Spectroscopic Quantification Methodology

Hall B                        Tuesday 13:30-15:30                                                                                                 

                  898.       The Case of the Missing Glutamine

Ileana Hancu1, Mark Frye2, John Port2

1GE Global Research Center, Niskayuna, NY, United States; 2Mayo Clinic, Rochester, MN, United States

A theoretical study is performed to understand the accuracy and repeatability of multiple pulse sequences in quantifying glutamine concentration at 3T.  Variable repeatability (12% to >50%) and significant bias (-30% to +70%) is noted for the seven pulse sequences considered. Data acquired in vivo using three of the pulse sequences used for simulations matches the predicted repeatability well. Following correction for the expected bias of each pulse sequence, consistent glutamine measurements, all in the 1mM range, are reported with the 3 sequences. An explanation for the mismatch between the in vivo 1H MRS and ex vivo results is attempted.

                  899.       Human Breast Lipid Composition Determination by in Vivo Proton MRS at 7T

Ivan Dimitrov1, Deborah Douglas2, Jimin Ren2, Andrew G. Webb3, A Dean Sherry2, Craig R. Malloy2

1Philips Medical Systems, Cleveland, OH, United States; 2Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, United States; 3Radiology, Leiden University Medical Center, Leiden, Netherlands

The role of diet and fat consumption in the pathogenesis of breast cancer is an important subject. We report on the non-invasive determination of lipid composition in human breast by 1H-MRS at 7T. Two respiratory-triggered TE-averaged STEAMs were performed in healthy volunteers where the second acquisition had all gradients inverted. T1 and T2 were also measured. Ten lipid peaks were typically resolved.  The average lipid composition was 30.5% saturated, 48.4% mono-unsaturated, and 21.1% di-unsaturated. In conclusion, we have shown that a chemical analysis of lipids in breast tissue can be determined quite simply and non-invasively by proton MRS at 7T.

                  900.       Is Human Glial TCA Cycle Rate Faster Than We Thought?

Napapon Sailasuta1, Brian D. Ross1,2

1Clinical MR Spectroscopy, Huntington Medical Research Institutes, Pasadena, CA, United States; 2Rudi Schulte Research Institute, Santa Barbara , CA, United States

13C MRS uniquely quantifies glutamine-glutamate cycle rate in either neurons or glia, driven by the substrate selection of their cellular membrane transporters.  Glial metabolic rate is of increasing interest as the range of human neurological disorders which appears selective to glia (Alzheimer’s, MS; TBI; epilepsy) increases and as selective medications are designed to correct such abnormalities.  13C enrichment followed by localized 13C MRS detection of many specific products has provided valuable background.  In a recent study we encountered a mismatch between prior metabolic models and a simplified method described here – with a 5 – 10 fold difference in the measured rate.

                  901.       Quantification Precision of Human Brain 1H MRS at Different Field Strengths: A Simulation Study

Dinesh K. Deelchand1, Isabelle Iltis1, Pierre-Francois Van de Moortele1, Pierre-Gilles Henry1

1Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, United States

1H MRS allows measurement of the concentration of a number of brain metabolites in vivo. It is generally accepted that the precision of quantification improves with B0. In principle, two factors may contribute to this increase in quantification precision: higher signal-to-noise ratio (SNR) and higher spectral resolution. In this work, we assess the respective contribution of these two factors using simulations. We report that, especially above 3-4 Tesla, increased SNR is the major contributor to the increase in quantification precision, as the gain in chemical-shift dispersion is offset by the increase in linewidth in vivo.

                  902.       Regularized Spectral Lineshape Deconvolution

Yan Zhang1, Shizhe Li1, Jun Shen1

1National Institute of Mental Health, Bethesda, MD, United States

The process of lineshape deconvolution is an inverse problem. A new referencing deconvolution method is proposed, which uses Tiknohov regularization to restrain the noise amplification. To determine the optimal regularization, the noise to signal ratio in frequency domain was defined as a function of the regularization parameter. It was found that this function yielded a well-defined L-curve with the transition point that marks the optimal regularization parameter. The method was validated on 1H spectral data which were acquired on human brain with single voxel at 3T.  The spectral quality was markedly improved after the data were processed with the proposed method.

                  903.       Electronic Reference for Absolute Quantification of Brain Metabolites by 1H-MRS on Clinical Whole Body Imager.

Hubert Desal1, Nashiely Pineda Alonso2, Serge Akoka2

1Neuroradiology, CHU de Nantes, Nantes, PdL, France; 2Chemistry, Université de Nantes, CEISAM, UMR 6230, Nantes, PdL, France

The ERETIC method is a promising avenue of research for absolute concentration quantification by MRS. However, in its initial form, this technique cannot be implemented on most clinical MR scanners. We propose a new strategy, which consists in transmitting the ERETIC signal before the localized spectroscopy acquisition. This approach was evaluated on phantoms and on volunteers. The results were compared to those obtained using the water signal as reference. A very good correlation between the values obtained using the two methods was observed. Moreover, the ERETIC method overcomes many of the drawbacks of the other absolute quantification methods.

                  904.       Sampling Strategy Effects on in Vivo 2D J-Resolved Spectroscopy Quantification

Tangi Roussel1, Sophie Cavassila1, Hélène Ratiney1

1CREATIS, CNRS UMR 5220, Inserm U630, INSA-Lyon, Université de Lyon 1, Université de Lyon, Villeurbanne, France

Till now, in vivo two-dimensional spectroscopy related studies did not investigate sampling strategies of the indirect dimension as a way of improving the quantification of metabolite concentrations. This paper presents a study carried out on simulated J-PRESS data containing macromolecular contamination. 2D J-Resolved spectroscopy quantification accuracy was evaluated for several sampling strategies and compared to 1D MRS quantification accuracy. In vivo 2D quantification following these strategies is shown. By handling macromolecular contribution by truncation strategy, a 2D MRS experiment leads to a more accurate quantification compared to 1D MRS time equivalent experiment, as demonstrated by a reduction of bias and standard deviation.


                  905.       In Vitro and in Vivo Validation of Absolute Quantitation of Brain Proton MR Spectra (1H-MRS) with Respect to Heterogeneous Tissue Compositions

Alexander Gussew1, Marko Erdtel1,2, Reinhard Rzanny1, Juergen R. Reichenbach1

1Medical Physics Group, Department of Diagnostic and Interventional Radiology, Jena University Hospital, Jena, Germany; 2University of Applied Sciences Jena, Jena, Germany

This work describes in vitro and in vivo validation of absolute quantitation of 1H-MRS brain data with respect to heterogeneous tissue distributions within the MRS-volume. NAA concentrations were estimated from metabolite and water spectra obtained from MRS-voxels containing different  metabolite and water concentrations and were compared with nominally adjusted values. The maximal error was 4% compared to 41%, if the tissue heterogeneity was neglected. Inter-individual distributions of NAA-, Cr- and tCho-concentrations obtained in insular cortex of volunteers had twice less scatter when taking into account the heterogeneous tissue composition in the voxel.

                  906.       Spectral Fitting of High Resolution Rat Brain Extract NMR Data by LCModel with a Simulated Basis Set

Andrew Borgert1,2, Kelvin O. Lim1,2, Pierre-Gilles Henry1,3

1Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, United States; 2Department of Psychiatry, University of Minnesota, Minneapolis, MN, United States; 3Department of Radiology, University of Minnesota, Minneapolis, MN, United States

Spectral fitting methods such as commercial metabolomics software (eg, Chenomx) or capabilities built into NMR system software (eg, Varian or Bruker) require significant user input and are generally not amenable to automation, making them time-consuming, cumbersome, and prone to user error. To address these issues, we have adapted the LCModel software package for use with high resolution in vitro NMR data, allowing for automated and consistent analysis of such data.  This adaptation utilizes a simulated basis set, with basis spectra generated for the majority of individual protons within each metabolite, as opposed to the metabolite as a whole.

                  907.       Simulating Human Brain Glutamate FMRS at 7.0 T to Determine Minimum SNR Requirements

Reggie Taylor1,2, Jean Théberge1,2, Peter Williamson, 1,3

1Medical Biophysics, University of Western Ontario, London, ON, Canada; 2Lawson Health Research Institute, London, ON, Canada; 3Department of Psychiatry, University of Western Ontario, London, ON, Canada

Human brain glutamate fMRS has the potential to provide dynamic information regarding normal and abnormal glutamate metabolism. With ultra-high field magnets (≤7T) increased spectral dispersion and SNR should result in more precise fMRS but how much SNR is required is not known. Using simulations of an in vivo spectrum acquired with a STEAM sequence (TE/TM 6/32ms) at 7T minimum numbers of spectra required to detect a 3% concentration change in glutamate between rest and activation were determined for various SNRs. A minimum SNR of 212 was needed to detect the 3% change when comparing only one spectrum from each state.

                  908.       Ultrafast 2D High-Resolution COSY Spectra in Inhomogeneous Fields

Congbo Cai1, Fenglian Gao1, Shuhui Cai1, Zhong Chen1

1Departments of Physics and Communication Engineering, Fujian Key Laboratory of Plasma and Magnetic Resonance, Xiamen University, Xiamen, Fujian, China

High-resolution COSY spectra can provide more information than 1D spectra. Recently, our group proposed a method to achieve high-resolution COSY spectra under inhomogeneous fields based on the intermolecular multiple-quantum coherences (iMQCs). However, 3D acquisition is necessary for a 2D COSY spectrum, which makes the experiment rather time-consuming. In this study, we introduced Hadamard technique to speed up the acquisition greatly. A high-resolution iMQC COSY spectrum can then be obtained in less than 10 minutes under inhomogeneous fields. Such a technique would widen the application field of iMQC methods.

                  909.       Handling Arbitrary Unknown Line-Shape Without Introducing Extra Parameters.

Emil Popa1, Enrico Capobianco2, Jan Willem van der Veen3, Ronald de Beer4, Dirk van Ormondt5, Danielle Graveron-Demilly1

1Université Lyon 1, Villeurbanne, France; 2CRS4 Bioinformatics Laboratory, Pula (Cagliari), Italy; 3NIH, NIMH, Bethesda, United States; 4Delft University of Technology; 5Applied Physics, Delft University of Technology, Delft, Zuid Holland, Netherlands

This work concerns a new way of dealing with in vivo spectral lineshapes for the case that a reference line is not available. It is based on dual-criterion non-linear least-squares fitting. All data-points are used simultaneously, in conjunction with the general a priori knowledge that a lineshape can be confined to a certain frequency region. The experimental lineshape at hand can be arbitrary, including asymmetric shapes. Modelling with analytical mathematical functions like splines, wavelets, or decaying sinusoids is circumvented. As a result, setting of hyper-parameters by a user is avoided. This favours automation.

                  910.       Precision and Robustness of Deep Brain Temperature Estimation Using Localised Proton Magnetic Resonance Spectroscopy in Normothermic and Hypothermic Newborn Infants

Alan Bainbridge1, Giles Kendall2, Enrico DeVita3, Cornelia Hagmann2, Andrew Kapetanakis2, Ernest Cady1, Nicola Robertson2

1Medical Physics and Bioengineering, UCL Hospitals NHS Foundation Trust, London, United Kingdom; 2Academic Neonatology, EGA UCL Institute for Women’s Health, University College London, London, United Kingdom; 3UCL Hospitals NHS Foundation Trust, Medical Physics and Bioengineering, London, United Kingdom

Therapeutic cerebral hypothermia is an effective and safe treatment for perinatal asphyxial encephalopathy. Precise knowledge of regional brain temperature is needed in order to optimise therapeutic hypothermia. Proton MRS can be used to estimates regional brain temperature. Reliable absolute temperature measurement depends on good calibration data and robust clinical spectrum acquisition.  Serial acquisition of subspectra allows both removal of motion-corrupted data and frequency correction of the remaining subspectra to remove effects of static magnetic field decay.  The magnetic field decay correction significantly reduced fitted peak linewidths and increased the precision of the measurement.

                  911.       Metabolite Nulling to Measure the Macromolecule Baseline for Quantitative 1H Magnetic Resonance Spectroscopy at 7 Tesla

Jacob Penner1,2, Andrew Curtis1,2, Martyn Klassen1, Joseph Gati1, Matthew Smith3, Michael J. Borrie3,4, Robert Bartha1,2

1Centre for Functional and Metabolic Mapping, Robarts Research Institute, London, ON, Canada; 2Medical Biophysics, University of Western Ontario, London, ON, Canada; 3Division of Aging, Rehabilitation, and Geriatric Care, Lawson Health Research Institute, London, ON, Canada; 4Department of Medicine, University of Western Ontario, London, ON, Canada

The purpose of this study was to determine the optimal inversion time to null metabolite signals allowing accurate measurement of the macromolecule baseline for quantitative 1H MR spectroscopy at 7T.  Spectra were acquired within a phantom using single-voxel localization by adiabatic selective refocusing (LASER).  The TI values that would result in complete suppression of NAA and Cr were found to be 0.47 seconds and 1.27 seconds, respectively.  Furthermore, T1 values were found to be 1.28 seconds for NAA and 2.45 seconds for Cr.  Future work will extend this method to determine the optimal TI values for in-vivo metabolite suppression.

                  912.       Decoupled Proton NMR Spectroscopy in Modest to Severe Inhomogeneous Fields Via Distant Dipolar Interactions

Yuqing Huang1, Shuhui Cai1, Zhong Chen1,2, Jianhui Zhong2

1Department of Physics, Xiamen University, Xiamen, Fujian, China; 2Departments of Radiology and Biomedical Engineering, University of Rochester, Rochester, NY, United States

The decoupled proton NMR spectroscopy can effectively simplify the spectra and improve the spectral resolution and sensitivity. In this abstract, two new pulse sequences based on homonuclear and heteronulcear intermolecular single-quantum coherences (iSQCs) were presented for high-resolution decoupled spectra in inhomogeneous fields. The experimental results indicate that the sequences are useful for obtaining high-resolution decoupled spectra in modest to severe inhomogeneous fields.

                  913.       Comparison of Quantification Strategies for Clinical 1H-MRS Using a Large Spectroscopy Database

Roberto Tarducci1, Andy Simmons2, Monica Pace3, Patrizia Mecocci3, Eric Westman4, Gianni Gobbi1

1S.C. di Fisica Sanitaria, Azienda Ospedaliera di Perugia, Perugia, Italy; 2Centre for Neuroimaging Sciences, King's College - London Institute of Psychiatry, London, United Kingdom; 3Department of Clinical and Experimental Medicine, University of Perugia - Institute of Gerontology and Geriatrics, Perugia, Italy; 4Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden


                  914.       Localized 31P Saturation Transfer in Rat Brain

Vladimir Mlynarik1, Cristina Cudalbu1, Yves Pilloud1, Rolf Gruetter1,2

1Laboratory of Functional and Metabolic Imaging, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; 2Departments of Radiology, Universities of Lausanne and Geneva, Switzerland

Phosphorus saturation transfer technique is sensitive to experimental imperfections such as partial direct saturation of the measured peak, incomplete saturation of the other peak under exchange and a problematic localization, which is usually done by an active volume of a surface coil used as a transceiver. In our study we compared the PCr <–> γ-ATP saturation transfer experiment using 1D ISIS localization combined or not combined with outer volume saturation. We observed a contaminating component from muscles in the PCr signal when using the 1D ISIS only. This contamination led to an underestimation of the calculated rate constant of the creatine kinase reaction.

                  915.       Non-Invasive Measurement of Fibrin Concentration by Fast Field-Cycling NMR Technique

Lionel Marc Broche1, Saadiya Rashid Ismail1, Nuala A. Booth2, David J. Lurie1

1Aberdeen Biomedical Imaging Centre, University of Aberdeen, Aberdeen, Scotland, United Kingdom; 2Institute of Medical Sciences, University of Aberdeen, Aberdeen, Scotland, United Kingdom

In this work we examine the feasibility of measuring the content of fibrin clots, which is the protein network that stabilises a thrombus, using fast field-cycling NMR. Fibrin, like proteins in general, is rich in 14N and its mobility is reduced due to the web-like structure of a clot. These two conditions are the cause of the apparition of a specific signal in the 1H dispersion plot, called the quadrupole signal, which can be used to measure the fibrin content.

                  916.       New View of Human Brain PH: MR Monitoring of Bicarbonate

Napapon Sailasuta1, Brian D. Ross1,2

1Clinical MR Spectroscopy, Huntington Medical Research Institutes, Pasadena, CA, United States; 2Rudi Schulte Research Institute, Santa Barbara , CA, United States

Human brain pH is a significant clinical measure usually accomplished directly through implantable pH electrodes, or indirectly from HCO and C02 together with Henderson-Hesselbach tables.  In recent 13C MRS studies we were able to directly quantify ‘bicarbonate’ in resting human brain and to monitor the changes produced by short or long term fasting.  pH estimated from 13C – HC03 differed significantly from accepted normal values and those obtained by direct 31P MRS.  Possible confounds, including binding, compartmentation and T1/T2 variances are considered before concluding that human brain [bicarbonate] is lower than previously thought.

                  917.       Glutamate and Glutamine Changes Induced by  Ethanol Treatment in the Rat Brain Detectable with CT-PRESS at 3T

Natalie May Zahr1,2, Meng Gu3, Dirk Mayer, 2,3, Daniel Mark Spielman3, Edith V. Sullivan1, Adolf Pfefferbaum, 12

1Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, United States; 2Neuroscience, SRI International, Menlo Park, CA, United States; 3Radiology, Stanford University, Stanford, CA, United States

Glutamate (Glu) and glutamine (Gln) were quantified individually to determine the effects of ethanol (EtOH) on rat brain metabolites. CT-PRESS was acquired at baseline (MRS1) and after 16 (MRS2) and 24 weeks (MRS3) of EtOH exposure. Previous analysis revealed an increase in the combined resonances of Glu+Gln (i.e., Glx) with escalating EtOH doses. The current investigation unveils that underlying the increase in Glx at MRS2 was an increase in Gln, and underlying the increase in Glx at MRS3 was an increase in Glu. These results caution against interpretations regarding changes to Glx as a surrogate marker for Glu or Gln.

                  918.       Quantization of ME-COSI Data with Prior Knowledge Fitting

Gaurav Verma1, Neil Wilson2, Scott Logan Lipnick2, Nagarajan Rajakumar3, Michael Albert Thomas3

1Biomedical Engineering, UCLA, Los Angeles, CA, United States; 2Biomedical Physics, UCLA, Los Angeles, CA, United States; 3Radiological Sciences, UCLA, Los Angeles, CA, United States

To quantify the 4D data generated by ME-COSI, eighteen scans of a physiological gray matter phantom were acquired. A central voxel from each acquisition was extracted and its spectrum was fitted using ProFit, a prior knowledge fitting algorithm for 2D MRS. Cramer-Rao Lower Bounds for the fit measured with ProFit were 0.3 to 16.5 for most metabolites. Across all acquisitions the coefficient of variation ranged from 2 to 21% for most metabolites. Glutamate/glutamine were overestimated possibly due to inclusion of an erroneous peak during quantization, and lactate peak showed poor fitting and reproducibility, likely due to its low concentration.

Methodology for MRS of Cells, Body Fluids, etc.

Hall B                        Wednesday 13:30-15:30                                                                                                        

                  919.       Vision and Oxygen Inhalation Affect Mitochontrial Activity: A 31P Magnetic Resonance Spectroscopy Study

Ren-hua Wu1,2, Hui Wang3, Poublanc Poublanc2, Karel terBrugge2, David Mikulis2

1Medical Imaging, Shantou University, Shantou, Guangdong, China; 2Medical Imaging, University of Toronto, Toronto, ON, Canada; 3Learning Science Center, Southeast University, Nanjing, China

Our aim was to know the relationship between oxygen inhalation and mitochondrial activity, and relationship between vision and mitochondrial activity as well. Eleven healthy volunteers underwent 31P MRS examination. ¦ÃATP, ¦ÁATP, ¦ÂATP, and ¡°potential of hydrogen¡± (pH) were measured. We can observe increased ¦ÃATP, ¦ÁATP, and ¦ÂATP peaks on the 3rd scan breathing hyperoxic air with eyes opening. Brain mitochondrial activities were increased and more ATPs were produced after oxygen inhalation in healthy volunteers. More energy is needed in visual status.

                  920.       Bacteria-Specific Biomarkers in Mouse-Models of Infections Investigated by NMR Spectroscopy

Verena Hoerr1, Lori Zbytnuik2, Paul Kubes2, Hans Vogel1

1Department of Biological Sciences, University of Calgary, Calgary, Alberta, Canada; 2Department of Physiology and Biophysics, University of Calgary, Calgary, Alberta, Canada

In mouse-models of Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa infections, serum was investigated by 1H NMR spectroscopy and distinguished by statistical pattern recognition techniques. By combining the results of the in vivo study with footprints of culture experiments, potential bacteria-specific biomarkers were identified. We also compared serum metabolite changes caused by lipopolysaccharides (LPS) treatment and E. coli infection in both wild-type and Toll-like receptor 4 (TLR4) deficient mice. In TLR4 deficient mice the immune response upon LPS treatment was suppressed. Taken together, our approach allows us to distinguish between innate immune and direct bacterial effects during an infection.

