Li An¹, Shizhe Li¹, and Jun Shen^1
1National Institute of Mental Health, National Institutes of Health, Bethesda, MD, United States

A data acquisition and quantification approach is proposed for simultaneous measurement of concentration, T₁, and T₂ of metabolites. The concentration, T₁, and T₂ of NAA, creatine, choline, glutamate and myo-inositol were determined reliably in less than 9 min using single voxel MRS at 7 Tesla.

Feng-Hua Ma¹, Guo-Fu Zhang¹, Jin-Wei Qiang², Ya-Min Rao³, Song-Qi Cai⁴, and Hai-Min Li^4
1Department of Radiology, Obstetrics & Gynecology Hospital, Shanghai Medical College,Fudan University., Shanghai, China, People's Republic of, ²Department of Radiology, Jinshan Hospital, Shanghai Medical College,Fudan University, Shanghai, China, People's Republic of, ³Department of Radiology, Obstetrics& Gynecology Hospital, Shanghai Medical College, Fudan University, Shanghai, China, People's Republic of, ⁴Department of Radiology, Jinshan Hospital, Shanghai Medical College, Fudan University, Shanghai, China, People's Republic of

Because of the overlap in the imaging appearances of the benign, borderline, and malignant tumors, a considerable portion of cystic epithelial ovarian tumors(EOT) cannot be correctly diagnosedon conventional MR imaging. Recently, the rapid development of software and hardware has enabled the increasing application of proton magnetic resonance spectroscopy (¹H-MRS) in ovarian tumors. However, 1H-MRS studies are still preliminary. To our knowledge, in vivo ¹H-MRS differentiation of a single type of histopathological and morphological tumors has not yet been studied. We prospectively performed in vivo ¹H-MRS of 86 patients with cystic EOT to understand the spectroscopic characteristics of different types of tumors and to investigate the ability of ¹H-MRS in the differentiation of benign, borderline and malignant EOT. The results shows that ¹H-MRS patterns of benign, borderline and malignant cystic EOT are different. The Cho/Cr ratio increases with the higher malignancy and a high Cho peak indicates a malignant tumor. A significantly elevated NAA peak indicates a borderline tumor.

Jong Bum Son¹, Sooyoung Shin¹, Ralph Noeske², Ersin Bayram³, Jingfei Ma¹, and Haesun Choi^1
1The University of Texas MD Anderson Cancer Center, Houston, TX, United States, ²GE Healthcare Technologies, Potsdam, Germany, ³GE Healthcare Technologies, Waukesha, WI, United States

Prostate MR spectroscopic imaging (MRSI) is limited with long acquisition time and need for an endorectal coil. Using an acquisition-weighted spectroscopic imaging sequence with an odd symmetric sampling scheme and a sorted singular value decomposition method for spectral processing of data from a multiple receive channels, we demonstrated that in vivo prostate MRSI can be performed at 3T in a substantially reduced scan time and without using an endorectal coil. Our proposed technique has the potential to help substantially expand the clinical use of prostate MRSI.

Rashmi Reddy¹, Imam Shaik¹, Arush Honnedevasthana¹, Pavan Poojar¹, and Sairam Geethanath^1
1Dayananda Sagar Institutions, Bangalore, India

Magnetic Resonance Spectroscopic Imaging (MRSI) is used as a tool to quantify metabolites in human brain and other organs. It is extensively used in clinical imaging and clinical research applications¹. However, the major drawback of this technology is its long acquisition time which is the primary reason for not being used in the clinics. A novel approach of accelerating MRSI using Magnetic Resonance Fingerprinting (MRF) has been proposed in the current work. 

Alejandro Santos Diaz¹, Alireza Akbari¹, and Michael Noseworthy^1,2,3
1School of Biomedical Engineering, McMaster University, Hamilton, ON, Canada, ²Imaging Research Centre, St Joseph's Healthcare, Hamilton, ON, Canada, ³Electrical and Computer Engineering, McMaster University, Hamilton, ON, Canada

Long acquisition time due to the low sensitivity is one of the main constrains for using 31P MRSI on a regular basis. Different methods have been proposed to accelerate the acquisition showing advantages and limitations. In this work we present for the first time an in vivo experiment using flyback-Echo Planar Spectroscopic Imaging readout and compare it with the traditional fidCSI sequence. Results suggest that the technique might be suitable for clinical applications.

Ariel Hafftka^1,2, Hasan Celik¹, Wojciech Czaja², and Richard G. Spencer^1
1Laboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health, Baltimore, MD, United States, ²Department of Mathematics, University of Maryland, College Park, MD, United States

Magnetic resonance (MR) relaxometry and related experiments provide useful information about tissues.  These experiments reveal the distribution of a parameter, such as T2-relaxation, in a sample.  The process required to recover the distribution from the observed data, an inverse Laplace transform (ILT), is highly ill-conditioned, meaning that small amounts of noise can create huge changes in the solution.  Recent work has shown using simulations that 2D MR experiments result in a problem substantially more stable than in 1D.  We present a theorem quantifying stability of the ILT and use it to explain the improved performance in 2D.  

Kristian Rink¹, Moritz C. Berger¹, Nadia Benkhedah¹, Christine Gnahm¹, Peter Bachert¹, and Armin M. Nagel^1,2
1German Cancer Research Center (DKFZ), Heidelberg, Germany, ²University Medical Center Ulm, Ulm, Germany

Phosphorus (³¹P)-containing biomolecules play a crucial role in the energy metabolism of all cells. Since the in vivo MR signal of ³¹P is four orders of magnitude smaller compared to hydrogen, strategies to improve the signal-to-noise (SNR) are required. Therefore, this study focuses on the development of a signal-effective ³¹P acquisition in combination with a constraint iterative reconstruction applying prior knowledge from recorded hydrogen (¹H) data.

James Grist¹, Martin J Graves¹, Josh Kaggie¹, Mary Mclean², Frank Riemer¹, and Ferdia A Gallager^1
1Radiology, University of Cambridge, Cambridge, United Kingdom, ²Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom

Sodium T₁ maps from three different Variable Flip Angle (VFA) methods were assessed against Inversion Recovery (IR) data, showing that the estimated method of slopes (eMOS) is superior to both linear and non-linear fitting methods in the healthy brain. eMOS requires two flip angle data sets to produce volumetric T₁ maps of the brain, in comparison to other techniques which require 4 or more data sets to produce maps, and therefore allows for shortening of the overall time spent scanning. Furthermore, T₁ maps may also give further insight in to the underlying tissue structure surrounding sodium nuclei.

Arthur Coste¹, Nicolas Chauffert^1,2, Alexandre Vignaud¹, Philippe Ciuciu^1,2, Fawzi Boumezbeur¹, Pierre Weiss³, Sandro Romanzetti⁴, Denis Le Bihan¹, and Cécile Lerman^1
1MR Imaging and Spectroscopy Unit, NeuroSpin, Gif sur Yvette, France, ²Parietal, INRIA Saclay, Saclay, France, ³Institut des Technologies Avancées du Vivant, Toulouse, France, ⁴University Clinic RWTH Aachen, Aachen, Germany

This work illustrates the application of a wavelet based least square regularized image reconstruction for non-Cartesian MR sampling trajectories in the framework of low concentration Phosphorus Imaging. We compared performances between 3D Cartesian Fast Imaging with Steady-state free Precession (FISP) and the TPI (FISP) sequence and show that in equivalent acquisition durations we are able to produce better images with the TPI sequence. Prospective sub-sampling was also performed and results open exciting possibilities to reduce acquisition time without impacting image quality for non-proton MRI.

Yuchi Liu¹, Yun Jiang¹, Charlie Yi Wang¹, Mark Alan Griswold^1,2, and Xin Yu^1,2,3,4
1Biomedical Engineering, Case Western Reserve University, Cleveland, OH, United States, ²Radiology, Case Western Reserve University, Cleveland, OH, United States, ³Physiology and Biophysics, Case Western Reserve University, Cleveland, OH, United States, ⁴Case Center for Imaging Research, Case Western Reserve University, Cleveland, OH, United States

In this study, a fast phosphocreatine (PCr) imaging method was developed by combining spectrally selective bSSFP with single-shot spiral-in/out encoding for measuring PCr distribution in vivo. 2 min acquisition yielded an SNR of ~9 in rat calf muscles with high spatial resolution (1.25 mm×1.25 mm×5 mm) at 9.4T. The SNR was increased to 25.5 with 30 min acquisition. This method also has the potential for imaging other metabolites such as ATP with a different carrier frequency, dynamic PCr imaging in exercise-recovery or ischemia-reperfusion studies, and quantification of the absolute metabolite concentration with appropriate T₁, T₂, and flip angle calibration/correction.

Hannes Michel Wiesner¹, Xiao-Hong Zhu¹, Kamil Ugurbil¹, and Wei Chen^1
1CMRR, Radiology, University of Minnesota Medical School, Minneapolis, MN, United States

In vivo ¹⁷O MRS imaging provides a valuable tool for quantitatively imaging the cerebral rate of oxygen metabolism, cerebral blood flow and oxygen extraction fraction from a brief inhalation of ¹⁷O-isotope labeled oxygen gas. In this study, we conducted a pilot test to examine the ¹⁷O sensitivity using the human head size water phantom in the world's first 10.5T whole-body human scanner at the CMRR, then compared it with that at 7T. We found approximately doubled ¹⁷O sensitivity at 10.5T after careful consideration signal and noise contributions at both fields.

Simon Konstandin¹ and Matthias Günther^1,2
1MR-Imaging and Spectroscopy, University of Bremen, Bremen, Germany, ²Fraunhofer MEVIS, Bremen, Germany

Sodium MRI can act as a biomarker for heart tissue viability. However, several aspects (blurring behavior of non-Cartesian ultra-short echo time sequences, blurring because of heart motion, small myocardial infarction (MI) regions) complicate MI detection due to resolution reasons. Optimal sequence parameters are difficult to find since many subject parameters (e.g., relaxation times, heart motion) must be considered. The presented simulation model of a beating heart can be used to optimize sequence parameters, among other things, for better visualization of MI and can be adapted to any kind of motion and to different subject/physiological parameters.

Arthur Coste¹, Alexandre Vignaud¹, Philippe Ciuciu^1,2, Fawzi Boumezbeur¹, Franck Mauconduit³, Alexis Amadon¹, Sandro Romanzetti⁴, Denis Le Bihan¹, and Cécile Lerman^1
1MR Imaging and Spectroscopy Unit, NeuroSpin, Gif sur Yvette, France, ²Parietal, INRIA Saclay, Saclay, France, ³Siemens Healthcare, Saint Denis, France, ⁴University Clinic RWTH Aachen, Aachen, Germany

This work describes a novel method accounting for MR acquisition properties (B₀, B₁⁺,B₁^-,T₁,T₂*) to perform concentration measurements in the framework of in vitro Phosphorus MRI. Our pipeline uses a non-Cartesian 3D sequence for efficient signal sampling and a wavelet regularized least square method for reconstruction. We demonstrated within an acceptable time for human experiment, for 5mm isotropic resolution, that we are able to calibrate and measure absolute ³¹P concentrations.

