Bhanu Prakash KN¹, Sanjay K Verma¹, Yevgen Marchenko¹, Sankar Seramani¹, Suresh Anand Sadananthan², Navin Michael², Charmaine Childs³, Lu Jia⁴, Andrew A. Maudsley⁵, and Sendhil Velan S^1,6
1Laboratory of Molecular Imaging, Singapore Bioimaging Consortium, Singapore, Singapore, ²Singapore Institute for Clinical Sciences, Singapore, Singapore, ³Centre for Health and Social Care Research, Faculty of Health and Wellbeing, Sheffield Hallam University, Sheffield, United Kingdom, ⁴Combat Protection and Performance Lab, Defence Medical and Environmental Research Institute, DSO National Laboratories, Singapore, Singapore, ⁵Miller School of Medicine, University of Miami, Miami, Florida, United States, ⁶Clinical Imaging Research Centre, Singapore, Singapore

Whole brain temperature mapping is of great interest for investigating traumatic brain injuries. Single-voxel-spectroscopy (SVS) and CSI approaches provides limited spatial coverage in the brain, whereas 3D Echo-planar spectroscopic imaging (EPSI), covers the entire brain for investigating temperature and metabolism in traumatic brain injury (TBI) subjects. Our study aims at implementation of EPSI, calibration and validation of the temperature measurement in brain phantoms using EPSI and SVS at pre-clinical and clinical scanners, to study and analysis of whole brain temperature in TBI studies on rodents and humans.

Jacob Penner^1,2 and Robert Bartha^1,2
1Centre for Functional and Metabolic Mapping, Robarts Research Institute, London, Ontario, Canada, ²Medical Biophysics, Western University, London, Ontario, Canada

Magnetic resonance spectroscopy suffers from inherent low sensitivity; it is advantageous to increase the magnetic field strength and therefore the signal-to-noise ratio. The purpose of this study was to develop a 7 Tesla in vivo short echo time semi-LASER MR spectroscopy protocol incorporating subject-specific macromolecule removal, yielding absolute metabolite concentrations. MRS data were obtained from the parietal-occipital region of five young healthy volunteers. Absolute levels were in good agreement with previous studies that reported in vivo metabolite concentrations at 7 Tesla in young healthy subjects. Therefore, this protocol is suitable for measuring metabolic changes in neuropathological conditions.

Jeffrey Adam Kasten^1,2, François Lazeyras², and Dimitri Van De Ville^1,2
1Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Vaud, Switzerland, ²Department of Radiology and Medical Informatics, Université de Genève, Geneva, Geneva, Switzerland

Both Fourier and traditional model-based approaches for MRSI reconstruction remain impeded by certain foundational confines, for example, the restriction to coarse rectangular voxels in the former, and the dependence upon water-based structural scans in the later. To overcome these limitations, we recently proposed a novel component-based method, which estimates a low-rank bilinear signal model from the raw measurements with the aid of a few geometrical assumptions. We demonstrate the efficacy of our routine on 1H in vivo 2D MRSI data, exploiting the full 3D information imparted by a static field map acquired over the MRSI slice thickness.

Thomas Kirchner¹, Ariane Fillmer¹, Klaas P Pruessmann¹, and Anke Henning^1,2
1Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland, ²Max Planck Institute for Biological Cybernetics, Tuebingen, Germany

Residual B₀ inhomogeneity after shimming leads to incoherent spatial averaging due to phase and frequency variations over the FOV. We extended the previously introduced Overdiscretized Target-Driven MRSI reconstruction method to take B₀ variations into account in a quasi-continuous manner. A gain in SNR is achieved compared to conventional voxel-wise B₀ correction.

Toru Shirai¹, Satoshi Hirata¹, Yo Taniguchi¹, Yoshihisa Soutome², Yoshitaka Bito², and Hisaaki Ochi^1
1Central Reseach Laboratory, Hitachi, Ltd., Kokubunji, Tokyo, Japan, ²MRI System Division, Hitachi Medical Corporation, Kashiwa, Chiba, Japan

We have applied a method that acquires simultaneously the water and metabolite signals using multi-coil sensitivities for proton chemical shift imaging (CSI) thermometry. The method consists of measurement shifting only the water signal on the image, and a data process separating the water and metabolite signals using the coil sensitivity difference. The results of a cooled phantom experiments revealed that the method may be useful for acquiring temperature map without increasing scan time and contaminating the frequency modulation sidebands caused by water signal.

Brian J. Soher¹, William E Wu², Ke Zhang², James S Babb², Assaf Tal², and Oded Gonen^2
1Radiology, Duke University Medical Center, Durham, NC, United States, ²Radiology, New York University School of Medicine, NY, United States

An automated paradigm for operator independent fit of whole-head proton MR spectra is shown. The means (12.9 and 12.9 mM) and standard deviations (2.7 and 2.0 mM) for previously validated manual integration versus the new automated fitting method are not statistically different, validating the new approach against the previous paradigm which also provides quantitative metrics for fit quality. The utility of WBNAA to monitor diffuse neurological diseases through neuronal integrity in the entire brain is improved and the susceptibility to operator and baseline bias is removed, enhancing the usefulness of the approach to monitor global disease progression and treatment effects.

Yi Zhang^1,2, Jinyuan Zhou^1,3, and Paul Bottomley^1,2
1Department of Radiology, Johns Hopkins University, Baltimore, MD, United States, ²Department of ECE, Johns Hopkins University, Baltimore, MD, United States, ³F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States

The low spatial resolution typical of chemical shifting imaging (CSI) studies causes partial volume errors and signal bleed, especially in voxels near the scalp. The standard solution is to apply spatial apodization filters, which adversely affect spatial resolution. Here, a novel automated strategy for partial volume correction employing grid shifting (PANGS), is presented that minimizes partial volume bleed without compromising spatial resolution. PANGS is applied to significantly reduce lipid artifacts in 1H brain CSI and metabolite maps, and to improve metabolite detection in cortical regions.

Sai Krishna Merugumala¹, Huijun Liao¹, Nick Bolo², Elisabetta Del Re³, Robert William McCarley³, and Alexander Paul Lin^1
1Radiology, Brigham and Women's Hospital, Boston, MA, United States, ²Psychiatry, Beth Israel Deaconess Medical Center, Boston, MA, United States, ³Psychiatry, Veterans Affairs Boston Healthcare System, Brockton, MA, United States

Abnormalities in the GABA levels in the brain are associated with the symptoms of Schizophrenia and Schizotypal Personality Disorder. Estimating GABA with MRS using MEGA-PRESS in brain ROIs like the auditory cortex is complicated by inherent problems with the spectral edited MRS and issues such has gray matter volume loss in the subjects. A method for improving the resulting MEGA-PRESS difference spectrum is spectral alignment where frequency and phased are optimized. After spectral alignment, the variation between subject scans is reduced and correlation with electrophysiology improved with the additional processing step.

Dimitri MARTEL¹, Jean-Baptiste Langlois², Denis Friboulet¹, Olivier Beuf¹, and Hélène Ratiney^1
1CREATIS; CNRS UMR 5220 ; INSERM U1044 ; Université Lyon 1 ; INSA Lyon, Villeurbanne, France, ²CERMEP-Imagerie du Vivant, Bron, France

Recent studies have demonstrated the ability of 1D MRS to assess in vivo hepatic fatty composition. In this study, we evaluate the use of the 2D Localized Correlation Spectroscopy (LCOSY) to analyze lipid composition of fatty liver of ob/ob mice and compare it to 1D MRS . Our results show that LCOSY can be used for the study of fatty liver to derive quantitative indexes in a more robust way than 1D MRS.

Tzai-You Wu¹, Chun-Hao Fang¹, Yi-Ru Lin¹, and Shang-Yueh Tsai^2
1Electronic and Computer Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan, ²Graduate Institute of Applied Physics, National Chengchi University, Taipei, Taiwan

Quantification of £^-Aminobutyric acid (GABA) assessed by MEGA-PRESS sequence need to be carefully investigated because of its low concentration and can be sensitive to editing efficiency. In this study the inter- and intra-subject reproducibility of GABA quantified using three quantification methods including integration, fitting using two Gaussian shape and LCModel is investigated. GABA spectra were collected from sixteen healthy subjects in visual cortex. Results showed that three quantification methods exhibit similar intra-subject CV ranging from 11.1% to 15.3%. GABA+ quantified by direct integration is relatively stable among three quantification methods, which implies simple quantification strategy is sufficient for GABA spectra.

Marianne Cleve¹, Alexander Gussew¹, Patrick Hiepe¹, Reinhard Rzanny¹, and Jürgen R. Reichenbach^1
1Medical Physics Group, Institute of Diagnostic and Interventional Radiology I, Jena University Hospital - Friedrich Schiller University Jena, Jena, Germany

In the present study in vitro measurements were performed to evaluate the accuracy and reproducibility of GABA detection with ¹H-MEGA-PRESS. Spectra were acquired in a phantom containing several metabolites of defined concentrations emulating their composition in the brain. The obtained spectra were used to simulate in vivo conditions by reducing SNR_GABA and broadening linewidths. It was figured out that for sufficiently small CVs (< 7 %) a SNR_GABA of at least 2 is required, whereas for SNR_GABA > 6 the CVs remain independent of FWHM. These results were compared to an in vivo investigation in one healthy volunteer.

Helen Wu¹, Dhruman Goradia², and Jeffrey Stanley^2
1Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, United States, ²Psychiatry and Behavioral Neurosciences, Wayne State University School of Mediciney, Detroit, MI, United States

When using a 1H or 31P multi-voxel technique for detecting biochemical changes in longitudinal studies, the precise and consistent voxel placement at desired anatomical regions of interest is frequently a great challenge. Here we propose a novel method which takes advantage of the ability to re-shift the CSI voxel grid after data has been collected as well as orientation information provided by same-session volumetric T1 image sets. This fully automated method is able to systematically place voxels in pre-defined anatomical locations, after which MRS signals are extracted from those voxels for quantification.

Anders Tisell^1,2 and Peter Lundberg^1,2
1Radiation Physics, Department of Medicine and Healths Sciences, Linköping University, Linköping, Sweden, ²Centre for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden

Quantitative Magnetic Resonance Spectroscopy (qMRS) provides direct information of the metabolic status of the investigated tissue. Unfortunately, most current approaches do not provide absolute metabolite concentrations. Recently a method was proposed for correction of the water relaxation effects based on the use of quantitative MRI (qMRI). The purpose of the present work was to investigate how large the concentration differences were between such measurements obtained using a 1.5 T system, or a 3.0 T MRI-scanner. Moreover, another aim was to determine to what extent the calibration method would improve the accuracy of the determined concentrations, compared to conventional water scaling. Using qMRI for calibration of the internal water increased the accuracy of the estimated metabolite concentrations significantly. Due to the relative simplicity of such measurements we would recommend such approach whenever absolute metabolite concentrations are required.

