Marco Palombo, Masoumeh Dehghani, Nicolas Kunz, Bernard Lanz, Rolf Gruetter, Julien Valette

While most brain metabolites detected by in vivo MRS are intracellular, some of them, in particular energy metabolism substrates such as glucose, lactate and acetate, are also known to be significantly present in the extracellular space. Although of high metabolic significance and of practical importance for metabolic flux quantification in labeling studies, the accurate determination of the extracellular fraction remains challenging. Here we propose to use diffusion-weighted MRS combined with modeling of tissue microstructure to estimate acetate’s extracellular fraction in the rat brain, which we find to be ~45%.

Nicole Fichtner, Ioannis-Angelos Giapitzakis, Nikolai Avdievich, Ralf Mekle, Daniel Zaldivar, Anke Henning, Roland Kreis

Ultra-high field strengths provide higher signal to noise ratio and improved separation of metabolites in spectroscopy, allowing for more precise characterization of peaks. In particular, this improved peak resolution may be of benefit for characterization of the downfield (5-10ppm) spectrum, which is not yet well characterized; this experiment aims to improve knowledge of downfield peaks by investigating their exchange rates and T₁ values at 9.4T, using inversion transfer experiments and metabolite cycling to allow for non-water suppressed acquisition.

Yudu Li, Fan Lam, Bryan Clifford, Zhi-Pei Liang

This work presents a novel spectral model for spectral quantification, which represents each spectral component using a subspace instead of a parametric basis function with unknown parameters. The proposed model enables efficient and effective incorporation of both spectral and spatial prior information to improve the quantification performance. The proposed method is validated using both simulation and experimental data, demonstrating superior performance to existing methods using parametric spectral bases. This method is expected to be useful for processing noisy MRSI data.

Jia Guo, Yanping Sun, Zhu Gang, Scott Small, Douglas Rothman

As of yet J-difference editing methods such as MEGA-PRESS have not been applied to in vivo mouse studies due to low sensitivity and the lack of an automated program to analyze the data. To overcome the obstacles, a fully automated software toolkit MRSMouse was developed for the quantitative analysis of MEGA-PRESS data of the mouse brain. With MRSMouse, we demonstrated the feasibility and reproducibility of MEGA-PRESS for detection of GABA in the mouse brain using a Bruker BioSpec 94/20 9.4T system. During anesthesia, significant decreases of mouse thalamic GABA levels caused by isoflurane were noticed in vivo for the first time.

Andrew Maudsley, Mohammed Goryawala, Sulaiman Sheriff

The resonance frequencies of tissue metabolite are affected by cellular-level variations in magnetic susceptibility and the compartmentation of each metabolite. One prominent finding for 1H MRS studies of the brain is differences of the N-Acetylaspartate (NAA) resonance frequency in white matter, which is hypothesized to reflect the inter-axonal localization of this metabolite and susceptibility variations that are dependent on the orientation of the major axonal bundles relative to the applied magnetic field. In this study, the dependence of the NAA frequency on axonal orientation was evaluated using voxel-based analysis of a whole-brain MRSI and diffusion-tensor imaging.

Eric Baetscher, Thomas Barbara, Manoj Sammi, Krista Vandenborne, Glenn Walter, William Rooney

A synthetic radio-frequency (RF) signal, which is received along with the ¹H magnetic resonance (MR) signal in magnetic resonance imaging (MRI), is used to determine absolute tissue water and lipid quantities. We show application of this ERETIC method (electronic reference to access in vivo concentration) to musculoskeletal imaging, with the potential to better track disease progression in Duchenne Muscular Dystrophy (DMD), and other muscle pathologies.

Dianning He, Devkumar Mustafi, Xiaobing Fan, Sully Fernandez, Erica Markiewicz, Marta Zamora, Jeffrey Mueller, Joseph Sachleben, Matthew Brady, Suzanne Conzen, Gregory Karczmar

Epidemiological studies show increased risk of breast cancer associated with Western diets containing high animal fat. The aim of this study was to evaluate changes in mammary fat composition due to a high animal fat diet (HAFD), compared to a low fat diet (LFD), in a mouse model of breast cancer. Localized MR spectroscopy and high spectral and spatial resolution (HiSS) MRI data were acquired at 9.4T. The saturated fat fractions increased and the polyunsaturated bond component decreased significantly in HAFD mice compared to LFD mice. Fat images obtained from HiSS demonstrated increased mammary fat concentration in HAFD mice than LED mice.

Linqing Li, Ningzhi Li, Li An, Jun Shen

A driven steady states technique for brain metabolite relaxation measurement is proposed. Multiple steady states driven by long pulse train were used to quantify T2 of brain metabolites in vivo. The proposed technique does not need to vary echo time of the measuring sequence such as PRESS. A simple linear equation for quantification of driven steady state spectra was derived using Bloch equations. The derived equation was verified by Bloch simulations, phantom and in-vivo experiments.

