in the expression of fear and anxiety, which is controlled by inhibitory GABA (γ-aminobutric acid)-ergic circuits. Measurement of GABA levels within the amygdala would allow to explore the neurochemical basis for conditioning and associated pathologies. However, performing MRS in this region is challenging due to its small size and testing B0 and B1 conditions. In this study, short TE 1H MR methodology using the SPECIAL technique was applied to overcome these limitations. GABA was reliably detected (CRLBs<20%) in N=8 volunteers, and slightly elevated concentrations were found.

4384.   51 How water T2 shortening affects 1H Magnetic Resonance Spectroscopy quantification
Virginia Mato Abad1,2, Juan Antonio Hernández-Tamames3,4, Roberto García-Álvarez5, Javier González González-Zabaleta3, Javier Pereira Loureiro1, Alejandro Pazos Sierra1, and Juan Álvarez-Linera2,6
1IMEDIR Centre, University of A Coruña, A Coruña, A Coruña, Spain, 2Neuroimaging Laboratory, CIEN Foundation – Queen Sofía Foundation, Madrid, Madrid, Spain, 3Biomedical Technology Center (CTB), Polytechnical University of Madrid, Madrid, Madrid, Spain, 4Rey Juan Carlos University, Madrid, Madrid, Spain, 5Research and Collaborations, GE Healthcare, Buc, France, 6Hospital Ruber Internacional, Madrid, Madrid, Spain

This work studies the relationship between Magnetic Resonance Spectroscopy (MRS) metabolite quantification and water T2 decay in vitro and in a cohort of 10 Parkinson’s patients. A correspondence was established between the iron accumulation and the shortening of water T2 relaxation times, which was later proposed as a source of error during the LCModel metabolite quantification. This work recommends introducing water T2 decay ratios as a confounding variable in clinical studies when quantification of single-voxel MRS is required, particularly in pathologies with evident signs of iron accumulation

4385.   52 Kinetic modelling of 13C Hyperpolarised Pyruvate Metabolism using Measured Arterial Input Function in Tumours
Samira Kazan1, Steven Reynolds2, Jo Bluff1, Aneurin Kennerley3, Emily Wholey4, Jason Berwick3, Vincent Cunningham5, Martyn Paley2, and Gillian Tozer1
1Oncology, University of Sheffield, Sheffield, United Kingdom, 2Human Metabolism, University of Sheffield, United Kingdom, 3Psychology, University of Sheffield, Sheffield, United Kingdom, 4Institute of Cancer Research, London, United Kingdom, 5Aberdeen Biomedical Imaging Centre, University of Aberdeen, Scotland, United Kingdom


4386.   53 Chemical shifts and coupling constants of the GABA spin system
Jamie Near1, Ivanhoe Leung2, Timothy Claridge2, Philip Cowen3, and Peter Jezzard1
1FMRIB Centre, University of Oxford, Oxford, Oxfordshire, United Kingdom, 2Department of Chemistry, University of Oxford, 3Department of Psychiatry, University of Oxford, Oxford, Oxfordshire, United Kingdom

In this study, the proton chemical shifts and scalar coupling constants of the GABA spin system were estimated using automated consistency analysis of a 500 MHz, high-resolution 1H-NMR spectrum of GABA. The newly estimated chemical shifts and coupling constants were then compared with previously published values by generating simulated GABA spectra for each set of chemical shifts and coupling constants, and then comparing the simulated spectra with the experimental data. Compared with previously published values, the newly estimated couplings and chemical shifts resulted in the best fit between simulated and experimental data.

4387.   54 Qualification of in vivo 1H MRS as a quantitative preclinical tool for evaluating drug efficacy in pharma research
Conny F. Waschkies1,2, Stephanie Schöppenthau2, Andreas Bruns2, Thomas Bielser2, Markus von Kienlin2, Markus Rudin1, and Basil Künnecke2
1Institute for Biomedical Engineering, ETH and University Zurich, Zurich, Switzerland, 2Magnetic Resonance Imaging & Spectroscopy, F. Hoffmann-La Roche, Basel, Switzerland

We have qualified preclinical 1H MRS as sensitive readout of changes in major neurotransmitters for its use in pharma discovery in psychiatric disorders. (i) Generic sensitivity of 1H MRS was assessed under our conditions in routine operation by way of a prospective power analysis in order to estimate the smallest changes reliably detectable. (ii) Pharmacological relevance was demonstrated by establishing dose-response relationships upon various pharmacological interventions and by corroborative evidence obtained with standard ex vivo biochemistry methods. (ii) Biological significance was demonstrated by unveiling region-specific differences in basal neurotransmitter levels and function-specific regional responses to pharmacological modulations.

4388.   55 Direct measurement of pyruvate T1 in vivo and the effect of blood oxygenation
Samira Kazan1, Steven Reynolds2, Jo Bluff1, Aneurin Kennerley3, Emily Wholey4, Jason Berwick3, Vincent Cunningham5, Martyn Paley2, and Gillian Tozer1
1Oncology, University of Sheffield, Sheffield, South Yorkshire, United Kingdom, 2Human Metabolism, University of Sheffield, Sheffield, United Kingdom,3Psychology, University of Sheffield, United Kingdom, 4Institute of Cancer Research, London, United Kingdom, 5Aberdeen Biomedical Imaging Centre, University of Aberdeen, Scotland, United Kingdom


4389.   56 Atlas-based analysis of brain MRSI data
Andreia Vasconcellos Faria1, He Zhu1, Richard Edden1, Peter van Zijl1, Michael Miller2, Susumu Mori1, and Peter Barker1
1Radiology, Johns Hopkins University, Baltimore, MD, United States, 2Biomedical Engineering, Johns Hopkins University, Baltimore, MD, United States

We present an automated, quantitative atlas-based analysis of high-resolution, multi-slice magnetic resonance spectroscopic images (MRSI). Using an accurate mapping algorithm, the brains are mapped to a common spatial reference. A 3D parcelation is then applied in each individual to obtain the average spectrum of dozens of structures anatomically defined. The atlas-based MRSI analysis yields results in good agreement with prior literature values obtained using manual analysis techniques. The signal/noise ratio of average parcel based spectra is higher than that of individual voxels. A future application of this method is, for example, the comparison of regional metabolism between patients and controls.

4390.   57 Evaluation of Improved Spatial and Spectral Resolution on Model Based Fitting of Prostate Spectroscopy at 7 Tesla
Gregory J. Metzger1, Edward Auerbach1, Christopher A. Warlick2, Diane Hutter1, Gregory Adriany1, and Ivan Tkac1
1Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, United States, 2Department of Urologic Surgery, University of Minnesota

The advantage of performing spectroscopy at higher magnetic fields is the improved quantification of metabolites due to increased spectral dispersion and SNR. An initial evaluation of the impact ultrahigh field has on the quantification of prostate spectroscopy is made in this work through simulations and fitting of in vivo data at field strengths of 3T and 7T. It is demonstrated that improved delineation between overlapping metabolites is possible at higher fields as indicated by reduced Cramer-Rao lower bounds and lower correlation coefficients. The ability to individually quantify prostate metabolites observable in vivo may prove clinically relevant for distinguishing aggressive from indolent disease and monitoring treatment response.

4391.   58 Reproducibility of Anterior Cingulate 1H MRS Data at 7T
S. Andrea Wijtenburg1, Laura M. Rowland1, Elena A. Spieker1, Richard A. E. Edden2,3, and Peter B. Barker2,3
1Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, United States, 2Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins School of Medicine, Baltimore, MD, United States, 3F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States

In this study, 7T spectroscopic data were acquired from healthy volunteers on two separate visits to determine the reproducibility of a short TE STEAM localization sequence. Voxels were placed in the anterior cingulate cortex, and all data were quantified using LCModel. Mean absolute differences were below 10% for most metabolites including GABA, suggesting that complex spectral editing techniques may not be necessary at higher field strengths.

4392.   59 The gland down under: effect of selective RF pulses on citrate lineshapes at 3T
James B. Murdoch1, Andrew J. Wheaton1, and Robert Anderson1
1Toshiba Medical Research Institute USA, Mayfield Village, OH, United States

Citrate is a strongly coupled AB system whose phases and amplitudes are sensitive to sequence timing at 3T. The citrate lineshape is affected by a slowing of J modulation that occurs during slice-selective or spectrally selective RF pulses. Both in PRESS simulations and in single-voxel prostate spectra, a pair of spectrally selective BASING pulses added for fat suppression also had a noticeable effect on the citrate lineshape, even though the citrate resonance was well beyond their inversion profile. Pulse shapes can therefore be designed that not only suppress fat robustly, but also sharpen citrate peaks akin to an MLEV sequence.

4393.   60 Automated partial volume calculation in single voxel 1H-MRS
Hedok Lee1, Elisabeth Caparelli2, Haifang Li3, Ruth Reinsel1, Amit Mandal1, David Smith4, Shaonan Zhang1, and Helene Benveniste1
1Anesthesiology, State University of New York at Stony Brook, Stony Brook, New York, United States, 2Neuroscience Center, State University of New York at Stony Brook, Stony Brook, New York, United States, 3Radiology, State University of New York at Stony Brook, Stony Brook, New York, United States, 4Medical, Brookhaven National Laboratory, Upton, New York, United States

In proton magnetic resonance spectroscopy (1HMRS), partial volume effect is inevitable and substantial uncertainty is introduced in metabolite concentration calculations when water is used as an internal reference. The present study focuses on methodological aspects pertaining to mapping the 1HMRS voxel onto the corresponding anatomical scan and results are compared on the basis of positional accuracy, positional reliability, and metabolite concentration estimates. We found computerized or manual voxel placement methods are equally valid. We also found significant correlation between metabolite concentrations and GM tissue volume fractions confirming previous studies.

4394.   61 Reduction of systematic errors in MRSI based brain temperature mapping.
Jehill Parikh1,2, Michael Thrippleton1,2, and Ian Marshall1,2
1Brain Research Imaging Centre, University of Edinburgh, Edinburgh, United Kingdom, 2Medical Physics, University of Edinburgh, Edinburgh, United Kingdom

Internal reference MRS thermometry can be used measure absolute brain temperature, using MRSI acquisitions it may be possible study regional brain temperature variation. However water suppression is commonly employed in MRSI and may introduce systematic errors in temperature maps estimated using MRSI data. This study will highlight the nature of this systematic bias and discuss the ways to reduce it.

4395.   62 Quantification of 31P NMR Spectra using LCModel
Dinesh K Deelchand1, Tra My Nguyen2, Fanny Mochel2, and Pierre-Gilles Henry1
1Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, United States, 2Inserm UMRS 975, Hôpital Pitié-Salpêtrière, Paris, France

This study demonstrates that human brain in vivo 31P NMR spectra can be quantified using the LCModel software, provided that adequate prior knowledge is used. This provides a new method for automated, operator-independent analysis of 31P spectra.

4396.   63 Parametric macromolecular baseline assessment using prior knowledge from inversion recovery signals measured at 9.4 T
Maria Isabel Osorio Garcia1,2, Diana M. Sima1,2, Flemming Ulrich Nielsen3, Tom Dresselaers3, Fred Van Leuven4, and Sabine Van Huffel1,2
1Dept. Electrical Engineering (ESAT), Katholieke Universiteit Leuven, Leuven, Belgium, 2IBBT-K.U.Leuven Future Health Department, Leuven, Belgium,3Biomedical Nuclear Magnetic Resonance Unit (MoSAIC), Katholieke Universiteit Leuven, Leuven, Belgium, 4Experimental Genetics Group LEGTEGG, Katholieke Universiteit Leuven, Leuven, Belgium

Besides the metabolites, MRS signals also contain macromolecules and lipids, which are normally observed in the frequency regions between 0.5 and 2 ppm. However, at high magnetic fields, numerous resonances appear along the whole spectrum band. In the frequency domain, these resonances appear as a baseline overlapping with the metabolite peaks, which complicates quantification. In the literature, several advanced acquisition techniques using inversion recovery, parametric and non-parametric methods have been widely used. We propose a parametric way of extracting characteristic resonances from a set of inversion recovery signals using AMARES and include them in the quantification method as additional components.