Diego Hernando¹, Nathan S. Artz¹, Gavin Hamilton², Alejandro Roldan¹, and Scott B. Reeder^1,3
1Radiology, University of Wisconsin-Madison, Madison, WI, United States, ²Radiology, University of California, San Diego, San Diego, CA, United States, ³Medicine, University of Wisconsin-Madison, Madison, WI, United States

Multi-echo liver spectroscopy enables rapid and robust fat quantification. However, post-processing of spectroscopy data is often cumbersome, requiring manual interaction (ie: semi-automatic), which has precluded its widespread dissemination. In this work, we have developed a fully automated algorithm for fat quantification from multi-echo spectroscopy datasets. This algorithm performs simultaneous fitting of spectra at multiple echo times. We have validated this automated algorithm on 425 datasets (1.5T: 152 datasets, 3T: 273 datasets), by comparing its results to the current semi-automatic technique. Excellent correlation and agreement was observed at both field strengths, demonstrating the potential of this approach for spectroscopy-based fat quantification.

Lucian A. B. Purvis¹, William T. Clarke², Luca Biasiolli², Matthew D. Robson², and Christopher T. Rodgers^2
1Department of Chemistry, University of Oxford, Oxford, United Kingdom, ²Department of Cardiovascular Medicine, University of Oxford, United Kingdom

The AMARES spectroscopic fitting algorithm was re-implemented in Matlab to facilitate the use of new types of prior knowledge. We demonstrate the new fitting code by implementing linewidths constraints. First, the relative linewidths were calculated for a batch of cardiac data. There were used as prior knowledge in constrained AMARES fitting, which was compared against unconstrained AMARES using Monte Carlo simulations and in the leg in vivo. We show that the linewidth constrained fitting is more accurate and more consistent in data with an SNR<30. This linewidth-constrained AMARES approach will be useful for exercise protocols and for saturation- and inversion-recovery.

Charlie Yi Wang¹, Ya Chen², and Xin Yu^1
1Biomedical Engineering, Case Western Reserve University, Cleveland, OH, United States, ²Case Western Reserve University, Cleveland, OH, United States

Estimation of intracellular redox state using measured NADH/NAD+ ratio through 31P spectroscopy is an attractive tool, as alternative methods for direct assessment are invasive in nature. In this study, we assess the ability of 31P MRS to quantify the NADH/NAD+ ratio during ischemia/reperfusion injury in perfused rat heart.

Chao Ma¹, Fan Lam^1,2, Curtis L. Johnson¹, and Zhi-Pei Liang^1,2
1Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States, ²Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States

Limited k-space data are often acquired in conventional 1H MRSI experiments. However, the strong leakage of nuisance lipid signals from the subcutaneous lipid layer of the brain can significantly complicate spectrum quantitation in brain MRSI. Removal of such lipid signals is desirable but challenging, because they appear as strong, multiple-peak, and broad spectra, overlapping with the spectra of other important brain metabolites. In this work, we propose a novel method to solve this classical problem using a new spatial-spectral model. In vivo experiments at 3T showed that the proposed method is very effective in removing lipid signals from brain MRSI data.

Yoojin Lee¹, Tae Kim¹, Tiejun Zhao², Jullie W. Pan¹, and Hoby P. Hetherington^1
1Department of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States, ²Siemens Medical Solution USA, INC., Siemens MediCare USA, Pittsburgh, Pennsylvania, United States

In this study, we use B1 inhomogeneity correction method in MPRAGE image to improve tissue segmentation at 7T and apply this accurate segmentation result for more precise metabolic analysis for MRSI. The data set of percent GM from segmentation results and Cr/NAA from MRSI data was used for linear regression analysis. The patient data was also acquired and compared with the linear regression result of normal subject data.

Jan Willem van der Veen¹, Stefano Marenco², and Jun Shen^1
1Magnetic Resonance Spectroscopy Core, NIH, NIMH, Bethesda, Maryland, United States, ²NIH, NIMH, Maryland, United States

Due to the time constraint of many clinical studies, it is highly desirable to acquire glutamate, glutamine and GABA in a single scan. In this study 141 GABA editing scans were fitted with a basis set of nine metabolite signals simulated by GAMMA with a novel fitting procedure to extract concentrations of glutamate, glutamine, and GABA, taking advantage of the partial spectral separation of glutamate and glutamine by the GABA editing pulse. The high SNR afforded by averaging the large number of spectra also allowed in vivo validation of metabolite chemical shifts and J coupling constants.

Elijah George^1,2, Steve Roys², and Rao Gullapalli^2
1Bioengineering, University of Maryland, College Park, Maryland, United States, ²Magnetic Resonance Research Center, University of Maryland Baltimore, School of Medicine, Baltimore, Maryland, United States

The aim of the current study is to optimize the precision with which low SNR metabolites in short echo time spectroscopic imaging data are quantified. We have developed an algorithm that can be used to minimize the glutamate/glutamine Cramer-Rao Lower Bound (CRLB) value generated by LCModel on a voxel-wise basis.

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

For a long time, muscle acidification and accumulation of lactate and acetyl groups have been measured either invasively by biopsies or noninvasively by separate MRS techniques targeting on each individual metabolites. The current study was designed to monitor exercise-induced changes in pH, lactate and acetyl-carnitine in human skeletal muscle using a single localized 1H MRS protocol, with pH reported by carnosine imidazole H4 signal, lactate by its methine signal at 4. 1 ppm and acetyl-carnitine by its acetyl signal at 2.12 ppm. This technique provides an easy access to important metabolic information on multiple pathways in skeletal muscle in vivo.

Christian Labadie¹, Thomas Siegert¹, Enrico Reimer¹, Maria Guidi¹, Miguel Martinez-Maestro¹, Harald E. Möller¹, Robert Turner¹, and Jessica Schulz^1
1Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany

The coherent accumulation of PRESS scans suffers from head motion and frequency drift. We present an adaptive approach consisting of fetching the current position of the head before each scan using an embedded set of three cameras placed near the head coil, and determining the frequency from the transverse magnetization of the water protons after the first frequency selective 90° saturation pulse of the WET water suppression scheme.

Andrew Bresnen¹ and Timothy Q. Duong^1
1UTHSCSA - Research Imaging Institute, San Antonio, Tx, United States

This study developed a quick and robust protocol for measurement of the forward creatine kinase rate of ATP synthesis (k_f,CK ) in the rat brain at 11.7T. We adopted the ³¹P Four Angle Saturation Transfer (³¹P FAST) experiment to minimize the TR, by using low flip angles, and the number of data points required to calculate to k_f,CK . Historically, in vivo ³¹P MT experiments suffer from low SNR resulting in long scan times, often on the order of hours. The optimized protocol provides robust measurements of k_f,CK in ~5mins.k_f,CK in normal rat brains was 0.31±0.03s-1.

Fan Lam^1,2, Chao Ma², T. Kevin Hitchens³, Curtis L. Johnson², Chien Ho³, and Zhi-Pei Liang^1,2
1Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, United States, ²Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, IL, United States, ³Pittsburgh NMR Center for Biomedical Research, Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, United States

We recently proposed a new approach to high-resolution MR spectroscopic imaging, called SPICE (SPectroscopic Imaging by exploiting spatiospectral CorrElation), which uses subspace modeling and hybrid acquisition of (k,t)-space data. In this work, we present experimental results from both rat and human brains to demonstrate the unprecedented capability of SPICE for in vivo high-resolution spectroscopic imaging. More specifically, SPICE obtained spatiospectral reconstructions with 0.5mm in-plane resolution from a rat brain in 34 minutes and 2.5mm in-plane resolution from a human brain in 12 minutes, both with minimal SNR loss compared to low-resolution CSI acquisitions and significant gain in SNR compared to high-resolution EPSI acquisitions.

Ioannis Angelos Giapitzakis¹, Tingting Shao¹, Nikolai Avdievich¹, Roland Kreis², and Anke Henning^1,3
1Dept. of High-Field Magnetic Resonance, Max Planck Institute for Biological Cybernetics, Tübingen, Baden-Württemberg, Germany, ²Departments of Radiology and Clinical Research, University of Bern, Bern, Switzerland, ³Institute for Biomedical Engineering, University and ETH Zürich, Zürich, Switzerland

Asymmetric adiabatic pulses have been used for metabolite cycled 1H-MRS at 3 Tesla and 7 Tesla enabling better spectral resolution and post-processing of the measured data without scan time prolongation. In this abstract, the frequency excitation profile of the adiabatic pulses was extensively studied with regards to time duration, the B₁⁺ field and the frequency sweep range. Optimum values for the characteristics of the inversion pulses were found for implementation in a STEAM sequence at 9.4T. Both phantom and in vivo measurements on a healthy volunteer verified the simulations and showed that metabolite cycled 1H-MRS is feasible at 9.4T.

Christopher T. Rodgers¹, William Clarke¹, Dominik Berthel², Stefan Neubauer¹, and Matthew Robson^1
1Radcliffe Department of Medicine, Univ Oxford, Oxford, United Kingdom, ²Rapid Biomedical GmbH, Germany

Applications of ³¹P-MRS have been hampered by low SNR. We recently introduced cardiac ³¹P-MRS at 7T with a 10cm loop, where SNR increased 2.8x vs 3T. Now, we introduce a 16-element cardiac array. This array has receive SNR 3.6x higher than our standard 3T coil in phantoms. In 5 men, extrapolating to fully-relaxed 90° spectra, we see 75% gains in potential SNR vs the 10cm loop. However, the array's B₁⁺ is inadequate, making skeletal muscle saturation difficult and necessitating short TRs for optimal SNR which exacerbate uncertainties in blood- and saturation-correction leading to implausibly high measured PCr/ATP ratios.

Sungtak Hong¹, Christoph Juchem¹, Peter B. Brown¹, Kevin L. Behar^1,2, and Robin A. de Graaf^1
1MR Research Center (MRRC), Yale University School of Medicine, New Haven, Connecticut, United States, ²Psychiatry, Yale University School of Medicine, New Haven, Connecticut, United States

In situ 3D magnetic resonance spectroscopic imaging (MRSI) was combined with focused-beam microwave irradiation (FBMI) and multicoil (MC) shimming. MC shimming has previously been shown to greatly improve the magnetic field homogeneity in vivo. Similar improvements were achieved on the FBMI samples as judged from B0 maps and water 3D MRSI datasets. As a demonstration of the improved data quality GABA-edited 3D MRSI was performed.

Alessandra Toncelli^1,2, Ralph Noeske³, Mauro Costagli⁴, Valentina Domenici⁵, Gianni Tiberi⁴, Mirco Cosottini⁶, and Michela Tosetti^7
1Department of Physics, University of Pisa, Pisa, Italy, ²Sezione di Pisa, INFN, Pisa, Italy, ³Applied Science Laboratory, GE Healthcare, Berlin, Germany, ⁴Fondazione IMAGO7, Italy, ⁵Dipartimento di Chimica e Chimica Industriale, University of Pisa, Italy, ⁶Dipartimento di Ricerca Traslazionale e delle Nuove Tecnologie in Medicina e Chirurgia, University of Pisa, Italy, ⁷Stella Maris Scientific Institute, Italy

We propose a novel spectroscopic method called STEAM-MIxing TIme Subtraction (STEAM-MiTiS) which consists in acquiring two different STEAM spectra with same TE, but different TMs peculiar for each J-coupled metabolite. This technique permits to cancel the contribution of singlet lines and leaves the J-coupled signals, only. The STEAM-MiTiS method has been optimized for the detection of Glutamate. Simulation results yielded the optimum parameter values that we used for both in-vitro and in-vivo validation. Experiments indicated an almost perfect cancellation of singlet and macromolecule signals, and resulted in clear editing of the Glutamate peak whose intensity scaled linearly with its concentration.

