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Digital Poster - Spectroscopy
Weekend and Oral

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Spectroscopy Digital Poster

New Techniques in MRS

2843 - 2920

MRS Reconstruction & AI

New Techniques in MRS
 Spectroscopy

2843
Evaluation of Convolutional Neural Network For Magnetic Resonance Spectroscopy of Lipids
Anmol Monga1, Dimitri Martel1, and Gregory Chang1

1Radiology, NYU Langone Health, New York, NY, United States

Recent progress in the convolutional neural network has provided new tools for signal processing and quantification. Magnetic Resonance Spectroscopy is a powerful quantitative tool, which allows notably to access lipid composition. We aim to design and evaluate a neural network for lipid MRS quantification using simulated data. 

2844
Water Scaling Strategy for Metabolites Quantified in MRS by Deep Learning
Yu-Long Huang1, Yi-Ru Lin1, Teng-Yi Huang2, Cheng-Wen Ko3, and Shang-Yueh Tsai4,5

1Department of Electronic and Computer Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan, 2Department of Electrical Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan, 3Department of Computer Science and Engineering, National Sun Yat-Sen University, Kaohsiung, Taiwan, 4Graduate Institute of Applied Physics, National ChengChi University, Taipei, Taiwan, 5Research Center of Mind, Brain and Learning, National ChengChi University, Taipei, Taiwan

Recently, it has been shown that MRS can be analyzed by a convolutional neural network (CNN) with concentrations quantified in a relative way. Here, we propose to scale in vivo MRS data according to water signal in simulated spectra and in vivo data so that CNN spectra can be scaled to institutional units for possible between subject comparison. Our results show that the quantified metabolites are at the same level as those quantified using LCModel with water scaling method but with less repeatability. A further phantom study is necessary to validate the proposed method. 

2845
31P Magnetic Resonance Spectroscopy analyzed and quantified by Convolutional Neural Network (CNN)
Julien Songeon1, Sebastien Courvoisier1, Antoine Klauser1, Alban Longchamp2, Jean-Marc Corpataux2, Leo Buhler3, and François Lazeyras1

1Department of Radiology and Medical Informatics, University of Geneva, Geneva, Switzerland, 2Department of Vascular Surgery, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland, 3Faculty of Science and Medicine, Section of Medicine, University of Fribourg, Fribourg, Switzerland

Phosphorus magnetic resonance spectroscopy imaging (31P-MRSI) allows the probing of biological compounds that hold  fundamental cellular information. High resolution MRSI at 3T suffers from low signal-to-noise ratio (SNR) inherent to the nuclear low sensitivity. This is accentuated in the MRSI in comparison to unlocalized free induction decay (FID) where acquired volumes are smaller and consequently lower the SNR. Our Convolutional Neural Network (CNN) based algorithm perform efficient quantification of metabolite and is compared to last-square fitting algorithm. Our model was trained with a simulated dataset and tested with both simulated spectra and real spectra from 3D 31P-MRSI acquired in kidneys.

2846
MRSI reconstruction pipeline in the age of Deep Learning
Stanislav Motyka1, Lukas Hingerl1, Philipp Moser1, Asan Agibetov2, Georg Dorffner2, and Wolfgang Bogner1

1Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria, 2Section for Artificial Intelligence and Decision Support (CeMSIIS), Medical University of Vienna, Vienna, Austria

Whole-brain MRSI measured with a concentric ring trajectories based FID-MRSI sequence generates large amounts of data, which makes post-processing very time-consuming (up to several hours). To speed-up the reconstruction, deep learning approaches could be applied. AUTOMAP provides an attractive solution to reconstruct data directly from non-Cartesian kSpace data. However, it requires single-channel data. Therefore, the coil combination needs to be performed in the kSpace domain. We showed that this strategy is in principle feasible, but requires future work on stability against noise.

2847
Deep learning-based target metabolite-specific signal isolation and big data-driven measurement uncertainty estimation in 1H-MRS of the brain
HyeongHun Lee1 and Hyeonjin Kim1,2

1Department of Biomedical Sciences, Seoul National University, Seoul, Republic of Korea, 2Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea

We developed convolutional-neural-networks(CNNs) for each individual metabolites capable of spectrally isolating target metabolite signal for quantification on simulated rat brain spectra at 9.4T. Although heuristically and empirically developed, a method of predicting measurement uncertainty is also proposed by exploiting the spectral isolation capability of the CNNs and the availability of big data. The quantitative accuracy of the proposed method was higher than that of the LC model. The measurement uncertainty predicted by the proposed method was highly correlated with the ground-truth error. The proposed method may be used for metabolite quantification with measurement uncertainty estimation in rat brain at 9.4T. 

2848
MRI-assisted Deep Learning-enhanced Actual Ultra-low-dose Amyloid PET Acquisitions
Kevin T Chen1, Dawn Holley1, Kim Halbert1, Tyler N Toueg1, Athanasia Boumis1, Elizabeth Mormino1, Mehdi Khalighi1, and Greg Zaharchuk1

1Stanford University, Stanford, CA, United States

We are aiming to greatly reduce the radioactive radiotracer dose administered to subjects during PET scanning. In this work we propose to leverage the perfect spatiotemporal correlation of hybrid PET/MRI scanning to synthesize diagnostic PET images from multiple MR images and a noisy PET image reconstructed from acquisitions with actual ultra-low-dose (as low as ~1% of the original) amyloid radiotracer injections, using trained deep neural networks. This technique can potentially increase the utility of hybrid amyloid PET/MR imaging and remove the limiting factors to large-scale clinical longitudinal PET/MRI studies.  

2849
Learning MR-guided PET reconstruction in image space using a convolutional neural network - application to multiple PET tracers
Georg Schramm1, David Rigie2, Thomas Vahle3, Ahmadreza Rezaei1, Koen van Laere1, Timothy Shepherd4, Johan Nuyts1, and Fernando Boada2

1Department of Imaging and Pathology, Division of Nuclear Medicine, KU Leuven, Leuven, Belgium, 2Center for Advanced Imaging Innovation and Research (CAI2R) and Bernard and Irene Schwartz Center for Biomedical Imaging, Department of Radiology, New York University School of Medicine, New York City, NY, United States, 3Siemens Healthcare GmbH, Erlangen, Germany, 4Department of Neuroradiology, NYU Langone Health, Department of Radiology, New York University School of Medicine, New York City, NY, United States

Recently, we could show that MR-guided PET reconstruction can be mimicked in image space using a convolutional neural network which facilitates the translation of MR-guided PET reconstructions into clinical routine. In this work, we test the robustness of our CNN against the used input PET tracer. We show that training the CNN with PET images from two different tracers ([18F]FDG and [18F]PE2I), leads to a CNN that also performs very well on a third tracer ([18F]FET) which was not the case when the network was trained on images from one tracer only.

2850
Magnetic Resonance Spectroscopy Denoising with the Automatic Regularization Parameter Estimation in Low-Rank Hankel Matrix Reconstruction
Tianyu Qiu1, Wenjing Liao2, Di Guo3, Zhangren Tu3, Bingwen Hu4, and Xiaobo Qu1

1Department of Electronic Science, Xiamen University, Xiamen, China, 2School of Mathematics, Georgia Institute of Technology, Atlanta, GA, United States, 3School of Computer and Information Engineering, Xiamen University of Technology, Xiamen, China, 4Department of Physics, East China Normal University, Shanghai, China

In Magnetic Resonance Spectroscopy (MRS), denoising is an important task for MRS due to its poor sensitivity. In this work, noise removal serves as a low rank Hankel matrix reconstruction from noisy free induction decay (FID) signals, since noiseless FID signals are commonly modeled as exponential functions and their Hankel matrices are usually low rank. A faithful denoising mainly depends on the regularization parameter helping to distinguish meaningful signal from noise. We further derived a theoretical bound to automatically set this parameter. Numerical experiments on the realistic MRS data show that noise can be effectively removed with the proposed approach.

2851
A Subspace-based Reliable NMR Spectroscopy Reconstruction
Di Guo1, Zhangren Tu1,2, Tianyu Qiu3, Xiaofeng Du1, Min Xiao2, Vladislav Orekhov4, and Xiaobo Qu3

1School of Computer and Information Engineering, Xiamen University of Technology, Xiamen, China, Xiamen, China, 2School of Opto-Electronic and Communication Engineering, Xiamen University of Technology, Xiamen, China, Xiamen, China, 3Department of Electronic Science, Xiamen University, Xiamen, China, Xiamen, China, 4Department of Chemistry and Molecular Biology and Swedish NMR Centre, University of Gothenburg, Gothenburg, Sweden, Gothenburg, Sweden

 Accelerating the data acquisition is one of the major developments in modern Nuclear Magnetic Resonance (NMR). Non-Uniform Sampling (NUS) acquires fewer data and reconstructs the spectra with proper signal processing methods1. Here, we introduce an approach to reconstruct faithful spectra from highly accelerated NMR. The FID signal is constrained by the self-learning signal subspace (SLS), in which a true representation of NMR should be in. Results on realistic NMR data demonstrate that the new approach provides much better spectra than the compared state-of-the-art method.

2852
Influence of parametrized MM and spline baseline in LCModel using in-vivo rat brain 1H-MR spectra and Monte Carlo simulations at 9.4T
Dunja Simicic1,2, Veronika Rackayova1, Lijing Xin1, Bernard Lanz2, and Cristina Cudalbu1

1CIBM, EPFL, Lausanne, Switzerland, 2LIFMET, EPFL, Lausanne, Switzerland

Reliable detection, post-processing and fitting of MM is crucial for quantifying short-TE 1H-MR brain spectra. In general, an in-vivo acquired full-MM spectrum is included in the basis-set together with a relatively free spline baseline (i.e.LCModel). Availability of high magnetic fields (better resolved  in-vivo MM) lead to a need for more sophisticated approaches such as MM parametrization. Furthermore, effect of the stiffness of fitted baseline on the resulting metabolite concentrations gained a lot of interest. We compared parametrized and full-MM basis-sets, with varying DKNTMN to assess the resulting changes in metabolite concentrations (in-vivo rat brain 1H-MRS and Monte-Carlo simulations at 9.4T).

2853
Comparison of 3T proton brain spectra quantified with basis sets simulated using experimental and ideal pulses
Michal Povazan1,2, Adam P Berrington3, and Peter B Barker1,2

1Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University, School of Medicine, Baltimore, MD, United States, 2F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, 3Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, United Kingdom

The most common method for proton MRS quantification is the linear combination of model basis spectra. Typically, these model spectra are simulated using density matrix formalism. Here we aimed to compare the quantification using two basis sets with full localization and real RF pulses and one basis set with non-localized ideal RF pulses. Statistically significant differences were found between metabolite concentrations quantified in LCModel with different basis sets. Whereas two models that used localized real RF pulses were not significantly different for the major metabolites, the ideal basis set differed in concentration for all metabolites except NAA.

2854
Separation of Metabolite and Macromolecule Signals for Short-TE $$$^1$$$H-MRSI Using Learned Nonlinear Models
Yahang Li1,2, Zepeng Wang1,2, Ruo-Jing Ho1,2, and Fan Lam1,2

1Department of Bioengineering, University of Illinois at Urbana-Champaign, URBANA, IL, United States, 2Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, URBANA, IL, United States

We report a novel method to separate metabolite and macromolecule signals from short-TE $$$^1$$$H-MRSI data using learned nonlinear low-dimensional models. A deep-learning-based strategy was developed to learn the nonlinear low-dimensional manifolds where the metabolite and MM signals reside, respectively. A constrained reconstruction formulation is proposed to incorporate the learned model as a prior to reconstruct and separate metabolite and MM signals. The performance of the proposed method was evaluated using both simulation and experimental short TE $$$^1$$$H-MRSI data. Promising results have been obtained, demonstrating the potential of the proposed method in addressing this challenging problem.

2855
Optimized truncation to integrate multi-channel MRS data using rank-R singular value decomposition (OpTIMUS)
Dongsuk Sung1, Benjamin B Risk2, Maame Owusu-Ansah3, Xiaodong Zhong4, Hui Mao3, and Candace Fleischer1,3

1Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, United States, 2Department of Biostatistics and Bioinformatics, Emory University, Atlanta, GA, United States, 3Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, United States, 4MR R&D Collaborations, Siemens Healthcare, Los Angeles, CA, United States

Multi-channel phased array coils facilitate acquisition of fast, localized, and high signal-to-noise ratio (SNR) magnetic resonance spectroscopy (MRS) data. As individual spectra are acquired from multiple coil channels, it is necessary to combine these data to form a final spectrum. Here, we present an improved approach for combining multi-channel phased array data using spectral windowing followed by a rank-R singular value decomposition (SVD). Our approach, termed ‘OpTIMUS’ was evaluated using SNR and compared to combination methods including whitened SVD (WSVD), S/N2 weighting, and the vendor-supplied reconstruction. OpTIMUS generated the highest SNR across all methods.

2856
Hunting the perfect spline: Baseline handling for accurate macromolecule estimation and metabolite quantification by in vivo 1H MRS
Kelley M. Swanberg1, Karl Landheer1, Martin Gajdosik1, Michael Treacy1, and Christoph Juchem1,2

1Biomedical Engineering, Columbia University School of Engineering and Applied Science, New York, NY, United States, 2Radiology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, United States

It has been previously established that inappropriately modeled spectral baselines can confound metabolite concentration estimates by in vivo 1H MRS even while contributing to visually reasonable fits. The systematic optimization of spectral quantification pipelines, including baseline modeling, continues nonetheless to be impeded by an under-utilization of validation methods both physically meaningful and involving perfect prior knowledge. Here we address the extant need for evidence-based spectral baseline handling by combining the practical utility of in vivo data with the prior knowledge enabled by simulated standards. We use this paradigm to compare various baseline models for macromolecule characterization and metabolite quantification accuracy.

2857
Comparison between Cartesian and Radial Under-sampling Schemes for Fast MRI using a Deep Cascade of Neural Network
Zhengxin GAO1,2, Zhuoran Jiang2,3, and Zheng Jim Chang2

1Medical Physics Program, Duke Kunshan University, Jiangsu, China, 2Department of Radiation Oncology, Duke Univeristy, Durham, NC, United States, 3Electronic Science and Engineering, Nanjing University, Nanjing, China

Cartesian under-sampling scheme was commonly applied in fast MRI using a deep neural network to simulate the process of fast image acquisition, however, it might not be optimal at a high under-sampling rate. Alternatively, radial under-sampling scheme was used and its efficiency was compared against that of Cartesian under-sampling scheme for T1- or T2-weighted brain, breast, prostate and cervical MRI data at various under-sampling rates. The quantitative evaluation results demonstrated that radial under-sampling scheme could outperformed Cartesian under-sampling scheme on reducing scan time while achieving comparable or better image quality.


MRS Technical 1

New Techniques in MRS
 Spectroscopy

2858
J-refocused semi-LASER spectroscopy at 7T: proof-of-concept and application in the human brain at 7T
Chloé Najac1, Vincent Boer2, Hermien E. Kan1, Andrew G. Webb1, and Itamar Ronen1

1C.J. Gorter Center for High Field MRI, Department of Radiology, Leiden University Medical Center, Leiden, Netherlands, 2Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Copenhagen, Denmark

Spin-echo sequences suffer from loss of signal due to J-modulation for coupled spins. Previously, it was shown that adding a π/2 pulse between two π pulses in a double spin-echo sequence partially refocuses some of the J-evolution. However, the potential of such sequence at ultrahigh field is limited due to the large chemical shift displacement error. Here, we propose a J-refocused variant of the sLASER sequence (J-sLASER) to improve quantification of J-coupled metabolites at ultrahigh field. Significant improvement in quantitation of J-coupled metabolites is illustrated using simulation, phantom and in vivo measurements in the human brain.

2859
FSL-MRS: A New MR Spectroscopy Fitting Tool
William T Clarke1, Jamie Near2, Uzay E Emir3,4, and Saad Jbabdi1

1Wellcome Centre for Integrative Neuroimaging, NDCN, University of Oxford, Oxford, United Kingdom, 2Douglas Mental Health University Institute, and Department of Psychiatry, McGill University, Montreal, QC, Canada, 3School of Health Sciences, Purdue University, West Lafayette, IN, United States, 4Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, United States

FSL-MRS is a new Python-based MRS fitting tool. The model is based on a linear combination of basis spectra, and fitting is achieved with a sampling approach which gives full posterior distributions of fitted parameters. Results are stored both as text files and an interactive HTML report. On publication the tool will be open source and free as part of the FSL package. The tool will be developed to handle MRSI and model fMRS as time-series. Here we demonstrate an initial implementation in phantom data and three brain regions of 37 subjects and compare against another fitting software.

2860
Enabling Fast Metabolic Mapping of the Brain using Lipid Crushing and an EPSI Readout at 7T
Kyung Min Nam1, Arjan Hendriks1, Vincent O. Boer2, Dennis D.J. Klomp1, Jannie P. Wijnen1, and Alex Bhogal1

1Imaging & Oncology, UMC Utrecht, Utrecht, Netherlands, 2Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark

Metabolic mapping at ultra-high field benefits from increased SNR and large chemical shift dispersion, enabling high spatial resolution and more resolved metabolite resonances. By exploiting increased SNR, MRSI acquisitions can be accelerated using echo-planar readout gradients (EPSI) or parallel imaging techniques. However, signal contamination from extra-cranial lipids can degrade the spectral quality and/or introduce fold-over artefacts. Therefore, suppression of extra-cranial lipids during acquisition is imperative for fast spectroscopic imaging. This work aimed to use a “crusher coil” to suppress extracranial lipid signals while acquiring metabolic information using a pulse-acquire acquisition with EPSI readout.

2861
Spatiospectral Reconstruction from Hybrid FID/SE J-Resolved MRSI Data with Limited Coverage of (k,t,tJ)-Space
Yibo Zhao1,2, Yudu Li1,2, Jiahui Xiong1,2, Rong Guo1,2, Yao Li3,4, and Zhi-Pei Liang1,2

1Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, United States, 2Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, United States, 3School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China, 4Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China

J-resolved MRSI using hybrid FID/SE signals has recently been proposed as an effective approach to achieving rapid, high-resolution mapping of brain metabolites and neurotransmitters, an elusive goal of the MRSI community. The new data acquisition scheme poses new problems for data processing, from removal of nuisance signals to reconstruction of spatiospectral distributions. This paper presents an effective method to address these problems, utilizing a union-of-subspaces framework to absorb complementary and prior  information. The proposed method has been evaluated using experimental data, producing high-quality spatiospectral distributions of metabolites and neurotransmitters from hybrid FID/SE J-resolved MRSI data with limited coverage of (k,t,tJ)-space.

2862
Semi-LASER single-voxel spectroscopic sequence with minimal echo time of 20.1 ms: Application in the human brain at 3T
Karl Landheer1, Martin Gajdosik1, and Christoph Juchem1,2

1Biomedical Engineering, Columbia University, New York, NY, United States, 2Radiology, Columbia University, New York, NY, United States

The aim of this work was to develop an optimized sLASER sequence which is capable of acquiring artefact-free data with an echo time as short as 20.1 ms on a whole-body clinical 3 T MR system. This was achieved through the use of specialized pulses and optimizing the crusher scheme and phase cycling schemes. High quality spectra were obtained and quantified in 6 healthy volunteers, both in the prefrontal and the occipital cortex.