                  921.       In Vivo Metabolic Analysis of Pseudomonas Aeruginosa Live Bacteria Using High Resolution Magic Angle Spinning NMR Spectroscopy

Valeria Righi1,2, Caterina Constantinou3, Meenu Kesarwani3, Laurence G. Rahme3, A Aria Tzika1,2

1NMR Surgical Laboratory, Department of Surgery, Massachusetts General Hospital and Shriners Burns Institute, Harvard Medical School, Boston, MA, United States; 2Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Athinoula A. Martinos Center for Biomedical Imaging, Boston, MA, United States; 3Molecular Surgery Laboratory, Department of Surgery, Massachusetts General Hospital and Shriners Burns Institute, Harvard Medical School, Boston, MA, United States

We tested the feasibility of H1 High Resolution Magic Angle Spinning (HRMAS) NMR in determining metabolic profiles of live bacteria. We used Pseudomonas aeruginosa, a human opportunistic pathogen responsible for chronic and acute infections, and a major cause of morbidity and mortality in cystic fibrosis patients. We found that HRMAS is powerful technique for monitoring the metabolic fingerprint of in vivo models, including live bacterial cells. This technique may prove to be a helpful tool in gene function validation, the study of pathogenesis mechanisms and the testing of anti-bacterial agents.

                  922.       Metabolic Aspects of N-3 PUFAs Supplementation to Rat Cardiomyocytes: A HR-MAS NMR and GC/MS Study

Valeria Righi1,2, Mattia Di Nunzio1,3, Francesca Danesi1,4, Elisa Boschetti1,4, Luisa Schenetti2, Adele Mucci2, Alessandra Bordoni1,4, Vitaliano Tugnoli1

1Dipartimento di Biochimica "G. Moruzzi", Universita' di Bologna, Bologna, Italy; 2Dipartimento di Chimica, Universita' di Modena, Modena, Italy; 3Nutrition Research Center , Bologna, Italy; 4Nutrition Research Center, Bologna, Italy

Cardiovascular diseases (CVD) are responsible for significant morbidity and mortality throughout the world. We present a first investigation using HR-MAS NMR Spectroscopy in combination with GC/MS of neonatal rat cardiomyocytes supplemented with two different PUFAs, EPA and DHA, in order to understand the metabolic change occurring in these cells following the increase of their n-3 PUFA content. EPA and DHA are of special importance for human health, and fish oil feeding has been associated to reduced mortality in several studies.

                  923.       A Metabonomic Analysis of Serum from Wilson’s Disease Rats Using 1H NMR Spectroscopy and Pattern Recognition

Yangyang Wei1, Huaizhou Jiang2, Jingjing Xu1, Jiyang Dong1, Shuhui Cai1, Zhong Chen1

1Department of Physics, Fujian Key Laboratory of Plasma and Magnetic Resonance, Xiamen University, Xiamen, Fujian, China; 2Hubei University of Traditional Chinese Medicine, Wuhan, Hubei, China

The biochemical variations of serum from control and Wilson¡¯s disease (WD) rats were investigated using NMR-based metabolomics. Two groups can be discriminated according to the score plot of principle component analysis. The WD group shows increased levels of lactate, glycoprotein, glutamine, creatine, creatinine£¬arginine and decreased levels of glucose, trimethylamine-N-oxide, betaine, lipid and choline. The results may further our understanding of the disease.

                  924.       Classifying 31P NMR Phospholipid Profiles from Postmortem Schizophrenic Brain: Multivariate Model Selection and Cross-Validation

J A. Welge1,2, Richard A. Komoroski2

1Environmental Health, University of Cincinnati, Cincinnati, OH, United States; 2Center for Imaging Research, University of Cincinnati, Cincinnati, OH, United States

Using prior 31P NMR data for the composition of phospholipid (PL) and PL metabolites in postmortem schizophrenic and matched control brains, we searched for multivariate regression models to classify these samples. Because the number of measurements exceeded the number of samples, variable selection was required. We employed Akaike’s Information Criterion in conjunction with repeated cross-validation using random splits of the data into model-building and validation subsets. This procedure addressed the risk of over-fitting the sample data and generated predictions from data not used to select the model. Certain metabolites that were not individually significant produced accurate classification when modeled jointly.

                  925.       Probing Radiation Biomarkers in Human Urine by 1H NMR

Congju Chen1, David J. Brenner2, Truman R. Brown1

1Department of Radiology, Columbia University, New York, NY, United States; 2Center for Radiological Research, Columbia University, New York, NY, United States

In previous work we have identified a dozen biomarkers in urine from radiation-exposed mice by NMR spectroscopy. The mouse model allowed us to understand the effect of key parameters such as dose, time post-exposure on the urinary biomarkers. To validate these biomarkers in humans, in this work we investigate urinary biomarkers associated with radiation exposure in acute leukemia patients undergoing a series of total body irradiation treatments in preparation for a hematopoietic stem cell transplant. The results indicated that besides some common urinary radiation biomarkers from both mice and human, there are some unique radiation signatures in human urine.

                  926.       Acute Effect of Gamma Irradiation in Mice by NMR Based Metabolic Profiling of Urine

Ahmad Raza Khan1, Poonam Rana1, M Memita Devi1, Shubhra Chaturvedi2, Subash Khushu1

1NMR Research Centre, INMAS, Delhi, India; 2Division and Cyclotron & Radiopharmaceutical Sciences, INMAS, Delhi, India

A high resolution 1H NMR spectroscopy based metabonomic approach has been used to study acute effect of gamma irradiation at biochemical levels. Urine samples were collected from mice at 6, 24 and 96 hrs post irradiation with dose of 3, 5 and 8 Gy. Significant changes were observed in high dose of gamma irradiation even after 6 hrs, while maximum changes observed in low and moderate dose after 24 hrs of exposure. These alterations in metabolites could be helpful for identification of potential biomarkers associated with radiation induced changes and may find applications in biological dosimeters.

                  927.       Statistical Total Correlation Spectroscopy (STOCSY) for Identifying Contaminants and Their Effect on 1H- HRMAS of Cervical Tissue Samples

Robert Leslie Davidson1, Sonali S. deSilva1, Simon J. Doran1, Geoffrey S. Payne1

1Clinical Magnetic Resonance, Institute of Cancer Research, Sutton, Surrey, United Kingdom

Statistical Total Correlation Spectroscopy (STOCSY) applied to contaminated 1H HR-MAS spectra of cervical tissue samples. 2D and 1D STOCSY plots show the highly correlated,  structurally linked, contaminant peaks and allow identification of the compound as lignocaine (anaesthetic). The lack of other correlations with these peaks suggests that there is no significant, observable metabolic effect of lignocaine on these spectra. This means that a simple peak removal algorithm, such as that used to remove residual water, would be enough to allow this data to be analysed by pattern recognition techniques.

                  928.       The 1.28 Ppm Biomarker: Not Specific for Neural Progenitor Cells, But Also in the Mesenchymal Stem Cells and Differentiated Adipocytes Measured by NMR Spectroscopy

Zhi-Feng Xu1, Chong-Yang Shen2, Lin-Ping Wu2, Ye-Yu Xiao, Yao-Wen Chen, Ren-Hua Wu

1medical imging, the 2nd Affiliated Hospital, the Medical College of Shantou University, shantou, guangdong, China; 2Multidisciplinary Research Center of Shantou University, shantou, guangdong, China

Our study, we research the properties of the NMR spectroscopy of the human  mesenchymal stem cells (MSCs) and non-stem cells (EC109), in order to demonstrate that whether the 1.28ppm is unique for the neural progenitor cells (NPCs). Meanwhile, we want to approach this biomarker changes with adipogenic differentiation£¬and to study the relationship of the 1.28 ppm biomarker with mobile lipid droplets. In brief, we found that the 1.28ppm also resides in MSCs, and this biomarker increased remarkablely after 2 weeks adipogenic differentiation. In addition, this biomarker is not just due to the lipid droplets in the cytoplasm. as the previous studies advanced.

Other Spectroscopy Methodology

Hall B                        Thursday 13:30-15:30                                                                                                           

                  929.       SPECIAL-COSY at 7T

Alexander Fuchs1, Anke Henning1, Peter Boesiger1

1Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland

The ability of 2D spectroscopy to spread spectral information that is otherwise hard to detect into a second frequency dimension makes these type of techniques very interesting. On ultra-high field strength the short relaxation time of interesting metabolite signals makes commonly used localized sequneces like L-COSY or PRESS localized COSY impractical. Hence  a suitable localized COSY sequence at 7T was implemented using the SPECIAL sequence. The successful application of SPECIAL for localized COSY at 7T is demonstrated in a phantom and in-vivo measurements.

                  930.       SPECIAL-J-Resolved Spectroscopy at 7T

Alexander Fuchs1, Anke Henning1, Peter Boesiger1

1Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland

Unambiguous detection of coupled spin systems like Glutamate, Glutamine or GABA can be a quite challeging task with regular one dimensional spectroscopy.

2D J-resolved spectroscopy can be used to decrease the spectral overlap by encoding the phase evolution behaviour of coupled spin systems in second frequency dimension. At ultra-high fields typical localization schemes can often limit the minimum achievable echo times and therefor hampering the actual 2D experiment. To circumvent this problem SPECIAL was implemented on a Philips 7T system and j-resolved spectra were acquired in a phantom and a healthy volunteer.

                  931.       Implementation and Validation of Localized Constant-Time PRESS on a  7T MRI/MRS Scanner

Bhaskaran David Prakash1, Loyola D'Silva1, Kishore Bhakoo1, David Townsend1, S. Sendhil Velan1

1Laboratory of Molecular Imaging, Singapore Bioimaging Consortium, Singapore, Singapore

We have implemented and validated the LCT-PRESS technique in healthy rat brain. This sequence clearly demonstrates superior resolution and permits reliable detection of several brain metabolites that overlap in conventional techniques.  The LCT-PRESS sequence performs this separation due to its incorporation of constant-time evolution, resulting in spin-spin decoupling along the F1 dimension.

                  932.       The Benefits of Higher Order B0 Shimming of the Human Brain at 7T

Hoby Patrick Hetherington1, Kai-Ming Lo2, William Punchard2, Piotr Starewicz2, Jullie W. Pan1

1Neurosurgery, Yale University, New Haven, CT, United States; 2Resonance Research Inc., Billerica, MA, United States

With the advent of ultrahigh field systems, 7T, significant improvements in spectroscopic imaging studies of the human brain have been anticipated. However, these gains are dependent upon the achievable B0 homogeneity, both globally (over the entire ROI or slice) and locally (the linewidths of individual SI voxels within the ROI). Our 7T human brain data demonstrates that substantial improvements in both global and local homogeneity can be achieved using 1st-3rd and higher order shims. The required strengths to achieve higher order terms (4th and 5th orders) can be obtained using a shim insert and modest strength power supplies.

                  933.       Early Metabolic Changes of Mild Traumatic Brain Injury Revealed by 3D MRSI at 3T

Duan Xu1,2, Natalie Charlton1, Srivathsa Veeraraghavan1, Geoffrey T. Manley3, Pratik Mukherjee1,2

1Dept of Radiology, UCSF, San Francisco, CA, United States; 2UCSF/UC Berkeley Joint Graduate Group in Bioengineering, San Francisco and Berkeley, CA, United States; 3Dept of Neurosurgery, UCSF, San Francisco, CA, United States

Conventional MR imaging does not accurately predict outcome in mild TBI, but MR diffusion and proton spectroscopy has shown promise as potential biomarkers for injury severity and long-term neurocognitive and functional outcome.  In this study, we utilized 3D MRSI at 3T with wide anatomic coverage to assess TBI in specific association, commissural, and projection white matter tracts.

                  934.       Constant-TE Difference Editing of Serine at 3T: Simulation and Phantom Study

Changho Choi1, Aditya Patel1

1Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, United States

Serine (Ser) in human brain, which has coupled proton resonances at 3.98, 3.94, and 3.83 ppm, is difficult to measure because of its relatively low concentration (~0.5 mM) and the spectral overlap with the creatine (Cr) 3.92 ppm resonance.  Constant-TE difference editing strategies for detection of Ser at 3T have been explored.  Echo time dependence of the Ser multiplet was investigated, with density-matrix simulation, for point-resolved spectroscopy and triple refocusing. The Ser multiplets in sub- and difference-spectra were in good agreement between simulation and phantom experiments. In vivo feasibility of the difference editing methods is discussed with results from a phantom with physiological concentrations of Ser and Cr.

                  935.       Short VAPOR-Like Water Suppression with Improved Water Suppression Performance Suitable for High Field MRS and MRSI Exploiting the Residual Water Signal as a Reference

Zenon Starcuk jr. 1, Zenon Starcuk1, Jana Starcukova1

1Magnetic Resonance & Bioinformatics, Institute of Scientific Instruments, Acad. Sci. Czech Rep., Brno, Czech Republic

A short VAPOR-like water suppression sequence is presented, exhibiting similarly low B1 and T1 sensitivity and improved excitation profiles. The improvements are based on optimization of flip angles and pulse durations of chemical-shift selective pulses interleaved with fixed short delays. The sequence consists of 6-pulse water presaturation with asymmetric RF pulses, followed by B1-insensitive inversion and the localization module. The improved robustness may be utilized for an accurate control of residual water signal and exploiting it as a reference. Thanks to the reduced length and reduced impact on metabolites, the sequence should improve quantifiability and be suitable for spectroscopic imaging.

                  936.       Anomalous Lipid Signal Investigation When Measuring Water/Lipid Signal with Unsuppressed 1H MR Spectroscopy

Victor Rakesh Lazar1, David J. Manton2, Timo Schirmer3, Ralph Noeske3, Gary P. Liney4, Martin Lowry5, Mark Lorch6, Lindsay W. Turnbull5

1Centre for MR Investigations, University of Hull, Hull, North Humberside, United Kingdom; 2CMRI, University of Hull, Hull, United Kingdom; 3GE Healthcare; 4Radiotherapy Physics, Queen's Centre for Oncology, Hull, North Humberside, United Kingdom; 5CMRI, University of Hull, Hull, North Humberside, United Kingdom; 6Department of Chemistry, University of Hull, Hull, North Humberside, United Kingdom

Water:lipid signal ratio (WLSR) can be measured with unsuppressed 1H MR spectroscopy and such data can be used to characterise breast cancer and bone disease.  It is important, however, to be aware of potential bias (systematic errors) in these measurements as caused by chemical shift-induced voxel offsets which will be relatively large for the 3.4 p.p.m. water-lipid separation. Preliminary investigation and results related to this condition has been explained.

                  937.       Using 3T Magnetic Resonance Spectroscopy to Assess the Long Term Effects of Mild Traumatic Brain Injury

Lisa Maria Harris1, Phil Dean1, Annette Sterr1

1Psychology, University of Surrey, Guildford, Surrey, United Kingdom

Mild traumatic brain injury (mTBI) typically induces a set of symptoms, including poor memory, collectively referred to as Post Concussion Syndrome (PCS). A combination of a working memory task and magnetic resonance spectroscopy was used in a study to investigate the link between metabolite alterations, PCS symptoms and working memory ability in mTBI participants at least one year post injury.  Lactate showed a significant positive correlation with PCS symptoms, this is usually elevated in the acute phase. There was also a trend towards high lipids and macromolecules in those with more PCS symptoms.

                  938.       Determination of Brain Histidine Concentrations and Kinetic Modeling of Human Blood Brain Barrier Transport

Daniel Guo Quae Chong1, Jean-Marc Nuoffer2, Christine Sandra Bolliger1, Peter Vermathen1, Chris Boesch1, Roland Kreis1

1Department of Clinical Research, University Bern, Bern, Switzerland; 2Departement Hämatologie, Onkologie, Infektiologie, Labor-Medizin und Spitalpharmazie (DOLS), Inselspital, Bern, Switzerland

Normal human blood and brain histidine concentrations were measured over a 10 hour period after an oral load. On average, blood histidine concentrations reached a maximum of 3.5 mM while brain histidine peaked at 1.9 mM, 5 hours after blood. Applying the symmetric Michaelis-Menten kinetics resulted in kinetic parameters of maximum transport of 23 nmol/g/min, an apparent Michaelis constant of 2.1 mM and a cerebral metabolization rate of 0.3 nmol/g/min. The complexity of the system investigated and various factors render the data inconclusive upon the appropriate kinetic model and potential subject dependence of the kinetics.

                  939.       Single Voxel 1H Spectroscopy in the Human Hippocampus at 3 T Using LASER: A Reproducibility Study.

Najib Allaïli1,2, Malgorzata Marjanska3, Edward J. Auerbach3, Eric Bardinet1, Philippe Fossati4, Romain Valabrègue1, Stéphane Lehéricy1

1CRICM (CENIR), UPMC/INSERM UMRS 975/ CNRS UMR 7225, Hôpital Pitié-Salpêtrière, Paris, France; 2Centre Emotion CNRS USR 3246, Paris, France; 3Center for Magnetic Resonance Research and Department of Radiology, University of Minnesota, Minneapolis, MN, United States; 4Centre Emotion CNRS USR 3246, Hôpital Pitié-Salpêtrière, 47 bd de l'Hôpital 75013 Paris, France

Scan to scan reproducibility is challenging, especially in the deep brain regions such as hippocampus where lower SNR and poor magnetic field homogeneity can lead to larger uncertainties in metabolite quantification. Few studies have investigated 1H-MRS reproducibility in the hippocampus either at low magnetic field strength or with few subjects.  Relatively large VOI were used in most of these studies, resulting in partial volume effects.  In this study, we investigated the reproducibility of spectroscopic measurements in the hippocampus at 3 tesla using a LASER sequence . We performed our measurements in a 2.4 mL volume to minimize partial volume effects.

                  940.       Simultaneously Assessed GABA/Glutamate/Glutamine Concentration Gender Differences at 3.0T

Peter Sheffield1,2, Michael D. Noseworthy, 2,3

1School of Biomedical Engineering, McMaster University, Hamilton, ON, Canada; 2Brain-Body Institute, St. Joseph's Healthcare, Hamilton, ON, Canada; 3Electrical and Computer Engineering, School of Biomedical Engineering, McMaster University, Hamilton, ON, Canada

Herein we demonstrate the necessity for separating control subjects by gender when analyzing the metabolites of the GABA/glutamate/glutamine (Glx) spin system. Seven male and five female subjects were recruited to assess differences in these metabolites using a STEAM sequence optimized for Glx quantification. Results indicate that GABA concentrations in the anterior cingulate cortex of females are significantly lower than in males, in contrast to previous occipital GABA studies. Therefore, care must be taken when developing control groups for Glx metabolite analysis. Our results also illuminate a possible etiology for executive mood disorder obscured by previous reports.

                  941.       Can You Really Use the Creatine Equilibrium to Calculate Free ADP Concentrations?

Christine Nabuurs1, Cees Hilbers2, Arend Heerschap1

1Radiology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands; 2Laboratory of Physical Chemistry, Faculty of Science, Nijmegen, Netherlands

31P saturation transfer experiments in MAK=/= and WT muscle demonstrated a neglegible effect of CK and AK mediated enzymatic phosphoryl exchanges between â-ADP and â-ATP. These results are in conflict with the expected 65% reduction of â-ATP upon saturation of the (ãATP/)â-ADP resonance. Hence, the major ADP pool which is available to the CK reaction cannot be saturated. We propose a solid-state like ADP pool, which is in exchange with a transient ADP pool that associates with CK. The inability to saturate the âADP spin system challenges the validity of calculating the free ADP concentration from the CK equilibrium.

                  942.       In Vivo GABA Measurement of Sensorimotor Cortex

Pallab Bhattacharyya1, Micheal Phillips1, Lael Stone1, Mark Lowe1

1Cleveland Clinic, Cleveland, OH, United States

Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain. Abnormal GABA has been implicated in several neuropsychiatric disorders. Using a variant of MEGA point resolved spectroscopy (MEGA-PRESS)

sequence with interleaved water scans to detect subject motion, GABA level of sensorimotor cortex in healthy volunteers was measured, where the spectroscopy voxel was identified from a functional MRI scan. In addition, using linear regression analysis, GABA concentration in gray matter and white matter in the sensorimotor region were obtained.

                  943.       Performance Analysis of the Two Spectroscopic Imaging Sequences LRE and EPSI

Rudolf Fritz Fischer1, Kilian Weiss1, Christof Baltes1, Markus Rudin1, Peter Boesiger1, Sebastian Kozerke1

1Swiss Federal Institute of Technology and University Zurich, Zurich, Switzerland

We compare the sensitivity of the two spectroscopic imaging sequences Echo Planar Spectroscopic Imaging  (EPSI) and Linear Response Equilibrium (LRE), a steady state free precession sequence with intrinsic suppression of  periodic bands. Simulations and phantom experiments were performed revealing a good SNR performance of LRE especially at low spectral bandwidth.

