Claudiu Schirda¹, Tiejun Zhao², Hoby Hetherington¹, Victor Yushmanov¹, and Jullie Pan^1
1Radiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States, ²Siemens Medical Solutions, Pittsburgh, PA, United States

Rosette Spectroscopic Imaging (RSI) has been shown to provide similar or superior encoding speed and sensitivity to echo-planar (EPSI) and spiral spectroscopic imaging (SSI), while using much lower peak gradient and slew rates. Fully encoded k-t space 3D acquisitions with 0.4ml voxel size in 7.2mins (20x20x12, spectral width SW=1923Hz --6.47ppm, Gmax=7.1mT/m and Smax=86mT/m/ms), and 2D acquisitions as short as 36s (1cc) to a 9.5min dual-echo TE=17/34ms J-refocused with 0.16ml voxel (4mm in-plane, 48x48, SW=2778Hz --9.35ppm, Gmax=5.1mT/m and Smax=18mT/m/ms) were collected at 7Tesla in phantoms, controls and patients with epilepsy and tumors.

Neil Wilson¹, Hari Hariharan¹, M. Albert Thomas², and Ravinder Reddy^1
1Radiology, University of Pennsylvania, Philadelphia, PA, United States, ²Radiology, University of California, Los Angeles, CA, United States

We use concentric circular echo planar k-space readout to spectroscopic sampling at high field. At high field, higher bandwidths are required which are difficult to achieve using echo planar techniques due to gradient limitations. Often temporal interleaving is employed to mitigate this. Circular k-space sampling is unique among the echo planar trajectories in that different rings can be sampled at different rates, requiring only partial temporal interleaving.

Mohammed Azeem Sheikh¹, Fan Lam², Chao Ma², Bryan Clifford³, and Zhi-Pei Liang^3
1Physics, University of Illinois at Urbana-Champaign, Urbana, IL, United States, ²Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, IL, United States, ³Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, United States

In 1H-MRSI, data is typically acquired with spin echo sequences with relatively long acquisition delay, often motivated by the need for water, lipid, and baseline suppression. Here, we present a new method to obtain high-resolution 1H-MRSI data with an FID-based acquisition that has a very short acquisition delay, enabled by a new scheme for nuisance signal removal. The new acquisition method enables short repetition time and rapid acquisition of spectroscopic data. Experimental results demonstrate in vivo 3D 1H-MRSI of the brain with isotropic 3 mm resolution in 15 minutes.

Gilbert Hangel¹, Bernhard Strasser¹, Michal Považan¹, Martin Gajdošík¹, Stephan Gruber¹, Marek Chmelík¹, Siegfried Trattnig^1,2, and Wolfgang Bogner^1
1MRCE, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria, ²Christian Doppler Laboratory for Clinical Molecular MR Imaging, Vienna, Austria

Reliable lipid suppression is essential for robust quantification of parallel imaging accelerated high- resolution MRSI. This work compared the performance of non-selective lipid suppression using double inversion recovery (DIR) with the application of L1- and L2-regularisation during data processing for single-slice MRSI with a 64×64 matrix and a GRAPPA-acceleration of nine in five volunteers. While DIR featured the best lipid suppression, it increased the measurement time and reduced metabolite SNR. L1 and L2 did not have these downsides, but twice as much lipid signal remained, with L1 increasing the data pre-processing time before spectral quantification by a factor of six.

Karim Snoussi^1,2, Joseph S. Gillen^1,2, Michael Schär^1,2, Vincent O. Boer³, Richard A.E. Edden^1,2, and Peter B. Barker^1,2
1Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ²Kennedy Krieger Institute, Baltimore, MD, United States,³Department of Radiology, University Medical Center Utrecht, Utrecht, Netherlands

Suppression of extra cranial lipid signals is a significant challenge for MR spectroscopy at high field. This study describes the use of a crusher coil in a volumetric proton echo-planar spectroscopic imaging (EPSI) sequence for 7T. It is shown in vivo that the application of the crusher coil improves the spin-echo 7T EPSI sequence and allows to record high quality spectroscopic imaging data with extended 3D coverage and low RF power deposition.

Fan Lam¹, Chao Ma¹, Qiegen Liu¹, Bryan Clifford^1,2, and Zhi-Pei Liang^1,2
1Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, IL, United States, ²Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, United States

We present a novel strategy to achieve high spatiotemporal resolution for 1H-MRSI of the brain. The proposed acquisition scheme is characterized by: (a) the use of EPSI-based rapid spatiospectral encoding with an extended k-space coverage; (b) sparse sampling of (k,t)-space; (c) time-interleaved k-space undersampling, and (d) acquisition and use of navigator signals for determining subspace structures. This special acquisition is enabled by a subspace-based data processing and reconstruction method that can effectively remove nuisance signals and obtain high-quality reconstructions from sparse and noisy data. Experimental data have been acquired to demonstrate the potential of the proposed method in producing time-resolved spatiospectral distributions.

Petra Hnilicová¹, Michal Považan², Bernhard Strasser², Ovidiu C Andronesi³, Dušan Dobrota¹, Siegfried Trattnig², and Wolfgang Bogner^2
1Department of Medical Biochemistry, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia, ²Department of Biomedical Imaging and Image-guided Therapy, MR Center of Excellence, Medical University of Vienna, Vienna, Austria, ³Department of Radiology, Martinos Center for Biomedical Imaging, Harvard Medical School, Boston, MA, United States

In vivo assessment of neurotransmitter levels can improve the understanding of several pathological processes. For non-invasive GABA⁺ and Glx mapping in vivo within one scan, we applied a spiral-encoded GABA-edited MEGA-LASER 3D-MRSI sequence with real time corrections, achieving the ~3 cc nominal resolution in ~20 minutes. Via test-retest assessment in 14 healthy volunteers (7 men/7 women) we confirmed the measurement reproducibility and inter- and intra-subject variability of GABA⁺ and Glx ratios and thus validated that our method may be used in (pre)clinical studies of neurotransmitters alterations in the brain at 3T.  

Eva Heckova¹, Stephan Gruber¹, Bernhard Strasser¹, Michal Povazan¹, Gilbert Hangel¹, Siegfried Trattnig^1,2, and Wolfgang Bogner^1
1High Field MR Center, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria, ²Christian Doppler Laboratory for Clinical Molecular MR Imaging, Vienna, Austria

Magnetic resonance spectroscopic imaging (MRSI) allows to measure different metabolites in the brain. SNR and spectral resolution increases at higher magnetic fields. We compared FID-MRSI with ultra short acquisition delay (1.5 ms) and a very high spatial resolution in the same group of healthy subjects at 3T and 7T. We found 1.87-fold increased SNR and decreased CRLBs at 7T in comparison with 3T. The higher spectral resolution at 7T allows to distinguish between NAA and NAAG and reliable detect other metabolites like Glx or Tau. Accelerating the acquisition techniques leads to lower SNR, however not to substantially decreased quantification precision.

Grzegorz L. Chadzynski^1,2, Jonas Bause², G. Shajan², Rolf Pohmann², Klaus Scheffler^1,2, and Philipp Ehses^1,2
1Biomedical Magnetic Resonance, Eberhard-Karls University of Tübingen, Tübingen, Germany, ²High-field Magnetic Resonance Center, Max Planck Institute for Biological Cybernetics, Tübingen, Germany

The aim was to design a MRSI-FID sequence for ultra-high field applications with high acquisition speed and sampling efficiency. The sequence allows acquisition of a 32×32 voxel matrix within approximately 2 min, down to 30 sec using parallel imaging. We have examined the suitability of this approach for assessing biochemical changes in the human visual cortex during a visual stimulus. Obtained results were in accordance with other functional MRS studies and indicate that the developed sequence is suitable for rapid monitoring of stimulus evoked changes in human brain biochemistry at a very high spatial resolution.

Byeong-Yeul Lee¹, Xiao-Hong Zhu¹, and Wei Chen^1
1Center for Magnetic Resonance Research, Radiology, University of Minnesota, Minneapolis, MN, United States

Spatial averaging of multiple high-resolution CSI (hrCSI) voxels is commonly employed to gain SNR and improve quantification of metabolites. Using in vivo 17-oxygen 3D CSI, we compared SNR between spatial averaging of multiple hrCSI voxels and a single voxel acquired with low-resolution CSI (lrCSI) with matched sample volume and position. SNR from voxel averaging was much lower than that of lrCSI caused mainly by the increased noise level by spectral summation. This study clearly demonstrates that the acquisition of high-resolution data with spatial averaging faces a large trade-off of SNR. Therefore, it should be taken consideration carefully for the choice of an appropriate voxel size of high-resolution CSI for in vivo study of neurological or metabolic diseases. 

