MRS-Animal Models & Non-Proton MRI

Thursday 4 June 20155

Tetyana Konak¹, Jaivijay Ramu¹, and Serguei Liachenko^1
1Neurotoxicology, NCTR / FDA, Jefferson, AR, United States

There are an indications that males and females might differ in the development of the tobacco smoke addiction, women being more susceptible and showing higher degree of depression disorders during cessation therapy. We used non-invasive ¹H-MRS to look for the gender differences in the changes of neurometabolites in rats after single acute nicotine administration. The differences detected are consistent with the involvement of the glutamate cycle in the brain reward circuitry, rendering MRS as a powerful tool for the development of the addiction biomarkers.

Joao M.N. Duarte¹, Freya-Merret Girault¹, and Rolf Gruetter^1,2
1LIFMET, EPFL, Lausanne, Vaud, Switzerland, ²Radiology, UNIL and UNIGE, Lausanne and Geneva, Vaud & Geneva, Switzerland

It is still not clear how blood-born lactate is utilised to fuel brain metabolism. We now measured labelling incorporation into carbons of glutamate and glutamine in the rat brain with ¹³C MRS at 14.1 T upon ¹³C-lactate infusion. Metabolic modelling of ¹³C MRS data revealed that the rates of brain metabolism were similar to those measured with ¹³C-enriched glucose, the main brain fuel, and that exogenous lactate led to larger enrichment in neuronal than glial pyruvate, suggesting that it is mainly utilised by neurons.

Chloe Najac^1,2, Brice Tiret^1,2, Julien Flament^1,3, Martine Guillermier^1,2, Diane Houitte^1,2, Romina Aron Badin^1,2, Philippe Hantraye^1,2, Emmanuel Brouillet^1,2, Vincent Lebon^1,2, and Julien Valette^1,2
1CEA-MIRCen, Fontenay-aux-Roses, France, ²CEA-CNRS URA 2210, Fontenay-aux-Roses, France, ³Inserm US27, CRC-MIRCen, Fontenay-aux-Roses, France

We measured for the first time the cerebral metabolic rate of oxygen (CMRO₂) of one healthy and one 3-NP treated (used as a model for Huntington’s disease) macaques using direct ¹⁷O MRI at 7 T. CMRO₂ was quantified voxel-by-voxel (8.75 mm isotropic) using a three-phase metabolic model. Although values were lower (< 1.2 μmole/g of brain tissue/min) than expected, a strong difference in CMRO₂ was observed when comparing values in the healthy and treated macaque brains. This illustrates the sensitivity of direct ¹⁷O MRI to detect brain energy metabolism alteration, as observed in neurodegenerative diseases.

Puneet Bagga¹, Komal Kumari Mandal¹, and Anant Bahadur Patel^1
1NMR Microimaging and Spectroscopy, Centre for Cellular and Molecular Biology, Hyderabad, Andhra Pradesh, India

Although glycolysis via pyruvate dehydrogenase pathway (PDH) is the major pathway of glucose metabolism, pentose phosphate pathway (PPP) accounts for a significant fraction of glucose oxidation in brain. Hypometabolism has been reported in patients and in animal models of Parkinson’s disease (PD) but the flux through PPP is not yet evaluated. In this study, we measured rate of glucose metabolism via PPP and PDH in cerebral cortex and midbrain of mice treated with MPTP by ¹³C-NMR spectroscopy together with infusion of [1,2-¹³C₂]glucose. The PDH and PPP fluxes were found to be reduced suggesting a compromised antioxidant defense system in PD.

Hyeong Hun Lee^1,2, Sungjin Kim^1,2, Hye Rim Cho^1,2, Hwon Heo^1,2, Seung Hong Choi^1,2, and Hyeonjin Kim^1,2
1Biomedical Sciences, Seoul National University, Seoul, Korea, ²Radiology, Seoul National University Hospital, Seoul, Korea

Given the importance of detecting the onco-metabolite 2-hydroxyglutarate (2-HG) in vivo in isocitrate dehydrogenases (IDH)-mutated gliomas and the increasing availability of high-field clinical scanners, we have evaluated the feasibility of assessing IDH-mutational status and metabolic profiling at 9.4T in rodent brains with IDH-mutated gliomas by using 1H-MRS with a double inversion sequence module for subject-specific baseline modelling. Our results support that the in vivo assessment of IDH-mutational status in gliomas may be feasible at 9.4T. Our results also support the feasibility of preclinical animal studies for the development of novel therapeutic strategies for IDH-mutated gliomas in vivo.

Jose Luis Izquierdo Garcia¹, Marina Radoul¹, Myriam M Chaumeil¹, Pia Eriksson¹, Pavithra Luis Viswanath¹, and Sabrina M Ronen^1
1University California San Francisco, San Francisco, California, United States

Mutations in isocitrate dehydrogenase 1 (IDH1) have been reported as an early oncogenic event in over 70% of low-grade gliomas and secondary glioblastomas. We have recently shown that the introduction of the IDH1 R132H mutation into U87 genetically engineered cellular model leads a significant increase in HP lactate production. The goal of this study was to validate in-vivo our previous findings in cells. HP 1-13C Piruvic Acid MRS showed a significant 73% increase in lactate production in U87 IDH1 mutant tumors associated with a drop in PDH activity, which likely reflects the metabolic reprogramming of mutant IDH1 tumors.

Honghao Cai¹, Liangjie Lin¹, Xiaohong Cui¹, and Zhong Chen^1
1Electronic Science Department, Xiamen University, Xiamen, Fujian, China

Intermolecular double-quantum coherence (iDQC) ¹H-NMR spectroscopy, which serves as a method in the analyses of fatty acids compositions, is investigated by experiments on the intact salmon muscle and the whole zebra fish. The pure fatty acids spectroscopy of the intact salmon muscle, whose resonances are overlapped with metabolites peaks in conventional NMR, is recovered from the severe intrinsic structural inhomogeneity without pretreatments in a few minutes. In order to improve the practicability of iDQC method, a localized module was combined with iDQC method. By the localized iDQC method, fatty acids of the whole zebra fish are detected non-invasively. ¹H-NMR spectroscopy, which serves as a method in the analyses of fatty acids compositions, is investigated by experiments on the intact salmon muscle and the whole zebra fish. The pure fatty acids spectroscopy of the intact salmon muscle, whose resonances are overlapped with metabolites peaks in conventional NMR, is recovered from the severe intrinsic structural inhomogeneity without pretreatments in a few minutes. In order to improve the practicability of iDQC method, a localized module was combined with iDQC method. By the localized iDQC method, fatty acids of the whole zebra fish are detected non-invasively.

Mamta Aryabhushan Gupta¹, Poonam Rana¹, Richa Trivedi¹, Seenu Haridas², Kailash Manda², B S Hemanth Kumar¹, and Subash Khushu^1
1NMR Research Centre, INMAS,DRDO, Delhi, Delhi, India, ²Division of Radiation Biosciences, INMAS,DRDO, Delhi, Delhi, India

Hippocampus has been recognized as a key region sensitive to γ-irradiation. Hippocampal impairment has been widely studied in cranial irradiation but there are no reports elucidating impairment after whole body exposure during early delayed phase. In this study, we addressed the microstructural, metabolic and behavioral changes at 5 months post whole body γ-irradiation exposure in mouse model. Our results demonstrated altered FA, AD and mI changes in hippocampus along with reduced cognitive index. The results are suggestive of radiation induced persistent oxidative stress and gliosis as the main contributory factor for these early delayed changes post whole body irradiation.

Hyeon-Man Baek^1,2, Jooyun Kim¹, Youngjae Jeon¹, and Mirim Bang^1
1Center for MR Research, Korea Basic Science Institute, Ochang, Chungbuk, Korea, ²Department of Bio-Analitical Science, University of Science & Technology, Daejeon, Chungnam, Korea

1H-MRS permits longitudinal assessment of fat fraction, saturated and unsaturated. The aim of this study was to characterize early hepatic lipid changes in fatty liver rat model by in vivo short-echo time (TE) 1H-MRS. 1H-MRS permits longitudinal assessment of fat fraction, saturated and unsaturated [4]. The aim of this study was to characterize early hepatic lipid changes in fatty liver rat model by in vivo short-echo time (TE) 1H-MRS. Therefore, 1H-MRS is useful in detecting and characterizing various hepatic lipid alterations as early as 2 weeks for the start high fat diet.

Puneet Bagga¹, Anup N Chugani¹, Mavuri Suresh Kumar¹, and Anant Bahadur Patel^1
1NMR Microimaging and Spectroscopy, Centre for Cellular and Molecular Biology, Hyderabad, Andhra Pradesh, India

Pitx3 knockout (Pitx3^-/-) mouse model is a well-established genetic model of chronic Parkinson’s disease (PD) due to developmental malformation of substantia nigra, leading to loss of dopamine innervations in striatum. Striatal metabolite levels were measured with in vivo ¹H MRS and cerebral metabolism was evaluated by infusion of [1,6-¹³C₂]glucose for 10 min in conjunction with ¹H-{¹³C}-NMR spectroscopy of mice brain tissue extracts. Glu and GABA level was found to be elevated in the striatum of Pitx3^-/- mice indicating their role as biomarkers. Additionally, reduced glucose oxidation by glutamatergic and GABAergic neurons was observed in different brain regions.

Kyu-Ho Song¹, Hyeon-Man Baek², Do-Wan Lee¹, and Bo-Young Choe^1
1Department of Biomedical Engineering, and Research Institute of Biomedical Engineering, College of Medicine, The Catholic University of Korea, Seoul, Seoul, Korea, ²Center for Magnetic Resonance Research, Korea Basic Science Institute, Chungbuk, Korea

Quantification of Choline-Containing Compounds and Lipid Content

Jadegoud Yaligar¹, Swee Shean Lee¹, Elma Faylon Ilanto², Sanjay K Verma¹, Kanaga Sabapathy², and S Sendhil Velan^1
1Laboratory of Molecular Imaging, Singapore Bioimaging Consortium, Singapore, Singapore, Singapore, ²Laboratory of Molecular Carcinogenesis, National Cancer Center, Singapore, Singapore

Hepatic fibrosis is associated with chronic liver injury by various stimuli (metabolic, inflammatory, parasitic and toxins) increasing the risk for hepatocellular carcinoma. Liver fat and lipid composition tend to play an important pathogenic role during the progression of liver fibrosis and cirrhosis. In our current study, we have investigated the longitudinal alterations in lipid composition and sodium content at early stage to later stages of hepatic fibrosis. An alteration in lipid metabolism was observed as early as 2 weeks of carbon tetrachloride induction. Lipid fraction, total saturated and mono-unsaturated lipids contents were higher in fibrotic livers indicating the reduction in hepatic fatty acid oxidation and triglyceride export compared to control livers

David Price¹, Alan Bainbridge¹, Kevin Broad², Go Kawano², Igor Fierens², Mojgan Ezzati², Magdalena Sokolska³, Aaron Oliver-Taylor², Jamshid Rostami², Robert Sanders⁴, Ernest Cady¹, Xavier Golay⁵, and Nicola Robertson^2
1Dept Medical Physics & Bioengineering, UCLH NHS Foundation Trust, London, United Kingdom, ²Institute for Womens Health, University College London, London, United Kingdom, ³Dept. Medical Physics and Bioengineering, University College London, London, United Kingdom, ⁴Department of Anaesthesia & Surgical Outcomes Research Centre, University College London, London, United Kingdom, ⁵Institute of Neurology, University College London, London, United Kingdom

The aim of this study was to evaluate whether Argon is neuroprotective using a piglet model of perinatal asphyxia; based on 31P and 1H MRS cerebral biomarkers measured at 9.4T. Results showed a significant preservation of whole brain NTP/(exchangeable phosphate pool) at 48hrs post transient hypoxic ishaemia (HI) in a group exposed to 50% Argon plus therapeutic hypothermia (TH) versus a group exposed to TH alone. Neuroprotection occurred predominantly in the white matter as significantly reduced white matter Lac/NAA was observed at 24hrs and 48hrs post HI. Argon may provide a cheaper alternative to Xenon as an augmentation to TH.