Anja M. Marschar¹, Moritz C. Berger¹, Mark E. Ladd¹, Peter Bachert¹, and Armin M. Nagel^1,2
1Medical Physics in Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, ²Diagnostic and Interventional Radiology, University Medical Center Ulm, Ulm, Germany

Both lower legs of three male healthy volunteers were examined at 3 T and 7 T by means of ¹H and ²³Na MRI to obtain quantitative maps of the sodium and water content in muscle tissue. Corrections for T₂^* and T₁ relaxation and RF profiles (B₁⁺, B₁^–) were performed. The resulting water content value in calf muscle tissue was in the range of 75–85 mol/l, the level of sodium was 15–21 mmol/l (sodium-to-water content ratio: 0.20–0.27 ‰).

Yongxian Qian¹, Tiejun Zhao², Steven Baete¹, Karthik Lakshmanan¹, Graham Wiggins¹, and Fernando E Boada^1
1Radiology, New York University, New York, NY, United States, ²Siemens Medical Solutions USA, New York, NY, United States

A transmit/receive (Tx/Rx) array coil has high efficiency in transmission and thus reduces specific absorption rate (SAR), which is highly desired in clinical applications for sodium (23Na) MR imaging. However, a Tx/Rx array coil at 3T usually produces a spatially-varying excitation (B1+) field and does not provide a uniform sum-of-squares of coil sensitivities (B1- fields) for quantitative sodium MRI. Here we present a solution to this problem and demonstrate its effectiveness with studies on phantoms and subjects with neurological disorders such as multiple sclerosis (MS), epilepsy, and mild traumatic brain injury (mTBI). 

Qiang Ning^1,2, Chao Ma², Fan Lam², Bryan Clifford^1,2, and Zhi-Pei Liang^1,2
1Electrical and Computer Engineering, University of Illinois, Urbana-Champaign, Urbana, IL, United States, ²Beckman Institute for Advanced Science and Technology, University of Illinois, Urbana-Champaign, Urbana, IL, United States

A new method is proposed for spectral quantitation of MRSI data. The method has two main features: 1) incorporation of prior spectral knowledge in the form of basis functions obtained by quantum simulation, and 2) incorporation of prior spatial knowledge by penalizing smoothness within each type of tissue. An efficient algorithm is also proposed to solve the underlying optimization problem, and its effectiveness for extracting quantitative spectral information from noisy MRSI data is demonstrated by comparing it with one of the state-of-the-art methods.

Ralph Noeske¹ and Rolf F Schulte^2
1GE Healthcare, Potsdam, Germany, ²GE Global Research, Munich, Germany

Echo-Planar Spectroscopic Imaging (EPSI) reduces the long acquisition time of Chemical Shift Imaging. “Flyback” trajectories sampling the lobe only along one direction are commonly used for robustness and artifact reasons. Main challenge in the design is that  there is no analytic solution for an SNR optimized readout/flyback trapezoid pair. The goal of this work was to implement a fast SNR optimized algorithm that takes Peripheral Nerve Stimulation into account to calculate waveforms on the fly for any given spectral and spatial resolution and therefore doesn’t require pre-calculated waveforms.  

Manoj Kumar Sarma¹, Zohaib Iqbal¹, Rajakumar Nagarajan¹, and M. Albert Thomas^1
1Radiological Sciences, UCLA School of Medicine, Los angeles, Los Angeles, CA, United States

Phase encoded MR spectroscopic imaging (MRSI) is a time-consuming protocol because there is a large number of phase encodings to be collected. Non-uniform undersampling (NUS) and Compressed Sensing (CS), which has been widely used in MRI/MRS can be used to speed up the acquisition further.  In this study, we have implemented a novel CS based multi -echo echo planar J-Resolved spectroscopic imaging (ME-EP-JRESI) acquisition and CS reconstruction in in human brain at 3T. We were able to detect and quantify several metabolites using a modified ProFit algorithm. The CS reconstructed spectra were of high quality, with metabolite ratios matching the fully encoded data closely.

Manoj Kumar Sarma¹, Paul Michael Macey², Zohaib Iqbal¹, Rajakumar Nagarajan¹, Ravi Aysola³, and M. Albert Thomas^1
1Radiological Sciences, UCLA School of Medicine, Los angeles, Los Angeles, CA, United States, ²School of Nursing, UCLA School of Medicine, Los angeles, Los Angeles, CA, United States, ³Division of Pulmonary and Critical Care Medicine, UCLA School of Medicine, Los angeles, Los Angeles, CA, United States

With the rise of people with obesity and older age, obstructive sleep apnea (OSA) has become a potentially disabling health problem. Continuous positive airway pressure (CPAP) is the most common treatment method for OSA patients. Here we examined neurochemical changes of untreated and CPAP treated OSA patients versus healthy controls in several brain region including parietal gray/white, insular cortex and frontal gray/white regions to demonstrate the nature of tissue changes using an accelerated five-dimensional (5D) echo-planar J-resolved spectroscopic imaging (EP-JRESI) sequence. We observed statistically significant differences between OSA patients and healthy control subjects in the occipital gray NAA/Cr, frontal gray Ch/Cr and mI/Cr, and occipital white Ch/Cr regions. Most of the differences were seen to be reversed in the OSA patients’ with CPAP cohort except that the differences in occipital gray NAA/Ch and frontal gray mI/Cr remained significance. To validate our findings, further longitudinal studies using a large cohort of OSA subjects before and after CPAP are required. These pilot findings demonstrate that the 5D EP-JRESI sequence can be easily combined with any MRI protocol. 
 

Rohini Vidya Shankar¹, Houchun Harry Hu², John C Chang³, and Vikram D Kodibagkar^1
1Biomedical Engineering, Arizona State University, Tempe, AZ, United States, ²Radiology, Phoenix Children's Hospital, Phoenix, AZ, United States, ³Banner MD Anderson Cancer Center, Gilbert, AZ, United States

The spatial variations in brain metabolite concentrations can be mapped using magnetic resonance spectroscopic imaging (MRSI). The long scan times in MRSI do not permit its inclusion in pediatric imaging protocols. MRSI accelerated by compressed sensing was used to image the pediatric brain for various acceleration factors 2X-5X. The retrospectively undersampled reconstructions showed high data fidelity for up to 80% undersampling when compared with the fully sampled reference dataset. Studies are underway to prospectively acquire and validate CS accelerated MRSI data in pediatric patients. 

Maryam Vareth^1,2, Yan Li², and Sarah Nelson^1,2
1UCBerkeley/UCSF Joint Graduate Group in Bioengineering, University of California Berkeley, Berkeley, CA, United States, ²Department of Radiology and Biomedical Imaging, Surbeck Laboratory of Advanced Imaging, San Francisco, CA, United States

This work investigates the feasibility of using GRAPPA-EPSI based reconstruction of the short-echo 3D MRSI to shorten the acquisition time and to increase the spatial resolution for future routine clinical purposes.  Fully sampled data were retrospectively under-sampled to achieve effective acceleration rate of 2, 3 and 4 using variety of sampling patterns.  GRAPPA algorithm was modified to take advantage of the FID time points and handle the arbitrary sampling patterns.  Additional technique was also developed to prospectively udner-sample in-vivo data with various patterns for future studies.

Zohaib Iqbal¹ and M. Albert Thomas^1
1Radiological Sciences, University of California - Los Angeles, Los Angeles, CA, United States

Measuring the transverse relaxation times (T₂s) of metabolites from different regions of the brain provides important insight into different pathologies, but requires long acquisition. A novel k-space acquisition using a hybrid technique involving both echo planar spectroscopic imaging (EPSI) and concentrically circular echo planar trajectories (SI-CONCEPT) was applied to simulated brain tumor spectroscopic imaging data. In addition, an algorithm incorporating the backprojection information from the EPSI scan was developed to enhance the spectroscopic images. This novel acquisition and reconstruction technique, called SI-WEB, decreases the total duration of the scan while producing similar results when compared to the true T₂ spectroscopic images. 

Rajakumar Nagarajan¹, Zohaib Iqbal¹, Manoj K Sarma¹, Mario Guerrero ², Vanessa Correa ², Eric S Daar², and M.Albert Thomas^1
1Radiological Sciences, University of California Los Angeles, Los Angeles, CA, United States, ²Department of Medicine, Harbor-UCLA Medical Center, Torrance, CA, United States

HIV affects more than 1 million individuals In the US and over 40 million people worldwide. CNS is commonly involved in the early stage HIV infection. Conventional 3D MRSI is time-consuming because it involves a large number of phase encodings. EPSI approaches have been used to reduce the long acquisition time required for multiple spatial encoding steps. In our study, non-uniformly undersampled (NUS) semi LASER based 3D EPSI was used to quantitate changes in brain metabolites, NAA, Cr, Cho and myo-inositol in a group of HIV adults in comparison to age matched control sample using compressed sensing reconstruction by minimizing total variation.

Abas Abdoli¹, Radka Stoyanova², and Andrew A. Maudsley^1
1Radiology, University of Miami, Miami, FL, United States, ²Radiation Oncology, University of Miami, Miami, FL, United States

In this study we evaluate a new principal components analysis (PCA) based denoising method for volumetric MRSI data that employs a statistical test for the selection of the significant noise-free principle components (PCs).

Chao Ma¹, Fan Lam¹, Qiang Ning^1,2, Bryan A. Clifford^1,2, Ryan Larsen¹, and Zhi-Pei Liang^1,2
1Beckman Institute, University of Illinois Urbana-Champaign, Urbana, IL, United States, ²Electrical and Computer Engineering, University of Illinois Urbana-Champaign, Urbana, IL, United States

Conventional Fourier based phosphorus (31P)-MRSI methods have been limited by spatial resolution due to the low concentrations of phosphate-contained chemical compounds in the human body and the relatively low sensitivity of 31P NMR. This work presents a subspace-based data acquisition and reconstruction method to achieve accelerated, high-resolution 31P-MRSI. The feasibility of the proposed method is demonstrated using both phantom and in vivo experimental studies on a 3T scanner, which have yielded very promising results. The proposed method can be used in a range of 31P-MRSI applications.

