Joint Annual Meeting ISMRM-ESMRMB • 16-21 June 2018 • Paris, France

Electronic Poster Session
Spectroscopy & Non-Proton MR
Tuesday, 19 June 2018
Electronic Poster

Non-Edited MRS/MRSI
Electronic Poster
Spectroscopy & Non-Proton MR

Tuesday, 19 June 2018
 Exhibition Hall 08:15 - 09:15

Electronic Poster
Spectroscopy & Non-Proton MR

Tuesday, 19 June 2018
 Exhibition Hall 08:15 - 09:15

 Computer # 3864. 73 Assessment of Bound Sodium using Triple Quantum Selection vs. Inversion Recovery at 21.1 T Nastaren Abad, Ghoncheh Amouzandeh, Jens Rosenberg, Michael Harrington, Samuel Grant This study evaluates Triple Quantum (TQ) and Inversion Recovery (IR) techniques at 21.1 T with regards to bound sodium quantification. Using both gel phantoms imitating physiological concentrations/bound fractions as well as in vivo animal pathological models, the efficiency, SNR and selectivity of 23Na TQ and IR techniques were compared with the ultimate goal of localizing specific sodium changes within intra- and extracellular compartments related to disease progression. 3865. 74 Investigating Bound Sodium Signals using a Novel Chemical Shift Imaging Triple Quantum Technique Nastaren Abad, Ghoncheh Amouzandeh, Jens Rosenberg, Michael Harrington, Samuel Grant 23Na-based MRI techniques can be used to separate sodium signal originating from the extracellular and intracellular compartments. Triple Quantum (TQ) schemes can select the coherence pathway that evolves in slow moving/restricted regimes, such as in the intracellular compartment. In this study, a novel TQ technique based on a modified chemical shift imaging sequence (CSI-TQ), which yields higher signal-to-noise ratios, is introduced for studies at 21.1 T. The CSI-TQ is compared to a more conventional gradient recalled echo variant (GRE-TQ) with respect to SNR and efficiency. 3866. 75 Simultaneously Acquired Single- and Triple-Quantum Spectroscopic Imaging with Density-Adapted Projection Reconstruction and Time Proportional Phase Increment Ruomin Hu, Matthias Malzacher, Michaela Hoesl, Dennis Kleimaier, Lothar Schad Multi-quantum filtered spectroscopic imaging methods utilize the spin-3/2 characteristic of 23Na nuclei to generate multi-quantum coherences reflecting on the binding of 23Na+ to macromolecules. In this work, a spectroscopic density-adapted radial imaging modality was developed to simultaneously acquire single-quantum and triple-quantum signal under identical condition using time proportional phase increments. In vivo rat head images with 1 mm resolution were acquired in under an hour. This method may be applied to monitor the single-quantum and triple-quantum signal development in diseases such as stroke and cancer and lead to a deeper understanding of metabolic processes in healthy and diseased tissue. 3867. 76 Sodium imaging with an UTE technique to study the effects of exercise on muscle. Benjamin Prestwich, Charlotte Buchanan, Andrew Hale, Andrew Peters, Susan Francis Sodium (23Na) imaging can provide insight into the effects of exercise on muscle. Here we perform a 3D dual TE UTE scheme with radial FID readout to assess the alterations in sodium tissue concentration in the gastrocnemius and soleus muscles; immediately after exercise performed inside the scanner using a Trispect pedal system. In addition an mDIXON proton scan was acquired for delineation of the muscle groups. Following exercise, the time course of the 23Na signal intensity in the medial gastrocnemius and soleus muscles was found to return to baseline after approximately 30 minutes, with a 10 – 20 % signal change. 3868. 77 Design of a Dual Saddle Coil Setup for High Resolution 1H/23Na MRI of Ex Vivo Rat Tail Intervertebral Discs at 14.1T Lance Williams, John Clark, Lukas Neuberger, Gangchea Lee, Daniel Cortes, Thomas Neuberger Rat-tail intervertebral disc puncture is a commonly used model for studying treatment options and the pathology of Degenerative Disc Disease (DDD). However, longitudinal studies are impossible as analysis through biochemistry and histology requires euthanization. High-field MRI provides a possible solution to this problem as initial structural and compositional changes related to disc degeneration are observable. In this work, a dual saddle coil was constructed for 1H/23Na imaging at 14.1T. It was concluded from ex vivo rat-tail proton and sodium images that sodium MRI is feasible, and it could be an effective method for rat-tail intervertebral disc degeneration evaluation. 3869. 78 Effect of B0 and B1 Field Inhomogeneity Correction on Region-of-Interest Analysis on 3T Sodium 23Na-MRI Elaine Lui, Vijay Venkatraman, Christopher Steward, Tie-Qiang Li, Patricia Desmond Evaluation of the effect of B0 and B1 correction on region-of-interest (ROI) analysis in forty-one 3T brain 23Na-MRI scans shows average change from B0, B1 and B0B1 correction of 1.0% (p=0.05), -3.7% (p<0.001) and -4.7% (p<0.001) respectively. Effect is more for B1 than B0 correction, and depending on the anticipated effect size of the neurologic disease of interest, B0 +/- B1 correction may not be required, potentially reducing scan time by 66% and thus encourage quantitative 23Na-MRI research in a clinical environment. 3870. 79 Double quantum filtered 23Na MRI with magic angle excitation in presence of B0-inhomogeneities Lena Gast, Bernhard Hensel, Michael Uder, Armin Nagel In 23Na MRI it is possible to selectively detect signal from sodium ions bound to anisotropic structures by applying a double quantum filter with magic angle excitation (DQ-MA). In this work, the influence of B0-inhomogeneities on the DQ-MA filtering capacity was examined both theoretically and experimentally. We found that under practical conditions (|ΔB0| ≈ 50 Hz at 3T) a significant amount of unwanted odd rank double quantum coherence signal may pass the filter even in case of perfect magic angle excitation. Therefore, B0-inhomogeneities may cause an over-estimation of the degree of anisotropy. 3871. 80 Investigating the 23Na Flip-Angle Effect in Cartilage, Skin, and MuscleVideo Permission Withheld Atefeh Kordzadeh, Jade Duchscherer, Christian Beaulieu, Robert Stobbe The measurement of sodium concentration in cartilage, skin, and muscle with 23Na MRI requires the knowledge and minimization of spin 3/2-related signal losses. Here, a common B1 mapping experiment is used here to show that greater than prescribed flip-angles are produced in healthy human cartilage, skin, and muscle and that this effect is increased with longer RF excitation pulses. This points to the presence of residual quadrupole interactions in these tissues. To avoid the concomitant signal loss associated with residual quadrupole interactions, very hard (short) RF excitation pulses may be required. 3872. 81 Improved Encoding Efficiency in Sodium MRI with Zero-Gradient-Excitation Ramped Hybrid Encoding (zGRF-RHE) Yasmin Blunck, Bradford Moffat, Scott Kolbe, Roger Ordidge, Jon Cleary, Leigh Johnston The fast signal decay in sodium MRI makes high quality image acquisition challenging. Here we enhance image quality by improving encoding time (tenc) efficiency using a special case of ramped hybrid encoding , zero-gradient-under-RF-excitation RHE (zGRF-RHE). This provides 1) gradient-free-excitation for high flip angle, non-selective excitation profiles necessitated by low signal in sodium MRI and 2) gradient ramping during deadtime for optimised tenc, to reduce T2 decay influence during acquisition. The performance of zGRF-RHE is demonstrated in simulations, phantom and in vivo experiments and improves image quality (SNR and T2 blurring). It is applicable to any centre-out trajectory design. 3873. 82 Influence of motion and partial volume effects on measured tissue sodium concentration in cardiac $$^{23}$$Na MRI Johanna Lott, Jonathan M. Lommen, Sebastian C. Niesporek, Tanja Platt, Nicolas G.R. Behl, Mark E. Ladd, Armin M. Nagel Sodium (23Na) ions are involved in many biological processes. The tissue sodium concentration can be determined with 23Na MRI; however, fast relaxation times, breathing and heart motion as well as the high sodium concentration of blood render quantitative determination of the myocardial sodium concentration challenging. We present a method to analyze the tissue sodium concentration within the myocardium by utilizing a partial volume correction as well as correction of motion effects. The presented workflow can reduce the bias by up to 49%. 3874. 83 Voxel localization for sodium NMR triple-quantum signal; sequence design and test in agarose phantoms and in-vivo rat Michaela Hoesl, Dennis Kleimaier, Matthias Malzacher, Ruomin Hu, Lothar Schad The TQTPPI – sequence is a global spectroscopic method, which can be used to study the sodium metabolism of cells in-vitro with the foremost interest in the occurrence of the triple-quantum signal. This spectroscopic analysis could offer precise knowledge of sodium metabolic processes in pathology versus healthy tissue. To address clinical questions, we aim for transferring this method to in-vivo patient acquisitions where the need for a localization arises. Two different localization strategies, which preserve the quantum coherences, were successfully implemented and tested in-vitro and in-vivo on a rat using a 9.4T small-animal scanner. 3875. 