Byeong-Yeul Lee, Xiao-Hong Zhu, Myung Kyun Woo, Wei Chen

Functional/metabolic changes in different brain regions of interest are of importance for better understanding of the pathophysiological mechanism underlying the human brain diseases. In this work, we present a novel design of the dual-channel ³¹P MRS system for simultaneous measurements of cerebral high-energy phosphate metabolism from two brain regions of interest by incorporating a new pulse sequence and two separated RF surface coils with a transistor-transistor logic (TTL) controller. By successfully implementing this method, we are able to obtain high quality in vivo ³¹P MR spectra from both frontal and occipital lobes within the same amount of time as the traditional method covering one brain region. From an engineering perspective, this new approach provides a cost-effective solution for in vivo ³¹P MRS study of multiple brain regions with a conventional single-channel transmitter-receiver configuration. Therefore, this valuable MR tool can be used in examining the cerebral energy metabolism across different brain regions, and the same approach could be employed to other spin applications.  

Zohaib Iqbal, M. Albert Thomas

The two dimensional J-resolved spectroscopy technique is capable of resolving many metabolites in vivo from a volume of interest. However, the spectral resolution along the indirect dimension is generally very poor in these acquisitions. One solution is to apply a covariance transformation along the indirect dimension to yield a resulting Covariance J-resolved (CovJ) spectrum with high spectral resolution. While spectral resolution is enhanced, currently there are no methods available to fit the non-linear aspects of the covariance reconstruction. Here, we have developed a non-linear fitting algorithm capable of yielding Glutamate, Glutamine, GABA, and Glutathione concentrations in vivo using CovJ spectra. 

Dhritiman Das, Eduardo Coello, Axel Haase, Rolf Schulte, Bjoern Menze

We present a data-driven technique for denoising 3D Magnetic Resonance Spectroscopic Imaging (MRSI) data. Our proposed method involves a novel spectral de-phasing and re-phasing approach which increases the phase dimension of the spectra to deal with the arbitrary complex phase in the data. This is coupled with an anisotropic non local means (NLM) filter-based pattern-recognition across the multi-slice data to select similar spectra patches having a similar phase for denoising. We show that our method leads to a mean SNR improvement by an average factor of 4.5 while preserving the spectral resolution of the metabolites.

Eva Heckova, Bernhard Strasser, Michal Považan, Gilbert Hangel, Siegfried Trattnig, Wolfgang Bogner

The unsuppressed internal water signal is a standard reference method used for quantification of brain metabolites in 1H-MRSI, however it requires additional water unsuppressed acquisition, which is in case of MRSI time demanding. Therefore we compared the performance of water signal reference acquired with unsuppressed MRSI and with ~2s long gradient echo imaging integrated into MRSI sequence. Our findings indicates that gradient echo imaging can be used as a concentration reference for 1H-MRSI.

Nassim Tayari, Jiri Obels, Thiele Kobus, Tom Scheenen, Arend Heerschap

Proton 3D MR spectroscopic imaging (MRSI) provides spatial metabolic information of the prostate for improved cancer detection, localization, and staging. Clinical application of  MRSI of prostate requires automatic quality control of spectra. We propose Qratio, a ratio balancing constructive spectral components of choline and citrate signals with destructive elements of lipid signals, water residuals and noise.  We demonstrate that Qratio can serve as a general, fast and automated tool for quality control of prostate MRSI data, independent of field strength (1.5-7T) and acquisition protocol. The Qratio can be displayed as maps and performs with an accuracy of 88±3% and AUC=0.93. 

Nuno Pedrosa de Barros, Richard McKinley, Roland Wiest, Johannes Slotboom

MRSI-data frequently contains bad-quality spectra, what can prevent proper quantification and consequently lead to data misinterpretation. Machine-learning based methods have been proposed for automatic quality control of MRSI-data with performance levels identical to expert’s-manual-checking and that can classify thousands of spectra in a matter of a few seconds. Besides this, a considerable amount of time needs to be spent labelling data required to train these algorithms. Here we present a method that allows to actively select those spectra that carry the most information for the classification, allowing to reduce drastically the amount of time needed for labelling.

Sophie Peereboom, Maximilian Fuetterer, Sebastian Kozerke

A phase-rotation acquisition scheme is able to separate different signals in PRESS. In this work phase-rotation PRESS measurements were complemented by simulations to assess origins of spectral distortions in cardiac spectroscopy. Simulations show that, when using a phase-rotation acquisition scheme for PRESS without spoilers, more motion is acceptable when pulses are better calibrated. However, because of non-ideal pulse profiles, spoilers cannot be fully omitted if moving tissue is studied. It is shown that phase-rotation acqusition can, by combining simulations and measurements, be used as an elegant tool to investigate spectral distortions and optimize sequence parameters in PRESS of moving tissue.