Charlie Yi Wang¹, Yuchi Liu¹, Shuying Huang¹, Mark Alan Griswold^1,2, and Xin Yu^1,2
1Biomedical Engineering, Case Western Reserve University, Cleveland, OH, United States, ²Radiology, Case Western Reserve University, Cleveland, OH, United States

We propose a novel ³¹P Creatine Kinase encoding Magnetic Resonance Fingerprinting method (CK-MRF) to efficiently measure high energy phosphate metabolism through creatine kinase (CK). Measurement reproducibility of CK rate constant (k_f,CK) using CK-MRF was compared with both conventional ³¹P saturation transfer method, and Four Angle Saturation Transfer method in rat hind limb.  CK-MRF measurement showed comparable or superior reproducibility using 20 s experiment time compared to 160 s experiment time of either comparison method.  Changes in k_f,CK following Ischemia/Reperfusion (IR) were also measured. 

Frits H.A. van Heijster¹, Vincent Breukels¹, Kees (C). J. Jansen², Jack A. Schalken², and Arend Heerschap^1
1Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, Netherlands, ²Urology, Radboud University Medical Center, Nijmegen, Netherlands

Citrate production by prostate cancer cell lines LNCaP and VCaP were studied with ¹³C-NMR spectroscopy. Glucose acts as carbon source for citrate production in LNCaP and VCaP cell lines, but not aspartate, in contrast to expectation. Also pyruvate and glutamine can act as carbon sources for citrate production in LNCaP. Anaplerosis via pyruvate carboxylase is found to be low in these cells. Glutamine label only ends up in citrate via isocitrate instead of downstream in the Krebs cycle. These typical features of citrate metabolism might serve as valuable biomarkers for transition from healthy prostate cells to malignant cells.

Limiao Jiang¹, Mary C Stephenson¹, John J Totman¹, Stephanie Marchesseau¹, Arthur Mark Richards², and Lieng H. Ling^2
1Clinical Imaging Research Center, A*STAR & National University of Singapore, Singapore, Singapore, ²Department of Medicine, Yong Loo Lin School of Medicine and Cardiovascular Research Institute, National University Health System, Singapore, Singapore

31P MRS can noninvasively reflect the in vivo energy metabolism without using ionizing radiation. It has been widely applied in the clinical studies of cardiac energetics under different pathophysiological conditions. The aim of the present study was to evaluate the myocardial energetics in 30 patients with moderate or severe degenerative mitral regurgitation (DMR) using 31P MRS.

Jimin Ren¹, A. Dean Sherry¹, and Craig R. Malloy^1
1Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, United States

Despite recent advances in measuring ATP energy metabolism using 31P magnetization transfer, there is still a lack of localized techniques capable of assessing the regional ATP synthesis.  The importance of measuring regional ATP rates and fluxes in the human brain is highlighted by the heterogeneity in normal brain functions and also in many cerebral metabolic abnormalities.   In this study, we demonstrate that, by combining wide-band inversion transfer with image selected in vivo spectroscopy (ISIS), quantitative information regarding ATP synthesis reaction Pi ==> γ-ATP can be obtained from the localized regions in the human brain.

Lucian A. B. Purvis¹, William T. Clarke¹, Michael Pavlides¹, Matthew D. Robson¹, and Christopher T. Rodgers^1
1OCMR, Department of Cardiovascular Medicine, University of Oxford, Oxford, United Kingdom

Phosphomonoesters (PME) and phosphodiesters (PDE) are emerging biomarkers in cirrhosis and fatty liver disease. In this study, phosphorus (³¹P) liver metabolite concentrations were quantified at 7T for 10 healthy volunteers using a 28 minute, 3D UTE-CSI sequence and an endogenous 2.5mM ATP reference. The inorganic phosphate concentration was 1.95 ± 0.18mM (1.25-2.43mM in the literature). Summing individual ester peaks, the total PME and PDE concentrations were 1.90 ± 0.29mM (cf. 1.98-3.89mM) and 4.31 ± 0.80mM (cf. 8.01-11.40mM). We attribute this apparent reduction in PDE to a broadening of the underlying phospholipid bilayer resonance and the increased spectral resolution at 7T.

Ming Lu¹, Xiao-Hong Zhu¹, Yi Zhang¹, Walter Low², and Wei Chen^1
1Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, United States, ²Neurosurgery, University of Minnesota, Minneapolis, MN, United States

Recently, we developed a novel 3D-Deuterium MR (DMR) approach able to simultaneously image glucose consumption rate and TCA cycle flux in rat brain at ultrahigh field. To evaluate its sensitivity in detecting altered metabolism, in this study, we acquired localized DMR spectra in rat brains with gliosarcoma following a brief infusion of deuterated glucose at 16.4 T. We observed accelerated glucose consumption and lactate accumulation accompany with decreased glutamate/glutamine turnover in brain regions with tumor. This pilot study demonstrates the feasibility of the in vivo DMR imaging approach for investigating abnormal glucose metabolism in brain tumor at ultrahigh field.

Ruomin Hu¹, Andreas Neubauer¹, Jorge Chacón-Caldera¹, Javier Uranga Solchaga¹, Christian Schuch², Tilo Gläser², Cordula Nies³, Eric Gottwald³, Stefan Giselbrecht⁴, and Lothar R. Schad^1
1Computer Assisted Clinical Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany, ²NUKEM Isotopes Imaging GmbH, Alzenau, Germany, ³Institute for Biological Interfaces 5, Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen, Germany, ⁴Department of Complex Tissue Regeneration, MERLIN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, Netherlands

In this work we present a novel in vitro oxygen-17 NMR method using ¹⁷O-labeled glucose to investigate the metabolic process of cells cultivated in a MR-compatible microbioreactor. The metabolization of ¹⁷O-labeled glucose was demonstrated to produce MR-detectable H₂¹⁷O on the one hand and to not intervene with the inherent cellular physiology on the other hand, thus proving the method to serve as a neutral observation platform. The presented method has the potential to aid the modeling of fundamental physiological processes and to become a key element in cellular vitality assessment applications.

Robert Borowiak^1,2, Wilfried Reichardt^1,2, Dmitry Kurzhunov¹, Christian Schuch³, Jochen Leupold¹, Thomas Lange¹, Marco Reisert¹, Axel Krafft^1,2, Elmar Fischer¹, and Michael Bock^1
1University Medical Center Freiburg, Dept. of Radiology - Medical Physics, Freiburg, Germany, ²German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany,³NUKEM Isotopes Imaging GmbH, Alzenau, Germany

In this work, we demonstrate the feasibility of monitoring glucose uptake in mouse brain using direct ¹⁷O-MRS at 9.4 Tesla for the first time. Time-resolved ¹⁷O-MRS spectra (temporal resolution: 42 s) are acquired in vivo after injection of D-glucose with ¹⁷O-labeled hydroxyl groups. The cerebral rate of glucose metabolism CMR_Glc is estimated using a pharmacokinetic model in an anesthetized (1.25% isoflurane) mouse to 0.43 ± 0.21 µmol/g/min, which is of the same order of magnitude as reported by ¹⁸F-FDG PET.

Sebastian C. Niesporek¹, Reiner Umathum¹, Thomas M. Fiedler¹, and Armin M. Nagel^1,2
1Medical Physics in Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, ²Diagnostic and Interventional Radiology, University Medical Center Ulm, Ulm, Germany

Functional information of cell and tissue viability can be obtained via dynamic ¹⁷O-MRI. The quantification of H₂¹⁷O-concentration as a turnover product of oxidative phosphorylation in combination with ¹⁷O₂-inhalation enables mapping of the cerebral metabolic rate of oxygen consumption (CMRO₂). Due to low MR-sensitivity of the ¹⁷O-nucleus, spatial as well as temporal resolution is limited. Induced partial volume effects hinder accurate and stable signal quantification which is essential for dynamic studies. High resolution ¹⁷O-data with (4.5mm)³ was acquired with a Golden Angle acquisition scheme which allowed reconstruction of arbitrary time-frames. A partial volume correction algorithm was applied to test correction capability of data of different temporal resolution.

Sebastian C. Niesporek¹, Reiner Umathum¹, Thomas M. Fiedler¹, and Armin M. Nagel^1,2
1Medical Physics in Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, ²Diagnostic and Interventional Radiology, University Medical Center Ulm, Ulm, Germany

The energy balance of a cell is closely connected to in-vivo H₂¹⁷O-concentration which also is the turnover product of oxidative phosphorylation. ¹⁷O-MRI during inhalation of ¹⁷O₂ enables localized mapping of cerebral metabolic rate of oxygen consumption (CMRO₂). Larger voxel sizes due to a low MR-sensitivity and short relaxation times induce partial volume effects which reduce quantification accuracy. For accurate signal correction exact T₂^*-values are essential. A partial volume correction algorithm for improved T₂^*-determination where T₂^*-values are adapted iteratively is presented. Consistent results to simulations were obtained for phantom and in-vivo data. The iteratively corrected in-vivo T₂^*-values were used for improved ¹⁷O-MRI-signal quantification. 

Ningzhi Li¹, Shizhe Steve Li¹, and Jun Shen^1
1National Institute of Mental Health, Bethesda, MD, United States

The present study proposes and evaluates a novel under-sampled decoupling strategy in which no decoupling was applied during randomly selected segments of data acquisition. By taking advantage of the sparse spectral pattern of carboxylic/amide region of in vivo ¹³C spectra of brain, an iterative algorithm was developed to reconstruct spectra from under-sampled data. Simulations and in vivoexperiments show that this novel decoupling and data processing strategy can effectively reduce decoupling power deposition by >30%. 

Sarah Sonnay¹, Nathalie Just², Rolf Gruetter³, and João M.N. Duarte^4
1Laboratory of Functional and Metabolic Imaging (LIFMET), Ecole Polythechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland, ²Universitätsklinikum Münster, Münster, Germany, ³Center for Biomedical Imaging (CIBM) and Laboratory of Functional and Metabolic Imaging (LIFMET), Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland, ⁴Laboratory of Functional and Metabolic Imaging (LIFMET), Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland

Cerebral function relies on cooperative interaction between neuronal and glial cells. Anaesthetics modulate basal neuronal activity, and therefore the so-called neurometabolic coupling, by targeting different receptors, such as γ-aminobutyric acid type A (GABA_A) receptors, in the case of thiopental or α-chloralose anaesthesia. We investigated cortical metabolism in vivo using ¹³C magnetic resonance spectroscopy (MRS) during infusion of [1,6-¹³C]glucose under thiopental anesthesia. Data indicate glycolysis inhibition, decreased mitochondrial oxidative metabolism and possible oxidation of three-carbon molecules, namely lactate, which plasma concentration increased two-fold (compared to α-chloralose anaesthesia).