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

A novel nuisance removal method is proposed for ¹H-MRSI. The method uses spectral bases generated for water and subcutaneous lipids using quantum simulation, and can perform nuisance signal removal directly from (k,t)-space data. Consequently, the proposed method is able to handle sparsely sampled MRSI data, which provides a desirable flexibility for designing accelerated ¹H-MRSI data acquisition schemes.  Experimental results demonstrate that the proposed method is capable of removing nuisance signals from 1H-MRSI data acquired from the brain without water and lipid suppression pulses.

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

Obstructive sleep apnea syndrome (OSAS), which have many comorbidities including hypertension and other cardiovascular diseases, leads to autonomic, cognitive, and affective abnormalities. The thalamus, and midbrain are key structures that serve such functions through critical relays in nuclei but the status of this region is unclear OSAS. Here, we examined neurochemical changes in the thalamus and midbrain of OSAS patients to better understand the nature of tissue changes using compressed sensing based 4D echo-planar J-resolved spectroscopic imaging (EP-JRESI) and prior knowledge fitting (ProFit) algorithm for metabolite quantification. We observed significantly increased mI/Cr in midbrain and bilateral thalamus. Significantly increased Glx/Cr, Glu/Cr was found in right thalamus and midbrain, and decreased tNAA/Cr, NAA/Cr in left thalamus and midbrain respectively. Thalamus showed significantly reduced tCho/Cr bilaterally. We also found significantly decreased GPC/Cr, increased Gln/Cr, Asc/Cr in right thalamus and increased Asc/Cr in midbrain. The findings will help to explain structural brain changes in OSAS. Most of these metabolites can be manipulated through pharmacological approaches, and could serve as a biomarker of any possible intervention.

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

The five dimensional echo planar spectroscopic imaging (5D EP-JRESI) sequence uses an echo planar readout, non-uniform sampling (NUS), and compressed sensing reconstruction to obtain two dimensional spectra from three spatial dimensions. However, the effects of NUS and reconstruction on quantitation results and fit quality parameters, such as the Cramer Rao Lower Bound (CRLB), are unknown. This study uses the new Prior knowledge Fitting (ProFit) algorithm to fit the 5D EP-JRESI results acquired using retrospective as well as prospective NUS. Comparison to the full data demonstrates that the 5D EP-JRESI method can sample 8-times faster while retaining accurate metabolite ratios and CRLB values.      

Jetse S. van Gorp¹, Paul W. de Bruin², and Peter R. Seevinck^1
1Image Sciences Institute, University Medical Center Utrecht, Utrecht, Netherlands, ²Radiology, Leiden University Medical Center, Leiden, Netherlands

Sodium relaxation behavior has been related to structural and cellular integrity, which is of interest for early disease detection. However, the short T₂* values, bi-exponential relaxation behavior and low sensitivity makes accurate signal characterization challenging. In this work a 3D-UTE-FID-SI sequence was developed to measure the sodium decay curve with a 32kHz temporal resolution and sub-ms TE to characterize the bi-exponential signal decay characteristics of sodium in vitro and in vivo.

Ashley D Harris^1,2,3,4,5, Nicolaas AJ Puts^1,5, Laura Rowland⁶, S. Andrea Wijtenburg⁶, Mark Mikkelsen⁷, Peter B Barker^1,5, C. John Evans⁷, and Richard AE Edden^1,5
1FM Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, ²CAIR Program, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada,³Radiology, University of Calgary, Calgary, AB, Canada, ⁴Hotchkiss Brain Institute and Alberta Children's Hospital Research Institute, Calgary, AB, Canada, ⁵Russell H Morgan Department of Radiology and Radiological Science, The Johns Hopkins University, Baltimore, MD, United States, ⁶Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, United States,⁷CUBRIC, School of Psychology, Cardiff University, Cardiff, United Kingdom

Differences in GABA+ MEGA PRESS acquisitions between vendors are quantified in terms of the editing efficiency of GABA and the fractional co-editing of macromolecules. Accounting for these two parameters results in moderate agreement among the different vendors considered.

Florian Schubert¹, Ralf Mekle¹, Simone Kühn², Jürgen Gallinat³, and Bernd Ittermann^1
1Physikalisch-Technische Bundesanstalt (PTB), Braunschweig and Berlin, Germany, ²MPI for Human Development, Berlin, Germany, ³Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany

Since disturbed amygdala function is linked to psychiatric conditions insight into its biochemistry, particularly the neurotransmitters, is required. We combined the SPECIAL MRS sequence with FAST(EST)MAP implementation, corrections for frequency drift, relaxation, CSF volume, and a basis set including a measured macromolecule spectrum for quantification of metabolites in the amygdala in 20 volunteers at 3T. Beyond quantification of the three main metabolites plus myo-inositol with excellent precision, for the first time glutamate was determined reliably and separately from glutamine. Using a basis set without macromolecules introduced a systematic overestimation of concentrations. Glutamine and glutathione was quantifiable only in a subset of spectra.

Moyoko Tomiyasu^1,2, Noriko Aida³, Jun Shibasaki⁴, Katsutoshi Murata⁵, Keith Heberlein⁶, Mark A. Brown⁷, Eiji Shimizu², Hiroshi Tsuji¹, and Takayuki Obata^1
1National Institute of Radiological Sciences, Chiba, Japan, ²Chiba University, Chiba, Japan, ³Department of Radiology, Kanagawa Children's Medical Center, Yokohama, Japan, ⁴Kanagawa Children's Medical Center, Yokohama, Japan, ⁵Siemens, Tokyo, Japan, ⁶Biomedical Imaging Technology Center, Burlington, MA, United States, ⁷University of Colorado, Cary, NC, United States

We examined in vivo brain γ-aminobutyric acid (GABA) levels of neonates and compared them with those of children. In this study, 32 normal neonates and 12 normal children (controls) had their brain GABA levels measured using clinical 3T edited-MRS. The neonates exhibited significantly lower GABA+ levels than the children in both the basal ganglia and cerebellum, which is consistent with previous in vitro data. While significantly higher GABA+/Cr levels were detected in the neonatal cerebellum, care should be taken when comparing GABA+/Cr levels between different ages. This is the first report about the in vivo brain GABA levels of neonates.

Rajakumar Nagarajan¹, Raissa Souza¹, Edward Xu¹, Manoj K Sarma¹, S. Sendhil Velan², Cathy C Lee³, Theodore Hahn³, Catherine Carpenter⁴, Vay-Liang Go⁵, and M.Albert Thomas^1
1Radiological Sciences, University of California Los Angeles, Los Angeles, CA, United States, ²Laboratory of Molecular Imaging, Singapore Bioimaging Consortium, Singapore, Singapore, ³Geriatrics, VA Greater Los Angeles Healthcare System, Los Angeles, CA, United States, ⁴UCLA Schools of Nursing, Medicine, and Public Health, Los Angeles, CA, United States, ⁵UCLA Department of Medicine, Los Angeles, CA, United States

Obesity is a serious public health problem associated with high rates of morbidity and mortality. One-dimensional MR spectroscopy suffers from overlapping spectral resonances which can complicate metabolite identification and quantitation. Two-dimensional spectroscopic techniques have been demonstrated in calf muscle to reduce the problem of spectral overlap. In this study, we used the four dimensional (4D) multi-echo echo planar correlated spectroscopic imaging (ME-EPCOSI) technique to quantify the lipids and metabolites in soleus, tibialis anterior and gastrocnemius calf muscles of obese and normal healthy subjects. The 4D ME-EPCOSI acquired data enabled less ambiguous quantitation of metabolites, unsaturated and saturated fatty acids in different calf muscle regions using IMCL ratios and unsaturation indices.