                  944.       Accurate Brain Tumor Biopsy Using 3D 1H-MRS Neuronavigation

Berkay Kanberoglu1, Josef P. Debbins2, Lina J. Karam1

1Electrical Engineering, Arizona State University, Tempe, AZ, United States; 2Keller Center for Imaging Innovation, Barrow Neurological Institute, Phoenix, AZ, United States

To correlate the 3D H-MRS voxel spectra of tumors with genetic and ex-vivo NMR data, it is imperative that the biopsy of the tissue of interest be as accurate as possible. The goal of this work is to present a method to make biopsies more accurate by creating regions of intests (ROIs) from MRS data and overlaying them onto the structural datasets during the biopsy. The overlaid ROI masks illuminate the biopsy regions on the surgical navigation system and act as markers like the markers used in fMRI.

                  945.       Open Coil Arrangement for Interventional Magnetic Particle Imaging

Timo Frederik Sattel1, Tobias Knopp1, Sven Biederer1, Thorsten M. Buzug1

1Institute of Medical Engineering, University, Luebeck, Germany

Magnetic particle imaging is a method capable of determining the spatial distribution of super-paramagnetic iron oxide particles. To obtain information about the particle distribution, a field-free point is steered on a trajectory through the field-of-view. For magnetic field generation and particle signal reception, electromagnetic coils are used. In their original paper, Gleich and Weizenecker proposed a tube-like scanner setup. In this contribution, a new coil geometry is introduced. It provides lateral access to the specimen and thus allows for interventional MPI. To prove feasibility, 2D FFP trajectories are simulated, which give promising results.

                  946.       Reconstruction of Phase Rotation Spectroscopy Data on Partial Parallel Array MRI Systems

Sarah Andrea Wijtenburg1,2, Jack Knight-Scott1

1Radiology, Children's Healthcare of Atlanta, Atlanta, GA, United States; 2Biomedical Engineering, University of Virginia, Charlottesville, VA, United States

Current algorithms for combining coil signals from partial parallel array MRI systems negate the effects of the phase rotation technique in 1H-MRS. Here, we present an altered processing method to overcome these challenges.

                  947.       A New Detection Scheme for Ultrafast 2D COSY

Shuhui Cai1, Mingfang Zhao1, Zhong Chen1

1Department of Physics, Xiamen University, Xiamen, Fujian, China

Two-dimensional NMR techniques greatly extend the application fields of NMR spectroscopy. Unfortunately, the collection of numerous t1 increments leads 2D experiments fairly time-consuming. The spatial encoding ultrafast technique enables fast acquisition of 2D NMR spectra. In this abstract, a new ultrafast 2D COSY method based on continuous constant-time phase-modulated spatial encoding was proposed. Compared to the previous real-time phase-modulated method, the present method not only gives much better spectral signal-to-noise ratio and resolution, but also is much easier to implement.

                  948.       Characterizing Intermolecular Multiple-Quantum Coherence Signals Between Spin-1/2 and Spin-3/2 Nuclei

Wen Zhang1, Shuhui Cai1, Zhong Chen1

1Department of Physics, Xiamen University, Xiamen, Fujian, China

The intermolecular multiple-quantum coherence (iMQC) signals between 1H (spin-1/2) and 23Na (spin-3/2) nuclei were studied theoretically and experimentally using the CRAZED pulse sequence. The results show that no matter which spin is detected, the dependences of the iMQC signal intensities on the RF pulse flip angles follow the same rules and are identical to those for other heteronuclear systems, implying that heteronuclear iMQCs have same properties in liquid NMR.

                  949.       Removal of FM Sidebands Artifacts in NWS MRS by QZ-Bac Algorithm

Jyh-Miin Lin1, Hsiao-Wen Chung2, Shang-Yueh Tsai3

1Department of Radiology, Mackay Memorial Hospital, Taipei, Taiwan; 2Department of Electrical Engineering, National Taiwan University, Taipei, Taiwan; 3Department of Electrical Engineering, Chang Gung University, Tao Yuan, Taiwan

1H non-water suppressed(NWS) MRS is a developing technique to in vivo metabolites concentration, with high accuracy than conventional water suppressed(WS) MRS. In NWS MRS, complete removal of water signal is critical for quantifying metabolites concentration. We propose a novel postacqusitional (QZ-bac) algorithm to eliminate water peaks and water related sidebands. With this method, the water related frequency modulation signals were completely removed by exploiting the antisymmetry property. Computer simulations and in vivo demonstration were shown.

                  950.       High Precision Calibration of MRS Thermometry Using Validated Temperature Standards

Elena Vescovo1, Andrew Levick2, Sha Zhao1, Graham Machin2, Charmaine Childs3, Timothy Rainey3, Steve Williams1

1Imaging Science and Biomedical Engineering, The University of Manchester, Manchester, Greater Manchester, United Kingdom; 2Temperature Group, National Physical Laboratory, Teddington, Middlesex, United Kingdom; 3Brain Injury Research Group, The University of Manchester, Manchester, Greater Manchester, United Kingdom

Estimation of temperature by MRS from the chemical shift of water relative to N-acetylaspartate (NAA) relies on a calibration curve. To date these have never been related back to primary standards. We describe extremely stable temperature control of an MRS phantom at 1.5T using a circulating water bath and organic fixed-point materials, with measurements related back to the International Temperature Scale 1990 (ITS-90) at the UK National Physical Laboratory. Frequency differences (water-NAA) were highly reproducible (SD<10-4 ppm) at fixed temperature and R2 for the fit was 0.9996. Ionic strength affected the intercept but not slope of the temperature calibration.

                  951.       In Vivo Temperature Brain Map Using Jmrui V4.X: A Plugin Development

Elena Vescovo1, Federico Di Cesare2, Dan Stefan2, Danielle Graveron-Demilly2, Steve Williams3

1Image Science and Biomedical Engineering,, The University of Manchester, Manchester, Greater Manchester, United Kingdom; 2Laboratoire CREATIS-LRMN, CNRS UMR 5220, Universite' Claude Bernard Lyon 1, Lyon, France; 3Image Science and Biomedical Engineering, The University of Manchester, Manchester, Greater Manchester, United Kingdom

Magnetic resonance spectroscopy can provide a non-invasive approach to measure the internal temperature of the brain; it relies on the linear relationship between the 1H MR resonance frequency of  water in the tissue and the tissue’s temperature. The absolute temperature is obtained by measuring the chemical shift of water relative to a reference compound such as N-Acetylaspartate (NAA). To convert the frequency difference between these two signals into temperature, it is necessary to apply a calibration curve. All these procedures could be performed using a plugin of jMRUI, a Java-based Graphical User Interface that allows time-domains analysis of MRS, MRSI and HRMS-NMR signals. In this work we used jMRUI v4.x, a new version of the software that enabled the user to add their own plugin.

                  952.       Efficient Generation of a Magnetic Field-Free Line

Tobias Knopp1, Marlitt Erbe1, Timo F. Sattel1, Sven Biederer1, Thorsten M. Buzug1

1Institute of Medical Engineering, University of Lübeck, Lübeck, Germany

Spatial encoding in magnetic particle imaging (MPI) is achieved by moving a field-free point (FFP) through the imaging volume. Recently, it was shown that the sensitivity of MPI can be increased by taking advantage of a field-free line (FFL) for spatial encoding. However, until today the power loss of an FFL scanner was thousand times higher than the power loss of an FFP scanner. In this work, the first feasible coil setup is presented, which has a power loss of the same order as an FFP scanner.

                  953.       Relaxation Enhancement by Longitudinal Multispin Orders

Loyola D'Silva1, S. Sendhil Velan1

1Laboratory for Molecular Imaging, Singapore Bioimaging Consortium, Singapore, Singapore

There is a great interest in increasing the longitudinal relaxation of nuclear spins for hyperpolarized imaging experiments. Longitudinal multispin orders (LOMO) correspond to the non-equilibrium population distribution and can be created in spin systems that exhibit J couplings, dipolar couplings or quadrupolar couplings. It can also be created via cross-correlated relaxation between different relaxation pathways present for the given spin system. A two fold increase in longitudinal magnetization is achieved using the frequency cycling approach.

                  954.       Improved Estimation of the Magnetic Nanoparticle Diameter with a Magnetic Particle Spectrometer and Combined Fields

Sven Biederer1, Tobias Knopp1, Timo Frederik Sattel1, Marlitt Erbe1, Thorsten M. Buzug1

1Institute of Medical Engineering, University of Luebeck, Luebeck, Germany

In Magnetic Particle Imaging the iron-core size distribution is a very important criterion for the imaging quality as well as for a model based reconstruction. An estimation of such a distribution is possible by using magnetization spectra of a Magnetic Particle Spectrometer. In this contribution a method is presented to improve the condition of the minimization problem. For this purpose offset fields are added to the sinusoidal excitation of the Magnetic Particle Spectrometer. This leads to a more stable and robust estimation of the iron-core size distribution.

                  955.       Assignment of the NMR 2H Double Quantum Filtered Signals in Nerves and Spinal Cords to Their Anatomical Compartments

Hadassah Shinar1, Tal Ben -David1, Uzi Eliav1, Gil Navon1

1School of Chemistry, Tel Aviv University, Tel Aviv, Israel

2H double quantum filtered (DQF)  NMR of nerves and spinal cords enabled the assignment of the different signals to their anatomical compartments. In nerves the signals with the quadrupolar splittings of approximately 1500, 500, and 200 Hz were assigned to the water in the epineurium, myelin sheaths and endoneurium respectively. A narrow signal was also observed and assigned to intraaxonal water. In spinal cords only the 500 Hz satellites and the narrow signal were detected. The assignment was based on a series of experiments including the effects of collagenase, stretching, Wallerian degeneration, diffusion and was corroborated by histology. 

                  956.       In Vivo Proton MR Spectroscopic (1H-MRS) Investigations of Metabolic Changes in Human Brain Associated with Unspecific Low Back Pain

Alexander Gussew1, Reinhard Rzanny1, Hans Christoph Scholle2, Juergen R. Reichenbach1

1Medical Physics Group, Department of Diagnostic and Interventional Radiology, Jena University Hospital, Jena, Germany; 2Division Motor Research, Pathophysiology and Biomechanics, Department of Trauma, Hand and Reconstruc, Jena University Hospital, Jena, Germany

In vivo 1H-MRS detection of metabolic changes associated with chronic pain may provide deeper understanding of biochemical neuronal dysfunctions caused by chronification and may potentially help to specify therapeutic approaches. In this study absolute concentrations of metabolites N-acetyl aspartate, creatine, total choline, myo-Inositol and glutamate were measured by single voxel 1H-MRS at 3 T in anterior insular, anterior cingulate cortex and thalamus of six patients with chronic low back pain and corresponding healthy controls. In all investigated brain regions, concentration decrease of all metabolites up to 36% was observed in patients.

Spectroscopy Localization & Imaging Methodology

Hall B                        Monday 14:00-16:00                                                                                                  

                  957.       Simultaneous Acquisition of Metabolite and Water Signals in 3D Echo Planar Spectroscopic Imaging

Toru Shirai1, Satoshi Hirata1, Yoshitaka Bito1

1Central Research Laboratory, Hitachi, Ltd., Kokubunji, Tokyo, Japan

We have developed a technique for simultaneously acquiring of metabolite and water signals in 3D echo planar spectroscopic imaging (EPSI). The pulse sequence of this technique includes three CHESS pulses the amplitude of which is switched alternately in accordance with slice encoding steps to reverse the polarity of the water signal. The metabolite signal is separable from the water signal, because the water signal is shifted to the top and bottom of the reconstructed 3D image. The results of phantom experiments showed that this technique effectively corrected the eddy current influence, suggesting the usefulness of the proposed method.

                  958.       Accelerated Reconstruction Using Parallel Computing for Spiral Spectroscopic Imaging

Dong-Hyun Kim1, Yoon-Ho Oh1, Yoon-Ho Nam1, Meng Gu2, Won-Woo Ro1

1Electrical and Electronic Engineering, Yonsei University, Seoul, Korea, Republic of; 2Radiology, Stanford University, Stanford, United States

Fast spectroscopic imaging such as spiral CSI can be used for applications such as real time metabolite imaging or real time temperature mapping. While methods to reduce the data acquisition time have been continuously developed, reconstruction times have been prolonged. We demonstrate the usage of parallel computing to reduce the reconstruction time of spiral CSI. By using a multi-threading approach, reconstruction times during the gridding routine can be shortened to by a factor of eight.

                  959.       Water Suppression for Diffusion-Weighted Line-Scan Echo-Planar Spectroscopic Imaging

Yoshitaka Bito1, Koji Hirata1, Toshihiko Ebisu2, Yuko Kawai3, Yosuke Otake1, Satoshi Hirata1, Toru Shirai1, Yoshihisa Soutome1, Hisaaki Ochi1, Masahiro Umeda3, Toshihiro Higuchi4, Chuzo Tanaka4

1Central Research Laboratory, Hitachi, Ltd., Kokubunji-shi, Tokyo, Japan; 2Neurosurgery, Nantan General Hospital, Nantan-shi, Kyoto, Japan; 3Medical Informatics, Meiji University of Integrative Medicine, Nantan-shi, Kyoto, Japan; 4Neurosurgery, Meiji University of Integrative Medicine, Nantan-shi, Kyoto, Japan

A water suppression (WS) technique for diffusion-weighted line-scan echo-planar spectroscopic imaging (DW-LSEPSI) is presented. DW-LSEPSI uses a single chemical shift selective (CHESS) pulse for WS at each acquisition of a line suitable for a short acquisition time and to reduce a water signal using a steady state effect. The signal attenuation of the water signal is numerically analyzed and demonstrated by applying this technique to phantoms and a rat brain in vivo.

                  960.       An Investigation of the Acceleration Factor in TE-Averaged Data-Sharing Radial Proton Echo Planar Spectroscopic Imaging (DsrPEPSI)

Chin-Yu Lu1, Yi-Ru Lin2, Stefan Posse3,4, Shang-Yueh Tsai5

1Biomedical Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan; 2Eletronic Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan; 3Department of Neurology, University of New Mexico School of Medicine, Albuquerque, Albuquerque, New Mexico 87131, United States; 4Electrical and Computer Engineering Department, University of New Mexico, Albuquerque, NM, United States; 5Electrical Engineering, Chang Gung University, Taoyuan, Taiwan

Previous dsrPEPSI study which measured glutamate (Glu) shown the feasibility to reduce scan time from 16 mins to 1min. However, as scan time reduced, the SNR decreased and poor spectra qualities were observed. This study conducted to investigate and optimize the spectra quality versus scan time by tuning the arrangement of radial trajectories and TEs. From our result, 4-fold dsrPEPSI is feasible to acquire Glu at a 3T system while maintaining spectral quality. And the scan time was 4 minutes, which was a reasonable length for clinical use.

                  961.       High-Speed GABA Mapping in Human Brain with MEGA-PEPSI at 3 Tesla

Ulrike Dydak1,2, Malgorzata Marjanska3, Stefan Posse4,5

1School of Health Sciences, Purdue University, West Lafayette, IN, United States; 2Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, United States; 3Center for Magnetic Resonance Research and Department of Radiology, University of Minnesota, Minneapolis, MN, United States; 4Department of Neurology, University of New Mexico School of Medicine, Albuquerque, NM, United States; 5Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, NM, United States

The feasibility of GABA-edited magnetic resonance spectroscopic imaging with short scan times is demonstrated both in a phantom and in vivo by combining the high-speed (Proton-Echo-Planar-Spectroscopic-Imaging) PEPSI sequence with the MEGA editing scheme. We show MEGA-PEPSI spectra from an axial slice in the human brain acquired at 3 T within < 5 min with a nominal resolution of 8 ml. The signal of GABA and co-edited macromolecules is clearly discernable in most spectra and was fitted with LCModel, using a simulated basis for this sequence. Spectral fitting of the GABA resonance was feasible with Cramer Rao lower bounds < 20 %.

                  962.       Correction of Eddy Currents for Time-Domain-Interleaved Blipped-Phase-Encoding Echo-Planar Spectroscopic Imaging

Yoshitaka Bito1, Koji Hirata1, Satoshi Hirata1, Toru Shirai1, Toshihiko Ebisu2, Yuko Kawai3, Yosuke Otake1, Yoshihisa Soutome1, Hisaaki Ochi1, Masahiro Umeda3, Toshihiro Higuchi4, Chuzo Tanaka4

1Central Research Laboratory, Hitachi, Ltd., Kokubunji-shi, Tokyo, Japan; 2Neurosurgery, Nantan General Hospital, Nantan-shi, Kyoto, Japan; 3Medical Informatics, Meiji University of Integrative Medicine, Nantan-shi, Kyoto, Japan; 4Neurosurgery, Meiji University of Integrative Medicine, Nantan-shi, Kyoto, Japan

High-speed spectroscopic imaging using the echo-planar technique is sometimes distorted by eddy currents. We developed an eddy current correction technique for time-domain-interleaved blipped-phase-encoding echo-planar spectroscopic imaging (TDI-BPE-EPSI). This technique uses correction of spatial shift due to chemical shifts in the blipped-phase-encoding direction before applying eddy current correction based on the water signal. Correction of eddy currents is demonstrated by applying this technique to a phantom and a rat brain in vivo. This technique is shown to be also useful in diffusion-weighted spectroscopic imaging, which causes more eddy currents due to strong diffusion gradients.

                  963.       Comparison of Automatic and Manual Prescription Protocols for Brain 3D MRSI

Eugene Ozhinsky1,2, Daniel B. Vigneron1,3, Susan M. Chang4, Sarah J. Nelson1,3

1Surbeck Laboratory of Advanced Imaging, Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, United States; 2UCSF/UCB Joint Graduate Group in Bioengineering, University of California, San Francisco, San Francisco, CA, United States; 3Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, United States; 4Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, United States

In this work we have evaluated the coverage volume and data quality of 3D MRSI protocols with manual and automatic prescription of outer-volume suppression and selected volume. Automatic oblique prescription allowed approximately 3x increase in coverage volume with no decline in data quality.

                  964.       Inductively Coupled Reference Signal Injection Method for Quantitative MRI

Donghoon Lee1, Kenneth Marro1, Mark Mathis1, Cecil Hayes1

1University of Washington, Seattle, WA, United States

We report our efforts on continuous development of a synthetic signal injection method for metabolite quantification using MRS and MRI. This work demonstrates that calibrated synthetic voxels (instead of pseudo-FID: free induction decay), injected during or separately from real image acquisition, can be used to quantify metabolite content in real 19F image voxels. Images of vials containing different concentrations of sodium fluoride (NaF) were converted to units of moles by reference to precalibrated synthetically-injected voxels. Additional images of vials containing variable sodium chloride (NaCl) demonstrate that the quantification process is robust and immune to changes in coil loading conditions.

                  965.       Iterative CSI Reconstruction with High-Resoluiton Spatial Priors for Improved Lipid Suppression

Joonsung Lee1, Elfar Adalsteinsson1,2

1Electrical engineering and computer science, Massachusetts Institute of Technology, Cambridge, MA, United States; 2Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, United States

We have developed and demonstrated an iterative reconstruction with spatial priors for improved lipid suppression. By imposing the spatial locality constraint on the lipid spectra inside the brain, we are able to substantially improve lipid suppression from the subcutaneous fat into the brain.

                  966.       Skewed Adiabatic Pulses for Outer Volume Suppression in Single Voxel Spectroscopy

Federico Giove1,2, Francesco Marcocci1, Fabrizio Fasano, 1,3, Mauro DiNuzzo1, Gisela E. Hagberg3, Bruno Maraviglia1,2

1Department of Physics, Sapienza University of Rome, Rome, RM, Italy; 2MARBILab, Enrico Fermi Center, Rome, RM, Italy; 3Neuroimaging Laboratory, Fondazione Santa Lucia IRCCS, Rome, RM, Italy

We developed an outer volume suppression approach for nulling the external signal in single voxel spectroscopy, based on trains of adiabatitic skewed selective pulse. The pulses shape allowed the saturation bands to be prescribed adjacent to the voxel, without loss of signal. The train was tested before STEAM and PRESS acquisition schemes at 3T, and showed excellent performaces both in vitro and in vivo, in particolar for the suppression of exravoxel lipids in the visual cortex. Optimal performances were observed with VAPOR water suppression and short TE STEAM, but the approach worked eqaully well before PRESS at intermediate (30ms) TE

                  967.       Atlas-Based Automated Positioning of Outer Volume Suppression Slices in Short-TE 3D MR Spectroscopic Imaging of the Human Brain

Kaung-Ti Yung1, Chenguang Zhao1, Weili Zheng1, Manel Martinez-Ramon2, Andre van der Kouwe3, Stefan Posse1,4

1Neurology, University of New Mexico School of Medicine, Albuquerque, NM, United States; 2Dept. of Signal Processing and Communications, Universidad Carlos III de Madrid, Madrid, Spain; 3Radiology, Massachusetts General Hospital, Boston, MA, United States; 4Electrical and Computer Engineering, University of New Mexico, Albuquerque, NM, United States

Manual placement of  outer volume suppression (OVS) slices in short TE proton MR spectroscopic imaging (MRSI) is time consuming and prone to human error.  Here, we introduce an atlas-based approach to optimally positions both the 3D MRSI slab and up to 16 OVS slices in a subject’s head using affine transformation of MRSI slab and OVS slice positions that are optimally placed  in MNI space.  In vivo 3D short TE (11 ms) Proton-Echo-Planar-Spectroscopic-Imaging (PEPSI) demonstrates consistent spectral quality with the MRSI volume and comparable lipid suppression for automatic and manual OVS placement, which is desirable for clinical research studies.