Clark Lemke¹, Aaron Hess², Velicia Bachtiar¹, Stuart Clare¹, Charlotte Stagg¹, Peter Jezzard¹, and Uzay Emir^1
1FMRIB, University of Oxford, Oxford, Oxfordshire, United Kingdom, ²OCMR, University of Oxford, Oxford, Oxfordshire, United Kingdom

Dynamic B0 shimming enables rapid switching between different B0 shim solutions for multiple locations to better optimize spectroscopy sequence performance. This can further be improved by dynamically applying different flip angles for each location. This technique is employed to acquire metabolite concentrations from 2 voxels located in the motor cortex of each hemisphere in an interleaving fashion. This procedure is presented alongside single voxel measurements and the neurochemical profiles from 3 subjects are presented. Results suggest that dynamic B0 shimming and flip angles allow for accurate measurement of 14 metabolites in multiple locations in one spectroscopy session.

Maryam Vareth^1,2, Yan Li², Janine M Lupo², and Sarah J Nelson^1,2
1UCSF/UC Berkeley Joint Group in Bioengineering, University of California, Berkeley, CA, United States, ²Radiology and Biomedical Imaging, University of California, San Francisco, CA, United States

In this work we showed that MRSI at 7T can be accelerated up to a factor of 5 (under 3 minutes) while providing high spectral quality with a good fit among the metabolites and their ratios by utilizing a fully-sampled non-water suppressed calibration region for modified SPIRiT.

Xiao-Qi Ding¹, Andrew A. Maudsley², Mohammad Sabati², Sulaiman Sheriff², and Heinrich Lanfermann^1
1Institute of Diagnostic and Interventional Neuroradiology, Hannover Medical School, Hannover, Lower Saxony, Germany, ²Department of Radiology, University of Miami School of Medicine, FL, United States

A short TE whole brain MR spectroscopic imaging (wbMRSI) for detection of focal metabolite concentrations in human brain within a clinically acceptable scan time has been evaluated. Twenty healthy volunteers were scanned both with wbMRSI and Single-Voxel Spectroscopy (SVS), and the measurements compared. The results showed that short TE wbMRSI could be used to estimate focal concentrations of NAA, Cho, tCr, mI, and Glx as well as those with SVS, with additional advantages that metabolite concentrations could be evaluated at more brain regions.

Junmo An¹, Ahmet E. Sonmez¹, Mahmut Unan¹, Robert D. Darrow², Ileana Hancu², R. Jason Stafford³, Andrew G. Webb⁴, and Nikolaos V. Tsekos^1
1University of Houston, Houston, Texas, United States, ²GE Global Research Center, New York, United States, ³University of Texas MD Anderson Cancer Center, Texas, United States, ⁴Leiden University, Leiden, Netherlands

The aim of this work is to implement a dual modality optical/NMR probe for intraoperative loco-regional and spatially co-registered collection on light-induced fluorescence and NMR spectra. The multi-fiber optical sensor that functions as an emitter and receiver is surrounded by a solenoid microcoil for 1H spectroscopy or MR imaging. The probe is mounted on an MR compatible manipulator for intraoperative biosensing in situ and mechanical scanning to map the spatial distribution of optical/NMR signal sources. Testing was conducted on a multi-compartment phantom of fluorophores and metabolites demonstrated the MR compatibility of the device and the spatial matching of the distribution of optical and MR signal sources.

Ladislav Valkovic^1,2, Barbara Ukropcová^3,4, Marek Chmelík¹, Ivica Just Kukurová¹, Timea Kurdiová³, Monika Christina Kipfelsberger¹, Patrik Krumpolec³, Wolfgang Bogner¹, Martin Meyerspeer⁵, Ivan Frollo², Iwar Klimes³, Jozef Ukropec³, Siegfried Trattnig¹, and Martin Krssák^1,6
1High Field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria, ²Department of Imaging Methods, Institute of Measurement Science, Slovak Academy of Sciences, Bratislava, Slovakia, ³Obesity Section, Diabetes and Metabolic Disease Laboratory, Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia, ⁴Institute of Pathophysiology, Faculty of Medicine, Commenius University, Bratislava, Slovakia, ⁵Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria, ⁶Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria

In this study, a performance of the depth resolved surface coil MRS (DRESS) sequence was assessed in exercising gastrocnemius muscle at 7T. Two dynamic examinations (one non-localized and one DRESS-localized) were performed and the measured metabolic parameters were compared. Significantly higher PCr drop and no Pi split in the DRESS localized spectra point towards good ³¹P signal localization from the gastrocnemius muscle.

Grzegorz L. Chadzynski^1,2, Anke Henning^2,3, Philipp Ehses^1,2, Jens Hoffmann², G. Shajan², and Klaus Scheffler^1,2
1Biomedical Magnetic Resonance, University Hospital Tuebingen, Tuebingen, Germany, ²High-Field Magnetic Resonance Center, Max Planck Institute for Biological Cybernetics, Tuebingen, Germany, ³Institute for Biomedical Engineering, University and ETH Zuerich, Zuerich, Switzerland

The FID-MRSI technique is a promising tool to be used for spectroscopic imaging at ultra-high magnetic field as it enables short TE and avoids in-plane chemical shift displacement. However, due to the acquisition delay, the first points of the acquired FID signals are missing, giving rise to phase problems which may hamper quantitative analysis. Our aim was to examine the feasibility of high-resolution FID-MRSI of the healthy human brain at the field strength of 9.4 T. The missing FID points were reconstructed with an autoregressive model so that the phase problems present in the acquired spectra could be minimized.

Sofie Tapper¹, Anders Tisell^1,2, and Peter Lundberg^1,2
1Radiation Physics, Department of Medicine and Healths Sciences, Linköping University, Linköping University, Linköping, Sweden, ²Centre for Medical Image Science and Visualization (CMIV), Linköping University, Linköping, Sweden, Linköping University, Linköping, Sweden

In many recent experiments BOLD-fMRI has been combined with quantitative measurements of GABA-concentrations in order to elucidate the correlation between positive or negative BOLD and GABA and Glutamate concentrations in connection with a range of diseases affecting the CNS. GABA MRS is in many cases performed subsequent to the fMRI data-acquisition. As a consequence, the quality of the GABA-measurements heavily depend on the short term stability of the MR-scanner. Our aim was to determine the possibly deleterious effects a BOLD-fMRI (GRE-EPI) experiment had on the stability of MEGA-PRESS measurements, and we have performed investigations of the drift in synthesizer frequency and phase. All measurements were performed both before and after GRE-EPI. The conclusion was that the large influence of EPI-induced gradient heating on quantitative GABA-concentration measurements needs to be corrected for using a procedure taking both the frequency- and phase-drift in each individual dynamic into account.

Mark Mikkelsen¹, Petroc Sumner¹, Krish D. Singh¹, and C. John Evans^1
1CUBRIC, School of Psychology, Cardiff University, Cardiff, United Kingdom

In vivo quantification of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) is possible with J-difference edited proton magnetic resonance spectroscopy (MRS), but concentration measurements suffer from macromolecule (MM) contamination. This is a result of a co-edited MM resonance being partially excited during acquisition. Using symmetric editing-based suppression, however, the MM signal can be suppressed. Here, the repeatability of GABA-edited MRS with and without MM suppression is evaluated and compared. It is shown that MM suppression is comparable in repeatability to standard GABA-editing. MM-suppressed GABA measurement offers increased measurement specificity and potentially an increased ability to discriminate between participants.

Petr Bednarik^1,2, Amir Moheet¹, Dinesh K Deelchand¹, Uzay E Emir³, Elizabeth R Seaquist¹, and Gulin Oz^1
1University of Minnesota, Minneapolis, MN, United States, ²Central Europeran Institute of Technology, Masaryk University, Brno, Czech Republic, ³FMRIB Centre, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom

Hippocampus dysfunction may be involved in multiple neurologic and neuropsychiatric diseases. We investigated the feasibility of obtaining high quality hippocampal spectra and the test-retest reproducibility of hippocampal neurochemical profiles using standard 3T hardware with an in-house implemented single-voxel, short-echo semi-LASER sequence. Neurochemical profiles were highly reproducible between subjects (N=6) and between sessions (each subject scanned twice). Six metabolites were quantified with mean CRLB ≤ 10% and another 4 with CRLB ≤ 30%. Mean intersession CV was <10% for 8 metabolites. This methodology will allow novel investigations of hippocampal neurochemistry in many common clinical conditions with widely available hardware.

Karl Landheer¹, Sunit Das², and Simon Graham^1
1Medical Biophysics, University of Toronto, Toronto, Ontario, Canada, ²St. Michael's Hospital, Toronto, Canada

A novel technique was developed that can measure the spectra of discrete voxels simultaneously, without the need for a gradient readout. The technique utilizes a modified PRESS sequence to excite multiple voxels, measures their spectra simultaneously using multichannel receiver coils, and reconstructs the individual voxel spectra using SENSE. Good agreement was demonstrated in vivo using both qualitative and quantitative measurements of the technique’s efficacy when compared to single voxel spectroscopy, in healthy adults and in a patient with low-grade glioma.

Geoffrey S Payne¹ and Martin O Leach^1
1Institute of Cancer Research and Royal Marsden Hospital, Sutton, Surrey, United Kingdom

Lactate is an important potential cancer biomarker but measurement is hampered by intense signals of overlapping lipids, especially in the presence of motion. Here a single-shot lactate sequence has been conceived, implemented and evaluated on a Philips 3T scanner. Based on the adiabatic semi-laser single-voxel sequence, it uses FOCI RF-and-gradient pulses with large bandwidth to overcome the chemical shift displacement effect. In phantoms this “flaser” sequence more than doubled the lactate signal of standard PRESS. MQF-flaser included at TE/2 a 90^o-180^o-90^o multiple-quantum filter segment with -1:2 gradients. Lactate signals were 40% of flaser alone, while 1.3ppm lipid was totally eliminated.

Alexander R Craven¹, Renate Grüner^2,3, Lars Ersland⁴, Gerard E Dwyer¹, Maiken Kirkegaard Brix^1,2, and Kenneth Hugdahl^1,5
1Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway, ²Department of Radiology, Haukeland University Hospital, Bergen, Norway,³Department of Physics and Technology, University of Bergen, Norway, ⁴Department of Clinical Engineering, Haukeland University Hospital, Bergen, Norway, ⁵Division of Psychiatry, Haukeland University Hospital, Bergen, Norway

Despite increasing usage of the MegaPRESS GABA-editing MRS sequence for measurement of GABA concentrations in the human brain, optimal values for some basic sequence parameters such as the number of repetitions (hence, scan time) have not been established in literature. The present investigation examines the effects of increasing scan time on reproducibility, leading to a recommendation of 256 averages (13 minutes) as a starting point. Furthermore, an upper limit on scan time to 20 minutes is recommended, whereafter cumulative disturbances begin to outweigh gains in signal quality.