2863
UTE-SPECIAL for 3D Localization at an Echo Time of 4 ms on a Clinical 3 Tesla Scanner
Karl Landheer1, Ralph Noeske2, Michael Garwood3, and Christoph Juchem1,4

1Biomedical Engineering, Columbia University, New York, NY, United States, 2GE Healthcare, Berlin, Germany, 3Center for Magnetic Resonance Research and Radiology, University of Minnesota, Twin Cities, MN, United States, 4Radiology, Columbia University, New York, NY, United States

A previously developed magnetic resonance spectroscopy method is improved upon which is now able to obtain spectra with an echo time as short as 4 ms, while recovering the entirety of the available magnetization. This method obtains full 3D spatial localization through a 2D adiabatic inversion pulse which is cycled “on” and “off” every other repetition, in combination with a slice-selective excitation pulse. Both 1D and 2D spectra with an ultrashort echo time of 4 ms are demonstrated at 3T. High quality spectra were obtained for all experiments.

2864
A non-water-excitation MRS sequence with zero-echo time to investigate exchangeable moieties in the human brain at 3T
Martyna Dziadosz1, Wolfgang Bogner2, and Roland Kreis1

1Departments of Radiology and Biomedical Research, University of Bern, Bern, Switzerland, 2Department of Biomedical Imaging and Image-guided Therapy, Medical University Vienna, High-field MR Center, Vienna, Austria

Most clinical MRS studies concentrate on the upfield part of the spectrum, neglecting the downfield region, since it is mainly composed of labile protons with intensities depending on the water suppression scheme. For reliable and sensitive quantification, a non-water-suppressed or even better a non-water-excitation (NWE) technique is required.

We introduce a non-echo technique based on ISIS localization for optimal detection of (moderately) fast exchanging protons at 3T with minimal signal loss due to T2 or exchange and with optimized water magnetization path for longitudinal relaxation enhancement.


2865
Radial Flyback Echo-Planar Spectroscopic Imaging with Golden Angle Sampling and Total Variation-based Compressed Sensing Reconstruction
Andres Saucedo1, Manoj Sarma1, and M. Albert Thomas1

1Radiological Sciences, University of California, Los Angeles, Los Angeles, CA, United States

In this pilot study, we implement a radial echo-planar spectroscopic imaging (rEPSI) sequence and compare its performance to the Cartesian (EPSI) sequence under multiple rates of retrospective undersampling, for the case of 2D acquisitions in which a single phase-encoded direction is undersampled for EPSI, and a reduced number of radial profiles using golden angle view ordering are reconstructed for rEPSI. Fully sampled data from a healthy volunteer brain and from a brain phantom are acquired. The retrospectively undersampled data is reconstructed using compressed sensing with Total Variation regularization, and the performance of both methods are compared.

2866
Metabolite-cycled echo-planar spectroscopic imaging of the human heart
Sophie M. Peereboom1 and Sebastian Kozerke1

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

Cardiac triglyceride levels can be assessed using proton MR spectroscopy. While metabolite cycling has already been applied to cardiac proton MRS, the combination of metabolite cycling and spectroscopic imaging for cardiac applications remains to be demonstrated. In this work metabolite-cycled echo-planar spectroscopic imaging is proposed to asses triglyceride-to-water (TG/W) ratios in different regions of the human heart. Results were compared to conventional single-voxel measurements in the interventricular septum. Although SNR is limited for metabolite-cycled EPSI, the method allows for detection of regional TG/W and therefore holds promise to provide insights into regional TG variations.

2867
Phased-array combination of 2D MRS for lipid composition quantification in patients with breast cancer
Vasiliki Mallikourti1, Sai Man Cheung1, Tanja Gagliardi 2,3, Nicholas Senn1, Yazan Masannat4, Trevor McGordlrick5, Ravi Sharma5, Steven Heys1,4, and Jiabao He1

1Institute of Medical Sciences, School of Medicine, University of Aberdeen, Aberdeen, United Kingdom, 2Department of Clinical Radiology, Aberdeen Royal Infirmary, Aberdeen, United Kingdom, 3Department of Radiology, Royal Marsden Hospital, London, United Kingdom, 4Breast Unit, Aberdeen Royal Infirmary, Aberdeen, United Kingdom, 5Department of Oncology, Aberdeen Royal Infirmary, Aberdeen, United Kingdom

Signal combination algorithms, designed for 1D MRS, were adapted for lipid composition spectra acquired using 2D MRS of double quantum filtered correlation spectroscopy (DQF-COSY). The algorithms of adaptively optimised combination (AOC), noise decorrelated combination (nd-comb), and whitened singular value decomposition (WSVD) were evaluated on lipid composition spectra from healthy volunteers and patients with breast cancer (tumour and peritumoural adipose tissue). WSVD provided maximal SNR uniformly across all spectral peaks. WSVD, through the elimination of additional acquired reference spectrum, shortens acquisition in patients to less than 11 min instead of 17 min while maintaining sensitivity.

2868
Using Simultaneous Multi-echo Fitting to Accelerate Magnetic Resonance Spectroscopic Relaxometry
Patrick J Bolan1, Gregory J Metzger1, Dinesh Deelchand1, and Malgorzata Marjanska1

1Radiology / Center for Magnetic Resonance Research, University of Minnesota-Twin Cities, Minneapolis, MN, United States

Measurements of metabolite T2 relaxation constants can be valuable biomarkers of aging and disease. The conventional method for measuring multiple metabolite T2s is to independently fit spectra from a multi-TE and then separately fit the amplitudes to an exponential decay to estimate T2. In this work we implement a simultaneous fitting approach to fit all of the multi-TE spectra at the same time by incorporating the transverse relaxation in the model. This approach greatly reduces the degrees of freedom and enable T2 estimation in noisy data, which may be used to shorten acquisition times and/or measure smaller regions.

2869
Frequency and Phase Correction of J-Difference Edited Spectra using Deep Learning
Sofie Tapper1,2, Mark Mikkelsen1,2, Blake E. Dewey2,3, and Richard A. E. Edden1,2

1Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States, 2F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, 3Department of Electrical and Computer Engineering, Johns Hopkins University, Baltimore, MD, United States

Frequency-and-phase correction is an important step in the processing of single-voxel magnetic resonance spectroscopy data, and is required for J-difference editing, which relies on subtraction to reveal a low-SNR signal. We investigated an approach for frequency-and-phase correction using deep learning. Our networks were trained using simulated spectra manipulated with different frequency-and-phase offsets. During validation, the network returned spectra that were corrected to within 1.76 ± 1.19 degrees of phase and 0.09 ± 0.05 Hz of frequency, giving a difference spectrum very similar to the true unmanipulated spectrum. Frequency-and-phase correction is a promising application for deep learning in in vivo MRS.

2870
Assessment of partial volume effects in MRS voxels applying an Altas-based brain segmentation to high-resolution 3D MRI of rat brain
Chi-Hyeon Yoo1,2, Hyeon-Man Baek2, and Bo-Young Choe1

1The Catholic University of Korea, Seoul, Republic of Korea, 2Gacheon University, Incheon, Republic of Korea

The aim of this study was to apply the atlas-based brain segmentation to high-resolution 3D MRI of the mice brain, to assess a partial volume effect in the voxel. The altas-based segmentation successfully decomposed high-resolution 3D MRI into various anatomical compartments, and by volumetrically analyzing binary masks of the tissue compartment and voxels, a true contribution of the intended tissue compartment in the localized voxel can be assessed. By analyzing the metabolite-specific volume masks, an agreement of the localization between metabolites was evaluated. By evaluating the true contribution of the intended compartment and metabolite-specific agreement, localization reliability can be improved.

2871
Osprey: Open-Source Processing, Reconstruction & Estimation of Magnetic Resonance Spectroscopy Data
Georg Oeltzschner1,2, Helge Jörn Zöllner1,2, and Richard Anthony Edward Edden1,2

1Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, 2F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States

Magnetic resonance spectroscopy (MRS) offers a wide range of methods to study in vivo metabolism. As a result of this diversity, data acquisition and analysis are far from standardized, and researchers frequently develop customized and therefore highly heterogeneous pipelines, often interfacing with commercial or closed-source external fitting software. Here, we present “Osprey”, an all-in-one software package that incorporates all steps of state-of-the-art pre-processing, linear-combination modeling, tissue correction, quantification, and visualization of MRS data from the human brain. Osprey provides a modular, fully open-source framework, allowing the community to rapidly incorporate future methodological developments, accelerate their adaptation, and foster standardization.

2872
Optimized PRESS Echo Time for Quantifying Relative ω-3 Fat Content at 9.4T In Vivo
Clara J. Fallone1, Anthony G. Tessier 1,2, Catherine J. Field3, and Atiyah Yahya1,2

1Department of Oncology, University of Alberta, Edmonton, AB, Canada, 2Department of Medical Physics, Cross Cancer Institute, Edmonton, AB, Canada, 3Department of Agricultural, Food, and Nutritional Science, University of Alberta, Edmonton, AB, Canada

Omega-3 (ω-3) fat content in adipose tissue is relevant to the study of disease. It is challenging to quantify with Magnetic Resonance Spectroscopy (MRS) due to its low concentration in vivo. In addition, its resonance is difficult to resolve from that of the non-ω-3 protons, even at 9.4T.  A PRESS (Point RESolved Spectroscopy) echo time of 109ms was determined to yield resolved ω-3 (≈ 0.98ppm) and non-ω-3 (≈ 0.9ppm) methyl peaks at 9.4T. The efficacy of the sequence was verified on oil phantoms and on rats fed a high ω-3 fat diet. 

2873
In Situ Quantification of the Longitudinal Relaxation Time of Phophatidylcholine in Human Bile at 7T
Lorenz Pfleger1,2, Albrecht Ingo Schmid2,3, Stefan Wampl2,3, Martin Gajdošík1,2,4, Siegfried Trattnig2,5, Michael Krebs1, and Martin Krššák1,2,5

1Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Vienna, Austria, 2High-field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria, 3Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria, 4Department of Biomedical Engineering, Columbia University, New York, NY, United States, 5Christian Doppler Laboratory for Clinical Molecular MR Imaging, Vienna, Austria

This study focuses on the in vivo determination of the longitudinal relaxation time (T1) of phosphatidylcholine (PtdC) in the gallbladder at 7T and its challenges. In most cases, it was possible to assess T1 with a 1D-ISIS sequence. In cases where the gallbladder is further away from the coil a STEAM sequence, which does not depend on 180° RF pulses, can be used. The T1 values of PtdC ranged between 290 and 480ms.


MRS Technical 2

New Techniques in MRS
 Spectroscopy

2874
Development of absolute quantitation method in 1H MRS at high magnetic field
Hidehiro Watanabe1, Nobuhiro Takaya1, and Fumiyuki Mitsumori1

1Center for Environmental Measurement and Analysis, National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan

The method for absolute quantitation of 1H MRS in a human brain at high B0 field was proposed. A water phantom as a concentration reference and a human brain area measured separately. The ratio of the reception sensitivities between uniform areas in the phantom and in the human brain can be computed from measured B1+s. The ratio between the VOI and the uniform area in the human brain can be computed by our previously reported ratio map method. Then, concentration in the VOI can be calculated. Our method was demonstrated in the phantom experiments.

2875
Development of hydroxyl radical imaging using dynamic nuclear polarization MRI
Shinichi Shoda1, Fuminori Hyodo1, Norikazu Koyasu1, Yoko Tachibana2, Hinako Eto2, and Masayuki Matsuo1

1Gifu University, Gifu, Japan, 2Kyushu University, Fukuoka, Japan

  Oxidative stress is implicated in various diseases such as inflammation, neurodegenerative disorders (Alzheimer’s disease, Parkinson’s disease), atherosclerosis, diabetic and cancer. Excess reactive oxygen species (ROS) are produced during altered cellular metabolism in various diseases. Among ROSs, hydroxyl radicals (•OH) is one of the most reactive molecules in biological systems. Therefore, it is considered that monitoring of •OH is could be useful technologies for evaluation of redox mechanism and oxidative diseases. In this study, we developed the hydroxyl radical imaging technique using combining DNP-MRI and DMPO.

2876
Large denoising effect of ultrahigh dielectric constant (uHDC) materials
Navid Pourramzangandji1, Christopher Sica2, Byeong-Yeul Lee3, Hannes Wiesner3, Maryam Sarkarat4, Michael Lanagan4, Xiao-Hong Zhu3, Wei Chen3, and Qing Yang1

1Department of Neurosurgery, PennState University College of Medicine, Hershey, PA, United States, 2Department of Radiology, PennState University College of Medicine, Hershey, PA, United States, 3CMRR, Department of Radiology, University of Minnesota, Minneapolis, MN, United States, 4Department of Engineering Science and Mechanics, Pennsylvania State University, State College, PA, United States

We investigated the effect of ultrahigh dielectric constant (uHDC) materials on reducing the noise and enhancing B1 efficiency at 78-MHz for low-γ nuclear applications (23Na and 13C at 7T or 61-MHz for 17O at 10.5 T). By employing uHDC materials, the conservative E-field can be reduced in the sample, which makes the non-conservative field dominant and increases the transmit efficiency and receive sensitivity. We calculated the normalized noise level and extracted the B1+ efficiency map for baseline (no uHDC) and when uHDC is used, and show experimentally that noise level is reduced considerably in the presence of the UHDC material.

2877
Targeted fast spectroscopic imaging at 7T
Jullie W Pan1, Victor Yushmanov1, Chan H Moon1, Frank Lieberman2, and Hoby P Hetherington1

1Radiology, University of Pittsburgh, Pittsburgh, PA, United States, 2Neurology, UPMC, Pittsburgh, PA, United States

The increased SNR at 7T and high efficiency of spatial encoding from fast readout trajectories means that substantially accelerated spectroscopic imaging acquisitions are practical. In this report, we implement targeted multi-slice Hadamard encoded cascaded and simultaneous acquisitions. With the cascaded rosette, minimal CSDE is incurred, generating 4slices in 8min12s. The J-refocused sequence achieves excellent CRLB in <2.3min for a single slice. With a B1 reduction strategy that allows multiple simultaneous Hadamard encoding, the J-refocused sequence is also demonstrated with 4slice acquisitions. As performed in brain tumor patients, the targeted Hadamard rosette is well tolerated and sensitive for detection of pathology.

2878
Elliptical Localization with Pulsed Second-Order fields (ECLIPSE) for Lactate and BHB Edited Human Brain Proton MRSI
Chathura Kumaragamage1, Henk M De Feyter1, Peter B Brown1, Scott McIntyre1, Terence W Nixon1, and Robin A de Graaf1

1Radiology and Biomedical Imaging, Yale University, New Haven, CT, United States

Βeta-hydroxybutyrate (BHB) and lactate (Lac) are MRS visible metabolites important for brain energy metabolism. In this work we investigate the feasibility to detect elevated levels of BHB with proton MRSI following oral consumption of an energy drink containing 25g of a keto-ester. A gradient-modulated ECLIPSE-OVS method with minimal chemical shift displacement was implemented for lactate and BHB edited MRSI of the human brain. Elevated levels of BHB following oral intake of a keto-ester energy drink were observed in an 8 mL nominal volume MRSI acquired within  9-min  at 4 T.

2879
ECLIPSE utilizing Gradient Modulated Offset-Independent Adiabaticity (GOIA) Pulses for Human Brain Proton MRSI
Chathura Kumaragamage1, Henk M De Feyter1, Peter B Brown1, Scott McIntyre1, Terence W Nixon1, and Robin A de Graaf1

1Radiology and Biomedical Imaging, Yale University, New Haven, CT, United States

At high magnetic field strengths (≥3T), the utility of MRSI is impeded by challenges such as increased B1 field heterogeneity, increased RF power requirements for reduced chemical shift displacement errors (CSDE), and water/lipid contamination. In this work, the utilization of gradient modulated (GOIA) RF pulses, is investigated, with elliptical localization with pulsed second order fields (ECLIPSE) for MRSI. A 15 kHz GOIA pulse based ECLIPSE double-spin-echo MRSI sequence was developed. In vivo data demonstrate that the GOIA based MRSI method provides full-intensity metabolite spectra in edge of the brain voxels, and undetectable extracranial lipid signals within or outside the brain.

2880
The impact of receiver bandwidth and number of points on MRS fitting accuracy
Maria Yanez Lopez1 and Peter J Lally2

1Centre for the Developing Brain, School of Biomedical Engineering and Imaging Sciences, King's College London, London, United Kingdom, 2Department of Brain Sciences, Faculty of Medicine, Imperial College London, London, United Kingdom

The aim of this work was to investigate the effect of receiver bandwidth and number of points in the fitting of MRS spectra acquired in healthy controls, using a LASER MRS sequence at 3T. Our results highlight the need for harmonisation between different studies in terms of BW/number of points wherever possible, since variations across clinical populations might not be detected due to systematic errors induced from variations in these parameters alone. Optimisation of BW/number of points is also encouraged when setting up a new study.

2881
Comparison of an advanced, fieldmap-based shimming approach and FASTESTMAP for single-voxel 1H MR spectroscopy at 7T
Ana Gogishvili1,2, Michael Schwerter1,3, Ezequiel Farrher1, Ketevan Kotetishvili2, and N. Jon Shah1,4,5,6

1Institute of Neuroscience and Medicine 4, Foschungszentrum Jülich, Jülich, Germany, 2Engineering Physics Department, Georgian Technical University, Tbilisi, Georgia, 3Faculty of Mathematics, Computer Science and Natural Sciences, RWTH Aachen University, Aachen, Germany, 4Department of Neurology, Faculty of Medicine, RWTH Aachen University, Aachen, Germany, 5JARA - BRAIN - Translational Medicine, RWTH Aachen University, Aachen, Germany, 6Institute of Neuroscience and Medicine 11, Foschungszentrum Jülich, Jülich, Germany

Proton MRS only benefits from ultra-high field strengths if good Bhomogeneity is achieved. For this, projection-based B0 shim techniques, e.g. FASTMAP, are commonly used in single-voxel acquisitions. However, FASTMAP and its variants typically only use up to 2nd order shim coils and only provide shim values for a specific voxel position. In contrast, fieldmap-based approaches for Bshimming have no shim order restrictions and can be used to calculate multiple shim settings over different ROIs from a single acquisition. Here we compare projection and fieldmap-based shim approaches in brain areas known to be problematic in terms of B0 homogeneity.

2882
Five-minute GABA: Halving the scan time of GABA-edited MRS measurements
Mark Mikkelsen1,2 and Richard A. E. Edden1,2

1Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, 2F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States

Measurement of lower-concentration metabolites at ≤3T using edited MRS requires relatively long scan times (~10 min for a 27-mL voxel). We investigated whether scan times can be halved to ~5 min without a significant increase in group-level variance. GABA-edited MEGA-PRESS data from the Big GABA repository were analyzed by quantifying GABA+/Cr levels for complete datasets (320 averages; ~10 min) versus the first half of each (160 averages; ~5 min). There were no significant differences in group-level variance or GABA+/Cr levels. It appears that for a large, high-SNR voxel, GABA editing scan times of ~5 min are feasible.

2883
Performance of Compressed Sensing for detecting low SNR 19F MRI in the Murine Brain using Prospective Undersampling
Ludger Starke1, Joao dos Santos Periquito1, Christian Prinz1, Andreas Pohlmann1, Thorald Niendorf1,2, and Sonia Waiczies1

1Berlin Ultrahigh Field Facility (B.U.F.F.), Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Berlin, Berlin, Germany, 2Charité Campus Buch, Experimental and Clinical Research Center (ECRC), Berlin, Germany

Fluorine-19 (19F) MRI is an established tool for tracking inflammatory cells in vivo due to its excellent detection specificity. Nonetheless, low signal-to-noise ratios remain a major challenge, especially when studying inflammatory cell distribution in the brain. It was shown that compressed sensing (CS) increases 19F MRI sensitivity, yet prospective undersampling using dedicated CS sequences has only been reported in proof of concept experiments. Since false positives were observed in CS reconstructions, this work provides a thorough assessment of detection performance of in vivo CS as a tool for enhancing 19F MRI sensitivity.