Victor Adalid Lopez¹, André Doering¹, Sreenath Pruthviraj Kyathanahally ¹, Christine S. Bolliger¹, and Roland Kreis^1
1Depts. Radiology and Clinical Research, University Bern, Bern, Switzerland

Diffusion weighted spectroscopy can provide information on the diffusion of metabolites and the microstructure of brain tissue. A method for simultaneous fitting of spectra related by mono-exponential diffusion weighting is introduced, which is similar to simultaneous fitting of a 2DJ or inversion recovery data set. As shown for simulated white matter data, the method improves both, accuracy and precision of ADC estimation for all metabolites. It is also illustrated with diffusion data obtained from human gray matter at 3T.

Zhongxu An¹, Sandeep Ganji¹, Vivek Tiwari¹, and Changho Choi^1
1Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, United States

Reliable detection of GABA is important for research studies in neuro-psychiatric diseases.  In vivo ¹H GABA resonances extensively overlap with the neighboring resonances of glutamate and glutamine. We present an optimized single-shot triple-focusing 1H MRS method which fully resolved GABA 2.29-ppm signal at 3T. 

Chu-Yu Lee¹, In-Young Choi^1,2,3, Peter Adany¹, and Phil Lee^1,3
1Hoglund Brain Imaging Center, University of Kansas Medical Center, Kansas city, KS, United States, ²Department of Neurology, University of Kansas Medical Center, Kansas City, KS, United States, ³Department of Molecular & Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, United States

Frequency drifts during MRS acquisition results in broad and distorted spectral lineshapes, a reduced SNR and quantification errors. The consequence of frequency drifts is particularly significant in spectral-editing sequences, because spectral editing critically relies on narrow-band frequency selective pulses or accurate spectral alignments among scans for subtraction/addition of spectra. Frequency drift can occur due to subject’s movement and/or MR system instability. Even in advanced MR systems with self-shielded gradients, significant frequency drifts occur due to eddy current-induced heating and cooling of passive shim materials, particularly after MR scans with heavy gradient duty cycles. The effects of frequency drifts can be mitigated through prospective and retrospective frequency corrections.  Currently, most spectral-editing methods use post-processing approaches to correct the effects of frequency drifts retrospectively. In this study, we have developed a prospective frequency correction method and implemented it in a semi-LASER based TE-averaged sequence for glutamate detection.

Yafei Wang¹, Yue Zhang¹, Lingyi Xu¹, Yu Sun¹, Lei Xiang², Meiping Ye², Suiren Wan¹, Bing Zhang², and Bin Zhu^2
1The Laboratory for Medical Electronics, School of Biological Sciences and Medical Engineering, Southeast University, Nanjing, China, People's Republic of, ²Department of Radiology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China, People's Republic of

Classification or grading of brain tumor alone would not be enough for clinical use, therefore we designed a comprehensive multi-layer system combining the two functions together. Firstly, we designed it as a three-layer system according to clinic workflow. Then, we extracted new features from multi-modality MRI and patients’ clinical information, which were easily ignored or difficult found by eyes. And then we implemented SVM and Tumor Model to classify tumor type and tumor grade. This study proposed a novel multi-layer system for clinic use by reducing the diagnosis uncertainty.

Muhammad Gulamabbas Saleh¹, A Alhamud¹, Jamie Near², Frances Robertson¹, André J.W. van der Kouwe³, and Ernesta M Meintjes^1
1Human Biology, MRC/UCT Medical Imaging Research Unit, University of Cape Town, Cape Town, South Africa, ²Douglas Mental Health University Institute and Department of Psychiatry, McGill University, Montreal, QC, Canada, ³Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States

Several studies have characterized short and long term reproducibility of Glx and GABA+, but not macromolecule (MM) suppressed GABA. Further, gender-related differences have been observed in GABA+, but these may, in part, be due to inter-individual variations of MM. Motion and magnetic field inhomogeneity can hamper the consistent application of frequency-selective pulses at 1.7ppm necessary for effective GABA editing.  We demonstrate that the shim and motion-navigated MEGA-SPECIAL sequence produces well-edited GABA and Glx spectra. LCModel quantification yields the best reproducibility. Observed gender-related differences in GABA highlight the need for gender-matching in studies investigating differences in GABA concentrations.

Jan Weis¹, Fredrik Rosqvist², Joel Kullberg¹, Ulf Risérius², and Håkan Ahlström^1
1Department of Radiology, Uppsala University, Uppsala, Sweden, ²Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden

Proton MR spectroscopy of healthy human liver was performed at 3 T MR scanner. The purpose of this study was to estimate glycogen (Glycg), choline-containing compounds (CCC), water, and lipid (-CH₂-)_nrelaxation times T₁, T₂, and absolute concentration of Glycg, CCC, and fat. Experiments were performed using multiple breath-hold technique. Spectra were processed by LCModel. T₁ and T₂ values were obtained by mono-exponential fitting spectral intensities versus repetition or echo times. Quantification of liver Glycg, CCC and lipids is important for understanding changes in lipid and glucose metabolism due to metabolic disorders. 

Benjamin C Rowland¹, Fatah Adan¹, Huijun Liao¹, and Alexander P Lin^1
1Centre for Clinical Spectroscopy, Brigham and Women's Hospital, Boston, MA, United States

B0 frequency drift is a well-known phenomenon which can have a significant impact on MR spectroscopy, affecting both peak resolution and metabolite quantification. B0 drift is particularly associated with gradient-heavy EPI sequences like DTI. In a study of 53 subjects receiving DTI and MRS, the mean FWHM more than doubled as a result of frequency drift and metabolite concentrations were often misestimated by LC Model.

Nicole D Fichtner^1,2, Anke Henning^2,3, Niklaus Zoelch², Chris Boesch¹, and Roland Kreis^1
1Depts. Radiology and Clinical Research, University of Bern, Bern, Switzerland, ²Institute for Biomedical Engineering, UZH and ETH Zurich, Zurich, Switzerland, ³Max Planck Institute for Biological Cybernetics, Tuebingen, Germany

Characterization of the full ¹H spectrum may allow for better monitoring of pathologies and metabolism in humans. The downfield part (5-10ppm) is currently less well characterized than upfield; this work aims to benefit from higher field strength in order to quantify T₁ and T₂ in the downfield spectrum in human grey matter at 7T. We fitted downfield spectra to a heuristic model and obtained relaxation times for twelve peaks of interest. The T₁’s are higher than those at 3T downfield; peaks with lower T₁’s may include macromolecules. The T₂’s are mostly shorter than those reported for upfield peaks at 7T.

Ashley D Harris^1,2,3,4, Eric Porges⁵, Adam J Woods^5,6, Damon G Lamb^5,7, Ronald A Cohen⁵, John B Williamson^5,8, Nicolaas AJ Puts^3,4, and Richard AE Edden^3,4
1Radiology, University of Calgary, Calgary, AB, Canada, ²CAIR Program, Hotchkiss Brain Institute and Alberta Children's Hospital Research Institute, Calgary, AB, Canada, ³Russell H Morgan Department of Radiology and Radiological Science, The Johns Hopkins University, Baltimore, MD, United States, ⁴FM Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, ⁵Center for Cognitive Aging and Memory (CAM), McKnight Brain Institute, Department of Aging and Geriatric Research, University of Florida, Gainesville, FL, United States, ⁶Department of Neuroscience, University of Florida, Gainesville, FL, United States, ⁷Brain Rehabilitation and Research Center, Malcom Randall Veterans Affairs Medical Center, Gainesville, FL, United States, ⁸Brain Rehabilitation and Research Center, Brain Rehabilitation and Research Center, Gainesville, FL, United States

There are various strategies for tissue correction for MRS. Here, using data from a healthy aging cohort, we show that the selection of tissue correction method can change the conclusions that are drawn from data.

Nallathamby Devasahayam¹, Randall H. Pursley², Thomas J. Pohida², Shingo Matsumoto³, Keita Saito⁴, Sankaran Subramanian⁵, and Murali C. Krishna^4
1Radiation Biology Branch, National Cancer Institute, Bethesda, MD, United States, ²Center for Information Technology, Bethesda, MD, United States, ³Graduate School of Information Science and Technology, Sapporo, Japan, ⁴National Cancer Institute, Bethesda, MD, United States, ⁵Indian Institute of Technology Madras, Chennai, India

Electron Paramagnetic Resonance (EPR) imaging  is suited well for small animal physiological imaging with its unique capability of generating in vivo quantitative oxygen maps. The main bottleneck in scaling up pulsed EPR imaging to human anatomy is that the required RF power of US federal food and drug administration (FDA), specific absorption rate (SAR) limits. In Frank Sequence we are using power levels on the order of 250 microwatts in a crossed coil resonator with ~35 dB isolation. Using a 256 pulse polyphase Frank Sequence, it was possible to obtain images with good SNR.

