Sophie Malaquin¹, Eloïse Mougel¹, Melissa Vincent¹, and Julien Valette^1
1Université Paris-Saclay, Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), Centre National de la Recherche Scientifique (CNRS), Molecular Imaging Research Center (MIRCen), Laboratoire des Maladies Neurodégénératives, Fontenay aux Roses, France

Diffusion-weighted NMR spectroscopy allows non-invasive measurement of the diffusion properties of brain metabolites. Lactate is of particular interest but has low concentration thus requiring the development of new sequences to maximize signal-to-noise ratio. In this work, we compare a reference stimulated echo sequence and two spin echo sequences using either a broad pulse, or a selective polychromatic pulse suppressing J-modulation, by measuring the signal attenuation as a function of diffusion-weighting. Suppression of J-modulation with the polychromatic spin echo sequence leads to a significant signal gain and a better precision in lactate signal attenuation.

Muhammad G Saleh¹, Steve Hui², Helge Zöllner², and Richard A Edden^2
1University of Maryland School of Medicine, Baltimore, MD, United States, ²The Johns Hopkins University School of Medicine, Baltimore, MD, United States

Phosphorylethanolamine/ethanolamine (PE) serves as an important precursor for choline-containing compounds that are crucial for cell-membrane formation and maintenance. As such, PE can be influenced by pathways involving choline production in brain diseases that cause neuroinflammation. PE is also implicated in diseases that are known to cause neuronal damage. Therefore, PE may be a potential marker for investigating brain integrity. MEGA-PRESS, a spectral editing method, allows direct detection and in vivo measurement of PE. Here, we demonstrate the optimal editing of PE using MEGA-PRESS to facilitate unambiguous in vivo measurements of PE.

Jullie W Pan¹, Victor W Yushmanov², Chan H Moon³, Brian Soher⁴, Frank H Lieberman⁵, and Hoby P Hetherington^2
1Radiology, University of Pittsburgh, Pittsburgh, PA, United States, ²university of pittsburgh, pittsburgh, PA, United States, ³University of Pittsburgh, Pittsburgh, PA, United States, ⁴Radiiology, Duke University, Durham, NC, United States, ⁵Neurology, University of Pittsburgh, Pittsburgh, PA, United States

The J-refocused double spin echo sequence is applied at 7T using the 8x2 transceiver and demonstrated in the frontal-parietal and temporal lobe regions. Spectral quality parameters based on the Cramer Rao lower bound, linewidth and SNR are calculated and considered for multiplet and singlet compounds, finding that the variance in highly overlapped compounds  such as myo-Inositol are more steeply dependent on spectral uncertainty compared with singlet compounds. With fast encoding methods, the J-refocused acquisition is achieved in clinically acceptable imaging times (<3min, single slice) and can detect abnormalities in Glutamine in brain tumor patients.

Kiwamu Matsuoka^1,2, Yuhei Takado¹, Kenji Tagai¹, Manabu Kubota³, Yasunori Sano¹, Keisuke Takahata¹, Maiko Ono¹, Chie Seki¹, Hideki Matsumoto^1,4, Hironobu Endo¹, Hitoshi Shinotoh¹, Jamie Near⁵, Kazunori Kawamura¹, Ming-Rong Zhang¹, Hitoshi Shimada¹, and Makoto Higuchi^1
1National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan, ²Department of Psychiatry, Nara Medical University, Kashihara, Japan, ³Department of Psychiatry, Kyoto University Graduate School of Medicine, Kyoto, Japan, ⁴Department of Oral and Maxillofacial Radiology, Tokyo Dental College, the city of Chiyoda-ku, Japan, ⁵Douglas Mental Health University Institute and Department of Psychiatry, McGill University, Montréal, QC, Canada

Apathy is characterized by lack of motivation. We investigated the mechanisms underlying apathy in progressive supranuclear palsy (PSP), which is characterized by tau aggregate accumulations causing oxidative stress in the brain. Using magnetic resonance spectroscopy and tau positron emission tomography, we found associations of apathy levels with glutathione levels in the posterior cingulate cortex (PCC), tau aggregate accumulation levels in the angular gyrus/PCC, and atrophy of the right inferior frontal gyrus and anterior cingulate cortex. The vulnerability of the anterior and posterior brain regions where apathy is related is suggested as possible underlying mechanisms for apathy in PSP.