2884
Simultaneous Measurement of Glutamate, Glutamine, and Glutathione by Single-Step Spectral Editing
Li An1, Maria Ferraris Araneta1, Milalynn Victorino1, and Jun Shen1

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

A single-step spectral editing MRS sequence is described for simultaneously measuring glutamate, glutamine, and glutathione at 7 T. Same as a previously described three-step editing technique, the editing pulse induces the collapse of targeted multiplets into high intensity pseudo singlets at a medium echo time. No data subtraction is necessary. In the current example, the editing pulse acts on the H3 protons of glutamate, glutamine, and glutathione near 2.12 ppm to generate sharp and high intensity pseudo singlets of glutamate, glutamine, and glutathione H4 protons. Signal enhancement of the three metabolites is analyzed in detail.

2885
Leveraging large publicly available datasets to benchmark new 1H-MRS modeling methods against established algorithms
Helge J. Zöllner1,2, Georg Oeltzschner1,2, Michal Povazan1,2, and Richard A. E. Edden1,2

1Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, 2F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States

Contemporary linear-combination modeling (LCM) methods for MRS data are usually implemented in compiled, ‘black-box’ fashion. The ability to modify underlying algorithms and/or introduce novel quantification approaches may improve the transparency, robustness and accuracy of metabolite estimation, but there is no established framework for rapid prototyping of modeling algorithms and benchmarking their performance. Here, we use a large, publicly available 3T PRESS dataset from multiple sites and vendors to assess the performance of a new open-source LCM algorithm, featured in a new MRS data analysis toolbox (‘Osprey’, github.com/schorschinho/osprey). Quantification of four major metabolites is compared to the widely used LCModel algorithm.

2886
Semi LASER Localized Echo Planar Total Correlated Spectroscopic Imaging
Manoj Kumar Sarma1, Andres Saucedo1, Uzay E. Emir2, and M. Albert Thomas1

1Radiological Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States, 2School of Health Sciences, Purdue University – West Lafayette, West Lafayette, IL, United States

We implemented a semi-LASER localized total correlated spectroscopic imaging (EP-TOCSI) sequence on a 3T MRI scanner.  Compared to L-COSY the coherence transfer 900 RF pulse was replaced by a spin-lock module consisting of adiabatic train of RF pulses using MLEV4 phase cycling; also, multi-voxel encoding included EPI read-out combined with phase-encoding. After evaluating the performance of the 4D EP-TOCSI sequence using a corn oil phantom, we investigated calf muscle of 2 healthy and 1 type 2 diabetic subjects.  There were relayed cross peaks in addition to COSY cross peaks conventionally recorded by L-COSY or EP-COSI. 

2887
Improved MultiNet GRAPPA performance with semi-synthetic calibration data for accelerated 1H FID MRSI at 7T
Kimberly Chan1, Theresia Ziegs2, and Anke Henning1,2

1Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, United States, 2Max Planck Institute for Biological Cybernetics, Tuebingen, Germany

It has been shown that neural networks combined with variable k-space undersampling (MultiNet GRAPPA) is superior to a conventional GRAPPA reconstruction at 9.4T.  Here, the feasibility of performing MultiNet GRAPPA for 1H FID-MRSI at 7T is investigated with and without novel modifications to the original acquisition/reconstruction scheme.  In this study, it is shown that MultiNet GRAPPA is shown to be feasible for 1H MRSI acceleration at 7T with a new k-space undersampling scheme for higher signal-to-noise and increased map reliability and use of a novel technique to increase SNR retention using semi-synthetic calibration data without an increase in acquisition time.

2888
Proton NMR metabolomics guided prediction of anti-obesity properties of medicinal plants
Rama Jayasundar1, Aruna Singh1, and Dushyant Kumar1

1Department of NMR, All India Institute of Medical Sciences, New Delhi, India

Given the alarming increase in obesity and associated NCDs, use of nutritional and medicinal plants in obesity management have come into focus. There is growing interest in pungent  thermogenic plants with anti-obesity activity. With this in view, the study has explored the potential of NMR metabolomics to identify plants with anti-obesity activity based on their chemosensory and thermogenic properties, the latter evaluated by Differential Scanning Calorimeter. Multivariate analysis of NMR data discriminated thermogenic (pungent) and non-thermogenic (sweet) plants and also correlated well with the calorimetry analyses. NMR can identify quickly plants with anti-obesity potential using their chemosensory associated thermogenic properties.

2889
Singlet state encoded magnetic resonance (SISTEM) spectroscopy
Andrey Pravdivtsev1, Frank D. Sönnichsen2, and Jan-Bernd Hövener1

1Medical faculty, MOIN CC, Kiel University, Kiel, Germany, 2Otto Diels Institute for Organic Chemistry, Kiel University, Kiel, Germany

MRS provides a non-invasive window into an in vivo biochemistry – basically a virtual biopsy. Here, we present two novel MRS sequences (SISTEM-1 and 2) and method to selectively prepare and detect the signal of endogenous metabolites. The long-lived signal of NAA-CH2 protons was isolated by the strong suppression of H2O and lipid signals using broad-band saturation or double-quantum filter. The frequency of the modulated NAA-CH2 signal was measured and associated with a pH value. Non-invasive measurement of pH value, imaging of drug distribution are only some of the possible applications.


MRS Technical 3

New Techniques in MRS
 Spectroscopy

2890
T2 relaxation times of seven individual macromolecules in rat brain 1H MR Spectra at 9.4T: single inversion recovery and AMARES post processing
Dunja Simicic1,2, Veronika Rackayova2, and Cristina Cudalbu2

1LIFMET, EPFL, Lausanne, Switzerland, 2CIBM, EPFL, Lausanne, Switzerland

At short echo times 1H-MR spectra contain the contribution of mobile macromolecules (MM), i.e. broader resonances characterized by shorter relaxation times (T1,T2) which underlie the narrower peaks of metabolites. There are very few studies assessing MM T2 relaxation times, with only one study reporting T2-s of individual MM peaks in the full ppm range at 9.4T in the human brain. In this work we present a new approach: single inversion recovery with an optimized inversion time combined with AMARES post-processing. Using this technique we quantified 10-MM components and estimated T2 relaxation times (for 7-MM components) in rat brain at 9.4T.

2891
Measuring transverse relaxation rates of major brain metabolites from a single spin-echo: Demonstration using single voxel PRESS acquisitions
Reyhaneh Nosrati1,2, Mukund Balasubramanian1,2, and Robert Mulkern1,2

1Radiology, Boston Children's Hospital, Boston, MA, United States, 2Harvard Medical School, Boston, MA, United States

Several studies have reported strong correlations between transverse relaxation rate (R2) of the brain metabolites and neurological/psychiatric diseases. Typically, R2 quantification requires several PRESS acquisitions at different echo-times leading to long scan times. Here, we evaluated the feasibility of a novel technique based on a single-echo PRESS acquisition with full echo sampling for R2 estimation of major brain metabolites (NAA, Cr and Cho) and compared those to the values obtained using five PRESS acquisitions. The proposed method allowed for R2 estimation with 87.7±6.8% accuracy compared to the multiple PRESS acquisitions representing a five-fold decrease in acquisition time in this case.

2892
Determination of Brain Metabolite T1 Without Interference from Macromolecule Signals
Li An1, Maria Ferraris Araneta1, Milalynn Victorino1, and Jun Shen1

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

Optimal detection of many metabolites requires a specific TE, at which significant macromolecule signals are often present. The presence of macromolecule signals complicates the measurement of metabolite T1 because different spectral models may be necessary for macromolecules at different inversion recovery stage, therefore, potentially introducing additional errors. To minimize interference from macromolecules, we chose inversion times in such a way that the metabolite signals were changed by as much as 60% while the macromolecule signals were essentially unchanged. This avoided the T1 relaxation effect of macromolecules, and thus simplified data acquisition and post-processing.

2893
Test-Retest Reproducibility of in vivo Cortical GABA and Glx Measurements with MEGA-PRESS: Comparing 32-Channel and 8-Channel Head Coils
Peter Truong1, Napapon Sailasuta1,2, and Sofia Chavez1,2

1Research Imaging Centre - MRI, Centre for Addiction and Mental Health, Toronto, ON, Canada, 2Psychiatry, University of Toronto, Toronto, ON, Canada

Higher-numbered phased-array coils have been associated with significant increases in SNR. For this gain, one would expect more accurate and precise MRS measurements for a regular PRESS sequence processed with a fully automated program such as LCModel. However, the effects of increased SNR on a J-edited technique such as MEGA-PRESS for GABA measurements are not as straight-forward. In this study, we wish to compare the reproducibility of GABA+ and Glx measurements from an 8-channel and a 32-channel head coil in two cortical regions of interest: Anterior Cingulate Cortex (ACC) and Left-Dorsolateral Prefrontal Cortex (Lt-DLPFC).

2894
Reproducibility of neurochemicals in sub-microlitre MRS
Alireza Abaei1, Dinesh K Deelchand2, Francesco Roselli3, and Volker Rasche1

1Core Facility Small Animal Imaging, Ulm University, Medical Center, ulm, Germany, 2Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, United States, 3German Center for Neurodegenerative Diseases (DZNE), ulm, Germany

Using sub-microlitre voxel size in magnetic resonance spectroscopy (MRS) is advantageous to investigate specific small brain region without any partial volume effect. The aim of this study was to determine the intra-individual coefficient-of-variation of neurochemical concentrations when using sub-microlitre MRS voxel measured during 3 consecutive days. This study was performed in adult mice at 11.7T. The intra-individual CV for the major and high concentration brain metabolites was ≤ 9% for MRS data collected in pre-clinically feasible scan times. This in turn shows that sub-microlitre can be used in pre-clinical application to detect subtle changes in neurochemical profile in diseased brain.

2895
Effect of water suppression and metabolite cycling on quantification of 1H MRS spectra in the human brain at 3 Tesla
Dinesh K Deelchand1 and Pierre-Gilles Henry1

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

This study investigates the effect of water suppression and metabolite cycling on metabolite quantification and macromolecules in 1H MRS. Single-voxel semi-LASER spectra and metabolite-nulled spectra (macromolecules) were acquired in the posterior cingulate cortex in the human brain at 3T using three different schemes: VAPOR, metabolite-cycling (MC), and metabolite-cycling combined with a single water suppression pulse. Results show that macromolecule signal and several metabolites (ascorbate, total creatine, glutamate, and glutathione) have higher in concentration when using MC compared to VAPOR. Combining MC with a single water suppression pulse results in concentrations in between those obtained with VAPOR and MC.

2896
An Untargeted Metabolomics Approach to MRS in the Human Brain: A Comparison between LCModel  and MRS-based Classifier-Development System
Srijyotsna Volety1, Elizabeth Seaquist2, Gulin Oz3, and Uzay Emir1,4

1Health Sciences, Purdue University, West Lafayette, IN, United States, 2Department of Medicine, Medical School, University of Minnesota, Minneapolis, MN, United States, 3Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota, Minneapolis, MN, United States, 4Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, United States

MRS quantification tools such as LCModel require the use of prior knowledge and can be time-consuming. Therefore, we propose an untargeted metabolomics approach to in vivo 1H-MRS using pattern recognition and machine learning to analyze spectral features. The ability of our approach to measure changes in brain glucose while blood glucose levels were increased was studied using high quality spectra and reliable data acquisition methods. Results showed similar time-course glucose signals and sensitivity to changes in glucose concentrations for both LCModel and our pattern recognition analysis. Thus, demonstrating that untargeted metabolomics techniques can be used for in vivo MRS quantification.

2897
MODIFIED HERCULES MULTI-METABOLITE EDITING with SEMI-LASER LOCALIZATION at 3T
Steve CN Hui1,2, Muhammad G Saleh1,2, Georg Oeltzschner1,2, Mark Mikkelsen1,2, Sofie Tapper1,2, and Richard AE Edden1,2

1Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University, Baltimore, MD, United States, 2F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States

An improved editing scheme was proposed for the Hadamard Editing Resolves Chemicals Using Linear-combination Estimation of Spectra (HERCULES). The original editing pulse at 4.18 ppm was replaced by a new wider-band pulse at 4.04 ppm to facilitate signal acquisition for aspartate, ascorbate and lactate. Furthermore, the new scheme (HERCULES-2) was implemented within the semi-LASER and PRESS sequences. HERCULES-2 with semi-LASER yielded increases in overall signal intensities in most targeted metabolites, robust to B1 inhomogeneity, facilitating the precise quantification of edited spectra.

2898
Dual-voxel 1H MR spectroscopy in mouse brain at 14.1T with dynamic shim update (DSU) acquisition scheme
Hikari Yoshihara1, Nicolas Kunz2, Jean-Claude Martinou3, and Hongxia Lei2

1Laboratory for Metabolic Imaging, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, 2Animal Imaging and Technology Core (AIT), Center for Biomedical Imaging (CIBM), Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, 3Faculty of Science, University of Geneva, Geneva, Switzerland

Dynamic shimming updates with first- and second-order shims are essential for dual-voxel spectroscopy of mouse cortex and hippocampus at high magnetic field. We show that DSU is feasible for studying pharmacological effects in transgenic mice at 14.1 T.

2899
A method to estimate GABA free from homocarnosine and macromolecular overlap through a combination of STEAM and J-difference editing sLASER at 7T
Karl Landheer1, Hetty Prinsen2, Ognen A Petroff3, Douglas L Rothman2, and Christoph Juchem1,4

1Biomedical Engineering, Columbia University, New York, NY, United States, 2Radiology and Biomedical Imaging, Yale University, New Haven, CT, United States, 3Neurology, Yale University, New Haven, CT, United States, 4Radiology, Columbia University, New York, NY, United States

The aim of this work was to develop a novel method to assess accurately both the relative concentrations of homocarnosine as well as GABA free from overlapping creatine, homocarnosine and macromolecule signal. This was achieved via the combination of short echo time STEAM and MEGA-sLASER experiments at 7T. The metabolites GABA and homocarnosine were measured in 6 healthy control subjects, and in a single subject medicated with isoniazid. It was found that (16.6 ± 10.2)% of the supposed GABA signal originated from homocarnosine, and that isoniazid caused a significantly elevated concentration of GABA and homocarnosine in a single subject.

2900
Improved GABA editing and macromolecule suppression with adiabatic and highly selective Gaussian pulses at 7T
Song-I Lim1 and Lijing Xin1

1Centre d'Imagerie BioMédicale (CIBM), Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland

The aim of the study is to improve the efficiency of GABA editing and macromolecule suppression at 7T. An asymmetric adiabatic pulse with broad inversion bandwidth was applied at 1.9 ppm to invert 1.5 – 1.9 ppm range and a narrow Gaussian pulse with 95 Hz of bandwidth (0.95 < Mz) was applied at 1.7 ppm to suppress macromolecule. In the GABA and lysine phantom tests, this scheme shows ± 9 Hz of signal loss threshold in comparison with highly selective inversion pulse without macromolecule suppression (± 6 Hz of threshold) and symmetric pulses (± 3 Hz of threshold).

2901
Optimal and efficient crushing for semi-LASER at 7T – a comparison
Zahra Shams1, Vincent Oltman Boer2, Dennis W.J. Klomp1, Jannie P. Wijnen1, and Evita Wiegers1

1Radiology, University Medical Center Utrecht, Utrecht, Netherlands, 2Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark

This study compares different crushing schemes for short-TE semi-LASER at 7T; minimal crushers, DOTCOPS and newly designed Adaptive crusher scheme. Maintaining a short echo time is traded for optimal spoiling of unwanted coherences.

2902
Optimal phased-array signal combination for polyunsaturated fatty acids measurement in breast cancer using MQC MR Spectroscopy at 3T
Vasiliki Mallikourti1, Sai Man Cheung1, Tanja Gagliardi 2,3, Yazan Masannat4, Steven Heys1,4, and Jiabao He1

1Institute of Medical Sciences, School of Medicine, University of Aberdeen, Aberdeen, United Kingdom, 2Department of Clinical Radiology, Aberdeen Royal Infirmary, Aberdeen, United Kingdom, 3Department of Radiology, Royal Marsden Hospital, London, United Kingdom, 4Breast Unit, Aberdeen Royal Infirmary, Aberdeen, United Kingdom

Phased-array signal combination algorithms of adaptively optimised combination (AOC), noise decorrelated combination (nd-comb), whitened singular value decomposition (WSVD), S/N2, S/N, and Signal Weighting, were evaluated for enhancing the SNR of polyunsaturated fatty acids spectra acquired using MQC MRS from breast cancer. Data were acquired from seventeen breast tumours excised from patients, fifteen healthy volunteers and five patients with breast cancer. AOC yielded the maximum SNR improvement and was independent from voxel volume, PUFA content, or water/fat ratio. AOC improved SNR by 24% (relative to non-noise decorrelated algorithms) and shortened acquisition time in patients by 1.5 times while maintaining SNR. 

2903
High-resolution measurements on heterogeneous samples by spatially-selective pure shift NMR spectroscopy
Yuqing Huang1, Haolin Zhan1, and Zhong Chen1

1Department of Electronic Science, Xiamen University, Xiamen, China

Measurements on heterogeneous samples, such as semisolid food and biological tissues, constitute a significant research topic in various fields. However, measurements on heterogeneous samples by conventional 1D 1H NMR generally suffer from two challenges, namely magnetic field inhomogeneity caused by anisotropic interactions and spectral congestion induced by crowded NMR resonances. In this report, we introduce a spatially-selective pure shift NMR approach for high-resolution measurements on heterogeneous samples based on the suppression on effects of magnetic field inhomogeneity and J couplings, thus useful for investigating heterogeneous sample systems with extensive chemical and biological applications.

2904
Potential benefits from Multi-Echo Single-Shot Spectroscopy with a combined fitting process
Rudy Rizzo1 and Roland Kreis1

1Department of Radiology and Biomedical Research, University of Bern, Bern, Switzerland

The benefits of multi-echo single-shot (MESS) spectroscopy are explored aiming at simultaneous determination of metabolite content and T2 times through simultaneous linear-combination model fitting of partially sampled echoes. Cramer-Rao lower bounds (CRLB) and Monte-Carlo simulations are used to judge this benefit. The novel scheme was compared with traditional multi-echo multi-shot and single-echo methods, exploring different TE settings for spectra of the major brain metabolites. Results indicate that MESS outperforms older methods for simultaneous determinations of T2s and concentrations, with improvements ranging at 20-30% for T2s and 30-50% for areas.  However, for concentrations alone traditional single-echo sequences are more sensitive.


MRS Technical 4

New Techniques in MRS
 Spectroscopy

2905
High-Resolution Whole-Brain 3D Magnetic Resonance Spectroscopic Imaging
Mohammed Goryawala1, Sulaiman Sheriff1, Ronald Ouwerkerk2, Hari Hariharan3, Peter Barker4, Hyunsuk Shim5, and Andrew Maudsley1

1Radiology, University of Miami, Miami, FL, United States, 2Biomedical and Metabolic Imaging Branch, The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Bethesda, MD, United States, 3Center for Magnetic Resonance & Optical Imaging, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States, 4Department of Radiology and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, United States, 5Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA, United States

Whole-brain Magnetic Resonance Spectroscopic Imaging (MRSI) is an effective technique for non-invasive quantification of brain metabolite levels 1-3 that can be used to create maps for the study of both regional or diffuse metabolic alterations in various pathologies. Improved spatial resolution can result in significantly better mapping but is often limited by the signal-to-noise ratio (SNR). This abstract presents a whole-brain 3D MRSI acquisition scheme that uses hypergeometric dual-band (HGDB) pulses for lipid suppression over the brain volume, real-time frequency drift correction, and novel post-processing methods to generate whole-brain metabolite maps in humans at 3T.