4397.   64 Improving In Vivo 1H-MRS with Robust Automated Shim Techniques: A Comparison Study of FASTESTMAP and GRESHIM
Xiaodong Zhong1, Yevgeniya M Lyubich2, Timothy DeVito3, Saurabh Shah4, and Jack Knight-Scott2
1MR R&D Collaborations, Siemens Healthcare, Atlanta, GA, United States, 2Department of Radiology, Children's Healthcare of Atlanta, Atlanta, GA, United States, 3Siemens Canada Limited, London, Ontario, Canada, 4MR R&D Collaborations, Siemens Healthcare, Chicago, IL, United States

In this study, we examined the robustness of three automated shimming techniques for single-voxel spectroscopy at 3T: FASTESTMAP, GRESHIM, and a standard vendor-offered product. Qualitative and quantitative results across six brain regions over five participants – anterior cingulate, posterior cingulate, centrum semiovale, hippocampus, Broca’s area, and thalamus – show that FASTESTMAP and GRESHIM provide the robustness and reliability necessary for implementation in the clinical environment, while the vendor-supplied shimming technique did not. Of the six regions examined, only the iron-rich thalamus could not be shimmed appropriately. Our results suggest that FASTESTMAP and GRESHIM should greatly improve the reliability of clinical spectroscopy.

4398.   65 Quantification of Cervical Tumor Choline Concentration by Proton MR Spectroscopy at 3 Tesla: a Pilot Study
Yao Ding1, Roderick McColl1, Ralph Mason1, Robert Sims1, Jayanthi Lea1, and Paul Weatherall1
1Radiology Department, UT Southwestern Medical Center at Dallas, Dallas, Texas, United States

In vivo 1H-MRS is a non-invasive technique that provides information on tumor metabolism, which may be used in tumor diagnosis and tumor response to therapy. Recently, several studies have demonstrated that Cho can be detected in human cervical tumors using 1H-MRS at 1.5 T. However, in some of these studies, Cho signals were also detected in post-treatment residue tissues and in normal cervix tissues. Thus, a quantitative method is necessary for quantifying the accurate levels of Cho for differentiating between different pathologies. The current study applied an internal water reference method to investigate the absolute quantification of Cho levels in cervical tumor system. We hope 1H MRS can be used to improve diagnostic accuracy and monitor cervical cancer response to therapy.

4399.   66 The influence of template metabolite omissions on 1H-MRS quantification
Reggie Taylor1,2, Peter Williamson1,3, and Jean Théberge1,2
1Medical Biophysics, University of Western Ontario, London, ON, Canada, 2Medical Imaging, Lawson Health Research Institute, London, ON, Canada,3Psychiatry, University of Western Ontario, London, ON, Canada

Many metabolites contribute to the area in a 1H-MRS spectrum, but not all are accounted for in every basis set. If they are not included in the basis set, their area may likely lead to an error in another metabolite’s concentration estimate. The purpose of this study was to systematically identify which metabolites compensate for a metabolite’s area when it has been omitted from a fitting template using Monte Carlo simulations. Every metabolite studied, with the exception of lactate, lead to an error of at least 10% in another metabolite’s concentration estimate when it was omitted from the template.

4400.   67 Combination of Multichannel Single-Voxel MRS Data Using Generalized Least Squares
Li An1, Jan Willem van der Veen1, David M Thomasson2, and Jun Shen1
1National Institute of Mental Health, National Institutes of Health, Bethesda, MD, United States, 2National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States

In recent years, various methods have been proposed for combining multichannel single-voxel MRS data. We propose to use a generalized least square (GLS) method to combine multichannel single-voxel MRS data. The proposed method was compared with two recently reported methods using data collected from two normal volunteers with an 8-channel receiver coil and data collected from a phantom with a 32-channal receiver coil. The experimental results show that the GLS method has the lowest coefficient of variation compared to the two existing methods, which will lead to improved precision in metabolite quantification in multi-measurement MRS studies.

4401.   68 SNR and voxel bleed comparison between 3D CSI and 3D HSI
Ouri Cohen1,2, and Oded Gonen1
1Center for Biomedical Imaging, NYU, New York, NY, United States, 2Biomedical Engineering, Columbia University, New York, NY, United States

A comparison of the voxel bleed and signal to noise ratio (SNR) in 3D chemical shift imaging (CSI) and 3D Hadamard spectroscopic imaging (HSI). It is shown that HSI has both lower bleed and higher SNR than CSI.

4402.   69 Measuring Glucose Concentrations in the Rat Brain Using TE-Averaged PRESS at 7T
Jeffrey Steinberg1, and Sendhil Velan1
1Singapore Bioimaging Consortium, Agency for Science, Technology and Research, Singapore, Singapore, Singapore

Glucose overlaps with several metabolites in the 3.2-3.9 ppm range in a typical spectrum in proton magnetic resonance spectroscopy. In order to resolve the glucose peaks from neighboring peaks, spectra at multiple TE values between 60 and 95 ms were averaged, resulting in a peak and a trough at 3.7 and 3.85 ppm respectively. Using voxels in the hippocampi of six rats, the TE averaged sequence obtained glucose estimates relative to creatine of 0.43 ± 0.07, whereas glucose estimates for data at a TE of 13 ms was 0.37 ± 0.35. The lower standard deviation for TE-averaged data indicates a much more reliable estimate of glucose than the standard short TE PRESS sequence.

4403.   70 The potential underestimation of amino acids for the MR spectra analyzed by LCModel: the study of model spectra.
Hsiu-Fen Lin1, Cheng-Wen Ko1, Shang-Yueh Tsai2,3, Ping-Hong Lai4,5, and Thomas Lange6
1Dept. of Computer Science and Engineering, National Sun Yat-sen University, Kaohsiung, Taiwan, 2Graduate Institute of Applied Physics, National Chengchi University, Taipei, Taiwan, 3Research Center for Mind, Brain and Learning, National Chengchi University, Taipei, Taiwan, 4Dept. of Radiology, Veterans General Hospital-Kaohsiung, Kaohsiung, Taiwan, 5School of Medicine, National Yang-Ming University, Taipei, Taiwan, 6Department of Radiology, University Medical Center Freiburg, Freiburg, Germany

Amino acids such as valine, isoleucine and leucine have been recognized as key metabolites to categorize brain abscesses. In this study, we investigated the potential underestimation of amino acids caused by basis spectra for abscess patients. Short TE spectra were analyzed by LCModel using basis set of AA and that of valine, isoleucine and leucine respectively. Cramer-Rao lower bounds were used as the criteria to identify the presence of amino acids in MRS. Our result suggests that using individual model spectra as basis sets would achieve better fitting than using synthetic multiple model spectra for J-coupled metabolites.

4404.   71 mISIS-CPMG: a Method for Localized Multicomponent T2 Measurement Immune to Very Short T2 Relaxation Effects
Ericky C. A. Araujo1, Alexandre Vignaud2, Paulo L. de Sousa1, and Pierre G. Carlier1
1Institut de Myologie, AIM and CEA, Paris, 75013, France, 2Siemens Healthcare, Saint-Denis, France

T2 spectrum measurements in skeletal muscle have revealed four T2 compartments, with T2's ranging from 1 to 200ms. Changes in T2 spectrum may reflect physiological and pathological process. Current methods give accurate results only for T2>10ms. Fast spin-spin relaxation perturbs the response of shorter T2 components to RF pulses, leading to unreliable quantification results. The ISIS technique was modified with the insertion of specially designed quadratic phase pulses, immune to T2 relaxation effects. The modified ISIS was combined to the Carr-Purcell-Meiboom-Gill sequence. The resulting method is suited for localized T2 spectrum measurement including T2 as short as 1ms.

4405.   72 Human Cardiac 31P Metabolite Concentrations at 3T
AbdEl-Monem M El-Sharkawy1, Refaat E Gabr1, Michael Schär1,2, Robert G Weiss1,3, and Paul A Bottomley1
1Division of MR Research, Department of Radiology, Johns Hopkins University, Baltimore, MD, United States, 2Philips Healthcare, Cleveland, OH, United States, 3Cardiology Division, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States

Cardiac 31P MRS with surface coils promises better quantification at 3T compared to 1.5T. However, T2-decay, power deposition limitations and increased field inhomogeneities, pose greater challenges for determining absolute metabolic concentrations at 3T. Using a recently developed 31P cardiac setup, we developed a semi-automated measurement and analysis protocol that compensates for the nonuniform sensitivity and provides measurements of human cardiac high-energy phosphate concentrations. The method was validated in one-dimensional-chemical-shift-imaging phantom studies, demonstrating errors of 8% on average. The measured 31P MRS cardiac metabolite concentrations were [PCr]=9.3±1.7 and [ATP]=5.2±1.0 µmol/g in healthy volunteers, in agreement with prior measures at lower fields.
Electronic Poster Session - MRS, non-H1 & ESR

MRS of Metabolism Plus
Click on to view the abstract pdf and click on to view the video presentation. (Not all presentations are available.)
Thursday 10 May 2012
Exhibition Hall  14:30 - 15:30

  Computer #  
4406.   49 The Addition of Rituximab to First-Line Chemotherapy for Newly-Diagnosed Diffuse Large B-Cell Lymphoma Does Not Modify the Prediction of Therapy Outcome by Phosphorus MR Spectroscopy
Fernando Arias-Mendoza1, Kristen Zakian2, Geoffrey S. Payne3, Marion Stubbs4, Hamed Mojahed1, Amita Shukla-Dave2, Franklyn Howe5, Harish Poptani6, Mitchell R. Smith7, Owen A. O'Connor8, Daniel Heitjan6, Mary McLean4, Martin O. Leach3, Jason A. Koutcher2, John R. Griffiths4, Arend Heerschap9, Jerry D. Glickson6, and Truman R. Brown10
1Columbia University Medical Center, New York, NY, United States, 2Memorial Sloan-Kettering Cancer Center, New York, NY, United States, 3Royal Marsden Hospital and Institute of Cancer Research, London, United Kingdom, 4Cancer Research UK Cambridge Research Institute, Cambridge, United Kingdom, 5St. George's Hospital, London, United Kingdom, 6University of Pennsylvania Medical Center, Philadelphia, PA, United States, 7Fox Chase Cancer Center, Philadelphia, PA, United States, 8New York University Medical Center, New York, NY, United States, 9Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands, 10Medical University of South Carolina, Charleston, SC, United States

We have used in vivo phosphorus MR spectroscopy to measure phosphoethanolamine and phosphocholine in tumors of newly diagnosed diffuse large B-cell lymphoma patients prior to the start of first-line chemotherapy and normalized to nucleoside triphosphates (PME/NTP) with the aim to assess whether the correlation of the pretreatment tumor PME/NTP value with treatment outcome differs between those patients treated with first-line chemotherapy alone and those treated with added rituximab.

4407.   50 Metabolic Changes of Human Embryonic Stem Cells During Cardiomyocyte Differentiation
Anna V Naumova1, Daciana H Margineantu2, Kareen L Kreutziger3, Nathan J Palpant3, James Fugate3, and Charles E Murry3
1Radiology, University of Washington, Seattle, WA, United States, 2Fred Hutchinson Cancer Research Center, Seattle, WA, United States, 3Department of Pathology, University of Washington, Seattle, WA, United States

Despite the literature data demonstrating that anaerobic glycolytic metabolism sufficient for mouse embryonic stem cell homeostasis, we demonstrated that undifferentiated human embryonic stem cells have active mitochondrial metabolism reflected by a high respiratory rate. Our data also demonstrate greater metabolic flexibility of differentiated cardiomyocytes characterized by a quick shift of ATP production from respiration to glycolysis in conditions where mitochondrial ATP production is impaired. Measurement of respiration and glycolysis rates by extracellular flux analysis using Seahorse analyzer and assessment of high energy phosphates by 31P NMR spectroscopy are complementary to each other for evaluation of metabolic activity on live cells.