Selda Yildiz^1,2, Miranda M. Lim^2,3,4,5,6, Manoj K. Sammi^1,7, Katherine Powers¹, Charles F. Murchison^2,8, Jeffrey J. Iliff^{9,10,11,12,13}, and William D. Rooney^1,2,5,10
1Advanced Imaging Research Center, Oregon Health & Science University, Portland, OR, United States, ²Department of Neurology, Oregon Health & Science University, Portland, OR, United States, ³VA Portland Health Care System, Portland, OR, United States, ⁴Department of Medicine, Division of Pulmonary and Critical Care Medicine, Oregon Health & Science University, Portland, OR, United States, ⁵Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, United States, ⁶Oregon Institute of Occupational Health Sciences;, Oregon Health & Science University, Portland, OR, United States, ⁷BENFRA Botanical Dietary Supplements Research Center, Oregon Health & Science University, Portland, OR, United States, ⁸Department of Biostatistics, University of Alabama, Birmingham, AL, United States, ⁹Department of Anesthesiology and Perioperative Medicine, Oregon Health & Science University, Portland, OR, United States, ¹⁰Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR, United States, ¹¹VISN 20 Mental Illness Research, Education and Clinical Center (MIRECC), VA Puget Sound Health Care System, Seattle, WA, United States, ¹²Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, United States, ¹³Department of Neurology, University of Washington, Seattle, WA, United States

This study describes a non-invasive combined magnetic resonance spectroscopy and polysomnography approach to measure brain metabolite levels together with simultaneous characterization of sleep or wake states.  The results provide the first in-vivo demonstration of reductions in brain lactate concentration and diffusivity during sleep versus wakefulness in young healthy human brain. These findings are consistent with invasive small-animal studies showing the loss of extracellular lactate during sleep, and support the notion of altered lactate metabolism and/or increased glymphatic activity in sleeping human brain.

Ralf Mekle¹, Jochen B. Fiebach¹, and Heiner Stuke^2
1Center for Stroke Research Berlin, Charité – Universitätsmedizin Berlin, Berlin, Germany, ²Department of Psychiatry and Psychotherapy, Charité – Universitätsmedizin Berlin, Berlin, Germany

The neurophysiological and neurochemical alterations involved in the formation of hallucinations are not sufficiently understood. fMRI was used during a face detection task, and neurotransmitter levels in the visual cortex were measured by ¹H MRS at 3T to elucidate processes involved in the false (hallucinatory) detection of faces in pure noise patterns. Increased hallucinatory face detections were related to decreased activation of the fusiform face area. In addition, decreased face-dependent activation was related to reduced glutamate levels. These findings substantiate theories of hallucinatory misperceptions, which implicate impaired glutamatergic transmission in a reduced ability to differentiate between meaningful information and noise.

Kadir Şimşek¹, André Döring^1,2, André Pampel³, Harald E. Möller³, and Roland Kreis^1
1Department of Radiology and Biomedical Research, University of Bern, Bern, Switzerland, ²Cardiff University Brain Research Imaging Centre (CUBRIC), School of Psychology, Cardiff University, Cardiff, United Kingdom, ³Max-Planck Institution for Human Cognitive and Brain Sciences, Leipzig, Germany

Diffusion-weighted MRS was successfully applied at short TE with ultra-high b-values on a 3T Siemens Connectom system. Additional motion compensation based on macromolecule signals was implemented to complement water-signal-based motion compensation, especially at high b-values. By extending simultaneous fitting of interrelated datasets to a biexponential diffusion model, non-Gaussian diffusion behavior of metabolites can be established in a more rigorous fashion. Finally, also the definition of macromolecular background signals by diffusion rather than relaxation properties benefits from these more robust methods and the patterns can now be used as bases for quantification in clinical studies at short-TE.