2906
Fast spectroscopic imaging of GABA at 7T
Jullie W Pan1, Victor Yushmanov1, Chan H Moon1, and Hoby P Hetherington1

1Radiology, University of Pittsburgh, Pittsburgh, PA, United States

We have developed and implemented a fast spectroscopic imaging acquisition for selective homonuclear polarization transfer sequence for the detection of GABA at 7T. With the high SNR available at 7T, whole slice studies of 1.65cc nominal resolution are achievable with acquisition durations (5 to 10min) conventionally used in single voxel studies. As this editing is performed with longitudinal magnetization, this method is single shot and is flexible for evaluation of multiple coupled spins.

2907
Ex vivo whole brain metabolic fingerprinting at 7T - protocol optimization and preliminary results
Alexandra Lipka1,2, Lukas Hingerl1, Gilbert Hangel1, Eva Heckova1, Stanislav Motyka1, Verena Endmayr3, Romana Höftberger3, Simon Hametner4, Siegfried Trattnig1,2, and Wolfgang Bogner1,2

1Highfield 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, 3Institute for Neurology, Medical University of Vienna, Vienna, Austria, 4Center for Brain Research, Institute of Neuroimmunology, Medical University of Vienna, Vienna, Austria

MRS has rarely been applied for postmortem measurements except for single-voxel studies, which can be explained by the fact that rapid degradation of metabolite levels makes scanning of fresh specimen highly critical.SVS contrary to MRSI cannot cover whole affected regions, while pathological changes may not be visible on anatomical images, yet. To investigate changes ex-vivo, a true whole-brain MRSI approach is critical. Our study shows the potential of ultra-highfield whole-brain FID-MRSI for metabolic fingerprinting of fresh postmortem brains for correlation with histology, as the link between neurochemical changes and underlying cell-types in many demyelinating/neurodegenerative disorders is still not fully understood.


2908
Silent EPSI using a gradient axis driven at 20 kHz
Edwin Versteeg1, Kyungmin Nam1, Dennis Klomp1, Jeroen Hendrikse1, Alex Bhogal1, Jeroen Siero1,2, and Jannie Wijnen1

1Radiology, University Medical Center Utrecht, Utrecht, Netherlands, 2Spinoza Centre for Neuroimaging Amsterdam, Amsterdam, Netherlands

Echo planar spectroscopic imaging (EPSI) can be used for fast spectroscopic imaging, however, the gradient hardware greatly limits the spectral bandwidth. Moreover, the associated fast switching gradient produces uncomfortable levels of acoustic noise. In this work, we show the feasibility of spectroscopic imaging at high spectral bandwidth using a silent gradient axis driven at 20 kHz and a segmented EPSI sequence. We report results on the silent segmented EPSI compared to the conventional EPSI approach on a phantom containing NAA, creatine and glutamate and show the first silent and high bandwidth in-vivo measurements.

2909
Improvement of the selective multiple quantum coherence chemical shift imaging sequence for lactate imaging of lymphoma patients at 3T
Seung-Cheol Lee1, Hari Hariharan1, Fernando Arias-Mendoza1, Gabor Mizsei1, Kavindra Nath1, Sanjeev Chawla1, Stephen J. Schuster1, Ravinder Reddy1, and Jerry Glickson1

1University of Pennsylvania, Philadelphia, PA, United States

Lactate is an important marker of tumor metabolism. We have previously reported the Hadamard slice selected, selective multiple quantum coherence chemical shift imaging sequence for a 3T clinical scanner to image lactate in the human body. Here we report modification and optimization of the sequence for reducing motion effect and increasing lipid suppression while retaining lactate. A coherence selection gradient ratio of a:-1:2 with nonzero a provided improved suppression of lipid resonances at 1.3 ppm and 0.9 ppm compared to the previous 0:-1:2 ratio. Optimization of RF pulses blocked occurrence of MQC between lipid 2.0 ppm and 5.3 ppm resonances.

2910
Comparison of short echo-time spiral MRSI and single-voxel spectroscopy in the human brain at 3T
Dinesh K Deelchand1 and Pierre-Gilles Henry1

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

The goal of this study was to compare the spectral quality and metabolite concentrations obtained with short echo-time 2D spiral MRSI and single-voxel spectroscopy (SVS) in the human brain at 3T. Semi-LASER was used for localization (SVS) or pre-localization (MRSI). MRSI was acquired in a transverse slice through the posterior cingulate cortex (PCC), and SVS was from PCC. Results show comparable spectral quality between acquisitions. Differences in concentrations between the two techniques is likely due to the MRSI point-spread function. This study shows feasibility of acquiring high-quality spiral MRSI data similar in spectral quality to SVS within a few minutes.

2911
B0 Inhomogeneity Corrected Reconstruction for Low-Resolution J-resolved MRSI Using Low-Rank and Spatial Constraints
Zepeng Wang1,2 and Fan Lam1,2

1Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL, United States, 2Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, United States

This work presents a new method for B0 inhomogeneitycorrected reconstruction of J-resolved (multi-TE) MRSI datawith limited k-space coverage. A constrained reconstruction formulation was proposed to simultaneously reconstruct the data at all TEs, using a joint low-rank constraint that exploits the spatial-spectral-TE correlation in the data and a spatial constraint that exploits prior edge information from high-resolution anatomical images. Simulation and in vivo experiments using a customized 3D J-resolved EPSI acquisition have been performed to evaluate the proposed method. Experimental results demonstrated improved lineshape and SNR achieved by the proposed method over existing B0 correction methods.

2912
3D CSI downfield 1H MR spectroscopy using EBURP1 spectrally selective excitation pulse
Puneet Bagga1, Hari Hariharan1, Walter R Witschey1, and Ravinder Reddy1

1Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States

Downfield MRS provides a great tool to detect and quantify metabolites downfield to water including NAD and ATP. Acquisition of downfield MR spectrum in vivo without water suppression leads to the possibility of detection of many cross-relaxing/exchanging resonances. The T2 of many species occurring downfield of water are relatively short which require short echo time MRS methods. EBURP pulses have been shown to reliably excite narrow spectral region with minimum phase response. In this study, we generated new pulse sequences for single voxel and 3D spectral selective EBURP excitation to detect cerebral NAD from human brain at 7T.

2913
Rapid acquisition of semi-LASER MR spectroscopic imaging using symmetric EPSI encoding: A preliminary study in phantom and human brain
Sunitha Thakur1, Olivia Sutton1, Eduardo Coello2, Alexander Lin2, Ralph Noeske3, Ricardo Otazo1, and Robert Young1

1Memorial Sloan Kettering Cancer Center, New York, NY, United States, 2Brigham and Women’s Hospital, Boston, MA, United States, 3MR Applied Science Lab, GE Healthcare, Berlin, Germany

 The aim of this study was to develop and test rapid MR spectroscopic imaging (MRSI) in patients with brain tumors. We implemented and optimized rapid MRSI at 3T using semi-localization by adiabatic selective refocusing pulses (semi-LASER), fast spatial encoding using symmetric echo planar spectroscopic imaging (EPSI), and robust water suppression with variable power and optimized relaxation delays. This rapid imaging approach was tested in a phantom and subsequently in a volunteer and a patient. In vivo studies demonstrated that high quality MRSI data with voxel volumes less than 0.5 mL can be collected within a clinically feasible time (2 minutes).

2914
Over-discretized reconstruction to correct for B0 inhomogeneity and improve localization in 1H-MRSI of the prostate
Carlijn Tenbergen1, Loreen Ruhm2, Arend Heerschap1, Anke Henning2,3, and Tom Scheenen1

1Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, Netherlands, 2High-Field MR Center, Max Planck Institute for Biological Cybernetics, Tübingen, Germany, 3Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, United States

In in vivo MRSI spatial inhomogeneities of the main magnetic field cause spectral line broadening and location dependent frequency shifts in the spectra. An over-discretized reconstruction method is applied to existing prostate 1H-MRSI data, consisting of spatial over-discretization of the MRSI grid, frequency shift correction according to a high resolution B0map and weighted spatial averaging to the target resolution. Intravoxel B0 variations are corrected for and resampling to a new target resolution results in improved localization of signals. This could lead to detection of signals with lower spectral intensity and to improved visualization of smaller cancer lesions in the prostate.

2915
Examination of methods to optimize Glutamate-Glutamine separation at 3T
Tiffany Bell1,2,3, Dana Goerzen4, Jamie Near4, and Ashley D Harris1,2,3

1Department of Radiology, University of Calgary, Calgary, AB, Canada, 2Hotchkiss Brain Institute, Calgary, AB, Canada, 3Alberta Children's Hospital Research Institute, Calgary, AB, Canada, 4Douglas Mental Health Institute, Centre d’Imagerie Cerebrale, Montreal, QC, Canada

Separating glutamate (Glu) from its precursor, glutamine (Gln) at 3T is challenging due to signal overlap. Multiple sequence optimisations have been suggested, with simulated data used to assess accuracy. Here, using 7T data as a reference, we investigate the ability of four PRESS sequences with different echo times of separating Glu and Gln. We found that Glu measured at 3T using TE=20ms shows the highest agreement with 7T data. Gln measured using TE=20ms, 30ms and 40ms all agree with Gln measured at 7T. Therefore, we conclude PRESS with TE=20ms is the most effective at separating and quantifying Glu and Gln.

2916
Reproducibility of Auditory Functional Magnetic Resonance Spectroscopy at 7T
Eduardo Coello1, Nicolas R. Bolo2, Huijun Liao1, Angelina Awad3, Margaret A. Niznikiewicz3, and Alexander Lin1

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, Boston, MA, United States

This work describes a methodology to perform reproducible functional MR spectroscopy (FMRS) experiments to study auditory processing at 7T. A processing pipeline and quality control steps are proposed to remove distortions and temporal instabilities in the dynamic experiment. The designed experiment was successfully tested, producing highly correlated results in healthy volunteers and patients with schizophrenia scanned multiple times.

2917
Diffusion MR spectroscopy at 7T with no water suppression is sensitive to measuring diffusion properties of metabolites in the corpus callosum
Yasmin Mzayek1,2, Francesca Branzoli3, Thomas Troalen4, Yann Le Fur1,2, Patrick Viout1,2, Tangi Roussel1,2, Stanislas Rapacchi1,2, Maxime Guye1,2, Itamar Ronen5, Wafaa ZAARAOUI1,2, and Jean-Philippe RANJEVA1,2

1Aix-Marseille Université, CNRS, CRMBM, Marseille, France, 2APHM, Hôpital de la Timone, Pôle d’Imagerie Médicale, CEMEREM, Marseille, France, 3Brain and Spine Institute - ICM, Centre for NeuroImaging Research - CENIR, Paris, France, 4Siemens Healthineers SAS, Saint-Denis, France, 5Department of Radiology Leiden University Medical Center, Leiden, Netherlands

We implemented a diffusion-weighted semi-LASER single voxel spectroscopy sequence with no water suppression to measure mean diffusivity and fractional anisotropy within two volumes-of-interest in the corpus callosum. Without water suppression, we were able to decrease acquisition time and use the water signal for phase, frequency, and eddy current corrections. We measured the signal decay of N-acetylaspartate (tNAA), creatine (tCr), choline (tCho), and water to derive diffusion outcomes and compare between the two volumes-of-interest. Our implementation was done in feasible time for in vivo measurements. Further development can lead to more specific assessments of brain microstructure and pathophysiology.

2918
Determination of Metabolite T2-Relaxation in the Medial Prefrontal Cortex at 7T Using an 8Tx/8Rx Channel Head Coil
Ariane Fillmer1, Layla Tabea Riemann1, Frank Seifert1, Semiha Aydin1, Harald Pfeiffer1, and Bernd Ittermann1

1Physikalisch-Technische Bundesanstalt (PTB), Braunschweig und Berlin, Germany

To investigate underlying mechanisms of psychiatric diseases, such as schizophrenia, magnetic resonance spectroscopy is a powerful tool. Here, the medial prefrontal cortex is a region of high interest, however, high quality measurements are technically challenging, and proper absolute quantification is hindered by the lack of literature values for metabolite relaxation times. This work presents the acquisition of high-quality MR spectra from the medial prefrontal cortex, and the preliminary calculation of metabolite T2 relaxation times, using an 8Tx/8Rx channel coil with a dedicated phase set optimized for B1 efficiency in the frontal cortex.

2919
Ultrafast diagonal-suppressed 2D MR correlation spectroscopy
Liangjie Lin1,2 and Zhong Chen2

1Philips Healthcare, Beijing, China, 2Department of Electronic Science, Xiamen University, Xiamen, China

Two-dimensional (2D) MR spectroscopy enables feasible detection of low-concentration scalar-coupled metabolites in human tissues. However, the traditional acquisition of 2D MRS can be time consuming, and cross peaks which contain crucial spectral information in 2D correlated spectra (COSY) usually get contaminated by nearby strong diagonal peaks. Here, a pulse sequence is developed for ultrafast recording of diagonal-free 2D MR correlated spectra, thus allowing improved recognition and measurement of scalar-coupled metabolites.

2920
Multi-site/Multi-vendor reproducibility of advanced MRS at 3T in a clinical cohort
James M Joers1, Dinesh K Deelchand1, Bin Guo2, Lynn E Eberly2, Young Woo Park1, Adam Berrington3, Michal Povazan4, Andre van der Kouwe5, Khalaf Bushara6, Chiadi U Onyike7, Jeremy Schmahmann8, Peter B Barker4,9, Eva Ratai5, and Gülin Öz1

1CMRR/Radiology, University of Minnesota, Minneapolis, MN, United States, 2Division of Biostatistics, University of Minnesota, Minneapolis, MN, United States, 3Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, United Kingdom, 4Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States, 5A.A. Martinos Center for Biomedical Imaging / Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States, 6Neurology, University of Minnesota Medical School, Minneapolis, MN, United States, 7Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, United States, 8Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States, 9Kennedy Krieger Institute, Johns Hopkins University School of Medicine, Baltimore, MD, United States

The reproducibility of an advanced single voxel MRS protocol was tested in a clinical cohort and control subjects at 3T in a multi-site setting. A standardized MRS protocol was implemented on two MR system vendors (Siemens, Philips) over three sites. This protocol utilized automated voxel placement and an sLASER pulse sequence with identical radiofrequency waveforms, pulse durations, interpulse delays and gradient spoilers. Spectral quality, metabolite concentrations and test-retest reproducibility results from three voxels are reported from both the healthy control group and subjects with genetically-confirmed spinocerebellar ataxia type 3 (SCA3), a hereditary movement disorder. 


1H-MRS Non-Cancer Applications 1

Proton MRS and Other Nuclei MR
 Spectroscopy

1785
Metabolite activity in the anterior cingulate cortex during a painful stimulus using functional MRS
Jessica Archibald1,2, Erin L MacMillan3,4,5, Carina Graf2,6, Piotr Kozlowski2,7,8, Cornelia Laule2,9,10, and John LK Kramer1,2,11

1Experimental Medicine, University of British Columbia, Vancouver, BC, Canada, 2International Collaboration on Repair Discoveries (ICORD), Vancouver, BC, Canada, 3Radiology, University of British Columbia, Vancouver, BC, Canada, 4Image Tech Lab, Simon Fraser University, Vancouver, BC, Canada, 5Philips Healthcare Canada, Vancouver, BC, Canada, 6Physics and Astronomy, University of British Columbia, Vancouver, BC, Canada, 7Radiology, University of British Columbia, vancouver, BC, Canada, 8UBC MRI Research Centre, Vancouver, BC, Canada, 9Physics and Astronomy, University of British Columbia, vancouver, BC, Canada, 10Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada, 11School of Kinesiology, University of British Columbia, Vancouver, BC, Canada

Current treatment evaluation procedures of pain conditions are dependent on self-reported measures. The objective of this study was to determine changes in excitatory neurotransmitters (i.e., glutamate and glutamate+glutamine) in the anterior cingulate cortex as an objective measure of pain during a painful stimulus using single voxel functional magnetic resonance spectroscopy (fMRS). Glutamate concentration changes during the painful stimulus suggest a role for glutamate in detecting pain which was not related to self-reported pain ratings. An exploratory analysis on sex revealed an 8.63% (p=0.08) increase in glutamate at pain onset in female participants compared with a 7.45% (p=0.31) increase in males.

2921
Excitability of the Glutamatergic Neurotransmission in the Anterior Cingulate During Appraisal of Emotional Stimuli
Paul R Burghardt1, Dalal Khatib1, Andrew Neff1, Katherine Nowak1, Katlin Chappelle1, and Jeffrey Stanley1

1Wayne State University, Detroit, MI, United States

Personality and fitness impact emotional regulation, however the neurobiological mechanisms underlying these relationships are poorly understood. dACC glutamate modulation was quantified during appraisal of emotional images using ¹H fMRS. Additionally,  aerobic fitness and trait personality were assessed in participants. The dACC glutamate was lower during positive images compared to neutral images, which was associated with trait openness. Glutamate levels during appraisal of negative emotional images did not differ from neutral images, but was negatively associated with aerobic fitness. These results shed light on the mechanisms that modulate the impact of trait personality and fitness on ACC response during emotional regulation.  

2922
Effect of age on in vivo GABA and glutathione levels in a pediatric sample
Muhammad Gulamabbas Saleh1, Afroditi Papantoni2, Georg Oeltzschner1, Mark Mikkelsen1, Nicolaas A Puts1, Richard A Edden1, and Susan Carnell2

1Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, 2Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD, United States

GABA is the primary inhibitory neurotransmitter in the human brain and is implicated in several neuropathologies. Glutathione is a major antioxidant in the brain and is considered a marker of oxidative stress. Several studies have reported age-related declines in GABA levels in adulthood, but the aging dynamics of both GABA and glutathione have not been well explored in childhood. We demonstrate increases in GABA and no differences in glutathione with age in a healthy pediatric sample (5.7-13.9 years). This study provides insight into neuronal maturation in children and may facilitate better understanding of the pathophysiology of developmental disorders.

2923
Detection of acetyl-carnitine in the human heart in vivo using long echo-time 1H-MRS at 3T
Joe Pollacco1,2, William Clarke3, Aaron Hess1, Dragana Savic1,4, Christopher T Rodgers1,5, Damian Tyler1,4, Jack JJ Miller1,2,4, and Ladislav Valkovic1,6

1Oxford Centre for Clinical Magnetic Resonance Research, RDM Cardiovascular Medicine, University of Oxford, Oxford, United Kingdom, 2Department of Physics, University of Oxford, Oxford, United Kingdom, 3Wellcome Centre for Integrative Neuroimaging, University of Oxford, Oxford, United Kingdom, 4Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom, 5Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom, 6Department of Imaging Methods, Slovak Academy of Sciences, Bratislava, Slovakia

Cardiac acetyl-carnitine plays an important role in fat metabolism. Decreased carnitine concentration has been reported in heart failure, but it has previously been difficult to measure acetyl-carnitine in-vivo. We show for the first time that it is possible to detect a clear acetyl-carnitine resonance at δ=2.1ppm without lipid contamination within the heart using a long echo time semi-LASER sequence at 3T. This validates the finding in skeletal muscle that the T2 of acetyl-carnitine is much longer than its surrounding lipid signals. Further work is underway to investigate variability of the acetyl-carnitine signal postprandially.