84 Can sodium triple-quantum signal separate extra- and intracellular signals? – investigation on HEP G2 liver cells, liposomes and nanoparticles Michaela Hoesl, Dennis Kleimaier, Ruomin Hu, Matthias Malzacher, Eric Gottwald, Cordula Nies, Lothar Schad Sodium MRI is increasing in popularity albeit the apparent challenges of low SNR and fast bi-exponential decay. Currently, intra- and extra cellular sodium can only be resolved by introducing a chemical shift reagent which is unusable in human studies due to toxicity. There is discussion on whether triple-quantum signal (TQS) could provide a discriminator for resolving intra- and extracellular signal due to motion restriction of sodium ions within the cell. This work investigates the TQS behavior using a triple quantum sequence with time proportional phase increment (TQTPPI) on liposomes, HEP G2 liver cells and nanoparticles to disentangle the reasons for occurring TQS. 3876. 85 Multi-pulse Sodium Magnetic Resonance Imaging for Multi-compartment Quantification in Brain at 7TVideo Permission Withheld Martin Gajdošík, Alina Gilles, Ivan Kirov, Guillaume Madelin We propose a new approach to investigate intra- and extracellular sodium in vivo. In this preliminary study we could differentiate brain compartments and provide an estimate of intracellular and extracellular sodium concentrations as well as intracellular, extracellular and cerebrospinal fluid volume fractions. 3877. 86 Application of 3D-Dictionary Learning Compressed Sensing Reconstruction En Route to Isotropic Submillimeter Spatial Resolution Sodium (23Na) In Vivo MRI of the Human Eye at 7.0 Tesla Daniel Wenz, Nicolas Behl, Armin Nagel, Mark Ladd, Thoralf Niendorf Sodium ion (Na+) is a very important factor in the physiology of the human eye. However sodium (23Na) MRI is limited by its low sensitivity. Compressed sensing provides means to overcome this challenge. This work demonstrates the feasibility of high spatial resolution (1mm isotropic) 23Na in vivo MRI of the eye using a dedicated six-channel transceiver array in conjunction with a 3D dictionary learning compressed sensing algorithm. This approach showed distinct noise reduction along with substantial reduction in total acquisition time if benchmarked against conventional reconstruction employing standard gridding. 3878. 87 Simulation of 13C labeling Effects of Glutamate and Glutamine in 1H MR Spectra with different Pulse Sequences at 9.4 T Theresia Ziegs, Anke Henning Glutamate related metabolism can be measured considering the 13C labeling effects from an administered 13C labeled substrate in pure 1H MRS spectra without a 13C channel. In this work, simulated 1H MRS spectra with FID, semi-Laser, and two PRESS sequences have been compared to optimize spectral resolution for glutamate and glutamine measurements at 9.4 T. Furthermore, spectral changes according to a two-compartment model were analyzed. As a result, this work indicates the fastest possible acquisition can be obtained with an FID sequence, while the best resolution possible can be obtained with a PRESS sequence. 3879. 88 Minimum echo-time PRESS-localized proton observed carbon edited (POCE) magnetic resonance spectroscopy for rat brain imaging using simultaneous editing and localization pulses. Chathura Kumaragamage, Dan Madularu, Axel Mathieu, Derek Lupinsky, Robin de Graaf, Jamie Near Dynamic Carbon-13 (13C) magnetic resonance spectroscopy (MRS) remains to be the only noninvasive method capable of measuring neuroenergetics and neurotransmitter cycling in the brain1. Proton observed carbon edited (POCE) MRS2 is an attractive alternative to direct 13C methods due to improved signal-to-noise-ratio (SNR). This study reports a PRESS localized POCE sequence utilizing simultaneous editing and localization (SEAL-PRESS), which allows the TE to be reduced to a theoretically optimal value of ~1/JHC (8.1ms, in this implementation). The sequence was validated in phantom and in a rat preparation, and demonstrated >17% improvement in 13C labeled metabolites relative to a 12.6-ms PRESS-POCE sequence. 3880. 89 Evaluation of three different broadband ¹H decoupling techniques for 13C-MRS at high field using double-tuned array coils Guillaume Donati, Rolf Gruetter synopsis 3881. 90 Coil Combination Methods for 16-channel Hyperpolarized 13C Spectroscopic Imaging Studies of Liver Metastases Patients Zihan Zhu, Xucheng Zhu, Michael Ohliger, Peng Cao, Shuyu Tang, Jeremy Gordon, Lucas Carvajal, Peter Shin, Rahul Aggarwal, Robert Bok, John Kurhanewicz, Pamela Munster, Peder Larson, Daniel Vigneron Effective coil combination methods for human hyperpolarized 13C spectroscopy data remain relatively unexplored. This study implemented several coil combination methods, including sum-of-squares (SOS), singular value decomposition (SVD), and pyruvate map based sensitivity calibration (PyrMap). These methods were evaluated by both simulation and in human cancer studies. Overall, both the SVD and PyrMap methods demonstrated better accuracy and robustness than SOS, and the PyrMap best preserved the phase information. 3882. 91 The effects of iodinated CT contrast agent on phosphorus MRS Ladislav Valkovic, Justin Lau, Ines Abdesselam, Oliver Rider, Damian Tyler, Christopher Rodgers, Jack Miller Contrast-enhanced CT examination can influence 1H-MRI measurements performed within 24h after the CT scan, due to a reduction in water T1 and T2 caused by the iodinated contrast agents used in CT. We have investigated whether contrast from a previous CT examination would also influence metabolic measurements made using 31P-MRS, by measuring the T1 of 1H and 31P signals in human blood. We find that iodinated CT contrast agent has no effect on phosphorus T1s. Therefore, 31P-MRS examinations will not be influenced by prior CT (unlike 1H-MRI scans). 3883. 92 In vivo 31P MRI at 7 Tesla in humans using a 3D spectrally selective SSFP sequence and TPI k-space sampling. Arthur Coste, Sandro Romanzetti, Denis Le Bihan, Cécile Rabrait-Lerman, Fawzi Boumezbeur Spectrally selective 31P MRI can be of interest for the study of brain energetics for clinical research. Using a 3D SSFP sequence with non-Cartesian Twisted Projection Imaging sampling, we obtained whole-brain images of ATP and PCr in healthy volunteers at 7 Tesla with a higher normalized SNR than with CSI. Local concentration quantification was performed using the phantom replacement approach after accounting for the T1/T2-weighting and the transmission and reception profiles of our coil yielding consistent results. 3884. 93 Retrospective frequency correction for fluorine (19F) MRS using an external reference Chu-Yu Lee, In-Young Choi, Jean Dinh, William Brooks, Steven Leeder, Phil Lee Fluorine MR Spectroscopy (19F MRS) allows in vivo quantification of fluorine-containing antipsychotic and antidepressant drug concentrations in the brain. To detect the low concentration of the drugs (~ 5-30 µM) in the brain, it requires multiple repeated acquisitions to increase SNR and the scan time is relatively long. Therefore, it is important to ensure consistent frequency alignment across the repeated acquisitions. However, MR system instability induces drifts of the scanner frequency, particularly following MR scans with a high gradient duty cycle. Previous frequency correction methods for 1H MRS require internal reference signals, such as under- or un-suppressed water, and cannot be applied to 19F MRS, where the SNR of 19F signals is low at each repeated acquisition. The purpose of this study is to investigate the feasibility of using an external reference for retrospective frequency correction in 19F MRS. 3885. 94 Measurement of oxygen consumption in a high density 3D cell culture on chip by 19F spectroscopy Dennis Kleimaier, Michaela Hoesl, Andreas Neubauer, Matthias Malzacher, Cordula Nies, Eric Gottwald, Lothar Schad Drug-induced mitochondrial dysfunction is of major clinical interest. An NMR-compatible bioreactor system was used to investigate the oxygen consumption of HepG2 cells by measuring T1 of perflubron. The oxygen consumption was measured by stopping the perfusion. This resulted in a reduction of the oxygen concentration from (19.29 ± 0.96)% to (11.41 ± 0.92)% in 104.24 min. Our results might allow for detecting a drug-induced mitochondrial dysfunction of cells in a well-controlled environment by using the two compartments of the bioreactor. 3886. 95 Low Intensity Spectral Peaks Reconstruction with Weighted Nuclear Norm Minimization on Low Rank Hankel Matrix Di Guo, Xiaofeng Du, Yu Yang, Meijing Lin, Xiaobo Qu To speed up the acquisition time of multi-dimensional magnetic resonance spectroscopy (MRS), one typical way is to sparsely acquire free induction decay (FID) data reconstruct the spectrum from the incomplete observations. Recently, a low rank Hankel matrix (LRHM) approach, that explores the sparse number of spectral peaks, has shown great ability to reconstruct the spectrum. When the data are highly undersampled, however, low intensity spectral peaks are compromised in the reconstruction. In this abstract, a weighted LRHM approach is proposed. A weighted nuclear norm is introduced to better approximate the rank constraint, and a prior signal space is estimated from the pre-reconstruction to reduce the number of unknowns in reconstruction. Results on both synthetic and real MRS data demonstrate that the proposed approach can reconstruct low intensity spectral peaks better than the state-of-the-art LRHM method. 3887. 96 Quintuple tuned coil configuration for multi-nuclear metabolic MRI at 7 tesla Tijl van der Velden, Anh Pham, Carel van Leeuwen, Debra Rivera, Mark Gosselink, Dennis Klomp Metabolic and anatomic imaging by combining X-nuclei imaging with 1H imaging has shown great potential in clinical research. Traditional multi-nuclear coil setups are however limited to 2 or 3 frequencies, and often birdcage for 1H. In this study we propose a coil array setup tuned for acquiring 5 different nuclei in a single scan session practically without compromising efficiency on any nuclei. MRS Applications Electronic Poster Spectroscopy & Non-Proton MR Tuesday, 19 June 2018  Exhibition Hall 08:15 - 09:15  Computer # 3888. 