Vincent O. Boer¹, Dennis W.J. Klomp¹, and Rene Mandl^2
1radiology, UMC Utrecht, Utrecht, Utrecht, Netherlands, ²Psychiatry Department, UMC Utrecht, Utrecht, Utrecht, Netherlands

GABA is the primary inhibitory neurotransmitter of the brain and is believed to be implicated in various psychiatric diseases. Due to its low concentration, obtaining sufficient SNR during acquisition is mandatory to ensure reliable GABA measurements. In this work we compare the SNR of GABA editing sequences applied to 3T and 7T and observed an twofold increase in SNR for GABA.

Ivan Tkac¹, Diana Wallin², Michael K Georgieff², and Raghu Rao^2
1Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, United States, ²Department of Pediatrics, University of Minnesota, Minneapolis, MN, United States

The neurochemical profile of the mouse brain is changing extremely fast during the developmental period. Therefore, mice have to be scan at exactly the same age to avoid a bias caused by age dependent neurochemical changes. This study demonstrates that by optimizing the scanning protocol, high throughput ¹H MRS is feasible without compromising the data quality. The performance of this approach is demonstrated by using the anemia mouse model. An optimized scanning protocol enabled to scan 12 mice in a single study session.

Stephen John Sawiak^1,2, Bianca Jupp³, Daniele Caprioli³, T Adrian Carpenter¹, and Jeffrey W Dalley^3
1Wolfson Brain Imaging Centre, University of Cambridge, Cambridge, England, United Kingdom, ²Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, England, United Kingdom, ³Department of Psychology, University of Cambridge, England, United Kingdom

The inhibitory neurotransmitter GABA plays a role in many psychiatric and neurological conditions. It is difficult to measure with in vivo 1H-MRS due to overlap with more abundant metabolites. The spectral-editing technique MEGAPRESS can be used to isolate the GABA signal. We demonstrate for the first time that this technique can be used in rats, and we give mean and variability values of the concentrations obtained in the ventral striatum.

Norbert W Lutz¹ and Patrick J Cozzone^1
1CRMBM, Faculté de Médecine, Aix-Marseille University, Marseille, France

Jamie Near^1
1Department of Psychiatry, McGill University, Montréal, Québec, Canada

It has been shown previously that when LCModel is used for spectral quantification of short-TE MRS data, increasing spectral linewidth results in a decrease in the estimated concentration of several major metabolites. However, the source of these systematic errors is not clearly understood. The primary aim of this study is to investigate the underlying cause of the strong dependence between spectral linewidth and LCModel measurement bias. These investigations are achieved through LCModel analysis of a large number of simulated MRS datasets with varying linewidths. The results indicate that reduced concentration estimates are due to an increase in the LCModel baseline estimate at higher spectral linewidths.

Rebecca Birch^1,2, Andrew C. Peet^2,3, Theodoros N. Arvanitis^2,4, and Martin Wilson^2,3
1PSIBS Doctoral Training Centre, University of Birmingham, Birmingham, United Kingdom, ²Department of Oncology, Birmingham Childrens Hospital NHS Foundation Trust, Birmingham, United Kingdom, ³School of Cancer Sciences, University of Birmingham, United Kingdom, ⁴Institute of Digital Healthcare, WMG, University of Warwick, Coventry, United Kingdom

Water reference scans for Magnetic Resonance Spectroscopic imaging (MRSI) provide absolute quantification of metabolites; long acquisition times mean it is not used routinely in clinic. Sensitivity encoding (SENSE) is a parallel imaging technique which can reduce scan time. SENSE and its reconstruction of water reference data is compared with a default reduced resolution technique. 2D MRSI water reference data were collected for a phantom and three volunteers at 3T. Water amplitude and line width maps were created and variance with the full acquisition assessed. SENSE was found to be more successful, validating its use for routine water reference data collection.

Ayano Enomoto¹ and Hiroshi Hirata^1
1Graduate School of Information Science and Technology, Hokkaido University, Sapporo, Hokkaido, Japan

To extend the area of visualization, we demonstrated a method of parallel image acquisition using a two-channel surface coil array and two RF bridges. For decoupling between the two coils, the two different resonant frequencies were set to individual channels. Multiplexing of EPR detection in the frequency domain was demonstrated. We obtained the three-dimensional (3D) EPR imaging of a phantom using the method of parallel image acquisition.

Hirohiko Imai¹, Yuki Takayama¹, and Tetsuya Matsuda^1
1Department of Systems Science, Graduate School of Informatics, Kyoto University, Sakyo-ku, Kyoto, Japan

We demonstrate the feasibility of a ¹H-¹³C heteronuclear multiple quantum coherence (HMQC) MRSI for imaging metabolite dynamics. The ¹H-¹³C HMQC MRSI was performed for the whole-body acquisition of four tumor-bearing mice after sacrifice at 5min, 8min, 30min, and 20hr post injection of [U-¹³C]glucose. Form acquired 4D data set (two spectral and two spatial dimensions), the signal intensity ratio of lactate (Lac) to glucose (Glc) was mapped. When focusing on the tumor, the Lac/Glc value increased with time, reflecting the accumulation of Lac as a metabolic end product from Glc in the tumor.

Sebastian Rupprecht¹, Byeong-Yeul Lee², Wei Luo¹, Xiao-Hong Zhu², Wei Chen², and Qing X Yang^1,3
1Radiology, Penn State College of Medicine, Hershey, PA, United States, ²Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota, Minneapolis, MN, United States, ³Neurosurgery, Penn State College of Medicine, Hershey, PA, United States

High-field X-nuclei MRS for human application at high/ultrahigh field often suffers from high SAR, limited SNR and long scanning time. In this report, we demonstrate that more than 130% SNR gain was achieved with ultra high dielectric constant (uHDC) materials incorporated into the RF coil for 31P MRS and CSI at 7T. Concomitantly, the RF power optimized for acquiring the spectra was reduce by 43% with the uHDC material. Our results suggest that uHDC material can be incorporated into the RF coil for high-field X-nuclear MRS to significantly improve SNR and reduce transmission power.

Christina Stahl¹, Gaelle Diserens², Martina Vermathen³, Anna Oevermann⁴, Torsten Seuberlich⁴, Josiane Lauper¹, Francesca Amati⁵, Chris Boesch², and Peter Vermathen^2
1Department of Clinical Veterinary Medicine, Bern University, Bern, Bern, Switzerland, ²Departments of Clinical Research and Radiology, Bern University, Bern, Switzerland,³Department of Chemistry and Biochemistry, Bern University, Bern, Switzerland, ⁴Department of Clinical Research and Veterinary Public Health, Bern University, Bern, Switzerland, ⁵Department of Physiology, Lausanne University, Lausanne, Switzerland

Lipid resonances from mobile lipids can be observed by 1H NMR spectroscopy in multiple tissues and have also been associated with malignancy. The purpose of our study was to investigate the effect of spinning rate variation on the HR-MAS pattern of lipid resonances in non-neoplastic brain and muscle biopsies. We observed a substantial increase in the relative integral of mobile lipid resonances with high spinning rates in non-neoplastic brain tissue biopsies, but only a mild increase in skeletal muscle biopsies.

Albrecht Ingo Schmid^1,2, Kiril Schewzow^1,2, Sigrun Goluch^1,2, Georg Fiedler^1,2, Fabian Niess^1,2, Elmar Laistler^1,2, Michael Wolzt³, Ewald Moser^1,2, and Martin Meyerspeer^1,2
1Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria, ²MR Centre of Excellence, Medical University of Vienna, Vienna, Austria, ³Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Vienna, Austria

During exercise, skeletal muscle T2* relaxation times are known to change. In this study, repeated EPI and localised 31P MRS were acquired in healthy volunteers at 7 T in one scanning session. A highly significant cross correlation (R2 = 0.72±0.16) between EPI signal and intracellular pH was found during 5 min. of plantar flexion exercise. Apparently T2* changes during exercise are driven by pH-dependent cellular water shift.

Jan Weis¹, Francisco Ortiz-Nieto¹, and Håkan Ahlström^1
1Department of Radiology, Uppsala University Hospital, Uppsala, Sweden

Proton single-voxel PRESS magnetic resonance spectroscopy of the human prostate at 3 T was performed using a surface coil. The aim of the study was estimation prostate water, choline, creatine, and citrate relaxation times T1, T2. Spectra were processed by LCModel and AMARES algorithms. T1 and T2 values were obtained by mono-exponential fitting of the spectral intensities versus repetition or echo times. Knowledge of the relaxation times enables quantification of prostate metabolite concentrations using water as the internal concentration reference.

Hirotada G Fujii¹ and Miho C Emoto^1
1Center for Medical Education, Sapporo Medical University, Sapporo, Hokkaido, Japan

Methamphetamine (METH)-induced neurotoxicity is known to be caused in part by oxidative stress. The purpose of this study was to examine the effect of oxidative stress in METH-treated mice using a redox-sensitive nitroxide, 3-methoxycarbonyl-PROXYL (MCP), and to visualize brain redox status by noninvasive EPR imaging. Rates of reduction of MCP in the mouse brain were significantly accelerated after treatment with METH, which was remarkably suppressed by a dopamine synthesis inhibitor. The present results suggest that METH induced oxidative conditions in the mouse brain which resulted in oxidative damage. Using a blood-brain barrier (BBB)-impermeable gadolinium contrast agent, MRI of METH-treated mice displayed dysfunction of the BBB.

Christian C. Mirkes^1,2, G. Shajan¹, Jens Hoffmann¹, Daniel Brenner³, Rolf Pohmann¹, and Klaus Scheffler^1,2
1High-Field MR Center, Max Planck Institute for Biological Cybernetics, Tübingen, BW, Germany, ²Department for Biomedical Magnetic Resonance, University of Tübingen, Tübingen, BW, Germany, ³MR Physics, German Center for Neurodegenerative Diseases (DZNE), Bonn, NRW, Germany

Accurate sodium B₁ field mapping is a key requirement for quantitative sodium imaging at ultra-high field strength. In this study the performance of three B₁ mapping techniques was evaluated in a phantom at 9.4 T. Compared to the double angle and the Bloch-Siegert shift based methods, the phase sensitive method provided the most reliable maps, especially in regions of weak B₁.

Nadia Benkhedah¹ and Armin M. Nagel^1
1Medical Physics in Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany

Two pulse biexponentially weighted sodium imaging has been proposed to provide the desired contrast with good image quality in short acquisition times. The purpose of this work was the evaluation of benefits of biexponentially weighted sodium imaging compared to a difference image generated from a conventional double-echo sequence. It was shown that the biexponentially weighted sequence is more suitable for future approaches for quantifying the intracellular sodium content. Also, biexponentially weighted imaging leads to higher SNR and less B₀ sensitivity.