2924
Association of brain metabolite concentrations and pain perception in a cohort of patients with chronic pain
Maame Owusu-Ansah1, Candace C. Fleischer1, and Daniel E. Harper2

1Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, United States, 2Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA, United States

A proof-of-concept generalized linear model to characterize the relationships between brain metabolite concentrations and pain perception is presented, explicitly accounting for differences in regional grey matter (GM) density. Brain metabolite concentrations measured with magnetic resonance spectroscopy (MRS), and pain perception characterized using quantitative sensory testing (QST), were significantly associated in a cohort of patients with chronic pain. These results contribute to the expanding literature that supports the utility of neuroimaging to understand the underlying mechanisms of centralized chronic pain.

2925
Ultrashort-TE Liver 1H MR Spectroscopy in Alcohol Use Disorder at 3 T
Martin Gajdosik1, Jonathan Wai2,3, Karl Landheer1, Diana Martinez2,4, and Christoph Juchem1,5

1Department of Biomedical Engineering, Columbia University, New York City, NY, United States, 2Department of Psychiatry, Columbia University Irving Medical Center, New York City, NY, United States, 3New York State Psychiatric Institute, New York City, NY, United States, 4Department of Psychiatry, New York State Psychiatric Institute, New York City, NY, United States, 5Department of Radiology, Columbia University College of Physicians and Surgeons, New York City, NY, United States

Accurate detection of hepatocellular lipid content (HLC) in individuals with alcohol use disorder (AUD) is needed for early diagnosis of hepatic steatosis, a harbinger of serious liver diseases such as cirrhosis. Using a standard clinical 3T system and ultrashort-TE liver MRS, the proposed sequence employed asymmetric RF pulses with spoiler gradient cycling to achieve minimal TE of 5ms and minimal T2 errors for reliable signal quantification. No difference was found in HCL and choline levels between controls and AUD subjects. After a 3-week abstinence period, changes in hepatic fat and choline levels were observed in subjects with AUD.

2926
A 9-month follow-up study in patients with delayed neurologic sequelae after CO intoxication using absolute quantification of 1H MRS and DKI
Yi-Chen Tsai1, Hui-Ru Tsai1, Ming-Chung Chou2, Ping-Hong Lai3,4, Jie-Yuan Li5,6, and Cheng-Wen Ko1

1Dept. of Computer Science and Engineering, National Sun Yat-sen University, Kaohsiung, Taiwan, 2Dept. of Medical Imaging and Radiological Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan, 3Dept. of Radiology, Veterans General Hospital-Kaohsiung, Kaohsiung, Taiwan, 4School of Medicine, National Yang-Ming University, Taipei, Taiwan, 5Dept. of Neurology, E-Da Hospital, Kaohsiung, Kaohsiung, Taiwan, 6School of Medicine, I-Shou University, Kaohsiung, Kaohsiung, Taiwan

In this study, we explored the metabolic changes in WM of patients with and without DNS using 1H MRS and DKI longitudinally at 1 week and 1, 3, and 9 months after CO intoxication. Increased Cr and Cho were observed at early stage in WM of patients with DNS.  Decreased tNAA showed higher correlation with the presence of WM lesion than of DNS.  The chronic change of Ins and Glx in patients with DNS implies themselves as potential indices to provide valuable information for monitoring DNS development.

2927
Neurometabolic Mapping of RRMS patients using multi-slice Spiral-MRSI and support vector machine techniques
Oun Al-iedani1,2, Karen Ribbons2, Jeannette Lechner-Scott2,3,4, Neda Gholizadeh1, Scott Quadrelli5, Rodney Lea2, Ovidiu Andronesi6, and Saadallah Ramadan1,2

1School of Health Sciences, University of Newcastle, Newcastle, Australia, 2Hunter Medical Research Institute (HMRI), Newcastle, Australia, 3School of Medicine and Public Health, University of Newcastle, Newcastle, Australia, 4Department of Neurology, John Hunter Hospital, Newcastle, Australia, 5Faculty of Medicine, University of Queensland, Herston, Australia, 6Harvard Medical School, Massachusetts General Hospital, Boston, MA, United States

The study designed a novel neurometabolic mapping using multi-slice Spiral-MRSI with multi-voxel segmentation and support vector machine(SVM)  techniques to demonstrate the true nature of NAWM and WML of RRMS patients, compared to HCs. 3D-Spiral-MRSI covering 75% of the brain on 16 RRMS and 9 HCs were used. Multi-slice-MRSI was processed using novel pipeline with 3-model SVM classifications. Neurometabolic mapping revealed that (NAA/tCr) in WM-lesions was significantly lower than NAWM-MS and HCs with HCs vs WML model achieving highest sensitivity and specificity. Multi-slice-spiral-MRSI may enhance diagnosis and clinical monitoring of RRMS patients, and is sensitive in diagnosing RRMS even in NAWM.

2928
Respiratory-triggered quantitative MR spectroscopy of the human spinal cord at 7 T
Tangi Roussel1,2, Yann Le Fur1,2, Jean-Philippe Ranjeva1,2, and Virginie Callot1,2

1Aix-Marseille Univ, CNRS, CRMBM, Marseille, France, 2APHM, Hôpital Universitaire Timone, CEMEREM, Marseille, France

1H MR spectroscopy (MRS) is of great interest to help characterizing human spinal cord pathologies. However, few studies have been reported so far because of challenging experimental difficulties caused by the small size of the structure, static and radiofrequency field heterogeneities, as well as physiological motion and especially breathing. In this work, we demonstrate the necessity of respiratory-gated acquisition to collect robust 1H MRS data from the cervical spinal cord at 7T. We also present dedicated post-processing and quantitative approaches for SC metabolic assessment.

2929
1H MRS at 3T reveals reduced GABA and glutamate levels in the visual cortex induced by pharmacologically increased dopamine
Ralf Mekle1, Jochen B Fiebach1, and Heiner Stuke2

1Center for Stroke Research Berlin, Charité – Universitätsmedizin Berlin, Berlin, Germany, 2Department of Psychiatry and Psychotherapy, Charité – Universitätsmedizin Berlin, Berlin, Germany

Schizophrenia frequently manifests psychotic symptoms, such as delusions and hallucinations. However, its neurochemical mechanisms are not well deciphered, though dysfunctional dopaminergic neurotransmission is suggested. In this study, single volume 1H MRS using MEGA-PRESS at 3 T was applied to investigate possible neurochemical changes in the visual cortex induced by pharmacologically increased dopamine levels in healthy volunteers that also performed a visual detection task. Increased dopamine yielded decreased GABA and reduced glutamate quantities. Furthermore, an inverse correlation of glutamate with false perceptions in the detection task supports the theory that glutamate hypofunction might contribute to the formation of hallucinations in schizophrenia.

2930
Effect of DNA methylation levels of dopamine D4 receptor gene on GABA concentrations in the mPFC in children with primary nocturnal enuresis
Zijun Li1, Xiaoyang Li1, and Bing Yu1

1Shengjing Hospital of China Medical University, Shenyang, China

In the current study we investigated  the effect of DRD4 DNA methylation levels on the GABA concentrations in mPFC in PNE children.

Our results suggested the DNA methylation level of DRD4 is associated with increased GABA concentrations in the mPFC in PNE children. The effects of epigenetic variation of the DRD4 DNA on GABA concentrations in mPFC may help us understand the epigenetic susceptibility of the DRD4  DNA methylation to PNE.


2931
Metabolic Profile Differences in Serum of Sepsis Patients may Identify Survivors and Non-Survivors
Virendra Kumar1, Naveen Kumar MS2, sujeet kumar mewar1, Pradeep Kumar1, Naveet Wig2, Prayas Sethi2, and Sanjeev Sinha2

1Department of NMR, All India Institute of Medical Sciences, New Delhi, India, 2Department of Medicine, All India Institute of Medical Sciences, New Delhi, India

The present study reported the differences in metabolic profile of serum samples from patient with sepsis to identify survivor and non-survivor (day 0) using NMR metabolomics. A significantly higher concentration of tyrosine, histidine, methionine, betaine, creatine, phosphocreatine and choline in the serum of sepsis patients who did not survive septic shock compared to survivors. These findings suggest that metabolic alterations at day 0 may predict the survival of the septic patients. 

2932
Proton magnetic resonance spectroscopy (1H-MRS) in degenerative cervical spinal cord compression.
Petr Bednarik1, Tomas Horak2, Magda Horakova3, Alena Svatkova4, Zdenek Kadanka3, Zdenek Kadanka jr3, Petr Kudlicka5, Jan Valosek6, Dinesh Deelchand7, Pierre-Gilles Henry7, and Josef Bednarik3

1Departement of Medical Imaging and Image-guided Therapy, High Field MR Center, Vienna, Austria, 2Masaryk University, Brno, Czech Republic, 3Department of Neurology, University Hospital Brno, Brno, Czech Republic, 4Department of Internal Medicine, Medical University of Vienna, Vienna, Austria, 5Multimodal and Functional Imaging Laboratory, Central European Institute of Technology, Brno, Czech Republic, 6Departments of Neurology and Biomedical Engineering, University Hospital Olomouc, Olomouc, Czech Republic, 7Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, United States

While cervical spinal cord (CSC) compression occurs almost ubiquitously with aging, early metabolic changes in CSC that might develop into irreversible clinical myelopathy symptoms have not been described yet. Thus, we utilized fine-tuned semi-LASER 3T MRS protocol that addresses limitations of standard MRS methods to unravel metabolic damage in the cranial parts of the CSC in 50 patients with non-myelopathic degenerative cervical cord compression and 10 with clinically symptomatic degenerative cervical myelopathy  in comparison to 35 healthy controls. Higher tNAA/tCr and myo-Ins/tNAA levels suggest axonal loss  above the level of stenosis, indicating that CSC impairment exceeds the level of compression.

2933
Detection of metabolic abnormalities in different genotypes of Shank3 deficiency in mice using MRS at 11.7T
Ying Liu1,2, Lei Wei1,2, and Xiaoyong Zhang1,2

1Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China, 2Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence (Fudan University), Ministry of Education, Shanghai, China

Shank3 plays an important role in the functioning of glutamatergic synapses. In this work, we investigated whether Shank3 deficiency could induce neuroimaging changes in a transgenic autism mouse model using structural MRI and MRS at 11.7T. Our data showed that the neurochemical metabolites in medial prefrontal cortex (mPFC) are significantly changed in Shank3 deficiency models of heterozygous and homozygous genotypes, relative to wildtype controls. However, the volume of mPFC does not show significant alteration among three groups. We concluded that metabolic abnormalities are closely related to different phenotypes of Shank3 deficiency in mice.


1H-MRS Non-Cancer Applications 2

Proton MRS and Other Nuclei MR
 Spectroscopy

2934
Metabolomic profiling of wildtype and transgenic Giardia lamblia strains by 1H Magic Angle Spinning NMR spectroscopy.
Martina Vermathen1, Norbert Mueller2, David Leitsch3, Damian Hertig4, Peter Vermathen4, and Joachim Mueller2

1Department of Chemistry and Biochemistry, University Bern, Bern, Switzerland, 2Institute of Parasitology, Vetsuisse Faculty, University Bern, Bern, Switzerland, 3Institute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Vienna, Austria, 4DBMR & DIPR, University Bern, Bern, Switzerland

The intestinal protozoan parasite Giardia lamblia is a major cause of persistent diarrhea in humans and animals worldwide. Treatment of giardiasis with nitro-prodrugs relies on intrinsic enzymes in G.lamblia that are involved in activating or deactivating the prodrugs. To elucidate more about the physiologic function of these pathways and their potential roles in drug resistance, G.lamblia wildtype and transgenic strains were metabolomically characterized based on 1H HR-MAS NMR data and specific metabolites that may be related to nitroreductase activity were identified and discussed.

2935
Diurnal fluctuation of glutathione measured with MR spectroscopy
Shin-ichi Urayama1, Yujiro Yoshihara2, Masaki Fukunaga3, and Toshiya Murai2

1Human Brain Research Center, Kyoto University, Kyoto, Japan, 2Department of Psychiatry, Kyoto University, Kyoto, Japan, 3National Institute for Physiological Sciences, Okazaki, Japan

Glutathione (GSH) is a powerful and general antioxidant found in cell of various animals. Since its concentration in central nervous system has been thought to related to psychiatric disease, several studies has carried out but the results are still controversial. Here, we investigated GSH diurnal fluctuation of healthy subjects and compared with the results of the reproducibility study. Our results shows GSH concentration in brain fluctuates by 10 to 20% during the daytime. This finding indicates that conditions of MRS examination must be regulated strictly and the fluctuation should be took into account at interpretation of GSH studies.

2936
Glutamate, GABA and Excitatory/Inhibitory Ratios observed by Short-TE STEAM proton MRS measurements of young healthy subjects at 7T.
Tomohisa Okada1, Koji Fujimoto1, Dinh Ha Duy Thuy1, Hideto Kuribayashi2, Yuta Urushibata2, Ravi Teja Seethamraju3, Sinyeob Ahn4, and Tadashi Isa1

1Kyoto University, Kyoto, Japan, 2Siemens Healthcare K.K., Tokyo, Japan, 3Siemens Healthineers USA, Burlington, MA, United States, 4Siemens Healthineers USA, Berkeley, CA, United States

Relationship between glutamate and GABA as well as their regional differences have not been much investigated.  Focused on the posterior cingulate cortex (PCC), the primary motor area (M1) and the primary visual area (V1), this study found significantly higher glutamate concentration and E/I ratios at PCC than others, whereas GABA concentration was significantly higher at V1 than others.  Region-wise correlation analysis between glutamate and GABA found statistically significant correlation only at M1 (r = 0.69, p = 0.0005).  These differences may reflect difference in functional status at rest, but further investigation is required to clarify the reasons.

2937
Detection of metabolic alterations in the thalamus of the TMEV mouse model of multiple sclerosis at 9.4 Tesla
Poonam Choudhary1,2, Suyog Pol2, Marilena Preda2,3, Robert Zivadinov2,3, and Ferdinand Schweser2,3

1Department of Medical Physics, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, United States, 2Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, United States, 3Center for Biomedical Imaging at the Clinical and Translational Science Institute, University at Buffalo, The State University of New York, Buffalo, NY, United States

This study aimed to characterize the metabolic alterations in the thalamus throughout the disease course of Theiler's murine encephalomyelitis virus (TMEV) in mice using 9.4T MRS, and relate the findings to the known effects of microglia activation on neurotransmitter homeostasis. Our study confirmed that TMEV models metabolite alterations in Multiple Sclerosis. Dynamics of neurotransmitter imbalance suggest that early thalamic dyshomeostatis is driven by neuronal loss in basal ganglia input.

2938
Effects of lisinopril on arterial stiffness, hippocampal blood flow, N-acetyl aspartate and cortical thickness in hypertensive Dahl-s rats
Samuel Ajamu1, Rachel Fenner1, Nikkita Khattar2, Yulia Grigorova1, Edward Lakatta1, Ondrej Juhasz1, Peter Rapp3, Mustapha Bouhrara2, Richard Spencer2, Olga Fedorova1, and Kenneth Fishbein2

1Laboratory of Cardiovascular Science, National Institute on Aging, Baltimore, MD, United States, 2Laboratory of Clinical Investigation, National Institute on Aging, Baltimore, MD, United States, 3National Institute on Aging, Baltimore, MD, United States

Central arterial stiffness (CAS), associated with hypertension, is likely associated with attendant cerebral hypoperfusion, neuronal density loss and cognitive decline, and stiffening of cerebral arterial wall. We previously found associations between pulse wave velocity (PWV), a marker of CAS, and hippocampal cerebral blood flow (CBF) and neuronal density in 6 months old hypertensive Dahl salt-sensitive (Dahl-S) rats, which exhibit age-associated memory loss. The present study showed the ACE inhibitor, lisinopril, resulted in stabilized hippocampal blood flow and NAA concentration compared to nontreated age-matched animals. We also observed significant changes in cortical thickness for treated animals compared to nontreated control.

2939
Association of multiple sclerosis central fatigue with inhibitory and excitatory neurotransmitters
Jameen ARM1,2, Georg Oeltzschner3,4, Oun Al-Iedani1,2, Rodney Lea5,6, Jeannette Lechner-Scott5,7,8, and Sadallah Ramadan1,5

1School of Health Sciences, University of Newcastle, Newcastle, Australia, 2Imaging centre, Hunter Medical Research Institute, Newcastle, Australia, 3The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States, 4F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, 5HMRI Imaging centre, Hunter Medical Research Institute, Newcastle, Australia, 6School of Biomedical Sciences, Queensland University of Technology, Brisbane, Australia, 7Faculty of Health and Medicine, University of Newcastle, Newcastle, Australia, 8Department of Neurology, John Hunter Hospital, Newcastle, Australia

Despite neuro metabolic and morphological alterations linked to central fatigue in multiple sclerosis (MS), the pathophysiology of this symptom is not fully understood. Dysfunction of the GABAergic/Glutamatergic pathways involving inhibitory and excitatory neurotransmitters such as γ-aminobutyric acid (GABA) and glutamine+glutamate pools (Glx) have been implicated in several neurological disorders, including MS.  In this study, we evaluated if GABA and Glx levels are associated with central fatigue in MS. Our results showed significant correlations of GABA and Glx levels with fatigue scores which suggest dysregulation of GABAergic/glutamatergic neurotransmission is possibly implicated in the mechanisms of mediating central fatigue in MS

2940
In-vivo 1H-MRS Shows Differences in Polyunsaturated Fatty Acid Content between White and Brown Adipose Tissue in Humans.
Ronald Ouwerkerk1, Jatin Raj Matta1, Ahmed Hamimi1, Aaron M Cypess2, Kong Y Chen3, and Ahmed Medhat Gharib1

1Biomedical and Metabolic Imaging Branch, NIDDK/NIH, Bethesda, MD, United States, 2Translational Physiology Section, Diabetes, Endocrinology, and Obesity Branch, NIDDK/NIH, Bethesda, MD, United States, 3Energy Metabolism Section, Diabetes, Endocrinology, and Obesity Branch, NIDDK/NIH, Bethedsa, MD, United States

Localized 1H-MRS was used to compare the fatty acid composition and MR relaxation in PET proven metabolically active brown adipose tissue (BAT) in humans with white adipose tissue (WAT). Paired comparison of BAT and WAT results from the same individuals the showed differences in MR relaxation of fatty acid resonances and unsaturated fatty acid content between metabolically activatable brown fat and white adipose tissue

2941
Neurochemical Deregulation in Post-traumatic Stress Disorder
Nathan Tosh1,2, Scott Quadrelli2, Chris Foster2, Graham Galloway2, David Crompton2,3, and Carolyn Mountford2

1School of Clinical Sciences, Queensland University of Technology, Brisbane, Australia, 2Translational Research Institute, Woolloongabba, Australia, 3Griffith University, Brisbane, Australia

2D L-COSY has previously been used to demonstrate neurochemical differences between PTSD and healthy cohorts but requires a 19 minute acquisition. Single Voxel Spectroscopy (SVS), acquired in 3 minutes, was used to collect data from 3 brain regions in healthy controls and patients with Post-traumatic Stress Disorder. Neurochemical differences were seen in all the ACC, Thalamus and PCG. Data, analysed using LC Model, showed elevated levels of NAA, Lactate, GABA and Glutathione as well as glutamatergic dysfunction. Thus, SVS can be used to identify PTSD in a shorter time frame than 2D L-COSY.