Kamal Saba¹, Niharika Rajnala¹, Subhash Chandra Lakhotia², and Anant Bahadur Patel^1
1Centre for Cellular and Molecular Biology, Hyderabad, India, ²Department of Zoology, Banaras Hindu University, Varanasi, India

Alzheimer's disease (AD) is characterized by progressive dementia associated with β-amyloid plaque formation and intra-neuronal neurofibrillary tangles, and has no effective treatment. The present study evaluated the efficacy of Rasa-Sindoor (RS), an Ayurvedic medication, for the improvement of energy metabolism in AlCl₃ model of AD using ¹H-[¹³C]-NMR spectroscopy in conjunction with an infusion of [1,6-¹³C₂]glucose. Chronic AlCl₃ exposure led to reduction in memory and neuronal metabolic activity, which were restored to the control level by RS intervention. These data suggest that RS intervention has potential for the management of memory and metabolism in AD.

Sarah Sonnay¹, Nathalie Just², Rolf Gruetter^3,4, and João M.N. Duarte^1
1Laboratory of Functional and Metabolic Imaging (LIFMET), Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland, ²Center for Biomedical Imaging (CIBM), Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland, ³Center for Biomedical Imaging (CIBM) and Laboratory of Functional and Metabolic Imaging (LIFMET), Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland, ⁴Department of Radiology, University of Geneva and Lausanne, Switzerland

Brain energy metabolism is compartmentalized between neurons and astrocytes. However, the exact contribution of glial pathways coupled to neuronal metabolism during brain activity is still unclear. In this study, we investigated the contribution of glial and neuronal metabolic fluxes by direct ¹³C MRS in vivo during prolonged cortical activation and [1,6-¹³C]glucose infusion. The results indicate that focal brain activity increases both neuronal and glial oxidative metabolism, supporting neurotransmission.

Jonathan Lommen^1,2, Simon Konstandin^1,3, and Lothar R Schad^1
1Computer Assisted Clinical Medicine, Heidelberg University, Mannheim, Germany, ²Medical Physics in Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, ³MR-Imaging and Spectroscopy, Faculty 01 (Physics/Electrical Engineering), University of Bremen, Bremen, Germany

We propose a time-efficient modality for simultaneous B1 mapping and imaging. The phase-sensitive B1 mapping method, which was shown to yield the most accurate B1 maps for sodium MRI, is used. We compared the proposed method to the standard double-angle technique and found 13% higher SNR and only small B0 susceptibility. This protocol allows for faster and more accurate tissue sodium quantification (TSC) and could allow for a better clinical applicability of TSC quantification.

Bhavana S Solanky¹, Patricia Alves Da Mota¹, Ferran Prados², Torben Schneider¹, Frank Riemer¹, Wallace Brownlee¹, Francesco Grussu¹, Manuel Jorge Cardoso², Sebastian Ourselin², Hui Zhang³, David H Miller¹, Xavier Golay⁴, and Claudia A M Wheeler-Kingshott^1
1NMR Research Unit, Department of Neuroinflammation, Queen Square MS Centre, UCL, Institute of Neurology, London, England, United Kingdom,²Translational Imaging Group, CMIC, Department of Medical Physics & Biomedical Engineering, UCL, London, England, United Kingdom, ³CMIC, Department of Computer Science, UCL, London, England, United Kingdom, ⁴Brain Repair & Rehabilitation, Institute of Neurology, UCL, London, England, United Kingdom

Total sodium concentration, measured using 23Na-MRI, is made up of intra- and extra-cellular compartments. Separating these two compartments, to isolate the intracellular concentration, using 23Na-MRI is challenging and requires the use of complex, long, low resolution scans. Conversely, extracellular sodium in the human body is tightly regulated at 140mM, therefore, given knowledge of the intra and extra-cellular volume fractions of each voxel would enable intracellular sodium concentrations to be calculated. Here we exploit NODDI, which uses 1H-DWI to measure intraneurite, extraneurite and extracellular volume fractions, and combine this with sodium MRI to obtain intracellular and intraneurite sodium concentrations in vivo.

Stefan Zbyn¹, Vladimir Juras¹, Nadia Benkhedah², Olgica Zaric¹, Vladimir Mlynarik¹, Pavol Szomolanyi¹, Wolfgang Bogner¹, Armin M. Nagel², and Siegfried Trattnig^1
1High Field MR Center, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria, ²Department of Medical Physics in Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany

Manuela B. Rösler¹, Nadia Benkhedah¹, Armin M. Nagel¹, Peter Bachert¹, and Reiner Umathum^1
1Medical Physics in Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany

Potassium ions are of fundamental importance for the physiology of living organisms. First in vivo potassium (³⁹K) MR images of human muscle and brain have been published recently. We were able to acquire first ³⁹K in vivo TQF images of human thigh muscle with reasonably high resolution and in an acceptable total acquisition times. The achieved signal intensity was in the expected range. In addition, we determined in vivo the slow component of transverse relaxation time constant of ³⁹K in human thigh muscle T_2s^* = (8.6 ± 0.3) ms, which due to oscillations in the T₂^*-decay was not yet possible.

Christian Mirkes^1,2, G. Shajan¹, Jonas Bause¹, Kai Buckenmaier¹, Jens Hoffmann¹, and Klaus Scheffler^1,2
1High-Field MR Center, Max Planck Institute for Biological Cybernetics, Tuebingen, BW, Germany, ²Department for Biomedical Magnetic Resonance, University of Tübingen, BW, Germany

Sodium triple-quantum-filtering (TQF) is challenging at ultra-high field due to the high specific absorption rate. In order to alleviate this problem, the feasibility to modulate the flip angle of the TQ preparation along the partition-encoding direction was investigated. As demonstrated by simulations, this approach allowed to increase the efficiency and sensitivity of the TQ acquisition. TQF images of the human brain could be acquired at 9.4 T within 20 min with an acceptable signal-to-noise ratio.

Robert Borowiak^1,2, Dmitry Kurzhunov², Philipp Wagner², Marco Reisert², and Michael Bock^2
1German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany, ²Dept. of Radiology · Medical Physics, University Medical Center Freiburg, Freiburg, Baden-Württemberg, Germany

In this work we demonstrate for the first time in two experiments at nominal resolutions of 10/ 8 mm and for a temporal resolution of 1 min the feasibility of direct dynamic ¹⁷O-MRI at a clinical field strength of 3 Tesla. The measurement setup included a transmit\receive ¹⁷O head coil and a dedicated re-breathing system for efficient supply of 70%-enriched ¹⁷O gas. For gray matter and white matter and for a voxel size of 10 mm CMRO₂ values of 1.59 ± 0.16 and 0.71 ± 0.07 [µmol/g*min] were found to be in good agreement with PET literature values.

Guillaume Madelin¹, Ryan Brown¹, and Linda Moy^1
1Department of Radiology, New York University Langone Medical Center, New York, NY, United States

We propose to develop a method based on sodium MRI in vivo to estimate the (pseudo) intracellular sodium concentration (C1) and extracellular volume fraction (alpha2) in breast at 3T. These two parameters could give new quantitative biochemical information on cell viability and ion homeostasis in breast tissue non-invasively. Changes in C1 and alpha2 can correlate with angiogenesis and cell proliferation, which are characteristics of tumor malignancy and aggressiveness. The goal of this project is to increase the specificity of breast cancer screening in order to reduce overdiagnosis and overtreatment.

Paul W. de Bruin¹, Maarten J. Versluis², Peter Koken³, Sebastian A. Aussenhofer¹, Wouter den Hollander⁴, Ingrid Meulenbelt⁴, Peter Börnert^1,3, and Andrew G Webb^1
1Radiology, Leiden University Medical Center, Leiden, Netherlands, ²Philips Healthcare, Eindhoven, Netherlands, ³Philips Research Hamburg, Germany,⁴Medical Statistics and Bioinformatics, Molecular Epidemiology, Leiden University Medical Center, Netherlands

Interleaving ²³Na and ¹H reduces scan acquisition time. In this work we combine four scans: a ¹H Dixon, a ¹H T₂^*, and two ²³Na scans with and without long T₂-suppression prepulse for sodium content quantification. Using interleaving reduces scan time for these four scans from 39 minutes to 24 minutes.

Miho EMOTO¹, Shingo Sato², and Hirotada G Fujii^1
1Center for Medical Education, Sapporo Medical University, Sapporo, Hokkaido, Japan, ²Graduate school of Science and Engineering, Yamagata University, Yamagata, Japan

The new medical approach using �gtheranostics�h, defined as use of materials for both therapy and diagnostic imaging, can be designed to offer targeted, safe, and efficient pharmacotherapy. In this study, theranostics were designed for MRI and EPR imaging and used to treat septic mice. EPR images show that the novel theranostic probes work well as brain imaging probes for septic mice. Biochemical assays of generated NO in the septic mouse brain indicate that the novel theranostic probes function as anti-inflammatory drugs. The novel theranostics acted as therapeutic compounds as well as diagnostic EPR and MRI imaging probes.