97 Probing alterations of cellular metabolism in a mouse model of Huntington’s disease (R6/1) using in vivo MRS and DW-MRS Clémence Ligneul, Edwin Hernandez-Garzon, Marco Palombo, Julien Flament, Julien Valette Huntington’s disease is a genetic neurodegenerative disorder caused by the abnormal repetition of the CAG triplet in the gene coding for huntingtin (Htt). R6/1 mouse model, expressing a human form of mutated huntingtin, exhibits a progressive neuronal alteration in the striatum. We use in vivo MRS and diffusion-weighted MRS at various diffusion-weightings and diffusion times to detect changes in cellular metabolic content and structure R6/1 mice striatum. We report massive metabolic remodeling, especially for N-acetyl aspartate (NAA) and Glutamine (Gln), as well as changes in glutamate diffusion properties that we tentatively relate to variations in glutamate cellular compartmentation. 3889. 98 Metabolite concentration changes associated with positive and negative BOLD signal in the human visual cortex: a functional magnetic resonance spectroscopy study at 7T. Yohan Boillat, Lijing Xin, Wietske Van der Zwaag, Rolf Gruetter The metabolite correlates of the negative BOLD signal were investigated using functional MRS and compared to the changes produced by the positive BOLD response. The participants were scanned in a 7-T MRI while passively viewing visual checkerboards. For the positive BOLD response, increases of glutamate and lactate concentrations were observed, while the negative BOLD response in a similar voxel was linked to a decrease of glutamate, lactate and GABA concentrations. This measured decrease of oxidative metabolism during the negative BOLD response suggest a reduction a glutamatergic activity in the visual cortex. 3890. 99 Changes of brain metabolites in response to acupuncture therapy in migraine are correlated with clinical outcomes: Result from a magnetic resonance spectroscopy imaging Study Tao Gu, Min Chen, Ryan CN D’Arcy , Xiaowei Song Migraine is a common neurological disease. Acupuncture has been proven to be effective but the mechanisms remain unclear. A proton magnetic resonance spectroscopy imaging (MRSI) study was used to investigate biochemical changes in brain regions key for the transmission of pain in response to acupuncture treatment. Results showed acupuncture treatment was associated with a significantly increased NAA/Cr in bilateral thalamus in migraine patients. A strong significant correlation between NAA/Cr and headache intensity was found in thalami. Our data provided the first evidence suggesting a brain biochemical change in response to acupuncture therapy in migraine, in correlation with clinical outcomes. 3891. 100 Synergy between probiotics and antibiotics for the treatment of chronic hepatic encephalopathy: a longitudinal in vivo 1H MRS study of brain metabolism. Emmanuelle Flatt, Cristina Cudalbu, Olivier Braissant, Stefanita Mitrea, Dario Sessa, Valérie A. Mc Lin, Rolf Gruetter Chronic hepatic encephalopathy(HE) is a well-accepted complication of chronic liver disease(CLD), and finding the right treatment to reduce HE episodes before liver transplant remains a challenge. Both rifaximin and probiotics are currently used to reduce HE symptoms, but their precise effect on brain metabolites have never been studied. Our aims were first to assess in vivo and longitudinally the effect of the combination of probiotics and rifaximin on a rat model of chronic HE; and second to compare the results obtained to groups of non-treated/rifaximin-only treated rats. 1H-MRS at high field combined with biochemical and behavioral tests were used. 3892. 101 Shorter apparent T2 relaxation times of metabolites in the older human brain Dinesh Deelchand, J. McCarten, Laura Hemmy, Edward Auerbach, Malgorzata Marjanska The goal of this study was to compare the apparent transverse relaxation time constants (T2) of metabolites obtained in young and older subjects in three brain regions (occipital cortex (OCC), posterior cingulate cortex (PCC) and prefrontal cortex (PFC)) using LASER at 3T. A lower apparent T2s of N-acetyl aspartate and tissue water were measured in older adults in all three regions. T2 for total creatine and myo-inositol were also shorter in older adults in OCC and PCC. In conclusion, differences in T2 values of metabolites during normal brain aging are region-dependent. 3893. 102 Magnetic Resonance Spectroscopy biomarkers predict patient outcome in subacute spinal cord injury Patrik Wyss, Peter Zweers, Anne Brust, Corinne Funk, Markus Berger, Anke Henning Spinal cord injury (SCI) is a very heterogeneous disease that makes it difficult to identify a single biomarker during rehabilitation therapy in order to predict the future patient status. In this study, we applied Magnetic Resonance Spectroscopy to examine specific metabolic markers in the pons 10 weeks after injury and correlated them with changes of the clinical status obtained twice during early rehabilitation. 3894. 103 Partial Normalization of altered brain acetate metabolism in alcohol-dependent subjects after one month of sobriety Lihong Jiang, Gustavo Angarita, Kevin Behar, Elizabeth Guidone, Barbara Gulanski, Stuart Weinzimer, Robin de Graaf, Graeme Mason The purpose of this study is to analyze the adaptation of brain acetate metabolism of AD subjects upon detoxification in order to understand the mechanism of alcohol addiction. Using 13C-magnetic resonance spectroscopy in combination of 2-13C-acetate infusion, and monitor the turn over rates of brain 13C-labeled glutamate/glutamine neurotransmitter, we have found increased brain acetate metabolism after detoxification treatment, suggesting the compromised acetate uptake/metabolism in AD subjects. 3895. 104 Investigation of ethanol stimulation on HepG2 cells in a high density cell culture on chip by correlation spectroscopy Dennis Kleimaier, Andreas Neubauer, Michaela Hoesl, Cordula Nies, Eric Gottwald, Lothar Schad Ethanol-induced toxicity leads to alterations of certain cellular functions such as mitochondrial dysfunction. This study investigated the feasibility to detect changes induced by 2‰ ethanol stimulation on HepG2 cells in an NMR-compatible bioreactor system by double quantum filtered correlation spectroscopy. During ethanol stimulation, the spectra with cells led to an increased SNR of the glucose (15.5±2.1 %) and lactic acid (10.8%) cross peaks. These changes were larger than the SNR reproducibility of (3.94±2.44)%. Our results show that the DQF-COSY sequence can be used for the investigation of ethanol-induced damage on cells in a bioreactor system (worse shim condition). 3896. 105 Response to glutaminase inhibition in patient-derived breast cancer xenograft models Maria Grinde, Jana Kim, Ida Henriksen, Hanna Tunset, Siver Moestue We used ex vivo 13C HR MAS MRS to determine glutamine consumption and conversion in two patient-derived xenograft models of breast cancer, aiming to identify metabolic differences between a responding (luminal-like) xenograft and a resistant (basal-like) xenograft. CB-839 inhibited tumor growth in luminal-like, but not basal-like, xenograft tumors. Response to treatment was associated with differences in glutamine utilization. Depletion of proline in responding tumors indicate that the effect of glutaminase inhibitors may be associated with metabolic adaption to tumor hypoxia. 3897. 106 Energy Metabolism Differences in Rat Skeletal Muscle Due to Restricted Ambulation Following SCI Celine Baligand, Fan Ye, Sean Forbes, Ravneet Vohra, Jonathon Keener, Prodip Bose, Floyd Thompson, Glenn Walter, Krista Vandenborne Classic rodent models of SCI can rapidly and spontaneously recover locomotor function, muscle mass, and energy metabolism within weeks after injury. This is attributed to “self training” and does not replicate the conditions experienced by human patients who are often confined to bed rest for an extended period of time. Using 31P-MRS during electrically stimulated exercise to assess mitochondrial oxidative capacity in vivo, we show that restricted activity by cast immobilization delays spontaneous recovery of skeletal muscle metabolism in a rat model of severe SCI. 3898. 107 Noninvasive biomarkers for the early diagnosis and staging of hepatic fibrosis : A real-time in vivo hyperpolarized 13C MR spectroscopy Chung-Man Moon, Yong-Yeon Jeong, Il-Woo Park, Sang-Soo Shin Hepatic fibrosis associated with chronic liver injury can progress to cirrhosis and ultimately hepatocellular carcinoma. To date, liver biopsy has been regarded as the gold standard for detecting hepatic fibrosis but with practical constraints. Therefore, alternative non-invasive diagnostic methods that can precisely evaluate progression of hepatic fibrosis are urgently needed. However, an in vivo study for hepatic fibrosis using hyperpolarized 13C-labeled pyruvate has not yet been attempted until now. The purpose of this study was to investigate the cellular metabolic changes at different stages of hepatic fibrosis for the early diagnosis. 3899. 