2942
Lactate change during visual stimuli detected by MEGA-PRESS at 3T
Ya-Tien Liu1, Dian-Han Yang1, Cheng-Wen Ko1, Tzu-Chao Chuang2, and Shang-Yueh Tsai3,4

1Department of Computer Science and Engineering, National Sun Yat-sen University, Kaohsiung, Taiwan, 2Department of Electrical Engineering, National Sun Yat-sen University, Kaohsiung, Taiwan, 3Graduate Institute of Applied Physics, National Chengchi University, Taipei, Taiwan, 4Research Center of Mind, National Chengchi University, Taipei, Taiwan

In this study, we investigate the feasibility of using MEGA-PRESS to detect Lac response to the visual stimuli in visual cortex in fMRS experiment at 3T.  The significant raise in Lac level was found either by averaging the whole fMRS scan or by averaging over the stimuli blocks.  Our results show consistency with the published results.  More sophisticated approach to analyze fMRS data may be necessary to facilitate reliable metabolic quantification.

2943
Simultaneous characterization of individual macromolecule resonances and metabolites in the Fischer 344 rat during healthy aging
Caitlin Fowler1, Dan Madularu2, Masoumeh Dehghani2, Gabriel Devenyi2, and Jamie Near3

1Biological and Biomedical Engineering, McGill University - Douglas Hospital Research Centre, Verdun, QC, Canada, 2Douglas Hospital Research Centre, Verdun, QC, Canada, 3Psychiatry, McGill University - Douglas Hospital Research Centre, Montréal, QC, Canada

To better understand pathological aging, we must first have a thorough understanding of changes that occur in the brain during healthy aging. This project employs Magnetic Resonance Spectroscopy to characterize longitudinal changes in the neurochemical profile of healthy Fischer 344 rats. In addition to the commonly reported metabolites, nine macromolecular resonances were included in the basis set and quantified, based on parameterization of a group-averaged metabolite-nulled spectrum. For the first time, longitudinal age-related changes in metabolites and individual macromolecules were simultaneously characterized in the Fischer rat. Sex-specific differences were also identified in metabolites and macromolecules.

2944
Effects of  High Fat Diet  on the adipose tissues and brain metabolism of a transgenic mouse which over-expresses human hydrolase hMTH1
Rossella Canese1, Gabriele De Luca2, Ambra Dell'Orso3, Egidio Iorio1, Mattea Chirico1, Maria Elena Pisanu1, Paola Fortini3, and Valeria Simonelli3

1NMR and MRI unit, Core facilities, Istituto Superiore di Sanita', Rome, Italy, 2Oncology and Molecular Medicine Department, Istituto Superiore di Sanita', Rome, Italy, 3Environmental and Health department, Istituto Superiore di Sanita', Rome, Italy

Oxidative stress is implicated in the pathogenesis of cancer, neurodegeneration and aging. hMTH1 is a hydrolase able to protect cells by oxidative damage. Overexpression of hMTH1 in transgenic mice (hMTH1‐Tg) confers significant protection against neurodegeneration and motor impairment. In this study, we use the hMTH1‐Tg mouse model and we found that oxidative damage is able to affect brain metabolism and adipose organ composition and extension.  Moreover, we investigated the protective role of hMTH1-tg against an environmental oxidative stimulus like the assumption of a diet at high content of fat.

2945
Effects of Housing, Age, Strain, and Signal to Noise Ratio on Magnetic Resonance Spectroscopy in the Rat Brain
Wendy Oakden1 and Greg J Stanisz1,2,3

1Physical Sciences, Sunnybrook Research Institute, Toronto, ON, Canada, 2Medical Biophysics, University of Toronto, Toronto, ON, Canada, 3Neurosurgery and Paediatric Neurosurgery, Medical University of Lublin, Lublin, Poland

Changes in metabolite levels as a result of treatment can be quite small. This study investigated the variability of MRS detectable metabolites so that the effects relating to the treatment would not be confounded by other experimental factors.  A four-way ANOVA was used to separate the effects of differences in housing conditions (single housing, pairs, or enriched environment) as well as age (5-15 weeks), strain (Long Evans vs Sprague Dawley), and SNR. Significant changes in MRS were observed due to age, strain, and SNR, but any changes due to housing conditions were small in comparison.

2946
Evaluating Apparent T2* values of Metabolites in Healthy Adults and Youths using TIDEL-COSY
Zohaib Iqbal1, Rajakumar Nagarajan2, Manoj Sarma3, Andres Saucedo3, and Michael Albert Thomas3

1Radiation Oncology, UT Southwestern Medical Center, Dallas, TX, United States, 2Human Magnetic Resonance Center, UMass, Amherst, MA, United States, 3UCLA, Los Angeles, CA, United States

For decades, one-dimensional (1D) spectroscopy has aided in the diagnosis of several pathologies. However, 1D approaches suffer from severe spectral overlap, possibly limiting their application. Two-dimensional (2D) spectroscopy allows for greater spectral separation, and many studies have successfully quantified metabolites with the localized correlated spectroscopy (L-COSY). Here, we combine the L-COSY technique with a T2* weighted deconvolution (TIDE) approach and develop the TIDEL-COSY method. We show the capability of the novel TIDEL-COSY method and compare the apparent T2* values between healthy youths and adults for a variety of metabolites.

2947
Detection of beta-hydroxybutyrate in human brain after oral administration of a ketone ester
Jan Willem van der Veen1, Corinde Wiers2, and Jun Shen3

1Magnetic Resonance Spectroscopy Core, NIMH, NIH, Bethesda, MD, United States, 2NIH, NIAAA, Bethesda, MD, United States, 3Magnetic Resonance Spectroscopy Core, NIH, NIMH, Bethesda, MD, United States

Beta-Hydroxybutyrate (BHB) is a marker of metabolic ketosis in brain. To study ketogenic treatment spectral editing was developed to invert the signals in the 3.2-4.6 ppm spectral region for detecting BHB and co-edited signals. Using this spectral editing technique we found markedly elevated BHB signal in the human brain shortly after oral administration of 1,3-butanediol monoester of beta-hydroxybutyrate as compared to the control scan without consumption of the ketone ester.


MRS Cancer Applications

Proton MRS and Other Nuclei MR
 Spectroscopy

2948
Downfield Magnetic Resonance Spectroscopy in a mouse model of Brain Glioma
Sónia Isabel Gonçalves1, Rui V. Simões1, and Noam Shemesh1

1Champalimaud Research, Champalimaud Centre for the Unknown, Lisbon, Portugal

MRS allows non-invasive in-vivo exploration of tissue metabolism. However, about half of the proton spectrum (downfield of water) has been nearly ignored over the decades of MRS application due to water suppression. We show that ISIS-based Relaxation Enhanced MRS (iRE-MRS) which uses frequency selective excitation and ISIS localization offers short echo times and enhances exchange-broadened resonances. For the first time, we measure in-vivo downfield spectra in mouse glioma tumors (and controls) and show remarkable spectral signatures for the tumor downfield.

2949
MR Spectroscopic Differences of Low and High Grade TERTp-only Gliomas
Banu Sacli-Bilmez1, Ayhan Gursan2, Ayca Ersen Danyeli3, Cengiz Yakicier4, M.Necmettin Pamir5,6, Koray Ozduman5,6, Alp Dincer5,7, and Esin Ozturk-Isik1

1Institute of Biomedical Engineering, Bogazici University, Istanbul, Turkey, 2Department of Radiology, University Medical Center Utrecht, Utrecht, Netherlands, 3Department of Medical Pathology, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey, 4Department of Molecular Biology and Genetics, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey, 5Center for Neuroradiological Applications and Reseach, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey, 6Department of Neurosurgery, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey, 7Department of Radiology, Acıbadem Mehmet Ali Aydinlar University, Istanbul, Turkey

Gliomas that only have the telomerase reverse transcriptase promoter mutation (TERTp-only)  are known to have the worst overall survival. The aim of this study was to analyze magnetic resonance spectroscopic (MRS) differences of different grades of TERTp-only gliomas, and classify these groups using machine learning. The results indicated that the ratios of glycerophosphocholine (GPC), glutathione (GSH), total choline (tCho), and glutamine and glutamate complex (Glx) to total creatine increased along with the tumor grade, and machine learning models classified low- and high-grade TERTp-only gliomas with a high accuracy.

2950
GSH and GABA decreases in IDH1 mutated low-grade gliomas detected by HERMES spectral editing at 3 T in vivo
Tao Gong1, Richard Edden2,3, and Guangbin Wang1

1Shandong Medical Imaging Research Institute, Jinan, China, 2Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States, 3F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States

IDH1 mutation could result in better prognosis compared with wild-type, but the mechanisms remain largely unknown. GABA and GSH are low-concentration metabolites, could not be detected using conventional MRS, but playing an important role in energy production of glioma. HERMES can be thought of as two MEGA-PRESS experiments with the benefit of saving half the acquisition time to simultaneously detect GABA and GSH. The results demonstrated that HERMES is a reliable tool for the simultaneous detection of GABA and GSH signals, and both of them decreased significantly in IDH1 mutated low-grade gliomas.

2951
High-grade gliomas: Metabolic and structural assessment using high resolution 3D-MRSI at 7T
Gilbert Hangel1,2, Cornelius Cadrien1,2, Philipp Lazen1, Alexandra Lipka1, Philipp Moser1, Eva Hečková1, Lukas Hingerl1, Stanislav Motyka1, Stephan Gruber1, Bernhard Strasser3, Georg Widhalm2, Barbara Kiesel2, Mario Mischkulnig2, Julia Furtner4, Thomas Rötzer5, Karl Rössler2, Siegfried Trattnig1,6, and Wolfgang Bogner1

1High Field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria, 2Department of Neurosurgery, Medical University of Vienna, Vienna, Austria, 3Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States, 4Division of Neuroradiology and Musculoskeletal Radiology, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria, 5Clinical Institute of Neurology, Medical University of Vienna, Vienna, Austria, 6Christian Doppler Laboratory for Clinical Molecular MR Imaging, Vienna, Austria

We applied high resolution 3D-MRSI covering the whole brain at 7T to 16 high-grade glioma measurements and evaluated our findings in regards of quantifiable metabolites and their structure in the glioma compared to histology and clinical imaging. Our findings include 14 apparently quantifiable metabolites that resolve glioma structure. Especially the pattern of Glycine to myo-Inositol could be indicative of glioma type and proliferation beyond morphological visibility, making 3D-MRSI an interesting lead for preoperative biomarkers with spatial resolution. Other less-researched metabolites such as Serine and Cysteine could lead to new investigations of glioma metabolism.

2952
Identification of Potential Biomarkers for Human Esophageal Cancer: NMR-based metabolomics of paired tissue-serum samples
Yan Lin1, Wei Ye1, Jiayun Zhao1, Ouyang Ting1, and Wan Tang1

1Radiology Department, Second Affiliated Hospital of Shantou University Medical College, Shantou City, China

This was a parallel investigation of esophageal tumor tissues and adjacent normal mucosal tissues alongside patient-matched serum samples by nuclear magnetic resonance (NMR)-based metabolomics, to investigate how serum metabolic phenotypes were linked to the changes in the biochemical landscape of esophageal tumors. These associations provide evidence of distinct metabolic signatures and pathway disturbances between tumor tissues and serum of esophageal cancer patients, and changes in serum metabolic signature could reflect reprogramming of the aforementioned metabolic pathways in EC tissues.  

2953
Metabolic Differences in Blood Plasma of Type 2 Diabetic and Non-diabetic Prostate Cancer Patients using NMR Spectroscopy
Virendra Kumar1, Pradeep Kumar1, Rajeev Kumar2, Sanjay Sharma3, Sanjay Thulkar4, Siddhartha Dattagupta5, S Senthil Kumaran1, Rama Jayasundar1, and N R Jagannathan6

1Department of NMR, All India Institute of Medical Sciences, New Delhi, India, 2Department of Urology, All India Institute of Medical Sciences, New Delhi, India, 3Department of Radio-diagnosis, RPC, All India Institute of Medical Sciences, New Delhi, India, 4Department of Radio-diagnosis, IRCH, All India Institute of Medical Sciences, New Delhi, India, 5Department of Pathology, All India Institute of Medical Sciences, New Delhi, India, 6Present address: Department of Radiology, Chettinad Academy of Research and Education, Kelambakkam, Tamil Nadu, India

The present study evaluates the metabolic profile of blood plasma for distinguishing prostate cancer (PCa) patients with type 2 diabetes mellitus (T2DM), PCa and healthy controls using 1H-NMR spectroscopy. Our data showed significant lower concentration of glycine, glycerophosphocholine, choline and higher concentration of glucose in PCa patients with T2DM as compared to PCa patients and healthy control. Results provided an insight into the alterations in the metabolic pathways in T2DM-PCa and indicated that NMR spectroscopy may help in determining metabolic changes associated with PCa patients with T2DM and may help in diagnosis.

2954
Lactate detection in breast cancer using optimised multiple quantum coherence MR spectroscopy and effective phased-array signal combination
Vasiliki Mallikourti1, Sai Man Cheung1, Yazan Masannat2, Tanja Gagliardi 3,4, Steven Heys1,2, and Jiabao He1

1Institute of Medical Sciences, School of Medicine, University of Aberdeen, Aberdeen, United Kingdom, 2Breast Unit, Aberdeen Royal Infirmary, Aberdeen, United Kingdom, 3Department of Clinical Radiology, Aberdeen Royal Infirmary, Aberdeen, United Kingdom, 4Department of Radiology, Royal Marsden Hospital, London, United Kingdom

Lactate, as a central metabolite in aerobic glycolysis, is associated with cancer aggressiveness and disease progression. The non-invasive detection of lactate in breast cancer requires the minimal contamination signal from high amplitude lipid signal and maximal amplitude lactate signal, demanding the optimisation of coherent pathway encoding gradients and sequence timing in multiple quantum coherence (MQC) MRS. Furthermore, phased-array coils allows additional signal gain through appropriate combination algorithms. Adaptively optimised combination (AOC) coupled with the optimal MQC gradient at 50 ms mT m-1 provided more than 40% improvement of lactate SNR with complete lipid suppression.

2955
Metabolic Characterization of Pre-Surgical Lower Grade Glioma Using Spectroscopic Imaging Optimized for 2-HG Detection
Marisa Lafontaine1, Adam Autry1, Llewellyn Jalbert1, Elizabeth Phillips1, Susan Chang2, and Yan Li1

1Radiology and Biomedical Imaging, UCSF, San Francisco, CA, United States, 2Neurological Surgery, UCSF, San Francisco, CA, United States

2-HG optimized MR spectroscopic imaging showed 2HG was detected in 37 out of 40 IDH1+ patients. Although it was not significantly different between IDH+ and IDH- gliomas, significant correlation was found with progression free survival in newly-diagnosed grade II and grade III gliomas.

2956
Investigation of lung cancer early detection with serum MRS biomarkers
Leo Ling Cheng1, Tjada A. Schult1,2, Mara J. Lauer1,3, Lindsey A. Vandergrift1, Mari A. Mino-Kenudson4, and David C. Christiani5,6

1Pathology, Massachusetts General Hospital, Charlestown, MA, United States, 2Charite Medical University, Berlin, Germany, 3Julius-Maximilians University, Wuerzburg, Germany, 4Pathology, Massachusetts General Hospital, Boston, MA, United States, 5Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, United States, 6Department of Medicine, Massachusetts General Hospital, Boston, MA, United States

To improve the survival rate of non-small cell lung cancer (LuCa) patients, an economically efficient screening method without radiation hazard is preferred. Based on our previously reported potential serum biomarkers for predicting survival and differentiating LuCa stages and types, we investigated the potential for these biomarkers to be used for early detection screening using LuCa serum samples from patients prior to their diagnoses and compared with those measured at the time of diagnosis. If developed, our findings could be used as a minimally-invasive early diagnosis scheme. 

2957
A metabolomics approach for phenotyping IDH mutant gliomas using 1 and 2D NMR spectroscopy
Thomas Leather Leather1, Marie Phalen2, Khaja Sayed3, Nitika Rathi3, Michael Jenkinson4, Kumar Das4, and Harish Leather Poptani1

1University of Liverpool, Liverpool, United Kingdom, 2NMR Centre, University of Liverpool, Liverpool, United Kingdom, 3Neuropathology, Walton Centre NHS Foundation Trust, Liverpool, United Kingdom, 4Walton Centre NHS Foundation Trust, Liverpool, United Kingdom

The world health organisation has recognised mutations in the IDH1/2 gene as integral in diagnosis and prognostication of gliomas. The mutation facilitates production of the oncometabolite 2-hydroxygluarate (2-HG). The direct mechanisms behind the production and accumulation of 2-HG are well known, however we are yet to understand its effect on prognosis. Although the focus of in vivo studies has been on detection of the  2-HG peak,  it is often impeded by spectral overcrowding. Here we used an NMR metabolomics approach to assess metabolome-wide alterations in the presence of the mutation to seek additionally detectable changes in metabolites in these tumours.

2958
Detection of 2-Hydroxyglutarate using JPRESS Magnetic Resonance Spectroscopy
Yan Zhang1 and Jun Shen1

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

A J-resolved PRESS (JPRESS) technique is proposed for detecting 2-hydroxyglutarate (2HG) in IDH mutant glioma patients at 3T. Spin density simulations and phantom experiments show that the spectral overlap between 2HG and glutamate at ~2.3 ppm is substantially reduced using the one-dimensional cross-sections at J = 0 and J = 7.5 Hz. These two cross-sections can be combined to quantify the 2HG concentration.

2959
Metabolic Biomarkers of TERT expression in glioblastoma
Vinay Ayyappan1, Georgios Batsios2, Nick Stevers3, Abigail R Molloy2, Aliya A Lakhani2, Joseph F Costello3, Pavithra Viswanath2, and Sabrina M Ronen2

1John Hopkins University, Baltimore, MD, United States, 2Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, United States, 3Neurological Surgery, University of California San Francisco, San Francisco, CA, United States

Expression of telomerase reverse transcriptase (TERT) is essential for tumor proliferation, including in primary glioblastomas. Inhibiting TERT expression is also a therapeutic strategy for glioblastomas. The goal of this study was to identify non-invasive magnetic resonance spectroscopy (MRS)-detectable metabolic biomarkers of TERT expression in glioblastoma cells. Our studies indicate that TERT expression is linked to redox, as indicated by higher 1H MRS-detectable reduced glutathione, and higher 13C MRS-detectable flux of glucose via the pentose phosphate pathway in TERT-expressing GBM cells. Hyperpolarized [U-13C, U-2H]glucose can monitor TERT expression in GBM cells, and may serve to noninvasively probe TERT expression in glioblastomas.

2960
Metabolic profiles of blood plasma in prostate cancer patients having different dietary patterns
Pradeep Kumar1, Rajeev Kumar 2, Sanjay Sharma3, Sanjay Thulkar4, S. Datta Gupta5, S. senthil Kumaran1, Rama Jayasundar1, N. R. Jagannathan6, and Virendra Kumar1

1Department of NMR, All India Institute of Medical Sciences, New Delhi, India, Ansari nagar, India, 2Department of Urology, All India Institute of Medical Sciences, New Delhi, India, Ansari nagar, India, 3Department of Radio-diagnosis, RPC, All India Institute of Medical Sciences, New Delhi, India, Ansari nagar, India, 4Department of Radio-diagnosis, IRCH, All India Institute of Medical Sciences, New Delhi, India, Ansari nagar, India, 5Department of Pathology, All India Institute of Medical Sciences, New Delhi, India, Ansari nagar, India, 6Present address: Department of Radiology, Chettinad Academy of Research and Education, Kelambakkam, Tamil Nadu, India

In the present study we reported the effect of dietary lifestyle on metabolic profile of blood plasma in prostate cancer (PCa) patients using NMR spectroscopy the long term effects of dietary patterns our metabolic profiles and PCa have been reported in literatures. A significantly higher concentration of choline, glutamate, creatine, succinate, 1-methylhistidine and methionine were observed in non-vegetarians patients compared to vegetarians. Our results suggested that the metabolic pathway alterations seen in amino acids, phospholipids and energy may be related to changes due diet to and PCa progression.