Fan Lam^1,2, Hoby Hetherington³, and Jullie Pan^3
1Bioengineering, 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, ³Radiology, University of Pittsburgh, Pittsburgh, PA, United States

We present here a new method for rapid MRSI of the brain on 7T that combines fast rosette trajectories and subspace-based processing from the SPICE MRSI framework. Results from in vivo experiments demonstrated substantial improvement in spectral quality and SNR achieved by the subspace imaging method over the standard reconstruction of rosette MRSI data. The ability to obtain single-slice rapid MRSI of the brain with an only 1.1 min acquisition was also demonstrated using the subspace-based reconstruction. These results highlight the potentials of integrating subspace imaging and fast acquisitions to push the performance of ultrahigh-field MRSI. 

Graeme A. Keith¹, Amir Seginer², David A. Porter¹, and Rita Schmidt^3
1Institute of Neuroscience and Psychology, University of Glasgow, Glasgow, Scotland, ²Siemens Healthcare Ltd, Rosh Ha’ayin, Israel, ³Neurobiology Department, Weizmann Institute of Science, Rehovot, Israel

Echo-planar spectroscopic imaging (EPSI) is a fast method of acquiring metabolic information in the human brain. When applied at high-fields, such as 7T however, it suffers from limited spectral-width, as well as the inconsistencies between readout lines, seen at all field strengths, which lead to ghosts in the spectra. In this work, we present the readout-segmented COKE method, which removes the spectral-width limitation at 7T and provides a coherent phase evolution that avoids Nyquist artefacts in the spectra. Simulations and phantom scans are also presented, which seek to increase understanding of residual lipid contamination due to the readout-segmented spatial-encoding scheme.

Lukas Hingerl¹, Wolfgang Bogner¹, Bernhard Strasser¹, Petr Bednarik¹, Stanislav Motyka¹, Eva Heckova¹, Ivica Just¹, Alexandra Lipka¹, Ovidiu Andronesi², Stephan Gruber¹, Siegfried Trattnig^1,3, and Gilbert Hangel^1,4
1Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, High Field MR Centre, Vienna, Austria, ²Department of Radiology, Massachusetts General Hospital, Martinos Center for Biomedical Imaging, Boston, MA, United States, ³Christian Doppler Laboratory for Clinical Molecular MR Imaging, Vienna, Austria, ⁴Department of Neurosurgery, Medical University of Vienna, Vienna, Austria

3D-FIDESI-MRSI combines a free-induction-decay-readout with an echo-readout to permit the measurement of whole-brain lactate as an important tumor biomarker in approximately 40 min. This enables the acquisition of signals at short TE with reduced T2-weighting as well as spectra at long TE without lipid contamination. Sufficient SNR is ensured by a smaller and oversampled spherical k-space coverage for the echo-readout using fast concentric ring trajectories. A test in a healthy volunteer successfully demonstrates feasible mapping of the major metabolites.

Theresia Ziegs^1,2, Johanna Dorst^1,2, and Anke Henning^1,3
1MRZ, MPI for Biological Cybernetics, Tuebingen, Germany, ²IMPRS for Cognitive and Systems Neuroscience, Tuebingen, Germany, ³Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, United States

Glutamate related metabolism can be measured considering the 13C labeling effects from an administered 13C labeled substrate by short TE 1H MRS spectra without the need for 13C channels, RF coils or scan software as required for direct 13C MRS or 13C edited 1H observed MRS. In this work, the labeling effects were followed in the frontal cortex and the occipital lobe using a short TE 1H MC-semiLASER sequence at 9.4T in healthy volunteers after oral intake of [13C-1]glucose. The spectral time series acquired show obvious 13C labelling related changes in the 1H observed Glu and Gln spectral pattern.

Diana Rotaru¹, Georg Oeltzschner^2,3, Richard Edden^2,3, and David Lythgoe^1
1Neuroimaging, King's College London, London, United Kingdom, ²Russell H. Morgan Department of Radiology and Radiological Science, The 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

Precise and accurate quantitation of GABA and GSH on 3T MR platforms is a great challenge in MR Spectroscopy. Despite this aspect, the reproducibility and repeatability of GABA and GSH measurements have been given little attention. In this study, test-retest repeatability was assessed for HERMES GABA and GSH estimates determined in LCModel using conventional single-spectrum analysis of Hadamard-reconstructed spectra (GABA difference, GSH difference and sum) and a novel analysis approach that models the Hadamard-reconstructed spectra simultaneously, hence using all spectral information acquired. The concatenated method allows simultaneous quantitation of GABA and GSH and provides comparable repeatability to traditional single-spectrum analysis.