108 In vivo characterization of glucose metabolism in pancreatic cancer xenografts. Shun Kishimoto, Jeffrey Brender, Tomohiro Seki, Ayano Enomoto, Kazutoshi Yamamoto, Murali Krishna Recently, we developed a post processing denoising algorithms that are based on singular value decomposition and its multidimensional analogue Tucker decomposition. These algorithms allow more than 10-fold improvement in signal to noise ratio in dynamic spectroscopy and more than 50-fold in dynamic spectral imaging studies. Using this technique, we successfully characterize the metabolic profiles of two pancreatic ductal adenocarcinoma xenografts, MiaPaca-2 and Hs766t tumors by injecting 50 mg of 13C6 glucose. This imaging is potentially applicable to human subject and provides even more information than PET or 13C DNP MRI alone. 3900. 109 High-Resolution Cardiopulmonary Imaging in Free-Breathing Mice using Hyperpolarized Xenon-129 Luis Loza, Mehrdad Pourfathi, Stephen Kadlecek, Kai Ruppert, Hooman Hamedani, Sarmad Siddiqui, Faraz Amzajerdian, Yi Xin, Ryan Baron, Mary Spencer, Tahmina Achekzai, Ian Duncan, Rahim Rizi Hyperpolarized gas MRI is a well-established tool for assessing lung structure and function in both humans and large animals. However, its utility in small animal models has been limited to terminal studies, as proper gas delivery requires an MR-compatible ventilation scheme that has thus far only been achievable using a terminal intubation process. In this study, we developed a method for delivering hyperpolarized xenon-129 gas to free-breathing mice. An array of pulse sequences were used to acquire high-resolution gas- and dissolved-phase images of the heart and lung structure. 3901. 110 Feasibility of the in vivo measurement of acetate metabolism by 1H-[13C] MRS at 14.1T in the mouse hypothalamus Blanca Lizarbe, Irene Guadilla, Rolf Gruetter Astrocytic metabolism is impaired in many central nervous system diseases, like obesity or diabetes. Using 1H-[13C] MRS together with [2-13C]acetate infusion in a 14.1T magnet, we have measured the incorporation of 13C labeling in the mouse hypothalamus in vivo, and calculated its metabolic fluxes using a two-compartment metabolic model that distinguishes between neurons and astrocytes. We think that these results open the possibility of investigating local variations of astrocytic metabolism in the mouse hypothalamus in vivo. 3902. 111 Stress Induced bioenergetic perturbations in CMS rat model of Depression – An invivo phosphorousMRS study at 7T.Did Not Present Hemanth Kumar B S, Dinesh Deelchand, Sushanta Mishra, Sadhana Singh, Subash Khushu A chronic mild stress (CMS) animal model for depression was developed and validated using behavioural studies like OFT, FST and SCT. Following anaesthesia, invivo Phosphorous MRS was acquired covering the entire brain using ISIS pulse sequence at field strength of 7T. The spectra thus acquired were processed using LC-model for bioenergy metabolites quantification. The overall study provides new evidence on brain energy related metabolites and redox balance in CMS rats as compared to controls, suggesting that compromised energy metabolism and altered NAD biology observed in CMS rats. The study also revealed changes in High energy phosphate metabolites and membrane phospholipids. 3903. 112 Assessment of gene therapy efficacy by neurochemical profiling Ivan Tkac, Igor Nastrasil, Kanut Laoharawee, Kelly Podetz-Pedersen, Kelley Kitto, Carolyn Fairbanks, Walter Low, Karen Kozarsky, R McIvor Mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome, is a rare X-linked recessive lysosomal disorder caused by defective iduronate-2-sulfatase (IDS). Enzyme replacement is the only FDA–approved therapy available for MPS II, but it does not improve neurologic outcomes in MPS II patients. The 1H MRS data acquired from the hippocampus and cerebellum of untreated and AAV9-IDS treated MPS II mice and heterozygote controls clearly demonstrate that the direct transfer of the missing IDS gene to the CNS at 12 weeks of age prevented neurochemical alternations typical for MPS II at 9 months of age. 3904. 113 Relationship of longitudinal changes in cerebral metabolite and diffusivity property during the early brain development Chun-Xia Li, Yuguang Meng, Hui Mao, Anthony Chan, Xiaodong Zhang In vivo Magnetic Resonance Spectroscopy (MRS) is widely used to characterize the cerebral metabolic disorders in the developing brains of human and animal models. Prior study has demonstrated the spatial and temporal difference in evolution pattern of each metabolite during early brain maturation. This study is aimed to investigate the relationship of the longitudinal change of each metabolite with the microstructural evolution during early brain development in the cingulate cortex (ACC) of rhesus monkeys. The results demonstrated the heterogeneity of correlation degree of each metabolite with the microstructural maturation, suggesting combined MRS/DTI examination could offer complementary information to characterize early brain maturation and related disorders in pediatric research. 3905. 114 Higher Vitamin C Concentration in Patients with Alzheimer’s Disease Malgorzata Marjanska, J McCarten, Laura Hemmy, Melissa Terpstra The concentrations of the antioxidants vitamin C (ascorbate, Asc) and glutathione (GSH) were quantified as components of the neurochemical profile using 7 T 1H MRS in patients with Alzheimer’s disease (AD) and age-matched controls. Spectra were measured at ultra-short echo time in the posterior cingulate cortex (PCC), which is involved in AD, and the occipital cortex (OCC) as a control region. In patients, the concentrations of Asc and myo-inositol were higher in both regions. In the PCC of patients, total choline concentration was also higher. 3906. 115 Differences in steady-state glutamate levels and variability between ‘non-task-active’ control conditions: Evidence from ¹H fMRS of the prefrontal cortex Jonathan Lynn, Eric Woodcock, Chaitali Anand, Dalal Khatib, Jeffrey Stanley Proton functional magnetic resonance spectroscopy (1H fMRS) is capable of detecting dynamic changes in brain glutamate related to task engagement compared to a “non-task-active” control condition. The selection of an appropriate control condition is critical, which may confound the magnitude change in glutamate modulation. The purpose of this 1H fMRS study was to compare the steady-state levels of glutamate and its variability in the left dorsolateral prefrontal cortex during four different putative control conditions. Results show significant differences in the glutamate level and variability between conditions, emphasizing the importance of the control condition for the detection of task-evoked glutamate modulation. 3907. 116 Metabolic basis of (de)activation fMRI paradigms: J-edited lactate and diffusion-weighted water 1H-MRS Yury Koush, Robin de Graaf, Ron Kupers, Laurence Dricot, Douglas Rothman, Fahmeed Hyder During task-based versus rest epochs, the BOLD signal increases in a task-positive region (activation paradigm) and decreases in a task-negative region (deactivation paradigm), also known as the default mode network (DMN). We investigated the metabolic basis of (de)activation paradigms using concurrent 1H-MRS acquisitions of J-edited lactate and diffusion-weighted water. Using (de)activation paradigms, we detected associated increase of water (i.e., BOLD signal) and lactate in visual cortex (non-DMN area), whereas in posterior cingulate cortex (DMN area) water decreased but lactate did not change. These results suggest similar degrees of aerobic glycolysis in both DMN and non-DMN areas. 3908. 117 Neurochemical profiling in the rat model of Tourette’s Syndrome @ 11.7T Alireza Abaei, Francesca Rizzo, Dinesh K Deelchand, Tobias M. Böckers, Volker Rasche Tourette’s syndrome (TS) is a neurodevelopmental disorder characterized primarily by motor tics probably due to dysfunctions of the cortico-striato-thalamic-cortical loop (CSTC) but the underlying molecular reason why tic occur is not yet known. In this study, a dedicated optimized STEAM sequence with single-shot phase and frequency correction, and image-based shimming was applied to uncover the metabolic “signature” of a tic using in vivo 1H-MRS at 11.7T. Despite a clear ticking phenotype observed in our animal model, the unaltered striatal neurochemical profile suggest questions on the role of the striatum within the supposed dysfunctional cortical-striatal-thalamic-cortico circuitry in TS. 3909. 118 Correlations Between Brain Structural Volumes and Brain Metabolite Concentrations in Alzheimer’s Disease: Preliminary Results from the NeuroMet Project Ariane Fillmer, Theresa Köbe, Semiha Aydin, Laura Goeschel, Agnes Flöel, Florian Schubert, Bernd Ittermann The NeuroMet project aims to identify new biomarkers for Alzheimer’s disease (AD) and to reduce measurement uncertainties for known biomarkers for AD. This work presents first NeuroMet results with a focus on ultra-high field MR imaging and MR spectroscopy. Significant correlations were found between volumes of cortical and subcortical gray matter structures and concentrations of NAA, glutamate and GABA. 3910. 119 Brain lithium and myo-inositol levels in lithium treated and non-lithium treated bipolar disorder patients Fiona Smith, Peter Thelwall, Carly Flowers, Matthew Birkbeck, Joe Necus, Andrew Blamire, David Cousins The action of lithium in bipolar disorder (BD) is incompletely defined but the inositol depletion hypothesis1 states that lithium inhibits IMPase to deplete myo-inositol, confirmed in vivo using proton magnetic resonance spectroscopy (1H-MRS) following acute treatment2,3 Chronic treatment may upregulate IMPase, with trend-level increases in grey matter myo-inositol reported.4 This 1H-MRS study compares frontal white matter myo-inositol/creatine levels (8cm3 voxel) in BD subjects (lithium-treated versus BD controls taking other medication), supplemented by measuring brain lithium signal intensity using 3D 7Li-MRI. Myo-Ino/Cr levels were significantly lower in the lithium-treated group, but their levels did not correlate with 7Li-MRI signal intensity. 