4408.   51 MRI assessment of Slow training effect on focal fat metabolism in skeletal muscle
Yoshikazu Okamoto1, Shintaro Mori2, and Tomonori Isobe2
1University of Tsukuba Hospital, Tsukuba, Ibaraki, Japan, 2University of Tsukuba, Japan

Eleven volunteers in group A performed gcalf raiseh training regularly for 3 months, and were followed by proton (H1) magnetic resonance spectroscopy (H1-MRS) in 3 Tesla. Twelve volunteers in group B (control) performed no training .Slow training (calf raise) exercise appeared to induce a gradual decrease after 1 month of training in intramyocellular lipid (IMCL) showing statistically significant at the end of training (P<0.05). Extramyocellular lipid (EMCL) and calf muscle size did not markedly change. We clarified a novel, long-term slow training effect that can decrease focal IMCL content of skeletal muscle using MRI.

4409.   52 Investigating Lactate Pool-Size Effects in Cancer using Metabolic Activity Decomposition and Hyperpolarized Carbon-13 MR
Christine M Leon1,2, Larson EZ Peder1, Ralph E Hurd3, Robert Bok1, Kristen R Scott1, John Kurhanewicz1, and Daniel B Vigneron1
1Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, United States, 2UC Berkeley | UCSF Graduate Group in Bioengineering, University of California, Berkeley and University of California, San Francisco, San Francisco, CA, United States, 3GE Healthcare, Menlo Park, CA, United States

As hyperpolarized carbon-13 MR progresses to new disease applications and clinical research, this study investigated considerations of pool-size for accurate interpretation of HP MR dynamics. This work showed that lactate enters the cell, as it significantly affected conversion. With high co-factor availability, [1-13C]-lactate is less likely to convert to [1-13C]-pyruvate because more 12C-lactate molecules are available. Therefore, the lactate-to-pyruvate ratio increases in tumors even without a lactate pool-size limit and no change in KPyrright arrowLac from the significant decrease in KLacright arrowPyr. Meanwhile, normal tissues have limited NADH availability, such that the observed isotope exchange (KPyrright arrowLac) increases significantly with larger pool-sizes.

4410.   53 Imaging TCA Cycle Metabolism in a Rat Brain by Hyperpolarization.
Pratip Bhattacharya1, Niki M Zacharias1, Napapon Sailasuta1, Henry R Chan1, William H Perman2, Alan L Epstein3, and Brian D Ross1
1Enhanced MR Laboratory, Huntington Medical Research Institutes, Pasadena, CA, United States, 2Department of Medical Physics, St. Louis University, St. Louis, MO, United States, 3Department of Pathology, University of Southern California, Los Angeles, CA, United States

Real time metabolic imaging of the brain by MR opens up exciting applications for early detection and treatment monitoring of stroke, brain tumors and Alzheimer’s Disease. The main limitation for imaging agents to be used in the brain is their ability to cross the blood-brain barrier (BBB). The neutral compound hyperpolarized diethyl succinate has the potential of being an affective imaging agent for the brain. Diethyl 1-13C 2,3-d2 succinate is generated through the hydrogenation of diethyl 1-13C 2,3-d2 fumarate and hyperpolarized by PHIP (parahydrogen induced polarization) method, which increases the 13C MR signal by 5000 fold. In the research described here, we have employed hyperpolarized diethyl succinate to detect metabolism in a rat brain as well as to demonstrate that the compound crosses the BBB in real time.

4411.   54 Anisotropic Diffusivity of Creatine in Rat Hindleg Muscles Revealed by Diffusion Weighted Proton MRS
Anna M. Wang1,2, Peng Cao1,2, Zhong wei Qiao1,2, and Ed X. Wu1,2
1Laboratory of Biomedical Imaging and Signal Processing, The University of Hong Kong, Hong Kong SAR, China, 2Department of Electrical and Electronic Engineering, The University of Hong Kong, Hong Kong SAR, China

The cytosolic creatine pool and phosphorylctreatine shuttle of the high-energy phosphate transport have been proposed to have important roles in the high-energy demanding tissues. The diffusion characterization of creatine could be used as a probe to detect the subcellular structure and the metabolic changes. In this study we described the anisotropic diffusion character of the cytosolic creatine with two orthogonal diffusion directions. From the experience acquired from this study, we can look forward to see more possibility of using the diffusion characters of creatine or other metabolites to probe the subcellular structure and microenvironment dynamics.

4412.   55 Investigating the Effect of Inhibiting p53 on Glioma Metabolism
Rachel Erin Smith1, Anders Persson2, Ken Smith3, and Tracy Richmond McKnight3
1Radiology & Biomedical Imaging, University of California at San Francisco, San Francisco, CA, United States, 2Neurology, University of California at San Francisco, San Francisco, Ca, United States, 3Radiology & Biomedical Imaging, University of California at San Francisco, San Francisco, Ca, United States

The purpose of our study is to evaluate differences in metabolism between gliomas with functional and non-functional p53 protein. P 53 is commonly mutated in gliomas, and its mutation has been correlated with increased response to therapy. We used high-resolution magic angle spinning spectroscopy to compare the metabolism of p53 functional and non-functional glioma. We found significant differences in glycerophosphocholine, phosphocholine, and glutamate between the two populations. We also found that inhibition of the p53 protein slowed the growth rate and did not induce apoptosis. We continue our studies to relate these findings to the increased therapeutic response.

56 Assessment of lactate in LDH-A silenced 4T1 tumors with selective multiple-quantum coherence transfer
Asif Rizwan1,2, Inna Serganova3, Xiaohui Ni1, Sunitha Thakur1,4, Kristen Zakian1,4, Ronald Blasberg3,4, and Jason Koutcher1,4
1Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, NY, United States, 2Physiology and Biophysics, Weill Cornell Medical College, New York, NY, United States, 3Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY, United States, 4Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY, United States

Metabolic changes in primary tumors can lead to the development of the metastatic phenotype. The objective of this study is to demonstrate the link between LDH-A expression and lactate level in tumors. The LDH-A silenced 4T1 tumors have slower growth rate compare to the control 4T1 tumors. Both nonlocalized- and localized-spectra are acquired using the selective multiple-quantum coherence transfer (SelMQC) sequence in vivo. The LDH-A silenced 4T1 tumors showed a lower level of lactate compare to 4T1 control tumors.

4414.   57 Proton NMR metabolomics and genomics show induction of insulin resistance in murine skeletal muscle in response to treatment with a small volatile bacterial molecule
Valeria Righi1, Caterina Constantinou2, Nikolaos Psychogios1, Julie Wilhelmy3, Michael Mindrinos3, Laurence G. Rahme2, and Aria A. Tzika1
1NMR Surgical Laboratory, Department of Surgery, Massachusetts General Hospital and Shriners Burns Institute, Harvard Medical School, Boston, Massachusetts, United States, 2Molecular Surgery Laboratory, Department of Surgery, Massachusetts General Hospital and Shriners Burn Institute, Harvard Medical School, Boston, Massachusetts, United States, 3Department of Biochemistry, Stanford University School of Medicine, Stanford, CA, United States

We applied HRMAS 1H NMR metabolomics to intact muscle samples from animals treated with a volatile aromatic low molecular weight molecule, 2-AA, in order to identify at high-resolution concomitant metabolic and molecular aberrations associated with insulin resistance and metabolic dysfunction. These changes might also reflect mitochondrial dysfunction, as some of the genes downregulated in response to 2-AA treatment encode mitochondrial-dependent metabolic functions. The strength of HRMAS is that it allows dual investigation of metabolic and molecular changes since the same specimens studied with HRMAS can subsequently be used for transcriptome studies.

4415.   58 Autophagy alters lipid metabolism in human colon carcinoma cells evaluated using 1H NMR
Gigin Lin1, Dow-Mu Koh1, Simon P Robinson1, Martin O Leach1, and Yuen-Li Chung1
1CRUK and EPSRC Cancer Imaging Centre, The Institute of Cancer Research, Sutton, Surrey, United Kingdom

The intracellular storage and utilization of lipids are critical for cancer cells to maintain energy homeostasis, which is shown to relate to autophagy. In this study, we observed a unique change of lipid profile resulting from drug-induced autophagy. The lipid profile of autophagy shares some common changes with apoptosis, such as increased levels of fatty acids, triacylglycerol and sphingomyelin, which differentiates responsive cell lines from the non-responsive group. The increases of unsaturated fatty acids and phosphatidylcholine could further distinguish autophagy from early stage of apoptosis.

4416.   59 Investigation of NAA dynamics underlying visual stimulation using MEGA-PRESS
Ricardo C. G. Landim1,2, Richard A. E. Edden3, Bernd Foerster2,4, Li M. Li2,5, Roberto J. M. Covolan1,2, and Gabriela Castellano1,2
1Institute of Physics Gleb Wataghin, University of Campinas, Campinas, SP, Brazil, 2CInAPCe Program (Cooperação Interinstitucional de Apoio a Pesquisas sobre o Cérebro), São Paulo, SP, Brazil, 3Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, United States, 4Philips Medical Systems, São Paulo, SP, Brazil, 5School of Medical Sciences, University of Campinas, Campinas, SP, Brazil

Possible N-acetyl-aspartate (NAA) variations with stimulation are a controversial discussion topic in the literature. Individual measurement of this metabolite is difficult due to the superposition of its spectrum with N-acetyl-aspartyl-glutamate's (NAAG). We designed a functional MRS experiment using the editing sequence MEGA-PRESS to evaluate the individual dynamics of NAA underlying brain activation during visual stimulation.

4417.   60 Functional MRS in the Anterior Cingulate
Reggie Taylor1,2, Peter Williamson1,3, and Jean Théberge1,2
1Medical Biophysics, University of Western Ontario, London, ON, Canada, 2Medical Imaging, Lawson Health Research Institute, London, ON, Canada,3Psychiatry, University of Western Ontario, London, ON, Canada

Functional magnetic resonance spectroscopy (fMRS) has potential to be a powerful tool for dynamically studying metabolite concentrations. Three subjects were scanned to test the feasibility of applying fMRS to the anterior cingulate using a 7T MRI. Using a Stroop Task for functional activation we demonstrated that fMRS is feasible in the anterior cingulate and can alter the PCr concentration upon activation.

4418.   61 Efficient broadband set-up using travelling wave and strong loading for simultaneous fluorine and proton MRI at 7T
Anna Andreychenko1, Jim Craane1, Wouter Koning1, Peter R. Luijten1, Jan J.W. Lagendijk1, Cornelis A.T. van den Berg1, and Dennis W.J. Klomp1
1Imaging Division, UMC Utrecht, Utrecht, Netherlands

Fluorinated drugs are frequently used in chemotherapy and can be monitored with Fluorine MRSI but reference proton MRI is needed. Use of double tuned coils is prevented by small difference in frequency between 1H and 19F spins. At 7T, a new transmit and receive RF concepts exploiting this small frequency difference can be applied. Waveguide concept with dielectric lining can be used to excite both nuclei. At 7T tissue load increases the bandwidth of receive coil and the same single tuned RF coil can detect both nuclei. Set-up with shared transmit and receive fields for proton/fluorine MRI was successfully demonstrated.

4419.   62 Ultra-High-Field Sodium Imaging of the Human Brain at 9.4 Tesla
Sandro Romanzetti1, Daniel Fiege1, Jörg Felder1, Avdo Celik1, Christian Mirkes1,2, and N.Jon Shah1,3
1Institute of Neuroscience and Medicine - 4, Forschungszentrum Jülich, Jülich, Germany, 2Max Planck Institute for Biological Cybernetics, Tübingen, Germany, 3JARA - Faculty of Medicine, RWTH Aachen University, Aachen, Germany

Monitoring the strongly regulated sodium content in vivo is of great interest for a variety of diseases. Imaging this nucleus is difficult due to its low concentration and fast relaxation. Using an ultra-high field scanner at 9.4 Tesla, a dedicated RF coils and the efficient Twisted Projection Imaging sequence, 2mm nominal isotropic sodium images of the human brain were acquired. Comparison with an MP-RAGE image shows the fine anatomical details, while a 4T comparison shows the great SNR improvement.