Karl Landheer¹, Martin Gajdošík¹, and Christoph Juchem^1,2
1Biomedical Engineering, Columbia University, New York City, NY, United States, ²Radiology, Columbia University, New York City, NY, United States

Water suppression is a necessary component to magnetic resonance spectroscopy experiments due to its roughly 5000-fold higher intensity than the metabolites of interest. Here we introduce a novel algorithm for water suppression which operates in a similar manner to that originally proposed by WET and expanded upon by VAPOR, but is flexible in that it can accommodate an arbitrary number of RF pulses, minimum duration between pulses, total module duration and maximum flip angles. This method is referred to as Constrained Optimized Water Suppression. We demonstrated the improvement of COWS over the gold standard VAPOR in simulations and in vivo.

Hikari Yoshihara¹, Nicolas Kunz², and Hongxia Lei^2,3
1EPFL-LIFMET, Lausanne, Switzerland, ²EPFL-CIBM, Lausanne, Switzerland, ³United-Imaging Co. Ltd, Wuhan, China

¹³C MRS of the very same mouse hippocampus and hypothalamus at 14.1T is feasible using dynamic shimming update

Ralph E. Hurd¹, Meng Gu¹, Phil Adamson², Kirk Riemer³, Ryan Beckman³, Michael Ma³, Kenichi Okamura³, Frank Hanley³, and Daniel Spielman^1
1Radiology, Stanford, Stanford, CA, United States, ²Electrical Engineering, Stanford, Stanford, CA, United States, ³Cardiothoracic Surgery, Stanford, Stanford, CA, United States

The basic mantra for in vivo MR spectroscopy is to look beyond the dominant water and lipid signals. Although water is very well characterized by MRI, partially suppressed water can provide unique information in proton MR spectra. In the results presented, residual water-by-design strategy is demonstrated to extend beyond use as a reference. For the protocol described, water derived measurements of temperature and hypoxia, add critical value at no compromise.

Oun Al-iedani^1,2, Jeannette Lechner-Scott^2,3,4, Rodney Lea², Ovidiu Andronesi⁵, and Saadallah Ramadan^2,6
1School of Health Sciences, University of Newcastle, Newcastle, Australia, ²Hunter Medical Research Institute, Newcastle, Australia, ³Department of Neurology, John Hunter Hospital, Newcastle, Australia, ⁴School of Medicine and Public Health, University of Newcastle, Newcastle, Australia, ⁵Harvard Medical School, Massachusetts General Hospital, Boston, MA, United States, ⁶Faculty of Health and Medicine, University of Newcastle, Newcastle, Australia

The study designed a novel multi-dimensional metabolic mapping using multi-slice-spiral-MRSI with multi-voxel segmentation and differential metabolic regions(DMRs) techniques to demonstrate the true nature of NAWM and WM-lesions of RRMS patients,compared to HCs. 3D-spiral-MRSI covering majority of the brain in 16 RRMS and 13 HCs were used. Multi-slice-MRSI was processed using novel pipeline with DMRs classifications. Neurometabolic mapping of  multi-DMRs revealed that(NAA/tCr) in WM-lesions was significantly lower than NAWM-MS and HCs,while (m-Ins/tCr) in WM-lesions were significantly higher than NAWM-MS and HCs. Multi-slice-spiral-MRSI coupled with DMRs may enhance a clinical monitoring of RRMS patients, and is sensitive in diagnosing NAWM in RRMS

Samuel W. Holder^1,2, Michael Graham Harrington³, and Samuel Colles Grant^1,2
1National High Magnetic Field Laboratory, Florida State University, Tallahassee, FL, United States, ²Chemical & Biomedical Engineering, FAMU-FSU College of Engineering, Tallahassee, FL, United States, ³Molecular Neurology Program, Huntington Medical Research Institutes, Pasadena, CA, United States

Spontaneous Trigeminal Allodynia (STA) occurs within ~50% of male Sprague-Dawley rats, presents symptoms analogous to migraine and may be alleviated by migraine treatments. Relaxation-enhanced MRS implemented in the female rat thalamus at 21.1 T examined metabolic effects of STA using a nitroglycerin-injected model of migraine. It was found that STA generates glutamate/glutamine and limited lactate responses with even saline injection. However, the STA response is rendered negligible when given a conventional dose of 10-mg/kg nitroglycerin. Future spectroscopic examinations of neurological disorders, particularly those focused on excitotoxicity/neuroprotection, should account for this potential effect.