Miho C Emoto¹, Hideo Sato-Akaba², Hiroshi Hirata³, and Hirotada G Fujii^1
1Sapporo Medical University, Sapporo, Hokkaido, Japan, ²Osaka University, Osaka, Japan, ³Hokkaido University, Hokkaido, Japan

Piperidine nitroxides such as TEMPONE and TEMPOL are useful redox-sensitive probes for redox research, but due to their short lifetime in vivo, they have not been fully employed in EPR imaging studies. In this study, we developed an improved EPR imaging system with a rapid-field scanning capability, and obtained three-dimensional EPR images of piperidine nitroxides in mouse heads in 15 s. The co-registered EPR and MRI images of mouse heads clearly depict detailed distributions of TEMPONE. With this improved EPR imaging system, it is likely that piperidine nitroxides can be used to estimate redox status in in vivo systems.

Christoph Jacoby¹, Thomas Oerther², Sebastian Temme¹, Jürgen Schrader¹, and Ulrich Flögel^1
1Molecular Cardiology, Heinrich Heine University, Düsseldorf, NRW, Germany, ²Bruker BioSpin GmbH, Rheinstetten, Baden-Württemberg, Germany

In the present study a multi chemical shift selective (MCSS) RARE sequence was used for artifact-free ¹⁹F MR imaging of perfluorocarbons (PFC) with complex spectra and compared to conventional methods in terms of sensitivity and quantifiability. Reliable quantification was demonstrated by simultaneous imaging of various mixtures of different PFC emulsions ex vivo and in vivo. The average enhancement factor was determined to be more than two-fold as compared to single excitation RARE without any loss of information due to intrinsic spatial averaging mechanisms. MCSS-RARE may also be useful for other nuclei, e.g. simultaneous imaging of all phosphorus of ATP.

Jonathan Lommen¹, Simon Konstandin¹, Philipp Krämer¹, and Lothar R. Schad^1
1Computer Assisted Clinical Medicine, Heidelberg University, Mannheim, Germany

Quantitative sodium MRI requires corrections for rf field inhomogeneities in order to determine the total tissue sodium concentration. The low SNR and fast decay of the sodium signal are hard restrictions for mapping techniques. Thus, the performance of four common methods (PS, BSS, DAM, AFI) has been compared to find the adequate method. The PS method shows best SNR and fastest acquisition time. This enables more accurate and fast in-vivo sodium quantification being a sign of tissue viability.

Simon Konstandin¹, Philipp Krämer¹, and Lothar R. Schad^1
1Computer Assisted Clinical Medicine, Heidelberg University, Mannheim, Germany

SNR-efficient sequences with short echo times are required for imaging of spin>1/2 nuclei. Established ultra-short echo (UTE) time sequences are 3D radial techniques with density adaption and twisted projection imaging. However, so far no UTE sampling strategy exists for anisotropic resolution with uniform k-space sampling for highest SNR efficiency. In this study, projections are distributed on rings so that uniform sampling and optimal SNR efficiency is achieved for UTE imaging with anisotropic resolution if no postfiltering is required.

Anna Kollefrath¹, Manuela Rösler¹, Reiner Umathum¹, and Armin M. Nagel^1
1Medical Physics in Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany

With a customer made solenoid coil ³⁷Cl imaging at a 7T whole- body MRI system at a frequency of 24.3 MHz was performed although the natural abundance of ³⁷Cl is lower than that of the for measurements preferred ³⁵Cl. For phantoms with 0.9% sodium chloride solution and different agar concentrations the relaxation times (T2^* and T1) were determined and compared to the relaxation times of ³⁵Cl. The relaxation times are longer than the ones of ³⁵Cl. In-vivo imaging of a narcotized rat showed the feasibility of MRI using the ³⁷Cl isotope in comparison with ³⁵Cl and showed high signal intensities.

Alina Gilles¹, Nadia Benkhedah¹, and Armin M Nagel^1
1Medical Physics in Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany

We present the first in vivo biexponentially weighted ³⁵Cl images and provide optimized sequence parameters for ³⁵Cl TQF imaging. Selective imaging of ³⁵Cl nuclei which are exposed to quadrupolar interaction, i.e. intracellular ³⁵Cl, is now feasible with better resolution in the same measurement time as compared to TQF ³⁵Cl imaging.

Jonathan Goodwin^1,2, Katsuya Yachi³, Masaki Nagane⁴, Hironobu Yasui⁴, Yusuke Miyaki³, Osamu Inanami⁴, Andrey Bobko⁵, Valery Khramstov⁵, and Hiroshi Hirata^3
1Department of Radiology, Hokkaido University Hospital, Sapporo, Hokkaido, Japan, ²Division of Ultrahigh Field MRI, Iwate Medical University, Yahaba, Iwate, Japan,³Division of Bioengineering and Bioinformatics, Hokkaido University, Sapporo, Japan, ⁴Laboratory of Radiation Biology, Hokkaido University, Sapporo, Japan, ⁵Division of Pulmonary, Allergy, Critical Care & Sleep Medicine, The Ohio State University, Columbus, Ohio, United States

Accurate measurement of extra cellular pH (pHe) in tumour may offer valuable information regarding cell viability and therapeutic response. In this work, 750 MHz CW-EPR spectroscopy was used to assess pHe of C3H HeJ mice hind leg squamous cell tumour after intra-venous tail vein injection during stages of normal tumour growth, and in response to a single 10 Gy dose of X-ray irradiation. Through measurement of the hyperfine coupling constant, an inverse relationship was observed between tumour pHe and volume, with an accuracy of less than 0.1pH units. This relationship was disrupted by a single 10 Gy radiotherapy dose.

Yongxian Qian¹, Ashok Panigrahy², Charles M. Laymon¹, Vincent K. Lee², Jan Drappatz³, Frank S. Lieberman³, Fernando E. Boada⁴, and James M. Mountz^1
1Radiology, University of Pittsburgh, Pittsburgh, PA, United States, ²Radiology, Childrens Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States, ³Neurology, University of Pittsburgh, Pittsburgh, PA, United States, ⁴Radiology, New York University, New York, New York, United States

This work presents an alternative to triple-quantum filtering (TQF) techniques for quantifying intracellular sodium concentration (ISC) on clinical 3T MRI scanners with a much shorter scan time under SAR restriction. The new technique acquires two single-quantum (SQ) sodium images at ultrashort and long echo times (TE=0.44 and 5 ms) respectively, and then subtracts them to attain the short-T2 component intensity in the bi-exponential T2 relaxation of bound sodium. The experiments on phantoms and brain tumor patients showed the feasibility of the proposed idea.

Jose Luis Izquierdo Garcia¹, Pia Eriksson¹, Myriam Chaumeil¹, Russell O Pieper², Joanna J Phillips², and Sabrina M Ronen^1
1Radiology, UCSF, San Francisco, CA, United States, ²Neurological Surgery, Helen Diller Research Center, UCSF, San Francisco, CA, United States

This study demostrates that the activity of mutant IDH1 results not only in production of the oncometabolite 2-HG, but also in a wider metabolic reprogramming. Two cell models were investigated by 1H-MRS: the U87-based and the E6/E7/hTERT Normal Human Astrocyte (NHA)-based models. Metabolic profiling discriminated between wild-type and mutant IDH cells. A significant drop in the concentration of acetate, aspartate, glutamine and myo-inositol was observed in U87IDHmut cells and lower creatine and lactate concentration was observed in NHAIDHmut cells. In both models, IDHmut cells showed a lower concentration of glutamate and phosphocholine as well as the expected elevation in 2-HG

Xiao-Hong Zhu¹, Byeong-Yeul Lee¹, Susan Rolandelli², Paul Tuite², and Wei Chen^1
1CMRR, Department of Radiology, University of Minnesota Medical School, Minneapolis, MN, United States, ²Department of Neurology, University of Minnesota Medical School, MN, United States

Parkinson’s disease (PD) is the second most common neurodegenerative disorder, which affects men slightly more often than women. Mitochondrial dysfunction has been suspected as a pathogenic mechanism of PD. However, direct in vivo evidence of mitochondrial abnormalities and accompanying impairments in energy metabolism is incomplete in PD. Fortunately with developments of in vivo ³¹P MRS at 7 tesla, it is now possible to obtain high quality quantitative cerebral phosphorus metabolite profiles which give insight into brain metabolism. In our evaluation of individuals with PD and matched controls we demonstrated significant differences between male and female PD subjects in the phosphorus metabolite profiles. These preliminary findings highlight the feasibility of this non-invasive MR method that may further understanding of PD as well as potential gender effects on the disease.

Golam M. I. Chowdhury¹, Larry Park², Oxana Lavrova², Monique Thomas¹, Xiaoxian Ma³, Gerard Sanacora¹, Douglas L Rothman³, and Kevin L Behar^1
1Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, United States, ²CHDI Foundation, Inc, Los Angeles, California, United States,³Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut, United States

Alterations in brain energy metabolism, including reduced glucose utilization and mitochondrial respiration, is observed in Huntington’s Disease (HD) and HD animal models. ¹H-[¹³C]-MRS can be readily adapted to measure metabolic pathway flux by use of ¹³C -labeled substrates. In this study we measured the flow of ¹³C label into glutamate, glutamine and GABA in 6 or 8 week old R6/2 and control mice following timed intravenous infusions of [1,6-¹³C₂]glucose or [2-¹³C]acetate. Decreased ¹³C labeling was observed at 6 weeks and was more pronounced in 8 week old R6/2 mice indicating impaired neuroenergetics and glutamate and GABA neurotransmitter cycling.

Frank C.G. van Bussel¹, Walter H. Backes¹, Paul A.M. Hofman¹, Alfons G.H. Kessels², Nicolaas A.J. Puts³, Richard A.E. Edden³, Tamar M. van Veenendaal¹, Harm J. van de Haar¹, Martin P.J. van Boxtel⁴, Miranda T. Schram⁵, Coen D.A. Stehouwer⁵, Joachim E. Wildberger¹, and Jacobus F.A. Jansen^1
1Radiology, Maastricht University Medical Center, Maastricht, Netherlands, ²Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Center, Maastricht, Netherlands, ³Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, ⁴Psychiatry and Neuropsychology, Maastricht University Medical Center, Maastricht, Netherlands, ⁵Internal Medicine, Maastricht University Medical Center, Maastricht, Netherlands

Type 2 Diabetes Mellitus (T2DM) is associated with cerebral abnormalities, accelerated cognitive decline, and dementia. T2DM risk factors such as blood glucose levels are associated with developing of dementia. Magnetic resonance spectroscopy provides the opportunity to study cerebral metabolites. Altered cerebral metabolic concentrations may be associated with neurodegeneration. The aim of this study is to examine if cerebral metabolites constitute a MRI biomarker for i) T2DM, ii) blood glucose measures, and/or iii) cognitive status. This study is the first study to report higher GABA+ levels in subjects with poor blood glucose control. Unfortunately, no relationship with cognitive status was observed.