Human Brain MRS

Thursday 4 June 20155

Marianne Cleve¹, Alexander Gussew¹, Lisa Janetzki², Constanze Borys², and Jürgen R. Reichenbach^1
1Medical Physics Group, Institute of Diagnostic and Interventional Radiology, Jena University Hospital - Friedrich Schiller University Jena, Jena, Germany,²Institute of Psychosocial Medicine and Psychotherapy, Jena University Hospital, Jena, Germany

We applied MR spectroscopy in 25 healthy volunteers measuring Glu and GABA to investigate potential metabolic associations between brain regions revealing functional connectivity in the resting state. Significant positive correlations (p < 0.05) of Glu levels were observed between PC and ACC and between PC and Ins as well as a trend towards positive correlation (p < 0.1) between Ins and ACC. Negative associations of Glu and GABA levels were identified between ACC and Ins as well as between PC and Ins. These findings suggest a close interrelation between functional neuronal networks and the excitatory and inhibitory neurotransmitters.

Miguel Martínez-Maestro¹, Maria Guidi¹, Laurentius Huber¹, Štefan Holiga¹, Jöran Lepsien¹, Henrik Marschner¹, Harald E. Möller¹, and Christian Labadie^1
1Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany

In this fMRS study with PRESS TE 30 ms at 3T, a block design alternating 30 sec rest (R) and 30 sec visual activation (A) was averaged 16 times during 16.7 min. The BOLD effect was canceled by estimating concentrations with water references acquired with the same paradigm (averaged 4 times). We observed no significant concentration changes: glutamate (R: 5.60 ± 0.06 mM, A: 5.65 ± 0.07 mM), GABA (R: 1.50 ± 0.04 mM, A: 1.49 ±0.06 mM), and lactate (R: 0.42 ± 0.07 mM, A: 0.39 ±0.05 mM). Despite the large variation of the data, a slight increase of glutamate during activation is in agreement with previous studies.

Ashley D Harris^1,2, Nicolaas AJ Puts^1,2, Brian A Anderson³, Steven Yantis³, James J Pekar^1,2, Peter B Barker^1,2, and Richard A. E. Edden^1,2
1The Russell H Morgan Department of Radiology and Radiological Sciences, The John Hopkins School of Medicine, Baltimore, MD, United States, ²F.M. Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, ³Department of Psychological and Brain Sciences, The Johns Hopkins University, Baltimore, MD, United States

The relationship between measured GABA and BOLD activation is examined in 5 regions with 5 relevant tasks. We do not replicate previously observed correlations. This appears to indicate additional complexity not shown in previous models or underlying confounds.

Candace C. Fleischer^1,2, Xiaoping Hu^1,2, Andrew H. Miller^3,4, and Ebrahim Haroon^3,4
1Biomedical Imaging Technology Center, Emory University, Atlanta, GA, United States, ²Biomedical Engineering, Emory University, Atlanta, GA, United States, ³Psychiatry and Behavioral Sciences, School of Medicine, Emory University, Atlanta, GA, United States, ⁴Winship Cancer Institute, Atlanta, GA, United States

Chronic inflammation and immune system activation are believed to be at the basis of many neurological and behavioral disorders. We hypothesize that the link between inflammation and resulting behaviors is a dysregulation of neurotransmitters such as glutamate. We report a study of 53 subjects diagnosed with major depression, categorized into three inflammation groups based on serum C-reactive protein levels. Using multi-voxel MRS, we show that subjects with high inflammation, compared to low or average inflammation, have significantly higher concentrations of glutamate/creatine and myo-inositol/creatine. These findings will provide valuable insight into the immunological basis of neuropsychiatric disorders for developing future treatments.

Fei Gao¹, Bin Zhao¹, Guangbin Wang¹, Wen Ma², Muwei Li³, Fuxin Ren¹, Bo Liu¹, Weibo Chen⁴, and Richard A.E. Edden^5,6
1Shandong Medical Imaging Research Institute, Shandong University, Jinan, China, ²The Central Hospital of Jinan City, Shandong University, Jinan, China,³College of Electronics and Information Engineering, Sichuan University, Chengdu, China, ⁴Philips Healthcare, Shanghai, China, ⁵Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, MD, United States, ⁶FM Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, MD, United States

Reduced GABA levels were found in auditory regions of patients with presbycusis. Significant negative relations between GABA level and auditory function were found.

Alexander Peter Lin¹, Sai Krishna Merugumala^1,2, Vera Anastosie³, Stephanie Couchell³, Xi April Long¹, Huijun Vicky Liao¹, and Susan Waisbren^3
1Center for Clinical Spectroscopy, Brigham and Women's Hospital, Boston, MA, United States, ²Texas Tech University Health Sciences Center, Lubbock, TX, United States, ³Metabolism Research, Boston Children’s Hospital, Boston, MA, United States

In patients with Phenylketonuria (PKU) the blood Phenylalanine (Phe) level is not always a direct indicator of neurological and neuropsychological deficits. Measuring the Phe concentration in the brain noninvasively with MRS provides a more direct assessment of the severity of the disease in patients with PKU. Nine subjects with early treated classic PKU underwent a protocol that included 2D COSY MRS. The Phe resonance from the 2D COSY spectrum allows the measurement of Phe in the brain directly with less signal contamination from other brain metabolites.

Subash Khushu¹, Sadhana Singh¹, Poonam Rana¹, Pawan Kumar¹, and L Ravi Shankar^2
1NMR Research Centre, INMAS, DRDO, Delhi, Delhi, India, ²Thyroid Research Centre, INMAS, DRDO, Delhi, Delhi, India

The aim of our study was to investigate metabolic alterations in the brain of adult hypothyroid patients using in-vivo proton magnetic resonance spectroscopy (1H MRS). 1H MRS was performed in both control and hypothyroid subjects (N = 12). Our results revealed significant decrease of glutamate and myoinositol levels in the hippocampus of hypothyroid patients as compared to controls. These findings suggest that the metabolic alterations in the hippocampus region of brain may contribute to underlying dysfunction in memory in hypothyroidism.

Bo Liu¹, Bin Zhao¹, Guangbin Wang¹, Fei Gao¹, Zhensong Wang¹, and Weibo Chen^2
1Shandong Medical Imaging Research Institute, Shandong University, Jinan, Shandong, China, ²Philips Healthcare, Shanghai, China

Thyroid hormones play a critical role in the adult brain impacting mood and cognition. The accumulated evidence has indicated that thyroid hormones have effects on the¦Ã-aminobutyric acid (GABA) system, the main inhibitory neurotransmitter in human brain . MEGA-PRESS sequence was used to investigate whether hypothyroidism is associated with alterations in GABA levels. For the first time, we found decreased ACC/mPFC GABA+ levels in hypothyroidism women compared to controls. Altered GABA neurotransmission may be an important neurobiological mechanism underlying neuropsychiatric and cognitive changes in hypothyroidism. Our preliminary findings could help to better understand thyroid-brain interaction in hypothyroidism.

Nuttawadee Intachai¹, Artit Rodkong¹, Suwit Saekho^1,2, Napapon Sailasuta³, Apinun Aramrattanan⁴, Kanok Uttawichai⁵, Mekkla Thomson⁶, Bangorn Sirirojn ⁷, Daralak Thavornprasit⁷, Sineenart Taejaroenkul⁷, Kamolrawee Sintupat⁷, Victor Valcour⁸, and Robert Paul^9
1Department of Radiological Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand, ²Biomedical Engineering Center, Faculty of Engineering, Chiang Mai University, Chiang Mai, Thailand, ³Huntington Medical Research Institute, California, United States,⁴Department of Family Medicine, Faculty of medicine, Chiang Mai University, Chiang Mai, Thailand, ⁵Thanyarak Hospital, Chaing Mai, Thailand, ⁶Westat, Maryland, United States, ⁷Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand, ⁸Department of Neurology, University of California, San Francisco, California, United States, ⁹Department of Psychology, Behavioral Neuroscience, University of Missouri-St.Louis, St. Louis, United States

The study aims to explore the association between the change of MRS in 4 voxel locations and the change of brain morphology at the same brain region in MA users and HC. The results show that significant increase or decrease of metabolites in MA correlated to the change of brain morphology.

Mona A Mohamed¹, Peter B Barker¹, Richard L Skolasky², Heidi Vornbrock Roosa³, and Ned Sacktor^3
1Radiology, Johns Hopkins Medical Institutions, Baltimore, MD, United States, ²Orthopedic Surgery, Johns Hopkins Medical Institutions, MD, United States,³Neurology, Johns Hopkins Medical Institutions, MD, United States

Synopsis: Using 7T MRS, more reliable in vivo determination of brain metabolites concentrations (in particular, compounds such as glutamate and glutamine) can be achieved than at lower field strengths. In this study, the feasibility of measuring multiple brain metabolites in 5 different brain regions in patients with HIV infection is demonstrated. Differences between brain metabolites support glial cell proliferation in HIV+ patients and neuronal white matter involvement in patients with symptomatic HIV associated cognitive impairment.

Dandan Zheng¹, Bing Wu¹, Huimao Zhang², Jue Zhang³, and Zhenyu Zhou^1
1GE Healthcare China, Beijing, Beijing, China, ²Radiology Department, The First Hospital of Jilin University, Changchun, Jilin, China, ³Peking University, Beijing, China

MELAS is one of the most common multisystem mitochondrial disorders. It is characterized by disorders in mitochondrial function due to point mutations of mitochondrial DNA. However, the underlying mechanism of MELAS has not been fully elucidated. DWI and MRS have respectively been demonstrated to be viable tools to study the physiopathology of the stroke-like events in MELAS patients. Diffusion weighted MRS permits the evaluation of the intrinsic diffusion properties of the metabolites that may provide valuable information understanding of pathphysiological process. In this study, the DWMRS is used to probe the mechanisms underlying the pathogenesis of MELAS.

Jannie P. Wijnen^1,2, Ronald Zielman³, Gerrit L.J. Onderwater³, Andrew Webb², Gisela M. Terwindt³, Michel Ferrari³, Hermien E. Kan², and Mark C. Kruit^2
1University Medical Centre Utrecht, Utrecht, Utrecht, Netherlands, ²Radiology, Leiden University Medical Centre, Leiden, Zuid Holland, Netherlands,³Neurology, Leiden University Medical Centre, Leiden, Zuid Holland, Netherlands

In this study we assessed the interictal (between attacks) glutamate concentrations of migraine patients with and without aura and compared the concentrations to age and gender matched healthy controls. Ultra high field Magnetic Resonance Spectroscopy (7Tesla) of the visual cortex was performed in 27 migraine patients without aura, 23 migraine patients with aura and 24 controls. Linear regression of between subject effects was performed on the glutamate concentration with the fraction of gray matter (GM) in the voxel as covariate. This analysis revealed interictal elevated glutamate concentrations in patients with migraine without aura. At ultra-high field, glutamate can be robustly detected, which opens opportunities to study the role of glutamate in migraine in more detail.