Scott Quadrelli^1,2, Carolyn Mountford³, and Saadallah Ramadan^2
1Queensland University of Technology, Brisbane, Australia, ²The University of Newcastle, Newcastle, Australia, ³The Translational Research Institute, Brisbane, Australia

Whilst many studies have detailed the impact of partial volume effects on proton magnetic resonance spectroscopy quantification, there is a paucity of literature explaining how voxel segmentation can be achieved using freely available neuroimaging packages. Here we aim to demonstrate a practical guide to magnetic resonance spectroscopy (MRS) voxel segmentation, partial volume correction and detail how to extract other MR metrics (such as DTI, fMRI) from a MRS voxel. 

Ayano Enomoto¹, Gadisetti V. R. Chandramouli², Alan P Koretsky³, Chunqi Qian⁴, Murali K Cherukuri¹, and Nallathamby Devasahayam^1
1Radiation Biology Branch, National Cancer Institute, Bethesda, MD, United States, ²GenEpria Consulting Inc., Columbia, MD, United States, ³National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States, ⁴Department of Radiology, Michigan State university, East Lansing, MI, United States

Sensitivity enhancement is required to detect the weak signals with Fourier transform Electron Paramagnetic Resonance (FT-EPR).  In the proposed method, a small amount of sample was placed at a distance less than half the diameter of the receiving surface coil. The signal was enhanced by a wirelessly pumped coil. Presently, we used the TCNQ for our studies to study signal enhancement. Here, we achieved 7-fold of improvement in signal intensity in compared with conventional FT-EPR acquisition. We will show the results of in vivo oximetry using oxygen sensing solids LiPc and LiNc in in vivo applications to measure tissue oxygenation.

Homa Javadzadeh^1,2 and Jean Théberge^1,2,3
1Department of Medical Biophysics, University of Western Ontario, London, ON, Canada, ²Imaging Division, Lawson Health Research Institute, London, ON, Canada, ³Diagnostic Imaging Department, St. Joseph's Health Care, London, ON, Canada

D-serine supplements alleviate some of the most debilitating features of schizophrenia believed to be associated with glutamatergic abnormalities. Assessment of endogenous serine is impossible using standard proton Magnetic Resonance Spectroscopy (¹H-MRS). This work employs a novel^?1H-MRS sequence called DANTE-PRESS (D-PRESS) and presents test-retest reliability study for serine levels acquired at 3T in phantoms and initial data in two human subjects. We conclude that reproducibility and precision of serine measurements on a 3.0T scanner is sufficient to assess endogenous levels in vivo and is a valuable tool to examine abnormalities in schizophrenia and monitor supplementation.

Byeong-Yeul Lee¹, Xiao-Hong Zhu¹, Sebastian Rupprecht², Michael T. Lanagan³, Qing X. Yang^2,4, and Wei Chen^1
1Center for Magnetic Resonance Research, Radiology, University of Minnesota, Minneapolis, MN, United States, ²Center for NMR Research, Radiology, The Pennsylvania State College of Medicine, Hershey, PA, United States, ³Engineering Science and Mechanics, The Pennsylvania State College of Engineering, University Park, PA, United States, ⁴Neurosurgery, The Pennsylvania State College of Medicine, Hershey, PA, United States

Compared to ¹H MRS, X-nuclei MRS for human application faces two challenges: higher requirement of RF power (thus, higher SAR) for achieving the same RF pulse flip angle due to a relatively lower gyromagnetic ratio, and still limited SNR even at high/ultrahigh field. In this report, we demonstrate that up to 200% SNR gain was achieved with ultra high dielectric constant (uHDC) materials incorporated into the RF volume coil for ³¹P MRS at 7T. Concomitantly, the RF power optimized for acquiring the spectra was significantly reduced by 200%. Our data demonstrated that incorporating uHDC with RF coil can significantly boost SNR and reduce RF transmission power X-nuclei MRS applications on top of using high field strength magnet that has approached to its technologic limits.

Nicola Bertolino¹, Paul Polak¹, Marilena Preda^1,2, Robert Zivadinov^1,2, and Ferdinand Schweser^1,2
1Buffalo Neuroimaging Analysis Center, Department of Neurology,Jacobs School of Medicine and Biomedical Sciences, The State University of New York at Buffalo, Buffalo, NY, United States, ²MRI Molecular and Translational Research Center, Jacobs School of Medicine and Biomedical Sciences, The State University of New York at Buffalo, Buffalo, NY, United States

In-vivo 1H-MR spectroscopy is a non-invasive technique able to detect metabolites providing important information from investigated tissue. GABA and Glutamate are two metabolites altered in many neurological diseases, although challenging to quantify in vivo because of a number of technical issues: voxel localization, low concentration, short T2, overlapping peaks and spin-spin coupling. In this work we developed an optimized parameter set for an ultra-short TE STEAM.

Kyle W. Sexton¹, Hasan Celik¹, Kenneth W. Fishbein¹, and Richard G. Spencer^1
1National Institute on Aging, National Institutes of Health, Baltimore, MD, United States

Quantification of cartilage matrix components with nuclear magnetic resonance has potential applications to the early diagnosis of osteoarthritis. Ex-vivo cartilage samples are often used to observe the MR parameters of healthy and degraded cartilage. To ensure the accuracy of MR parameters, the storage of the explants is extremely important. DPBS is often used to immerse cartilage tissue specimens during imaging, with the assumption that it prevents dehydration. In this study it was found that storing BAC tissue explants in DPBS can rapidly and significantly increase the observed T2 values. An alternative storage medium to maintain T2 stability is Fluorinert.

Nicolaas AJ Puts^1,2, Kimberly L Chan¹, Ashley D Harris^1,2,3,4, Peter B Barker^1,2, and Richard AE Edden^1,2
1Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, United States, ²F.M. Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, ³Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada, ⁴Radiology, University of Calgary, Calgary, AB, Canada

MM-suppressed GABA measurements use symmetric editing of both MM and GABA signals. Frequency drift, either by gradient induced heating/cooling, or motion, significantly affects the editing efficiency of GABA and MM. To stabilize the center frequency, we interleaved the unsuppressed water acquisition throughout the scan and used it to correct the frequency, in eight healthy participants, and compared this to a condition without frequency correction. Frequency correction improves spectral quality of MM-suppressed GABA editing in vivo.

Albert P Chen¹, Ralph E Hurd², Angus Z Lau³, and Charles H Cunningham^4,5
1GE Healthcare, Toronto, ON, Canada, ²GE Healthcare, Menlo Park, CA, United States, ³Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom, ⁴Physical Sciences, Sunnybrook Health Sciences Centre, Toronto, ON, Canada, ⁵Medical Biophysics, University of Toronto, Toronto, ON, Canada

A method for single volume dynamic hyperpolarized 13C MRS acquisition is proposed.  Using a slice selective pulse-acquire pulse sequence with 2D spiral readout this technique enables 3D localization of the MRS data.  By confining the readout trajectory to each dwell time, the raw data sampled during the trajectory are averaged by the digital filter, thus the output data represent only the center voxel and no k-space data sorting and reconstruction are required.  This sequence can be used practically the same way as a standard pulse-acquire acquisition for HP13C experiments, but the spectrum will be localized to a 3D volume. 

Sarah E. Hoch¹, Ivan I. Kirov², and Assaf Tal^3
1Radiology, Sheba Medical Center, Ramat-Gan, Israel, ²Radiology, New York University Langone Medical Center, New York, NY, United States, ³Chemical Physics, Weizmann Institute of Science, Rehovot, Israel

Metabolite ratios are often used to simplify metabolic quantification. It is often implicitly assumed that they are also statistically favorable when both numerator and denominator metabolites change in opposing manners. Herein, we show that even for such cases, both sample size requirements and statistical significance depend non-trivially on taking the ratio. We conclude that care must be taken when deciding between ratios and absolute quantification during study design. 