Eva-Maria Ratai^1,2, Nandita Shetty³, Shantanu Ghosh^2,3, Mohamad Alshikho^2,3, Avi Ringer³, Katherine Martien^2,4, David Holtzman^2,5, and Martha Herbert^2,3
1Department of Radiology, Massachusetts General Hospital, A. A. Martinos Center for Biomedical Imaging, Charlestown, MA, United States, ²Harvard Medical School, Boston, MA, United States, ³Department of Neurology, Massachusetts General Hospital, A. A. Martinos Center for Biomedical Imaging, Charlestown, MA, United States, ⁴Department of Pediatrics, Massachusetts General Hospital, MA, United States, ⁵Pediatric Neurology, Massachusetts General Hospital, A. A. Martinos Center for Biomedical Imaging, Charlestown, MA, United States

The objective of this study was to investigate biomarkers related to neuronal hyperexcitation, excitotoxic injury, and inflammation in white matter of boys with autism spectrum disorders (ASD) and typically developing (TD) age-matched controls, 17 ASD and 30 TD subjects, using MRS. Glutamate+Glutamine/N-Acetylaspartate (Glx/NAA) ratio decreased with age in TD children but not in ASD. Myo-Inositol (mI) significantly increased with age only in ASD, consistent with increased inflammation but not in TD. The failure of Glx/NAA to decrease with age may contribute to the substantial seizure risk seen in ASD children as they enter puberty.

Ivan Kirov¹, Assaf Tal¹, Kathryn Iwata², Joseph Herbert³, and Oded Gonen^1
1Radiology, New York University Langone Medical Center, New York, NY, United States, ²School of Medicine, New York University Langone Medical Center, New York, NY, United States, ³Multiple Sclerosis Comprehensive Care Center, New York University Langone Medical Center, New York, NY, United States

Despite a well-documented involvement of the thalamus in multiple sclerosis, its metabolism in early disease has not been studied. We used 3D multivoxel proton MR spectroscopy and software-generated segmentation masks to (i) determine the optimal tradeoff between partial volume and reproducibility; and to (ii) apply this threshold to study 18 recently diagnosed patients and 10 controls. Absolute concentrations of thalamic N-acetyl-aspartate, creatine, choline and myo-inositol were not different between the two groups, and there was no thalamic atrophy. We interpret these results as evidence for thalamic sparing, but note the very low levels of clinical disability and lesion load in our cohort.

Bo Liu¹, Bin Zhao¹, Guangbin Wang¹, and Fei Gao^1
1Shandong Medical Imaging Research Institute, Shandong University, Jinan, Shandong, China

Most women of reproductive age suffer from premenstrual syndrome(PMS) ,which is affecting their daily life .Evidences have shown the involvement of gamma-aminobutyric acid(GABA) neurotransmitter system in PMS. In this study , significantly reduced GABA levels were observed in PMS women in the anterior cingulate cortex (ACC)/medial prefrontal cortex (mPFC) ,whereas no difference was found in ltBG. The ACC/mPFC was suggested to be involved in negative emotions and in modulation of automatic nervous systems, and dysfunctions in this region may partly underlie the variety of psychosomatic premenstrual symptoms. Premenstrual GABA deficit may be an important neurobiological mechanism contributing to the pathophysiology of PMS.

Elijah George^1,2, Steve Roys², Jiachen Zhuo², Chandler Sours², Joseph Rosenberg², and Rao Gullapalli^2
1Bioengineering, University of Maryland, College Park, Maryland, United States, ²Magnetic Resonance Research Center, University of Maryland Baltimore, School of Medicine, Baltimore, Maryland, United States

Mild traumatic brain injury (mTBI) patients represent 75% of the viable TBI population. The aim of the current study is to acutely predict the symptomatic outcome of mTBI patients 6 months post injury (PI) neurometabolic measurements from magnetic resonance spectroscopy (MRS). Herein, we applied acute neurometabolic information to the support vector machine (SVM) algorithm in order to differentiate between patients with and without post concussive syndrome (PCS) 6 months PI

Ben Babourina-Brooks¹, Martin Wilson², Theo Arvanitis³, Andrew Peet², and Nigel Davies^4
1University of Birmingham, Birmingham, West Midlands, United Kingdom, ²University of Birmingham, West Midlands, United Kingdom, ³Birmingham Children’s Hospital NHS Foundation Trus, West Midlands, United Kingdom, ⁴University hospitals Birmingham trust, West Midlands, United Kingdom

MRS thermometry has been used to show differences in childhood brain tumours. In this study we investigate what the chemical shift measures in terms of tumour malignancy. This was done through metabolite concentration correlations with the PRF.

Pallab K Bhattacharyya¹, Blessy Mathew¹, Robert Bermel¹, Micheal Phillips¹, Lael Stone¹, and Mark Lowe^1
1Cleveland Clinic, Cleveland, OH, United States

Correlating cerebral gamma amino butyric acid (GABA) level with fMRI activation is of recent research interest. As a quantitation of fMRI activation, different investigators have used (i) activation volume within a region of interest, or (ii) amplitude of blood oxygen level dependent (BOLD) signal change. Robustness of activation volume in comparison with BOLD signal change was recently reported. We compared GABA level correlation with both fMRI activation volume and BOLD signal change, and demonstrate that for a population with higher variablity in noise (as in patients with multiple sclerosis), activation volume is a more sensible metric of fMRI activation.

Gokce Hale Hatay¹, Emre Okeer², Bahattin Hakyemez², and Esin Ozturk-Isik^3
1Department of Electrical and Electronics Engineering, Yeditepe University, Istanbul, Turkey, ²Department of Radiology, Uludag University, Bursa, Turkey, ³Department of Biomedical Engineering, Yeditepe University, Istanbul, Turkey

This study aims to investigate the relative performances of 2D iterative frame based and a 3D direct improve the feasibility of 3D direct compressed sensing reconstruction for faster phosphorus MR spectroscopic imaging (31P MRSI) with comparing 2D iterative frame based reconstruction. A 31P MR spectrum was acquired from the frontoparietal lobe of a volunteer at 3T, and two dimensional 31P MRSI datasets that included a tumor region and a healthy region were created. k-space data was randomly undersampled with two patterns while preserving the central part for reduction factor of 4.26 for 16x16 and 3.71 for 32x32 arrays. This study showed that 3D direct compressed sensing reconstruction works better than 2D iterative frame based reconstruction.

Andreas Neubauer¹, Awais Akbar Bajwa², Michaela Ruttorf¹, Michael Schwerter¹, Lothar Schilling², and Lothar Schad^1
1Computer Assisted Clinical Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, Baden-Wuertemberg, Germany, ²Division of Neurosurgical Research, Medical Faculty Mannheim, Heidelberg University, Mannheim, Baden-Wuertemberg, Germany

Tracking pathological processes in vivo is still of great interest in clinical research. Therefore, ²³Na - MRI has become a useful tool to monitor the total sodium concentration in brain tissue. Unfortunately, conventional techniques are not capablo to resolve changes in intra- and extracellular sodium reliably. In this study, we present a method to transiently open the blood brain barrier and load the brain tissue with the sodium shift agent Tm[DOTP]^5-

Bhavana Shantilal Solanky¹, Frank Riemer¹, Xavier Golay², and Claudia AM Wheeler-Kingshott^1
1NMR Research Unit, Department of Neuroinflammation, Queen Square MS Centre, UCL Institute of Neurology, London, United Kingdom, ²Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, London, United Kingdom

In tissue ²³Na T₂ relaxation is bi-exponential, resulting in a short T₂ and a long T₂ fraction. We have developed ²³Na MRS protocols (FUSS and FAHS) both based on ISIS for²³Na-MRS of the spinal cord. Both sequences result in a single resonance and similar SNR. A single resonance is often fit to a single peak, however as the bi-exponential behavior of sodium in tissue is known this information could also be factored into the analysis. Here we investigate mono-exponential, bi-exponential and combination fits to the data to determine the most accurate quantification method.

Milan Scheidegger^1,2, Andreas Hock^1,2, Alexander Fuchs¹, and Anke Henning^1,3
1Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Zurich, Switzerland, ²Department of Psychiatry, Psychotherapy and Psychosomatics Hospital of Psychiatry, University of Zurich, Zurich, Zurich, Switzerland, ³Institute for Biological Cybernetics, Max Planck Institute, Tuebingen, Baden Württemberg, Germany

The determination of accurate transverse (T2) relaxation times for brain metabolites is essential for volume tissue composition correction methods including relaxation correction. Therefore, T2 relaxation times of 18 brain metabolites at 3T are presented for the first time as measured in predominantly grey matter of 83 healthy volunteers.

Akshay Madan¹, Sandeep Ganji¹, Zhongxu An¹, Elizabeth Maher¹, and Changho Choi^1
1UT Southwestern Medical Center, Dallas, Texas, United States

Lactate (Lac) is elevated in tumors and has been extensively studied because of its potential use in clinical diagnosis. Lac resonance at 1.31 ppm is overlapped with lipid signals which are also elevated in many tumors, thus Lac is often measured using long echo times. We aim to accomplish precise measurement of Lac T2 and absolute quantification of its concentration with corrections for the T2 relaxation effects. We measured Lac T2 in 18 glioma patients using PRESS at 8 TE's (58 - 268ms). The T2 of Lac was estimated to be 246[plusmn]20ms and was similar between tumor grades and subtype.

Alan Bainbridge¹, Cheong LY Jeannie^2,3, Peter J Anderson^3,4, Deanne K Thompson³, Alan Connelly⁵, Peter J Lally⁶, Nicola J Robertson⁶, and Lex W Doyle^2,3
1Medical Physics, UCLH NHS Foundation trust, London, United Kingdom, ²Royal Women's Hospital, Melbourne, Australia, ³Murdoch Children's Research Institute, Melbourne, Australia, ⁴University of Melbourne, Melbourne, Australia, ⁵Florey Institute of Neurosciences and Mental Health, Melbourne, Australia, ⁶Institute for Women's Health, University College London, London, United Kingdom

Preterm birth is associated with increased risk of white matter (WM) injury resulting in disrupted WM maturation and neurodevelopmental deficits. Extremely preterm infants(EP) are at increased risk of cerebral palsy, and other motor and cognitive impairments. We aimed to compare the metabolite ratios NAA/Cr, Cho/Cr and NAA/Cho between EP and term controls at age 18 years and to explore the association between these metabolite ratios and full scale IQ at 18 years. This is the first study to report long term brain metabolite differences in PC WM in EP with Naa/Cr. Naa/Cho and Cho/Cr significantly different compared to controls.

Zhongxu An¹, Sandeep Ganji¹, and Changho Choi^1
1Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, Texas, United States

We report in vivo ¹H spectroscopy of Glutamate, Glutamine, N-acetyl aspartyl glutamate (NAAG) and other metabolites in human brain using PRESS at 3T. With test- retest experiment, we present the ability to reliably detect and quantify these technically challenging metabolites. With the segmentation of gray matter and white matter, we also demonstrate variation of the metabolites in different brain regions.

Sandeep K Ganji^1,2, Akshay Madan¹, Zhongxu An¹, and Changho Choi^1,2
1Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, TX, United States, ²Radiology, UT Southwestern Medical Center, Dallas, TX, United States

We report in vivo spectroscopic imaging of N-acetyl aspartyl glutamate (NAAG) at 3T using PRESS-based localization method. We present in vivo data from five healthy volunteers. Repeatability, reproducibility results and linear regression with white matter fraction are also reported. Metabolites concentration maps are presented to visualize the regional distribution.