4420.   63 In vivo Potassium-39 MRI at 9.4 Tesla using a room-temperature surface resonator: does cryogenic cooling help?
Ibrahim A. Elabyad1, Friedrich Wetterling1, Nagesh Shanbhag2, Lothar Schilling2, and Lothar R. Schad1
1Computer Assisted Clinical Medicine, Heidelberg University, Mannheim, Germany, 2Pre-clincial Neurosurgery Department, Heidelberg University, Mannheim, Germany

In the current feasibility study, a single-tuned 39K surface resonator was developed and tested for the measurement of 39K signal in the normal live rat brain. Compared with the previous published results, the herein used CSI technique in conjunction with improved resonator sensitivity achieved approximately 5 times higher SNR in half the acquisition time. Additionally, the S/N improvement by cryogenic cooling the resonator was estimated from simulated copper RF-coil at room-temperature (RT) of 293 K and cryogenic temperature (CT) of 90 K. For both coils, full-wave Electro-Magnetic (EM)-simulations were computed for a single loop resonator with 35-mm diameter and 1.5-mm wire thickness for unloaded and loaded conditions. Results show that, 2.3-fold sensitivity improvement is expected when the coil is cooled down to 90 K, which could further improve the available signal in future 39K-MR imaging studies of the rat brain at 9.4T. In conclusion, 39K-MRI of the rat brain is possible at 9.4T using a CSI sequence and a single-tuned surface resonator and 39K resonator sensitivity can be further improved by cryogenic cooling.

4421.   64 Improved PCr/ATP Ratio Mapping of the Human Head by Simultaneously Imaging of Multiple Spectral Peaks with InterLeaved Excitations and Flexible Twisted Projection Imaging Readout Trajectories (SIMPLE-flexTPI) at 9.4 Tesla
Aiming Lu1, Ian C Atkinson1, and Keith R Thulborn1
1Center for MR Research, University of Illinois at Chicago, Chicago, IL, United States

Quantitative MR imaging of phosphocreatine (PCr) and ATP concentrations in human brain can provide useful information about the metabolic flux through the central high-energy metabolic pathways but are hindered by the low MR detection sensitivity of 31P. An efficient acquisition strategy, now termed SIMPLE-flexTPI has been used to simultaneously sample PCr and γ-ATP signals. By optimizing the acquisition software and hardware, significantly improved 31P imaging results on entire human head has been achieved at 9.4T. The PCr and γ-ATP images demonstrate meaningful resolution and SNR. The obtained PCr/γ-ATP ratios are in agreement with literature values.

4422.   65 Accelerated In-vivo Liver 31P MRSI using GRAPPA
Anshuman Panda1,2, Scott Jones1,2, Rahul Srinivasa Raghavan1, Keith Heberlein3, Radhouene Neji3, and Ulrike Dydak1,2
1School of Health Sciences, Purdue University, West Lafayette, Indiana, United States, 2Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana, United States, 3Siemens Healthcare, Erlangen, Germany

31P magnetic resonance spectroscopic imaging (MRSI) of the human liver is of clinical interest but requires long scan times. We investigated the feasibility of accelerating in-vivo 31P MRSI of the human liver using GRAPPA and a dual tuned 8-channel 31P/1H coil. Successful implementation of 31P GRAPPA MRSI on the scanner allowed for reduction of the scan time for 2D 31P MRSI data across a whole liver slice from 25.75 min to 15.17 min, while maintaining quantifiable spectral data quality and alias-free metabolite maps. It was concluded that acceleration of 31P in-vivo liver MRSI is feasible using GRAPPA reconstruction.

4423.   66 Quantitative Comparison of 31P Relaxation Time and NMR Sensitivity between 9.4T and 16.4T
Ming Lu1,2, Yi Zhang1,2, Kamil Ugurbil1,2, Wei Chen1,2, and Xiao-Hong Zhu1,2
1Center for Magnetic Resonance Research, University of Minnesota Medical School, Minneapolis, Minnesota, United States, 2Department of Radiology, University of Minnesota Medical School, Minneapolis, Minnesota, United States

31P MRS provides a unique tool to directly investigate the mechanisms of synthesis, transfer and utilization of the cerebral high-energy phosphate compounds, which has significantly advanced our understanding of bioenergetics in the brain. In this study, we examined the 31P relaxation time and NMR sensitivity from phantom solution and rat brain at high/ultrahigh fields, i.e., 9.4 and 16.4 Tesla. The measured in vivo T1 relaxation times of PCr were 3 s and 1.5 s at 9.4T and 16.4T, respectively. The results also showed an improvement of the 31P SNR at 16.4T as compared with 9.4T (1.6-fold higher for both of the phantom and rat brain studies). These findings suggest that the increasing field strength could improve the in vivo 31P MRS quality and spatial resolution, and shortening total acquisition time for localized 31P MRS. It benefits the application of in vivo 31P MRS in detecting altered bioenergetics associated with brain function and neurological diseases.

4424.   67 Dynamic 31P-MRS during visual stimulation protocols in healthy young adult subjects
Felipe Rodrigues Barreto1,2, Carlos Garrido Salmon1,2, Thiago Bulhões3,4, Ricardo Landim3,4, and Gabriela Castellano3,4
1Department of Physics, University of São Paulo, FFCLRP, Ribeirao Preto, SP, Brazil, 2CInAPCe (Cooperação Interinstitucional de Apoio a Pesquisas sobre o Cérebro), Ribeirao Preto, SP, Brazil, 3Neurophysics Group, UNICAMP, Institute of Physics Gleb Wataghin, Campinas, SP, Brazil, 4CInAPCe (Cooperação Interinstitucional de Apoio a Pesquisas sobre o Cérebro), Campinas, SP, Brazil

31P-MRS combined with visual stimulation has been widely used to investigate energy metabolism in healthy subjects and patients. In this work we used a large number of subjects to assess metabolic variability in resting conditions and metabolic changes resulting from two visual stimulation protocols (short and long). Both protocols showed significant differences among on and off states for Pi (higher in on blocks) and for the PCr/Pi ratio (lower in on blocks), with a mean relative change of 13.4% (Pi, p=0.04) and -17.4% (PCr/Pi, p=0.007) for the short protocol and 5.3% (Pi,p=0.009) and -5.9% (PCr/Pi, p<0.001) for the long protocol.

4425.   68 Towards 13C NMR spectroscopy of human muscle at 7T using broadband 1H decoupling
Eulalia Serés Roig1, Lijing Xin1,2, Arthur W. Magill1,2, and Rolf Gruetter1,3
1Laboratory of Functional and Metabolic Imaging, École Polytechnique Fédérale de Lausanne, Lausanne, Vaud, Switzerland, 2Department of Radiology, University of Lausanne, Lausanne, Switzerland, 3Department of Radiology, Universities of Lausanne and Geneva, Geneva, Switzerland

The main difficulty while implementing 13C MRS in human scanners at high field is the need for decoupling of the single-bond 13C-1H hetero-nuclear J coupling by respecting the IEC guidelines for SAR. In this study we present a successful implementation of in vivo 13C MRS applicability at a 7T human Siemens system within a clinical platform, including the detection of in vivo Glycogen together with an experimental evaluation of an existing decoupling technique Waltz16 by exploring its feasibility in humans at 7T and comparing to CW decoupling.

4426.   69 Adiabatic Multi Echo Spectroscopic ImagiNG (AMESING) for boosted 31P sensitivity at 7 Tesla
Wybe JM van der Kemp1, Vincent O Boer1, Peter R Luijten1, and Dennis WJ Klomp1
1Radiology, UMC Utrecht, Utrecht, Utrecht, Netherlands

For metabolites where T2 values are an order of magnitude larger than T2* effects, as is the case for 31P MRS in many locations in the human body at high fields, multi echo sequences can boost sensitivity. Here we show the potential of Adiabatic Multi Echo Spectroscopic Imaging ¬with spherical k-space sampling at 7 Tesla. We tested the sequence for 31P MRSI on the calf muscle and the human breast of healthy volunteers. SNR weighted sum spectra that were acquired had an SNR of up to 2 times higher than the SNR of the FID spectra

4427.   70 Comparison of Two Fast MR Acquisition Strategies for Simultaneously Imaging of PCr and γ-ATP in the human brain at 9.4T
Aiming Lu1, Ian C Atkinson1, and Keith R Thulborn1
1Center for MR Research, University of Illinois at Chicago, Chicago, IL, United States

The PCr/γ-ATP concentration ratio provides an important measure of the balance of fluxes between the anabolic and catabolic ATP pathways. The low MR signals of these compounds demand tailored efficient data acquisition strategies to be used for imaging. The performance of a recently proposed acquisition strategy termed SIMPLE-flexTPI and its equivalent with a RARE readout, termed SIMPLE-RARE has been investigated. Our results showed that both the sequences achieved comparable SNR efficiency for PCr imaging. However, the SIMPLE-flexTPI sequence performed better for γ-ATP imaging due to its short TE capability, and therefore is more suitable for mapping the PCr/γ-ATP ratio.

4428.   71 Proton-decoupled 13C MRS of the Breast at 7T
Sergey Cheshkov1,2, Ivan Dimitrov1,3, Joseph Rispoli4, Elias Gonzalez4, Craig Malloy1,2, Mary McDougall4,5, and Steve Wright4,5
1Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, United States, 2Radiology, University of Texas Southwestern Medical Center, Dallas, TX, United States, 3Philips Medical Systems, Cleaveland, OH, United States, 4Biomedical Engineering, Texas A&M University, College Station, TX, United States, 5Electrical Engineering, Texas A&M University, College Station, TX, United States

Studies indicate that composition of breast fat, which is sensitive to diet, may predispose to cancer with lower case Greek omega6/lower case Greek omega3 lipid ratio being of particular importance. We demonstrate for the first time artifact free proton-decoupled breast 13C MRS at 7T using home built 1H/13C breast coil. This approach has the potential to provide lower case Greek omega6/lower case Greek omega3 information on lipid composition, which may shed further light on the relations between obesity, diet, and cancer. Further improvements in 13C coil sensitivities may be required in order to achieve higher SNR and shorter acquisition times.