Antoine Cherix¹, Blanca Lizarbe¹, Hongxia Lei^2,3, and Rolf Gruetter^1,2,4
1Laboratory for Functional and Metabolic Imaging (LIFMET), Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, ²Department of Radiology, University of Geneva, Geneva, Switzerland,³Animal Imaging and Technology Core (AIT), Center for Biomedical Imaging (CIBM), Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, ⁴Department of Radiology, University of Lausanne, Lausanne, Switzerland

¹H-[¹³C] MRS was applied in a mouse dorsal hippocampus to investigate brain metabolism in vivo. The measured fractional enrichments allowed to measure metabolic fluxes using a one compartment model of glucose metabolism. Results were similar to previous study using a 3 times bigger voxel. This study shows that metabolism of the mouse dorsal hippocampus, which is one of the most studied structures of the brain, can be assessed in vivo.

Steven Reynolds¹, Sarah Calvert², Jack Pearson², Allan Pacey², and Martyn Paley^1
1Academic unit of radiology, University of Sheffield, Sheffield, United Kingdom, ²Academic Unit of Reproductive and Developmental Medicine, University of Sheffield, Sheffield, United Kingdom

Two main metabolic pathways provide energy for sperm swimming; glycolysis and oxidative phosphorylation, producing different biomarkers, including lactate (glycolysis) and bicarbonate/CO₂ (Oxphos) that can be detected by MR spectroscopy. By incubating ¹³C labeled exogenous metabolites with human spermatozoa we identify metabolic pathways and quantify rates of metabolism in spermatozoa. The rate constants for glucose and pyruvate conversion to lactate were estimated as 1.1±0.5x10^-6s^-1 and 2.4±1.1x10^-6s^-1 per million sperm respectively (mean±SD, n=4). Metabolic pathways used by live sperm were assessed and work is being done to estimate the relative importance of different metabolic activity in sperm of normozoospermic and asthenozoospermic patients.

Eulalia Serés Roig^1,2, Lijing Xin³, and Rolf Gruetter^4,5
1Laboratory of Functional and Metabolic Imaging (LIFMET), Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland, ²Image Guided Interventions Laboratory, Radiology Department, University of Geneva (UNIGE), Geneva, Switzerland, ³Centre d'Imagerie Biomédicale - Animal and Imaging Technology (CIBM-AIT), Lausanne, Switzerland, ⁴Department of Radiology, University of Lausanne (UNIL), Lausanne, Switzerland, ⁵Department of Radiology, University of Geneva (UNIGE), Geneva, Switzerland

Glycogen is the main energy store in the human body, while its concentration is particularly abundant in muscle tissue. In vivo ¹³C MRS is unique for investigating glycogen metabolism, as it allows the non-invasive measurement of natural abundance glycogen C₁ resonance in the human muscle. However, spatial localization is desirable to detect glycogen C₂-C₆ resonances due to their overlap with the glycerol C₂  and C₁, C₃ resonances. In this study, we designed a pulse-acquire sequence for localized ¹³C MRS using ISIS-1D and OVS schemes. The localization performance of the sequence was validated in vitro and in vivo in human muscle at 7T.  

Victor Schepkin¹, Andreas Neubauer², Armin Nagel³, and Thomas Budinger^4
1NHMFL/FSU, Tallahassee, FL, United States, ²University of Heidelberg, Mannheim, Germany, ³German Cancer Research Center (DKFZ), Heidelberg, Germany, ⁴Lawrence Berkeley National Laboratory/ UCB, Berkeley, CA, United States

A comparison of the TQ MR signals without filtration from three in vivo ions was performed in a rat head at 21.1 T using a time proportional phase increment.  A strong and competitive binding of potassium relative to sodium was demonstrated and confirmed using agarose samples.  The TQ signal from in vivo chloride was the lowest. Our results support a model that normal cells have similar ion binding in intracellular and extracellular spaces.  Visualization of TQ magnetization was demonstrated using matching angular dependence of  spherical harmonics and corresponding irreducible tensors.

Miho C Emoto¹, Hideo Sato-Akaba², and Hirotada G Fujii^1
1Center for Medical Education, Sapporo Medical University, Sapporo, Japan, ²Osaka University, Osaka, Japan

Nitroxides have unique biochemical properties, and thus they have been used for many biomedical applications. However, although piperidine nitroxide (4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl: Tempol) has been presently tested in clinical trials, details concerning the distribution and kinetics of Tempol in vivo have not been thoroughly studied. In particular, it is not clear whether Tempol enters the brain as paramagnetic materials with an unpaired electron. To examine this matter, electron paramagnetic resonance (EPR) imaging study of mouse brains was conducted using a modified EPR imager. The obtained EPR images clearly showed that Tempol could enter the brain with an unpaired electron.

Jonathan M. Lommen¹, Frank Resmer², Nicolas G.R. Behl¹, Michael Sauer², Nadia Benkhedah¹, Andreas K. Bitz¹, Reiner Umathum¹, Mark E. Ladd¹, Titus Lanz², and Armin M. Nagel^1,3
1Medical Physics in Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, ²Rapid Biomed, Rimpar, Germany, ³Diagnostic and Interventional Radiology, University Medical Center Ulm, Ulm, Germany

A 30 channel Rx array for ²³Na MRI at 7 Tesla is compared with a reference Tx/Rx birdcage. Strong SNR improvement by the array technology is acknowledged and good B₁ homogeneity could be found. Images were reconstructed using der adaptice combine algorithm which provides a near perfect channel combination.

Nicolas G.R. Behl¹, Peter Bachert¹, Mark E. Ladd¹, and Armin M. Nagel^1,2
1Medical Physics in Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, ²Diagnostic and Interventional Radiology, University Medical Center Ulm, Ulm, Germany

Due to the low concentration of ²³Na in the human body, 23Na-MRI suffers from long acquisition times Taq, especially for high nominal spatial resolutions. In this work we investigated the performance of homodyne data processing prior to the iterative 3D-Dictionary-Learning Compressed Sensing reconstruction (3D-DLCS) for the reconstruction of asymmetrically undersampled radial ²³Na-data, in order to take advantage of the point-symmetry in k-space.

Ian D Driver¹, Robert W Stobbe², Richard G Wise¹, and Christian Beaulieu^2
1CUBRIC, School of Psychology, Cardiff University, Cardiff, United Kingdom, ²Department of Biomedical Engineering, University of Alberta, Edmonton, AB, Canada

We show for the first time that venous sodium MRI signals in the human brain are elevated with respect to grey and white matter in-vivo. These results have implications for studies using sodium MRI signals to investigate pathologies such as stroke and cancer, with abnormal cerebrovasculature. Observed signal changes in these groups may be partially due to changes in vascular structure, rather than metabolic dysfunction or disruption of cell integrity. Also, potential studies aiming to use sodium MRI for direct detection of neuronal activity will need to account for functional hyperaemia changing the venous sodium signal.

Tanja Platt¹, Thomas M Fiedler¹, Armin M Nagel^1,2, Andreas K Bitz¹, Peter Bachert¹, Mark E Ladd^1,3, and Reiner Umathum^1
1Medical Physics in Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, ²Diagnostic and Interventional Radiology, University Medical Center Ulm, Ulm, Germany, ³Erwin L. Hahn Institute for Magnetic Resonance Imaging, University Duisburg-Essen, Essen, Germany

Up to now only a few ²³Na abdominal MRI studies have been performed at 7T. In this work, a versatile ²³Na transceive elliptical-shaped body coil for 7T with a large FOV and a high transmit/receive efficiency was designed, simulated, and implemented on a 7T scanner. The setup was applied for in-vivo imaging of the human torso. The obtained 3D ²³Na image data set contains ²³Na signals from heart to pelvis. High regional ²³Na signals are especially present in the areas of kidney, liver, cartilage, vessels, vertebral disks, spinal canal, and heart.

Damien J. McHugh^1,2, Frank Riemer^2,3, Hamied A. Haroon¹, Geoff J.M. Parker^1,2,4, and Ferdia A. Gallagher^2,3
1Centre for Imaging Sciences, The University of Manchester, Manchester, United Kingdom, ²CRUK & EPSRC Cancer Imaging Centre in Cambridge & Manchester, United Kingdom, ³Department of Radiology, University of Cambridge, Cambridge, United Kingdom, ⁴Bioxydyn Ltd., Manchester, United Kingdom

This work investigates the repeatability and reproducibility of total sodium concentration (TSC) estimates in the human brain. Healthy volunteers were scanned twice at two different sites using comparable 3D Cones acquisitions, and region of interest TSC values were compared. Consistent TSC estimates were observed across repeated scans at different sites, and, for robust multi-site comparisons, a need was identified for standardisation of non-Cartesian data reconstruction. These preliminary results provide an initial step in the technical validation of sodium MRI-derived cancer biomarkers.

Chang-Hoon Choi ¹, YongHyun Ha¹, Pandichelvam Veeraiah¹, Jörg Felder¹, Klaus Möllenhoff¹, and N. Jon Shah^1,2
1Institute of Neuroscience and Medicine-4, Research Centre Juelich, Juelich, Germany, ²Faculty of Medicine, Department of Neurology, JARA, RWTH Aachen University, Aachen, Germany

Non-proton MRI has recently been of great interest with the increased availability of ultra high-field MRI system. A translational multinuclear MRI system for ¹H, ¹³C, ¹⁷O, ¹⁹F, ²³Na and ³¹P was developed using six optimised single-tuned RF resonator sets and implemented at the home-assembled 9.4T small animal MRI scanner. This system demonstrated its capability of identifying the concentration difference and sensitivity of these X-nuclei without signal-to-noise-ratio loss for any nuclei, subject interruption and degrading in the static shim condition.

Dennis WJ Klomp¹, Joost Löring¹, Joep WM van Oorschot¹, Peter R Luijten¹, and Wybe JM van der Kemp^1
1Radiology, UMC Utrecht, Utrecht, Netherlands

We have integrated a body RF coil tuned at the ³¹P frequency in a 7T MR system that includes pick-up probes for fast and reliable power calibration. With this setup, full body and broadband ³¹P MRSI can be obtained in single breath-holds. When averaged over less than 5 minutes, excellent ³¹P spectra can be shown from liver and heart as demonstrated in healthy volunteers.

Marek Chmelik^1,2, Diana Bencikova³, Christian Mirkes⁴, Christopher T. Rodgers⁵, Gunamony Shajan⁴, Klaus Scheffler^4,6, Siegfried Trattnig^1,2, and Wolfgang Bogner^1
1High Field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria, ²Christian Doppler Laboratory for Clinical Molecular MR Imaging, Vienna, Austria, ³Department of Nuclear Physics and Biophysics, Faculty of Mathematics, Physics and Informatics, Comenius University, Bratislava, Slovakia, ⁴High-Field MR Center, Max Planck Institute for Biological Cybernetics, Tuebingen, Germany, ⁵OCMR, RDM Cardiovascular Medicine, University of Oxford, Oxford, United Kingdom, ⁶Department for Biomedical Magnetic Resonance, University of Tuebingen, Tuebingen, Germany

The purpose of this study was to quantitatively compare the SNR of brain ³¹P-MRS coils capable of covering the whole brain at various B₀ field strenghts. SNR was compared using phantoms and in vivo in clinically acceptable measurement times at 3T (birdcage), 7T (23ch-array) and 9.4T (27ch-array).  Data showed approximately 3-fold higher SNR at 7T than at 3T. 9.4T provided an additional -more than linear- increase. WSVD coil combination outperformed Brown’s coil combination. Especially with the 7T coil the necessity of advanced coil combination algorithms is apparent. 