Michal Považan^1,2, Lukas Hingerl¹, Bernhard Strasser¹, Gilbert Hangel¹, Eva Heckova¹, Stephan Gruber¹, Siegfried Trattnig^1,2, and Wolfgang Bogner^1
1High Field MR Center, Department of Biomedical Imaging and Image-guided Therapy, Medical University Vienna, Vienna, Austria, ²Christian Doppler Laboratory for Clinical Molecular MR Imaging, Vienna, Austria

MR spectroscopy (MRS) profits from ultra-high field (UHF) with higher SNR and enhanced spectral resolution. However, the higher demand on bandwidth of RF pulses together with power limitations complicate the utilization of localization sequences such as PRESS or STEAM. A semi-LASER sequence appears to be a suitable candidate for UHF MRS if properly optimized. We aimed to implement selective GOIA refocusing pulses and optimize the gradient scheme to yield shortest echo time possible on a volume coil. Our semi-LASER sequence outperformed the conventional sequences in terms of SNR and chemical shift displacement artifact and proved to be applicable at UHF.

Jan Weis¹, Lina Carlblom¹, Lars Johansson¹, Olle Korsgren², and Håkan Ahlström^1
1Department of Radiology, Uppsala University, Uppsala, Sweden, ²Department of Immunology, Genetics and Pathology, Uppslala University, Uppsala, Sweden

A 1.5 T clinical scanner was used for proton MR spectroscopy (¹H-MRS) of human pancreas allografts. The main purpose was to estimate intracellular lipid content in non-adipose pancreatic cells. The secondary aim was to quantify total fat and choline-containing compounds. Spectrum processing was performed in the time domain using MRUI software package. It was demonstrated that ¹H-MRS is an effective method for non-invasive estimation of intracellular lipid content in non-adipose pancreatic cells. This knowledge could be helpful in studies of various aspects of β-cell function (insulin production).      

Michael Dacko¹, Benjamin Knowles¹, Patrick Hucker¹, Maxim Zaitsev¹, and Thomas Lange^1
1Medical Physics, University Medical Center Freiburg, Freiburg, Germany

Diffusion-weighted spectroscopy of the brain is a highly motion-sensitive MR method as a consequence of the large voxel size and low metabolite diffusion coefficients. In this work, we correct for voxel displacement during DWS experiments with prospective motion correction and investigate the signal attenuation due to rotation-induced intra-voxel dephasing.  Phantom experiments with 'synthetic' rotations confirmed the theoretically predicted signal attenuation. High correlation between rotational motion and attenuation of the residual water peak was observed in vivo. Retrospective rejection criteria based on the recorded motion tracking data and on the residual water peak amplitude are compared.

Young Woo Park¹, Dinesh K. Deelchand², James M. Joers², Brian J. Soher³, Peter B. Barker⁴, HyunWook Park¹, Gülin Öz², and Christophe Lenglet^2
1School of Electrical Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Korea, Republic of, ²Department of Radiology, Center for Magnetic Resonance Research, University of Minnesota Medical School, Minneapolis, MN, United States, ³Department of Radiology, Duke University Medical Center, Durham, NC, United States, ⁴Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States

During the typical acquisition of single-voxel Magnetic Resonance Spectroscopy (MRS) the corresponding voxel-of-interest (VOI) must be selected manually, which induces some degree of variability. To address this, several automated VOI positioning methods, using rigid registration and aimed at follow-up scans of the same subject, have been proposed. This approach can be generalized to cross-subject scans, but with additional considerations for the anatomical variability. We hypothesized that non-rigid registration methods will minimize inter-subject variability in the tissue content of the VOI. Here, we present an analysis of registration strategies aimed at a reliable cross-subject automatic VOI positioning for MRS data acquisition.

Richard Anthony Edward Edden^1,2, Ashley D. Harris^1,2,3,4, Nicolaas Puts^1,2, Kimberly L. Chan^1,2,5, Michael Schar¹, and Peter B. Barker^1,2
1Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University, Baltimore, MD, United States, ²F.M. Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, ³Department of Radiology, University of Calgary, Calgary, AB, Canada, ⁴Hotchkiss Brain Institute and Alberta Children's Hospital Research Institute, Calgary, AB, Canada, ⁵Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, MD, United States

J-difference-edited measurements of GABA are usually contaminated up to 50% by macromolecular (MM) signal.  It is possible to suppress this signal using a symmetrical editing motif, which relies upon partially inverting the MM signals to an equal degree in the two halves of the edited experiment.  In the event of B₀  field offset, the symmetry breaks down and either positive or negative MM signal rapidly contaminates the measured GABA signal.  Here, we investigate this issue using simulations and in vivo experiments.

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

Hadamard Encoding and Reconstruction of MEGA-Edited Spectroscopy, HERMES, is a novel method of the simultaneous, separable detection of overlapping metabolite signals. Classic J-difference editing involves the acquisition of two subspectra, with editing pulses applied to the target molecule (ON) or not (OFF).  HERMES edits multiple metabolites simultaneously by acquiring all combinations of OFF/ON for each (i.e. four experiments to edit two metabolites) and uses a Hadamard-like addition-subtraction reconstruction to generate separate edited spectra for each target metabolite.  In this abstract, we describe the method and demonstrate its application to NAA/NAAG editing, using simulations, and phantom and in vivo experiments.

Marissa E. Fisher¹, Brennen J. Dobberthien¹, Anthony G. Tessier^1,2, and Atiyah Yahya^1,2
1Department of Oncology, University of Alberta, Edmonton, AB, Canada, ²Department of Medical Physics, Cross Cancer Institute, Edmonton, AB, Canada

The Cho peak at 3.2 ppm contains significant signal contamination from the taurine (Tau) resonance in rat and mouse brain spectra, even at the high field strength of 9.4 T.  The purpose of this work it to optimise TE₁and TE₂ (echo times) of a Point RESolved Spectroscopy (PRESS) sequence to minimize Tau signal in the Cho spectral region at 9.4 T by exploiting the J-coupling evolution of the Tau protons.  The determined optimal {TE₁, TE₂} combination was found to be {25 ms, 50 ms}.  The efficacy of the timings was verified on rat brain in vivo.   

André Döring¹, Victor Adalid Lopez¹, Vaclav Brandejsky¹, Roland Kreis¹, and Chris Boesch^1
1Depts. Radiology and Clinical Research, University Bern, Bern, Switzerland

A non-water suppressed diffusion-weighting MR spectroscopy sequence based on metabolite-cycling and STEAM is presented and tested in-vitro and in-vivo.  The water peak as an inherent reference facilitates a post processing correction of the signal drop induced in individual acquisitions by cardiac and other motion. The correction leads to improved spectral resolution on one hand, but more importantly also to more accurate fitting of ADC values that are found to be smaller than without correction and most likely closer to the true values - and hence better suited for physiological interpretation.

Harshal Jayeshkumar Patel¹, Sandro Romanzetti^2,3, Antonello Pellicano¹, Kathrin Reetz^2,3, and Ferdinand Binkofski^1,4
1Division of Clinical Cognitive Sciences, Department of Neurology, RWTH Aachen University Hospital, Aachen, Germany, ²Department of Neurology, RWTH Aachen University Hospital, Aachen, Germany, ³Jülich Aachen Research Alliance (JARA) — Translational Brain Medicine, Aachen and Jülich, Germany, ⁴Research Center Jülich GmbH, Institute of Neuroscience and Medicine, Jülich, Germany

Transcranial direct current stimulation (tDCS) modulates cortical excitability. In this study we investigated long term effects of anodal stimulation on inhibitory neurotransmitter concentration using proton magnetic resonance spectroscopy (MRS). Our results indicates that excitatory tDCS cause locally reduction in GABA and it remains in decreased state over a period of 60 minutes presumably due to the decrease of activity of glutamic acid decarboxylase(GAD)67.

Lukas Hingerl¹, Martin Gajdošík¹, Michal Považan¹, Bernhard Strasser¹, Gilbert Hangel¹, Martin Krššák¹, Siegfried Trattnig^1,2, and Wolfgang Bogner^1
1High Field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria, ²Christian Doppler Laboratory for Clinical Molecular MR Imaging, Medical University of Vienna, Vienna, Austria

We present a method for detecting omega-3 fatty acids (FA) at 7 T by 1H-MR spectroscopy (MRS) using a MEGA-sLASER editing sequence with 12 kHz AFP GOIA-WURST(16,4) pulses for localization. sLASER localization offers reduced sensitivity to B₁ inhomogeneities, lowers pulse power requirements compared to PRESS or STEAM and the localization pulses substantially reduce the 4-compartment effect. The spectra of in vivo measurements at the echo times TE=332 ms ,465.4 ms and 1130 ms show the omega-3 signal very well.