                  968.       Targeted Fat Characterization with MQC Pathways

Gigi Galiana1, Robert Todd Constable1

1Diagnostic Radiology, Yale University, New Haven, CT, United States

We report a method to quantify and characterize lipids in vivo.  The method can generate simultaneous maps of saturated lipid, unsaturated lipid, and water, or it can also be run as a spectroscopic sequence to generate high resolution and very edited spectra.  We present results from both implementations and show that the method can be used to discriminate lipids that are indistinguishable by other means.

                  969.       Exotic Phase Cycling in 1H MRS

Sarah Andrea Wijtenburg1,2, Jack Knight-Scott1

1Radiology, Children's Healthcare of Atlanta, Atlanta, GA, United States; 2Biomedical Engineering, University of Virginia, Charlottesville, VA, United States

Exotic phase cycling refers to utilizing more complex phase cycling schemes to eliminate signals from unwanted coherence pathways. Here, we outline the general steps for designing an exotic phase cycle.

                  970.       Wavelet-Encoded MR Spectroscopic Imaging Incorporating Parallel Imaging to Further Reduce Acquisition Time: In-Vitro Results.

Yao Fu1,2, Hacene Serrai1

1National Research Council Institute for Biodiagnostics, Winnipeg, Manitoba, Canada; 2Electrical and Computer Engineering, University of Manitoba, Winnipeg, Manitoba, Canada

We here report our recent phantom results using wavelet encoding (WE) combined with parallel imaging (PI, WE-PI) to acquire 1D magnetic resonance spectroscopic imaging (MRSI). Two sets of experiments are performed with the same acceleration factor (R = 2) and two different resolutions (N = 4 and N = 8). The results confirm that WE-PI reduces further the acquisition time by approximately the acceleration factor R, and preserves the spatial metabolite distribution with minimal loss of the signal-to-noise ratio (SNR) as compared to the WE-SI technique.

                  971.       In-Vivo Wavelet Encoding Spectroscopic Imaging Results at 3 Tesla: Comparison to Chemical Shift Imaging.

Yao Fu1,2, Hacene Serrai1

1National Research Council Institute for Biodiagnostics, Winnipeg, Manitoba, Canada; 2Electrical and Computer Engineering, University of Manitoba, Winnipeg, Manitoba, Canada

We present our first in vivo results demonstrating wavelet encoded 3D spectroscopic imaging (WE-SI) at high magnetic field (3T) compared with standard, Fourier-encoded, chemical shift imaging (CSI).  As previously demonstrated with phantom results, we confirm a reduction in acquisition time and pixel bleed for equivalent number of encodes as compared to CSI, with the predicted drop in SNR. In-vivo results show that WE-SI preserves metabolite signal distributions while reducing acquisition time, demonstrating that WE-SI is providing accurate MRSI results with higher sensitivity at higher fields.

                  972.       Trapzoidal Volume Selection Using Adiabatic Pulses

Bu S. Park1, Jun Shen1

1National Institute of Mental Health (NIMH), National Institute of Health (NIH), Bethesda, MD, United States

Because of high immunity to RF inhomogeneity and excellent slice profiles, adiabatic pulses are widely used for special localization in MR spectroscopy. Here we propose a scheme for selecting a trapezoidal volume using adiabatic ð pulses since non-rectangular volume is often preferred in localized spectroscopy. In this scheme, a time-varying gradient orthogonal to a stationary slice-selection gradient is used to change the initial and final boundaries of the slice profile from parallel to non-parallel.

                  973.       SAR-Reduced Spectroscopic FAST Imaging with Variable Flip Angles

Linda Becker1, Wolfgang Dreher1, Dieter Leibfritz1

1Dept. Chemistry, University of Bremen, Bremen, Germany

A variation of the SSFP-based fast spectroscopic imaging technique spFAST is presented. By flip angle variation the specific absorption rate (SAR) can be reduced considerably with only a minor loss in the signal-to-noise ratio (depending on the relaxation times). Additionally, the oscillating signal intensities can be exploited for k-space weighting in one spatial phase encoding direction which enables better spatial localization. Simulations and experiments at 7T showed that a gaussian flip angle series offers good results for all tested relaxation times.

                  974.       Neurochemical Profiles of Several Brain Regions Determined by Short-Echo, 1H MRS at 7T

Uzay Emrah Emir1, Melissa Terpstra1, Ivan Tkac1, Gulin Oz1

1University of Minnesota, Minneapolis, MN, United States

All studies that obtained a neurochemical profile from short echo 1H MRS at 7T so far utilized data from the occipital lobe acquired with surface coils. In this study, we demonstrate the feasibility of acquiring and quantifying short-echo (TE = 8 ms), single voxel STEAM spectra by utilizing 16 channel transmit/receive transmission line coils and B1 shimming at 7T.  Representative spectra and neurochemical profiles are reported from brain regions that are of interest for various neurological disorders, such as the frontal white matter, posterior cingulate, putamen, and the substantia nigra.

                  975.       In Vivo Characterisation of Orthotopic Prostate Tumor and Healthy Rat Prostate Metabolism Using 1H MRS at 4.7 T

Xavier Tizon1, Peggy Provent1, Sebastien Parfait2, Gilles Crehange3, Johel Miteran2, Philippe Genne1, François Brunotte2, Olivier Duchamp1, Paul Michael Walker2

1Oncodesign, Dijon, France; 2Laboratoire Le2i - UMR CNRS 5158, Dijon, France; 3Centre Georges-Francois Leclerc, Dijon, France

1H-MRS appears to be a sensitive technique to detect prostate cancer in the clinic. The aim of this study was to establish an experimental setting to monitor the metabolism of orthotopic prostate cancer in rats, as a candidate biomarker of efficacy for anticancer drugs.

The metabolism of healthy prostates and orthotopic PC3-MM2 tumor models was monitored by 1H-MRS on Nude rats. Despite the highlighted differences between human and rat prostate metabolism, we show that the follow-up of prostate tumor metabolism in rats is possible and that the tumor metabolism is different from its host gland.

                  976.       Investigation of Region Specific Frequency Differences Between Water and N- Acetyl Aspartate Resonances Within the Human Brain

Grzegorz Lukasz Chadzynski1, Adriane Groeger2, Uwe Klose3

1Department for Diagnostic and Interventional Neuroradiology, University Hospital Tuebingen, Tuebingen, Baden- Wuerttemberg, Germany; 2Department of Neurodegeneration, Hertie Institute for Clinical Brain Research, Tuebingen, Baden-Wuertemberg, Germany; 3Department for Diagnostic and Interventional Neuroradiology, University Hospital Tuebingen, Tuebingen, Baden-Wuertemberg, Germany

Recent studies showed that the frequency distance between water and NAA measured with 1HMRS may be used for temperature evaluation. We examined regional difference of this distance in the human brain at the level of the lateral ventricles. CSI measurement were performed for 11 healthy volunteers. Spectra were acquired at 3T with PRESS localization without water suppression. We found water to NAA frequency distance to be greater in white than in gray matter with mean difference value of 0.013 ppm. According to the literature this would be approximately equal to 1oC. More reliable results can be obtained after calibration measurements.

                  977.       An Optimized Frequency Offset for Refocusing RF Pulses in Measurement of Lactate Using PRESS MR Spectroscopy

Yan Zhang1, Jun Shen1

1National Institute of Mental Health, Bethesda, MD, United States

This work demonstrates the use of an optimized RF frequency offset for the point resolved spectroscopy (PRESS) in measurement of Lactate.  The partially refocused methine proton spins due to limited RF bandwidth give rise to anomalous J-modulation for methyl proton spins, resulting in signal cancellation. With the offset of 4.1ppm, all selected methine proton spins are on resonance, and therefore no methyl proton spins are anomalously modulated, except there is a portion of the methyl proton spins are outside the RF bandwidth due to the chemical shift. But this part of methyl proton spins are to be saturated by the out volume suppression. The phantom experiment shows the net signal (ratio to NAA at 2 ppm) is enhanced by ~50% compared with that using the offset at 1.3ppm.

                  978.       Feedback-Based Interleaved Reference Spectroscopy

Thomas Lange1, Martin Buechert1, Maxim Zaitsev1

1Dept. of Diagnostic Radiology, Medical Physics, University Hospital Freiburg, Freiburg, Germany

Magnetic resonance spectroscopy experiments can be severely affected by frequency drifts, for example when a spectroscopy scan is run right after an imaging experiment involving a high gradient duty cycle. In this work we propose a feedback-based interleaved reference scan (IRS) method which updates the carrier frequency of RF pulses and ADCs in real time, using water reference spectra acquired in an interleaved fashion. Compared to a frequency lock using the residual water peak in the actual spectrum, the proposed method is more robust, particularly in the presence of strong lipid contamination. Additionally, it allows for retrospective phase correction.

                  979.       Highly Efficient Square Wave Distant Dipolar Field and Its Applications for in Vivo MRI

Zhong Chen1, Congbo Cai1, Shuhui Cai1, Jianhui Zhong2

1Departments of Physics and Communication Engineering, Fujian Key Laboratory of Plasma and Magnetic Resonance, Xiamen University, Xiamen, Fujian, China; 2Departments of Radiology and Biomedical Engineering, University of Rochester, Rochester, NY, United States

The iMQC signal intensity can be enhanced by replacing the conventional sinusoidal distant dipolar field (DDF) with square wave DDF. In this abstract, instead of a series of adiabatic inversion pulses proposed previously, a more efficient composite adiabatic inversion pulse was applied to create square wave DDF. The square wave DDF was applied to MR imaging for the first time. The experimental results show that using the proposed square wave DDF in the ZEBRA sequence can enhance the iMQC signal intensity by about 1.5 times in comparison to the conventional CRAZED sequence.

Non-Proton MRI

Hall B                        Tuesday 13:30-15:30                                                                                                 

                  980.       Initial Experience with 31P Imaging of Human Brain Using a Multi-Resonance, Spectral-Selective Sequence at 9.4Tesla

Aiming Lu1, Ian C. Atkinson1, Xiaohong Joe Zhou1,2, Keith R. Thulborn1

1Center for MR Research, University of Illinois at Chicago, Chicago, IL, United States; 2Departments of Neurosurgery, Radiology, and Bioengineering, University of Illinois at Chicago, Chicago, IL, United States

Phosphocreatine (PCr) concentration can provide vital bioenergetic information in brain. Due to their low detection sensitivity, 31P MR signals are often detected with MRS or CSI approaches, which are either time consuming or spatial resolution limited. In this work, we report initial 31P imaging results using a spectral selective twisted projection imaging (TPI) sequence to achieve high data acquisition efficiency on a 9.4T human scanner. PCr and γ-ATP images were simultaneously obtained with whole brain coverage and reasonable SNR, temporal and spatial resolution. The ratio of the two resonances images can potentially allow detection of variation in PCr concentration.

                  981.       In Vivo Chlorine-35, Sodium-23 and Proton Magnetic Resonance Imaging of the Rat Brain

Stefan Kirsch1, Mark Augath2, David Seiffge3, Lothar Schilling3, Lothar Rudi Schad1

1Computer Assisted Clinical Medicine, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany; 2Department of Physiology of Cognitive Processes, Max Planck Institute for Biological Cybernetics, Tuebingen, Germany; 3Division of Neurosurgical Research, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany

In this study we demonstrate the feasibility of combined chlorine-35, sodium-23 and proton magnetic resonance imaging (MRI) at 9.4 Tesla and, to the best of our knowledge, present the first in vivo chlorine-35 images obtained by means of MRI. With the experimental setup all measurements could be done in one session without changing the setup or moving the subject. Multinuclear MR images were acquired from a healthy rat and from a rat displaying a focal cerebral infarction. Combined in vivo chlorine-35, sodium-23 and proton MRI may provide a new approach to study diseases which involve changes in the concentration of chloride or sodium ions.

                  982.       Hadamard-Type Pulse-Phase Encoding for Imaging of Multi-Resonant Fluorine-19 Nanoparticles in Targeted Molecular MRI

Jochen Keupp1, Samuel A. Wickline2, Gregory M. Lanza2, Shelton D. Caruthers2

1Philips Research Europe, Hamburg, Germany; 2C-TRAIN, Washington University, St. Louis, MO, United States

19F-MRI allows the direct quantification of nanoparticles (NP) or fluorinated drugs in molecular imaging. Previously, α ν β 3-integrin targeted NP have been shown to detect and quantify angiogenesis in tumor models. Towards human translation, clinically-relevant NP-substrates like perfluoro-octyl-bromide (PFOB) should be applied, but rich spectra and large chemical shifts (CS) add significant complexity. Many methods have been developed to manage CS-artifacts, but tradeoffs like long encoding time or a need for complex corrections remain. Herein, Hadamard-type pulse phase encoding is introduced in the CS domain as a robust and efficient method to detect multi-resonant 19F labels. Feasibility is demonstrated in vitro and in vivo for angiogenesis-targeted PFOB-NP in Vx2 tumor bearing rabbits.

                  983.       Sodium Boost SPRITE Imaging of the Human Brain

Sandro Romanzetti1, Eberhard D. Pracht1, N. Jon Shah1,2

1Institute of Neuroscience and Medicine 4, Medical Imaging Physics, Forschungszentrum Juelich, Juelich, Germany; 2Faculty of Medicine, Department of Neurology, RWTH Aachen, Aachen, Germany

Imaging of nuclei such as 23Na, 31P, and 17O is becoming very important to understand the physiology of the cell. However, due to the low concentration and short relaxation times of theses nuclei in tissues, dedicated sequences and high optimisation are required. The SPRITE sequence has shown its ability to image the sodium in the in vivo human brain at ultrashort encoding times. In this work, a novel way to improve the sensitivity of the standard SPRITE sequence by a factor 2 is presented. This is of particular relevance for all applications where the SNR is very low.

                  984.       Thrombin-Absorbing Perfluorocarbon Nanoparticles for Treatment and 19F Tracking of Acute Thrombosis

Jacob Wheatley Myerson1, Li He2, Douglas M. Tollefsen2, Samuel A. Wickline1,2

1Biomedical Engineering, Washington University, Saint Louis, MO, United States; 2Department of Medicine, Washington University, United States

Perfluorocarbon nanoparticles were functionalized with the direct thrombin inhibitor PPACK. PPACK nanoparticles outperformed heparin in stopping acute thrombosis in mice. The particles had high affinity and specificity for thrombin and were visible with 19F magnetic resonance spectroscopy and imaging. PPACK nanoparticles are proposed a first-in-class anticoagulant with intrinsic magnetic resonance contrast, concentrated therapeutic impact defined by a thrombin-absorbing particle surface, and pharmacokinetics optimized by the base particle.

                  985.       Flyback Twisted Projection Imaging for Fast Quantitative Sodium Imaging Demonstrated on the Human Brain at 9.4 Tesla

Ian C. Atkinson1, Aiming Lu1, Keith R. Thulborn1

1Center for MR Research, University of Illinois- Chicago, Chicago, IL, United States

Quantitative sodium MR imaging predicts tissue viability and may offer information about diseases that disrupt tissue sodium ion homeostasis.  The series of acquisitions necessary for computing the tissue sodium concentration bioscale from quantitative sodium MR imaging data often requires up to 30 minutes of human scanning and 30 minutes of phantom scanning.  A new TPI-based technique is proposed that allows for rapid quantitative sodium MR imaging.  Fast quantitative sodium imaging using this new data acquisition scheme that saves 20-40% of the total acquisition time is demonstrated in the human brain at 9.4 Tesla.

                  986.       Fast 31P Metabolic Imaging of Human Muscle

Isabell Kristin Steinseifer1, Jannie Petra Wijnen1, Bob Christian Hamans1, Arend Heerschap1, Tom Wilhelmus Scheenen1,2

1Radiology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands; 2Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen, Germany

We present a 31P MRI technique to obtain images of PCr and β-ATP simultaneously by excitation of these resonances with a dual frequency selective Shinnar-LeRoux pulse at 7T. With proper choice of bandwidth of the 3D gradient echo imaging technique the chemical shift difference between the two resonances was used to completely separate images of the resonances within one large field of view. The concept of fast 31P metabolic imaging can also be applied to the brain, and even further expanded to other MR-detectable nuclei.

                  987.       Oxygen Partial Pressure and Uptake Rate in the Lung with Hyperpolarized 129Xe MRI: Preliminary Results

Mikayel Dabaghyan1, Isabel Maria Dregely2, Iga Muradyan1, Mirko I. Hrovat3, Hiroto Hatabu1, James P. Butler4, Samuel Patz1

1Department of Radiology, Brigham and Women's Hospital, Boston, MA, United States; 2Department of Physics, University of New Hampshire, Durham, NH, United States; 3Mirtech, Inc, Brockton, MA, United States; 4Department of Environmental Health, Harvard School of Public Health, Boston, MA, United States

In this study we measured the regional partial pressure of oxygen in human lungs, using hyperpolarized xenon, whose signal depends on the presence of oxygen’s paramagnetic molecules. Similar studies have been conducted in the past using HP helium. A number of images was acquired and the evolution of the signal in each pixel was fit to a model describing its decay with time, taking into account the longitudinal relaxation time (T1), which is affected by the partial pressure of oxygen. Other parameters obtained from fitting the data to the model were the oxygen uptake rate RO2 and the flip angle for each pixel.

                  988.       Simple 19F /1H Coil

Ileana Hancu1, Keith Park1, Randy Giaquinto1

1GE Global Research Center, Niskayuna, NY, United States

Fluorine MRI is becoming a powerful tool for studying drug distribution and metabolism. For such studies, transmit/receive RF structures, capable of providing anatomical information at the 1H frequency and drug distribution/metabolism at the 19F frequency are needed. Past approaches for accomplishing this purposes include coil swapping or dual tuned coils. From difficult repositioning logistics, difficult construction, or SNR loses, none such methods has proven ideal. A very simple and efficient RF structure (a solenoid coupled to a loop) is presented in this work, which can operate at both frequencies of interest through a simple opening/closing of a mechanical/electrical switch.

                  989.       Quantification and Temporal Study of Physiologic Lung Changes in Animal Models of Lung Disease Using 2D and 3D-CSI with Xe-129.

Jaime Mata1, Kai Ruppert1, Isabel Dregely2, Talissa Altes1, G. Wilson Miller1, Peter Sylvester1, Stephen Ketel3, Jeff Ketel3, Iulian Ruset3, F. William Hersman3, Klaus Hagspiel1, James Brookeman1, John Mugler III1

1University of Virginia, Charlottesville, VA, United States; 2University of New Hampshire, Durham, NH, United States; 3Xemed, LLC, Durham, NH, United States

We report the preliminary evaluation of an optimized 2D-CSI and 3D-CSI technique with hyperpolarized Xe-129, using a rabbit model of lung fibrosis and another of emphysema. We report also for the first time, the acquisition of multiple contiguous slices images with a 3D-CSI version, that covers the entire lung in ~15s. From the CSI data, we directly calculate images reflecting the amount of Xe-129 in the airspaces, and dissolved in the lung tissue, blood, and other compartments thus obtain detailed spatial information regarding how Xe-129 is distributed in those different compartments, providing regional information about lung physiology. High-resolution 2D-CSI maps of the animal in the lung fibrosis group, show the presence of a third dissolved-phase chemical shift peak at around 185ppm from the alveolar gas peak, and adjacent to the dissolved-phase tissue peak. Quantification of the CSI maps for the animal in the fibrosis model group, show an almost two fold increase in the normalized tissue and blood peaks (tissue/gas and blood/gas). Maps of the 2D-CSI acquisitions for each one of the resolved peaks show that blood and tissue lung maps are identically spatially distributed at 1.5Tesla, perhaps due to signal contamination from their very close spectral proximity at this magnetic field. 2D and 3D-CSI acquisitions at magnetic fields higher than 1.5T should create a larger separation of the chemical shift peaks for each lung compartment and produce more detailed anatomical and physiological information. The single breath-hold 3D-CSI maps presented in here, show a promising development of this technique.

                  990.       Drug Distribution Imaging of Anticancer Drug 5-FU Using 19F/1H Double-Tuned RF Coil

Yosuke Otake1, Koji Hirata1, Yoshihisa Soutome1, Yoshitaka Bito1

1Central Research Laboratory, Hitachi, Ltd., Kokubunji, Tokyo, Japan

Imaging of 19F-labeled drug distribution was demonstrated using a developed 19F/1H double-tuned RF coil and anticancer drug 5-FU administered rats. Fast spin echo with frequency selective pulses was used to efficiently obtain distribution images of 5-FU, its active anabolites, and its catabolites at the same time. The spatial change in signal intensity among several organs and tissue in images may be used to analyze the pharmacokinetics. The developed double-tuned RF coil will be a powerful tool for 19F-labeled compounds distribution imaging and pharmacokinetics research.