Manuela Barbara Rösler^1,2, Nicolas G.R. Behl¹, Nadia Benkhedah¹, Armin Michael Nagel^1,3, and Reiner Umathum^1
1Medical Physics in Radiology, German Cancer Research Center, Heidelberg, Germany, ²Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland, ³Diagnostic and Interventional Radiology, University Medical Center Ulm, Ulm, Germany

Theory predicts that the residual quadrupole interaction of spin-3/2 nuclei with electrical field gradients and the dipole-dipole interaction of coupled spin-1/2 nuclei depend similarly on the angle between the privileged direction and the static magnetic field. In this work, we compare the splitting of the ³⁹K resonance with the splitting of the total creatine resonance in ¹H MR spectroscopy in vivo at human calf muscle. We find similar behavior under variation of the angle between B₀ and tibia. Therefor we conclude that the potassium ions and creatine are located in an equivalent electromagnetic environments.

Rohan S. Virgincar¹, Scott H. Robertson², Simone Degan³, Geoffry Schrank⁴, Mu He⁵, John Nouls⁴, and Bastiaan Driehuys^4
1Biomedical Engineering, Duke University, Durham, NC, United States, ²Medical Physics Graduate Program, Duke University, Durham, NC, United States, ³Center for Molecular and Biomolecular Imaging, Duke University, Durham, NC, United States, ⁴Radiology, Duke University, Durham, NC, United States, ⁵Electrical and Computer Engineering, Duke University, Durham, NC, United States

Inhaled ¹²⁹Xe exhibits chemical shifts which carry useful information about the underlying physiology. However, their resonant frequencies have been reported with a variability of 2-3 ppm likely attributable to using simplistic peak finding methods and inconsistent reference frequencies. In this work, we use robust non-linear curve fitting of the complex dissolved-phase spectrum in mice to identify resonances, and report shifts relative to an accurate reference frequency. At short ¹²⁹Xe replenishment times curve fitting identified two peaks at 197.4±0.9 and 193.0±0.7 ppm, but as replenishment time was increased, five distinct peaks became apparent at 198.4±0.4, 195.5±0.4, 193.9±0.2, 191.3±0.2, and 190.7±0.3 ppm.

Svetlana Sergeevna Batova¹, Andrei Valerievich Manzhurtsev², Maxim Vadimovich Ublinskii^2,3, Irina Sergeevna Lebedeva⁴, Tolibjon Abdullaevich Akhadov³, Petr Evgenevich Menshchikov⁵, and Natalia Alexandrovna Semenova^2,3,5
1Lomonosov Moscow State University, Moscow, Russian Federation, ²Emanuel Institute of Biochemical Physics of Russian Academy of Sciences, Moscow, Russian Federation, ³Radiology, Scientific Research Institute of Children's Emergent Surgery and Trauma, Moscow, Russian Federation, ⁴Scientific Centre of Mental Health, Moscow, Russian Federation, ⁵Semenov Institute of Chemical Physics of Russian Academy of Sciences, Moscow, Russian Federation

Using dynamic ¹H MRS we have separated T2* and water concentration contributions to changes of MRS detectable water signal in motor cortex after activation by a single short stimulus. We revealed effects of schizophrenia on both parameters in the period of hemodynamic response to stimulation. Decreased changes of T2* and water concentration in schizophrenia might reflect a lower vasodilation caused by a single short stimulus.

Chi-Hyeon Yoo^1,2, Do-Wan Lee¹, Kyu-Ho Song¹, Song-I Lim^1,2, Dong-Cheol Woo², and Bo-Young Choe^1
1Department of Biomedical Engineering, and Research Institute of Biomedical Engineering, The Catholic University of Korea College of Medicine, Seoul, Korea, Republic of, ²Asan Institute for Life Science, Asan Medical Center, Seoul, Korea, Republic of

To investigate schizophrenia (SZ)-induced effects in the glutamatergic activity on prefrontal cortex of rat, we used proton magnetic resonance spectroscopy (¹H MRS) to estimate the concentration of glutamate (Glu) and glutamine (Gln). With a short echo time (TE) and 9.4 T of our study, Glu, Gln and glutamate-complex (Glx) were reliably quantified with a low Cramer-Raw low bound (CRLB) value, and Glu, Glx showed significant increase. As our results the SZ-induced change in the glutamatergic activity can be reliably detected by ¹H MRS.

Alexander Gussew¹, Lisa Janetzki², Marianne Cleve¹, Constanze Borys³, and Jürgen r Reichenbach^1
1Medical Physics Group, Institute of Diagnostic and Interventional Radiology, Jena University Hospital - Friedrich Schiller University Jena, Jena, Germany, ²Institute of Psychosocial Medicine and Psychotherapy, Jena University Hospital - Friedrich Schiller University Jena, Jena, Germany, ³Department of Psychiatry and Psychotherapy, Jena University Hospital - Friedrich Schiller University Jena, Jena, Germany

¹H-PRESS and MEGA-PRESS spectroscopy was performed in anterior cingulate cortex (aCC), insula (Ins) and posterior cortex (PC) of 13 matched pairs of chronic low back pain patients and healthy volunteers to quantify regional and interregional Glx and GABA associations in the resting state. Volunteers had negative correlations between GABA in aCC and Glx in Ins and PC (rho < -0.55) as well as positive correlations between Glx in aCC, Ins and PC (rho > 0.65). In contrast, patients had no any comparable metabolic associations, which may be ascribed to disordered functional pathways between brain regions due to the disease.

Song-I Lim^1,2, Kyu-Ho Song¹, Chi-Hyeon Yoo^1,2, Dong-Cheol Woo², and Bo-Young Choe^1
1Department of Biomedical Engineering, and Research Institute of Biomedical Engineering, The Catholic University of Korea College of Medicine, Seoul, Korea, Republic of, ²Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea, Republic of

Nicotine effects the activation of nicotinic acetylcholine receptors (nAChRs) in multiple areas of the brain. Varenicline is a partial agonist acting at the α4β2 nAChRs. The purpose of the study is to compare the in vivo effects of nicotine and varenicline that contribute to the reward system. The results show the tendency of increased Glu level in nicotine group. Moreover, GSH and NAA levels tended to decrease in the nicotine group. It satisfies that high resolution and short TE component adequately spilt the overlapped metabolite spectra and quantify the cerebral neurochemicals. We found that varenicline effectively inhibits the reward cycle.

Pavithra Viswanath¹, Jose Izquierdo-Garcia¹, Larry Cai¹, Joanna Phillips², Russell Pieper², and Sabrina M Ronen^1
1Radiology, University of California San Francisco, San Francisco, CA, United States, ²Neurological Surgery, University of California San Francisco, San Francisco, CA, United States

Abnormal choline metabolism with increased levels of phosphocholine (PC) driven by overexpression of choline kinase α is considered a hallmark of cancer. For the first time, we show that glioma cells with the IDH1 mutation reprogram choline metabolism differently. Using ¹³C-MRS to quantify [1,2-¹³C]-choline flux to PC in IDH1 mutant cells from two genetically engineered glioma models, we show that reduced PC synthesis is characteristic of mutant IDH1 cells. Furthermore, reduced PC synthesis is driven by down-regulated choline kinase α expression. Our study points to unusual reprogramming of choline metabolism in IDH1 mutant glioma cells, pointing to novel therapeutic opportunities. 

Niklaus Zoelch¹, Andreas Hock^1,2, and Anke Henning^1,3
1Institute for Biomedical Engineering, UZH and ETH Zurich, Zurich, Switzerland, ²Department of Psychiatry, Psychotherapy and Psychosomatics, University of Zurich, Zurich, Switzerland, ³Max Planck Institute for Biological Cybernetics, Tuebingen, Germany

At 1.5 T reciprocity principle based quantification strategies have been successfully used to quantify brain metabolites. But these methods all rely on the assumption that the magnitude of the RF transmission field B₁⁺ and the reception field B₁^- are equal at all points in the subject. This is not true at higher field strengths and for example differences in the concentrations measured in the left and right hemisphere are observed when these methods are directly applied at higher fields. Here a further development is presented, proposing a correction for deviations of B₁⁺ from B₁^- to allow concentration measurements at 3T and even higher field strength without the need of assumptions about concentrations of an internal reference. The obtained metabolite concentrations in vivo in 31 healthy volunteers highly agree with values estimated with internal water referencing, demonstrating the capabilities of this new method, which might make concentration measurements in diseased tissue more reliable.    

Niklaus Zoelch¹, Andreas Hock^1,2, and Anke Henning^1,3
1Institute for Biomedical Engineering, UZH and ETH Zurich, Zurich, Switzerland, ²Department of Psychiatry, Psychotherapy and Psychosomatics, University of Zurich, Zurich, Switzerland, ³Max Planck Institute for Biological Cybernetics, Tuebingen, Germany

With ERETIC (Electric Reference To access In vivo Concentrations) metabolite signals measured in vivo are referenced to a signal measured in a phantom while directly correcting for differences in the coli loading conditions between the in vivo and in vitro measurement. This is beneficial compared to using an internal reference because no assumption about the concentration or the relaxation rate of the internal reference is need. However in contrast to the signal of an internal reference the ERETIC signal contains no information about B₁ during transmission or reception and changes in B₁ between the in vivo and in vitro measurement or at different positions are misinterpreted as metabolite concentration changes. The aim of this work was to tackle this problem by incorporating reception sensitivity corrections into the ERETIC method and by using a volume based power optimization to avoid differences during transmission. As a result, the obtained metabolite concentrations agree well with the values obtained with internal water referencing in healthy volunteers.  

Zhengchao Dong^1,2, Joshua Kantrowitz^1,2, and Hong Wang^1,3
1Columbia University, New York, NY, United States, ²New York State Psychiatric Institute, New York, NY, United States, ³Tianjin University, Tianjin, China, People's Republic of

Magnetic field drift and subject motion during J-editing proton MRS scan will not only cause frequency and phase drifts in the spectrum but also alter the linewidth and lineshape. When the linewidths/shapes of edit-on and edit-off spectra do not match, the J-difference spectrum will have residue of Cr peaks; even when edit-on/off spectra match each other, the linebroadening and distortion will deteriorate the quality of the difference spectrum. In this study, we used the partially suppressed water signals to match and to transform the edit-on and edit-off spectra so as to improve the quality of the J-edited spectrum.