31P MRS & MRI

Proton MRS and Other Nuclei MR
 Spectroscopy

2961
31P MRSI of the human brain: do we need 7T to detect two Pi pools, UDPG signals and determine the NAD+/NADH ratio?
Arend Heerschap1, Tom H Peeters2, Andor Veltien2, and Tom W.J, Scheenen2

1Radiology, Radboud University Nijmegen Medical centre, Nijmegen, Netherlands, 2Radboud University Nijmegen Medical centre, Nijmegen, Netherlands

All resonances in human brain 31P MR spectra detectable at 7T and higher can also be detected at 3T provided that 1H decoupling, 1H-31P NOE and a 31P receive-array are used. This includes a alkaline peak for extracellular Pi and peaks assigned to UDPG. A NAD+/NADH redox state similar to that reported at 7T was observed. A comparison of measured T1 values with those reported at different field strengths and NOEs measured at 3 and 7T indicates that CSA is not dominant in 31P relaxation and hence there is no sensitivity benefit from shorter T1s at higher fields.    



2962
Quantification of 31P Human Brain spectra at 9.4T using ISIS and SPECIAL-semiLASER
Johanna Dorst1, Loreen Ruhm1, Nikolai Avdievich1, Wolfgang Bogner2, and Anke Henning1,3

1High-Field MR Center, Max Planck Institute for Biological Cybernetics, Tübingen, Germany, 2High-Field MR Center, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria, 3Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, TX, United States

For phosphorus single voxel MR spectroscopy, ISIS is often the method of choice, but it requires an 8 steps encoding scheme and post-acquisition signal combination which makes it prone to motion. Therefore, a SPECIAL-semiLASER sequence for 31P MRS was implemented in this study, which only needs two encoding steps for 3D localization. Spectra from the human brain acquired at 9.4T with both sequences are compared in terms of absolute SNR and SNR efficiency. Absolute SNR as well as SNR efficiency is lower for SPECIAL-semiLASER, but calculated concentrations are comparable.

2963
31P Transversal Relaxation Times in the Human Brain at 9.4T
Johanna Dorst1, Tamas Borbath1, Loreen Ruhm1, Nikolai Avdievich1, and Anke Henning1,2

1High-Field MR Center, Max Planck Institute for Biological Cybernetics, Tübingen, Germany, 2Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, TX, United States

31P transversal relaxation times in the human brain at 9.4T are reported. These values are useful to optimize measurement protocols, and to perform absolute quantification. Measurements were performed using a STEAM sequence. To account for J-evolution of homonuclear spin-spin coupled metabolites, basis sets were modeled in VeSPA and spectra were fitted in LCModel. The measured T2 relaxation times are between 93ms and 116ms for phosphomonoesters and –diesters and PCr, and between 25ms and 45ms for Piintra, ATP and tNAD.

2964
Differential modulation of the cerebral energy consumption by two different tDCS settings as measured by 31P MR spectroscopy
Chang-Hoon Choi1, Elene Iordanishvili2, Lea-Sophie Stollberg2, Harshal Patel2, N. Jon Shah1,3,4,5, and Ferdinand Binkofski1,2,4

1INM-4, Forschungszentrum Juelich, Juelich, Germany, 2Department of Neurology, RWTH Aachen University Hospital, Aachen, Germany, 3INM-11, Forschungszentrum Juelich, Juelich, Germany, 4JARA-BRAIN-Translational Medicine, Aachen, Germany, 5Department of Neurology, RWTH Aachen University, Aachen, Germany

Abnormalities in energy regulation are thought to be linked to neurodegenerative and neuropsychiatric disorders. Here, we modulated the brain activity in M1 using sham/anodal tDCS with two different settings, and examined the effect on high-energy metabolites using in vivo 31P-MRS. PCr/Pi and ATP/Pi values showed a decreasing trend following the stimulation compared to the sham measurements and a statistically significant difference was shown between Pre-stimulation and Post-stimulations. However, differences in both PCr/Pi and ATP/Pi were not statistically significant when either a 10- or 20-minute stimulation protocol was applied, but longer stimulation showed a prolonged decrease in both PCr/Pi and ATP/Pi.  

2965
Volumetric mapping of the intracellular magnesium ion concentration in human calf muscles using 31P MRSI at 7 Tesla
Vanessa L. Franke1, Mark E. Ladd1, Peter Bachert1, and Andreas Korzowski1

1Division of Medical Physics in Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany

Intracellular free magnesium ion concentration [Mg2+free] is an important parameter in the regulation of the energy metabolism and can be assessed non-invasively by the use of 31P MRSI. The purpose of this study is to show that volumetric mapping of [Mg2+free] in the human calf muscle is possible at B0=7T with a voxel size of 1 ml. The [Mg2+free] maps of healthy volunteers showed local differences, presumably resulting from different muscle fiber compositions. Two different approaches employed for the calculation of [Mg2+free] yielded comparable maps but different absolute values, indicating the need for further investigation.

2966
Accelerating volumetric 31P MRSI of the human calf muscle at 7 Tesla: can low-rank denoising filters replace the need for signal averaging?
Andreas Korzowski1, Johannes Breitling1, Vanessa L. Franke1, Mark E. Ladd1, and Peter Bachert1

1Medical Physics in Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany

Volumetric 31P MRSI in the human calf muscle at 7T in principle enables acquisitions with high spatial resolution, but may require signal averaging to improve signal-to-noise ratios of low-concentrated metabolites. To minimize the acquisition duration of volumetric 31P MRSI, in this study we demonstrate that the acquisition of signal averages can be reliably substituted by application of low-rank denoising filters without the introduction of a quantification bias. This allows acquisition of 31P MRSI data with 1 ml voxels in measurement durations of only 14 minutes that have the same quality as if acquired in 56 minutes with signal averaging.

2967
Under-sampled spiral 31P-MRSI for dynamic exercise applications at 3T
Jabrane Karkouri1,2,3, Magalie Viallon1, Arthur Coste1, Josef Pfeuffer4, Thomas Troalen2, Sylvain Grange1, Remy Prost1, Fabien Millioz1, Pierre Croisille1, and Helene Ratiney1

1Université de Lyon, INSA-Lyon, Université Claude Bernard Lyon 1, UJM-Saint Etienne, CNRS, Inserm, CREATIS UMR 5220, U1206, Lyon, France, Lyon, France, 2SIemens Healthcare SAS, Saint-Denis, France, 3Wolfson Brain Imaging Center, University of Cambridge, Cambridge, United Kingdom, 4SIemens Healthcare SAS, Erlangen, Germany

In this abstract, a novel approach based on spiral MRSI and under-sampling of the temporal dimension is applied in the case of dynamic phosphorus at 3T. The goal was to assess mitochondrial capacity of different individual muscles within the calf at once.

2968
Feasibility of 31P MR Imaging at 7T
Tijl van der Velden1, Mark Gosselink1, Giel Mens1, Hans Hoogduin1, Jeanine Prompers1, Dennis Klomp1, and Martijn Froeling1

1Center of Image Sciences, UMC Utrecht, Utrecht, Netherlands

Typical 31P CSI acquisitions have long scan times with a course resolution. Recent technical developments have incorporated a transmit body coil and receiver array for 31P in 7T systems. This opens up the possibility to acquire 31P data similar to conventional 1H imaging. In this study, we investigated the feasibility of 31P gradient echo MRI to measure the 31P distribution in human muscle.

2969
Perfusion system for studying dynamic metabolomics in neonatal rat brain slices exposed to oxygen deprivation using 1H and 31P NMR
Alicja Molska1, Deborah Katherine Hill1, Trygve Andreassen1, and Marius Widerøe1

1Department of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), Trondheim, Norway

We designed an NMR-compatible bioreactor that allows real-time metabolic measurements of viable rat brain slices under normal conditions and under conditions mimicking hypoxic-ischemic (HI) brain injury. Special emphasis was put on providing physiological temperature in the system, a significant factor in the HI model. 1H NMR spectra were acquired to assess changes in brain metabolites. Peaks of lactic acid, NAA, glutamate, aspartate, and creatine were detected. By acquiring a time series of proton spectra, we observed significantly increased lactate levels over time when switching from normoxia to hypoxia while other metabolites remained stable over the whole experiment. 

2970
A Perfusate Comparison for Ex-Vivo Lung Preservation: Using 31P MRS to Assess Cold Perfadex and Modified Krebs–Henseleit Buffer
Jonathan Snow1, Mehrdad Pourfathi1, Sarmad Siddiqui1, Ian Duncan1, Harrilla Profka1, Federico Sertic1,2, Stephen J Kadlecek1, Gabriel Unger1, Hooman Hamedani1,3, Yi Xin1,3, Luis Loza1, Faraz Amzajerdian 1,3, Tahmina Achekzai1, Kai Ruppert1, Ryan Baron1, Yiwen Qian1,3, Michael Rosalino1, Maurizio Cereda1,4, Shampa Chatterjee5, and Rahim R. Rizi1

1Radiology, University of Pennsylvania, Philadelphia, PA, United States, 2Surgery, University of Pennsylvania, Philadelphia, PA, United States, 3Bioengineering, University of Pennsylvania, Philadelphia, PA, United States, 4Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, PA, United States, 5Physiology, University of Pennsylvania, Philadelphia, PA, United States

Ex-vivo lung perfusion (EVLP) is a procedure used in clinical care to support lung viability during transplantation. Here, we used magnetic resonance spectroscopy (MRS) to monitor and compare the energy status of ex-vivo rat lungs flushed and stored in cold Perfadex or perfused with a modified warm Krebs-Henseleit buffer. The results demonstrate decreasing energy status over the course of the 3hr experiment under both conditions, with a slightly lower rate of decline in lung viability using cold Perfadex.

2971
Neurodegenerative changes in the brain of Alzheimer’s mice investigated by high-field 1H-31P MRS and segmentation on high-resolution MRI
Chi-Hyeon Yoo1,2, Hyeon-Man Baek2, and Bo-Young Choe1

1The Catholic University of Korea, Seoul, Republic of Korea, 2Gacheon University, Incheon, Republic of Korea

The aim of this study was to investigate morphological and metabolic changes in the brain of model mice with AD by using combined 1H-31P MRS and 3D T2 MRI in an integrated way. To investigate the AD-related metabolic changes, mean concentrations and /PCr relative ratios were compared between the groups for all major metabolites. In addition, a volumetric analysis was conducted on the volume of hippocampus, entorhinal cortex, and PFC between the groups. The AD-related changes in brain can be investigated by high-field and short-TE 1H MRS and high-resolution T2-weighted MRI in conjugate with the altas-based automatic brain segmentation.

2972
Probing Creatine Phosphorylation in Human Brain by Combining Phosphorus and Proton MRS
Shizhe Li1, Jan Willem van der Veen1, JoEllyn Stolinski1, Christopher Johnson1, Maria Ferraris-Araneta1, Milalynn Victorino1, and Jun Shen1

1National Institutes of Health, Bethesda, MD, United States

Cerebral creatine is affected by many CNS disorders. Combining phosphorus and proton MRS to evaluate both phosphocreatine and creatine may provide important insight into brain energetics associated with abnormal creatine levels as the creatine kinase reaction is strongly coupled to energy metabolism in the CNS. Here we show that the PCr to total phosphate ratio is highly immune to T1 saturation effect. By combining phosphorus and proton MRS of healthy subjects we demonstrate that it is feasible to characterize creatine phosphorylation with high immunity to T1 saturation.

2973
Bloch-Siegert flip angle calibration for phosphorus at the human brain at 9.4 T using ISIS localization
Loreen Ruhm1, Johanna Dorst1, Nikolai Avdievich1, and Anke Henning1,2

1Max Planck Institute for Biological Cybernetics, Tuebingen, Germany, 2Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, TX, United States

Correct calibration of the transmit field B1+ is crucial to achieve optimal SNR. However, fast and robust B1+ calibration is difficult for X-nuclei due to the low signal sensitivity. In this work, we proposed a fast B1+ calibration method based on the Bloch-Siegert shift and single voxel ISIS localization. With the proposed sequence, the B1+ calibration can be done in less than 5 min for the human brain at B0 = 9.4 T.

2974
Fast 31P-MRSI of the brain at 3T using concentric ring (CONCEPT) MRSI
William T Clarke1, Lukas Hingerl2, Wolfgang Bogner2, Christopher T Rodgers3,4, and Ladislav Valkovic4,5

1Wellcome Centre for Integrative Neuroimaging, NDCN, University of Oxford, Oxford, United Kingdom, 2High-field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria, 3Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom, 4Oxford Centre for Clinical Magnetic Resonance Research, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom, 5Department of Imaging Methods, Institute of Measurement Science, Slovak Academy of Sciences, Bratislava, Slovakia

A density-weighted concentric ring trajectory MRSI sequence is created for 31P-MRSI of the human brain at 3T. The sequence is assessed in three subjects at five different acquisition times (7:28 – 1:07 minutes) and compared against resolution and time-matched 3D cartesian CSI sequences. The proposed CONCEPT MRSI sequences robustly measure 3D localised PCr/ATP ratios of the human brain 1.5 times faster than the minimum possible with CSI at a matched repetition time. This opens the possibility of fast dynamic measurements of PCr/ATP in whole human cerebrum at 3T.


X-Nuclei MRI & MRS, 23Na, 39K & 2H

Proton MRS and Other Nuclei MR
 Spectroscopy

2975
Therapeutic Efficacy of Stem Cell Donors for Stroke as Determined by 23Na MRI and 1H MRS at 21.1 T
Shannon Helsper1,2, Xuegang Yuan1,2, F. Andrew Bagdasarian1,2, and Samuel Colles Grant1,2

1National High Magnetic Field Laboratory, Florida State University, Tallahassee, FL, United States, 2Chemical & Biomedical Engineering, FAMU-FSU College of Engineering, Tallahassee, FL, United States

This study evaluates the therapeutic efficacy of human mesenchymal stem cells (hMSC) from different donors applied to an ischemic rat model. Biochemical markers of tissue recovery were measured longitudinally over 21 d using sodium chemical shift imaging, relaxation enhanced MR spectroscopy, and T2-weighted proton imaging at 21.1 T. Ultra-high field provided increased sensitivity, enabling insight into ionic and metabolic regulation while demonstrating differential recovery based on donor characteristics evident only after extended culture. With trophic and immunomodulation effects, hMSC hold promise for cell-based stroke therapy, but donor variance must be evaluated for translation. MR metrics classify donor quality and effectiveness.

2976
Comparison Between Single Channel Dual Loop 23Na Coil and 6-Channel Flexible Wraparound 23Na Coil for Renal Sodium Imaging
Benjamin L Prestwich1, Matthew Clemence2, and Susan T Francis1

1University of Nottingham, Nottingham, United Kingdom, 2Philips Healthcare, Guildford, United Kingdom

Sodium (23Na) MRI has the potential to provide insight to many diseases however 23Na MRI requires nonstandard hardware. This work compares two different designs of RF coil; a single channel pair of transmit-receive (Tx/Rx) loops and a 1Tx-6Rx flexible wraparound coil. Firstly, a 3D gradient-recalled-echo (GRE) sequence was optimised for each coil, then the signal-to-noise ratio (SNR) and field of view (FOV) was compared in both a phantom and in-vivo in a healthy control. SNR was 7±3 and 12±4 for the loops coil and the 6-channel coil respectively.      

2977
Corrections of cardiac 23Na-MRI measurements in mice with an in-house build surface coil at 7T
Martin Christa1, Ibrahim A. Elabyad2, Wolfgang Rudolf Bauer1, and Maxim Terekhov2

1Comprehensive Heart Failure Center (CHFC), Department of Internal Medicine I, University Hospital Wuerzburg, Wuerzburg, Germany, 2Comprehensive Heart Failure Center (CHFC), Chair of Cellular and Molecular Imaging, University Hospital Wuerzburg, Wuerzburg, Germany

With higher field strength and, thus, better SNR available, 23Na-MRI is becoming increasingly popular in (pre-) clinical studies. Improving accuracy and repeatability will help to translate 23Na-MRI into routine. Therefore, we investigated the effect of respiratory and cardiac gating, as well as the influence of B1-field correction on cardiac total sodium quantification with a 2D radial UTE sequence in mice using a surface coil at 7T. We found that ungated and uncorrected measurements overestimate cardiac sodium concentration. Combined respiratory and cardiac gating and B1-field correction significantly decreased the measured cardiac tissue sodium concentration (-40.6%).

2978
Sodium TQ signal cancelation due to B0 inhomogeneities despite the use of a refocusing pulse
Dennis Kleimaier1 and Lothar R. Schad1

1Computer Assisted Clinical Medicine, Heidelberg University, Mannheim, Germany

The sodium TQ signal is sensitive to B0 inhomogeneities leading to TQ signal cancelation. In this study, we evaluated three different shim routines to assess the robustness to B0 inhomogeneities and the reproducibility of the sodium TQ signal. Using an optimized shim routine, the TQ signal dependence on potassium concentration was investigated. Severe B0 inhomogeneities caused a reduction in the TQ signal, despite using a refocusing pulse, without affecting the transversal relaxation times. To achieve reproducible TQ measurements, the FWHM of the sodium SQ signal must be specified. Addition of different amounts KCl caused a reduction in the TQ signal.

2979
Intracellular sodium changes in cancer cells using a microcavity array-based bioreactor and sodium triple-quantum signal
Dennis Kleimaier1, Victor Schepkin2, Cordula Nies3, Eric Gottwald3, and Lothar R. Schad1

1Computer Assisted Clinical Medicine, Heidelberg University, Mannheim, Germany, 2National High Magnetic Field Laboratory, Florida State University, Tallahassee, FL, United States, 3Institute of Functional Interfaces, Karlsruhe Institut of Technology, Karlsruhe, Germany

This study demonstrates the possibility of a microcavity array-based bioreactor to investigate intracellular sodium changes using sodium TQ signal. The response of HepG2 cells during 60min Na+/K+-ATPase inhibition by 1mM ouabain or K+-free medium was monitored. An improved TQTPPI sequence with almost four times TQ SNR increase allowed achieving cell sensitivity of 14*106. During cell experiments, the TQ signal increased to 128.9±3.9% and 165.0±7.4% for 1mM ouabain and K+-free medium, respectively. After reperfusion, the TQ signal recovered to 129.5±4.5%. This bioreactor design with improved TQ signal detection provides the capability to investigate a variety of cells using sodium TQ signal.

2980
Configuration Space Imaging of 23Na at 3T
Jessica Schäper1,2, Claudia Weidensteiner1,2, Philipp Madörin2, and Oliver Bieri1,2

1Department of Biomedical Engineering, University of Basel, Basel, Switzerland, 2Department of Radiology, University Hospital Basel, Basel, Switzerland

Configuration space is explored for sodium MRI with bSSFP in phantoms and for the brain of a healthy volunteer. To this end, a set of eight phase-cycled bSSFP scans are recorded and from the lowest order configuration modes, quantitative T1, T2 and sodium concentration maps are heuristically derived using the framework valid for spin-1/2 particles.