3911. 120 MR-Spectroscopic Imaging in the Spotlight of the 2016 WHO ClassificationDid Not Present Elie Diamandis, Carl Philipp Simon Gabriel, Horst Urbach, Irina Mader, Dieter Heiland The purpose of this study is to map spatial metabolite differences across the three molecular subgroups of glial tumors, defined by the IDH1/2 mutation and 1p19q-co-deletion, using chemical shift imaging. The classification was based on a radiomic approach to the spectroscopic data. J-Difference-Edited MRS/MRSI Electronic Poster Spectroscopy & Non-Proton MR Tuesday, 19 June 2018  Exhibition Hall 09:15 - 10:15  Computer # 3959. 49 Simultaneous Measurement of Glutamate, Glutamine, GABA, and Glutathione by Spectral Editing Without Subtraction Li An, Jun Shen A novel spectral editing approach was proposed to simultaneously measure glutamate, glutamine, GABA, and glutathione at 7 T. By using a single editing pulse, a relatively short echo time of 56 ms was achieved. The main targets of the signal detection were the H2 and H4 protons of GABA and the H4 protons of glutamate, glutamine, and the glutamyl moiety of glutathione. No motion-sensitive data subtraction was required. 3960. 50 High-Speed Density Matrix Simulation of PRESS with A Single Editing Pulse Li An, Jun Shen A single spectral editing pulse incorporated into the PRESS sequence produces large Bloch-Siegert shift. The lack of a general method to quantify these shifts for spectral editing experiments has made it necessary to use a second identical editing pulse to cancel the shift. Here we describe a high-speed density matrix simulation method to accurately simulate a PRESS sequence with a single editing pulse for simultaneous detection of glutamate, glutamine, GABA, and glutathione at TE = 56 ms and 7 Tesla. To facilitate in vivo quantification, the frequency dependent Bloch-Siegert shift is accurately calculated and removed from the spectra. 3961. 51 Simultaneous edited MR spectroscopy of glutathione and macromolecule-suppressed GABA Georg Oeltzschner, Kimberly Chan, Muhammad Saleh, Mark Mikkelsen, Nicolaas Puts, Richard Edden γ-aminobutyric acid (GABA) and glutathione (GSH) can be simultaneously measured in the human brain in vivo at 3T using Hadamard encoding and reconstruction of MEGA-edited spectroscopy (HERMES). A drawback of conventional HERMES of GABA/GSH is the contamination of the edited GABA peak with co-edited macromolecular signals (MM), reducing the specificity of the method. We propose the addition of symmetrical suppression into the HERMES framework, and demonstrate the successful implementation of this approach in ten healthy subjects. 3962. 52 Editing everything with HERCULES: Hadamard-encoded editing of seven low-concentration metabolites Georg Oeltzschner, Daniel Rimbault, Mark Mikkelsen, Muhammad Saleh, Nicolaas Puts, Richard Edden Low-concentration metabolites can be detected at 3T with J-difference-edited MR spectroscopy. However, long acquisition times (~10 min per metabolite) make edited studies of many metabolites unfeasible. Multiplexed editing experiments have increased the time efficiency of editing while maintaining its specificity. Here, we introduce HERCULES (Hadamard Editing Resolves Chemicals Using Linear-combination Estimation of Spectra), an advanced multiplexed approach to differentiate the evolution of eight editable spin systems (GABA, GSH, Asp, Asc, NAA, NAAG, Lac and 2-HG) within a single experiment. HERCULES quantifies a total number of 13 metabolites, providing a 7T-like neurochemical profile of neurotransmitters, antioxidants, and metabolic markers at 3T. 3963. 53 Bilateral functional MRS of GABA with real-time frequency and motion correction at 7T Anouk Marsman, Vincent Boer, Mads Andersen, Esben Petersen Brain function is largely controlled by inhibitory processes steered by main inhibitory neurotransmitter GABA. In this role, GABA is essential in brain development and plasticity as well as neuropsychiatric and neurodegenerative diseases. In order to accurately measure GABA responsiveness, we designed a bilateral edited fMRS sequence including real-time frequency and motion correction, as the relatively weak GABA signal is highly susceptible to frequency drift and motion. As acquisition of the macromolecule-uncontaminated GABA signal is challenging at lower field strengths, experiments were performed at 7T. 3964. 54 Test-retest reproducibility of quantitative proton MRS using short-TE STEAM and semi-LASER sequences in young adult volunteer brains at 7T. Tomohisa Okada, Hideto Kuribayashi, Lana Kaiser, Yuta Urushibata, Nouha Salibi, Ravi Seethamraju, Sinyeob Ahn, Tadashi Isa, Koji Fujimoto Recently, 7T-MR system has been approved for clinical use in Europe and USA; however, its clinical configuration is limited to single-channel transmit so B1+ shimming is not feasible. This study investigated reproducibility of single-voxel MRS using short-TE STEAM and semi-LASER using a single-transmit & 32-receiver head coil at 7T. Fifteen healthy young volunteers were scanned twice at the posterior cingulate. SNR was higher in semi-LASER, but coefficients of variation were comparable ranging mainly from 5-10% and better in short-TE STEAM in low-concentration J-coupled peaks. Even with clinical setups, 7T shows high reliability and will contribute to MRS investigation. 3965. 55 Impact of sub-echo timings of PRESS on quantitative glutamate/glutamine level using LCModel at 7T Tzu-Jung Fei, Cheng-Wen Ko, Moritz Braig, Jochen Leupold In this study, we investigated the signal variation of Glu and Gln along sub-echo timings (TE1, TE2) in PRESS acquisitions on a preclinical 7T system. Our results show that the choice of sub-echo timings (TE1, TE2) for PRESS may alter the quantitative outcome remarkably for strongly coupled metabolites, e.g. Glu, Gln. The basis-sets used for LCModel analysis has to be carefully simulated and take the sub-echo timings into account since J-evolution of strongly coupled resonances may vary with TE1/TE2 at high fields. Quantitative comparison on these metabolites with mismatched sub-echo timings (TE1, TE2) can result in invalid conclusion. 3966. 56 Non-water Suppressed GABA Edited Magnetic Resonance Spectroscopic Imaging using Density Weighted Concentric Rings k-space Trajectory Uzay Emir, Pingyu Xia, Xiaopeng Zhou, Mark Chiew, Adam Steel, M Albert Thomas, Ulrike Dydak In this study, we have developed and demonstrated a non-water suppressed GABA editing Magnetic Resonance Spectroscopic Imaging technique using density-weighted concentric rings k-space trajectory that performs robustly within a clinically feasible acquisition time at 3T. The method has been validated in a series of phantom experiments and its feasibility assessed in a healthy volunteer with a high in-plane resolution of 7.5 × 7.5 mm2. Experiments qualitatively demonstrate the advantage of the proposed method in terms of its improved resolution and reduced contamination of spectra from neighboring voxels. 3967. 57 Automated MR Spectrum Registration for In Vivo Mouse MEGA-PRESS Study at 9.4T And the Introduction of MRSMouse2.0 Jia Guo, Douglas Rothman, Scott Small The goal of this study was to develop the tailored automated processing and quantification software for Meshcher–Garwood point resolved spectroscopy (MEGA-PRESS) in research of mouse models at 9.4T. The proposed software, MRSMouse, consists of two modules: the data loading module, MRSMouseLoad, which reads the Bruker time-domain raw data and processes it into a frequency-domain GABA-edited spectrum with bandwidth, frequency and phase drift correction through spectrum registration; and the spectral fitting module, MRSMouseFit, which quantifies the metabolite concentrations by modeling the spectra as a linear combination of the simulated basis-set and a smooth-spline in the frequency domain. 3968. 58 Comparison of GABA and Glx Quantification from Edited and Unedited MR Spectra – assessment of age effects Akila Weerasekera, Diana Sima, Ronald Peeters, Tom Dresslaers, Oron Levin, Stephan Swinnen, Sabine Van Huffel, Uwe Himmelreich 1H-MR spectroscopy (MRS) is a well-established tool to provide in vivo measurement of gamma-aminobutyric acid (GABA), glutamine and glutamine (Glx) concentrations for a variety of conditions1. There is an increasing interest in using spectral editing methods to measure GABA and Glx in the human brain. The commonly used GABA-editing sequence MEGA-PRESS provides filtered GABA signals based on the molecule’s J-coupling2, 3. Nonetheless, quantitative comparison among presently used acquisition and analysis methods is lacking. Here we compare currently available spectral fitting methods to assess the in vivo concentration values for GABA and Glx derived from edited (MEGA-PRESS) and unedited (MEGA-PRESS-OFF) spectra. We have tested our approach to assess the inter-subject variability in neurotransmitter levels arising from age effects. 3969. 59 Towards repeatable GABA-MRS of the hippocampus: Development of an extended post-processing pipeline Yannik Völzke, Eberhard D. Pracht, Elke Hattingen, Tony Stöcker The low concentration and the overlap with more prominent resonances hamper the GABA quantification via MR spectroscopy. Strong B0 inhomogeneities in the hippocampus further impede reliable spectroscopic measurements. To increase the repeatability of the GABA quantification we developed a post-processing module for MEGA-sLASER measurements.The development of an optimized post-processing module reduces the coefficient of variation of the intra-session GABA/creatine signal ratio to (5-10)%. This is essential for clinical trials. 