Kimberly L Chan^1,2,3, Nicolaas AJ Puts^2,3, Karim Snoussi^2,3, Ashley D Harris^2,3,4,5,6, Peter B Barker^2,3, and Richard AE Edden^2,3
1Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, MD, United States, ²Radiology and Radiological Science, Johns Hopkins School of Medicine, Baltimore, MD, United States, ³F.M. Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, ⁴Radiology, University of Calgary, Calgary, AB, Canada, ⁵Hotchkiss Brain Institute and Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada, ⁶CAIR Program, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada

Glutathione is involved in maintaining redox balance, and can be detected in vivo in brain tissue using MEGA-PRESS editing.  In literature to-date, echo times from 68 to 131 ms have been stated as optimal; in this abstract, the TE-dependence of MEGA-edited GSH signals is investigated using simulations, and phantom and in vivo experiments.  It is shown that, in vivo, there is a moderate (15%) benefit of detecting GSH at TE 120 ms over 68 ms.  We also demonstrate that the longer echo time allows the use of higher-bandwidth, more rectangular slice-selective refocusing pulses, giving a further 57% gain in signal.

Jan Willem van der Veen¹, Stefano Marenco², Karen Berman², and Jun Shen^1
1Magnetic Resonance Spectroacopy Core, NIH, NIMH, Bethesda, MD, United States, ²NIH,NIMH,CTNB, Bethesda, MD, United States

Patient motion and magnetic field drift may shift the frequency of the GABA editing pulse relative to that of metabolites. Using the frequency location of the residual water we corrected for changes caused by frequency variations by using averaged reference signals simulated at specific editing frequency offsets. Our analysis also showed that GABA editing with a top-hat editing pulse is highly robust in the presence of frequency variations.

Meng Gu¹, Adam Kerr², Ralph Hurd³, and Daniel Spielman^1
1Radiology, Stanford University, Stanford, CA, United States, ²Electrical Engineering, Stanford University, Stanford, CA, United States, ³GE Healthcare, Menlo Park, CA, United States

MEGA PRESS has been used to edit the GABA resonance at 3ppm. Due to the wide transition bandwidth of the editing pulse, macromolecule resonances are coedited. To suppress macromolecule signals, a symmetric suppression method has been proposed resulting in reduced GABA signal. We present a new editing method by incorporating spatial and spectral selectivity into the SPECIAL refocusing RF pulses to achieve both GABA editing and macromolecule suppression. Phantom studies showed higher edited GABA signal compared with MEGA PRESS and 90% macromolecule suppression. In-vivo studies demonstrated significantly higher edited GABA signal compared with MEGA PRESS.  

Kimberly L Chan^1,2,3, Karim Snoussi^2,3, Richard AE Edden^2,3, and Peter B Barker^2,3
1Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, MD, United States, ²Radiology and Radiological Science, Johns Hopkins School of Medicine, Baltimore, MD, United States, ³F.M. Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States

Glutathione (GSH), a redox metabolite, and lactate, a product of anaerobic energy metabolism,  can both be detected in the human brain using J-difference editing.  Editing each will usually co-edit the other to some degree, as the GSH editing target spin is at 4.56 ppm and the lactate spin is at 4.1 ppm.  In this abstract, we investigate optimal simultaneous detection of both metabolites, using a combination of simulations, and phantom and in vivo experiments.  We demonstrate a new acquisition protocol applying 10 ms editing pulses at 4.35 ppm, which successfully edits both GSH and lactate signals with near maximal efficiency.

Kimberly L Chan^1,2,3, Richard AE Edden^2,3, and Peter B Barker^2,3
1Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, MD, United States, ²Radiology and Radiological Science, Johns Hopkins School of Medicine, Baltimore, MD, United States, ³F.M. Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States

2-hydroxyglutarate (2HG) is formed in some brain tumors due to a mutation of isocitrate dehydrogenase (IDH), and is becoming an important biomarker for tumor classification. Various approaches have been proposed for the in vivo measurement of 2HG using MR spectroscopy, including spectral-editing using the MEGA-PRESS technique.  This abstract investigates 2HG editing at 3T using density-matrix simulations and phantom experiments.  It is demonstrated that MEGA-PRESS detection of 2HG is best performed at an echo time of 100 ms, applying editing pulses to the 1.9 ppm spins and detecting the 4.0 ppm signal, and employing high-bandwidth refocusing pulses.

Muhammad Gulamabbas Saleh¹, Jamie Near², A Alhamud¹, Lindie du Plessis¹, André J.W. van der Kouwe³, and Ernesta M Meintjes^1
1Human Biology, MRC/UCT Medical Imaging Research Unit, University of Cape Town, Cape Town, South Africa, ²Douglas Mental Health University Institute and Department of Psychiatry, McGill University, Montreal, QC, Canada, ³Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States

During macromolecule (MM) suppressed GABA MRS acquisition, subject motion may cause the spectra to be acquired at an incorrect region of interest and with suboptimal shim. Furthermore, effective MM-suppression requires the editing pulses to be applied consistently at 1.7 ppm, necessitating real-time frequency updates, which can be exacerbated in the presence of motion.  We demonstrate that a pair of 3D EPI volumetric navigators acquired once per TR is able to perform accurate motion and magnetic field inhomogeneity correction in real time during MM-suppressed MEGA-SPECIAL GABA MRS.

Thomas Lange¹, Cheng-Wen Ko², Shang-Yueh Tsai³, Martin Buechert⁴, and Ping-Hong Lai^5
1Medical Physics, Department of Radiology, University Medical Center Freiburg, Freiburg, Germany, ²Dept. of Computer Science and Engineering, National Sun Yat-sen University, Kaohsiung, Taiwan,³Graduate Institute of Applied Physics, National Chengchi University, Taipei, Taiwan, ⁴Magnetic Resonance Development and Application Center, University Medical Center Freiburg, Freiburg, Germany,⁵Dept. of Radiology, Veterans General Hospital Kaohsiung, Kaohsiung, Taiwan

The MEGA-PRESS sequence allows difference editing of J-coupled metabolites on the basis of their specific coupling behavior. In this work, we demonstrate MEGA-PRESS editing of valine and lactate from a large background of lipid signal. Exploiting the very similar J-coupling constants of valine and lactate, it is demonstrated that both metabolites can be edited simultaneously with an echo time of 142 ms, allowing an editing efficiency of 100% with negligible lipid co-editing. Simultaneous valine/lactate editing is validated in vitro and successfully demonstrated in one brain abscess patient. The method may prove clinically useful for distinguishing brain abscesses from brain tumors.

Martin A Janich¹, Ralph Noeske², Timo Schirmer¹, and Rolf F Schulte^1
1GE Global Research, Munich, Germany, ²GE Healthcare, Potsdam, Germany

Outer Volume Suppression (OVS) applied to MR spectroscopy improves voxel localization and suppresses undesired signals. Goal of this work was the numerical optimization of a train of broadband SLR pulses for B₁-robustness and T₁ effects and its application to PRESS in the human brain at 3T. The technique improved localization and better suppressed subcutaneous fat at around 1.5ppm in MRS voxels close to the scalp.

Xiao-Hong Zhu¹, Byeong-Yeul Lee¹, and Wei Chen^1
1CMRR, Radiology Department, University of Minnesota, Minneapolis, MN, United States

We established a practical protocol for quantitatively imaging the cerebral metabolic rates of ATP production via ATPase and creatine kinase (CK) reactions in human brain at 7T using three dimensional (3D) chemical shift imaging (CSI) and in vivo ³¹P MR spectroscopy (MRS) in combine with magnetization transfer (MT) approach. Subsequently, we applied this 3D ³¹P-MT imaging protocol to quantify the regional phosphorous metabolites concentrations, ATPase and CK reaction rate constants and fluxes and the intracellular pH in human brain at rest and during visual stimulation.  The results of this study provide the values of key parameters relevant to ATP metabolism in absolute scale, which allow quantitative evaluation of regional cerebral energetics in resting human brain and its functional changes.

Frances C Robertson¹, Martha J Holmes¹, Francesca Little², Mark F Cotton³, Els Dobbels³, Andre JW van der Kouwe^4,5, Barbara Laughton³, and Ernesta M Meintjes^1
1Department of Human Biology, University of Cape Town, Cape Town, South Africa, ²Department of Statistical Sciences, University of Cape Town, Cape Town, South Africa, ³Department of Paediatrics & Child Health, Stellenbosch University, Stellenbosch, South Africa, ⁴A.A. Martinos Centre for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States, ⁵Department of Radiology, Harvard Medical School, Boston, MA, United States

For partial volume correction in ¹H-MRS the voxel fraction of brain matter (BM) and cerebral spinal fluid (CSF) can be calculated via biexponential fitting of T2 relaxation of the unsuppressed water signal or via segmentation of a high-resolution structural image. We compared voxel CSF percentages obtained using these two methods and investigated whether discrepancies could be explained by head movement between voxel positioning and MRS acquisition. Subjects with large differences in CSF% between methods tended to show greater displacement than those with no difference between methods. Inconsistencies may be due to segmentation inaccuracy in particular regions or subject motion.

Ralph Noeske^1
1GE Healthcare, Potsdam, Germany

The semi-LASER sequence is less prone to chemical shift displacement errors and shows higher B₁-robustness compared to PRESS. To achieve short echo times high amplitude crusher gradients are used to suppress unwanted coherence signals. Goal of this work was to implement an algorithm that prevents violation of gradient strength constraints due to unrestricted rotation of the voxel while optimizing for shortest possible echo time.  

Joo-Yeon Kim¹, Yeong-Jae Jeon^1,2, Sang-Woo Kim^1,2, and Hyeon-Man Baek^1,2
1Bioimaging Reseach Team, Korea Basic Science Institute, Ochang, Korea, Republic of, ²Bio-Analytical Science, University of Science and Technology, Ochang, Korea, Republic of

The aim of this study was to characterize hepatic lipid metabolites changes in high-fat diet induced liver steatosis model using in vivo 1H-MRS. MR imaging an single-voxel 1H-MRS was performed using a PRESS sequence at 9.4T. Significant increase in lipid signals at 0.9, 1.3, 2.1, 2.3, 2.8, 4.1, 4.3, and 5.3 ppm was found in mice with high-fat diet (p<0.001). TL, TUB, UI, and Cho were increased with high-fat diet.Therefore, 1H-MRS is useful in detecting and characterizing various hepatic lipid alterations at early phase in mouse liver steatosis prior to development of fibrosis.