Kirsten Kapteijns¹, Teije van Prooije¹, Jack JA van Asten², Bart van de Warrenburg¹, and Tom WJ Scheenen^2
1Dept of Neurology, Radboudumc, Nijmegen, Netherlands, ²Dept of Medical Imaging, Radboudumc, Nijmegen, Netherlands

Reliable biomarkers for SCA1 are necessary to reach trial-readiness. However, with small samples, it is important to interrogate the robustness of earlier biomarker findings. We performed single voxel ¹H-MRS on 23 patients and 7 controls in the pons, cerebellar white matter, and vermis. Participants were evaluated on ataxia severity (SARA scale). Differences between groups showed alterations in tNAA, glutamate, and myo-Inositol. Negative correlations of tNAA with SARA could be found in all VOIs, and glutamate showed a negative correlation with SARA in the cerebellar WM. These findings are in line with earlier studies, and support the idea of MRS biomarkers.

Julie M Joyce^1,2,3,4, Leah J Mercier^2,4,5, Parker L La^1,2,3,4, Tiffany Bell^1,2,3, Julia M Batycky^2,4,5, Chantel T Debert^2,3,4,5, and Ashley D Harris^1,2,3,4
1Department of Radiology, University of Calgary, Calgary, AB, Canada, ²Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada, ³Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada, ⁴Integrated Concussion Research Program, University of Calgary, Calgary, AB, Canada, ⁵Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada

Persistent post-concussive symptoms (PPCS) are debilitating symptoms that endure beyond the usual recovery period after concussion. Post-traumatic headache is one of the most common symptoms of concussion and its pathophysiology remains poorly characterized. Oxidative stress may contribute to the symptoms seen in PPCS patients. Here, we use edited magnetic resonance spectroscopy to investigate levels of the antioxidant glutathione in the anterior cingulate and sensorimotor cortices in adults with PPCS relative to controls. In the anterior cingulate—a critical hub in the default mode network—we found a significant positive correlation between glutathione and functional impact of headache in PPCS patients.

Anna M Chen¹, Teresa Gerhalter¹, Seena Dehkharghani^1,2, Rosemary Peralta¹, Fatemeh Adlparvar¹, Martin Gajdošík³, Mickael Tordjman^1,4, Julia Zabludovsky¹, Sulaiman Sheriff⁵, James S Babb¹, Tamara Bushnik⁶, Jonathan M Silver⁷, Brian S Im⁶, Stephen P Wall⁸, Guillaume Madelin¹, and Ivan I Kirov^1,2,9
1Center for Biomedical Imaging, Department of Radiology, New York University Grossman School of Medicine, New York, NY, United States, ²Department of Neurology, New York University Grossman School of Medicine, New York, NY, United States, ³Department of Biomedical Engineering, Columbia University School of Engineering and Applied Science, New York, NY, United States, ⁴Department of Radiology, Cochin Hospital, Paris, France, ⁵Department of Radiology, University of Miami Miller School of Medicine, Miami, FL, United States, ⁶Department of Rehabilitation Medicine, New York University Grossman School of Medicine, New York, NY, United States, ⁷Department of Psychiatry, New York University Grossman School of Medicine, New York, NY, United States, ⁸Ronald O. Perelman Department of Emergency Medicine, New York University Grossman School of Medicine, New York, NY, United States, ⁹Center for Advanced Imaging Innovation and Research, Department of Radiology, New York University Grossman School of Medicine, New York, NY, United States

We present initial results from a reproducibility study of ¹H MRSI in mild traumatic brain injury. In line with previous investigations in a separate cohort, linear regression analysis revealed white matter differences between patients and controls, which persisted when comparing only non-recovered patients to controls. In contrast to previous findings, however, the differences were not in N-acetyl aspartate (NAA), but in the glial markers creatine (Cr), choline (Cho), and myo-inositol (mI). Correlations were found between metabolites and neuropsychological testing in grey matter (GM), and between metabolites and symptomatology in white matter (WM).