4429.   72 Investigation of In Vivo Pyruvate Dehydrogenase Flux in Hypertension Induced Cardiac Hypertrophy
Damian J Tyler1, Vicky Ball1, Lucia Giles1, Carolyn A Carr1, Kieran Clarke1, and Anne-Marie L Seymour1,2
1Department of Physiology, Anatomy & Genetics, University of Oxford, Oxford, Oxfordshire, United Kingdom, 2Department of Biological Sciences, University of Hull, Hull, United Kingdom

Cardiac hypertrophy is an independent risk factor associated with heart failure and is characterised by significant metabolic adaptation which may underpin functional deterioration. In this study, we have investigated the relationship between cardiac structure/function and in vivo flux through the pyruvate dehydrogenase complex in an experimental model of cardiac hypertrophy caused by abdominal aortic constriction. Four weeks after the surgical induction of aortic constriction, a significant increase in cardiac mass was observed despite no alteration in cardiac function or metabolism. Future work will study the progressive development of cardiac functional and metabolic alterations in this cohort of animals.
Electronic Poster Session - MRS, non-H1 & ESR

MRS & Profiling
Click on to view the abstract pdf and click on to view the video presentation. (Not all presentations are available.)
Thursday 10 May 2012
Exhibition Hall  13:30 - 14:30

  Computer #  
4430.   73 1H Magnetic Resonance Spectroscopy Reports Osmotic Dysregulation in Brain during Whole Body Radiation Induced Radiation Sickness
Poonam Rana1, Ahmad Raza Khan1, Shilpi Modi1, Richa Trivedi1, B.S. Hemanth Kumar1, Rajendra P Tripathi1, and Subash Khushu1
1NMR Research Centre, Institute of Nuclear Medicine and Allied Sciences, Delhi, Delhi, India

Synopsis: Central nervous system is considered a radio-resistant organ during whole body exposure but function changes do occur after radiation exposure in terms of neurochemical metabolism. The present study based on 1H MRS was conducted to look for metabolic changes in mouse brain after giving graded whole body irradiation. The results exhibited time and dose dependent decrease in osmolytes; myoinositol and taurine in cortico-hippocampal region day 3 onwards post irradiation. Decreased levels of both the metabolites suggested oxidative stress induced osmotic dysregulation in brain that could have been associated with functional changes occurring in brain

4431.   74 Metabolic changes following Primary SIV-Infection in Rhesus Macaques: 3D multivoxel Proton MR Spectroscopy at 3 T
William E. Wu1, Assaf Tal1, Ivan Kirov1, Henry Rusinek1, James Babb1, Eva-Maria Ratai2, Chan-Gyu Joo2, R Gilberto Gonzalez2, and Oded Gonen1
1Radiology, New York University School of Medicine, New York, NY, United States, 2Neuroradiology, Athinoula A. Martinos Center for Biomedical Imaging and Neuroradiology, Charlestown, MA, United States

Because of its very similar pathology to HIV-infected humans, the simian immunodeficiency virus-infected rhesus macaque is often studied. Unfortunately, the relative dysfunction of global brain gray and white matter (GM, WM) remains unknown. To assess this, we performed three-dimensional proton MR spectroscopy over extensive, ~35% of the macaque brain, volume at 0.125cm3 spatial resolution and compared the absolute N-acetylaspartate (NAA), creatine (Cr), choline (Cho), and myo-inositol (mI) concentrations in five rhesus macaques at baseline and 4-6-weeks post-infection. We report Cho decline was characterized mostly by global GM pathology (down 20%), and NAA loss occurred mainly in the WM (down 8%).

4432.   75 HRMAS NMR spectroscopic analysis and quantification of marrow adiposity in the B6 mouse model after exposure to rosiglitazone treatment
Keerthi Shet1, Hikari Yoshihara1, John Kurhanewicz1, Ann Schwartz2, Cliff J Rosen3, and Xiaojuan Li1
1Radiology, University of California, San Francisco, San Francisco, CA, United States, 2Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, United States, 3Jackson Laboratory, Bar Harbor, Maine

Clinical 1H-MRS studies have shown that increased bone-marrow adiposity is associated with decreased BMD in patients with osteoporosis/osteopenia. Marrow adipose tissue(MAT) from the C57BL/6J(B6) mice was analyzed using HRMAS-NMR following exposure to type-2-diabetes-drug�rosiglitazone. We observed significant changes in MAT composition along with the rosiglitazone-induced increase in adiposity. In particular, the decreased unsaturated-lipids and increased saturated-lipids may be correlated with decreased bone strength with rosiglitazone treatment. Thus, consistent with recent observation in-vivo that decreased MAT unsaturation level is associated with fracture-risk, the fatty-acid unsaturation/saturation level of MAT can be a potential imaging marker for bone quality and fracture.

4433.   76 A Comparative Evaluation of Brain Metabolites following Whole Body and Cranial Irradiation: A Prospective 1H MRS Study
Poonam Rana1, Mamta Gupta1, Ahmad Raza Khan1, Richa Trivedi1, B.S. Hemanth Kumar1, Ravi Soni2, and Subash Khushu1
1NMR Research Centre, Institute of Nuclear Medicine and Allied Sciences, Delhi, Delhi, India, 2Division of Radiation Biosciences, Institute of Nuclear Medicine and Allied Sciences, Delhi, India

Synopsis: Central nervous system has a limited repertoire of responses to radiation injury and it responds differentially with the type of exposure of radiation given. The present study was conducted to identify metabolic changes in hippocampal region of mice brain after cranial and whole body irradiation using 1H NMR spectroscopy if any. The results exhibited time dependent decrease in two metabolites; myoinositol and taurine in hippocampal region day3 onwards post irradiation only in animals exposed to whole body radiation. While no significant difference in metabolite level was observed in whole brain irradiation. Differential response of whole body and cranial irradiation might be due to degree of difference in anti oxidant response of body and brain against radiation exposure.

4434.   77 Regional Neurochemical Profiles in the Non-human Primate Model by 1H MRS at 7T
Uzay Emrah Emir1, Noam Harel1, Essa Yacoub1, Gregor Adriany1, and Gulin Oz1
1University of Minnesota, Minneapolis, Minnesota, United States

Non-human primate models of neurological diseases serve as a critical link between basic research and human clinical applications. Therefore, reliably measuring neurochemical levels, which may serve as disease biomarkers and enhance understanding of mechanisms of neurological diseases, in the monkey brain is of great interest. Here we demonstrate the feasibility of acquiring and quantifying single voxel semi-LASER spectra by utilizing a custom build monkey coil at 7T. Representative spectra and neurochemical profiles are reported from brain regions that are of interest for various neurological disorders, namely the posterior cingulate, putamen and cerebellum. Neurochemical similarities between humans and monkeys were observed

Zaiyang Long1,2, Jun Xu1,2, Jennifer L McGlothan3, Richard A.E. Edden4,5, Peter B. Barker4,5, Tomas R Guilarte3, and Ulrike Dydak1,2
1School of Health Sciences, Purdue University, West Lafayette, IN, United States, 2Dept. of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, United States, 3Dept. of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York, NY, United States, 4Russell H. Morgan Dept. of Radiology and Radiological Science, The Johns Hopkins University, Baltimore, MD, United States, 5F.M. Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States

The baseline difference of brain metabolites, especially of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), was compared between monkeys and humans using the same imaging sequence on the same type of 3.0T MRI scanner. Short-echo-time spectra from the thalamus and frontal cortex and GABA-edited spectra using MEGA-PRESS from a volume containing the thalamus were acquired in 7 rhesus monkeys and 8 healthy humans. Monkey thalamus showed higher GABA/total creatine (tCr) than human thalamus. Monkeys had lower N-Acetyl-aspartate in the frontal cortex and thalamus. Glutamate and total choline were higher in human frontal cortex, while tCr was higher in human thalamus.

4436.   79 Neuroinflamatory evidence during early onset of depression in CMS rats as detected by proton MRS at 7T.
B.S. Hemanth Kumar1, Sushanta Kumar Mishra1, Poonam Rana1, Sadhana Singh1, Rajendra P Tripathi1, and Subash Khushu1
1NMR Research Centre, Institute of Nuclear Medicine and Allied Sciences (INMAS), Newdelhi, Newdelhi, India

Chronic Mild Stress (CMS) regime was applied to develop depression model in rats and the model was validated using behavioural studies. Magnetic Resonance Spectroscopy (MRS) was acquired on 10 Control and CMS induced rats in prefrontal cortex (PFC) and hippocampus regions to look for the neurometabolite changes duing the early onset of depression. The concentrations of the neurometabolites were calculated for analysis. The study revealed the metabolite fluctuations, altering the glial physiology within prefrontal cortex and hippocampus in CMS model. We conclude that there might be a neuroinflamation process ocucuring in the glia and the neurons of these brain regions to play a major role in onset of depression.

4437.   80 Three-dimensional Multivoxel Proton MR Spectroscopy Distinguishes Regional Gray Matter Metabolic Abnormalities in SIV-Infected Rhesus Macaques at 3T: Initial Findings
William E Wu1, Ivan Kirov1, Ke Zhang1, Eva-Maria Ratai, 2, Chang-Gyu Joo2, R Gilberto Gonzalez2, and Oded Gonen1
1New York University School of Medicine, New York, New York, United States, 2Neuroradiology, Athinoula A. Martinos Center for Biomedical Imaging and Neuroradiology, Charlestown, MA, United States


4438.   81 In vivo high-resolution localized 1H spectroscopy in the unanesthetized rat brain at 7 Tesla
Su Xu1,2, Yadong Ji3, Xi Chen4, Yihong Yang4, Rao Gullapalli1,2, and Radi Masri3
1Department of Diagnostic Radiology & Nuclear Medicine, University of Maryland School of Medicine, Baltimore, Maryland, United States, 2Core for Translational Research in Imaging @ Maryland, University of Maryland School of Medicine, Baltimore, Maryland, United States, 3Department of Endodontics, Prosthodontics and Operative Dentistry, University of Maryland Dental School, 4Neuroimaging Research Branch, National Institute on Drug Abuse, NIH

In vivo localized high resolution 1H MRS was performed in multiple regions of the rat brain without use of anesthetic or paralytic agents in head restrained rats using a Bruker 7 T MR system. From a MR spectrum of a voxel (27 – 32.4 lower case Greek mul) in the unanesthetized rat brain, eight to ten metabolites or combinations were reliably detected and quantified in the anterior cingulate cortex, somatosensory cortex, hippocampus and thalamus without any post processing correction scheme. The current development in technique offers a novel way to study major brain metabolites without the confounds of anesthesia or paralytic agents in rodents.

82 Lactoferrine supplementation following Hypoxia-Ischemia in the immature rat brain: macro-, micro-structural and metabolic assessment of the neuroprotective effect using multimodal MR
Yohan van de Looij1,2, Alexandra Chatagner1, Petra S Hüppi1, Rolf Gruetter2,3, and Stéphane Sizonenko1
1Division of Child Growth & Development, University of Geneva, Geneva, Switzerland, 2Laboratory for Functional and Metabolic Imaging, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, 3Department of Radiology, University of Geneva and Lausanne, Geneva and Lausanne, Switzerland

Animal models of preterm brain injury can be achieved by Hypoxia-Ischemia (HI) and Lactoferrine (Lf) has been shown to be neuroprotective in rat brain following prenatal exposure to glucocorticoids. Here we investigated the neuroprotective effect of Lf supplementation in a model of neonatal HI injury in the P3 rat brain using high-field multimodal NMR techniques: MRI, MRS, DTI and Phase imaging. This study shows a full characterization of the P3 HI model 22 days following insult by using multimodal NMR techniques. Lf seems to have a neuroprotective effect on tissue loss, white matter injuries as well as altered metabolism.

4440.   83 Methylphenidate's Effects on the Metabolomic Profile of the Rat Brain measured by 1H-MRS
Hedok Lee1, Shaonan Zhang1, Mei Yu1, Rany Makaryus1, David Smith2, Nora Volkow3, and Helene Benveniste1
1Anesthesiology, State University of New York at Stony Brook, Stony Brook, New York, United States, 2Medical, Broohaven National Laboratory, Upton, New York, United States, 3National Institute on Drug Abuse, Bethesda, Maryland, United States

There is lack of information as to the short- and long-term effects of MP on brain function and neurotransmission. In this study, we employed proton magnetic resonance spectroscopy (1HMRS) to characterize neurochemical status in the rodent brain anesthetized with isoflurane before and after an intravenous challenge with IV dose of 5mg/kg MP. We found significantly decreased [Glu] in the rat striatum. This is in agreement with human studies demonstrating that MP can decrease CMRglu in some individuals an effect that is accentuated under conditions of higher glucose demand.

4441.   84 T2 MR Relaxometry Study of Acute Heat Stress induced changes in Rat Brain at 7T
Sunil Koundal1, Sonia Gandhi1, Rajendra P Tripathi1, and Subash Khushu1
1NMR Research Centre, INMAS, Delhi, Delhi, India

Hyperthermia associated with heat stroke is a life threatening illness inducing CNS dysfunction, such as delirium, convulsion and coma. Heat stress induces neurotoxicity in brain caused due to oxidative stress resulting in neuronal cell degeneration. Present studies investigate changes in T2 relaxation on heat exposure & possible tool to track neuronal cell damage. There is a significant decrease in T2 values for hippocampus & thalamus regions due iron or reactive oxygen species accumulation on heat exposure which might reacts with lipids, proteins, DNA causing lipid peroxidation, altered protein conformations, & apoptosis. These studies will be useful in non-invasive tracking & evaluation of neuronal cell degeneration due to heat stress at an early stage.