Izabela Aleksanderek^1,2, Todd K Stevens², Sandy Goncalves^1,2, Robert Bartha^1,2, and Neil Duggal^1,3
1Medical Biophysics, Western University, London, Ontario, Canada, ²Robarts Research Institute, London, Ontario, Canada, ³University Hospital, LHSC, London, Ontario, Canada

The ideal timing of surgical intervention for cervical spondylotic myelopathy (CSM) patients, especially with early, mild symptoms, remains particularly controversial. Surgical intervention did not reverse the metabolic profile in mild CSM, nor did it preserve the normal metabolite level in moderate CSM. Mild CSM recruited surrounding cortex to enhance motor task performance prior to surgery. The neurological recovery experienced by moderate CSM could be associated with cortical reorganization which equalized to that observed in mild CSM. We propose that metabolic impairment in the primary motor cortex may trigger recruitment of adjacent healthy cortex to achieve functional recovery following successful surgery.

Ruoyun Ma^1,2, Anne Lotz³, and Ulrike Dydak^1,2
1School of Health Sciences, Purdue University, West Lafayette, Indiana, United States, ²Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, United States, ³Center of Epidemiology, Institute for Prevention and Occupational Medicine of the DGUV, Institute of the Ruhr-Universitӓt Bochum, Bochum, Germany

Measuring brain GABA levels is of high interest in studying Manganese (Mn) neurotoxicity in exposed subjects. Yet, Mn may decrease the T1 relaxation time of GABA and thus confound concentration changes. In this phantom study the effects of Mn2+ on T1 relaxation time of GABA, NAA and Cr were studied. No significant effect of Mn on GABA and Cr was observed. However T1 of water and of NAA decreased significantly with increasing Mn concentration. These results suggest that GABA and GABA/Cr measured by MEGA-PRESS may be used to indicate actual concentration changes in brain GABA levels due to Mn exposure.

Anirudha S. Rathnam¹, Jasloveleen Sohi², Dalal Khatib³, Jeremy J. Laukka⁴, John Kamholz^2,5, and Jeffrey Stanley^3
1Wayne State University School of Medicine, Detroit, Michigan, United States, ²Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Michigan, United States, ³Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Michigan, United States, ⁴Neurosciences, The University of Toledo, Ohio, United States, ⁵Psychiatry, University of Iowa Carver College of Medicine, Michigan, United States

Pelizaeus-Merzbacher disease (PMD) is an X-linked recessive leukodystrophy of the CNS caused by mutations affecting the major myelin protein, proteolipid protein 1 (PLP1). To better understand the cellular pathogenesis caused by PLP1 duplications, ³¹P magnetic resonance spectroscopy (31P MRS) was used for the first time to assess high-energy phosphate and membrane phospholipid (MPL) metabolism. Results showed significant and widespread increased phosphocreatine (PCr) and decreased glycerophosphocholine (GPC), as well as some significantly increased β-ATP. Results may indicate an environment of chronic hypoxia or a decreased demand in energy among PMD patients.

Xiaoyu Jiang¹, Hua Li¹, Ping Zhao¹, Jingping Xie¹, Stephanie L. Barnes¹, Thomas Yankeelov¹, Junzhong Xu¹, and John C. Gore^1
1Institute of Imaging Science, vanderbilt university, nashville, Tennessee, United States

ADC measured with pulse gradient spin echo methods is insensitive to subcellular structural changes due to the use of long diffusion time. Also the measured ADC is influenced by multiple morphological parameters, such as cell size, density and membrane permeability, resulting in an insufficient specificity for characterization of a single structural parameter. Here we show that temporal diffusion spectroscopy, which measures the variation of apparent diffusion coefficient (ADC) over a wide range of effective diffusion times, can quantify tumor microstructural variations in response to chemotherapy, and hence may serve as a specific and early imaging biomarker of tumor therapeutic response.

A. J. Bakermans¹, A. J. Nederveen¹, C. E. M. Hollak², J. Booij³, A. M. Bosch⁴, L. J. Bour⁵, S. C. J. Huijbregts⁶, R. Jahja⁷, F. J. van Spronsen⁷, D. H. Nieman⁸, N. G. G. M. Abeling⁹, and E. Boot^3
1Department of Radiology, Academic Medical Center, Amsterdam, Netherlands, ²Department of Internal Medicine, Academic Medical Center, Amsterdam, Netherlands, ³Department of Nuclear Medicine, Academic Medical Center, Amsterdam, Netherlands, ⁴Department of Pediatrics, Academic Medical Center, Amsterdam, Netherlands, ⁵Department of Neurology, Academic Medical Center, Amsterdam, Netherlands, ⁶Department of Clinical Child and Adolescent Studies, Leiden University, Leiden, Netherlands, ⁷Department of Metabolic Diseases, University Medical Center Groningen, Groningen, Netherlands,⁸Department of Psychiatry, Academic Medical Center, Amsterdam, Netherlands, ⁹Laboratory Genetic Metabolic Diseases, Academic Medical Center, Amsterdam, Netherlands

A noninvasive assessment of brain phenylalanine (Phe) levels is instrumental for investigations of phenylketonuria (PKU). Here, we used ¹H-MRS at 3 Tesla to measure brain Phe levels in PKU patients. We calculated difference spectra by subtracting an averaged baseline control spectrum (n = 5) from the PKU patient spectra (n = 14), and determined the area under the residual Phe peak at 7.37 ppm. Brain Phe levels were higher in PKU patients compared to controls (P = 0.00015), and correlated with plasma Phe concentrations (r = 0.74, P = 0.003). ¹H-MRS offers a feasible readout of cerebral metabolism in PKU.

Florian Schubert¹, Ralf Mekle¹, Bernd Ittermann¹, and Markus Bock^2
1Physikalisch-Technische Bundesanstalt, Berlin, Germany, ²ECRC, Charité Universitätsmedizin, Berlin, Germany

We studied the effect of ketogenic diet in human brain by quantifying beta-hydroxybutyrate (bHb), acetoacetate (AcAc), acetone (Ac) and glucose in two cortical voxels by MRS at 3T during mixed diet (M), ketogenic diet (K) and fasting (F). SPECIAL spectra (TE=8.5ms) were analyzed using LCModel with a basis set including the ketone bodies. Ketone bodies increased during ketogenic diet and were highest at fasting, with decreasing Glc. T-tests gave p<0.05 for changes in Glc (M>F, K>F) and bHb, AcAc and Ac (F>K). The method is tested to stratify patients in terms of response to ketogenic diet in neurological disorders.

William E. Wu¹, Marc Sollberger², Lidia Glodzik³, Andreas U. Monsch², Achim Gass⁴, and Oded Gonen^1
1Radiology, New York University School of Medicine, New York, NY, United States, ²Neurology and Neuroradiology, University Hospital Basel, Basel, Switzerland, ³Psychiatry, New York University School of Medicine, New York, NY, United States, ⁴Neurology, University of Heidelberg, Mannheim, Germany

Societal and economic burden to U.S. healthcare from neurological disorders in the elderly is expected to become staggering. It is therefore advisable to develop non-invasive biomarkers that can identify brain disease at its earliest, most treatable stage and monitor therapy response. Since brain disease often targets neurons, we measured their MR spectroscopic marker – N-acetylaspartate (NAA) – in the whole brain (WBNAA) using an automated, full spectral modeling method, and compared WBNAA in 41 cognitively-intact elderly versus in 20 young controls. We found no evidence of significant difference in mean WBNAA despite the effects of ›35 years of normal aging.

Zaiyang Long¹, Jonathan P Dyke², Ruoyun Ma^3,4, Chaorui C Huang⁵, Elan D Louis^6,7, and Ulrike Dydak^3,4
1Department of Radiology, Mayo Clinic, Rochester, MN, United States, ²Department of Radiology, Weill Cornell Medical College, New York, NY, United States, ³School of Health Sciences, Purdue University, West Lafayette, IN, United States, ⁴Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, United States, ⁵Brain and Mind Research Institute, Weill Medical College of Cornell University, New York, NY, United States, ⁶College of Physicians and Surgeons, Columbia University, New York, NY, United States, ⁷Mailman School of Public Health, Columbia University, New York, NY, United States

This study aimed to explore the feasibility and reproducibility of GABA MRS in the aging cerebellum at 3T and to examine the effect of voxel compartments on 10 healthy elderly volunteers (mean age 75.2 years). 5 subjects were scanned twice to assess short-term reproducibility. The MEGA-PRESS sequence was used for GABA detection in left and right cerebellar dentate. Averaged coefficients of variation for all GABA measurements within each individual ranged from 5.0 % to 14.1 %. Cerebral spinal fluid- and relaxation-corrected GABA significantly correlated with uncorrected GABA measurements. This information might be useful for studying GABA changes in aging brains.

Ben Babourina-Brooks^1,2, Theodoros N Arvanitis^2,3, Andrew C Peet^1,2, and Nigel P Davies^1,4
1School of Cancer Sciences, University of Birmingham, Birmingham, West Midlands, United Kingdom, ²Birmingham Children's Hospital NHS Foundation Trust, Birmingham, West Midlands, United Kingdom, ³3Institute of Digital Healthcare, WMG, University of Warwick, Coventry, West Midlands, United Kingdom, ⁴Imaging & Medical Physics, University Hospitals Birmingham NHS Foundation Trust, West Midlands, United Kingdom

The aim of this study was to investigate the MRS water proton resonance frequency (PRF) differences found among childhood brain tumours by combining with ADC measures from DWI. MRS can provide a measure of the water PRF relative to reference metabolite peaks, which is sensitive to temperature and micro-environmental factors. Separating the factors affecting the PRF is challenging but may provide unique measures to aid in tumor characterization. Correlating the ADC, a known marker for cellular density, with the water PRF will aid in the understanding of the measure and it's clinical potential.

Malgorzata Marjanska¹, J. Riley McCarten², Laura S Hemmy², and Melissa Terpstra^1
1Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, United States, ²Minneapolis VA Medical Center, Geriatric Research and Clinical Center, MN, United States

The resonances originating from high-molecular weight macromolecules (MM) underlie those of metabolites in brain ¹H NMR spectra. These resonances have different physical properties from those of metabolites such as shorter T₁ and T₂. In this study, we utilized a uniquely high field of 7 T to investigate differences in the MM pattern in the aging brain. We found that MM pattern in clearly different in elderly compared to young human subjects. This important finding suggests that when a measured MM spectrum is used in the basis set for metabolite quantification, it should be measured from an age matched cohort.

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

We report in vivo 1H spectroscopy of Glutamate (Glu), Glutamine (Gln), -aminobutyric acid (GABA), Glycine (Gly) and other metabolites in human brain using PRESS at 7T. With test- retest experiment, we present the ability to reliably detect and quantify these technically challenging metabolites. Coefficient of variances were smaller than 0.03 for most of the metabolites and intra-class correlations of GABA and Gly were higher than 0.90 while Glu and Gln were slightly lower (0.81 and 0.88). CRLBs were 2-3% for Glu, 4% for Gln, 8% for GABA and 6% for Gly.