                  991.       In Vivo Triple-Quantum (TQ) Sodium MRI on the Human Brain: SNR Benefits at 7T

Yongxian Qian1, Fernando E. Boada1

1MR Research Center, Radiology, University of Pittsburgh, Pittsburgh, PA, United States

Triple quantum (TQ) sodium imaging is an effective means decreasing the contribution from the intracellular and fluid spaces to the sodium (23Na) signal. The sodium TQ signal is, however, much weaker than the single quantum (SQ, or total tissue) signal (~1/10). In this study, we evaluate the SNR performance of TQ sodium MRI of the human brain at both 7T and 3T. Our results demonstrate that the theoretical SNR gains of 7T have tremendous benefits for TQ sodium MRI.

                  992.       Single - Channel Multi - Coil Array

Iga Muradyan1, Feng Zhou2, Pooja Soni2, Mikayel Dabaghyan1, Samuel Patz1, Mirko I. Hrovat3

1Department of Radiology, Brigham and Women's Hospital, Boston, MA, United States; 2University of Massachusetts, Lowell; 3Mirtech, Inc, Brockton, MA, United States

Here we report on a design and initial tests of a single-channel multi-coil array. As the name of the array suggests, this system will provide an efficient and simple way of using multiple coils on a single channel scanner. This has a significant cost advantage over multi-transmit channels. SCMC arrays would be beneficial to use when there is perfusion and/or T1 . One such case identified is white and gray matter measurements with hyperpolarized xenon.

                  993.       Dixon and Chimera: Two Methods for Fast Separation of PFC Compounds with Small Chemical Shift Difference

Thomas Christian Basse-Luesebrink1,2, Thomas Kampf1, Guido Stoll2, Peter Michael Jakob1

1Experimental Physics 5, University of Wuerzburg, Wuerzburg, Germany; 2Neurology, University of Wuerzburg, Wuerzburg, Germany

Fluorine markers can possess a unique spectral 19F signal. Therefore, chemical shift imaging (CSI) methods can be used to distinguish between targets labeled with different fluorine markers. Certain PFC compounds, however, have only a small difference in the chemical shift and thus spectrally selective imaging or standard CSI methods are difficult to apply. This study focuses on two alternative methods to separate PFC compounds with a small chemical shift difference: a TSE sequence based on Dixon's method, often used to separate fat from water signal, and a recently presented ssfp Chimera method providing a specific off-resonant behavior.

                  994.       Quantitative and Qualitative Renal Sodium-Imaging at 3T

Stefan Haneder1, Simon Konstandin2, Frank G. Zöllner2, Armin M. Nagel3, Lothar R. Schad2, Stefan O. Schönberg1, Henrik J. Michaely1

1University Medical Center Mannheim, Institute of Clinical Radiology and Nuclear Medicine, Mannheim, Baden-Württemberg, Germany; 2Heidelberg University, Computer Assisted Clinical Medicine, Mannheim, Baden-Württemberg, Germany; 3German Cancer Research Center, Department of Medical Physics in Radiology, Heidelberg, Baden-Württemberg, Germany

Sodium imaging before/after water load (1L) was performed with 9 healthy volunteers. A density adapted 3D radial trajectory gradient-echo sequence was used at a 3T clinical MR scanner. Linear cortico-medullary sodium gradients were assessed before/after water load. Using standardized sodium phantoms these gradients were quantified. A decrease of the quantitative sodium concentration of about 22% after water load was stated. This study suggests that sodium imaging might be an appropriate, noninvasive method for physiological imaging of the human kidney. The current technique is sufficient for the quantification of the renal sodium concentration and its change in different physiological conditions.

                  995.       2D and 3D Spectrally Selective 31P Imaging at 3 Tesla

Haoyang Xing1,2, Hao Shen3, Hehan Tang1, Xiaoqi Huang1, Qiyong Gong1, Xiaohong Joe Zhou2,4

1Center for MR Research, West China Hospital, Sichuan University, Chengdu, Sichuan, China; 2Center for MR Research, University of Illinois Medical Center, Chicago, IL, United States; 3GE Healthcare, Beijing, China; 4Departments of Radiology, Neurosurgery, and Bioengineering, Chicago, IL, United States

Characterization of phosphocreatine (or PCr) in biological tissues can provide valuable information on tissue physiology and metabolism and may lead to sensitive disease markers.  We have developed 2D and 3D spectrally selective PCr imaging techniques on a human 3T MRI scanner.  Low resolution PCr images (32x32) can be obtained in 10.8 minutes with an SNR of ~4, boding well for further developing these techniques for human applications.

                  996.       in Vivo Molecular Imaging of Angiogenesis in Murine Urogenital Organs with Targeted Perfluorocarbon Nanoparticles and 19F ultrafast Turbo Spectroscopic Imaging (F-uTSI)

Muhammed Yildirim1,2, Anke De Vries2, Monique Berben1, Caren van Cammen3, Klaas Nicolay2, Holger Gruell1,2, Rolf Lamerichs1

1Philips Research, Eindhoven, Netherlands; 2Biomedical NMR, Faculty of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands; 3Maastricht University, Maastricht, Netherlands

MR molecular imaging method based on 19F targeted nanoparticles and novel imaging sequences promises potential use in examining angiogeneic processes taking place in the ovaries and the endometrium  in situ. Angiogenesis in the urogenital organ of the femal plays a vital role endometriosis, endoendometrial cancer and infertility.

                  997.       19F Magnetic Resonance Quantification of SiRNA Delivery Via Perfluorocarbon Nanoparticle Emulsions

Jacob Wheatley Myerson1, Megan M. Kaneda1, Gregory M. Lanza1,2, Samuel A. Wickline1,2

1Biomedical Engineering, Washington University, Saint Louis, MO, United States; 2Department of Medicine, Washington University, Saint Louis, MO, United States

Perfluorocarbon nanoparticles were functionalized to deliver VCAM-1 siRNA to human melanoma cells. Delivery was quantified via 19F magnetic resonance spectroscopy. For future in vivo studies, an MR-trackable delivery agent would aid in the determination of localization of siRNA delivery to specific tissues.

                  998.       The Loss of Sodium Homeostasis and Apoptosis During Rodent Glioma Chemotherapy

Victor D. Schepkin1, Cathy W. Levenson2, Fabian F. Calixto-Bejarano2, William W. Brey1, Petr L. Gor'kov1

1CIMAR, NHMFL/FSU, Tallahassee, FL, United States; 2College of Medicine, FSU, Tallahassee, FL, United States

The goal of the present study was to assess the hypothesis that an in vivo increase of intracellular sodium is one of the first and a crucial stage during cancer therapy.  Experiments were performed using high resolution sodium and diffusion MRI at 21.1T and rodent glioma model.  During efficient BCNU chemotherapy, tumor sodium reaches a plateau indicating a complete loss of Na homeostasis at day 4 following the initiation of therapy.  Dose dependent responses of intracellular sodium can serve as a very early biomarker for the onset of apoptosis and forecast tumor elimination.

                  999.       In Vivo Multicolor Imaging of Perfluorocarbon Emulsions Using Ultrafast Spectroscopic Imaging (F-UTSI)

Muhammed Yildirim1,2, Shelton D. Caruthers3, Aart J. Nederveen4, Jaap Stoker4, Rolf Lamerichs1

1Philips Research, Eindhoven, Netherlands; 2Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands; 3Washington University, St Louis, MO, United States; 4Department of Radiology, Academic Medical Center, Amsterdam, Netherlands

In vivo 3D F-uTSI, can distinguish various 19F compounds based on chemical shift differences allowing for ‘multicolor’ imaging, without additional increase in scan time. 3D F-uTSI is an efficient spectral imaging technique; data with a resolution of 48x48x14 can be recorded with a scan-time of 6:23m. The spectra of several Perfluorocarbon emulsion can be uniquely identified from these data. Main advantage of the spectroscopic, multicolor, imaging approach is that the spectral images of the different PFC agents are recorded at the same time and, furthermore, complex biological process can be imaged using co-injection of differently functionalized PFC emulsions.

                  1000.     Sodium MR Imaging in the Study of Hepatic Encephalopathy

Nadim Jon Shah1,2, Vincent Gras1, Anna-Maria Oros-Peusquens1, Eberhard Daniel Pracht1, Sandro Romanzetti1, Gerald Kircheis3, Dieter Häussinger3

1Institute of Neuroscience and Medicine 4, Medical Imaging Physics, Forschungszentrum Jülich GmbH, Jülich, Germany; 2Faculty of Medicine, Department of Neurology, RWTH Aachen University, Aachen, Germany; 3Klinik f. Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Düsseldorf, Düsseldorf, Germany

Sodium MRI provides an new tool for the analysis of mechanisms involved in hepatic encephalopathy (HE), a neuropsychiatric complication of liver failure. Hyperintense regions observed in the basal ganglia in proton images of HE patients are expected to show changes in sodium images due to the involvement of hyponatraemia in HE. Using sodium MRI, expected subtle changes are investigated using the structural information - delineation of structures of interest - provided by anatomical MR images. Based on the analysis of a large group of patients versus controls, this research potentially provides novel, valuable information concerning metabolic changes in HE.

                  1001.     Efficient B0-Inhomogeneity Insensitive TQF 23Na Imaging.

Lazar Fleysher1, Niels Oesingmann2, Matilde Inglese3

1Department of Radiology, NYU School of Medicine, New York, United States; 2Siemens Medical Solutions USA, Inc., United States; 3Departments of Radiology and Neurology, NYU School of Medicine, New York, United States

We present a new 12-step triple-quantum filtering phase-cycling scheme based on three RF pulses which allows compensation of B0 variations both with and without ancillary B0-map information. The method offers 40% higher SNR efficiency compared to the previously developed phase-cycling schemes.

                  1002.     Sodium MRI Multi-Echo Sequence for Simultaneous Ultra-Short Echo Imaging and T2L* Mapping at 7T with a 12 Channel Phased-Array Coil

David Thomas Pilkinton1, Mark A. Elliott1, Jeremy Magland2, Ravinder Reddy1

1Center for Magnetic Resonance and Optical Imaging, University of Pennsylvania, Philadelphia, PA, United States; 2Department of Radiology, University of Pennsylvania, Philadelphia, PA

To maximize signal-to-noise ratio (SNR) and minimize relaxation weighting, ultra-short echo (UTE) readouts have been generally been favored for sodium MRI. UTE methods have also been used to measure total sodium concentration (TSC) in tissues, although this typically requires accurate mapping of the B1 field which is typically noisy and error prone.  A more reliable quantitative parameter for sodium MRI is the measurement of the long component of the transverse relaxation time, T2L*.  In this study, we have implemented a robust sodium imaging sequence for simultaneous UTE imaging and T2L* measurements.

                  1003.     Ex Vivo Assessment of Cervical Remodeling Via 23Na MRS

Xiang Xu1, Yucel Akgul2, Mala Mahendroo2, Alexej Jerschow1

1Department of Chemistry, New York University, New York, NY, United States; 2Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX, United States

Preterm birth occurs in 12.5% of births in the United States. Greater understanding by which the two main processes, uterine contraction and cervical remodeling are regulated is required to reduce rates of preterm birth. Understanding the changes in glycosaminoglycan (GAG) concentration during cervical remodeling will help elucidate the normal physiological process in the cervix. 23Na NMR spectroscopy is used to evaluate the changes in Na+ concentration in the mouse cervix during pregnancy, labor and postpartum as a means of evaluating the GAG changes during each stage of cervical remodeling.

                  1004.     The 17O Imaging for Regional Oxygen Consumption Rate in Tumor Bearing Mice at 7T

Michiko Narazaki1, Yoko Kanazawa2, Hiroo Ikehira2, Tetsuya Matsuda1

1Kyoto University, Kyoto, Japan; 2National Institute of Radiological Sciences, Chiba, Japan

The tumor oxygen consumption rate in mice using 17O images was investigated.  17O FISP images were acquired before and after the inhalation of 17O enriched oxygen gas.  The increment in the 17O image intensity due to the metabolically generated H217O from 17O2 was converted to the quantity of produced H217O, which was in good agreement with physiological data in literature.  We confirmed this method promising as a tool for monitoring the oxygen consumption rate in tumor.

                  1005.     Binomial Sequence for Selective Quadrupolar 23Na in Vitro and in Vivo NMR and MRI

Christoffer Laustsen1,2, Steffen Ringaard1, Michael Pedersen1, Niels Christian Nielsen, 2,3

1Klinisk Institut, The MR Research Centre, Aarhus University, Aarhus, Denmark; 2iNano, Aarhus University, Aarhus, Denmark; 3inSPIN, Aarhus University, Aarhus, Denmark

The ion potential has a crucial role en cell metabolism, and is therefore a potential diagnostic target for various diseases. The purpose of this study was to investigate the use of the well known water suppression techniques: “binomial sequences”, for sodium NMR and MRI. We show that the binomial sequences posses many interesting features for different applications for S=3/2 nuclei, mainly that the central peak and the satellite peaks is either excited or suppressed independently, the other feature is the QJR regime, where only the central peak of a given quadrupolar interaction is observed.

                  1006.     Characterising a Coil/sample System for Monitoring Gastrointestinal Transit Using Fluorine Markers

Elisa Placidi1, Robin C. Spiller2, Penny A. Gowland3

1SPMMRC, School of Physics and Astronomy , University of Nottingham, Nottingham, United Kingdom; 2Nottingham Digestive Diseases Centre Biomedical Research Unit, University of Nottingham, Nottingham, United Kingdom; 3SPMMRC, School of Physics and Astronomy, University of Nottingham, Nottingham, United Kingdom


                  1007.     In Vivo High-Resolution Imaging and T1 Mapping of Brain Sodium at 4T

Ana-Maria Oros-Peusquens1, Eberhardt Pracht2, Sandro Romanzetti, N. Jon Shah3

1INM-4, Research Centre Juelich, Juelich, Germany; 2INM-4, Research Centre Juelich, Germany; 3INM-4, Germany

High-resolution sodium imaging has been performed in vivo using a 4T whole-body system and a gradient echo sequence. In a monoexponential approximation T1 mapping can be performed in a manner similar to that for protons, using two gradient echo acquisitions. Careful parameter optimisation is required, as well as high SNR.

                  1008.     5-FU Monitoring by 19F MRI: A Quantitative Study by Liquid Chromatography / Tandem Mass Spectrometry

Koji Hirata1, Yosuke Otake1, Shuhei Hashiba1, Yuichiro Hashimoto1, Yoshitaka Bito1, Hisaaki Ochi1

1Central Research Laboratory, Hitachi, Ltd., Kokubunji, Tokyo, Japan

A therapeutic drug monitoring system of 5-FU and its metabolites used by 19F MRI is developed. It was demonstrated that 19F MRI can detect tissue distribution of 5-FU and fluoro-beta-alanine (FBAL) in tumor-bearing rats. A liquid chromatography / tandem mass spectrometry (LC/MS/MS) acquired the 5-FU and FBAL concentrations. The relationship between the signal intensity by 19F MRI and concentration by LC/MS/MS in a tumor and liver was evaluated. Clearly, well relationship coefficients were obtained (5-FU: R2>0.82, FBAL: R2>0.96).

                  1009.     Classification of Metabolic Parameters by Anatomically Superimposed Scans (COMPASS)

Ian C. Atkinson1, Aiming Lu1, Theodore Claiborne1, Keith R. Thulborn1

1Center for MR Research, University of Illinois- Chicago, Chicago, IL, United States

The limited resolution of quantitative sodium MR imaging data complicates interpretation.  We present a sceme for using tissue classifications from automatically segmented high-resolution proton data to classify the voxels of tissue sodium concentration maps.

                  1010.     Intra-Cellular Sodium Fraction in the Human Brain at 7T in-Vivo.

Lazar Fleysher1, Niels Oesingmann2, Ryan Brown3, Graham Wiggins3, Daniel K. Sodickson4, Matilde Inglese5

1Department of Radiology, NYU School of Medicine, New York, United States; 2Siemens Medical Solutions USA, Inc., United States; 3Department of Radiology and Center for Biomedical Imaging, NYU School of Medicine, New York, United States; 4Departments of Radiology, Physiology and Neuroscience, NYU School of Medicine, New York, United States; 5Departments of Radiology and Neurology, NYU School of Medicine, New York, United States

Single quantum and triple-quantum sodium imaging is used to obtain the intracellular sodium fraction from the human brain in-vivo. The fast and slow sodium relaxation rates from the human head at 7T are also reported.

                  1011.     Optimized Resolution of Flexible Twisted Projection Imaging for Sodium MR Imaging

Ian C. Atkinson1, Aiming Lu1, Keith R. Thulborn1

1Center for MR Research, University of Illinois- Chicago, Chicago, IL, United States

Flexible twisted projection imaging is optimized for true resolution in the setting of sodium MR imaging.  This optimization incorporates the effects T2-blurring  into the selection of the image acquisition parameters so that the true resolution of the resultant image is optimized.

Hyperpolarized Carbon-13 & Other Nuclei

Hall B                        Wednesday 13:30-15:30                                                                                                        

                  1012.     Metabolic Imaging of the Perfused Rat Heart Using Hyperpolarized [1-13C]Pyruvate

Philip Lee1, Marie Schroeder2, Daniel Ball2, Kieran Clarke2, George Radda1, Damian Tyler2

1Singapore Bioimaging Consortium, Biomedical Sciences Institute, Singapore, Singapore; 2Department of Physiology, Anatomy & Genetics, University of Oxford, United Kingdom

Imaging of cardiac metabolism using 13C-MRS is currently hindered by both a low sensitivity and a low natural abundance of 13C. The recent development of liquid state Dynamic Nuclear Polarization (DNP) techniques has dramatically increased the signal available from 13C-MRS experiments and has opened up new possibilities for metabolic imaging of the heart. By injecting hyperpolarized 13C-labeled pyruvate into a perfused rat heart, followed by high spatial resolution chemical shift imaging (CSI) during an optimum acquisition window, we were able to image the bio-distribution of lactate, bicarbonate and alanine within 46 s.

                  1013.     Investigation of Hepatic Metabolism of DNP Hyperpolarized 1,4-13C2 Succinate

Jeremy W. Gordon1, Kang Wang1, Sean B. Fain1,2, Ian J. Rowland2

1Medical Physics, University of Wisconsin-Madison, Madison, WI, United States; 2Radiology, University of Wisconsin-Madison, Madison, WI, United States

This work describes the successful hyperpolarization of 1,4-13C2 succinate using dynamic nuclear polarization (DNP). By optimizing the solubility of succinic acid in aqueous solution, levels of solid state similar to that of pyruvate can be reproducibly obtained. 3.0M solutions of hyperpolarized succinate were utilized to investigate hepatic metabolism in vivo. 13C spectra and imaging show that the biodistribution of succinate within the liver is homogenous. No metabolites were observed in the time frame of the hyperpolarized experiments. Metabolites were also not observed in ex vivo organ homogenates.

                  1014.     Imaging TCA Cycle Metabolism by PHIP Hyperpolarization of  1,3C Succinate In Vivo
Niki Zacharias Millward1, William Perman2, Brian Ross1, Pratip Bhattacharya1

1Enhanced Magnetic Resonance Laboratory, Huntington Medical Research Institutes, Pasadena, CA, United States; 2Saint Louis University

In vivo metabolic imaging of reactions in the Krebs TCA cycle using hyperpolarization was performed using 13C deuterated fumarate that was hydrogenated to 1-13C succinate and hyperpolarized to ~8% by PHIP.  On tail-vein injection of hyperpolarized succinate in tumor-bearing mice, hyperpolarized metabolic products were detected with 20,000 fold increased sensitivity over 3-5 minutes.  The metabolic fate of hyperpolarized succinate differed in two tumors: in RENCA renal carcinoma metabolic products malate, fumarate, glutamate and citrate were defined, and in Lymphoma A20 the metabolic products were limited to malate.  These differences are tentatively assigned to the presence of hypoxia inducing factor HIF1α.

                  1015.     Exploring Multi-Shot Non-CPMG for Hyperpolarized 13C Metabolic MR Spectroscopic Imaging

Yi-Fen Yen1, Patrick Le Roux2, Dirk Mayer3,4, Atsushi Takahashi1, James Tropp1, Dan Spielman3, Adolf Pfefferbaum4,5, Ralph Hurd1

1Global Applied Science Laboratory, GE Healthcare, Menlo Park, CA, United States; 2Global Applied Science Laboratory, GE Healthcare, France; 3Radiology, Stanford University, Stanford, CA, United States; 4Neuroscience Program, SRI International, Menlo Park, CA, United States; 5Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, United States

We explored the feasibility of a multi-shot non-CPMG sequence for hyperpolarized 13C metabolic imaging. The sequence is designed to stabilize the longitudinal magnetization while keeping the transverse magnetization refocused, permitting echo-train readouts following multiple low-flip-angle excitations. Thus, acquisition strategies can be developed to take advantage of the long T1 and T2 relaxation times of hyperpolarized 13C metabolites. We demonstrate two of the potential applications, 2D T2 mapping and 3D MR spectroscopic imaging, on 13C phantoms and animals with hyperpolarized 13C-pyruvate injections.