Masoumeh Dehghani M.¹, Bernard Lanz¹, Nicolas Kunz², Pascal mieville³, and Rolf Gruetter^1,2,4,5
1Laboratoire d'imagerie fonctionnelle et métabolique(LIFMET), École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland, ²Centre d’Imagerie Biomedicale(CIBM), École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland, ³Institute of Chemical Sciences and Engineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland, ⁴Department of Radiology, University of Lausanne, Lausanne, Switzerland, ⁵Department of Radiology, University of Geneva, Geneva, Switzerland

Metabolic modeling of metabolite ¹³C turnover curves in brain with ¹³C-labeled acetate infused as tracer substrate requires prior knowledge of the transport and uptake kinetics of Ace. The aim of this study was to determine the kinetics of transport and utilization for acetate uptake in the rat brain using specific distribution volume of Ace(V_d) in the rat brain. The dependency of estimated CMR_ace to distribution volume of Ace in the rat brain highlights the importance about a refined determination of V_d for Ace in brain metabolic studies.

Adrianus J. Bakermans¹, Chang Ho Wessel², Paul F.C. Groot¹, Erik S.G. Stroes², and Aart J. Nederveen^1
1Department of Radiology, Academic Medical Center, Amsterdam, Netherlands, ²Department of Vascular Medicine, Academic Medical Center, Amsterdam, Netherlands

Typically, dynamic MR studies of exercising skeletal muscle are limited to measurements of only one parameter. Obtaining multiple parameters simultaneously during a single experiment would provide more insight into (patho-)physiology. Here, we report on interleaved acquisitions of quantitative T₂^* maps for assessments of the BOLD response, and ³¹P-MR spectra for measuring phosphocreatine recovery kinetics during an exercise-recovery protocol in healthy subjects and peripheral artery disease (PAD) patients. We demonstrate that with such interleaved acquisitions, it is feasible to dynamically assess both tissue oxygenation as well as muscle energy metabolism in the human calf muscle during a single exercise session.

Qiu Wenqi¹, Wei Zhiliang¹, Ye Qimiao¹, Chen Youhe², Lin Yulan¹, and Chen Zhong^1
1Department of Electronic Engineering, Xiamen University, Xiamen, China, People's Republic of, ²Department of Mechanical and Electrical Engineering, Xiamen University, Xiamen, China, People's Republic of

High-resolution multi-dimensional nuclear magnetic resonance (NMR) spectroscopy serves as an irreplaceable and versatile tool in various chemical investigations. In this study, a method based on the concept of partial homogeneity is developed to offer two-dimensional (2D) high-resolution NMR spectra under inhomogeneous fields. Oscillating gradients are exerted to encode the high-resolution information, and a field-inhomogeneity correction algorithm based on pattern recognition is designed to recover high-resolution spectra. The proposed method improves performances of 2D NMR spectroscopy under inhomogeneous fields without increasing the experimental duration or significant loss in sensitivity, and thus may open important perspectives for studies of inhomogeneous chemical systems.

Kaipin Xu¹, Subramaniam Sukumar¹, John Kurhanewicz¹, and Xiaojuan Li^1
1Radiology, University of California, San Francisco, San Francisco, CA, United States

To better understand the pathological progression of osteoarthritis (OA), techniques based on high resolution magic angle spinning (HR-MAS) NMR spectroscopy are developed for the study of relaxation times (T1, T2, and T1ρ) and diffusion coefficient (D) of human knee synovial fluids (SF) harvested from 1 OA and 8 anterior cruciate ligament (ACL) injured patients.

Marlon Arturo Pérez Rodas^1,2, Jörn Engelmann¹, Hellmut Merkle¹, Rolf Pohmann¹, and Klaus Scheffler^1,3
1Ultra High-field Magnetic Resonance Center, Max Planck Institute for Biological Cybernetics, Tübingen, Germany, ²Graduate Training Centre of Neuroscience, IMPRS for Cognitive and Systems Neuroscience, University of Tübingen, Tübingen, Germany, ³Department for Biomedical Magnetic Resonance, University of Tübingen, Tübingen, Germany

The distinction of functional activity between cortical layers in the brain by MRI or MRS requires high spatial and temporal resolution. High spatial resolution can be achieved by increasing the gradient strength or by using the intrinsic volume selectivity of miniature coils, even in conventional animal scanner. In the present work, initial results for highly-localized spectroscopy within seconds are presented, for a phantom metabolite solution and cell cultures in a 14.1T animal scanner using a 2mm-diameter circular coil. The larger signals from the major metabolites in ~1.5µL were detected in 24sec on the phantom solution with an acceptable SNR.

Marjeta Tušek Jelenc^1,2, Marek Chmelík^1,2, Barbara Ukropcová^3,4, Wolfgang Bogner^1,2, Siegfried Trattnig^1,2, Jozef Ukropec⁴, Martin Krššák^1,2,5, and Ladislav Valkovic^1,2,6,7
1High Field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria, ²Christian Doppler Laboratory for Clinical Molecular MR Imaging, Vienna, Austria,³Institute of pathophysiology, Faculty of Medicine, Comenius University, Bratislava, Slovakia, ⁴Obesity section, Diabetes and Metabolic Disease Laboratory, Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia, ⁵Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria, ⁶Department of Imaging Methods, Institute of Measurement Science, Slovak Academy of Sciences, Bratislava, Slovakia, ⁷University of Oxford Centre for Clinical Magnetic Resonance Research, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom

The aim of the study was to investigate the relation between the maximum oxidative flux (Q_max), a valid measure of muscular mitochondrial capacity and ATP synthase flux (F_ATP) measured in exercising gastrocnemius medialis muscle in healthy young and elderly subjects. Furthermore, we explored the possibility of direct measurement of both, Q_max and F_{ATP_ex}, in a single experiment. The dynamic experiment consisted of the acquisition of baseline data during two minutes of rest, six minutes of aerobic plantar flexion exercise (during which a 3.5 minutes long FAST measurement was performed), and six minutes of recovery. Our data showed significant correlation between ATP synthase flux in exercising muscle and maximal oxidative flux.

Feng-Hua Ma¹, Jin-Wei Qiang², Guo-Fu Zhang¹, Ya-Min Rao³, Hai-Min Li⁴, and Song-Qi Cai^4
1Department of Radiology, Obstetrics & Gynecology Hospital, Shanghai Medical College,Fudan University., Shanghai, China, People's Republic of, ²Department of Radiology, Jinshan Hospital, Shanghai Medical College,Fudan University, Shanghai, China, People's Republic of, ³Department of Radiology, Obstetrics& Gynecology Hospital, Shanghai Medical College, Fudan University, Shanghai, China, People's Republic of,⁴Department of Radiology, Jinshan Hospital, Shanghai Medical College, Fudan University, Shanghai, China, People's Republic of

Coherent results obtained by ex vivo and in vivo measurements allow the translation of biomarker findings from studies of tissue specimens (ex vivo) to those of patients (in vivo), and therefore it is important to establish how well correlated these metabolic profiles are. Such correlation has been evaluated for brain tumors, prostate cancer and cervical cancer, but without comparison of ovarian tumors. In this study we try to investigate the relationship between the Cho/Cr from in vivo MRS and the Cho/TSP of ex vivo MRS from tissue samples and the potential to bridge molecular and imaging diagnostics.

Nathalie Just¹, Lydia Wachsmuth¹, Florian Schmid¹, and Cornelius Faber^1
1Translational Imaging Centre, University of Münster, Münster, Germany

Optogenetics is a more and more recognized technique for investigating neuronal populations in the rodent brain. Combined to fMRI (OfMRI), more understanding could be achieved. However, the effects of powerful light on the tissue remain poorly understood. Here, experiments were conducted to investigate the effects of blue laser light  on  the metabolism of the primary somatosensory cortex.