Andreas Hock^1,2, Niklaus Zoelch¹, Milan Scheidegger^1,2, Marcus Herdener², Erich Seifritz², and Anke Henning^1,3
1Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Zurich, Switzerland, ²Department of Psychiatry, Psychotherapy and Psychosomatics Hospital of Psychiatry, University of Zurich, Zurich, Zurich, Switzerland, ³Institute for Biological Cybernetics, Max Planck Institute, Tuebingen, Baden Württemberg, Germany

MRS measurements in small, specific human brain regions with high clinical relevance for neuropsychiatric disorders are executed using non-water suppressed MRS enabling frequency and phase alignment of individual FIDs prior averaging. Results obtained from 16 healthy volunteers from the anterior cingulate cortex, the nucleus accumbens, the amygdala, and the occipital cortex show, that Creatine, N-acetyl-aspartate, glutamate and the combination of Glu and glutamine, choline and myo-inositol could be quantified reliably in group average spectra and by far the most individual data sets. This may promote better understanding of possible dysfunctions of brain metabolism and neurotransmission in neuropsychiatric disorders.

Alfredo Liubomir Lopez Kolkovsky¹, Boucif Djemai¹, and Fawzi Boumezbeur^1
1CEA/Saclay/Neurospin, Commissariat a l'Energie Atomique, Gif-sur-yvette, Essonne, France

At ultra-high magnetic fields such as 17.2 T, it is crucial to establish T₁ and T₂ relaxation times in order to optimize MRS acquisition parameters and to achieve proper metabolite concentration quantification. In this study we present measurements of T₂ relaxation times of more than 18 metabolites and macromolecules in the rat brain in vivoat 17.2T. J-modulation of major brain metabolites such as glutamate and myo-inositol was adequately accounted for by our spin simulations. Compared to T₂ values measured at lower magnetic fields, our values are shorter which is consistent with the established field-dependence of T₂ to increased microscopic susceptibility gradients as B₀increases.

Mamta Aryabhushan Gupta¹, Poonam Rana¹, Seenu Haridas², Kailash Manda², BS Hemanth Kumar¹, and Subash Khushu^1
1NMR Research Centre, INMAS, DRDO, Delhi, delhi, India, ²Division of Radiation Biosciences, INMAS, DRDO, Delhi, delhi, India

Effect of whole body radiation exposure on central nervous system has not been explored much in brain. In the present study we investigate behavior evaluation and 1H MRS based early delayed cognitive and neurometabolite changes in hippocampus at 3 months following 5Gy whole body radiation exposure. Behavioral studies showed locomotory and discrimination ratio impaired in irradiated group.1H MRS revealed significant decrease in Glutamine and significant increase in myo inositol in irradiated group compared to controls. Our results demonstrate whole body radiation induced cognitive dysfunction and metabolic impairment at 3 months post whole body irradiation.

Henryk Faas¹, Maria Yanez Lopez¹, Samira Parhizkar², Stacey Knapp², Dorothee Auer¹, and Marie Christine Pardon^2
1Clinical Neurosciences, University of Nottingham, Nottingham, Nottingham, United Kingdom, ²Life Sciences, University of Nottingham, Nottingham, Nottingham, United Kingdom

Neuroinflammation plays a key role in a wide range of brain disorders, including stroke, Parkinson’s, and Alzheimer’s disease (AD). Using MR spectroscopy, we investigate the differential metabolic response of the brain to a standard neuroinflammatory challenge, comparing an AD mouse model with normal controls.

Helen Wu¹, Danielle Senador², Matthew Galloway³, Jeffrey Loeb^2,4, and Jeffrey Stanley^5
1Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, United States, ²Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, MI, United States, ³Psychiatry and Behavioral Neurosciences, Wayne State University, MI, United States, ⁴Neurology, University of Illinois at Chicago, IL, United States, ⁵Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, MI, United States

We used a chronic tetanus toxin rat model of interictal spiking as a platform to investigate longitudinal metabolite changes associated with epileptogensis. Our 1H MRS performed in vivo at 7T provides the opportunity to examine neocortical metabolite changes associated with the epileptogenic process in context of concurrent long term EEG changes. The goal of this study is to identify key biomarkers associated with epileptogensis in the neocortex, which we believe exhibits a different pattern of metabolite level changes than those observed in the hippocampus. Identification of such markers can help guide future clinical and pharmacological approaches.

Hasan Alsaid¹, Mary V Rambo¹, Tinamarie Skedzielewski¹, James R Armitage², Jon J Lyon², and Beat M Jucker^1
1Preclinical & Translational Imaging, LAS, PTS, GlaxoSmithKline, King of Prussia, PA, United States, ²Safety Assessment Tox/Path/Investigative, PTS, GlaxoSmithKline, Ware, Hertfordshire, United Kingdom

A clinically translatable 31P-MRS method was used to assess the high energy metabolite profile after the administration of GSK121A (50mg/kg or 25mg/kg), a known mitochondrial respiratory chain inhibitor. The results showed that liver ATP concentrations remained unchanged, Pi and Pi/ATP ratio were increased significantly in the GSK121A treated groups compared to vehicle, associated with a higher blood lactate level which correlated with the change in body temperature. While steady state ATP levels appear to be normal, there could potentially be a decrease in ATP synthesis associated with decreased body temperature and increase in Pi. This method may be used to assess drug effects on hepatic mitochondrial function in patients.

Elise Marie Vinckenbosch¹, João Miguel das Neves Duarte^1,2, and Rolf Gruetter^1,3
1Laboratory of functional and metabolic imaging, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, ²Faculty of Biology and Medicine, University of Lausanne, Switzerland, ³Department of Radiology, University of Lausanne and Geneva, Switzerland

Astrocyte importance in rat brain metabolism was highlighted by inhibiting glial TCA cycle at the level of aconitase with fluoroacetate. Changes in neurochemical profile upon glial-specific inhibition under hyperglycemia were measured by 1HMRS and brain compartmentalized metabolism adaptation was studied by following infused [1,6-13C] glucose degradation with 13C MRS at 14.1T. Glial aconitase inhibition had effects on alanine, lactate, aspartate, glutamate and glutamine brain concentrations. Disruption of ammonia homeostasis may be rescued by glutamine accumulation upon increased substrate supply. In 13C MRS, glial selectivity of fluoroacetate inhibition has been proved and observed glial metabolic failure didn’t affect glutamate TCA cycle.

Mahon L Maguire¹, Victoria Thornton¹, Sairam Geethanath², Vikram D Kodibagkar³, and Jurgen E Schneider^1
1BMRU, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, Oxon, United Kingdom, ²Dayananda Sagar College of Engineering, Bangalore, India, ³School of Biological and Health Systems Engineering, Arizona State University, Tempe, Arizona, United States

In vivo sodium quantification by MR offers direct insight into ion homeostasis and energy metabolism. Compressed sensing methods have the potential to dramatically shorten such lengthy experiments. We evaluate the effects of acceleration factor and signal-to-noise ratio on the fidelity of spectroscopic compressed sensing reconstruction. We also apply the reconstruction to high resolution ²³Na CSI in the beating mouse heart. Compressed sensing accurately reconstructs the spatial and spectral features of the fully sampled data even at high acceleration factors.

Aline Seuwen¹, Aileen Schröter¹, and Markus Rudin^1,2
1Institute for Biomedical Engineering, ETH & University of Zürich, Zürich, Zürich, Switzerland, ²Institute for Pharmacology and Toxicology, University of Zürich, Zürich, Switzerland

Glutamate is the most prevalent neurotransmitter in the brain and acts in excitatory synapses. During neuronal activity, glutamate levels can vary. In this study, we used slice selective proton spectroscopic imaging to measure changes in glutamate levels during electrical stimulation in the mouse hind paw. Glutamate levels were found to be increased in the contralateral somatosensory cortex, but remained almost constant on the ipsilateral side. This unilateral response is encouraging and indicates good specificity. Measuring glutamate level changes upon sensory stimulation might constitute an alternative to standard BOLD-fMRI in mice, for which systemic hemodynamic effects may contribute to the response.

Noam Shemesh¹, Jens T Rosenberg^2,3, Jean-Nicolas Dumez¹, Samuel Colles Grant^2,3, and Lucio Frydman^1,2
1Chemical Physics, Weizmann Institute of Science, Rehovot, Israel, ²National High Magnetic Field Laboratory, The Florida State University, Tallahassee, FL, United States,³Chemical & Biomedical Engineering, The Florida State University, Tallahassee, Florida, United States

Apparent metabolic T₁s are important for quantification of MRS spectra in vivo. Longitudinal Relaxation Enhancements (LREs) upon band-selective excitation are well-known for large, slowly tumbling molecules. The surprising existence of LREs for small endogenous Central Nervous System metabolites was only recently reported ex vivo. Here, we aim at developing and applying a localized LRE-MRS sequence capable of detecting LREs in vivo, testing their potential as stroke biomarkers in the rat. At 21.1 T, the Cre resonance showed a statistically significant LRE effect upon spectrally-selective excitation, which was time-dependent. Lac apparent T₁s also varied significantly upon stroke. These findings suggest LREs as novel potential stroke biomarkers.

Dong-Cheol Woo^1,2 and Robert E. Lenkinski^2
1Biomedical Research Center, ASAN Institute for Life Science, Asan Medical Center, Seoul, Seoul, Korea, ²Department of Radiology, UT Southwestern Medical Center, Dallas, Texas, United States

Our study is aimed at assessing neurochemical changes caused by scopolamine (SCP) induced memory impairment using proton in vivo MR spectroscopy. Adult male Swiss albino mice (n=32) were used. Mice were divided into four groups: SCP 0, 1, 3, and 5 (mg/kg). All mice underwent 1H MR spectroscopy twice: at 30 min and 72 hours after the injection of a solution containing SCP. Our results are in good agreement with previous published reports that showed that SCP reduced choline levels in the brain for about 2 hours. In vivo MR spectroscopy is a non-invasive method with which to evaluate the SCP induced memory impairment.

Igor Nestrasil¹, Chester B Whitley¹, Renee Cooksley², Brenda Koniar³, Roland Gunther³, and Ivan Tkac^4
1Department of Pediatrics, University of Minnesota, Minneapolis, MN, United States, ²Gene Therapy Center, University of Minnesota, Minneapolis, MN, United States,³RAR/Comparative Medicine, University of Minnesota, Minneapolis, MN, United States, ⁴Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, United States

Hurler syndrome, the severe form of mucopolysaccharidosis type I (MPS IH) is a lysosomal storage diseases caused by the deficiency in alpha-L-iduronidase (IDUA) enzyme which results in lysosomal accumulation of glycosaminoglycans. Knockout mice deficient for IDUA were used as a model of MPS IH. In vivo ¹H MRS and high-resolution MRI were used to investigate neurochemical and volumetric changes in MPS mice. The whole brain volumes and the relative sizes of ventricles were enlarges in MPS mice relative to controls. Increased levels of ascorbate (19%) in the hippocampus of MPS mice indicate a protective response against the oxidative stress.