                  1016.     Single-Shot Spiral Chemical Shift Imaging in the Rat In Vivo with Hyperpolarized [1-13C]-Pyruvate

Dirk Mayer1,2, Yi-Fen Yen3, Atsushi Takahashi3, James Tropp3, Brian K. Rutt2, Ralph E. Hurd3, Daniel M. Spielman2, Adolf Pfefferbaum1,4

1Neuroscience Program, SRI International, Menlo Park, CA, United States; 2Radiology, Stanford University, Stanford, CA, United States; 3GE Healthcare, Menlo Park, CA; 4Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, United States

Using undersampled 13C spiral chemical shift imaging (CSI) in combination with a high-performance gradient insert we achieved single-shot hyperpolarized 13C metabolic imaging of the rat in a clinical 3T MR scanner. With an acquisition time of 125 ms, the method produced metabolic images of pyruvate and its metabolic products lactate and alanine with similar quality as with conventional CSI using phase encoding, despite an almost 200-fold reduction in acquisition time. Because the longitudinal magnetization does not recover in hyperpolarized MRI, there is no intrinsic SNR disadvantage of the faster imaging method.

                  1017.     Double Spin-Echo Spiral Chemical Shift Imaging for Rapid Metabolic Imaging of Hyperpolarized [1-13C]-Pyruvate

Sonal Josan1,2, Yi-Fen Yen3, Ralph Hurd3, Adolf Pfefferbaum4, Daniel Spielman2, Dirk Mayer, 12

1SRI International, Menlo Park, CA, United States; 2Radiology, Stanford University, Stanford, CA, United States; 3Applied Sciences Laboratory, GE Healthcare, Menlo Park, CA, United States; 4Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, United States

Undersampled spiral CSI (spCSI) with free induction decay (FID) acquisition allows real-time metabolic imaging of hyperpolarized 13C. Phase correction of the FID acquisition can be difficult, especially with contributions from aliased out-of-phase peaks. This work extends the spCSI sequence to incorporate a double spin-echo obtaining high quality spectra in magnitude mode. It also provides an added benefit of attenuating signal from flowing spins.

                  1018.     In Vivo Detection of Radiation-Induced Metabolic Response in Rat Kidneys by 13C Hyperpolarized MRSI

Lasitha Senadheera1, Dirk Mayer2,3, Moses Darpolor2, Yi-Fen Yen4, Lei Xing1, Daniel Spielman2

1Radiation Oncology, Stanford University, Stanford, CA, United States; 2Radiology, Stanford University, Stanford, CA, United States; 3Neuroscience Program, SRI International, Menlo Park, CA, United States; 4Global Applied Science Laboratory, GE Healthcare, Menlo Park, CA, United States

Radiation dose to the tumors is often limited by the irradiation of adjacent organs at risk, such as kidneys. Unlike structural change, metabolic response may reflect early signs of radiation damage in tissues, offering opportunity to better design radiotherapy. Following hyperpolarized [1-13C]pyruvate injection, 13C MRSI was employed to detect radiation-induced metabolic response in rat kidneys at various radiation doses and postirradiation times. No trend in Lactate/pyruvate ratios was observed between irradiated and normal kidneys of the same animal. Metabolic response of irradiated kidneys might not be strong enough to become visible in 13C MRSI, within our experimental errors and conditions.

                  1019.     Dynamic and High-Resolution Metabolic Imaging of the Rat Brain In Vivo Using Hyperpolarized [1-13C]-Pyruvate

Dirk Mayer1,2, Yi-Fen Yen3, Atsushi Takahashi3, Sonal Josan1,2, James Tropp3, Adolf Pfefferbaum1,4, Ralph E. Hurd3, Daniel M. Spielman2

1Neuroscience Program, SRI International, Menlo Park, CA, United States; 2Radiology, Stanford University, Stanford, CA, United States; 3GE Healthcare, Menlo Park, CA; 4Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, United States

Time-resolved spiral chemical shift imaging was applied to investigate the uptake dynamics in the anesthetized rat brain after injection of hyperpolarized [1-13C]-pyruvate. Additionally, metabolic imaging at high spatial resolution was performed to better characterize the spatial origin of the metabolite signals. Higher lactate (Lac) and bicarbonate (Bic) signals were found in cortical regions of the brain. This could be due to higher flux of Pyr through the blood-brain barrier, faster substrate-to-product conversion, or both. Metabolite time courses from a region-of-interest in the cortex suggest slower production of Bic compared to Lac.

                  1020.     Simultaneous Proton and Hyperpolarized Carbon Imaging

Eric Peterson1, Kang Wang2, Krishna Kurpad3, Matthew Erickson2, Ian Rowland3, Sean Fain2,3

1Biomedical Engineering, University of Wisconsin - Madison, Madison, WI, United States; 2Medical Physics, University of Wisconsin - Madison, Madison, WI, United States; 3Radiology, University of Wisconsin - Madison, Madison, WI, United States

Current hyperpolarized carbon protocols call for all of the scans to be performed in series, including the proton localizer and carbon metabolic image.  The localizer image is typically acquired at a higher resolution than the carbon image, and eventually serves as an anatomical reference for the later carbon acquisition. By performing a simultaneous proton and carbon acquisition, several potential applications are possible such as continuous localization, motion tracking and compensation, or targeted excitation.

                  1021.     [1-13C]lactate Signal Derived from Hyperpolarized [1-13C]pyruvate Originates from the Brain, Not from the Blood.

Isabelle Iltis1, Dinesh Kumar Deelchand1, Malgorzata Marjanska1, Gregor Adriany1, Manda Vollmers1, Kamil Ugurbil1, Pierre-Gilles Henry1

1Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota, Minneapolis, MN, United States

Recently, we have shown detection of [1-13C]lactate in the normal brain in vivo after injection of hyperpolarized [1-13C]pyruvate. However, the spatial origin of the detected [1-13C]lactate signal has been a matter of debate. In the present work, a coil specifically designed to detect 13C resonances in the carotid of anesthetized, living rats was used to detect signals from the blood. We show that no lactate signal is detected in the carotid after injection of hyperpolarized [1-13C]pyruvate, hereby demonstrating that the lactate signal observed in the brain originates from tissue metabolism.

                  1022.     Multimodal Non-Invasive Imaging of Tumor Hypoxia and Metabolism Using EPR Oxygen Imaging and Hyperpolarized 13C-MRI

Shingo Matsumoto1, Doug Morris2, Martin Lizak2, Jeeva P. Munasinghe2, Keita Saito1, Jan Henrik Ardenkjaer-Larsen3, Sankaran Subramanian1, Nallathamby Devasahayam1, Kevin Camphausen1, Alan Koretsky2, James B. Mitchell1, Murali C. Krishna1

1National Cancer Institute, Bethesda, MD, United States; 2National Institute of Neurological Disorder and Stroke, Bethesda, MD, United States; 3GE Healthcare, Amersham, United Kingdom

Many tumor types can undergo aerobic glycolysis, where tumors can abnormally obtain as much as 50% of their energy (ATP) by metabolizing sugar glucose directly to lactate even in the presence of oxygen. Likewise, approximately one half of tumors exhibit marked hypoxia. Collectively, these traits can contribute to resistance to cancer treatments. Non-invasive assessment of altered tumor metabolism and tissue hypoxia might be useful for both diagnostic and treatment strategies. In this study EPR oxygen imaging and hyperpolarized MRI of 13C-labeled pyruvic acid, are coupled to provide a measure of tumor hypoxia and energy metabolism.

                  1023.     Metabolism of Hyperpolarized 1-13C-Lactate in Living Breast Cancer Cell Cultures

Talia Harris1, Galit Eliyahu2, Lucio Frydman1, Hadassa Degani2

1Chemical Physics, Weizmann Institute of Science, Rehovot, Israel; 2Biological Regulation, Weizmann Institute of Science, Rehovot, Israel

The enhanced polarization enabled by ex situ Dynamic Nuclear Polarization may allow us to follow metabolic processes non-invasively with unprecedented sensitivity and temporal resolution. In order to understand the altered metabolism of cancer and screen for additional biomarkers we have developed a perfusion-infusion bioreactor, allowing hyperpolarized metabolic measurements on living cell cultures. In this work we compare the metabolism of 1-13C-Pyruvate and 1-13C-Lactate in breast cancer cells. The kinetic measurements allow us to demonstrate that the metabolism of 1-13C-Lactate is transport limited, as was previously established for 1-13C-Pyruvate.

                  1024.     Modeling of Pyruvate/Lactate Kinetics Using a Two-Site Exchange Model

Aaron Keith Grant1, Elena Vinogradov1, Pankaj K. Seth1, Xiaoen Wang1, Robert E. Lenkinski1, Vikas P. Sukhatme1

1Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, United States

Hyperpolarized pyruvate undergoes rapid conversion into lactate, alanine, and bicarbonate in vivo.  Lactate is of particular interest as elevated lactate levels may serve as a biomarker for cancer.  Although lactate SNR has been shown to correlate with histological characteristics of tumors, quantitative measures of kinetics are desirable.  We present fits of a simple two-site exchange model to data acquired in an animal model of non-small lung cancer, and show that these methods can quantify reductions in lactate formation rates following administration of dichloroacetate, a drug that up-regulates the activity of pyruvate dehydrogenase.

                  1025.     A Feasibility Study in Mini-Pig for Heart Metabolism with Hyperpolarized [1-13C]pyruvate: MRS Cardiac Modelling and Kinetic Considerations

Francesca Frijia1, Luca Menichetti1, Vincenzo Positano1, Vincenzo Lionetti2, Claudia Forte3, Jan H. Ardenkjaer-Larsen4, Matteo Milanesi1, Giulio Giovannetti1, Daniele De Marchi1, Giovanni Aquaro1, Manuela Campan2, Fabio A. Recchia5, Luigi Landini1, Maria Filomena Santarelli1, Massimo Lombardi1

1MRI Lab, "G. Monasterio" Foundation and Institute of Clinical Physiology, Pisa, Italy; 2Sector of Medicine, Scuola Superiore Sant'Anna, Pisa, Italy; 3Istituto per i Processi Chimico Fisici, CNR,, Pisa, Italy; 4GE Healthcare, Huginsvej 8, 3400 Hillerod,, Denmark; 5Department of Physiology, New York College, Valhalla, New York

Changes in metabolic products of pyruvate can be correlated to the patho-physiological condition of the myocardium: The cardiac oxidation of pyruvate depends on oxygen delivery to myocardium and on the activation state of mitochondrial pyruvate dehydrogenase. The real time tracking of the metabolic fate of pyruvate in the intact heart with MRS would provide a key information on the state of myocardium in response to a variety of stimuli. This study deal with the real time in vivo cardiac metabolism after intravenous injection of hyperpolarized [1-13C]-pyruvate in the animal of mid size with a 3T scanner with regards to the typical kinetic profile of accumulation of each metabolite and if the typical pattern could be modelled with simple equations.

                  1026.     Multiplet Asymmetry and Multi-Spin Order in Liquid-State NMR Spectra of  Hyperpolarized Compounds

James Tropp1

1Global Applied Science Lab, GE Healthcare Technologies, Fremont, CA, United States

We present density matrix calculations of the carbon spectra of doubly labelled hyperpolarized [1, 2 -13C2] pyruvate at 3.0 tesla, showing the combined effects of hyperpolarization and strong scalar coupling upon the asymmetry of the multiplet lineshapes.  The possibility is discussed of using the asymmetry to measure hyperpolarization in situ.  The importance of multi-spin order in causing the asymmetry is discussed.

                  1027.     A Simple and Accurate Method for 13C Coil Sensitivity Estimation

Giulio Giovannetti1, Francesca Frijia2, Luca Menichetti1, Maria Filomena Santarelli1, Valentina Hartwig1, Luigi Landini3, Massimo Lombardi2

1Institute of Clinical Physiology, National Research Council, Pisa, Italy, Italy; 2"G. Monasterio" Foundation, Pisa, Italy; 3Department of Information Engineering, University of Pisa

Hyperpolarization methods have been proposed to enhance the polarization of nuclear spins such as 13C. Efficient imaging of such molecules requires new multifrequency coils. However, when the coil are tuned at lower frequency with respect to 1H frequency, such as for 13C experiments, the SNR decreases. Since the SNR performance increases as the sensitivity of the coils it is important to estimate this parameter for an optimized coil design. The purpose of this work is to verify the accuracy of perturbing spheres method for coil sensitivity estimation, by testing two 13C birdcages and demonstrating its efficacy for coil sensitivity estimation.

                  1028.     Effect of Binding on Hyperpolarized MR Signals

Kayvan R. Keshari1, David M. Wilson, Daniel B. Vigneron, Jeffrey M. Macdonald2, John Kurhanewicz

1University of California, San Francisco, San Francisco, Ca, United States; 2University of North Carolina, Chapel Hill

The purpose of this study was to use hyperpolarized 13C-spectroscopy in the benzoic acid-β-cyclodextrin system to understand the relationship between binding and loss of hyperpolarized signal. The apparent T1 relaxation times for the C1 and C2 carbons of benzioc acid decreased in the presence of β-cyclodextrin, and the changes in T1 relaxation with benzoic acid concentration were used to determine the binding constant (log K 1.68-1.74).  Hyperpolarized 13C-spectroscopy may have a role in the rapid screening of small molecular weight drug binding constants in vitro and determining the impact of enzymatic binding on hyperpolarized metabolic probe T1s.

                  1029.     Hyperpolarised Combretastatins: Potential Bio-Marker for Vascular Targeting of Tumours.

Steven Reynolds1, Joanne Bluff1, Gillian M. Tozer1, Martyn Paley1

1School of Medicine, University of Sheffield, Sheffield, United Kingdom

Combretastatin vascular targeting drug CA-4-P is a complementary approach to cancer therapy. For clinical evaluation of new agents we are developing bio-imaging markers to determine pharmakinetic and pharmadynamic response to rat tumour models.  Using Dynamic Nuclear Polarisation (DNP) we have shown that CA-4-P can be 13C hyperpolarised and observed by in vitro 13C NMR spectroscopy. By measuring 13C T1 relaxation times we discuss 13C labelling strategies to permit observation of this molecule and its daughter products in an in vivo tumour rat model.

                  1030.     In Vivo Hyperpolarized 89Y Studies in a 9.4T Animal Scanner

Matthew E. Merritt1,2, M Mishovsky3,4, T. Cheng3, Ashish Jindal5, Zoltan Kovacs5, Craig Malloy5,6, Rolf Gruetter3,7, A Dean Sherry5,8, Arnaud Comment3,9

1Advance Imaging Research Center, UT Southwestern Med. Center, Dallas, TX, United States; 2Radiology, UTSW Medical Center, Dallas, TX, United States; 3Laboratory for Functional and Metabolic Imaging, Ecole Polytechnique Federal de Lausanne, Lausanne, Switzerland; 4Radiology, Universite de Lausanne, Lausanne, Switzerland; 5AIRC, UTSW Medical Center, Dallas, TX, United States; 6Cardiology, North Texas VA Hospital, Dallas, TX, United States; 7Radiology, Universite de Geneve, Geneva, Switzerland; 8Chemistry, University of Texas at Dallas, Richardson, TX, United States; 9Institute of Condensed Matter Physics , Ecole Polytechnique Federal de Lausanne, Lausanne, Switzerland

In vivo 89Y MRS of a rat kidney was performed in a 9.4 T animal scanner after infusion of hyperpolarized 89Y(DOTA) -. The hyperpolarized solution was prepared by dynamically polarizing the 89Y nuclear spins of the Y3+ complexes at 5 T and 1.05 K using the TEMPO free radical. The rapid injection of the solution led to subsequent large in vivo 89Y signal detected in the rat kidney. It was observed that the decay time of the signal is long enough to perform hyperpolarized 89Y in vivo studies.

                  1031.     Measurement of Laser Heating in Spin Exchange Optical Pumping by NMR Diffusion Sensitisation

Steven Richard Parnell1, Martin H. Deppe1, Salma Ajraoui1, Juan Parra-Robles1, Stephen Boag2, Jim M. Wild1

1Unit of Academic Radiology, University of Sheffield, Sheffield, South Yorkshire, United Kingdom; 2ISIS Facility, STFC

We detail in-situ measurement of the temperature/pressure of alkali metal spin-exchange optical pumping (SEOP) cells containing 3He. A means of measuring cell temperature and laser heating with NMR is demonstrated using a simple 1-D gradient imaging system.

                  1032.     Single Scan Multi-Nuclear NMR at Earth Magnetic Field Using Para-Hydrogen Induced Polarization (PHIP-EF-NMR)

Bob C. Hamans1, Sybren S. Wijmenga2, Arend Heerschap1, Marco Tessari2

1Radiology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands; 2Biophysical Chemistry, Radboud University Nijmegen, Nijmegen, Netherlands

Hyperpolarization methods can increase nuclear polarization to the order of unity, which corresponds to a sensitivity enhancement of several orders of magnitude with respect to standard NMR techniques based on thermal polarization. In contrast to other hyperpolarization methods like e.g. DNP, PHIP can provide within seconds high degrees of hyperpolarization at moderate experimental conditions and at a relatively low cost per sample. Here we present the application of PHIP to the acquisition of single shot multi nuclear NMR spectrum in the earth magnetic field.

                  1033.     13C Hyperpolarized Anticoagulants

Joachim Bargon1, Johannes Bernarding2, Rahim Rizi3, Hans-Wolfgang Spiess4, Kerstin Münnemann4, Meike Roth4, Ute Bommerich5

1Institute of Physical and Theoretical Chemistry, University of Bonn, Bonn, NRW, Germany; 2Institute of Biometry, University of Magdeburg, Magdeburg, Germany; 3Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States; 4NMR, Max-Planck Institute of Polymers, Mainz, Germany; 5Institute of Neurobiology, Magdeburg, Germany

Anticoagulants like warfarin, phenprocoumon, and pentoxifylline are used to alleviate the disabling consequences of strokes, the leading cause of disability in the US and third leading cause of death. Similarly, the phosphodiesterase inhibitor pentoxifylline inhibits multiple processes including inflammation, coagulation, and edema that lead to neonatal hyperoxic lung injury, whereby. bronchopulmonary dysplasia is a leading cause of mortality and morbidity in preterm infants despite improved treatment. All of these anticoagulants can be 13C-hyperpolarized for 13C-MRI/MRS-studies upon parahydrogenation of suitably unsaturated precursors, preferably at low magnetic fields. Differing from DNP, this procedure can provide a steady flow of 13C-hyperpolarized drugs.

Electron Spin Resonance

Hall B                        Thursday 13:30-15:30                                                                                                           

                  1034.     Non-Invasive Demonstration of Instabilities in Tumor Oxygen Concentration Using Dynamic 3D EPR Oxygen Imaging

Hironobu Yasui1,2, Shingo Matsumoto1, Jeeva P. Munasinghe3, Nallathamby Devasahayam1, Sankaran Subramanian1, James B. Mitchell1, Murali C. Krishna1

1National Cancer Institute, Bethesda, MD, United States; 2Hokkaido University, Hokkaido, Japan; 3National Institute of Neurological Disorder and Stroke

Structural and functional abnormality of blood vessels within malignant tumors influences delivery of oxygen, a key radio-sensitizer, resulting in two different types of hypoxia. Chronic hypoxia is attributed to large diffusion distances between tumor microvessels and longitudinal oxygen gradient, whereas acute hypoxia is though to be the result of transient vascular occlusion and fluctuation in red blood cell flux. Electron paramagnetic resonance (EPR) imaging is a sensitive method to non-invasively map tissue oxygenation distribution. To investigate the fluctuation of tumor oxygen concentration, dynamic 3D EPR oxygen imaging was applied to two different types of tumor bearing in mouse.

                  1035.     Assessment of Rapamycin Effects on Tumor Oxygenation and Angiogenesis by Using EPRI and MRI

Keita Saito1, Shingo Matsumoto1, Nallathamby Devasahayam1, Sankaran Subramanian1, Jeeva P. Munasinghe2, Vyomesh Patel3, Silvio Gutkind3, James B. Mitchell1, Murali C. Krishna1

1National Cancer Institute, Bethesda, MD, United States; 2National Institute of Neurological Disorder and Stroke; 3National Institute of Dental and Craniofacial Research

Effects of anti-tumor drug rapamycin on tumor oxygenation and angiogenesis in tumor bearing mice were investigated by using pulsed electron spin resonance imaging and magnetic resonance imaging. Blood volume in tumor region was significantly decreased after 2 days from beginning of the rapamycin treatment. Tumor oxygenation did not drastically change by rapamycin treatments, but pO2 level slightly increased and the ratio of hypoxic area to tumor region slightly decreased after 2 days rapamycin treatments. These results suggest that rapamycin can normalize blood volume and suppress depletion of oxygen in the tumor region.

                  1036.     Spatial Distribution of Free Radicals in Dental Resins Using Electron Paramagnetic Resonance Imaging (EPRI)

Philippe Levêque1, Julian Leprince2,3, Ana Maria Dos Santos-Goncalvez2, Gaëtane Leloup2, Bernard Gallez1

1Biomedical magnetic resonance unit, Université catholique de Louvain, Brussels, Belgium; 2School of Dentistry and Stomatology, Université catholique de Louvain, Brussels, Belgium; 3Laboratory of Polymer Science, Université catholique de Louvain, Louvain-la-Neuve, Belgium

Methacrylate resins are highly popular in dentistry and are largely used in clinic for tooth restoration. Free radicals are created during the photopolymerization process and can be detected by EPR spectroscopy. EPR has been successfully used to study the mechanical properties of this material. This study focuses on the feasibility of EPRImaging using dental resins which exhibits complex signal. 2D imaging and 2D spectral spatial imaging were applied and give the unique possibility of non destructive characterization and mapping of free radicals in dentam resins and more generally in biomaterials and materials science.