Ivan Tkac¹, Igor Nestrasil², R Scott McIvor³, Kelley Kitto⁴, Carolyn A Fairbanks⁴, Karen Kozarsky⁵, Walter C Low⁶, Chester B Whitley², and Lalitha Belur^3
1Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, United States, ²Dept. of Pediatrics, University of Minnesota, Minneapolis, MN, United States, ³Dept. of Genetics and Cell Biology, University of Minnesota, Minneapolis, MN, United States, ⁴Dept. of Pharmaceutics, University of Minnesota, Minneapolis, MN, United States, ⁵REGENXBIO Inc., Rockville, MD, United States, ⁶Dept. of Surgery, University of Minnesota, Minneapolis, MN, United States

Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disease caused by the deficiency in α-L-iduronidase (IDUA) enzyme which results in lysosomal accumulation of glycosaminoglycans. The purpose of this study was to assess the ability of the adeno-associated virus (AAV) - mediated IDUA gene therapy to prevent the pathological neurochemical changes associated with the MPS I disease. The efficacy of the gene therapy was assessed by in vivo ¹H MRS at 9.4T using knockout mice deficient for IDUA, a well-established murine model of MPS I.

Alireza Abaei¹, Francesca Rizzo², Dinesh K Deelchand³, Anne Subgang¹, Johannes T. Schneider⁴, Andrea G. Ludolph⁵, and Volker Rasche^1,6
1Medical Faculty, Core Facility Small Animal MRI, Ulm University, Ulm, Germany, ²Institute of Anatomy and Cell Biology, University of Ulm, Ulm, Germany, ³University of Minnesota, Minneapolis, MN, United States,⁴Bruker BioSpin MRI GmbH, Ettlingen, Germany, ⁵Department of Child and Adolescent Psychiatry, University of Ulm, Ulm, Germany, ⁶Department of Internal Medicine II, University Hospital Ulm, Ulm, Germany

Assessment and reliable quantification of brain metabolites is of great interest for diagnosis and monitoring of neurodegenerative psychiatric disorders. Challenging in this context is the required spectral fidelity demanding a combination of rapid data acquisition, optimal frequency and phase correction, and excellent shimming of the volume of interest. In this contribution, an optimized STEAM sequence was combined with image-based shimming and single-shot frequency and phase correction. The method was applied to assessment of the difference between the metabolic profile of spontaneous hypertensive rats and Wistar-Kyoto rats. Statistically significant differences could be quantified in the striatum and the prefrontal cortex.

Nazem Atassi ^1,2, Maosheng Xu^3,4, Christina Triantafyllou⁵, Boris Keil ^2,6, Christopher Long⁷, Robert Lawson ^1,2, Paul Cernasov^1,2, Elena Ratti^1,2, Paganoni Sabrina^1,2, Nouha Salibi⁸, Ravi Seethamraju⁹, Bruce Rosen^2,3, Merit Cudkowicz^1,2, and Eva-Maria Ratai^2,3
1Neurology, Massachusetts General Hospital, Boston, MA, United States, ²A. A. Martinos Center for Biomedical Imaging, Charlestown, MA, United States, ³Radiology, Massachusetts General Hospital, Boston, MA, United States, ⁴Radiology, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China, People's Republic of, ⁵Siemens Healthcare, Erlangen, Germany, ⁶Massachusetts General Hospital, Boston, MA, United States, ⁷MIT Sloan Neuroeconomics Lab, Cambridge, MA, United States, ⁸Siemens Healthcare, Auburn, AL, United States, ⁹Siemens Healthcare, Charlestown, MA, United States

The purpose of this study was to quantify brain metabolites in Amyotrophic Lateral Sclerosis (ALS) patients using 7-Tesla MR spectroscopy and investigate how these metabolites correlate with clinical outcomes.  Patients with ALS had significantly decreased N-acetylaspartate (NAA), glutamate (Glu) and GABA in the left motor cortex consistent with neuronal injury or loss.  NAA/Cr and glutathione/Cr correlated with the revised ALS Functional Rating Scale. Increased pathological reflexes, a clinical marker of upper motor neuron degeneration correlated positively with myo-Inositol/Cr and choline/Cr, and negatively with NAA/Cr.  7T MRS can provide effective biomarkers in ALS patients which correlate well with clinical outcomes.

Gaëlle Diserens¹, Martina Vermathen², Nicholas T. Broskey³, Chris Boesch¹, Francesca Amati^1,3, and Peter Vermathen^1
1Depts Clinical Research and Radiology, University of Bern, Bern, Switzerland, ²Dept. Chemistry & Biochemistry, University of Bern, Bern, Switzerland, ³Dept. of Physiology, University of Lausanne, Lausanne, Switzerland

The aim of this ¹H HR-MAS NMR study was to investigate biopsies of skeletal muscles comparing athletes, sedentary slim and sedentary obese subjects. ¹H HR-MAS allows the direct assessment of glucose-phosphates contained in skeletal muscle biopsies, as was also previously shown. The current study is the first example for a potential application, demonstrating differences in glucose-phosphates between muscle tissues from athletes and sedentary subjects. The results suggest that quantitative assessment by ¹H HR-MAS NMR of Glc-1P and Glc-6P being key players in energy metabolism may prove important for metabolic studies in biopsies.

Vivian Youngjean Park¹, Dahye Yoon², Ja Seung Koo¹, Eun-Kyung Kim³, Seung Il Kim⁴, Ji Soo Choi¹, Suhkmann Kim⁵, and Min Jung Kim^1
1Yonsei University College of Medicine, Seoul, Korea, Republic of, ²2Department of Chemistry and Chemistry Institute for Functional Materials, Pusan National University, Busan, Korea, Republic of, ³Radiology, Yonsei University College of Medicine, Seoul, Korea, Republic of, ⁴Surgery, Yonsei University College of Medicine, Seoul, Korea, Republic of, ⁵Pusan National University, Busan, Korea, Republic of

We investigated whether intratumoral location and biospecimen type affect the metabolic characterization of breast cancer assessed by HR-MAS MR spectroscopy. This prospective study included 87 tumor tissue samples in 31 patients with invasive breast cancer, obtained from the center and periphery of surgical specimens and preoperatively by CNB. Specimens were assessed with HR-MAS MR spectroscopy. Overall, intratumoral location and biospecimen type had limited influence on the metabolic characterization of breast cancer assessed by HR-MAS MR spectroscopy. However, some metabolites are differentially expressed and caution is recommended in clinical decision-making based solely on metabolite concentrations, especially PC and PE. 

Suruchi Singh¹, Tanushri Chatterji², Manodeep Sen², Ishwar Ram³, and Raja Roy^1
1Centre of Biomedical Research, Lucknow, India, ²Department of Microbiology, Dr Ram Manohar Lohia Institute of Medical Sciences, Lucknow, India, ³Department of Urology, Dr Ram Manohar Lohia Institute of Medical Sciences, Lucknow, India

This study is a new approach for the diagnosis of Urosepsis using Proton MR spectroscopy along with serum procalcitonin levels. The study insights, NMR based metabolic profiling for differentiation of Urosepsis, a medical emergency which requires immediate patient care. The analysis takes less than one hour for disease identification, thus enabling quick and efficient patient management. The Principal Component Analysis (PCA) displayed that glucose and lactate in serum were the major confounders in differentiating Urosepsis cases from Healthy controls. The training set of Partial least square Discriminant analysis (PLS-DA) provided precise prediction of the test set in serum samples.

Rama Jayasundar¹ and Somenath Ghatak^1
1NMR, All India Institute of Medical Sciences, New Delhi, India

There is increasing interest in systems approach in healthcare, from clinical medicine, diet and nutrition, pharmacology to plant-based drug development. The potential of NMR to study medicinal plants as a whole to evaluate system parameters such as organoleptic properties have been explored in detail in this study. Since taste is a chemosensory effect, NMR has been used for this analysis of medicinal plants along with Electronic tongue based chemometrics for objective measurement of taste. The results indicate an active role for NMR in chemosensory research.

Amna Yasmin¹, Olli Gröhn¹, Asla Pitkänen¹, and Riikka Immonen^1
1Department of Neurobiology, A.I. Virtanen Institute University of Eastern Finland, Kuopio, Finland

Traumatic brain injury (TBI) is the main cause of mortality and morbidity worldwide. Up to 53 % of TBI patients with penetrating head injuries develop epilepsy in later part of life. Unavailability of biomarkers for epileptogensis is a major unmet clinical need, and is the greatest obstacle on the way of developing treatment in patients at risk, e.g., after TBI. Objective of this study is to determine metabolic profile in perilesional cortical area in clinically relevant TBI rat model and correlate MRS findings with EEG and histological outcomes in search for biomarkers. Results: Six out of 13 parameters showed changes at some follow point.  Findings of long TBI follow up will help to investigate cellular and molecular mechanisms underlying post-traumatic epileptogenesis and identify reliable biomarkers that could serve as therapeutic targets for the development of new antiepileptogenic and antiseizure compound.