Tamar M van Veenendaal^1,2, Walter H Backes^1,2, Richard AE Edden^3,4, Nicholaas AJ Puts^3,4, Dominique M IJff^2,5, Albert P Aldenkamp^2,5, and Jacobus FA Jansen^1,2
1Radiology and Nuclear Medicine, Maastricht University Medical Center, Maastricht, Netherlands, ²School for Mental Health and Neuroscience, Maastricht University, Maastricht, Netherlands, ³Russel H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, United States, ⁴F.M. Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, ⁵Epilepsy Center Kempenhaeghe, Heeze, Netherlands

Some authors claim that the 3.7 ppm Glx peak, measured with MEGA-PRESS, constitutes predominantly glutamate. This claim was tested measuring nine phantoms with different glutamate,  glutamine, and GABA concentrations using a MEGA-PRESS sequence on a 3T MR scanner. The spectra were analyzed with Gannet (to measure the Glx peak) and LCModel (as an alternative approach). The results show that both glutamate and glutamine attribute to the Glx peak, but that an exclusive estimation of glutamate and glutamine is possible by using LCModel for analysis.

Meining Chen¹, Gaiying Li¹, Zhuwei Zhang¹, Luguang Chen¹, Mengchao Pei¹, Xu Yan², and Jianqi Li^1
1Shanghai Key Laboratory of Magnetic Resonance and Department of Physics, East China Normal University, Shanghai, China, People's Republic of, ²MR Collaboration NE Asia, Siemens Healthcare, Shanghai, China, People's Republic of

Owing to relatively low concentration of GABA in the brain, a large voxel size is normally applied in MRS to achieve a high signal-to-noise ratio, but with combined signal from white matter, gray matter and cerebrospinal fluid. The tissue contribution in GABA measurement remains to be resolved. GABA levels from three closely adjacent voxels with varied tissue composition in the anterior cingulate cortex were acquired by using MEGA-PRESS. GABA level was found to be significantly higher in gray matter than in white matter.

Benoit Schaller¹, Watcharaphol Paritmongkol¹, Arthur W Magill², Matthew D Robson¹, and Christopher T Rodgers^1
1RDM Cardiovascular Medicine, University of Oxford, OXFORD, United Kingdom, ²Institute of Neuroscience and Medicine - 4, Forschungszentrum Juelich GmbH, Juelich, Germany

Phosphorus spectroscopy is a powerful tool for cardiac metabolism studies. Working at 7T gives a significant (2.8x) gain in SNR compared to 3T. However, with existing RF coils, it is hard to excite the heart uniformly and with sufficient peak B₁+. In this work we simulated 8 candidate coil designs and identified the best one for cardiac ³¹P-MRS. We built this quadrature pair of 15cm loops for ³¹P and a single 10cm loop for ¹H, decoupled with LCC traps, performed safety tests, validated its B₁⁺ in phantoms and recorded spectra in vivo in the human leg, liver and heart.

Clemence Ligneul^1,2, Marco Palombo^1,2, and Julien Valette^1,2
1CEA/DSV/I2BM/MIRCen, Fontenay aux Roses, France, ²CNRS Université Paris-Saclay UMR 9199, Fontenay aux Roses, France

Diffusion-weighted magnetic resonance spectroscopy is performed in a large voxel in the mouse brain at two diffusion times, up to very high b-values. We combine different echo times and mixing times to investigate the potential interplay between relaxation properties and diffusion attenuation. Under current experimental conditions, we don’t observe any significant dependence of metabolite diffusion properties on TE/TM, except for water (and possibly NAA at very high b-values), which supports the interpretation and modeling of metabolite diffusion based primarily on geometry, irrespective of relaxation properties.

Sinyeob Ahn¹, Tongbai Meng², Dieter J Meyerhoff^3,4, and Gerhard Laub^1
1Siemens Healthcare, San Francisco, CA, United States, ²Siemens Healthcare, Baltimore, MD, United States, ³Radiology and Biomedical Imaging, UCSF, San Francisco, CA, United States, ⁴CIND, Veterans Affairs Medical Center, San Francisco, CA, United States

Spectroscopy scan is highly sensitive to frequency drift during the acquisition. Although most spectroscopy sequences do not create large frequency drift themselves, it is problematic when they are run immediately after sequences with high gradient duty-cycle, as the frequency still drifts due to gradient cooling. In this paper, realtime frequency adjustment was implemented for MEGA-PRESS sequence for GABA J-editing. FID signal was read during water suppression and used to calculate and update the system frequency every TR cycle. It was tested on a phantom and in vivo and showed effectiveness by providing insensitivity to the frequency drifts during the acquisition.

Po-Yu Peng¹, Shang-Yueh Tsai^2,3, and Yi-Ru Lin^1
1Electronic and Computer Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan, ²Graduate Institute of Applied Physics, National Chengchi University, Taipei, Taiwan,³Reasearch Center for Mind,Brain and Learning, National Chengchi University, Taipei, Taiwan

Magnetic Resonance Spectroscopy (MRS) data were usually acquired with single voxel spectroscopy techniques (SVS), which is used to access metabolites concentrations from a predefined volume of interest (VOI). Currently, MRS has been linked to fMRI studies to access metabolic information. Therefore, it’s important to define the VOI on standard space (template) and transform the predefined VOI from standard space to subject space for each MRS scan. In this study, we developed a tool to guide the definition of VOI on template before MRS scan then automatically calculate VOI in subject space.

Nicole D Fichtner^1,2, Ioannis Giapitzakis³, Nikolai Avdievich³, Anke Henning^2,3, and Roland Kreis^1
1Depts. Radiology and Clinical Research, University of Bern, Bern, Switzerland, ²Institute for Biomedical Engineering, UZH and ETH Zurich, Zurich, Switzerland, ³Max Planck Institute for Biological Cybernetics, Tuebingen, Germany

Ultra high field strengths offer the benefit of higher signal to noise ratio as well as improved separation of metabolites in spectroscopy, which is beneficial for evaluating downfield peaks. In the current work, the metabolite cycling technique is implemented at 9.4T in order to evaluate the downfield part of the human brain spectrum. The 9.4T spectra confirm the 3T findings on exchanging peaks, and indicate that the higher field strength improves metabolite separation, allowing for better quantification of exchanging peaks, which is also of great interest for chemical exchange dependent saturation transfer experiments.

Peter Adany¹, Phil Lee^1,2, and In-Young Choi^1,2,3
1Hoglund Brain Imaging Center, University of Kansas Medical Center, Kansas City, KS, United States, ²Department of Molecular & Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, United States, ³Department of Neurology, University of Kansas Medical Center, Kansas City, KS, United States

Reliable localization of ¹H MRS in gray and white matter of the human brain was achieved using the BASE-SLIM technique. Distinctive spectral patterns of gray and white matter were measured from all subjects using BASE-SLIM, which were consistent with those measured in both tissue types using single-voxel ¹H MRS. BASE-SLIM spectroscopy promises 1) accurate and robust acquisition of MR spectra from gray and white matter with minimum cross contamination from other compartments, 2) shorter scan time and 3) flexibility in compartmental shapes that match anatomical structures.  

Paul de Heer¹, Maurice B Bizino², Hildo J Lamb², and Andrew G Webb^1
1CJ Gorter Center, Radiology, Leiden University Medical Center, Leiden, Netherlands, ²Radiology, Leiden University Medical Center, Leiden, Netherlands

Cardiac proton MR spectroscopy is a challenging technique to perform in a reliable manner. In this study data acquisition parameters are optimized in terms of signal-to-noise and reproducibility. The optimal protocol was determined to be a PRESS localized scan, local power optimization, pencil beam B0 shimming, a cardiac trigger delay of 200 ms, MOIST water suppression and pencil beam navigator-based respiratory compensation. With these parameters high intra- (r=1.000, p<0.0001) and inter- (r=1.000, p=0.0004) session reproducibilities were achieved. Bland-Altman analysis showed limits of agreement from -0.11 to 0.04 (intra) and -0.15 to 0.9.

Deepti Upadhyay¹, Uma Sharma¹, Govind Makharia ², Prasenjit Das³, Siddharth Datta Gupta³, and Naranamangalam R Jagannathan^1
1Department of NMR & MRI Facility, All India Institute of Medical Sciences, New Delhi, India, ²Department of Gastroenterology and human Nutrition, All India Institute of Medical Sciences, New Delhi, India, ³Department of Pathology, All India Institute of Medical Sciences, New Delhi, India

This study illustrates the potential of proton NMR based metabonomics in determining biomarkers for assessing severity of villous abnormality in patients with celiac disease (CeD). CeD patients with Grade 3c showed significantly higher concentration of pyruvate, alanine and succinate compared to Grade 3b patients, suggesting more impaired oxidative phosphorylation in Grade 3c compared to Grade 3b patients. Increased acetoacetate in Grade 3c compared to Grade 3b patients indicated utilization of ketone bodies by intestinal mucosa for energy generation.  Higher level of creatine seen in Grade 3c patients may probably be related to increased intestinal dysbiosis compared to Grade 3b patients.

Martin Gajdošík^1,2, Lukas Hingerl¹, Petr Šedivý³, Miloslav Drobný³, Monika Dezortová³, Michael Krebs⁴, Siegfried Trattnig^1,2, Wolfgang Bogner¹, and Martin Krššák^1,2,4
1High-field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria, ²Christian Doppler Laboratory for Clinical Molecular MR Imaging, Vienna, Austria, ³MR Unit, Institute for Clinical and Experimental Medicine, Prague, Czech Republic, ⁴Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria

Omega-3 (n-3) fatty acids are essential to human health. However, the knowledge about their tissue concentrations is not well established. The spectral dispersion at 7T yields a sufficient spectral separation of n-3 (n-3 CH₃) and non n-3 methyl (CH₃) groups. Large differences in the T₂ relaxation and  J-modulation of outer triplet lines allowed for excellent separation of the n-3 CH₃ signal and for estimation of its relative concentration in adipose tissue for the detection by ¹H MR PRESS with TE of 1000ms.

Shizhe Steve Li¹, Li An¹, Maria Ferraris Araneta¹, Christopher Johnson¹, and Jun Shen^1
1National Institute of Mental Health, National Institutes of Health, Bethesda, MD, United States

To further increase SNR of 7T Phosphorus (³¹P) MRS in human brain, Nuclear Overhauser Effect (NOE) has been utilized where WALTZ waveform was often applied during relaxation time with low RF peak power and long pulse width with inherent narrow bandwidth. At higher field with larger chemical shift dispersion of the protons, broadband saturation of protons is desirable. This study demonstrated the feasibility of broadband NOE at 7 Tesla for ³¹P MRS of human brain.