4442.   85 Employing Combined Quantitative MRI and MRS Markers to Distinguish Mild Cognitive Impairment
Thao T. Tran1, and Jessica Liu2
1Clinical MRS, Huntington Medical Research Institutes, Pasadena, CA, United States, 2UCLA, Los Angeles, CA, United States


4443.   86 Brain MRI and MRS detection of falx ossification or lipomas in a majority of older adults
Peter B. Kingsley1, and Marc L. Gordon2,3
1Radiology, North Shore University Hospital, Manhasset, New York, United States, 2Litwin-Zucker Research Center, Manhasset, New York, United States, 3Hofstra North Shore-LIJ School of Medicine, Hempstead, NY, United States

Lipids in brain MR spectra often suggest pathology, such as tumor, infection, or demyelination. We observed lipids in spectra of a majority of normal adult and aging human brains, ages 50-90. These lipids, usually found in the interhemispheric fissure, may be associated with falx ossifications (broad peaks) or lipomas (CH2 peak near 1.5 ppm). Previously, ossifications were reported in <1%, large lipomas in <0.1%, and small lipomas in 10% of elderly adults. Lipids in human brain MR spectra may not necessarily indicate pathology, especially if a midline voxel lipid peak is broad or shifted from 1.3 ppm to 1.5 ppm.

4444.   87 Magnetic Resonance Spectroscopy in Obsessive-Compulsive Disorder: Comparing Brain Metabolism in Selective Serotonin Responders and Non-Responders
Mona Adel Mohamed1, Richard Edden1, Manuel Uy2, Gerald Nestadt3, and Peter Barker1
1Radiology, Johns Hopkins Medical Institutions, Baltimore, MD, United States, 2Applied Physics Laboratory, Johns Hopkins University, Baltimore, MD, United States, 3Psychiatry, Johns Hopkins Medical Institutions, Baltimore, MD, United States

Through magnetic resonance spectroscopy (MRS), significant differences were found in myoinositol (mI) concentrations in the anterior cingulate cortex (ACC) of OCD patients as compared to controls, as well as differences in OCD patients who respond to selective serotonin reuptake inhibitors (SSRIs) and those who do not respond to SSRIs. Significant differences were also found in creatine (Cr) concentrations in the basal ganglia/Thalamus (BG/TH) region between the 2 groups. MRS can be a helpful tool in understanding of the pathophysiology of response to treatment which will lead to the development of new therapeutic approaches.

4445.   88 Glutamate reduces in grey matter of MS patients and correlates with cognitive impairment
Enrico De Vita1,2, Nils Mulhert3, Matteo Atzori4,5, David L Thomas2, Claudia Wheeler-Kingshott5, Jeroen JG Geurts6, Alan J Thompson5, and Olga Ciccarelli5
1Lysholm Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, London, United Kingdom, 2Academic Neuroradiological Unit, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, London, United Kingdom, 3NMR Research Unit, Department of Neuroinflammation, UCL Institute of Neurology, London, United Kingdom, 4Department of Neurology, University of Padova, Padova, Italy, 5NMR Research Unit, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, London, United Kingdom, 6MS Research Centre, Department of Radiology, VU University Medical Centre, Amsterdam, Netherlands

We performed single-voxel 3T 1H-MRS to assess glutamate concentrations ([Glu]) in grey matter (hippocampus, thalamus, cortex) of relapsing-remitting MS patients to establish whether it differs between patients and controls and relates to cognitive dysfunction. Intra-voxel tissue segmentation was employed to account for voxel water content. MS patients showed: lower [Glu] in the right hippocampus, parietal and cingulated cortices; lower NAA in the thalamus and cortical regions; lower choline-containing compounds and creatine-plus-phosphocreatine in the cortical regions, than controls. In patients, right hippocampal [Glu] significantly predicted visual memory scores, suggesting it may become a surrogate marker for memory impairment in clinical trials.

4446.   89 Reduced motor cortex GABA in amyotrophic lateral sclerosis
Bradley R Foerster1,2, Brian C Callaghan3, Myria Petrou1,4, Richard AE Edden4, Thomas L Chenevert1, and Eva L Feldman3
1Department of Radiology, Division of Neuroradiology, University of Michigan, Ann Arbor, MI, United States, 2Ann Arbor VA Healthcare System, Ann Arbor, MI, United States, 3Department of Neurology, University of Michigan, Ann Arbor, MI, United States, 4Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University, Baltimore, MD, United States

In this study, we investigate whether there are in vivo differences in GABA in the motor cortex and subcortical white matter of amyotrophic lateral sclerosis (ALS) patients compared with healthy controls. In 10 patients with ALS and 9 age- and sex-matched healthy controls, 3T edited proton magnetic resonance spectroscopy was performed to quantify GABA in primary motor cortex and subcortical white matter. Compared with healthy controls, ALS patients had significantly lower levels of GABA in the left motor cortex (1.42±0.27 i.u. vs 1.70±0.24 i.u., p=0.038). There was no significant difference in GABA levels between groups in the subcortical white matter (p>0.05). Findings are consistent with prior reports of alterations in GABA receptors in the motor cortex as well as increased cortical excitability in the context of ALS. Larger, longitudinal studies are needed to confirm these findings and to further our understanding of the role of GABA in the pathogenesis of ALS.

4447.   90 3D MRSI of Brain Neurochemical Changes in Breast Cancer Patients treated with Chemotherapy
Jun Xu1,2, Brenna C. McDonald1, John D West1, Ulrike Dydak1,2, and Andrew J Saykin1
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

Cancer patients treated with chemotherapy have typically shown decreased neuropsychological performance. To better understand the mechanisms behind such deficits caused by chemotherapy, we used 3D proton magnetic resonance spectroscopic imaging (MRSI) to obtain information on changes in brain metabolite levels before and after chemotherapy. We compared breast cancer patients treated with and without chemotherapy, and controls. No cross sectional differences were found between the three groups, but a significant decrease of NAA/Cr in the hippocampus was found in the chemotherapy group, and significant decreases of Cho/Cr in hippocampus were found in both patient groups over time.

4448.   91 Interferon-alpha Induced Metabolic Alterations in Basal Ganglia and Anterior Cingulate Cortex
Xiangchuan Chen1, Reena Anand2,3, Xiaoping Hu1, and Ebrahim Haroon2,3
1Biomedical Imaging Technology Center, Emory University, Atlanta, GA, United States, 2School of Medicine, Emory University, Atlanta, GA, United States, 3Winship Cancer Institute, Atlanta, GA, United States

Metabolic alterations induced by chronic administration of interferon (IFN)-alpha for the treatment of hepatitis C virus infection were examined with single voxel magnetic resonance spectroscopy. The results showed that the metabolisms of glutamate, myo-inositol and choline in the anterior cingulate cortex, left and right basal ganglia were altered by the treatment with IFN-alpha. These metabolic changes in the abovementioned brain regions may be the underlying mechanism for the behavioral alterations (e.g., depression) induced by the treatment.

4449.   92 Brain Biochemical Abnormalities and Cognitive Impairments in Patients with Type 2 Diabetes and Major Depression: A Combined 1H-MRS and Neuropsychological Study
Shaolin Yang1,2, Olusola Ajilore1, Melissa Lamar1, Laura Korthauer1, and Anand Kumar1
1Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, United States, 2Department of Radiology, University of Illinois at Chicago, Chicago, IL, United States

Type 2 diabetes and major depression are mutual risk factors. Previous studies have evidenced brain biochemical abnormalities in cortical and subcortical regions as well as cognitive deficits in patients with either disease alone or both. In order to better understand the pathophysiological mechanisms of these disorders, we examined whether brain biochemical abnormalities measured through 1H magnetic resonance spectroscopy are correlated with cognitive function and performance and whether there is any difference in the correlation profiles among these diseases.

4450.   93 Association of peri-infarct N-acetyl aspartate with recovery from stroke
Ruth L O'Gorman1, Laszlo K Sztriha2, Gareth J Barker3, Steven CR Williams3, and Lalit Kalra2
1University Children's Hospital, Zurich, Switzerland, 2Clinical Neurosciences, Institute of Psychiatry, King's College London, United Kingdom, 3Centre for Neuroimaging Sciences, Institute of Psychiatry, King's College London, United Kingdom

Peri-infarct tissue appears to play a crucial role in recovery following a stroke. This study investigated the concentrations of the major neuro-metabolites in peri-infarct tissue at 3 and 15 weeks after stroke onset, in relation to motor outcome. MR spectra were acquired from 6 stroke patients and 7 controls in the peri-infarct thalamus, the contralesional thalamus, and the anterior cingulate cortex. NAA in the ipsilesional thalamus was significantly lower in the patients than the controls, and decreased between 3 and 15 weeks after stroke onset. NAA in the ipsilesional thalamus at baseline significantly correlated with the final motor outcome scores.

4451.   94 Additive Effects of Type 2 Diabetes and Major Depression on Brain Biochemical Abnormalities
Shaolin Yang1,2, Olusola Ajilore1, Minjie Wu1, Melissa Lamar1, and Anand Kumar1
1Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, United States, 2Department of Radiology, University of Illinois at Chicago, Chicago, IL, United States

Type 2 diabetes and major depression are mutual risk factors. In this study, we examined whether the two diseases have additive or interactive effects on brain biochemical abnormalities using 1H MR spectroscopy. Patients with type 2 diabetes (with or without depression) had higher concentration ofmyo-inositol (Ins), the glial marker, in frontal white matter (FWM) & head of caudate nucleus (Caud) and higher choline-containing compounds (tCho) in anterior cingulate cortex (ACC) & Caud while patients with major depression (with or without diabetes) had higher tCho levels in FWM. Patients with both diseases showed additive effects on Ins and tCho, suggesting additional glial process/abnormalities due to the comorbid conditions.

4452.   95 Increased frontal glutamine in patients with idiopathic generalised epilepsy using MEGAPRESS spectroscopy
Fahmida A Chowdhury1, Ruth L O'Gorman2, Jonathan O'Muircheartaigh1, Mark P Richardson1, and Gareth J Barker3
1Department of Clinical Neuroscience, Institute of Psychiatry, KCL, London, United Kingdom, 2Center for MR Research, University Children's Hospital, Zurich, Switzerland, 3Department of Neuroimaging, Institute of Psychiatry, KCL, London, United Kingdom

Most previous spectroscopic studies have reported Glx levels, a combined measure of Glu (glutamate), the major excitatory neurotransmitter, and Gln (glutamine), the metabolic counterpart of glutamate. Increased Glx in frontal regions has been reported in patients with idiopathic generalised epilepsies (IGE). It has been suggested that glutamine is a useful surrogate marker for synaptically active glutamate. Recently MEGAPRESS acquisition has allowed detection of glutamine with greater sensitivity than that of the PRESS acquisition. Here we report increased frontal glutamine in a group of patients with IGE, which may represent a more sensitive measure for excitatory neurotransmission than Glx.

4453.   96 Similar global N-acetylaspartate in benign and non-benign multiple sclerosis patients of similar long disease duration
Daniel Rigotti1, Lutz Achtnichts2, Oded Gonen1, James Babb1, Yvonne Naegelin2, Kerstin Bendtfeld2, Jochen Hirsch2, Michael Amann2, Robert I Grossman1, Ludwig Kappos2, and Achim Gass2
1Radiology, New York University School of Medicine, New York, NY, United States, 2Radiology, University Hospital Basel, Basel, Switzerland

We test the hypothesis that neural preservation, reflected by whole-brain N-acetylaspartate (WBNAA) in benign multiple sclerosis (MS) is similar to healthy contemporaries and higher than more clinically disabled patients of similar disease duration. WBNAA was obtained from 24 benign and 16 non-benign MS patients and 17 age-matched controls. While control's had significantly higher WBNAA (12.2±2.3mM), than either group (benign: 10.5±2.4, non-benign:10.1±2.3mM, (p‹0.04)), patients were similar as they were in other metrics (atrophy and T2 hyperintense lesion volume but not T1 hypointense load). Surprisingly, neural integrity/preservation is not a characteristic of benign MS, possibly reflecting fortunate sparing of eloquent brain regions.
Electronic Poster Session - MRS, non-H1 & ESR

MRS: Methods, Tactics, Strategies
Click on to view the abstract pdf and click on to view the video presentation. (Not all presentations are available.)
Thursday 10 May 2012
Exhibition Hall  14:30 - 15:30

  Computer #  
4454.   73 High Resolution 2D CTPRESS with 2D Spiral Encoding
Trina Kok1, Borjan Gagoski1, and Elfar Adalsteinsson1,2
1EECS, Massachusetts Institute of Technology, Cambridge, MA, United States, 2Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, United States

32-element receive coil arrays offer significant SNR gains over birdcage coils, which can be traded for faster scans of improved spatial resolution. Here we demonstrate in vivo 2D CTPRESS on a 3T Siemens Tim Trio with spiral encoding at a spatial resolution of 0.85cc with minimum scan time of 5:16min. Four averages were taken for improved SNR, resulting in a total scan time of 20:32min.