3970. 60 Simulations of MEGA-PRESS spectra to achieve quality criteria for GABA quantification Helge Zöllner, Alfons Schnitzler, Hans-Jörg Wittsack The purpose of this study was to investigate the influence of diminished spectral quality on GABA quantification by using MEGA-PRESS simulations. Different levels of spectral quality were created by adding artificial noise and line broadening to a simulated spectrum to mimic shimming quality. Initial results revealed that the impact of signal to noise ratio (SNR) is much higher than the impact of line broadening. Furthermore the error of peak fitting does not seem to reflect the real quantification error of the known GABA levels of the simulated spectrum. Further simulations and analyses are needed to assure these initial results. 3971. 61 Spectral simulations of glutathione at 7T: Comparison of two different spin system parameter setsVideo Permission Withheld Muhammad Saleh, Mark Mikkelsen, Georg Oeltzschner, Kimberly Chan, Adam Berrington, Peter Barker, Richard Edden Glutathione (GSH) is a redox compound, providing protection against reactive oxygen species. Abnormal variation in GSH concentration has been associated with several neurological diseases. Several studies quantify low-concentration metabolites, such as GSH, using simulated basis sets derived from spin system parameters available in the literature. Through simulations and phantom experiments, we assess the accuracy of two different sets of spin system parameters of GSH-cysteine at 7T. The disagreement between the phantom and simulation GSH-cysteine spectra suggests a need for further refinement of the spin system parameters. 3972. 62 Simultaneous editing of GABA and glutathione at 7T Muhammad Saleh, Mark Mikkelsen, Georg Oeltzschner, Kimberly Chan, Adam Berrington, Peter Barker, Richard Edden HERMES has been shown to simultaneously edit GABA and GSH at 3T. Spectral editing at 7T provides better editing pulse selectivity, e.g. quantifying GABA with less contamination from macromolecules. In this abstract, simulations, phantom and in vivo experiments were performed at 7T using the sLASER sequence for simultaneous editing of GABA and GSH using HERMES. HERMES with sLASER localization at 7T provides uniform localization, doubles the acquisition rate, and provides excellent separation of the metabolites without any loss in spectral quality compared to sequentially acquired measurements of GABA and GSH using MEGA-PRESS. 3973. 63 High Spatial Resolution Simulated Basis Sets for HERMES and MEGA-PRESS Diana Rotaru, David Lythgoe Low concentration metabolites with J-coupled peaks are difficult to quantify using MRS, even using MEGA-PRESS or its recently propose HERMES implementation. Using LCModel with simulated basis sets can lead to inaccurate metabolite quantification, since the spatial-dependence of the signal is often not fully accounted for. This can be minimised by increasing the number of spatial positions simulated, at the expense of computation time. We simulated basis sets for MEGA-PRESS and HERMES using the recently introduced approach based on one-dimension projections, as a replacement for the commonly used three-dimensional method, providing more accurate basis sets in shorter computation time. 3974. 64 Multi-Step Frequency-and-Phase Correction for Multiplexed Edited MRS Data Mark Mikkelsen, Muhammad Saleh, Jamie Near, Kimberly Chan, Tao Gong, Ashley Harris, Georg Oeltzschner, Nicolaas Puts, Kim Cecil, Iain Wilkinson, Richard Edden Multiplexed edited MRS – more than one edited experiment combined in a single acquisition – involves acquiring subspectra with four or more distinct signal profiles. This technique therefore requires a tailored approach for correcting frequency and phase errors associated with participant head motion and scanner instability. Here, we demonstrate a novel alignment algorithm, termed multi-step frequency-and-phase correction (msFPC), designed to deal with the challenges of aligning individual transients in multiplexed edited data. Testing this method on simulated and in vivo datasets, msFPC was found to outperform other previously demonstrated algorithms (spectral registration and spectral registration with post hoc choline-creatine alignment). 3975. 65 Scan Duration, Signal-To-Noise Ratio and Sample Size Considerations in GABA-Edited MRS Studies Mark Mikkelsen, Rachelle Loo, Nicolaas Puts, Richard Edden, Ashley Harris We investigate the relationships between scan duration, signal-to-noise ratio (SNR) and group-level variance in GABA-edited MRS. Typically, GABA editing takes ~10 min for a 27-mL voxel. GABA+/Cr measurements from five voxels from 18 participants were analyzed by cumulatively binning the averages within each dataset to determine the effects on SNR and group-level variance. Sample size calculations estimated the required sample sizes needed for different predicted effect sizes in GABA-edited MRS studies. We show that the duration of GABA-edited acquisitions can be reduced if taking into account a statistically acceptable amount of group-level variance and the magnitudes of predicted effects. 3976. 66 Optimal phased-array signal combination from separate coil elements for GABA quantification at 7T Donghyun Hong, Seyedmorteza Rohani Rankouhi, Jan-Willem Thielen, David Norris Hitherto, signal combination strategies from separate coil elements have been evaluated on the basis of spectral SNR improvement. This study compared various combination methods for two representative GABA measurement techniques: GABA editing and short echo time acquisitions, and investigated which signal combination method is optimal in terms of GABA quantification using LCModel. 3977. 67 Feasibility of ultra-short TE MRS with full intensity to detect human brain glutathione, glutamine and GABA on 3 T and 4 T Xi Chen, Yihong Yang, Dost Ongur, Fei Du GABA, glutamine (Gln) and Glutathione (GSH) are important metabolites in human brain. However, with regular proton MRS, all of them are subject to J modulations during the moderate TE and hardly reliably observed. This study utilizes SPECIAL, an ultra-short TE MRS with full intensity, on 3T and 4T human scanners to test its feasibility to detect GABA, Gln and GSH. Compared to 3T PRESS, SPECIAL on 3T and 4T observed consistent Gln and GSH concentrations with higher reliabilities. Uniquely, 4T SPECIAL observed GABA+MM signal with significantly lower CRLB compared to 3 T measurements. 3978. 68 Increased Rostral Anterior Cingulate Cortex GABA+ Concentrations in IBS Patients with Anxiety Sofie Tapper, Adriane Icenhour, Olga Bednarska, Anders Tisell, Susanna Walter, Peter Lundberg The aim was to investigate whether Glutamate and GABA concentrations were altered in the rACC in patients with IBS compared to healthy controls, and to investigate if the GABA and Glutamate concentrations were associated with the level of anxiety in IBS patients. We observed higher rACC GABA+ concentrations in IBS patients, whereas Glx concentrations remained unaltered. Moreover, the changes in GABA concentrations were most pronounced in patients with high severity of anxiety. Thus, our findings provide first evidence of dysregulated rACC GABAergic neurotransmission in IBS, and suggest that altered inhibitory neurotransmission may be linked to comorbid anxiety in IBS patients. 3979. 69 Macromolecule Suppressed GABA Editing with Reduced Artifact in Region near Sinuses using Improved MEGA-SPECIAL Sequence Meng Gu, Ralph Hurd, Laima Baltusis, Frederick Chin, Daniel Spielman B0-inhomogeneity-insensitive GABA editing with MM suppression has been developed using improved MEGA-SPECIAL sequence using highly selective (30 ms) editing pulses allowed by 1D ISIS localization and 1D echo planar gradient in the logical S/I direction. MM suppressed GABA editing was successfully achieved in occipital lobe. However, GABA editing in regions near sinuses, e.g. anterior cingulate cortex (ACC), was compromised from imperfect subtraction in the ISIS localization. To reduce artifact in this region, the ISIS and 1D EP gradient were applied in the logical R/L direction together with a 16-step phase-cycled acquisition. These methods significantly improved edited spectra obtained from ACC. 3980. 70 Frequency-dependent cortical plasticity via GABA modulation Caroline Lea-Carnall, Faezeh Sanaei Nezhad, Nelson Trujillo-Barreto, Marcelo Montemurro, Wael El-Deredy, Laura Parkes Gamma-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the human brain and is thought to underlie plasticity processes. We tested the effect of repetitive tactile stimulation using two driving frequencies on GABA concentration using functional magnetic resonance spectroscopy (fMRS) and psychophysics testing. We were able to detect changes within a single scan session at 3 Tesla (3T) and relate these to well-established behavioural markers of plastic change demonstrating the utility of fMRS as a novel tool to understand the mechanisms of plasticity and the efficacy of therapeutic treatments. 3981. 71 Effect of DRD4 receptor -616 C/G polymorphism on thalamic GABA levels in pediatric primary nocturnal enuresis patientsDid Not Present Yi You, Zijun Li, Xiaoqi Wang, Bing Yu The objective of this study is to explore the effect of DRD4 −616 C/G single nucleotide polymorphism (SNP) on thalamic GABA levels in with primary nocturnal enuresis (PNE). Results indicates the DRD4 −616 C allele is associated with increased thalamic GABA levels and higher arousal from sleep (AS) scores in PNE children. This research helps us understand the genetic susceptibility of the DRD4 −616 C allele to PNE. 3982. 