Hall B                        Monday 14:00-16:00                                                                                                  

                  1037.     Characterization of Tumor Microvascular Structure and Permeability by MRI and Intravital Confocal Imaging

Nina Kristine Reitan1, Marte Thuen2, Pål Erik Goa3

1Department of Physics, NTNU, Trondheim, Norway; 2Department of Circulation and Medical Imaging, NTNU, Trondheim, Norway; 3Department of Radiology, St. Olavs Hospital, Trondheim, Norway

By using confocal laser scanning microscopy (CLSM) and MRI we studied microvascular architecture and permeability in tumors growing in dorsal window chambers in mice. 40 kDa dextran and Gadomer was used as molecular tracers for dynamic CLSM and DCE-MRI, respectively. Correlation was found between permeability measured by the two techniques and permeability further depended on structural parameters, like fractal dimension and vascular density. This study demonstrates that the dorsal window tumor model gives an opportunity to use CLSM and MRI as supplementary techniques and that CLSM provides insight into the spatial heterogeneous microenvironment on a microscopic level that is not accessible with MRI.

                  1038.     In Vivo High-Resolution Magic Angle Spinning Proton MR Spectroscopy of Small Whole-Model Organism C. Elegans

Valeria Righi1,2, Alex A. Soukas3, Gary Ruvkun3, A Aria Tzika1,2

1NMR Surgical Laboratory, Department of Surgery, Massachusetts General Hospital and Shriners Burns Institute, Harvard Medical School, Boston, MA, United States; 2Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Athinoula A. Martinos Center for Biomedical Imaging, Boston, MA, United States; 3Department of Genetics, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States

We demonstrate metabolic biomarker profiles with high-resolution magic angle spinning proton MR spectroscopy (HRMAS H1 MRS) of living Caenorhabditis elegans (C. elegans) worms. This work opens up perspectives for the use of H1 HRMAS-MRS as a metabolic profiling method for C. elegans. Because it is amenable to high throughput and is shown to be highly informative, this approach may lead to a functional and integrated metabolomic analytic approach of the small organism C. elegans, which has been used extensively in studies of aberrant metabolism, and should help in identifying, investigating, and even validating new pharmaceutical targets for metabolic diseases.

                  1039.     Morphologic Abnormalities of Mucopolysaccharidosis Type VII Characterized by High Resolution MRI in a Mouse Model

Ilya Michael Nasrallah1, Sungheon Kim2, Ranjit Ittyerah1, Stephen Pickup1, John H. Wolfe3,4, Harish Poptani1

1Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States; 2New York University; 3Departments of Pathobiology and Pediatrics, University of Pennsylvania; 4Children's Hospital of Philadelphia

Mucopolysaccharidosis Type VII (MPS VII) is one of the degenerative lysosomal storage diseases characterized by intracellular vacuolization.  Using high-resolution MRI in a mouse model of MPS VII with manual segmentation, we identify decreases in corpus callosum and anterior commisure volume and slight increase in hippocampus volume in mutant mice.  A decrease in corpus callosum volume thickness is confirmed at histology.  These parameters could be used for monitoring experimental response to gene therapy treatments.

                  1040.     MRI Phenotyping of Craniofacial Development in Transgenic Mice Embryos

Hargun Sohi1, Seth Ruffins1, Yang Chai2, Scott Fraser1, Russell Jacobs3

1Caltech; 2USC; 3Caltech, Pasadena, CA, United States

Microscopic MRI (μMRI) is an emerging technique for high-throughput phenotyping of transgenic mouse embryos, and is capable of visualizing abnormalities in craniofacial development. μMRI methods rely on reduction of the tissue T1 relaxation time by penetration of a gadolinium chelate contrast agent.  The use of contrast agents is aimed at reducing the T1 relaxation time of the sample thus permitting a decrease in acquisition scan time, and/or increase in image signal-to-noise ratio (SNR), and/or increase in spatial resolution. In this work we apply these technologies to delineating changes in a murine cleft palate model system.

                  1041.     Relaxivity Tissue Differentiation Among Gd-Based Contrast Agents in Ex-Vivo Mouse Embryo Imaging

Michael David Wong1, X Josette Chen1, R Mark Henkelman1

1Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario, Canada

The role of MRI in developmental biology, specifically in mouse embryo organogenesis and phenotyping, is significantly increasing due to technologies that allow for high image resolution and throughput.   The majority of ex-vivo MRI mouse embryo studies improve image contrast and SNR by immersing the sample into some concentration of Gd-based contrast agent.  It is widely believed that all gadolinium-based contrast agents have identical tissue interactions and provide similar MRI images despite the differences in Gd-chelates.  Here, relaxivity (r1) variation amongst mouse embryo organs is observed for one class of contrast agents, while homogeneity is seen throughout the embryo for another.

                  1042.     Contrast Enhancement in Preserved Zebra Finch Brains Utilizing Low Temperatures at High Magnetic Fields

Parastou Foroutan1,2, Susanne L. T. Cappendijk3, Samuel C. Grant1,2

1Chemical & Biomedical Engineering, The Florida State University, Tallahassee, FL, United States; 2CIMAR, The National High Magnetic Field Laboratory, Tallahassee, FL, United States; 3Biomedical Sciences, College of Medicine, The Florida State University, Tallahassee, FL, United States

Temperature is evaluated as an easy method of increasing contrast in preserved tissue. In this study, excised, fixed brains from the adult male zebra finch were scanned at multiple temperatures between 5-25 Celsius. Relaxation (T1, T2 and T2*), signal-to-noise, relative contrast and contrast-to-noise were measured at each temperature. In addition, high-resolution 3D gradient recalled echo scans were acquired at 40-micron isotropic resolution at each temperature. Although all relaxation mechanisms displayed decreases with temperature, only T2* contrast displayed structural enhancement. The ramifications of these findings are discussed with respect to microimaging studies of preserved tissue samples.

                  1043.     Phenotyping a Novel Mouse Model of Congenital Heart Disease Using μMRI

Jon Orlando Cleary1,2, Francesca C. Norris3,4, Karen McCue5, Anthony N. Price3, Sarah Beddow5, Roger J. Ordidge2,6, Peter J. Scambler5, Mark F. Lythgoe3

1Centre for Advanced Biomedical Imaging, Department of Medicine and UCL Institute of Child Health , University College London, London, United Kingdom; 2Department of Medical Physics and Bioengineering, University College London, London, United Kingdom; 3Centre for Advanced Biomedical Imaging, Department of Medicine and UCL Institute of Child Health, University College London, London, United Kingdom; 4Centre for Mathematics and Physics in the Life Sciences and EXperimental Biology (CoMPLEX), University College London, London, United Kingdom; 5Molecular Medicine Unit, UCL Institute of Child Health, University College London, London, United Kingdom; 6Wellcome Trust Advanced MRI Laboratory, University College London, London, United Kingdom

CHARGE and DiGeorge syndromes are conditions associated with haploinsufficiency of specific genes (CHD7 and TBX1) and are characterised by cardiovascular defects. Knockout mice are an important tool in genetic studies, allowing genes implicated in congenital defects to be identified and characterised. Micro-MRI is an emerging technique for high-resolution cardiac phenotyping, enabling the acquisition of 3D images of multiple embryo in a single scan. Given the phenotypic overlap of these conditions, we examined heart morphology in novel double-knockout mouse embryos (Chd7+/-Tbx1+/-), performing an assessment using MRI. In particular, we identified an increased incidence of ventricular septal defects in these mice.

                  1044.     Optimised µMRI for Phenotyping the Tc1 Model of Down Syndrome

Jon Orlando Cleary*1,2, Francesca C. Norris*3,4, Frances K. Wiseman5, Anthony N. Price3, ManKin Choy3, Victor L.J. Tybulewicz6, Roger J. Ordidge2,7, Elizabeth M.C. Fisher5, Mark F. Lythgoe3

1Centre for Advanced Biomedical Imaging, Department of Medicine and UCL Institute of Child Health , University College London, London, United Kingdom; 2Department of Medical Physics and Bioengineering, University College London, London, United Kingdom; 3Centre for Advanced Biomedical Imaging, Department of Medicine and UCL Institute of Child Health, University College London, London, United Kingdom; 4Centre for Mathematics and Physics in the Life Sciences and EXperimental Biology (CoMPLEX), University College London, London, United Kingdom; 5Department of Neurodegenerative Disease, UCL Institute of Neurology, University College London, London, United Kingdom; 6MRC National Insitiute for Health Research, London, United Kingdom; 7Wellcome Trust Advanced MRI Laboratory, University College London, London, *equal contribution

‘Staining’ brain tissue with MR contrast agents is a key part of MR microscopy, enabling enhanced delineation of structures. Although excised brains allow agent to quickly penetrate into tissue, brains left in-skull are less susceptible to damage during tissue extraction and imaging, resulting in more accurate morphometric analyses. We sought to develop an optimised preparation and scanning protocol for imaging adult mouse brains in-skull, determining the timecourse for agent to penetrate into intact brain. Using this protocol we assessed phenotype in Tc1 mice – a model of Down Syndrome. We identified ventricular enlargement in 10 of 14 transgenic Tc1+ mice imaged.

                  1045.     MR Microscopy of Zebrafish

Miriam Scadeng1, Ellen Breen2, Nathan Gray1, David Dubowitz1

1Radiology, UC San Diego, San Diego, CA, United States; 2Medicine, UC San Diego, San Diego, CA, United States

Being a relatively new animal model there is no comprehensive 3D anatomical atlas onto which temporal or spatial data can be projected. In addition, methods for in-vivo imaging of adult fish are needed if zebrafish researchers are to benefit from functional MR imaging techniques such as MRS, MEMRI, BOLD and even ASL that are routinely being used in mouse models of disease. The major challenges include the very small size of the fish, and imaging the live fish in water. We present methods for in-vivo MRI of zebrafish, and a 3D atlas of zebrafish anatomy.

                  1046.     Visualization of Vascular Casts Using 3D MR Imaging

Ian Rowland1, Joseph Heintz2, Douglas Steeber3, Ralph Albrecht2

1Department of Radiology, University of Wisconsin, Madison, WI, United States; 2Department of Animal Sciences, University of Wisconsin, Madison, WI, United States; 3Department of Biological Sciences, University of Wisconsin, Milwaukee, WI, United States

This study demonstrates that at 4.7T, using a standard 3D gradient echo sequence, images of vascular casts prepared using established corrosion casting techniques may be obtained with an isotropic resolution <50um. Immersion of the casts in aqueous contrast agent enabled 3D representations of the casts to be generated via the absence of MR signal. Despite the lower resolution of MR, surface rendering of the data is able to guide SEM studies to specific regions of interest. Accurate 3D data from vascular casts can be compared with in vivo angiography studies and may also be used to validate direct and indirect methods of measuring vascular dimensions.

                  1047.     EPI Microscopy with Uniplanar Magnetic Field Gradient Coils

Lin Zhao1, Andrey V. V. Demyanenko1, J. Michael Tyszka1

1California Institute of Technology, Pasadena, CA, United States

A localized small gradient design generates negligible eddy currents and is well-suited  for EPI microscopy. Here single shot EPI is demonstrated in both an ex vivo mouse embryo sample and in vivo mouse brain using a prototype  three-axis uniplanar gradient design.

                  1048.     MR-Microscopy on a Human 7T-Scanner

Andreas Berg1, Andreas Potthast2, Piotr Starewicz3

1MR-Center of Excellence, Center for Biomedical Engineering and Physics, Wien, Vienna, Austria; 2Healthcare Sector, Imaging & IT Division, Magnetic Resonance, Siemens AG, Erlangen, Germany; 3Resonance Research, Inc., Billerica, MA, United States

MR-microscopy can be looked upon as key technological tool in MRI-based molecular imaging in biological models and human pathology samples. Is it possible to achieve a pixel-size below 100 µm on high-field human MR-scanners (B≥7T) within 21min at acceptable Signal-to-Noise-Ratio? We present microscopic images at voxel-size of 25x51x200 µm3 and document a spatial resolution higher than 34µm using specifically designed grid-phantoms. The data, according to our knowledge, represents the highest documented spatial resolution obtained yet on such a scanner. The technical equipment based on a high gradient-strength insert coil and sensitive detectors is shortly explained.

                  1049.     An In-Ovo Longitudinal µ-Magnetic Resonance Imaging Study of Quail Eggs and Embryonic Development

Suzanne Louise Duce1

1College of Life Sciences, University of Dundee, Dundee, United Kingdom

Avian embryos are important models for understanding embryonic development. We undertook a 3D longitudinal μMRI study using 7.1T Bruker of quail eggs imaged daily for 8 days, changes in the extra- and non-embryonic components as well as in the embryo were studied. At Day 0 the yolk, albumen, latebra and chalaza are visible, additional aqueous region is visible from Day 2. The growth of the embryo in-ovo is visualised. The 3D surface reconstructions of the embryo, yolk, albumen, embryonic fluid, and latebra were produced, their respective volumes calculated and changes over time presented graphically.

Methodology for MR Elastography

Hall B                        Tuesday 13:30-15:30                                                                                                 

                  1050.     Intensity Speckle MR Elastography

Sebastian Papazoglou1, Sebastian Hirsch1, Dieter Klatt1, Kaspar Josche Streitberger1, Kerstin Riek1, Thomas Elgeti1, Jürgen Braun2, Ingolf Sack1

1Institute of Radiology, Charité - University Medicine Berlin, Berlin, Germany; 2Institute of Medical Informatics, Charité - University Medicine Berlin, Berlin, Germany

In this study we present a statistical analysis of shear wave intensity speckles in magnetic resonance elastography (MRE). The employed statistical model provides a single fit parameter that is related to characteristic structure-related length scales. Hence, the intensity speckle distribution offers the possibility to investigate the elastic heterogeneity of the brain without solving the ill-posed inverse problem associated with shear wave propagation. Results of speckle intensity MRE experiments on gel phantoms and the brain of a healthy subject demonstrate the feasibility of the proposed statistical analysis.

                  1051.     Elastography Liver Stiffness Estimates from Two Phase Samples

Roger C. Grimm1, Armando Manduca2, Richard L. Ehman

1Mayo Clinic, Rochester, MN, United States; 2Mayo Clinic, United States

Recently, Wang has shown that two phase samples are adequate to generate stiffness estimates in phantom and breast experiments. Acquiring only two phase samples is only justified if the vast majority of the applied energy is occurring at a single frequency. This paper finds that there is virtually no energy contained in the higher harmonics during liver exams. Stiffness maps from inversions of two and four phase samples show a highly linear relationship with a slight underestimation obtained from two phase sample data set due to the root 2 lower SNR.

                  1052.     Ergonomic Flexible Drivers for Hepatic MR Elastography

Jun Chen1, David Stanley2, Kevin Glaser1, Meng Yin1, Phillip Rossman1, richard Ehman1

1Department of Radiology, Mayo Clinic, Rochester, MN, United States; 2GE Healthcare, Milwaukee, WI, United States

Electromechanical drivers and pneumatic drivers are widely used for in vivo human hepatic MRE. Due to the small size and rigid nature of existing mechanical drivers, the human-driver contact is not able to accommodate the soft and contoured nature of the human body, therefore the mechanical coupling is not optimal and has the potential of causing discomfort to patients. The pneumatic driver system has the same limitations due to it current rigid passive driver, especially for female patients. Our goals were 1) to design an ergonomic pneumatic flexible passive driver to improve human-driver mechanical coupling and patient comfort; and 2) to compare the flexible driver with the rigid passive driver on volunteers and patients.

                  1053.     Characterization of Tumor Vascularization in Mice Using MRE

Lauriane Juge1, Bich-Thuy Doan2, Johanne Seguin2, Benoit Larrat3, Jean Herscovici2, Daniel Scherman2, Ralph Sinkus3

1RMN, ENSCP, PARIS, France, Metropolitan; 2UPCG/ENSCP; 3ESPCI

Assessment of neoangiogenesis are major challenges in cancerology. We develop a new application of Magnetic Resonance Elastography (MRE) for measuring the viscoelastic properties of tissue changing with the vascularization. Five, nine and fourteen days after implantation of CT26 tumors on Balb-C JRJ mice, MR experiments were performed at 7T. MRI supplied anatomic and quantitative T1 T2 maps. MRE (1000 Hz) measured Gd (elasticity) and Gl (viscosity) parameters, revealing a ring with higher hardness located at the periphery which should correspond to the expected neoangiogenesis. Histopathology was performed to assess the microvascular architecture and necrosis state in coherence with MRI and MRE.

                  1054.     A Convertible Pneumatic Actuator for Brain and Phantom Elastography

Peter Latta1, Patricia Debergue2, Marco L.H. Gruwel1, Brendon Matwiy1, Uta Sboto-Frankenstein1, Boguslaw Tomanek1

1MRTechnology, NRC-CNRC Institute for Biodiagnostics, Winnipeg, MB, Canada; 2NRC-CNRC Industrial Materials Institute, Boucherville, QC, Canada

We preset a convertible pneumatic actuator design to generate vibration for MRE experiments. The experimental results on both phantoms and volunteers showed that the actuator produces suitable shear waves for the calculation of viscoelastic properties of tissues and materials in the frequency range of 25-150Hz. The unique feature of our design is its flexibility and ease of use.

                  1055.     A Hydraulic Driver System for MR Elastography of Small Animals

Michael Neumaier1, Elmar Schuck2, Thomas Kaulisch1, Heiko G. Niessen1, Dieter Klatt3, Ingolf Sack3, Juergen Braun4, Detlef Stiller1

1In-Vivo Imaging Unit, Dept. of Drug Discovery Support, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, BW, Germany; 2Precision Mechanics, Dept. of Site Operations, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, BW, Germany; 3Dept. of Radiology, Charité - University Medicine Berlin, Berlin, Germany; 4Dept. of Medical Informatics, Charité - University Medicine Berlin, Berlin, Germany

MR elastography (MRE) is a powerful tool for the non-invasive assessment of liver diseases. It requires the reliable delivery of shear waves in the acoustic frequency range between 25 and 1000 Hz. We present a novel concept of motion generation suitable for MRE of small animals based on a piezoelectric wave generator and a hydraulic transmission system. The new system provides excellent wave penetration of rat liver in the desired frequency range and yields reproducible and consistent results.

                  1056.     Detecting Breast Phantom Lesions with Acoustic Radiation Force in MR Images: Experiment and Finite-Element Simulations

Jessica Mende1, Marcus Radicke1, Anna-Lisa Kofahl1, Judith Schindler1, Deniz Ulucay1, Jürgen Finsterbusch2, Bernd Weber3, Karl Maier1

1HISKP, University of Bonn, Bonn, Germany; 2University Medical Center, University of Hamburg, Hamburg, Germany; 3NeuroCognition, Life & Brain, Bonn, Germany

Acoustic radiation contrast in magnetic resonance phase images is a recently developed method to image and quantify non-invasively the viscoelastic properties of tissue. A displacement sensitive MRI spin-echo sequence was used to image the displacement caused by the acoustic radiation force of ultrasound with a frequency of 2.5 MHz, a pulse length of 20 ms and an intensity of 35 W/cm2. To show the feasibility of this method, results of the detection of lesions in a breast elastography phantom are presented. Finite-element simulations show good agreement with the experimental data.

                  1057.     Tissue Stiffness Estimation Using Gaussian Filters for Prostate MR Elastography

Frank Zhao1, Arvin Arani1,2, Don Plewes1,2, Rajiv Chopra1,2

1Imaging Research, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; 2Medical Biophysics, University of Toronto, Toronto, Ontario, Canada

Transurethral MR elastography offers the potential to obtain high resolution stiffness images of the prostate gland. The purpose of this study was to adapt the local frequency estimator algorithm for the radial shear wave geometry associated with this approach. The stiffness estimates were compared between the conventional and modified LFE method.

                  1058.     Acoustic Radiation Contrast in Magnetic Resonance: Detection of Microcalcifications

Judith Schindler1, Deniz Ulucay1, Jessica Mende1, Marcus Radicke1, Anna-Lisa Kofahl1, Jürgen Finsterbusch2, Robert Krieg3, Karl Maier1

1HISKP, University of Bonn, Bonn, Germany; 2University Medical Center, University of Hamburg, Hamburg, Germany; 3Siemens Healthcare, Erlangen, Germany

One promising application of acoustic radiation contrast in magnetic resonance (ARC-MR) phase images is the detection of microcalcifications (tiny abnormal deposits of calcium) in breast tissue. Acoustic radiation force was applied using a custom-made MR-compatible piezoelectric transducer with a resonance frequency of 2,5 MHz. The thus produced displacement in the phantom was made visible with a displacement sensitive spin-echo sequence. The phantom was an agar/de-ionized water solution containing glass beads to get tissue-like ultrasound absorption.  Results show that an eggshell (1mmx1mm) that mimics the microcalcification is only visible in MR phase images when the ultrasound is turned on.