4455.   74 Lipid Suppression in CSI with Highly-Undersampled Peripheral k-space and Spatial Priors
Berkin Bilgic1, Borjan Gagoski1, and Elfar Adalsteinsson1,2
1EECS, Massachusetts Institute of Technology, Cambridge, MA, United States, 2Harvard-MIT Division of Health Sciences and Technology, MIT, Cambridge, MA, United States

Mapping the concentration of brain metabolites using chemical shift imaging is made difficult by the presence of subcutaneous lipid signals, which contaminate the metabolites by ringing due to limited spatial resolution. Dual-density approach exploits the high-SNR property of the lipid layer to generate high-resolution lipid maps and suppress truncation artifacts. Another recent approach for lipid suppression makes use of the fact that the metabolite and the lipid spectra are approximately orthogonal, and seeks sparse metabolite spectra when projected onto lipid-basis functions. Our work combines and extends the dual-density approach and the lipid-basis penalty, while estimating the high-resolution lipid image from single-average k-space data to incur only minimal increase on the total scan time. Further, we also exploit the spectral-spatial sparsity of the lipid ring and propose to estimate it from substantially undersampled single-average in vivo data using compressed sensing, and still obtain excellent artifact suppression.

4456.   75 Human Brain Non Echo 3D Hadamard Spectroscopic Imaging
Ouri Cohen1,2, and Oded Gonen1
1Center for Biomedical Imaging, NYU, New York, NY, United States, 2Biomedical Engineering, Columbia University, New York, NY, United States

A non-echo multivoxel localized proton NMR spectroscopy (1H-MRS) method that is based on three dimensional (3D) Hadamard spectroscopic imaging (HSI) is introduced and demonstrated in vivo.

4457.   76 Algebraic chemical shift image reconstruction
Florian Wiesinger1, Jonathan I Sperl1, Markus Durst2, Axel Haase2, Markus Schwaiger2, and Rolf F Schulte3
1GE Global Research, Munich, Germany, 2Technische Universitaet Muenchen, Munich, Germany, 3GE Global Research, Germany

In this work a simple and general CSI reconstruction framework is presented based on a discretized forward model of the encoding process. Image reconstruction is then simply performed via direct matrix inversion. The method takes advantage of the generally low image resolution used in hyperpolarized 13C CSI and can readily be implemented on modern computers.

4458.   77 Development of Parallel Correlated Spectroscopic Imaging
Gaurav Verma1,2
1Radiology, University of Pennsylvania, Philadelphia, PA, United States, 2Radiological Sciences, University of California, Los Angeles, California, United States

A spectroscopic imaging technique was developed combining Sensitivity Encoding (SENSE) with Multi-Echo Correlated Spectroscopic Imaging (ME-COSI). In this initial application, parallel imaging acquisition was used to double the number of spatial points from 8x8 to 8x16 with a corresponding doubling of the effective Field-of-View (FOV). Testing in brain phantom demonstrated the presence of several expected diagonal and cross peak resonances throughout the excited volume including regions subject to residual folding artifacts. The sequence could be developed further, including accelerating acquisition by applying SENSE to both spatial dimensions. This sequence represents the first application of parallel imaging to correlated spectroscopic imaging.

4459.   78 Entrechat Templates May Help Overcome Scepticism on Combinining Forward and Reflected EPSI Readouts
Christian Labadie1,2, Stefan Hetzer3, Monique Aubert-Frécon2, and Harald E Möller1
1Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany, 2Laboratoire de Spectrométrie Ionique et Moléculaire, Université Claude Bernard, Lyon, France, 3Bernstein Center for Computational Neuroscience, Berlin, Germany

It is widely accepted that forward and reflected readouts may not be combined into a single series of EPSI k-spaces. Consequently, measurements must be repeated with opposite readout polarities. Crisscrossing the acquisition of two separate template scans with opposite readout polarities permits the comparison of forward and reflected template ADCs that were acquired during two separate TRs but at the same time in the FID.

4460.   79 B1-dependence of single-voxel MRS sequences: STEAM, PRESS and MEGA-PRESS
Nicolaas AJ Puts1,2, Michael Schär1,3, He Zhu1,2, Peter B Barker1,2, and Richard AE Edden1,2
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, 3Philips Healthcare, Cleveland, OH, United States

In this abstract, we investigate the extent to which 3 single-voxel MRS sequences (STEAM, PRESS and MEGA-PRESS) are sensitive to miscalibration (or inhomogeneity) of the B1 field. Experimental results at 7T show that the actual B1 dependence is much worse than a naive model of sin dependence for excitation pulses and sin-squared for refocusing. For MEGA-PRESS, even a 20% drop in B1 can result in over 50% loss in signal.

4461.   80 Sensitivity Decomposition of Water and Metabolites with Sensitivity Encoding for Unaliasing Lipid Contamination
Toru Shirai1, Satoshi Hirata1, Yo Taniguchi1, Yoshihisa Soutome1, and Yoshitaka Bito1
1Hitachi, Ltd., Central Research Laboratory, Kokubunji, Tokyo, Japan

We have developed a technique for sensitivity decomposition of water and metabolites combined with sensitivity encoding in order to acquire water and metabolites simultaneously and reduce aliased lipid. This technique consists of a measurement that shifts only water to the four corners on the image and a data process that separates each signal using the coil sensitivity difference. This technique reduces aliased lipid and acquires water and metabolites simultaneously without increasing the scan time. The results from phantom and healthy volunteer experiments showed that this technique is useful for acquiring water and metabolites simultaneously and reducing aliased lipid.

4462.   81 Accelerated Multi Echo based Echo-Planar J-Resolved Spectroscopic Imaging: Implementation and Quantitation of Cerebral Metabolites
Manoj Kumar Sarma1, Rajakumar Nagarajan1, Neil Wilson1, Jon Furuyama1, and M. Albert Thomas1
1Radiological Sciences, UCLA School of Medicine, Los Angeles, CA, United States

Four dimensional (4D) multi-echo (ME) echo planar (EP) based J resolved spectroscopic imaging (ME-EP-JRESI) technique is more robust and enables simultaneous recording of two dimensional (2D) JPRESS spectra in multiple regions with better spectral and spatial resolution than the conventional magnetic resonance spectroscopic imaging (MRSI) approaches recording one dimensional (1D) MRS. These results demonstrate that ProFit processing of 2D JPRESS spectra extracted from the ME-EP-JRESI data provides additional metabolites with reduced Cramér–Rao lower bound (CRLB) values (< 20%) in rhe healthy human brain.

4463.   82 Accelerated Echo-Planar Correlated Spectroscopic Imaging with Sensitivity Encoding
David Ouellette1, Neil Wilson1, Brian Burns2, Jon Furuyama3, Gaurav Verma3, Chris Roberts4, Cathy Lee5, Preethi Srikanthan5, Theodore Hahn5, and M. Albert Thomas3
1Biomedical Physics IDP, UCLA, Los Angeles, CA, United States, 2Biomedical Engineering IDP, UCLA, Los Angeles, CA, United States, 3Radiological Sciences, UCLA, Los Angeles, CA, United States, 4School of Nursing, UCLA, Los Angeles, CA, United States, 5Medicine, UCLA, Los Angeles, CA, United States

EP-COSI is a 4D spectroscopic imaging technique, acquiring 2 spatial and 2 spectral dimensions. One of the drawbacks of EP-COSI is the long acquisition times. In this work, SENSE was applied to the EP-COSI sequence to cut the scan time by half. The calf muscles of one healthy and one diabetic volunteer were investigated with EP-COSI SENSE. The resulting 2D spectra were accurately localized and were of sufficient quality to observe the olefinic cross peaks in the diabetic calf and the creatine 3.9 doublet in the tibialis anterior.

4464.   83 Proton magnetic resonance spectroscopic imaging (MRSI) in a clinical setting: a scheme to reduce chemical shift VOI misregistration-induced metabolite ratio bias in edge voxels
David J Manton1, Lawrence Kenning1, Ralph Noeske2, Timo Schirmer3, Gary P Liney4, Martin Lowry1, Martin D Pickles1, Richard Bartlett5, Christopher Rowland-Hill5, and Lindsay W Turnbull1
1YCR Centre for MR Investigations, The University of Hull, Hull, East Yorkshire, United Kingdom, 2Applied Science Laboratory Europe, GE Healthcare, Berlin, Germany, 3Applied Science Laboratory Europe, GE Healthcare, Muenchen, Germany, 4Radiation Physics, Hull & East Yorkshire Hospitals NHS Trust, Cottingham, East Yorkshire, United Kingdom, 5Radiology Department, Hull & East Yorkshire Hospitals NHS Trust, Hull, East Yorkshire, United Kingdom

Clinical PRESS-based proton magnetic resonance spectroscopic imaging (MRSI) choline:NAA ratios demonstrated chemical shift volume of interest misregistration-induced bias from 42% too low to 66% too high over a 7×9 cm 2D VOI in a homogenous phantom at 3 T. A phantom-based calibration protocol was developed to allow robust in vivo bias correction where other ameliorating methods are unavailable (e.g. on clinical scanners) or impractical (e.g. with tumours lying close to the skull). Water resonant frequency changed by 25 Hz between in vivo (body temperature) and phantom (room temperature) experiments and this was taken into account when calculating the calibration map.

4465.   84 Voxel selective Lactate editing at high magnetic field strengths using Sel-MQC
Gerd Melkus1, Myriam M Chaumeil1, Sharmila Majumdar1, and Sabrina M Ronen1
1Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, United States

A single voxel localization scheme for the Selective Multiple Quantum Coherence (Sel-MQC) filter for Lactate editing is presented. The method is based on the concept of inducing a spatial mismatch between the J-coupled CH- and CH3-Lactate resonances to achieve local chemical shift selectivity for the filter. The sequence was tested on a Lactate phantom and compared to LASER and PRESS acquisitions, showing that the theoretical signal intensity of 50% can be achieved using this localization technique for Sel-MQC. A localized Lactate spectrum was acquired at 14.1T from an orthotopic glioblastoma tumor in vivo using this technique.

4466.   85 A multimodal study, combining functional MRI, ASL perfusion, MR spectroscopy, and dynamic causal modelling
Karsten Specht1,2
1Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway, 2Department of Medical Engineering, Haukeland University Hospital, Bergen, Norway

In the recent years, an increasing number of studies includes magnetic resonance spectroscopy (MRS) in their functional magnetic resonance imaging (fMRI) study protocols, with a specific focus on the excitatory neurotransmitter glutamate (Glu). Using a simple motor task, the here presented study combines not only fMRI with MRS, but takes also arterial spin labelling (ASL) perfusion measures into account, and combines this with an analysis of effective connectivity. The results are demonstrating significant changes in the BOLD signal and regional perfusion in response to the motor task. In addition, medium correlations were detected between the connectivity parameter and neurotransmitter concentration.