72 Baseline GABA Concentration Predicts Treatment Response to Selective Serotonin Reuptake Inhibitors in Major Depressive Disorder Xiang He, Kenneth Wengler, Greg Perlman, Elizabeth Bartlett, Christine DeLorenzo Major depressive disorder (MDD) affects more than 350 million people world-wide. Large heterogeneities in patient symptoms has led to several different treatment courses. Although treatments, such as SSRIs, are generally effective, a large portion of patients (~30%) do not achieve remission. The ability to predict which treatment option will yield the best outcome would be of great use to clinicians and patients. The GABAergic system is implicated in MDD and affected by SSRIs. In this study GABA concentrations were measured with MEGA-PRESS MRS in MDD patients before and after treatment with a SSRI to determine predictive ability and treatment changes. Non-Proton MRS/MRI: Novel Applications Electronic Poster Spectroscopy & Non-Proton MR Tuesday, 19 June 2018  Exhibition Hall 09:15 - 10:15  Computer # 3983. 73 Relative quantification of the 23Na MRI signal of human intervertebral lumbar discs Stephan Gruber, Stefan Zbyn, Thomas Stulnig, Wolfgang Bogner, Siegfried Trattnig, Lenka Minarikova 23Na MRI was applied in five healthy volunteers to determine the feasibility of intervertebral discs sodium signal quantification using the cerebrospinal fluid signal from the spinal column as an internal reference. There were no significant differences between the five measured volunteers, or between the different discs (L1/2 – L5/S1), that were analysed. Therefore, internal referencing using CSF has the potential for sodium content quantification in intervertebral discs, which may be used as an indicator of disc degeneration. 3984. 74 23NA-MRI of the skeletal muscle and skin in patients with adrenal insufficiency Andreas Weng, Stephanie Burger-Stritt, Irina-Oana Chifu, Martin Christa, Bernhard Petritsch, Thorsten Bley, Herbert Köstler, Stefanie Hahner Patients with chronic primary adrenal insufficiency require life-long glucocorticoid- and mineralocorticoid- replacement therapy. Monitoring of treatment is mainly based on clinical parameters and additional measurement of electrolyte status and plasma renin levels. However, obtained values often do not correspond to the patients’ subjective well-being and thus may not fully reflect optimal treatment. The present study investigated sodium content in the calf muscle and the skin obtained via 23Na-MRI in patients with chronic primary AI and healthy controls. Sodium content assessed by 23Na-MRI correlates with further parameters of mineralocorticoid activity and may serve as an objective method to monitor hormone substitution therapy in patients with adrenal insufficiency. 3985. 75 Electrophysiological stimulation of excised rat muscle elicits a measurable change in tissue sodium concentration using 23Na-MRI Frank Riemer, Joshua Kaggie, Cormac O'Neill, Mary McLean, James Grist, Myfanwy Hill, Joe Guy, Rolf Schulte, Martin Graves, James Fraser, Ferdia Gallagher Changes in the tissue sodium gradient play an important role in cell signalling such as at the neuromuscular junction and as part of neuronal action potentials. 23Na-MRI has the ability to measure the macroscopic sodium distribution. In this study we investigated the changes in tissue sodium in an electrically stimulated and freshly excised rat leg muscle. 3986. 76 Comparison of quantitative imaging methods of sodium concentration in leg muscle Ryan Larsen, Luis Perez, Kenneth Wilund, Theodore Claiborne, Brad Sutton Quantitative imaging of tissue sodium content requires corrections for coil loading. This can be done by introducing external calibration standards within the scan, or by employing the principle of reciprocity to normalize the signal by the voltage required to obtain a signal maximum. A direct comparison of these two quantification methods shows that they are highly consistent. 3987. 77 Mapping Brain Tissue Sodium Parameters Using Fast 3D Multi-Echo Radial Imaging Jinhu Xiong, William Kearney, Ankit Parekh, Mathews Jacobs, Rolf Schulte, Baolian Yang, Vincent Magnotta We have developed 3D Multi-Echo Radial Imaging and Tikhonov reconstruction techniques for mapping brain tissue sodium concentration and R2* relaxation rate. The total acquisition time is about 6 minutes. Intra- and inter-cellular sodium concentrations and R2* relaxation rates were simultaneous estimated. Our long term aim is to develop 23Na imaging techniques for studies of brain function and diseases. 3988. 78 31P MRS of the frontal lobe of human brain at 7T Shizhe Li, Li An, Jan Willem van der Veen, Maria Ferraris Araneta, Johnson Christopher, Yu Shao, Shumin Wang, Jun Shen, Jun Shen The majority of neuropsychiatric disorders are thought to be originated in the frontal lobe. Increasing the SNR of frontal lobe 31P MRS using a surface coil can be very important because many MRS manifestations of psychiatric illnesses could be subtle. This study demonstrates the feasibility of high SNR 31P MRS of human frontal lobe using a surface coil and 3D CSI at 7 Tesla. Comparing to the occipital lobe spectra acquired from the same subject it was shown that the sensitivity and spectral resolution of 31P MRS spectra of the frontal lobe can be made comparable to that of the occipital lobe. 3989. 79 Influence of BMI and hepatic lipids on absolute quantification of 31P metabolites at 7T Lorenz Pfleger, Martin Gajdošík, Peter Wolf, Sabina Smajiš, Paul Fellinger, Sigfried Trattnig, Michael Krebs, Marek Chmelík, Martin Krššák This study focuses on absolute quantification of hepatic 31P metabolites at ultra-high field (7T) and the possible influence of BMI and hepatocellular content of lipids (HCL) on the calculated metabolite concentrations. Significant differences were found in γ- and α-ATP as well as in Pi content for population groups with normal and high BMI. With the assessment of HCL it is possible to correct for those differences and no significances could be reported after. 3990. 80 Unambiguous detection of cardiac Pi using long TM 31P STEAM Albrecht Schmid, Ladislav Valkovic, Elizabeth Tunnicliffe, Christopher Rodgers Inorganic Phosphate is a resonance that holds important information on the metabolic state of tissues. From its resonance frequency, intracellular pH can be derived. The ratio of Pi to PCr or ATP are also important markers. Unlike in other tissues, myocardial Pi is frequently hidden underneath blood 2,3-DPG signals. Using 7 T STEAM's TM delay to be one cardiac cycle, blood-pool originating signals are gone and the Pi resonance is clearly visible. In 3 subjects, Pi signal was detected and quantified. The signal was around 4.89±0.02ppm, corresponding to a pH of 7.08±0.02. This is a breakthrough for the investigation of cardiac metabolism. 3991. 81 First experiences with a phosphorus 30 channel receiver head array at 7T Benjamin Rowland, Ian Driver, Mohamed Tachrount, Dennis Klomp, Ria Forner, Anh Pham, Michel Italiaander, Richard Wise Multi-receiver arrays offer the high sensitivity of surface coils and the extended field of view of volume coils, as long as the individual receivers can be combined correctly. In 31P MRS, the low intrinsic SNR makes determining weighting factors challenging and data quality can suffer. We report on our experiences of working with a custom-built 30 channel head coil, dual-tuned for 1H and 31P at 7T, comparing its performance against a traditional birdcage, in phantom and in vivo. Our results are encouraging, with equal SNR in the centre of the brain and significantly enhanced signal in the periphery. 3992. 82 In vivo Phosphorus Metabolite Imaging on a 3T MRI Scanner in a Clinically Feasible Scan Time Yunhong Shu, Joshua Trzasko, Aiming Lu, Joel Felmlee, John Port We developed an MRI system (coil, sequence, reconstruction) capable of performing imaging of phosphorus metabolites in a clinically-feasible scan time on a conventional 3T MRI scanner. Each component of the system is explained, and results of a phantom scan and scan of a human thigh are presented. 3993. 83 Functional phosphorus spectroscopy of the human visual cortex at 9.4 T Rolf Pohmann, Sathiya Raju, Klaus Scheffler Functional 31P spectroscopy has been investigated in several studies with greatly varying results, which may be due to the low sensitivity of the 31P nucleus. We have taken advantage of the high SNR at 9.4 T to acquire spectra from the human visual cortex under stimulation. Experiments were performed with different localization volumes, defined by saturation pulses. In spite of the excellent quality of the obtained data, no stimulation-related changes in metabolite concentrations or resonance frequencies could be detected. 3994. 84 T1 values of phosphorus metabolites in the human visual cortex at 9.4 T Rolf Pohmann, Sathiya Raju, Klaus Scheffler Ultra-high field has the potential to improve the quality of 31P spectroscopic applications due to the increased SNR and spectral dispersion. In addition, previous studies have reported a decreasing T1 with increasing field strength, which would further contribute to an improved quantification quality. In this study, we have measured the longitudinal relaxation time T1 in the visual cortex of healthy human subjects at 9.4 T, using an inversion-recovery technique. The values obtained were consistently lower than published data at 7 T, confirming observations of a decreasing T1 with field strength. 3995. 