Ralf Mekle¹, Florian Schubert¹, Thoralf Niendorf², Till Huelnhagen², Antje Else², Simon Daniel Robinson³, Bernd Ittermann¹, Vince Madai⁴, Marta Skowronska⁵, Petr Dusek^6,7, Jens Wuerfel⁸, and Susanne A. Schneider^9
1Physikalisch-Technische Bundesanstalt (PTB), Braunschweig and Berlin, Germany, ²Berlin Ultrahigh Field Facility (B.U.F.F.), Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany, ³High Field MR Centre, Department of Biomedical Imaging and Image guided Therapy, Medical University of Vienna, Vienna, Austria, ⁴Department of Neurology and Center for Stroke Research Berlin, Charité Universitaetsmedizin, Berlin, Germany, ⁵2nd Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, Poland, ⁶Department of Neurology and Centre of Clinical Neuroscience, First Faculty of Medicine and General University Hospital in Prague, Charles University in Prague, Prague, Czech Republic, ⁷Institute of Neuroradiology, University Medicine Goettingen, Goettingen, Germany, ⁸Medical Image Analysis Center, Basel, Switzerland, ⁹Neurology Department, University of Kiel, Kiel, Germany

¹H MR spectroscopy (MRS) in the white matter (WM) of the precentral region and quantitative susceptibility mapping (QSM) of basal ganglia acquired at 7 Tesla in patients (homozygotes), non-manifesting heterozygotes, and control subjects were used to investigate mitochondrial membrane protein-associated neurodegeneration (MPAN). MPAN is a rare, but severe disorder from the neurodegeneration with brain iron accumulation (NBIA) group. Comparison of results for the different subject groups showed no abnormalities in heterozygotes. In contrast, metabolic changes in patients detected by MRS, in particular an increase in glutamate, suggests an underlying mechanism for MPAN related to neurotransmission in corticospinal pathway.

Stephen Bawden^1,2, Paul Glover¹, Peter Morris¹, Guruprasad Aithal², and Penny Gowland^1
1Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, United Kingdom, ²NIHR Nottingham Digestive Diseases Research Unit, University of Nottingham, Nottingham, United Kingdom

In this study the decoupling efficiency of in vivo 13C MRS measurements of glycogen levels was assessed. Due to SAR restrictions and surface coil decoupling field inhomogeneity, this study showed that short TR coupled spectroscopy provides improved SNR and better defined spectral parameters for fitting, whereas decoupled spectra reduces the number of averages in the same timeframe and runs the risk of varying residual coupling constants across a large field of view with inhomogeneous B₂

Lucas Lindeboom^1,2, Yvonne M.H. Bruls^1,2, Petronella A. van Ewijk¹, Matthijs K.C. Hesselink², Joachim E. Wildberger¹, Patrick Schrauwen², and Vera B. Schrauwen-Hinderling^1,2
1Radiology, Maastricht University Medical Center, Maastricht, Netherlands, ²Human Biology and Human Movement Sciences, Maastricht University Medical Center, Maastricht, Netherlands

The use of a long TE enables detection of acetylcarnitine with ¹H-MRS. However, in (very) obese subjects, suppression of overlapping lipid resonances becomes problematic, even with long TE. We here show short T₁ metabolites, such as lipids, can additionally be suppressed with a new T₁ editing approach.

Nikolaos Dikaios¹, Shonit Punwani¹, Henrik Gutte², Majbrit ME Larsen³, Annemarie T Kristensen³, Andreas Kjær², David Atkinson⁴, and Adam E Hansen^2
1Centre of Medical Imaging, UCL, London, United Kingdom, ²Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark, ³Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark, ⁴Centre for Medical Imaging, UCL, London, United Kingdom

Mathematical models based on kinetic parameters allow us to investigate ¹³C-pyruvate metabolism. Metabolic exchanges between pyruvate and its metabolites can differentiate benign from malignant tissue but their quantification is limited by the estimation of the arterial input function (AIF). This work suggests to model the AIF using a Gaussian pdf to account for the time pyruvate needs to travel and dispersion effects.  The proposed AIF fits the measured data better than the commonly used box-car AIF, and is in agreement with the model-free formalism which approximates the kinetics using the ratios of AUC of the injected and product metabolites.

Devashish Das¹, Andor Veltien¹, and Arend Heerschap^1
1Radiology, Radboud University Nijmegen, Nijmegen, Netherlands

Lactate is associated with mitochondrial and neuromuscular diseases. Therefore, its methylene (CH2) and methyl (CH3) proton assignment is necessary in the skeletal muscle. In particular for understanding mechanisms associated with the skeletal muscle ischemia in rodents. Unambiguous detection of lactate resonances in the ischemic and/or hypoxic rodent muscle remains challenging, however, necessary for the assessment of treatment in the dysfunctional muscle of transgenic animals. In vivo lactate resonances remain hidden under lipid pool. However, by tuning spinecho delays in the localized 2D proton correlation sequence we are able to separate lactate CH2 and CH3 protons from the lipid resonances in the F1 dimension of the 2D-spectrum.  

Christoph Juchem¹, Hetty Prinsen¹, Kevin L Behar¹, Robert K Fulbright¹, and Douglas L Rothman^1
1Yale University, New Haven, CT, United States

Altered lipid and protein contents have been detected with MR spectroscopy in acute multiple sclerosis lesions and speculated to reflect de- and remyelination processes. To date, however, neither the metabolites involved nor their pathological relevance have been satisfactorily described. Hofmann et al. introduced an elegant concept for the separation of biochemicals of varying metabolic weight based on differences in T1 relaxation behavior (MRM 46, 2001). Here, we describe T1-encoded MR spectroscopy at 7 Tesla, the extraction of individual, spectroscopically overlapping lipid/protein signals by two-dimensional processing and initial applications to the study of the pathological processes associated to multiple sclerosis tissue injury and repair.

Yang Chen¹, Jianghua Feng¹, Naishun Liao², Ying Su³, Changyan Zou³, and Zhong Chen^1
1Department of Electronic Science, Xiamen University, Xiamen, China, People's Republic of, ²The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, MengChao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China, People's Republic of, ³Laboratory of Radiobiology, Fujian Provincial Tumor Hospital, Fuzhou, China, People's Republic of

To explore metabolic characteristics of hepatocarcinoma cell lines associated with different metastasis potentials, ¹H NMR-based metabolomics conjugated with multivariate statistical analysis were performed to determine the molecular mechanisms of metastasis. Characteristic metabolites from both cell extracts and cultured medium were identified. Our results provide evidences that cells with different metastasis potentials exhibit different levels of glucose consumption, as well as the products of some intermediates of glycolysis.

Hidehiro Watanabe¹ and Nobuhiro Takaya^1
1Center for Environmental Measurement and Analysis, National Institute for Environmental Studies, Ibaraki, Japan

Absolute quantitation framework on highly resolved 2D CT-PRESS spectra with ¹H decoupling was proposed for measurement of concentration of glutamate and GABA. Although peaks of these metabolites are clearly resolved on the spectra, long constant time delay (T_ct) requires T₂ correction. To overcome this, we proposed a fast T₂ correction method using 2D FT with shared time domain data. After curve fitting of series of spectra with varied T_ct's, we obtained series of peak volumes that can be expressed as an exponential decay of T₂. In phantom experiments, we could measure the concentrations of glutamate and GABA by our method.

Liangjie Lin¹, Yanqin Lin¹, Zhiliang Wei¹, and Zhong Chen^1
1Electronic science, Xiamen University, Xiamen, China, People's Republic of

Magnetic resonance spectroscopy (MRS) is a powerful noninvasive tool in diagnoses, progressive monitoring, and studies of disease states of humans and animals. In this study, we present a MRS pulse sequence for localized one-dimensional in-phase proton MRS. The proposed pulse sequence can be utilized to reduce undesired broad resonances with short T2s and increasing signal intensity of Jcoupling metabolites. Moreover, it provides an approach of direct measurement of non-overlapping J coupling peaks at achievable arbitrary TEs and of their transverse relaxation times (T2).

Donghyun Hong¹, Jack JA van Asten², Seyedmorteza Rohani Rankouhi¹, Jan-Willem Thielen¹, and David G. Norris^1,3
1Erwin L. Hahn Institute for Magnetic Resonance Imaging, University of Duisburg-Essen, Essen, Germany, ²Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, Netherlands, ³Donders Institute for Brain, Cognition and Behavior, Radboud University, Nijmegen, Netherlands

GABA spectroscopy has two potential confounds widely ignored by the spectroscopic community: 1) a potential 5-10Hz frequency shift between grey and white matter shown in imaging experiment and 2) the fact that the GABA is circa 9 times more concentrated in grey matter. To investigate whether these confounds could affect GABA spectroscopy at 7T, we compute grey and white matter lineshapes by frequency mapping. We found a slight frequency shift and lineshape which can be ignored. Hence, we conclude that we can probably safely use a single lineshape for fitting using LCModel.

Miguel Martínez-Maestro¹, Christian Labadie², Karsten Mueller¹, and Harald E. Möller^1
1NMR Group, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany, ²Charité - Berlin Center for Advanced Neuroimaging (BCAN), Berlin, Germany

Dynamic changes of metabolite concentrations in the human brain have been successfully detected in response to stimulus at 7T. The present study focus on characterize the detection limits at 3T. 20min fMRS paradigm alternated 5min intervals with stimulus OFF/ON/OFF/ON. A significant intra-individual increase in glutamate+glutamine (Glx) was found in the group analysis (1.83%, p = 0.017). The cross-subjects averaged time course also indicated 1.98% concentration increase during the ON periods. A direct correlation between subtle changes of Glx concentrations and the application of a visual stimulus could be shown consistent with reports from ultra-high field studies.

Zhensong Wang^1,2, Aiying Zhang³, Jie Gan², Guangbin Wang¹, Bin Zhao¹, Huifang Qu⁴, Weibo Chen⁵, Bo Liu⁶, Fei Gao¹, Tao Gong⁷, and Richard A.E. Edden^8,9
1Shandong Medical Imaging Research Institute, Jinan, China, People's Republic of, ²Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China, People's Republic of,³Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China, People's Republic of, ⁴Shandong Chest Hospital, Jinan, China, People's Republic of, ⁵Philips Healthcare, Shanghai, China, People's Republic of, ⁶QiLu Hospital of Shandong University, Jina, China, People's Republic of, ⁷Shandong Medical Imaging Research Institute, Shandong University, Jinan, China, People's Republic of, ⁸Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA, Baltimore, MD, United States, ⁹FM Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA, Baltimore, MD, United States

The present study hypothesized that the GABA levels would be lower in postmenopausal women with mild-to-moderate depression. We investigate the cerebral GABA levels in postmenopausal women using the edited MRS technique MEGA-PRESS. 18 postmenopausal women with mild-to-moderate depression and 11 healthy controls with the age- and body index-, educationally matched were enrolled. GABA+ levels were quantified in the anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC) and the posterior cingulated cortex (PCC). Water-scaled GABA+ levels were significantly lower in the ACC/mPFC regions of patients group than in healthy controls, which suggesting that dysfunctional GABAergic system may be involved in depression in postmenopausal women.