4467.   86 Localized two-dimensional correlated spectroscopy based on Hadamard encoding technique
Yanqin Lin1, Qinta Zhang1, Shuhui Cai1, and Zhong Chen1
1Department of Electronic Science, Fujian Key Laboratory of Plasma and Magnetic Resonance, Xiamen University, Xiamen, Fujian, China

Localized two-dimensional (2D) magnetic resonance spectroscopy is increasing used in the study of in vivo tissue metabolites. However, long scan time limits its wide applications. Here, a new pulse sequence based on Hadamard encoding technique was devised to speed up the acquisition of 2D correlation spectroscopy. For the new scheme, the direct frequency-domain excitation is used in the indirect detection dimension, so the 2D acquisition was replaced by an array of one-dimensional acquisitions. A phantom built of two concentric glass cylinders was used to demonstrate the feasibility of this new sequence. The new method may provide a time-efficient way for 2D in vivo studies.

4468.   87 How to achieve a 100% success rate in cardiac 1H MR Spectroscopy
Åsa Carlsson1,2, Maja Sohlin2, Maria Ljungberg1,2, and Eva Forssell-Aronsson1,2
1Department of Medical physics and Biomedical Engineering, Sahlgrenska University Hospital, Gothenburg, Sweden, 2Department of Radiation Physics, University of Gothenburg, Gothenburg, Sweden

Localised proton MR-spectroscopy can be used for lipid quantification in the human myocardium but it is difficult as the method suffers from both motion and large susceptibility effects. It is, however, possible to achieve a 100% success rate in healthy volunteers and obtain good spectral quality every single time if following a strict measurement protocol where every step is optimised for each individual. The three most important steps were: 1) Planning the VOI completely within the ventricular septum, 2) using navigator triggered field mapping for shimming, and 3) optimising the cardiac triggering time delay using spectroscopy.

4469.   88 In vivo analysis of Pseudomonas Auriginosa Bacteria and the effects of a novel bacterial molecule by whole cell High Resolution Magic Angle Spinning (HR-MAS) NMR spectroscopy
Valeria Righi1,2, Meenu Kesarwani3, Laurence Rahme3, and Aria A. Tzika1,2
1NMR Surgical Laboratory, Department of Surgery, Massachusetts General Hospital and Shriners Burn Institute, Harvard Medical School, Boston, Massachusetts, United States, 2Athinoula A. Martino Center Biomedical Imaging Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States, 3Molecular Surgery Laboratory, Department of Surgery, Massachusetts General Hospital and Shriners Burn Hospital, Harvard Medical School, Boston, Massachusetts, United States

High Resolution Magic Angle Spinning (HRMAS) NMR spectroscopy was applied to determine the metabolite profile of live Pseudomonas aeruginosa bacteria. One-dimensional and 2-dimensional HRMAS NMR was performed on intact bacterial cells represents a promising method that could provide in vivo information of metabolomics in live bacteria. This in vivo NMR biomedical technique may prove to be a helpful tool in gene function validation, the study of pathogenesis mechanisms, the classification of microbial strains into functional/clinical groups and the testing of anti-bacterial agents and to distinguish the metabolic profile of different mutants.

4470.   89 High Resolution 1H NMR Approach to study the Effects of Cold Stress on the Metabolism of Rat Renal Tissue
Sonia Gandhi1, Hemant Kumar B S1, Sunil Koundal1, Shubhra Chaturvedi2, Rajendra P Tripathi1, and Subash Khushu1
1NMR Research Centre, INMAS, Delhi, Delhi, India, 2Division and Cyclotron & Radiopharmaceutical Sciences, INMAS, Delhi, Delhi, India

Cold stress may result in development of neuro-psychiatric symptoms such as depression, cognitive impairment, cardiovascular and respiratory diseases, immune suppression, gastrointestinal mucosal damage & potential dysfunction to adrenal glands, kidney & lungs. Present study investigates the changes in metabolic profiles of kidney tissue in rats due to prolonged cold stress using NMR & multivariate statistical analysis. Results shows marked increase in metabolites viz. Lactate, Creatine, Myoinisitol, Glycine & Glucose from day 1 to 5 & decrease on further exposure upto day 15 indicating increased anaerobic glycolysis, altered glomerular filtration rate & osmotic imbalance. Correlation with other parameters can detect early biomarkers for cold stress injuries & organ specific dosimetry.

90 Alginate encapsulated Lactate Dehydrogenase and Hyperpolarized MR as a Platform to Characterize Enzyme Kinetics
Deborah K. Hill1, Kayvan R. Keshari2, Renuka Sriram2, Bertram Koelsch2, Mark Van Criekinge2, Yuen-Li Chung1, Thomas R Eykyn1,3, Martin O. Leach1, and John Kurhanewicz2
1Clinical Magnetic Resonance, CRUK & EPSRC Cancer Imaging Centre, Royal Marsden NHS Trust & The Institute of Cancer Research, Sutton, Surrey, United Kingdom, 2Radiology and Biomedical Imaging, University of California, San Francisco (UCSF), United States, 3The Rayne Institute, Lambeth Wing, St. Thomas Hospital, London, United Kingdom

Hyperpolarized MR provides a means to acquire real time in vivo metabolic rates, such as the kinetics of lactate dehydrogenase, through the dramatically increased SNR of 13C substrates. The modeling of these kinetics is complicated by the number of parameters which can influence the derived rate. Ex- vivo studies that modulate these parameters are useful in delineating their impact. We present the use of alginate microspheres to encapsulate LDH for use in a bioreactor, thus providing a controlled ‘cell-like’ environment, to help elucidate the complicated kinetic system governing hyperpolarized 13C kinetics.

4472.   91 Development of a Robust MR-compatible 5mm bioreactor for Primary Human Tissue Cultures and Hyperpolarized MR
Kayvan R. Keshari1, Mark Van Criekinge1, Bertram Koelsch1, Renuka Sriram1, David M. Wilson1, Daniel B. Vigneron1, and John Kurhanewicz1
1Radiology and Biomedical Imaging, University of California, San Francisco (UCSF), San Francisco, CA, United States

Development of MR-compatible bioreactor systems to study cell metabolism non-invasively has been limited by the sensitivity of low γ nuclei, such as 13C and 15N. Dynamic nuclear polarization has afforded the necessary SNR to study hyperpolarized [1-13C] pyruvate and other metabolites using the bioreactor platform in immortalized cells. However, new methods are needed to study primary cell cultures and tissues, which are more clinically relevant. Here we report the construction of a 5mm MR-compatible platform interfaced with HP MR, and its application to primary renal tissue slice cultures, with HP metabolic studies performed at dramatically reduced cell and perfusate volumes.

4473.   92 Lab-on-chip for NMR microscopy: description and application for neurospheres imaging and spectroscopy studies
Bernardo Celda Muñoz1, Vicent Esteve2, and MCarmen Martinez-Bisbal2
1Quimica Fisica, Universitat de Valencia, CIBER-BBN, Burjassot (Valencia), Seleccione una opción, Spain, 2Quimica Fisica, Universitat de Valencia, CIBER-BBN, Burjassot (Valencia), Please Select, Spain

Extensive and continuous monitoring is one of the main challenges in the study of cell cultures and organotipic tissues. We have developed a lab-on-chip device allowing monitoring different parameters, as temperature, pH and pO2 or pCO2 by using optical fibres (Patent: PCT_ES2011_070173_ISRWO). Additionally, optical, fluorescence and confocal microscopy can be used together with NMR microscopy and spectroscopy. The aim of this communication is to describe the lab-on-chip and demonstrate the possibility of obtaining high resolution images and spectra at very low volumes by using NMR microscopy in a single neurosphere.

4474.   93 Perineural invasion in Oral Squamous Cell Carcinoma tissues: HR MAS NMR study revisited
Jaibodh Kumar1, Shatakshi Srivastava2, Nuzhat Hussain3, Jitendra Kumar Kushwaha1, Devendra Singh1, Abhinav Arun Sonkar1, and Raja Roy2
1Surgery, CSM Medical University, Lucknow, Uttar Pradesh, India, 2Center of Biomedical Magnetic Resonance, SGPGI, Lucknow, Uttar Pradesh, India,3Pathology, RML Institute of Medical Sciences, Lucknow, Uttar Pradesh, India

In the present work, HR-MAS NMR spectroscopic studies have been performed on human oral SCC tumor tissues, its neighboring margins and bed tissues (n=188), obtained from 48 patients (n=37 training set; n=11 unknown test set), for the identification of metabolic fingerprints. The proton NMR spectra were then subjected to PCA, OSC-filtered PCA and PLS-DA multivariate analysis. The training data-set (n=128 tissue specimens; 37 patients) of PLS-DA model allowed >90% correct classification of malignant tissues from benign samples and 82.5 % specificity and 100% sensitivity in unknown tissue specimens.

4475.   94 Identification of Bacterial Type in Urinary Tract Infection Using 1H NMR Spectroscopy
Ashish Gupta1, Mayank Dwivedi2, Abbas A Mahdi3, Chunni Lal Khetrapal1, and Mahendra Bhandari4
1Centre of Biomedical Magnetic Resonance, Lucknow, UP, India, 2Departments of Microbiology, Lady Hardinge Medical College, New Delhi, New Delhi, India, 3Department of Biochemistry, Chhatrapati Shahuji Maharaj Medical University, Lucknow, UP, India, 4Henry Ford Hospital System, Vattikuti Urology Institute, Detroit, MI, United States

Quantitative analysis of 682 urine samples from suspected UTI patients, and 50 healthy volunteers was carried out to identify the differential biomarkers between gram negative bacilli (GNB) (E. coli, P. aeruginosa, K. pneumonia, Enterobacter, Acinetobacter, Pr. mirabilis, Citrobacter frundii) and gram positive cocci (GPC) (Enterococcus faecalis, Streptococcus group B, Staphylococcus saprophyticus) uropathogenic urinary tract infection (UTI) using 1H NMR spectroscopy. Linear multivariate discriminant function analysis (DFA) reveals that 1H NMR measured metabolites can differentiate not only between healthy controls and infected urine samples but also GNB and GPC type of uropathogenic microorganism.

4476.   95 Phospholipid fingerprints of milk from humans and different animal species determined by 31P NMR: importance for human health
Cyrielle Garcia1, Norbert W. Lutz2, Sylviane Confort-Gouny2, Patrick J. Cozzone2, Martine Armand1, and Monique Bernard2
1UMR INSERM UF476/INRA1260, Université Aix-Marseille, Faculté de Médecine, Marseille, France, 2CRMBM UMR CNRS 6612, Université Aix-Marseille, Faculté de Médecine, Marseille, France

Phospholipids (PLs) play key roles in signaling pathways, inflammatory processes and lipid digestion. Milk contains PLs as important compounds that likely have positive health effects. We present an optimized 31P NMR spectroscopy protocol for comparing PLs in human milk vs. milk from cow, mare and camel, based on milk extracts. 12 PL classes were quantified, 6 of which were rather concentrated. Camel milk was particularly rich in PLs in general and in sphingomyelin and plasmalogens in particular. Thus, in arid countries camel milk appears as a promising dietary source due to the cardioprotective, hepatoprotective and brain protective effects of PLs.

4477.   96 A Proton NMR study of Serum and Urine in pre and post nutritional intervention in Buerger’s Disease
Abhinav Arun Sonkar1, shatakshi srivastava2, omprakash prajapati1, jitendra kumar kushwaha1, awanish kumar1, and raja roy2
1Surgery, CSM Medical University, Lucknow, Uttar pradesh, India, 2center of biomedical magnetic resonance, SGPGI, Lucknow, Uttar pradesh, India

Proton NMR spectroscopic studies of serum of patients of Beurger’s disease with simultaneous urine analysis have been performed. The detailed metabolic profile in serum demonstrated significant alterations in fatty acid metabolism and homocysteine metabolism of 16 patients suffering from Beurger’s Disease. The post-nutritional intervention follow up of patients (n=5) was also investigated. Whereas, fatty acid and homocysteine metabolism showed significant alterations in serum samples of diseased patients, urinalysis did not indicate disease related variations. The post-nutritional follow up of patients showed substantial clinical improvement which correlated well with Nitric Oxide levels and NMR metabolic profile of the serum.