85 Quantification of human cardiac inorganic phosphate content in vivo by 31P-MRSI at 7T Ladislav Valkovic, Albrecht Schmid, Lucian Purvis, Jane Ellis, Matthew Robson, Stefan Neubauer, Christopher Rodgers Determination of human cardiac Pi using 31P-MRS is challenging as the resonance frequency of Pi is concealed by a close resonating 2,3-DPG signal originating from blood. Long TR acquisition using adiabatic excitation at 7T can compensate for the rapid blood signal replacement in partially-saturated short TR scans. In order to quantify Pi concentration in vivo, knowledge about longitudinal relaxation of Pi is still required. We have measured the T1 of Pi in 4 healthy volunteers at 7T using dual-TR method and used this value to quantify cardiac Pi concentration in 8 healthy volunteers. 3996. 86 In Vivo Measurement of Cerebral NAD Contends and Redox State in Young Mouse. Radek Skupienski, Kim Do, Roger Marti, Lijing Xin Nicotimamide adenine dinucleotide (NAD+ and NADH) is a key player of cell energy metabolism. 31P-MRS has been demonstrated for in vivo measurement of NAD content and redox state in cat and human brain, however, there is no reports in mouse brain. In this study we established the in vivo measurement of NAD+, NADH and NAD+/NADH in young (prepubetrtal) mice and compared two different quantification methods (Least square fitting and LCmodel). This study demonstrated the feasibility of in vivo measurement of NAD+, NADH and redox state in mouse brain and it opens the prospect of studying longitudinally the energy metabolism and redox dysfunction in mouse models of brain pathologies. 3997. 87 SNR optimized $$^{31}$$P fMRS to measure energy metabolism in the visual cortex Arjan Hendriks, Wybe van der Kemp, Natalia Petridou, Dennis Klomp Energy metabolism of the human visual cortex was investigated, by performing 31P fMRS. The used setup was optimized for high SNR by using a dedicated 31P RF coil at 7T and a visual stimulus with a large visual angle. Changes in the up-field peak of inorganic phosphate (Pi) are observed, revealing new promising opportunities to measure energy metabolism in the human visual cortex. 3998. 88 Dietary modulation of metabolic enzyme activity assessed by dynamic in vivo 31P-MRS of hepatic fructose metabolism Christian Farrar, Gregory Tesz, Jeremy Wellen In this study, 31P-MRS was applied to monitor hepatic fructose metabolism of rats in response to IV fructose challenge.  Animals exposed to 7-days of sucrose-enriched diet experienced enhanced fructose clearance relative to animals on an isocaloric control diet.  The finding of more efficient fructose metabolism in the sucrose fed group corresponded with elevated KHK and AldoB gene expression, two key enzymes responsible for fructose clearance.  Treatment of animals on sucrose diet with a KHK inhibitor nearly completely blocked fructose metabolism and prevented increased expression of these enzymes, implying that metabolism of fructose elicits the enzyme induction rather than fructose itself. 3999. 89 In vivo  $$^{31}\hspace{0.1 mm}$$\$P-MRS of triple negative breast cancer patients Erwin Krikken, Wybe van der Kemp, Peter Luijten, Kenneth Gilhuijs, Dennis Klomp, Hanneke van Laarhoven, Jannie Wijnen 31P-MR spectra of breast cancer tissue have shown very high GPC/PC ratios in xenografts for triple negative (TN) tumors. We set out to investigate if this is also visible  in vivo  in six TN breast cancer patients. In two of the patients the phosphocholine (PC) peak is missing or approaching zero. To the best of our knowledge, this is the first time that this phenomenon is shown in vivo in breast cancer patients, however, the relation of the presence or absence of PC and TN subtype remains to be investigated. 4000. 90 Detection of 13C glucose metabolism in multiple human brain regions using dynamic 1H MRS Steven Zhang, Chathura Kumaragamage, Pedro Neto, Jamie Near In vivo carbon-13 magnetic resonance spectroscopy is a quantitative technique for studying brain metabolism.  Here, we demonstrate the use of 1H MRS to indirectly observe the metabolism of 13C labelled glucose, simultaneously in two brain regions in a single healthy volunteer. This was done using only standard proton (1H) MRS sequences and hardware. Our results demonstrate an accumulation of 13C label in glutamate and glutamine that is distinctly observable due to the pronounced effect of heteronuclear scalar coupling. This technique provides insight into neuronal metabolic rates and may provide complimentary information to 18F-FDG PET in the study of neurodegenerative disorders. 4001. 91 Detection of 5-Fluorouracil (5-FU) Tumor Trapping Using Fluorine-19 Chemical Shift Imaging in a Murine Model of Colorectal Cancer Yurii Shepelytskyi, Karen Davenport, Matthew Fox, Tao Li, Mitchell Albert, Eric Davenport Colorectal cancer is an increasing healthcare problem and is the third leading cause of cancer deaths worldwide. Fluorine-19 (19F) chemical shift imaging (CSI) can detect the distribution of 5-fluorouracil (5-FU) and its metabolites within a tumor over time. By measuring the 5-FU trapping, it is possible to determine the tumor response at the earliest stage of treatment (before changes in tumor size are observable). In this work, we present preliminary results of detecting the presence and absence of 5-FU trapping in mice bearing H-508 and HT-29 colorectal tumors, respectively. 4002. 92 Mapping longitudinal changes in brain oxygenation in vascular cognitive impairment using 19F-MRI Ahmed Khalil, Susanne Mueller, Marco Foddis, Janet Lips, Ulrich Dirnagl, Sebastian Temme, Ulrich Floegel, Philipp Boehm-Sturm We assessed tissue oxygenation with 19F-MRI using perfluorocarbon emulsions in a mouse model of vascular cognitive impairment. Brain T1 values were measured using a cryogenic 19F/1H coil at multiple timepoints before and after surgery to induce bilateral common carotid artery stenosis and converted to pO2. T1 values decreased with increasing concentration of inhaled oxygen, and we observed a decrease in tissue pO2 following surgery which gradually recovered over four weeks. 19F-MRI of perfluorocarbon emulsions can be used for long-term assessment of brain tissue pO2 in vivo and may be relevant for monitoring endogenous or induced regenerative processes. 4003. 93 3D 7Li Magnetic Resonance Imaging of Brain Lithium Distribution in Bipolar Disorder Fiona Smith, Peter Thelwall, Carly Flowers, Joe Necus, Andrew Blamire, David Cousins Lithium is a major treatment for bipolar disorder (BD) and the likelihood of a favourable response may be determined by its distribution in the brain. Lithium can be directly detected by magnetic resonance (MR), but this is challenging compared to proton MRI due to lithium’s low therapeutic concentration in brain (<1mM). To overcome this challenge, we implemented a highly efficient balanced steady state free precession (b-SSFP) 7Li-MRI method. We report a 3D 7Li-MRI acquisition with 25mm isotropic resolution, acquired in 8 minutes using a 3T clinical scanner, demonstrating heterogeneity in lithium concentration within the brain in subjects with BD (n=14). 4004. 94 Use of dissolved-phase 129Xe imaging to visualize gas uptake and distribution in the free-breathing mouse Luis Loza, Stephen Kadlecek, Mehrdad Pourfathi, Kai Ruppert, Hooman Hamedani, Ian Duncan, Rahim Rizi The lung is an intrinsically difficult organ to image using conventional MRI. Although global structural features and major abnormalities are detectable using conventional MRI, lung structure on the vascular level is prohibitively difficult to image. Hyperpolarized gas MRI provides high enough signal to obtain high-resolution images of lung structure at the acinar level. Furthermore, with the use of hyperpolarized xenon MRI, dynamic images of xenon dissolution are made obtainable given xenon’s high solubility in blood and tissue. By applying decreasingly destructive pulses, the uptake and distribution of the gas throughout the body becomes visible. 4005. 95 Effects of Fraction of Inhaled Oxygen on Hyperpolarized 129Xe MR Signals Acquired from the Rat Brain In Vivo Yonni Friedlander, Marcus Couch, Andrea Kassner, Giles Santyr                 A theoretical model was developed to describe the dependence of the signal strength of  129Xe dissolved in the rat brain on the fraction of inhaled oxygen (FiO2). To validate the model, 129Xe MR signals were measured in the rat brain in vivo for four different values of FiO2 using a continuous ventilation scheme. The measured 129Xe RBC signal showed a strong dependence on FiO2 in good agreement with the trends predicted by the theoretical model. These results underscore the need to optimize and control FiO2 when using 129Xe signals to probe brain function. 4006. 96 17O bolus fluxes in rat head at 21.1 T Victor Schepkin, Cathy Levenson, Andreas Newbauer, Christian Schuch, Tilo Glaeser, Michael Kievel, Steven Ranner, William Brey, Shannon Helsper, Lothar Schad 17O MRI is an attractive and promising goal utilizing ultra-high magnetic fields.  The current study is devoted to the time changes of 17O MR signals detectable in a rat head at 21.1 T using bolus injection of 17O labeled water-17O and glucose-17O.  The time course of 17O-water revealed a two stage process of distribution.  During glucose injection the time course has the same stages as for water, and the third stage represents glucose metabolism.  The shape of the high resolution glucose time course is important for the accurate determination of tissue glucose consumption.
Spectroscopy: NMR & Other
Electronic Poster
Spectroscopy & Non-Proton MR

Tuesday, 19 June 2018
 Exhibition Hall 09:15 - 10:15