Dinesh K Deelchand¹, Kejal Kantarci², Lynn E Eberly³, and Gulin Oz^1
1Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, United States, ²Department of Radiology, Mayo Clinic, Rochester, MN, United States, ³Division of Biostatistics, University of Minnesota, Minneapolis, MN, United States

Proton MR spectra were measured using sLASER with FAST(EST)MAP (FM) shimming and vendor-provided PRESS with advanced 3D shimming from the posterior cingulate cortex in 30 healthy elderly subjects at 3T. Clinical MR technicians were trained to run these protocols in randomized order. Similar spectral patterns were observed with both sequences, although the spectral linewidth was broader with the PRESS protocol. Quantification precision was higher with the sLASER+FM protocol. These findings suggest that an advanced MRS protocol can be utilized in the clinical setting by trained MR technicians, however further automation is needed.

SV MRS Acquisition Methods

Thursday 4 June 20155

Zhengsong Wang^1,2, Caroline Rae³, Guangqiang Geng⁴, Weibo Chen⁵, Fei Gao¹, Bo Liu¹, Jie Gan², Xue Bai⁶, Bin Zhao¹, and Guangbin Wang^1
1Shandong Medical Imaging Research Institute, Shandong University, Jinan, Shandong, China, ²Second Affiliated Hospital of Shandong university of Traditional Chinese Medicine, Jinan, Shandong, China, ³Neuroscience Research Australia,UNSW, Sydney, Australia, ⁴Philips Healthcare MR R&D, Suzhou, Jiangsu, China,⁵Philips Healthcare, Shanghai, China, ⁶QIlu Hospital, Shandong University, Jinan, Shandong, China

¦Ã-Aminobutyric acid (GABA), the major inhibitory neurotransmitter in brain, is present at low millimolar concentrations and is difficult to resolve at 3T due to resonance couplings and overlap. Several different methods have been proposed, the most commonly used of which involves use of selective editing (MEGA) along with PRESS, SPECIAL or Semi-LASER. Recently, a single-shot method optimized for GABA using an asymmetric PRESS variant (TE1 = 30 ms; TE2 = 75 ms) has been described. Here, we tested this method alongside standard MEGA-PRESS acquisitions.

Dimitri Martel¹, Dany Merhej², Remy Prost¹, Denis Friboulet¹, and Helene Ratiney^1
1CREATIS; CNRS UMR 5220; INSERM U1044; Université Lyon 1; INSA Lyon, Villeurbanne, France, ²ISAE CNAM, Beirut, Lebanon

Localized Correlation Spectroscopy is a 2D MRS method which allows acquisition of high resolved spectrum, which can have the property to be sparse, but at the cost of long acquisition time. Reducing this time is crucial for application but leads to a reduced quantitatification accuracy. The aim of this work is to evaluate a relevant non uniform sampling scheme for this method using sequential backward selection (SBS) in the LCOSY time domain indirect dimension.The feasibility to use such sampling for quantification purpose on in vivo data acquired in the adipose tissue of an obese mouse is demonstrated.

Zhiliang Wei¹ and Zhong Chen^1
1Department of Electronic Science, Xiamen University, Xiamen, Fujian, China

MRS serves an important tool for analyzing biological metabolites and medical treatments. Unfortunately, in vivo study inevitably suffers from magnetic-field inhomogeneity. In this study, a method addressed as line broadening interference (LBI) is proposed to provide high-resolution information under inhomogeneous fields by correlating the field inhomogeneity with gradients and recovering high-resolution information with the aid of an inhomogeneity correction algorithm. Experiments have been carried out on chemical solution to prove the principle and feasibility of LBI. It offers important perspectives for in vivo analyses of living inhomogeneous organisms.

Robin A. de Graaf¹, Henk M. De Feyter¹, and Douglas L. Rothman^1
1MRRC, Yale University, New Haven, CT, United States

13C MRS is hampered by an intrinsically low NMR sensitivity and high RF power deposition, which has largely prevented 13C MRS at high magnetic fields. 2D HSQC is a high sensitivity alternative that achieves intrinsic, broadband 1H decoupling and retains the high chemical specificity of direct 13C MRS. TR variation, in combination with controlled aliasing, was used to accelerate 2D NMR data acquisition 11.8-fold (or 2.4 min per average). High-quality, high-sensitivity 2D HSQC spectra were obtained from human leg adipose tissue at 7T. The detection of 19 unique resonances allowed detailed lipid characterization. 2D HSQC has strong potential to become a default method in natural-abundance or 13C-enriched studies of human metabolism in vivo.

Jamie Near^1,2 and Chathura Kumaragamage^3
1Department of Psychiatry, McGill University, Montreal, Quebec, Canada, ²Centre d'Imagerie Cérébrale, Douglas Institute, Montreal, Quebec, Canada,³Department of Biomedical Engineering, McGill University, Montreal, Quebec, Canada

In-vivo brain GABA levels are commonly detected using the localized J-difference editing method, MEGA-PRESS, in which the echo time is normally fixed at 68 ms. Here, we describe a modification to the conventional J-difference editing scheme to enable detection of GABA with extended echo times (≥115 ms), and with no loss in editing efficiency. This method may provide a simplified framework for the routine measurement of GABA T2 values. Furthermore the use of long echo times may enable the removal of macromolecule (MM) contamination from J-difference edited GABA measures, owing to the short T2 of MM.

Mohammad Abdi-Shektaei¹, Abbas Nasiraei Moghaddam^1,2, Rajakumar Nagarajan³, and M. Albert Thomas^3
1BME, Amirkabir University of Technology (Tehran Polytechnic), Tehran, Tehran, Iran, ²School of Cognitive Sciences, Institute for Research in Fundamental Sciences (IPM), Tehran, Iran, ³Radiological Sciences, UCLA School of Medicine, Los Angeles, CA, United States

To address the long signal acquisition problem due to iterative phase encoding along indirect time dimension in Localized Correlated Spectroscopy (L-COSY), a novel reconstruction method is introduced. The proposed method takes the advantage of high sparsity of L-COSY spectra for deterministic subsampling as reconstruction priors to find the location of diagonal and cross peaks. The amplitude of diagonal and cross peaks then is estimated through iterative Least-Square problem. Preliminary application of this method on phantom and in vivo data demonstrates its ability to the successfully reconstruct cross peaks which are of much greater interest in L-COSY.

Gaurav Verma¹, Michael Albert Thomas², and Harish Poptani^1
1Radiology, University of Pennsylvania, Philadelphia, PA, United States, ²Radiology, University of California at Los Angeles, Los Angeles, CA, United States

Two-dimensional localized correlated spectroscopy (2D L-COSY) offers the capacity to uniquely resolve more metabolites than conventional 1D techniques at the cost of longer scan times. This study aims to improve the acquisition efficiency and versatility of L-COSY by implementing average-weighting schemes matched to signal intensity expected from each ∆t1 increment. In three human brain studies and ten phantom studies, 12:48 duration average-weighted L-COSY sequences produced SNR comparable to uniformly-averaged sequences of 17:04 duration. Potential for further improvements in SNR through the selective emphasis of particular metabolites was also demonstrated. These enhancements could improve the clinical viability of 2D spectroscopy.

Brennen J. Dobberthien¹, Anthony G. Tessier^1,2, B. Gino Fallone^1,2, and Atiyah Yahya^1,2
1Department of Oncology, University of Alberta, Edmonton, Alberta, Canada, ²Department of Medical Physics, Cross Cancer Institute, Edmonton, Alberta, Canada

The levels of glycine (Gly) can be measured by magnetic resonance spectroscopy (MRS). However, its resonance is overlapped by that of myo-inositol (mI), even at 9.4 T. The presented work optimizes TE1 and TE2 (echo times) of a Point RESolved Spectroscopy (PRESS) sequence to minimize mI signal in the Gly spectral region by exploiting the J-evolution of the strongly-coupled mI protons. Signal from uncoupled spins of Gly at 3.55 ppm is retained. Using phantom solutions, the optimal {TE1, TE2} combination was found to be {60 ms, 100 ms}. The efficacy of the timings was verified on rat brain in vivo.

Mohammad Abdi-Shektaei¹, Felix Raschke², Franklyn A Howe³, and Abbas Nasiraei Moghaddam^1,4
1BME, Amirkabir University of Technology (Tehran Polytechnic), Tehran, Tehran, Iran, ²Radiological Sciences, Division of Clinical Neuroscience, University of Nottingham, Nottingham, United Kingdom, ³Cardiovascular and Cell Sciences Research Institute, St George's, University of London, London, United Kingdom,⁴School of Cognitive Sciences, Institute for Research in Fundamental Sciences (IPM), Tehran, Iran

Long acquisitions in 1H-MRSI that prevents its widespread clinical application can be accelerated with Compressive Sensing (CS). CS can reliably reconstruct MRSI data from non-uniform randomly subsampling of k-space through meaningful selection of regularizers that consider spars nature of MRS signals. In this work CS was implemented based on spatial-spectral sparsity of 1H-MRSI. Total Variation of spatial domain and L1 norm of spectra were considered in reconstruction. The study of 10 patients with glioma was performed for proposed method. Acceleration factors up to 3X were demonstrated to preserve metabolite content of spectra and abnormal boundaries of tumors.

Meng Gu¹, Ralph Hurd², Ralph Noeske³, Ariel Rokem⁴, Laima Baltusis⁵, and Daniel Spielman^1
1Radiology, Stanford University, Stanford, California, United States, ²GE Healthcare, Menlo Park, California, United States, ³MR Application & Workflow Development, GE Healthcare, Berlin, Germany, ⁴Psychology, Stanford University, Stanford, California, United States, ⁵Center for Cognitive and Neurobiological Imaging, Stanford University, Stanford, California, United States

A macromolecule suppressed GABA editing sequence based on single spin echo MEGA-SPECIAL is introduced, using 1D echo planar (EP) SIAM. EP-SIAM is employed as a sensitive point method for reducing the spatial subtraction burden created by the 1D ISIS component of the SPECIAL localization method. The technique was validated using a GABA phantom, a lysine phantom to represent the appropriate macromolecule fraction, as well as in vivo. GABA spectra from the striatum illustrated the impact of EP-SIAM. The macromolecule suppression was 93% and the retained GABA signal was 98%.

Chen Chen¹, Peter Morris¹, Susan Francis¹, and Penny Gowland^1
1Sir Peter Mansfield Imaging Centre (SPMIC), University of Nottingham, Nottingham, Nottinghamshire, United Kingdom

This study demonstrates that it is feasible to determine brain Lac concentration at 7T (B1,max=15uT) with conventional long TE approaches (TE=144 ms) with and without spectral editing, in a short acquisition time (~6 mins), using the optimised sLASER sequence. The optimised sLASER sequence uses wide bandwidth offset independent trapezoid (OIT) pulses (BW=4.8 kHz) to minimise the effect of the chemical shift displacement artefact (CSDA) on J-modulation of the weakly-coupled Lac spins. In addition, this work suggests that MEGA-sLASER gives better reproducibility.