Emmanuel Amabebe¹, Steven Reynolds², Victoria Stern¹, Jennifer Parker³, Graham Stafford³, Martyn Paley², and Dilly Anumba^1
1Academic unit of Reproductive and Developmental Medicine, University of Sheffield, Sheffield, United Kingdom, ²Academic unit of Radiology, University of Sheffield, Sheffield, United Kingdom, ³School of Dentistry, University of Sheffield, Sheffield, United Kingdom

We characterized the metabolite profile of cervicovaginal fluid (CVF) of a cohort of pregnant women presenting with symptoms of preterm labor by both ¹H Magnetic Resonance spectroscopy and spectrophotometric acetate enzyme assay. Acetate normalized integral (P=0.002) and spectrophotometry (P=0.006) were significantly higher in the women who delivered preterm compared to their term counterparts.  Both methods were predictive of PTB <37 weeks (acetate integral: AUC=0.75, spectrophotometry: AUC=0.74). Elevated CVF acetate in women with symptoms of preterm labor appears predictive of preterm delivery. In these women, a clinical assay of acetate in CVF may prove of clinical utility for predicting PTB.   

Tanushri Chatterji¹, Dr. Suruchi Singh², Dr. Manodeep Sen¹, Dr. Ajai Singh³, Prof. Raja Roy², and Dr. J.K Srivastava^4
1Microbiology, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, India, ²Centre of Bio-Medical Research, Lucknow, India, ³Neurology, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, India, ⁴Amity Institute of Biotechnology, Amity University, Lucknow, India

This study explored diagnostic utility based on the analysis of CSF, serum and urine for differential diagnosis of bacterial (BM) and tubercular meningitis (TBM) in adults using ¹H NMR metabolic profiling.This may render rapid diagnosis of meningitis resulting to the decline of mortality by appropriate and timely treatment regimen. The Discriminant Functional Analysis (DFA) identified acetate, alanine, malonate and choline containing compounds as significant metabolites among case and control. The Orthogonal Signal Correction Principal Component Analysis (OSC-PCA) of significant metabolites clearly differentiated case vs control group in serum and urine samples, while a clear classification could not be obtained for CSF samples.

Pawan Kumar¹, Sadhana Kumari¹, Senthil S Kumaran¹, Shefali Chaudhary¹, Vinay Goyal², Madhuri Behari², S N Dwivedi³, Achal Srivastava², and Naranamangalam R Jagannathan^1
1Department of NMR and MRI Facility, All India Institute of Medical Sciences, New Delhi, India, ²Department of Neurology, All India Institute of Medical Sciences, New Delhi, India, ³Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, India

We used ¹H NMR technique to investigate the serum samples of 6 patients with Parkinson’s disease (PD) and 6 healthy controls (HC) using 700 MHz NMR spectrometer and the data were processed using the Agilent software, Vnmrj2.3A. PLS-DA multivariate analysis was performed to explore biochemical dissimilarities between PD patients and HC using MetaboAnalyst (3.0) software. We observed significantly elevated levels of lactate, glutamate and methyl guanidine PD patients in comparison with HC on t-test, suggesting protein metabolism impairment, mitochondrial dysfunction and oxidative stress in PD patients.

Uma Sharma¹, Deepti Upadhyay¹, Govind Makharia², Prasenjit Das³, Siddharth Datta Gupta³, and Naranamangalam R Jagannathan^1
1Department of NMR and MRI Facility, All India Institute of Medical Sciences, New Delhi, India, ²Department of Gastroenterology and human Nutrition, All India Institute of Medical Sciences, New Delhi, India,³Department of Pathology, All India Institute of Medical Sciences, New Delhi, India

The present study demonstrated dietary induced variations on the metabolic profile of blood plasma of CeD patients. Increased valine was seen in CeD non-vegetarians compared to CeD vegetarians. Both CeD vegetarians and non-vegetarians showed increased concentrations of gluconeogenic amino acids like alanine and glycine compared to healthy subjects. Increased pyruvate and creatine in CeD vegetarians compared to healthy vegetarians indicates impaired energy supply. Decreased creatinine in CeD vegetarians and non-vegetarians compared to healthy subjects is due to protein malabsorption in CeD. The study illustrates the nutritional status of CeD patients and healthy subjects on the basis of their dietary intake.

Virendra Kumar¹, Tanmoy Bagui², Rashmi Mukherjee², Vertika Rai², Pawan Kumar¹, and Chandan Chakraborty^2
1Department of NMR, All India Institute of Medical Sciences, New Delhi, India, ²School of Medical Science & Technology, Indian Institute of Technology Kharagpur, Kharagpur, India

Diabetic retinopathy (DR), is a major cause of blindness, caused by prolonged diabetes. However, this morbidity is largely preventable and treatable. The progression of DR from prolonged diabetes involves complex metabolic de-regulations. ¹H NMR-based metabolomics of serum have potential to study dysregulation in metabolites of DR patients. Results of the PCA and PLS-DA analysis revealed metabolic differences in DR patients compared to healthy subjects. Using such a study, we may observe the severity of disease based on metabolic fingerprints and it may serve as a platform for screening of molecular targets for a more efficient therapeutic intervention.

Alka Singh¹, Suruchi Singh², Saloni Raj¹, Ravindra Kumar Garg³, Abbas Ali Mahdi⁴, Raja Roy², and Rajeshwar Nath Srivastava^1
1Orthopaedic Surgery, King George's Medical University, Lucknow, India, ²Centre of Biomedical Research, Lucknow, India, ³Neurology, King George's Medical University, Lucknow, India, ⁴Biochemistry, King George's Medical University, Lucknow, India

It mainly focuses on finding significant metabolites in serum using 1H NMR based spectroscopic methods and to study the variation of concentration of these metabolites during the recovery of the patient ongoing treatment after surgery.  Significant metabolites, namely, lactate, glycine, acetone and succinate were identified using statistical methods (ANOVA along with Mann- Whitney U test) and are found to be elevated during the time of injury. The levels gradually decrease as the patient recovers in an average period of six months.This is a prospective case-control preliminary study on recovery of the patient during acute spinal cord injury.

Ahmad Seif Kanaan^1,2, Sarah Gerasch², Isabel Garcia-Garcia¹, Leonie Lampe¹, André Pampel¹, Alfred Anwander¹, Jamie Near³, Kirsten Müller-Vahl², and Harald E. Möller^1
1Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany, ²Department of Psychiatry, Hannover Medical School, Hannover, Germany, ³Douglas Mental Health University Institute and Department of Psychiatry, Mcgill University, Montreal, QC, Canada

We hypothesized that glutamatergic signalling is related to pathophysiology of Gilles de la Tourette syndrome (GTS) and investigated glutamatergic metabolism within cortico-striatal regions using 1H-MRS at baseline and during treatment. Absolute metabolite concentrations were calculated with the consideration of voxel compartmentation following frequency and phase drift correction in the time domain. GTS patients exhibited reductions in striatal and thalamic [Glx], which were normalized with treatment and were correlated with clinical severity parameters. Our results implicate glutamatergic metabolism in GTS pathophysiology and indicate a possibly dysfunctional astrocytic-neuronal coupling system, which would have profound effects on the dopaminergic modulation of cortico-striatal input.

Mona A Mohamed¹, Peter B Barker¹, Richard L Skolasky², Heidi Vornbrock Roosa³, Yun Zhou¹, Weiguo Ye¹, Noble George¹, James Brasic¹, Dean F Wong¹, and Ned Sacktor^3
1Radiology, Johns Hopkins Medical Institutions, Baltimore, MD, United States, ²Orthopedics, Johns Hopkins Medical Institutions, Baltimore, MD, United States, ³Neurology, Johns Hopkins Medical Institutions, Baltimore, MD, United States

In this study, 7T MRS and 18F AV45 PET were used to measure brain metabolites and amyloid burden in Elderly HIV subjects. These reliable biomarkers can be used in assessing the relation between normal aging, HIV and the degree of HIV Associated Neurocognitive Disorders (HAND).