2981
Reduced brain sodium and elevated cerebral blood flow in women with lipedema
Kalen J. Petersen1, Maria Garza1, Paula Donahue2, Kevin Harkins3, Manus Donahue1,4,5, and Rachelle Crescenzi1

1Radiology, Vanderbilt University Medical Center, Nashville, TN, United States, 2Physical Medicine and Rehabilitation, Vanderbilt University Medical Center, Nashville, TN, United States, 3Biomedical Engineering, Vanderbilt University, Nashville, TN, United States, 4Neurology, Vanderbilt University Medical Center, Nashville, TN, United States, 5Psychiatry, Vanderbilt University Medical Cener, Nashville, TN, United States

Patients with the adipose disorder lipedema exhibit elevated sodium in the extremities, potentially due to blood or lymphatic vasculopathy. Despite evidence of psychological symptoms, these parameters have not been examined in the brain. We utilized multi-nuclear imaging (23Na-MRI) and arterial spin labeling to test whether dysregulation of brain sodium and perfusion is present in women with (n=15) versus without (n=18) lipedema. We observed lower brain sodium (61.3±6.9 vs. 67.9±5.8mmol/L; p=0.03) and higher cerebral blood flow (43.3±7.0 vs. 37.9±6.3ml blood/100mg tissue/min; p=0.03) in lipedema compared to control participants. Results suggest that brain sodium and hemodynamic dysregulation may exist in lipedema patients.

2982
Quantitative Human Cardiac 39K MRI at 7T: What is feasible?
Johanna Lott1,2, Tanja Platt1, Sebastian C Niesporek1, Daniel Wenz3, Peter Bachert1,2, Mark E Ladd1,2,4, Thoralf Niendorf5,6, and Armin M Nagel1,7,8

1Medical Physics in Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, 2Faculty of Physics and Astronomy, University of Heidelberg, Heidelberg, Germany, 3Center for Biomedical Imaging - Animal Imaging and Technology (CIBM-AIT), École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland, 4Faculty of Medicine, University of Heidelberg, Heidelberg, Germany, 5Berlin Ultrahigh Field Facility (B.U.F.F.), Max Delbrueck Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany, 6MRI. TOOLS GmbH, Berlin, Germany, 7Institute of Radiology, University Hospital Erlangen, Erlangen, Germany, 8Institute of Medical Physics, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany

Monitoring the viability of myocardial tissue is of prognostic value after an ischemic event1-3. Ultrahigh fields (B0≥7T) facilitates cardiac 39K MRI. However, short relaxation times, low signal-to-noise ratio, and low spatial resolution render the quantitative determination of the myocardial tissue potassium concentration (mTPC) challenging. We analyze the feasibility of quantitative cardiac 39K MRI at 7T with simulations. For realistic noise conditions the mTPC can be determined with a deviation of 14% from the ground truth by applying a partial volume correction. Quantitative cardiac 39K MRI would further benefit e.g. from higher magnetic field strengths (B0>7T) or iterative reconstruction techniques.    

2983
Non-Invasive Dynamic Assessment of Heart Energy Metabolisms using in vivo Deuterium MRS Imaging and Close Chest Model
Tao Wang1,2, Xiao-Hong Zhu1, Byeong-Yeul Lee1, Wei Zhu1,2, Hannes M Wiesner1, Yi Zhang1, and Wei Chen1

1Center for Magnetic Resonance Research, Radiology, University of Minnesota, Minneapolis, MN, United States, 2Medical Physics, Radiation Oncology, University of Minnesota, Minneapolis, MN, United States

Continuation from our previous open-chest rat heart project to exploit the in-vivo deuterium (2H) MRS (DMRS) or imaging (DMRSI) methods for dynamic measurement of the myocardial energy metabolism in rat heart at 16.4 T, we further tested its sensitivity and feasibility in response to cardiac glucose metabolism as compared with acetate using a non-invasive method on close-chest rats by using a 1H/2H dual-frequency surface coil. This work demonstrates that both fatty acids and glucose are the main sources of fuel for cardiac activities with a preference for fatty acids. 

2984
Rapid Dynamic Deuterium MR Spectroscopic Imaging Using Deep-SPICE
Yudu Li1,2, Yibo Zhao1,2, Rong Guo1,2, Fanyang Yu2,3, Xiao-Hong Zhu4, Wei Chen4, and Zhi-Pei Liang1,2

1Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, United States, 2Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, United States, 3Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL, United States, 4Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota, Minneapolis, MN, United States

Dynamic deuterium MR spectroscopic imaging (2H-MRSI) is emerging as a powerful tool for measurement of metabolic changes using deuterated substrates. In this work, we propose a novel method to reconstruct the often extremely noisy dynamic 2H-MRSI data, incorporating both physics-based subspace spectral model and deep learning-based data priors via an information-theoretical framework. The proposed method has been validated using both simulated and experimental data, showing a significant improvement over the conventional reconstruction and processing method.

2985
Development of a 4-channel body coil for Deuterium Metabolic Imaging of the liver at 7T
Ayhan Gursan1, Arjan D. Hendriks1, Dimitri Welting1, Pim A. de Jong1, Dennis W. Klomp1, and Jeanine J. Prompers1

1Department of Radiology, University Medical Center Utrecht, Utrecht, Netherlands

Deuterium Metabolic Imaging (DMI) is a new technique, which could potentially be used to study liver metabolism in vivo. The aim of this study was to develop a 4-channel 2H transmit/receive array for DMI of the liver at 7T, combined with 4 1H dipole elements for conventional anatomical MRI. Natural abundance DMI water and lipid maps measured on a phantom showed good correspondence with 1H Dixon water and lipid images. The multi-channel setup allowed us to pick up the natural abundance 2H water signal throughout the whole liver in a 3D DMI acquisition with a nominal resolution of 20x20x20 mm3.

2986
NMR and MRS studies of proteins delivered into cultured cells, towards MR analyses of proteins under physiological conditions
Airi Higashi1, Mitsuhiro Takeda1, Sosuke Yoshinaga1, and Hiroaki Terasawa1

1Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan

We seek to study proteins under physiological conditions, by delivering 13C-labeled proteins into mouse brains and observing them by 13C MRS. We previously observed 13C-labeled a-Synuclein (α-Syn) embedded in an agarose gel by 13C MRS. To examine the feasibility of MRS detection under more in vivo-like conditions, we delivered α-Syn into cultured mammalian cells and observed the cells by NMR, revealing that the delivered α-Syn underwent intracellular interactions and N-terminal acetylation. For MRS experiments with the cells, we constructed a system that perfuses the cells, to prevent cell death over a longer time period.

2987
Towards structure and metabolism of glycogen C1-C6 by 13C MRS at 7T using broadband 1H decoupling and low-power NOE by means of bi-level WALTZ cycles
Eulalia Serés Roig1 and Rolf Gruetter1,2,3

1Laboratory of Functional and Metabolic Imaging (LIFMET) - Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland, 2Centre d'Imagerie BioMédicale - Animal and Imaging Technology (CIBM-AIT) - Ecole Polytechnique de Lausanne (EPFL), Lausanne, Switzerland, 3Department of Radiology, Universities of Lausanne (UNIL) and Geneva (UNIGE), Lausanne, Switzerland

Glycogen metabolism is essential for glucose homeostasis in humans and may be disrupted in a variety of diseases. Largely neglected due to its low concentration, yet brain glycogen plays an active role in brain energy metabolism, such as during hypo-glycemia. Carbon-13 Magnetic Resonance Spectroscopy (13C MRS) allows the non-invasive detection of glycogen in vivo, while is typically done via the C1 carbon signal. In this study, we explore the potential of 13C MRS at 7T using uniform 13C excitation and bi-level broadband 1H-decoupling towards simultaneous detection of glycogen C1-C6 in vivo in human muscle, as a step towards brain studies.


X-Nuclei MRI & MRS & 31P, 13C, 19F, 17O & 2H

Proton MRS and Other Nuclei MR
 Spectroscopy

2988
Comparison of low-rank denoising methods for accelerating the acquisition of 31P-MRSI
William T Clarke1 and Mark Chiew1

1Wellcome Centre for Integrative Neuroimaging, NDCN, University of Oxford, Oxford, United Kingdom

Two new low-rank denoising methods are compared to an existing low-rank denoising method in 31P-MRSI data of human skeletal muscle and brain. All three methods increase the SNR of the noisy data above that of high SNR data acquired in 4-times the duration. Denoising algorithm parameters are examined using a grid search. Optimal algorithm choice is dataset dependent and incorrect selection of parameters can bias spectra.

2989
Development of a 2H birdcage volume coil for homogeneous deuterium metabolic imaging of the human brain at 7T
Ayhan Gursan1, Arjan D. Hendriks1, Stefan R. van Genderen1, Dimitri Welting1, Dennis W. Klomp1, and Jeanine J. Prompers1

1Department of Radiology, University Medical Center Utrecht, Utrecht, Netherlands

Deuterium metabolic imaging (DMI) is a new emerging technique, which can measure the metabolism in the brain non-invasively. In this work, a shielded 2H birdcage volume coil for the head was developed and compared with a 2H surface coil setup. In contrast to the surface coil, the 2H birdcage coil enabled high SNR DMI measurements over the entire brain. The homogeneous B1+ field of the birdcage coil allowed for T1 mapping of deuterated water in the brain. Overall, the developed 2H birdcage coil shows high potential for non-invasive metabolic imaging of the brain.

2990
Application of a BIlinear Rotation Decoupling (BIRD) filter for indirect 13C measurements using J-difference editing in the liver
Pandichelvam Veeraiah1, Kim Brouwers1, Joachim E Wildberger1, Vera B Schrauwen-Hinderling1,2, and Lucas Lindeboom1,2

1Departments of Radiology and Nuclear Medicine, Maastricht University Medical Center, Maastricht, Netherlands, 2Nutrition and Movement Sciences, Maastricht University Medical Center, Maastricht, Netherlands

Indirect 13C measurements provide a large signal gain when compared to direct 13C-MRS. The regular J-difference editing (JDE) techniques are quite challenging to apply in the liver, as respiratory motion will result in imperfect subtraction of the huge overlapping 1H-[12C] signal, which hampers accurate quantification of the 1H-[13C] signals. Here, we demonstrated that the application of a BIlinear Rotation Decoupling filter prior to a regular JDE (STEAM-ACED) to pre-suppress the hindering 1H-[12C] signal, leads to a robust detection of the 1H-[13C] signal irrespective of respiratory motion. We showed an application of measuring 1H-[13C] lipid signals from the liver in vivo.

2991
A Large FOV 3.0T 16Ch Highly Flexible Array for Body 13C Metabolic Imaging Studies.
Dashen Chu1, Bahareh Behzadnezhad2,3, Scott Lindsay1, Victor Taracila2, Galen Reed4, Albert Chen2, Robert Stormont1, and Fraser Robb2

1GE Healthcare, Inc, Waukesha, WI, United States, 2GE Healthcare, Inc, Aurora, OH, United States, 3University of Wisconsin (Madison), Madison, WI, United States, 4GE Healthcare, Inc, Dallas, TX, United States

Over the last decade, there has been a move toward ultra-flexible conformal coil technology. Similar to flexible H1 coils, there is an interest in developing multi-nuclear coil arrays that are more conformal to human anatomy with highly decoupled elements. In this work, we demonstrate a highly flexible 13C coil array with highly decoupled elements, showing significant improvements in SNR

2992
Detection of Human Muscle Glycogen by Natural Abundance Carbon-13 MRS at 7 T with Short Duration Proton Decoupling
Li An1, Shizhe Li1, Kalpana Manthiram2, Jyoti Singh Tomar1, Hirotsugu Oda2, Carlos R Ferreira2, and Jun Shen1

1National Institute of Mental Health, National Institutes of Health, Bethesda, MD, United States, 2National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United States

In this work, a continuous wave (CW) proton decoupling with a short duration of 15 ms was used to detect natural abundance 13C glycogen C1 signals in the human calf at 7 T. This short duration CW proton decoupling dramatically reduced RF power deposition, which allowed the TR to be shortened to 310 ms and additional NOE pulses to be used to ensure optimal SNR performance. The reconstructed glycogen spectra and the peak area ratio between decoupled and non-decoupled glycogen C1 resonances demonstrated that adequate proton decoupling was achieved.

2993
tcaCALC: MATLAB Software for Quantitative Analysis of 13C Metabolic Isotopic Tracer Experiments
Jeffry R. Alger1,2,3, Gaurav Sharma1, A. Dean Sherry1,4, and Craig R. Malloy1,5

1Advanced Imaging Research Center, University of Texas, Southwestern Medical Center, Dallas, TX, United States, 2Neurology, University of California, Los Angeles, Los Angeles, CA, United States, 3NeuroSpectroScopics LLC, Sherman Oaks, CA, United States, 4Department of Chemistry, Universiy of Texas at Dallas, Richardson, TX, United States, 5Department of Internal Medicine, University of Texas-Southwestern Medical Center, Dallas, TX, United States

tcaCALC has been developed as a MATLAB tool that facilitates the quantitative analysis of metabolic tracing experiments that use 13C enriched tracers. The most recent version of tcaCALC facilitates analysis by incorporating spectral fitting of J-coupled 13C NMR multiplets and modeling complex metabolic situations in which specific metabolic fluxes may be active or inactive. The MATLAB source code and a compiled version are available for sharing to interested research teams.

2994
Life monitoring of cellular metabolism and mitochondrial respiration in 3D cell culture system using NMR Spectroscopy
Damian Hertig1,2,3, Sally Maddah1,2, Roman Memedovski1,2, Andrea Debora Felser2, Aitor Moreno4, Matteo Pennestri4, Jean-Marc Nuoffer2,5, and Peter Vermathen1

1Departments of Clinical Research and Radiology, University of Bern, Bern, Switzerland, 2Institute of Clinical Chemistry, University Hospital Bern, Bern, Switzerland, 3Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland, 4Bruker Biospin AG, Fällanden, Switzerland, 5Department of Pediatric Endocrinology, University Hospital Bern, Bern, Switzerland

In this study we show the feasibility of simultaneous measure of oxygen consumption and metabolic data in living 3D cell culture in standard 5mm NMR tube. Using high cell density of 20 million fibroblasts we demonstrate high viability and reproducibility of the measurements over 12 hours. We describe the effect of the flow rate on the metabolic activity. Importantly, we show the required sensitivity to detect substrate degradation rates of major mitochondrial fuel pathways and ability to measure rapid O2 and lactate changes as surrogate marker of oxidative phosphorylation and anaerobic glycolysis.

2995
In vivo assessment of fluoxetine human brain concentrations using fluorine MR Spectroscopy at 3T
Chu-Yu Lee1, Phil Lee1,2, Jean C. Dinh3, Andrew T Fox1, Richard M. Dubinsky4, William M. Brooks1,4, J. Steven Leeder3,5, and In-Young Choi1,4,6

1Hoglund Brain Imaging Center, University of Kansas Medical Center, Kansas City, KS, United States, 2Department of Radiology, University of Kansas Medical Center, Kansas City, KS, United States, 3Division of Clinical Pharmacology, Toxicology & Therapeutic Innovation, Department of Pediatrics, Children’s Mercy, Kansas City, MO, United States, 4Department of Neurology, University of Kansas Medical Center, Kansas City, KS, United States, 5School of Medicine, University of Missouri-Kansas City, Kansas City, MO, United States, 6Department of Molecular & Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, United States

Fluoxetine is one of the most commonly used medications to treat mental disorders, however, 30-50% of patients fail to respond to the treatment. Thus, direct noninvasive measurements of Fluoxetine concentration in the brain may give insights into individual variations in their clinical responses. This study aimed to quantify fluoxetine concentrations in the human brain using 19F MRS at 3T. 19F MRS measurements were performed on 20 subjects with stable doses of fluoxetine over a month. The fluoxetine concentration was 30±28.2 μM and significantly correlated with their daily doses; r=0.78, p<0.0001, which promises the utility of 19F MRS for personalized medicine.  

2996
19F MRS Detection of Tau Aggregates Using Lansoprazole in an Ex Vivo Rat Model of Alzheimer’s Disease
Sarah K Yeo1, Yurii Shepelytskyi2, Vira Grynko2, Francis T Hane3,4, Tao Li3, and Mitchell S Albert3,4,5

1Biology, Lakehead University, Thunder Bay, ON, Canada, 2Chemistry and Materials Science, Lakehead University, Thunder Bay, ON, Canada, 3Thunder Bay Regional Health Research Institute, Thunder Bay, ON, Canada, 4Chemistry, Lakehead University, Thunder Bay, ON, Canada, 5Northern Ontario School of Medicine, Thunder Bay, ON, Canada

Neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau protein are pathological characteristics of Alzheimer’s Disease (AD). Thus, the use of biosensors that bind to NFTs are beneficial for in vivo detection of tauopathy. This study evaluates the use of Lansoprazole (LSZ) as an indicator of NFTs in AD brains. 19F MRS of AD and control brains with LSZ was acquired using a 3.0T clinical MRI scanner. We demonstrate that the 19F signal from LSZ interacts with NFTs in a rat model of AD. This shows potential in using LSZ to distinguish between AD and healthy brains with a clinical 3.0T scanner.

2997
Determination of the oxygen partial pressure in hind limb ischemia by 19F MRI
Tuba Gueden-Silber1, Nicolas Stumpe1, Rebekka Schnekkmann2, Maria Grandoch2, and Ulrich Floegel1

1Molecular Cardiology, University Clinic Duesseldorf, Düsseldorf, Germany, 2Pharmacology and Clinical Pharmacology, University Clinic Duesseldorf, Düsseldorf, Germany

Tissue hypoxia induces a variety of detrimental processes. Therefore, the determination of oxygen partial pressure can be helpful to assess the current oxygen supply of an organ. 19F MRI showed to be useful for the quantification of tissue pO2 by exploiting the paramagnetic effect of O2 on the longitudinal relaxation rate R1 of perfluorocarbon nanoemulsions. Thus, allowing the calculation of pO2 through experimental R1 data. In the present study, we applied this approach for monitoring the gradual recovery of tissue oxygenation in a murine model of hind limb ischemia. We observed tissue oxygenation recovery within 2 weeks post-occlusion.

2998
Dynamic Oxygen-17 MRI with Adaptive Reconstruction using Golden-Means-Based 3D Radial Sampling
Yuning Gu1, Huiyun Gao2, Kihwan Kim1, Ciro Ramos-Estebanez3, Yunmei Wang2, and Xin Yu1,4,5

1Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, United States, 2Case Cardiovascular Research Institute, Case Western Reserve University, Cleveland, OH, United States, 3Department of Neurology, Case Western Reserve University, Cleveland, OH, United States, 4Department of Radiology, Case Western Reserve University, Cleveland, OH, United States, 5Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH, United States

A golden-means-based 3D radial sampling and k-space weighted image reconstruction method was developed for dynamic tracking of intravenously injected 17O-water in mouse brain.  The method enabled image reconstruction with adaptive temporal resolution of 3 to 15 s to capture the regional differences in 17O-water uptake and washout kinetics in post-stroke mice, with an isotropic voxel size of 1.77 µL on a 9.4T scanner.

2999
A new approach involving combination of 1H MRS and [2,2,2′-2H3]acetate administration to assess cerebral neurotransmission in vivo
Puneet Bagga1, Laurie J Rich1, Neil E Wilson1, Mark Elliott1, Mitch D Schnall1, John A Detre2, Mohammad Haris3,4, and Ravinder Reddy1

1Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States, 2Department of Neurology, University of Pennsylvania, Philadelphia, PA, United States, 3Sidra Medicine, Doha, Qatar, 4LARC, Qatar University, Doha, Qatar

1H MR spectroscopy is currently the only technique that allows the non-invasive detection and quantification of a wide range of neurochemicals. In this study, we performed 1H MRS in conjunction with the administration of [2,2,2′-2H3]acetate to measure turnover kinetics of glutamate, glutamine and GABA in rat brain. As 2H is invisible on 1H MRS, the turnover of metabolites will lead to a corresponding drop in their 1H MR signal visualized by subtraction of the post-[2,2,2′-2H3]acetate administration from the Pre-administration 1H MR spectra. The fractional enrichment data can be fitted to evaluate the rates of cerebral glutamatergic and GABAergic neurotransmitter cycling.