Karim Snoussi^1,2, Subechhya Pradhan^1,2, Ashley D. Harris^1,2, Richard A.E. Edden^1,2, and Peter B. Barker^1,2
1Russel H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medidine, Baltimore, Maryland, United States,²Kennedy Krieger Institute, Johns Hopkins University, Baltimore, Maryland, United States

Editing with MEGA-PRESS at 3 Tesla is often used for the detection of GABA in the human brain; these experiments also usually co-edit a certain amount of glutamate and glutamine (Glx). This abstract explores variation in editing-pulse frequencies, using both simulations and experiments, in the MEGA-PRESS sequence in order to optimize the detection of both GABA and Glx simultaneously. It is demonstrated in vivo that this approach can be used to substantially increase the amplitude of the Glx signal compared to commonly used frequencies, without much loss in GABA-editing efficiency.

Alessandra Toncelli¹, Ralph Noeske², Mauro Costagli³, and Michela Tosetti^3,4
1INFN and Department of Physics, University of Pisa, Pisa, Italy, ²GE Healthcare, Berlin, Germany, ³Fondazione Imago7, Italy, ⁴Stella Maris Scientific Institute, Italy

A voxel-based implementation of the Bloch-Siegert phase shift method within a standard spectroscopy STEAM-based localization sequence that shows a high robustness to determine transmit gain (TG) for the same volume that is excited for the spectroscopy experiment is demonstrated at 7T. Phantom and in-vivo measurements show higher robustness over a large range of initial TG settings and voxel locations compared to a previously proposed PRESS-based approach resulting in a faster and more reliable calibration procedure to achieve good voxel selection and spectrum quality.

Ioannis Angelos Giapitzakis¹, Sahar Nassirpour¹, Nikolai Avdievich¹, Roland Kreis², and Anke Henning^1,3
1Max Planck Institute for Biological Cybernetics, Tuebingen, Baden-Wuerttemberg, Germany, ²Departments of Radiology and Clinical Research, University of Bern, Bern, Switzerland, ³Institute for Biomedical Engineering, UZH and ETH Zurich, Zurich, Switzerland

Metabolite cycled proton magnetic resonance spectroscopy (MC 1H-MRS) has been proved to enhance the frequency resolution and the signal to noise ratio (SNR) of the spectrum at static magnetic fields ranging from 1.5 to 7 Tesla. The purposes of this study were to: 1) develop a short duration WS scheme for implementation with a STEAM sequence [5] 2) examine the performance of MC H-MRS compared to a WS STEAM sequence and 3) create spectrum with high frequency resolution at 9.4T enabling the detection of several metabolites.

Manoj Kumar Sarma¹, Rajakumar Nagarajana¹, Paul Michael Macey², and M. Albert Thomas^1
1Radiological Sciences, UCLA School of Medicine, Los angeles, CA, United States, ²School of Nursing, UCLA School of Medicine, Los angeles, CA, United States

Multi-Echo (ME) based technique with two bipolar echo-planar imaging (EPI) read-out trains to collect dual phase encoded lines within a single TR has been used to reduce the scan time of 4D Echo-planar (EP)-based J-resolved spectroscopic imaging (JRESI). Like other point-resolved spectroscopy (PRESS) based in vivo MRSI techniques with conventional pulses, at 3T ME-based EP-JRESI pulse sequence also suffers from large chemical shift displacement error (CSDE), non-uniform excitation, lipid contamination on the boundary and additional J-refocused artifactual peaks. In this study, a localized by adiabatic selective refocusing (sLASER)-based ME-EP-JRESI sequence was proposed and successfully implemented on phantoms and human brains. Compared with ME-EP-JRESI using conventional pulses, sLASER based ME-EP-JRESI significantly reduced the CSDE, residual water and achieved better uniform slice profile. This technique is going to help for more reliable and accurate quantification of metabolites at 3T and higher field strengths.

Kaiyu Wang¹, Hao Chen¹, Zhiyong Zhang¹, Yuqing Huang¹, and Zhong Chen^1
1Electronic Science, Xiamen University, Xiamen, Fujian, China

Benefitting from separating chemical shifts and J couplings along two distinct dimensions, 2D J-resolved NMR experiment can be used to alleviate the spectral congestion in 1D NMR spectra of biological metabolites. Spatially encoded technique is a common way to reduce acquisition time in multidimentional experiments. However, both these two methods are sensitive to field inhomogeneity in biological systems, caused by variations in macroscopic magnetic susceptibility. An NMR approach, based on intermolecular double-quantum coherences and spatially encoded technique, is proposed to fast record high-resolution 2D J-resolved spectra from biological systems. Its feasibility was tested on pig brain tissue. Compared to magic angle spinning, it is non-invasive and potential for in vivo and in situ applications.

Muhammad Gulamabbas Saleh¹, A. Alhamud¹, Lindie Du Plessis¹, André J.W. van der Kouwe², Jamie Near³, and Ernesta M. Meintjes^1
1Department of Human Biology, MRC/UCT Medical Imaging Research Unit, University of Cape Town, Cape Town, Western Cape, South Africa, ²Massachusetts General Hospital, Charlestown, Massachusetts, United States, ³Douglas Mental Health University Institute and Department of Psychiatry, McGill University, Montreal, Canada

During GABA spectroscopy acquisition, subject motion may cause the spectra to be acquired at an incorrect region of interest (ROI), resulting in an inaccurate metabolite quantification. This problem is exacerbated if the ROI is in close proximity to the skull, potentially introducing large unwanted lipid signal and rendering the spectrum non-viable. Errors resulting from motion may, however, be subtle and difficult to assess in the final spectrum. The purpose of this work was to incorporate a volumetric navigator after each MRS measurement to track and correct in real-time subject motion before the next acquisition.

Michael S Dodd¹, Jack J Miller^1,2, and Damian J Tyler^1
1Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom, ²Department of Physics, University of Oxford, Oxford, United Kingdom

When undertaking metabolic studies using hyperpolarized ¹³C-labelled pyruvate, it is typical for 1.5 mM of a gadolinium based contrast agent to be added to the sample to significantly enhance the level of polarization achieved. Using the Oxford Instruments Hypersense polarizer (3.35T/1.2-1.4 K) and the GE Healthcare SPINlab polarizer (5T/0.8 K), the effect of gadolinium on polarization enhancement was investigated. The addition of Dotarem (Gd³⁺) significantly increased the polarization at 3.35T/1.2-1.4 K (Hypersense), whereas this same effect was not seen at 5T/0.8 K (SPINlab). Therefore, there appears to be no advantage to adding gadolinium to pyruvate samples for potential clinical applications on the SPINlab system.

Shizhe S Li¹, Li An¹, Maria Ferraris Araneta¹, Christopher Johnson¹, and Jun Shen^1
1NIMH, National Institutes of Health, Bethesda, Maryland, United States

NOE and proton decoupling for traditional ¹³C MRS of human brain at 7T are problematic due to safety concerns. One of the solutions is to detect carboxylic/amide carbons that have weak couplings with protons, thus require less decoupling power if broadband stochastic decoupling is used. ¹³C MRS was performed on a phantom and human brains to quantify signal enhancement at 7 Tesla. The results showed that ¹³C signal peak amplitudes were increased by a factor > 4 when both NOE and broadband stochastic decoupling were employed.

Silvia Rizzitelli¹, Alan Wong², Guillaume Radecki³, Luisa Ciobanu³, Gerard Raffard¹, Stephane Sanchez¹, Veronique Bouchaud¹, Leslie Mazuel¹, Anne-Karine Bouzier-Sore¹, and Yannick Crémillieux^1
1CRSMB, University of Bordeaux, Bordeaux, France, France, ²NIMBE/LSDRM, CEA-Saclay, Gif-sur-Yvette, France, France, ³CEA I2BM NeuroSpin, Gif-sur-Yvette, France, France

The challenge of this study was to investigate the ability of a custom-made microsolenoidal coil with an inner diameter of 600µm, for visualizing very small volumes (<400 nL) of 13C labeled compounds perfused in the rat brain through the use of a microdialysis catheter, carried out with the complementarity of MRI and MRS techniques. The addition of Gd-DOTA to the solution, with the aim of shortening the longitudinal relaxation time of 13C metabolites, allows the visualization and quantification of the release of the perfusate solution in brain tissue, while MRS gives us the possibility of monitoring in real-time the changes in metabolite concentration

Petr Šedivý¹, Monika Christina Kipfelsberger², Miloslav Drobný¹, Martin Krššák^2,3, Jan Rydlo¹, Marek Chmelík², Marjeta Tušek Jelenc², Milan Hájek¹, Siegfried Trattnig², Monika Dezortová¹, and Ladislav Valkovic^2,4
1MR-Unit, Department of Diagnostic and Interventional Radiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic, ²High Field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria, ³Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria, ⁴Department of Imaging Methods, Institute of Measurement Science, Slovak Academy of Sciences, Bratislava, Slovakia

The aim of this study was to assess the impact of experimental set-up (ergometer and RF-coil) and magnetic field (3T and 7T) on determination of mitochondrial capacity by dynamic ³¹P MRS. A group of volunteers was measured in three different MR systems, using two different ergometers and RF-coil designs at two different workloads. Using the same ergometer and similar coil at 3 and 7T lead to improved spectral quality at 7T, but there was no difference in calculated mitochondrial capacity. However, the use of different equipment at 3T caused discrepancies in the results that seem to decrease at higher workload.

Marjeta Tušek Jelenc¹, Marek Chmelík¹, Wolfgang Bogner¹, Martin Krššák^1,2, Siegfried Trattnig¹, and Ladislav Valkovic^1,3
1High Field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria, ²Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria, ³Department of Imaging Methods, Institute of Measurement Science, Slovak Academy of Sciences, Bratislava, Slovakia

The aim of our study was to test the feasibility and repeatability of the DRESS-localized FAST method at 7T for the measurement of Pi-to-ATP and PCr-to-ATP reaction rates in the human gastrocnemius muscle. Instead of adiabatic BIR4 pulses, which showed inhomogeneous frequency dependent behavior at 7T, conventional sinc pulse was used for excitation. For the test of repeatability the FAST measurement was repeated four times within one session. We could show that DRESS-localized FAST measurement, taking only 4 minutes, is highly repeatable at 7T and its results on exchange rate constants are not different from the results of conventional localized ST experiment.