Drug Discovery

Hall B                        Wednesday 13:30-15:30                                                                                                        

                  1059.     Exploration of Resting State FMRI Metrics as Biomarkers of Central Nervous System Activation by Drug: Placebo Controlled FMRI Study of the Effect of the Analgesic Buprenorphine

Alexandre Coimbra1,2, Richard Baumgartner, 2,3, Dai Feng, 2,3, Shubing Wang3, Jaymin Upadhyay, 2,4, Adam Schwarz, 2,5, Julie Anderson, 2,4, Lauren Nutile, 2,4, Gautam Pendse, 2,4, James Bishop, 2,4, Ed George, 2,4, Smiriti Iyengar, 2,5, David Bleakman, 2,5, Richard Hargreaves, 2,6, Jeff Evelhoch1,2, David Borsook, 2,4, Lino Becerra, 2,4

1Imaging, Merck Research Laboratories, West Point, PA, United States; 2Imaging Consortium for Drug Development, Belmont, MA, United States; 3Biometrics, Merck Research Laboratories, Rahway, NJ, United States; 4PAIN, McLean Group, Belmont, MA, United States; 5Lilly Research Laboratories, Indianapolis, IN, United States; 6Neurosciences, Merck Research Laboratories, West Point, PA, United States

It has been suggested that fMRI functional connectivity metrics may be useful tools to test efficacy of CNS therapeuticals. This work provides initial exploration of functional connectivity approaches based on Independent Component Analysis.  This is done in the context of a Placebo Controlled study of Buprenorphine, a partial opioid agonist and antagonist. A set of previously reported fundamental resting state networks (RSNs) were examined comprising of medial visual, lateral visual, auditory system, sensory motor system, default mode network, executive control, dorsal visual stream. Treatment effects of Buprenorphine on functional connectivity metrics associated with each of these fundamental RSNs were examined.

                  1060.     Spinal Cord and Brain Pain FMRI in Rats: Anatomical Sites of Analgesic Action of Buprenorphine on the Noxious Electrical Stimulation-Induced Pain

Fuqiang Zhao1, Denise Welsh1, Mangay Williams1, Alexandre Coimbra1, Mark O. Urban2, Richard Hargreaves2, Jeffrey Evelhoch1, Donald S. Williams1

1Imaging Department, Merck Research Laboratories, West Point, PA, United States; 2Neuroscience Department, Merck Research Laboratories, West Point, PA, United States

To validate the fMRI signals in the spinal cord and the brain of rats induced by noxious stimulation as a pain biomarker, and to determine its utility in elucidation of mechanisms of action of analgesics, the effect of buprenorphine (BPN), a partial ì-opioid agonist, on pain fMRI signals was investigated. The pain fMRI signals in the caudate putamen and thalamus region were totally suppressed, while those in spinal cord, cerebellum, thalamic relay of somatosensory pathway, and primary somatosensory cortex were only partially (if at all) suppressed. Such a suppression pattern is consistent with the density of ì opioid receptor distribution in brain, supporting the idea that fMRI can provide anatomical action sites of the analgesics, which should help to understand their mechanisms of action.

                  1061.     Pharmacologic Resting State-FMRI: Effects of Cannabis on Functional Brain Connectivity ‘at Rest’

Roelof Peter Soeter1,2, Linda E. Klumpers3, Naj Khalili-Mahani1,2, Mark A. van Buchem1,2, Serge A.R.B. Rombouts1,2, Joop M.A. van Gerven, 3,4

1Department of Radiology, Leiden University Medical Center (LUMC), Leiden, Netherlands; 2Leiden Institute for Brain and Cognition (LIBC), Leiden, Netherlands; 3Centre for Human Drug Research, Leiden, Netherlands; 4Department of Neurology, Leiden University Medical Center (LUMC), Leiden, Netherlands

‘Resting state’ FMRI is a promising technique for drug studies, because it allows a repeated task-independent assessment of functional interactions between brain regions (functional connectivity). Here we investigate the effects of THC, the psychoactive compound of cannabis, on functional brain connectivity. Nine healthy male volunteers participated in a randomised, double blind, placebo-controlled trial in which 8 RS-FMRI scans were obtained in each treatment occasion. THC administration decreased connectivity in different brain regions, including cerebellum and several cortical regions. Functional connectivity using RS-FMRI is a promising new technique to study pharmacologically induced changes in brain activity.

                  1062.     On the Complexity of the BOLD Response to Painful Heat, Relationship of the Response with Self-Assessment of Pain and Implications for FMRI Sensitivity to Analgesic Treatment

Alexandre Coimbra1,2, Richard Baumgartner, 2,3, Sonya Apreleva, 2,3, Jaymin Upadhyay, 2,4, Adam Schwarz, 2,5, Julie Anderson, 2,4, Lauren Nutile, 2,4, Gautam Pendse, 2,4, James Bishop, 2,4, Ed George, ,2,4, Smiriti Iyengar, 2,5, David Bleakman, 2,5, Richard Hargreaves, 2,6, Jeff Evelhoch1,2, Lino Becerra, 2,4, David Borsook, 2,4

1Imaging, Merck Research Laboratories, West Point, PA, United States; 2Imaging Consortium for Drug Development, Belmont, MA, United States; 3Biometrics, Merck Research Laboratories, Rahway, NJ, United States; 4PAIN, McLean Group, Belmont, MA, United States; 5Lilly Research Laboratories, Indianapolis, IN, United States; 6Neurosciences, Merck Research Laboratories, West Point, PA, United States

The complexity of the experience of pain is reflected in the functional MRI BOLD response to painful stimuli. Several publications reported on a biphasic BOLD response composed of an early phase closely locked with stimulus time, and a late phase which some have suggested is related to self-assessment of pain. In a placebo controlled study of painful heat, the GLM approach was used to generate quantitative measures and address the issue of sensitivity of these endpoints to Buprenorphine treatment (BUP); with a focus on endpoints related to early, stimulus-locked, and late phase modeled by self-assessment.

                  1063.     Repeated Resting State FMRI During Dose-Controlled Morphine and Alcohol Infusion Reveals Localized and Drug Specific Changes in Functional Brain Connectivity

Najmeh Khalili-Mahani1,2, Remco W. M Zoethout3, Christian F. Beckmann4,5, Evelinda Baerends6, Roelof P. Soeter, 2,6, Marike de Kam3, Mark A. Van Buchem6, Joop M. A. Van Gerven3, Serge A. R .B. Rombouts, 2,6

1Leiden University Medical Center, Department of Radiology, Leiden , Netherlands; 2Leiden Institute for Brain and Cognition, Department of Psychology, Leiden, Netherlands; 3Center for Human Drug Research, Leiden University Medical Center, Leiden, Netherlands; 4Oxford University, Oxford, United Kingdom; 5Imperial College London, London, United Kingdom; 6Leiden University Medical Center, Department of Radiology, Leiden, Netherlands

Using state of art pharmacological infusion techniques in a placebo-controlled two-way (treatment by time: 3x7) repeated measure study we show specific and meaningful variations in resting-state brain connectivity in response to dose-controlled administration of morphine and alcohol

                  1064.     Focal and Drug-Specific Changes in Cerebral Blood Flow in Response to Dose-Controlled Infusion of Alcohol and Morphine in Healthy Young Men

Najmeh Khalili-Mahani1,2, Mathiass J. P. Van Osch1, Remco W. M Zoethout3, Evelinda Baerends1, Mark A. Van Buchem1, Joop M. A. Van Gerven3, Serge A. R. B. Rombouts1,2

1Leiden University Medical Center, Department of Radiology, Leiden, Netherlands; 2Leiden Institute for Brain and Cognition, Department of Psychology, Leiden, Netherlands; 3Center for Human Drug Research, Leiden University Medical Center, Leiden, Netherlands

In a within-subject placebo-controlled pharma-fMRI study, we use pseudo-continuous ASL to show localized and drug-specific changes in CBF in response to dose-controlled infusion of morphine and alcohol. Results correspond to variations observed in the resting-state BOLD fluctuations in the same study.

                  1065.     Levo-Tetrahydropalmatine Treatment Attenuates Heroin-Priming Induced BOLD Responses in Heroin-Dependent Rats

Xiping Liu1, Zheng Yang2, Jun Xie3, Qian Yin1, Shi-Jiang Li1

1Biophysics, Medical College of Wisconsin, Milwaukee, WI, United States; 2Beijing Institute of Basic Medical Science, China; 3GE Healthcare, United States

Levo-tetrahydropalmatine (l-THP), purified from the Chinese herb, Stephanie, recently has been demonstrated to be effective in attenuating heroin craving and relapse in heroin addicts; it also inhibits cocaine¡¯s rewarding effects on animal models. Despite this behavioral evidence, the treatment mechanisms of l-THP for drug addiction have yet to be elucidated. Here, we applied high-field pharmacological MRI (phMRI) on heroin-dependent rats with or without chronic l-THP treatment. We found l-THP significantly attenuates heroin-priming induced BOLD responses in heroin-dependent rats in multiple addiction relevant neural circuitries.

                  1066.     Pharmacological Analysis in Experimental Lung Fibrosis Performed by MRI

Anna Louise Babin1, Catherine Cannet1, Christelle Gerard1, Clive P. Page2, Nicolau Beckmann1

1Global Imaging Group, Novartis Institutes for BioMedical Research, Basel, BS, Switzerland; 2Sackler Institute of Pulmonary Pharmacology, King's College, London, SE1 1UL, United Kingdom

Experimental studies of lung fibrosis in animals have usually examined the effects of treatments starting before or at the time of lung injury. However, treatment in humans only begins after disease has been established. Since timing of treatment initiation is critical in this chronic model, we used MRI to assess non-invasively the effects of steroids (budesonide and dexamethasone) in the lungs of bleomycin (BLM) treated rats. MRI relying on non-ionizing radiation opens new avenues in testing compounds in vivo as the responses at several time points during the course of treatment can be easily compared.

                  1067.     Tumor-Targeted Imaging and Delivery of SiRNA

Zdravka Medarova1, Mohanraja Kumar1, Anna Moore1

1Molecular Imaging Lab, Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, United States

Since their discovery in 1998, small interfering RNAs (siRNAs) have emerged as a powerful new tool for post-transcriptional gene silencing. Here, we describe the synthesis and testing of a tumor-targeted nanoparticle probe (MN-EPPT-siSurvivin) to specifically shuttle siRNA to tumor cells. The probe binds the tumor antigen uMUC-1, found on a range of adenocarcinomas, and useful as an imaging target. Human breast, pancreatic, and colorectal cancer cells took up high amounts of the probe. The uptake could be measured by MRI and resulted in significant knock-down of the target gene.

                  1068.     A Novel Mitochondrial Peptide Causes Recovery of Skeletal Muscle After Burn Trauma as Assessed with P31 NMR and Electron Paramagnetic Resonance in Vivo

Valeria Righi1,2, Caterina Constantinou, 1,3, Dionyssios Mintzopoulos1,2, Nadeem Khan4, Sriram P. Mupparaju4, Harold M. Swartz4, Hazel H. Szeto5, Ronald G. Tompkins6, Laurence G. Rahme3, A Aria Tzika1,2

1NMR Surgical Laboratory, Department of Surgery, Massachusetts General Hospital and Shriners Burns Institute, Harvard Medical School, Boston, MA, United States; 2Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Athinoula A. Martinos Center for Biomedical Imaging, Boston, MA, United States; 3Molecular Surgery Laboratory, Department of Surgery, Massachusetts General Hospital and Shriners Burns Institute, Harvard Medical School, Boston, MA, United States; 4EPR Center for Viable Systems, Department of Diagnostic Radiology, Dartmouth Medical School, Hanover, NH, United States; 5Department of Pharmacology, Joan and Sanford I. Weill Medical College of Cornell University, New York, NY, United States; 6Department of Surgery, Division of Burn, Massachusetts General Hospital and Shriners Burns Institute, Harvard Medical School, Boston, MA, United States

Using P31 NMR and Electron Paramagnetic Resonance (EPR) in vivo, we evaluated the effects of a novel (Szeto-Schiller) SS-31 peptide on ATP synthesis rate and redox status, respectively in a clinically relevant burn trauma model. Our results showed that SS-31 peptide induces ATP synthesis rate and causes recovery of the mitochondrial redox status at 6 hours after burn. Thus, EPR, can be used to complement NMR in investigating, and even validating novel mitochondrial agents for burn trauma and a variety of pathologies (i.e., stroke, heart failure, diabetes, degenerative disorders, trauma, cancer) associated with mitochondrial dysfunction, including normal aging.

                  1069.     A Texture Analysis Approach to Quantify Ventilation Changes in Hyperpolarised 3He MRI of the Rat Lung in an Asthma Model

Frank Risse1, Jelena Pesic1, Simon Young2, Lars E. Olsson1

1DECS Imaging & Antibodies, AstraZeneca R&D, Mölndal, Sweden; 2Bioscience, AstraZeneca R&D, Charnwood, United Kingdom

The effect of steroid (budesonide) treatment on lung inflammation in rats caused by ovalbumin can be visualised using hyperpolarised 3He MRI. The aim was to quantify the changes in lung ventilation in this asthma model using texture analysis. Four groups were investigated: controls, vehicle-treated, low and high dose budesonide-treated. First-order texture, geometrical features and features based on second-order statistics using run-length and grey-level co-occurrence matrices were calculated. Additionally, wavelet transforms were applied to compute first-order statistics on multiple scales. The texture analysis showed significant differences between the untreated and the budesonide-treated groups, which was in agreement with a biological marker.

                  1070.     Influence of Drug Substances with Different Solubility on Hydration Processes of Prolonged Release Tablets

Anna Mlynarczyk1, Marco Gruwel2, Piotr Kulinowski1, Krzysztof Jasinski1, Przemyslaw Dorozynski3, Boguslaw Tomanek, 12, Wladyslaw P. Weglarz1

1Department of Magnetic Resonance Imaging, Institute of Nuclear Physics Polish Academy of Sciences, Krakow, Poland; 2Institute for Biodiagnostics, National Research Council of Canada, Winnipeg, Manitoba, Canada; 3Department of Pharmaceutical Technology and Biopharmaceutics, Jagiellonian University, Krakow, Poland

MR microscopy was applied for study of water mobility and concentration in tablets, used for drug delivery. The tablets made of Hydroxypropylmethylcellulose-HPMC with and without addition of a drug substance of different solubility (L-dopa and ketoprofen) were tested. Two-dimensional T2 and proton density (PD) maps and their histograms were obtained. Spatial T2 and PD distributions along a tablet radius were also analyzed. Different mechanisms of tablets hydration were observed due to composition of the formulations, eg. for formulation with ketoprofen (low solubility of 0,24 mg/mL) the hydrogel formation was negligible.

                  1071.     Hepato and Renal Protective Effect of Bacosides Against Aluminium Insult in Rats: A Proton Magnetic Resonance Study on Serum and Urine

Deepa Prajapati1, Sundeep Tripathi2, Sanjay Annarao1, Abbas Ali Mahdi2, Mahdi Hasan3, Farzana Mahdi4, Raja Roy1, Chunni Lal Khetrapal1

1CBMR, Centre of Biomedical Magnetic Resonance, Lucknow, Uttar Pradesh, India; 2CSM Medical University; 3Anatomy, CSM Medical University; 4Era's Lucknow Medical College

Prolonged aluminium insults results in oxidative damage leading to hepato and nephrotoxicity in rats.1H NMR study of rat’s serum and urine have been utilized to evaluate the comparative protective effects of Bacosides and Donepezil drugs over continuous Aluminium- induced metabonomic changes. Bacosides was found to markedly attenuate the oxidative stress induced by Aluminium over long term (90 days) dose compared to Donepezil. This might be interpretated in terms of strong antioxidative property of Bacosides compared to Donepezil. The study suggests that 1H NMR metabolic profiling is an efficient method to explore the efficacy of potent molecules over metal toxicity.

                  1072.     Effect of Varenicline on BOLD and Neural Networks in Awake Animals

Wei Chen1, Joseph R. DiFranza2, Jean King3

1Department of Psychiatry, University of Massachusetts Medical School, Worcester, MA, , United States; 2Department of Family Medicine and Community Health,, University of Massachusetts Medical School, Worcester; 3Department of Psychiatry, University of Massachusetts Medical School, Worcester, MA, United States

Tobacco dependence is the most preventable cause of death. Varenicline is a partial nicotinic receptor agonist/antagonist that is widely used as a smoking cessation aid.  How varenicline helps smokers is unknown.  We sought to compare the brain Blood oxygenation level dependent (BOLD) activation produced by a high dose varenicline to a lower dose varenicline in awake naïve animals, which hopes to assist in understanding the action of this partial nicotinic receptor agonist/antagonist in patients.

Outcomes: Cost Effectiveness etc.

Hall B                        Thursday 13:30-15:30                                                                                                           

                  1073.     The EMITEL Multilingual Dictionary: A New Resource for the Global MRI Community

Stephen Frederick Keevil1,2, Gerard Boyle3, Emil Lindholm4, Franco Milano5, Freddy Stahlberg4, Ronnie Wirestam4, Slavik Tabakov2, Andrew Simmons6

1Medical Physics, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom; 2Imaging Sciences, King's College London, London, United Kingdom; 3St James's Hospital, Dublin, Ireland; 4University of Lund, Lund, Sweden; 5University of Florence, Florence, Italy; 6Centre for Neuroimaging Sciences, King's College London, London, United Kingdom

A mutilingual dictionary of terms used in MRI and other medical physics specialties has been developed by an international network of over 200 physicists and engineers. The dictionary (available free at www.emitel2.eu) allows translation of terms between 25 languages, with extension to additional languages planned for the future. The software platform was developed to be as simple as possible without compromising content, allowing easy update and maximising longevity. The dictionary can be used as a free-standing resource or as a portal to an e-encyclopaedia of medical physics. Together, the dictionary and encyclopaedia are valuable resources for the worldwide MRI community.

                  1074.     Long Term Vascular Access Ports as a Means of Sedative Administration in a Rodent FMRI Survival Model

Patrick C. Hettinger1, Rupeng Li2, Ji-Geng Yan1, Hani S. Matloub1, Young R. Cho1, Matthew L. Runquist2, Christopher P. Pawela1,2, James S. Hyde2

1Plastic Surgery, Medical College of Wisconsin, Milwaukee, WI, United States; 2Biophysics, Medical College of Wisconsin, Milwaukee, WI, United States

The purpose of this study is to develop a rodent survival model that enables fMRI at multiple time-points under sedation.  In this study, 9 Sprague-Dawley rats underwent surgical placement of a long-term vascular access port.  The animals were then imaged using fMRI during nerve stimulation at 1 week, 3 weeks, and 5 weeks post-operatively. During imaging, all animals breathed spontaneously while intravenous sedative was administered through the port.  To date, all animals have successfully been imaged at each time-point.  All vascular access ports have remained patent, making these devices a viable option for longitudinal MRI studies requiring venous access.

                  1075.     A Low-Cost Experimental Set-Up for Functional Magnetic Resonance Imaging

Carolina Arboleda1,2, Cristián Andrés Tejos1,2, Sergio Uribe, 2,3, Francisco Zamorano4, Francisco Aboitiz4, Pablo Irarrazaval1,2

1Electrical Engineering Department, Pontificia Universidad Católica de Chile, Santiago, Chile; 2Biomedical Imaging Center, Pontificia Universidad Católica de Chile, Santiago, Chile; 3Radiology Department, Pontificia Universidad Católica de Chile, Santiago, Chile; 4Cognitive Neuroscience Laboratory, Pontificia Universidad Católica de Chile, Santiago, Chile

An fMRI setup for stimuli presentation, should include a coupling circuit to connect the MR-scanner output pulse to the computer that presents the stimuli (scanner trigger detector, STD), and a Response-Detection Pad (RDP) which needs to be placed inside the scanner and, thus, can not contain any ferromagnetic materials. Currently, there are several RDC and STD commercially available, but their cost is significantly high (~3,000 USD + shipment). Here, we propose a cheap (~155 USD + shipment) setup that includes a fiber optic RDP and a photo coupler-based STD, and is compatible with current scanners and fMRI software.

                  1076.     NSF Risk Factors

Honglei Zhang1, Giles H. Roditi2, Tim Leiner3, Walter Kucharczyk4, Martin R. Prince1

1Radiology, Weill Medical College of Cornell University, New York, NY, United States; 2Radiology, Glasgow Royal Infirmary, Scotland; 3Maastricht University Hospital, Netherlands; 4University of Toronto, Toronto, Ontario, Canada

Concern about the association between GBCA and NSF has led to widespread screening of MRI patients for renal dysfunction and withholding GBCA when GFR is < 30 mL/min.  Analysis of 78 retrospective case series reporting 292 NSF cases explores the risk factors for NSF.  Elimination of multiple risk factors by using single dose GBCA, dialyzing dialysis patients quickly following GBCA administration, avoiding GBCA in acute renal failure while serum creatinine is rising, and avoiding non-ionic linear GBCA in renal failure patients, may reduce NSF risk more than a thousand fold, thereby allowing safe GBCA enhanced MRI in virtually all patients.