Hui Zhang¹, Mingming Huang², Lifeng Gao¹, and Hao Lei^1
1State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, Hubei, China, ²Guiyang Medical University, Guiyang, Guizhou, China

In this work, we used in vivo ¹H MRS to measure metabolic changes in the striatum, hippocampus and visual cortex of streptozotocin (STZ)-induced T1DM rats at 4 weeks after induction. We found that, for STZ-treated animals, Glu, NAA and tNAA levels were significantly lower than control in striatum and hippocampus, but not in visual cortex. Tau and Ins levels were significantly higher only in hippocampus, but not in striatum and visual cortex; Glx remained unchanged in all three regions. Our results suggested that the metabolic alterations in the brain of STZ-induced T1DM are region-specific.

Charlie Yi Wang^1,2, Ya Chen^2,3, and Xin Yu^1,4
1Biomedical Engineering, Case Western Reserve University, Cleveland, OH, United States, ²Case Center for Imaging Research, Case Western Reserve University, Cleveland, OH, United States, ³Case Western Reserve University, Cleveland, OH, United States, ⁴Radiology, Case Western Reserve University, Cleveland, OH, United States

The opening of the mitochondrial Permeability Transition Pore (mPTP) during reperfusion is a critical step in the pathogenesis of ischemia/reperfusion injury. mPTP inhibition during reperfusion has been shown to be cardioprotective. However, few studies have reported the effect of mPTP inhibition on myocardial energetics during IR. This study aimed at investigating whether mPTP inhibition can normalize myocardial energetics during reperfusion using 31P MR spectroscopy.

Jennifer M Taylor^1,2, Xiao-Hong Zhu², Yi Zhang², and Wei Chen^1,2
1Biomedical Engineering, University of Minnesota, Minneapolis, MN, United States, ²Center for Magnetic Resonance Research, Radiology, University of Minnesota, Minneapolis, MN, United States

Multi-nuclei ¹H/³¹P MRS and electrophysiology were applied to investigate rat brain energetics and neuronal activity changes during and after whole brain occlusion. PCr change was consistent among animals, while lactate trends split into 2 groups. ATP depletion was delayed following occlusion onset, before following the PCr trend, while pH and lactate were highly correlated. LFP bands showed different response dynamics from MRS measures, but exhibited recovery dynamics similar to ATP. LFP bursts, however, had a delayed recovery after reperfusion. These multimodal measures provide insight into the oxidative to nonoxidative phosphorylation transition and hint at underlying neuronal energy needs.

Juergen Baudewig¹, Juergen Finsterbusch², and Susann Boretius^1
1Section Biomedical Imaging, Department of Radiology and Neuroradiology, Christian-Albrechts-University, Kiel, Germany, ²Dept. of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

In mice the cuboidal shape of voxels in classical localized proton MR spectroscopy (MRS) in combination the low fraction of white matter in mice hinders an exclusive quantification of metabolites from white matter structures. Here we used a recently developed localization method based on 2D-selective RF excitations to measure the corpus callosum and cortical gray matter to compare their NAA concentrations. Reduced NAA values in white matter compared in gray matter structures of mice were found. 2DRF excitations in MRS to acquire anatomically defined volumes in mice brain are a promising tool to improve the specificity of MRS.

Do-Wan Lee¹, Jung-Hoon Lee^1,2, Jung-Whan Min³, Sang-Young Kim¹, Jin-Young Jung¹, Kyu-Ho Song¹, and Bo-Young Choe^1
1Department of Biomedical Engineering, and Research Institute of Biomedical Engineering, The Catholic University of Korea, College of Medicine, Seoul, Seoul, Korea,²Department of Radiology, Kyunghee Medical Center, Seoul, Korea, ³Department of Radiological Science, The Shingu University College of Korea, Seongnam, Seongnam, Korea

The aim of present study was to provide ex vivo evidence of changes in neurochemical-profiles of rat hippocampus after 4-day binge ethanol intoxication, using 500-MHz HR-MAS 1H-NMR spectroscopy. Our results showed that Glu/tCr and Glx/tCr ratios were significantly higher in binge-ethanol group than in control group. Our main findings suggest that glutamate signals and glutamate-glutamine-cycle in hippocampal region are particularly sensitive to binge ethanol consumption. Future studies using a combination of human patients and in vivo animal investigations, as well as other neuroimaging approaches, are required to strengthen our findings and to validate translational component in binge alcohol intoxicated condition.

Anant Bahadur Patel¹, K.S. Varadarajan¹, Puneet Bagga¹, and Anup Nirmal Chugani^1
1NMR Microimaging and Spectroscopy, CSIR-Centre for Cellular and Molecular Biology, Hyderabad, Andhra Pradesh, India

Lead is a highly poisonous heavy metal with widespread use in construction and industries. Chronic exposure to lead has shown to cause systemic damage leading to permanent cognitive and behavioral impairment. Glutamatergic and GABAergic neuro-energetics were evaluated in the cerebral cortex and hippocampus of adult male C57BL6 mice using¹H-[¹³C]-NMR spectroscopy in conjunction with infusion of [1,6-¹³C₂]glucose. Glutamatergic neuronal activity was found to be reduced in the cortical and hippocampal regions due to chronic lead toxicity while GABAergic function was perturbed only in the hippocampus.

Anant Bahadur Patel¹, Vivek Tiwari¹, Kamal Saba¹, and Subhash C. Lakhotia^2
1NMR Microimaging and Spectroscopy, CSIR-Centre for Cellular and Molecular Biology, Hyderabad, Andhra Pradesh, India, ²Department of Zoology, Banaras Hindu University, Varanasi, Uttar Pradesh, India

AβPP-PS1 mice have been shown to closely mimic the human Alzheimer's disease (AD) pathology. The present study was undertaken to evaluate the effect of Ayurvedic drug Amalaki Rasayana (AR) on cognitive function, and cerebral metabolism associated with glutamatergic and GABAergic neurons in AβPP-PS1 mice as compared with the changes brought about by the known AD drug, donepezil. Cerebral metabolism was studied using ¹H-[¹³C]-NMR spectroscopy together with infusion of [1,6-¹³C₂]glucose in 12 months old AβPP-PS1 mice. Intervention with AR significantly improved the learning/memory, and excitatory and inhibitory functions across brain regions in AβPP-PS1 mice similar to that following administration of donepezil.

Anant Bahadur Patel¹, Madhavi Adusmilli¹, Sandeep Saxena¹, and Mohammed M Idris^1
1CSIR-Centre for Cellular and Molecular Biology, Hyderabad, Andhra Pradesh, India

Brain metabolism was investigated in zebrafish by ¹H-[¹³C]-NMR spectroscopy. Zebrafish were anesthetized with tricane and [1,6-¹³C₂]glucose was administered through intracardiac injection. The concentration and ¹³C labeling of brain metabolites were measured using ¹H-[¹³C]-NMR spectroscopy in brain extract. The ¹³C turnover of brain amino acids from [1,6-¹³C₂]glucose in zebrafish is similar to the pattern observed in rat and mouse brain. Moreover, the brain energy metabolism in zebrafish is decreased with acute ethanol treatment. Zebrafish would be useful alternate model to study mechanism of various neurological disorders and screening of drugs.

Mark Aurel Augath¹, Aline Seuwen¹, Stefan Zwick², and Markus Rudin^1
1Inst. for Biomedical Engineering, ETH and University Zurich, Zurich, Switzerland, ²Bruker BioSpin, Fällanden, Switzerland

The assessment of CMRO2 with 17O-MRI is hampered by a 34000 times smaller signal than that of 1H. In this study we present a cryogenic RF coil for the use of 17O- MRI at 54.27 MHz and make a comparison with a home-built room temperature coil. The 16 mm cryogenic 17O coil was cooled to 30 K and had a Q of 480. Single pulse acquisitions yielded an SNR gain of about 5.3 and a gain in signal stability of more than 8 compared to the room temperature coil. 3D-FLASH images of H217O the mouse brain were acquired of with 1x1x2 mm3 resolution.

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

Although aluminium has been linked to dementia type diseases including Alzheimer’s and Parkinson’s disease in molecular aspects, the cerebral energy metabolism associated with glutamatergic and GABAergic neurons with aluminium exposure remains elusive. In this study, we have investigated the glutamatergic and GABAergic metabolism in the cerebral cortex, hippocampus and striatum regions of mice under sub-acute exposure of aluminium chloride by using ¹H-[¹³C]-NMR spectroscopy together with infusion of [1,6-¹³C₂]glucose. Both, glutamatergic and GABAergic metabolism were found to be enhanced in aluminium chloride treated mice, which may be due to inflammatory response of aluminium toxicity in brain.

Pravin Kumar Mishra¹ and Anant Bahadur Patel^1
1NMR Microimaging and Spectroscopy, CSIR-Centre for Cellular and Molecular Biology, Hyderabad, Andhra Pradesh, India

The current study investigates the response of ketamine in behavioral phenotype, and cerebral energy metabolism in the social defeat model of depression. Mice were subjected to social defeat (SD) paradigm for 10 days, and behavioral phenotypes were assessed using sucrose preference and social interaction. Ketamine was administered at sub-anesthetic dose in control and SD mice. Metabolic measurements were carried out by ¹H-[¹³C]-NMR spectroscopy in conjunction with infusion of [1,6-¹³C₂]glucose. Intervention with ketamine improved the sucrose preference and social interaction in SD mice. Moreover, the reduced neuronal metabolic activity in SD mice could recover to control value with ketamine treatment.

Anant Bahadur Patel¹, Pravin Kumar Mishra¹, and Madhavi Adusmilli^1
1NMR Microimaging and Spectroscopy, CSIR-Centre for Cellular and Molecular Biology, Hyderabad, Andhra Pradesh, India

The molecular mechanism responsible for depression is still elusive. The present study evaluate neural metabolism in the prefrontal cortex of mice subjected to chronic unpredictable mild stress (CUMS). Sucrose preference and forced swim test were carried out to assess the behavioral phenotype. The neuronal and astroglial metabolism were monitored by ¹H-[¹³C]-NMR spectroscopy together with infusion of [1,6-¹³C₂]glucose and [2-¹³C]acetate, respectively. Mice subjected to CUMS exhibit increased immobility in the forced swim test and less sucrose preference which are typical phenotype of depression. Most importantly, the glutamatergic, GABAergic and astroglial metabolic activities were found to decreased in CUMS treated mice.

Anant Bahadur Patel¹, Kamal Saba¹, Vivek Tiwari¹, and Pandichelvam Veeraiah^1
1NMR Microimaging and Spectroscopy, CSIR-Centre for Cellular and Molecular Biology, Hyderabad, Andhra Pradesh, India

Long term exposure of aluminium in rodents has been shown to form amyloid oligomer, similar to Alzheimer’s disease (AD) pathology. The present study evaluates the effects of chronic aluminium exposure on the cortical metabolism associated with glutamatergic and GABAergic neurons. The metabolism was studied using ¹H-[¹³C]-NMR spectroscopy in conjunction with infusion of [1,6-¹³C₂]glucose in mice treated with aluminium (i.p.). The chronic exposure of aluminium reduced TCA cycle and neurotransmitter cycle fluxes of the excitatory and inhibitory neurons.