Atiyah Yahya^1,2
1Department of Oncology, University of Alberta, Edmonton, Alberta, Canada, ²Department of Medical Physics, Cross Cancer Institute, Edmonton, Alberta, Canada

Measurements of lipid unsaturation by proton MRS have been shown to be relevant to the study of a number of diseases. The olefinic resonance at about 5.4 ppm enables measurement of lipid unsaturation. However, its peak is largely overlapped by that of water at clinical field strengths. The presented educational abstract summarizes methods that have been employed to resolve the olefinic resonance from that of water in vivo. The role of J-coupling interactions of the lipid olefinic protons in the design of spectral editing methods is discussed.

Sreenath Pruthviraj Kyathanahally¹, Nicole D Fichtner¹, Victor J Adalid¹, and Roland Kreis^1
1Depts. Radiology and Clinical Research, University Bern, Bern, Switzerland

A recent 1H MR spectroscopy study reported that the metabolite-to-water ratios were strongly reduced in the presence of superficial fat layers, thus questioning the clinical use of water as a reference for quantification and quantitative spectroscopy as a whole. We have attempted to verify this effect and pinpoint the potential causes by acquiring data with various acquisition settings, incl. different water suppression sequences, RF coils and field strengths. In our hands and with all settings tested, the reported effect could not be reproduced.

MRS Data Processing Quantitation of MRSI Aquisition Method

Thursday 4 June 20155

Manoj Kumar Sarma¹, Zohaib Iqbal¹, Brian Burns¹, Rajakumar Nagarajana¹, Cathy C Lee², and M. Albert Thomas^1
1Radiological Sciences, UCLA School of Medicine, Los angeles, CA, United States, ²Geriatrics, VA Greater Los Angeles Healthcare System, Los angeles, CA, United States

Echo-planar correlated spectroscopic imaging (EP-COSI) which combines localized correlated spectroscopy (L-COSY) with echo-planar spectroscopic imaging (EPSI) readout has been used to study neurochemical information of human calf muscles. A limitation of EP-COSI of multiple skeletal muscles is prolonged scan duration which have been tried to address using multi-echo (ME) based acquisition scheme. Using two bipolar readout trains ME-based EP-COSI, called multi-echo echo-planar correlated spectroscopic imaging (ME-EP-COSI) achieved a significant reduction in the total scan, but for clinical applications, it is still a constraint. In this study, we have implemented a non-uniform undersampling (NUS)-based ME-EP-COSI acquisition in human calf muscle at 3T where NUS was used along the t1 dimension only and reconstructed the data using compressed sensing (CS). We have demonstrated that acquisition time of the standard 4D ME-EP-COSI sequence can be reduced by half while maintaining sufficient spectral/spatial quality enabling ME-EP-COSI closer to a clinical reality.

Bart Philips¹, Miriam W. van de Stadt-Lagemaat¹, Mark J. van Uden¹, Eline K. Vos¹, Borjan Gagoski², Adam B. Kerr³, Marnix C. Maas¹, and Tom W.J. Scheenen^1
1Radiology and Nuclear Medicine, Radboud University Medical Centre, Nijmegen, Gelderland, Netherlands, ²Fetal-Neonatal Neuroimaging & Developmental Science Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States, ³Magnetic Resonance Systems Research Lab, Electrical Engineering, Stanford University, Stanford, CA, United States

Using spectral-spatial RF pulses in combination with a spiral MRSI acquisition the advantages of 7T (high SNR and greater chemical shift dispersion) can be exploited to perform prostate MRSI on 7T with high spatial resolution in feasible acquisition times. This method was tested on 8 prostate cancer patients using an 8 channel body array coil and B1 shimming for locally homogenous transmit field in combination with an endorectal receive coil. We obtained whole prostate MRSI with a true voxel size of 0.48 cc within 7 minutes of acquisition time.

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

This study aims at assessing the performance of compressed sensing method for faster proton MRSI of human brain. Non-uniformly under sampled (NUS) three dimensional (3D) echo planar spectroscopic imaging (EPSI) data of brain phantom and healthy brain were acquired in 3T MRI scanner and the data were processed using MATLAB for CS reconstruction and peak quantitation. The k-space data was randomly under sampled, and reconstructed using compressed sensing algorithm. The metabolites ratios with respect to creatine in various regions of brain were calculated using NUS based 3D EPSI. We have presented a technique combining 3D EPSI (2x under sampling) with compressed sensing reconstruction using total variation method showed better spatial profile without compromising spectral quality.

Michal Bittsansky¹, Petra Hnilicova¹, and Dusan Dobrota^1
1Jessenius Faculty of Medicine, Comenius University, Martin, Slovakia, Slovakia

We propose and test a fast and simple sequence for water scaling of 3D ¹H spectroscopic imaging. Our 3D FID sequence (pulse-phase_gradient-acquire, short TE, very low flip angle) with identical geometry and resolution to the metabolic sequence has a measurement time under 2 minutes. We tested the sequence in a phantom with brain metabolites, healthy volunteers and tumor patients. The method gave us precise quantification in the phantom and provided consistent brain metabolic mapping in vivo in the brain and pathological areas like tumors. Our results suggest usefulness of this approach in systems with whole-body excitation.

Sahar Nassirpour¹, Thomas Kirchner², Ioannis Angelos Giapitzakis¹, and Anke Henning^1,2
1Max Planck Institute for Biological Cybernetics, Tübingen, Germany, ²Institute for Biomedical Engineering, UZH and ETH Zürich, Zürich, Switzerland

Magnetic resonance spectroscopic imaging (MRSI) at ultra-high field strengths is a promising technique for mapping of the metabolites over the entire brain volume with a high signal to noise ratio. However, long acquisition time is a major limitation in MRSI. Along with short repetition times (TR) [4] parallel imaging strategies can help accelerate the scan by acquiring only a fraction of the data points in k-space, but an appropriate unfolding reconstruction algorithm is required. To that end, a target driven SENSE [3] reconstruction algorithm has been introduced [1], which minimizes the effects of voxel bleeding. This study represents the first demonstration of short TR twofold SENSE accelerated multi-slice FID MRSI of the human brain at 9.4T.

Tiejun Zhao¹, Julie W. Pan², and Hoby P. Hetherington^2
1Siemens Medical Solutions USA, Inc., Pittsburgh, PA, United States, ²Department of Radiology, Pittsburgh, PA, United States

This work investigated the feasibility of using GRAPPA to shorten the CSI scan time and its impacts on the metabolite quantifications. Fully sampled CSI data were retrospectively undersampled to achieve effective acceleration rates from 2.3 to 3.0 and the undersampled data were reconstructed using a modified GRAPPA method with weighted averaging scheme. Our data suggested a modest acceleration of 2.3 is feasible and could be applied to a routine clinical scanner to reduce the CSI scan time.

Miriam W van de Stadt-Lagemaat¹, Bart L van de Bank¹, Marnix C Maas¹, and Tom WJ Scheenen^1,2
1Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, Netherlands, ²Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen, Germany

The Nuclear Overhauser effect (NOE) is a technique in ³¹P spectroscopy to enhance the intrinsically low signal intensities. There are however concerns that NOE might add uncertainty, negating the SNR gain, since considerable spread is generally observed in NOE enhancement values. To this end, repeated measurements of ³¹P MRSI without and with NOE were performed. We conclude that NOE is beneficial for ³¹P MRSI in the brain at 7T, it does not introduce variation for most metabolites, but rather improves their accurate detection and fitting.

Yuchi Liu¹, Yun Jiang¹, Charlie Yi Wang¹, Mark Alan Griswold^1,2, and Xin Yu^1,2
1Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, United States, ²Radiology, Case Western Reserve University, Cleveland, Ohio, United States

In this study, a novel fast 31P chemical shift imaging (CSI) method using multi-spiral acquisition was developed. Spiral trajectory was designed and implemented for quantification of phosphorous metabolites. The k-space trajectory was measured. Using a multi-spiral acquisition scheme, an acceleration factor of 23 was achieved as compared to traditional Cartesian CSI method with the same spatial resolution.

Sungjin Kim^1,2 and Hyeonjin Kim^1,2
1Radiology, Seoul National University Hospital, Seoul, Korea, ²Biomedical Sciences, Seoul National University, Seoul, Korea

Given B₁ inhomogeneity being of great concern for successful implementation of MRSI sequences at high field and the excellent localization performance of the semi-localized by adiabatic selective refocusing (sLASER) and the LASER single voxel MRS pulse sequences, we have implemented sLASER- and LASER-based MRSI sequences at 9.4T and compared their performance. Given the comparable volume localization performance along with the shorter minimum TE attainable and less SAR with a sLASER-based MRSI sequence relative to a LASER-based MRSI sequence in our preliminary study, a sLASER-based MRSI sequence may be the sequence of choice for in-vivo MRSI at high field.

Benoit Schaller¹, William Clarke¹, Stefan Neubauer¹, Matthew Robson¹, and Christopher Rodgers^1
1Cardiovascular Department, Oxford Centre for Clinical Magnetic Resonance Research, Oxford, Oxfordshire, United Kingdom

31P-MRS provides direct insights into myocardial energy supply (ATP, ADP, phosphocreatine (PCr) and inorganic phosphate). However, the translation of more sophisticated 31P-MRS protocols to 7T is challenged by increased RF heating of tissue at 7T. In this work, we introduce the first crusher coil for cardiac 31P-MRS(I) at 7T. Crusher coil was simulated and designed to saturate skeletal muscle signal. Crusher coil provided additional 12-25% signal saturation in vitro and in vivo, compared to BISTRO saturation band at maximum SAR. This allows us to saturate more efficiently skeletal muscle signal removing the RF heating associated with RF saturation bands. The flexibility offered by using the crusher coil will allow us to employ sequence modules that would otherwise be SAR-prohibitive without having to compromise the skeletal muscle suppression.

Peng Cao¹, Hsin-Yu Chen¹, Jeremy Gordon¹, Peter Shin¹, Wenwen Jiang¹, and Peder Larson^1
1University of California, San Francisco, San Francisco, California, United States

The typically low bandwidth of the echo planar spectroscopic imaging (EPSI) requires the under-sampling of the sparse hyperpolarized 13C spectrum. However, at high field, the large frequency differences between 13C pyruvate and metabolites can cause pronounced spatial displacements along the EPSI readout direction. For the spectrally oversampled EPSI, this off-resonance-induced displacement can be corrected in k-t space implicitly by interpolating the EPSI sampling points onto a Cartesian grid, but the same algorithm cannot efficiently correct the spectrally undersampled EPSI. Notably, the correction for the off-resonance-induced blurring in the spectrally undersampled spiral CSI was reported previously. Inspired by these previous studies, this study aims to characterize the off-resonance-induced displacement in the spectrally undersampled flyback EPSI. The analytical result is further utilized to correct the displacements in both phantom and in vivo experiments at 7 and 3T.

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

In vivo X-nuclei MRS for human application at high/ultrahigh field often suffers from a high SAR demand and still limited SNR. To overcome the limitations, a novel technique based on the ultrahigh dielectric constant (uHDC) materials incorporated with a RF coil has shown a promise for enhancing SNR and reducing SAR. In this report, we quantitatively examined and observed significant SNR enhancement of up to 80% and 45% reduction of SAR for three-dimensional 31P chemical shift imaging (CSI) at 7 Tesla by using the uHDC material. The overall results collectively indicate that the uHDC technique provides a cost-effective engineering solution for significantly benefiting X-nuclear MRS at ultrahigh fields.

Ming Lu¹, Xiao-Hong Zhu¹, Yi Zhang¹, and Wei Chen^1
1Center for Magnetic Resonance Research, University of Minnesota Medical School, Minneapolis, Minnesota, United States

Cerebral glucose metabolism is of importance to brain function and neuroenergetics. Simultaneous assessment of cerebral glucose consumption rate and associated TCA cycle flux is crucial for understanding neuroenergetics under various physiopathological conditions. Recently, we developed a novel in vivoDeuterium (²H) MR (DMR) approach for noninvasively assessing glucose metabolisms in global rat brain with superior sensitivity at ultrahigh field. To evaluate its imaging capability, in this study, dynamic localized DMR spectra were acquired using 3D-chemical shift imaging (CSI) technique in rat brains at 16.4 T. Regional brain metabolic rates under two conditions (deep anesthesia with 2% isoflurane versus constant morphine infusion) were compared to evaluate the sensitivity of this new imaging method in detecting alteration in the metabolic/neuronal states. As expected, accelerated glucose consumption and labeled glutamate/glutamine (Glx) turnover were observed in rats under morphine treatment. The results of this work demonstrate excellent spectral quality, adequate sensitivity and temporal resolution of the in vivo 3D ²H CSI at ultrahigh field, which provides an opportunity to simultaneously map the glucose consumption rate and TCA cycle flux in animal and human brains.

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

The lipid signal in 1H MRS interferes strongly with spectroscopy in the cortical region. Previously, spectroscopy localization was demonstrated using a B0 Adjusted Sensitivity Encoded Spectra Localization by Imaging (BASE-SLIM) technique. BASE-SLIM can also be applied to eliminate the major lipid signal contamination that appears in conventional CSI. A full-width field of view CSI that includes skull and scalp was used to investigate lipid signal and metabolite signal separation capability. The capability of eliminating lipid signal contamination using BASE-SLIM in the human brain in vivo promises reliable MRS quantification in the cortical brain regions.

Hirohiko Imai¹, Kei Sano¹, Shota Momma¹, Toshiyuki Tanaka¹, and Tetsuya Matsuda^1
1Department of Systems Science, Graduate School of Informatics, Kyoto University, Sakyo-ku, Kyoto, Japan

We demonstrate the feasibility of compressed sensing (CS) to accelerate MRSI combined with a 2D ¹H-¹³C heteronuclear multiple quantum coherence (HMQC) for imaging metabolic dynamics. The 2D-HMQC MRSI with a pseudo-random undersampling was performed for tumor-bearing mice after the injection of [U-¹³C]glucose. From the acquired data set, spatio-temporal changes in densities of glucose, lactate and fat were estimated using CS. The estimated results showed that the glucose was decreased with time and the lactate was specifically accumulated in tumor, reflecting Warburg effect. This technique provided an 8-fold acceleration factor and made it possible to image tumor glycolysis in vivo.

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

Accurate, robust assessment of 1H MRS in gray and white matter of the human brain was achieved with the B0 Adjusted Sensitivity Encoded Spectra Localization by Imaging (BASE-SLIM) technique. BASE-SLIM based 1H MRS eliminates the need for Cartesian k-space acquisition and provides MR spectra from GM and WM with improved quality with minimum B0 and B1 inhomogeneity related errors. Comparison of metabolite quantification between BASE-SLIM and the extrapolated CSI regression method showed general agreement. The capability of spectroscopy localization using BASE-SLIM further promises 1H MRS with non-Cartesian k-space acquisition.

Wenqing Liao #¹, Wenbo Wu #², Yu Sun #¹, Renyuan Liu³, Zhenyu Yin², Huiting Wang³, Xin Zhang³, Ming Li³, Chuanshuai Tian³, Kun Wang³, Haiping Yu³, Weibo Chen⁴, Bin Zhu³, Suiren Wan*¹, Yun Xu*², and Bing Zhang*^3
1The Laboratory for Medical Electronics, School of Biological Sciences and Medical Engineering, Southeast University, Nanjing, China, ²Department of Neurology, The Affiliated Drum Tower Hospital of Nanjing Medical University, Nanjing, China, ³Department of Radiology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China, ⁴Philips Healthcare, Shanghai, China

Recent surveys showed higher sensitivity of hippocampal subfields atrophy over the whole hippocampal atrophy, and MRS over volumetric atrophy, in early diagnosis of Alzheimer's Disease.This article presents a method of studying metabolites in hippocampal subfields combining MRS and MRI segmentation, aiming at combining the advantages of both. We segmented the hippocampus and its subfields with the FreeSurfer Software, and obtained metabolite concentrations by processing MRS data with LCModel. After co-registering MRS VOI and freesurfer segmentation, we were able to label each VOI voxel with the hippocampal subfield which constitutes its majority volume. After averaging voxels labeled with the same subfield, metabolite profile of the subfield was obtained. Reliability and accuracy of the method was analyzed and real AD data was used to verify our method.

Victor Javier Adalid¹, Chris Boesch¹, Christine S. Bolliger¹, and Roland Kreis^1
1Depts. Radiology and Clinical Research, University Bern, Bern, Switzerland

Inhomogeneities in B0 and eddy currents cause the lineshape for metabolites and water to deviate from the Lorentzian type. Various approaches have been used to correct for this distortion in 1D spectra, but this has not been widely studied for 2D spectra. Restoring the original lineshape by deconvolution methods modifies the noise profile and/or introduces spikes. Here, a method is tested where the reference lineshape is applied to the model in order to fit the distorted spectra with equally distorted basis spectra, in particular as applied to 2DJ data with maximum echo sampling.

Victor E. Yushmanov¹, Yoojin Lee¹, Claudiu Schirda¹, Hoby P. Hetherington¹, and Jullie W. Pan^1,2
1Department of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States, ²Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States

Reliable automated protocols for standardized, non-biased, easy-to-execute and rapid analysis of MRSI of human brain with minimal operator intervention have been developed, refined and tested. Spectral processing was performed by LCModel software with subsequent automated data quality assessment for each voxel. Integration with tissue content analysis (gray matter fraction) as ascertained from tissue segmentation allows one to approach the significance of abnormality.

Jamie Near^1,2, Gabriel A. Devenyi³, and Robin Simpson^4
1Department of Psychiatry, McGill University, Montreal, Quebec, Canada, ²Centre d'Imagerie Cérébrale, Douglas Institute, Montreal, Quebec, Canada,³Centre d'Imagerie Cérébrale, Douglas Institute, Montréal, Quebec, Canada, ⁴Department of Medical Physics, Freiburg University, Freiburg, Freiburg, Germany

This abstract introduces a new, open-source software package for simulation of magnetic resonance spectroscopy (MRS) experiments, design and analysis of radiofrequency pulses, and processing of MRS data. The software is called FID-A, and is freely available for download (www.github.com/CIC-methods/FID-A). The FID-A software package is unique in the combination of functionalities that it provides, and in the way in which it stores and manages MRS data and header information together. The functionality of this software package is demonstrated through simulations of the MEGA-PRESS sequence with shaped editing pulses, as well as through processing of in-vivo short echo-time MRS data.

Jamie Near^1,2, Richard Edden³, John Evans⁴, Raphael Paquin⁵, Ashley Harris³, and Peter Jezzard^6
1Department of Psychiatry, McGill University, Montreal, Quebec, Canada, ²Centre d'Imagerie Cérébrale, Douglas Institute, Montreal, Quebec, Canada,³Kennedy Krieger Institute, Johns Hopkins University, Baltimore, Maryland, United States, ⁴Cardiff University, Cardiff, Wales, United Kingdom, ⁵Healthcare, Siemens Canada Limited, Montreal, Quebec, Canada, ⁶FMRIB Centre, University of Oxford, Oxford, Oxfordshire, United Kingdom

Frequency and phase drifts in magnetic resonance spectroscopy (MRS) data cause artifactual line broadening, lineshape distortion and SNR reduction, if not properly accounted for. Here, we present a simple new method of estimating and correcting frequency and phase drifts in MRS data. This new method is called spectral registration, and it involves alignment of each time domain average (FID) to a reference FID (usually the first FID in the series) via adjustment of frequency and phase terms. Using simulated data with known frequency and phase drifts, we demonstrate that spectral registration performs better than two existing drift correction methods.

Carlos E Garrido Salmon^1,2, Emma Louise Hall¹, Carolina Fernandes¹, Chen Chen¹, and Peter G Morris^1
1Sir Peter Mansfield Magnetic Resonance Centre, Nottingham, Nottinghamshire, United Kingdom, ²Department of Physics, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil

We applied the SENSE principle, assuming noise correlation between channels, as a general approach for SNR optimization of single voxel MRS data. Different reconstruction techniques were evaluated using phantom and brain data acquired on a 7T-32channels MR system. Even with correlated noise, only a very small difference in SNR was found among correlated, uncorrelated and sensitivity approaches. The general shape of the reconstructed spectra is independent of the reconstruction method; however metabolites with very low SNR can be affected. For in vivo brain data, reconstructions performed by the scanner have low SNR when compared with the weighting methods here discussed.

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

Quantification of magnetic resonance spectroscopy (MRS) signals provides metabolite concentrations of tissues under investigation. In spectra fitting, lineshape distortions due to magnetic field inhomogeneity need to be corrected using a reference signal. The present study introduces a novel method to spectral fitting in the presence of large magnetic field distortion. We distort the basis set based on measured magnetic field distribution within the MRS voxel and use the distorted basis set to fit the observed MRS signal. This novel approach avoids complex division and regularization and therefore is free of statistical bias inherent in regularized lineshape deconvolution.

Hidehiro Watanabe¹, Nobuhiro Takaya¹, and Fumiyuki Mitsumori^1
1Center for Environmental Measurement and Analysis, National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan

While Glu and GABA are major neurotransmitter in human brain, Gln is a precursor and storage form of Glu, which plays an important role in the Glu-Gln cycle in brain. Overlapped peaks of these metabolites on the conventional ¹H spectra due to strong coupling may lead to difficulty of accurate quantitation. Constant time (CT) methods have a feature of good peak resolution through ¹H decoupling along F₁. In this work, we first demonstrate phasing of 2D CT-PRESS spectra of a phantom and human brain for higher peak resolution. We also demonstrate curve fitting of these three peak volumes for quantitation.