Sreenath P Kyathanahally, Andre Doering, Roland Kreis

Ghosting artifacts in spectroscopy are problematic since they superimpose with metabolites and lead to inaccurate quantification. Detection of ghosting artifacts using traditional machine learning approaches with feature extraction/selection is difficult since ghosts appear at different frequencies. Here, we used a “Deep Learning” approach, that was trained on a huge database of simulated spectra with and without ghosting artifacts that represent the complex variations of ghost-ridden spectra. The trained model was tested on simulated and in-vivo spectra. The preliminary results are very promising, reaching almost 100% accuracy and further testing on in-vivo spectra will hopefully confirm its ghost busting capacity

Claudiu Schirda, Tiejun Zhao, Yoojin Lee, Hoby Hetherington, Jullie Pan

Highly efficient sampling strategies based on gradient trajectories can accelerate MRSI studies by 1-2 orders of magnitude compared to conventional acquisitions. However, increasing acceleration and gradient slew rates commonly result in a predictable decline in spectral quality. This report uses rosette trajectory spectroscopic imaging studies to assess how spectral quality and Cramer Rao lower bounds influence how sensitive the MRSI and metabolite ratios are to the expected variation of tissue gray matter.

Angeline Nemeth, Hélène Ratiney, Benjamin Leporq, Amandine Coum, Giulio Gambarota, Kevin Seyssel, Bérénice Segrestin, Pierre-Jean Valette, Martine Laville, Olivier Beuf

Interest in the follow-up of fatty acid composition(saturated, polyunsaturated and monounsaturated fatty acid) in the body is growing. Quantitative MR spectroscopy can give access to this fat composition. Today, several quantification methods are used (e.g LCModel, AMARES). However the statistical outcome issued from a quantitative analysis of the lipid signal can be greatly influenced by the used quantification method. We analyze 1) the impact of the time sample selection and design of the model function on the parameter identifiability 2) the quantification results obtained with different quantification models on acquisitions performed in vitro (oils) and in vivo (subcutaneous adipose tissue).

Michal Bittšanský, Milada Kovácová, Oliver Štrbák, Petra Hnilicová, Dušan Dobrota

We introduce an easily implementable quantification method in vivo based on unsuppressed water measurement (pulse-acquire FID sequence with low flip-angle, short TE and TR and geometry identical to metabolite MRSI). Our quantification is practically independent on water relaxation times, requires only short extra measurement time and is robust enough in pathologies like tumors. We tested its results in a homogeneous phantom, healthy volunteers and tumor patients using a head resonator and an 8-channel array coil for acquisition.

Donghyun Hong, Seyedmorteza Rohani Rankouhi, Jan-Willem Thielen, David Norris

Good B0 field homogeneity is an essential requirement for NMR single voxel spectroscopy. Previously proposed spectral fitting method assumes that all metabolite signals have a Lorentzian shape. However, B0 inhomogeneity may both broaden the linewidth, and modify the lineshape into an asymmetric form. This study has demonstrated a water lineshape fitting method to overcome B0 inhomogeneity using corresponding metabolite fitting models by water lineshape. We obtained similar relative metabolite signal intensities and improved spectral fitting quality regardless of the field homogeneity condition.

Adrianus Bakermans, Paul de Heer, Gustav Strijkers, S. Boekholdt, Aart Nederveen, Jeroen Jeneson

Changes in myocardial total creatine (tCr) and triglyceride (TG) content have been linked to the pathogenesis of cardiomyopathy. An assessment of repeatability for absolute quantification of myocardial [tCr] and [TG] is required for ¹H-MRS to be employed for longitudinal monitoring of therapeutic efficacy. This work reports intra- and inter-exam repeatability of [tCr] and [TG] measurements with ¹H-MRS at 3 Tesla. Our results indicate that the repeatability of the ¹H-MRS assay will be sufficient to detect a >50% depletion of the tCr pool, and >50% changes in myocardial TG levels with 95% confidence in a single subject.

Carolina Fernandes, Bernard Lanz, Chen Chen, Peter Morris

Estimation of metabolic changes during neuronal activation represents a challenge for in vivo MRS, particularly in the case of lactate, whose dissociation from other resonances is not straightforward. To reliably quantify lactate, the lipid and macromolecular signals were significantly reduced by using a long TE (144 ms) and the remaining macromolecular signals in the vicinity of the lactate peak were individually fitted with lorentzian peaks. Statistically significant changes in lactate and glutamate levels during 15 min of visual stimulation were detected in the visual cortex, unveiling a distinctive metabolic response pattern, which can provide further insight into brain activation mechanisms.  

Yan Zhang, Li An, Jun Shen

Numerical simulations of three-dimensionally localized MRS spectra have been very time-consuming for multi-spin systems because the current state-of-the-art requires computation of a large ensemble of spins pixel-by-pixel in three dimensional space. In this abstract it was found that spatial coordinates of the full set of spin density operators labeled by slice selection gradients can be projected onto one dimension after slice selection as long as the crusher gradients are refocused. Therefore, the conventional three-dimensional simulation can be converted to a one-dimensional problem in cases such as the commonly used PRESS or STEAM. The proposed method was implemented using a computer program written in Java language.

Patrick Bolan, Benjamin Herman, Gregory Metzger, Eunhee Kim, David Newitt, Savannah Partridge, Michael Garwood, Mark Rosen, Nola Hylton

The ACRIN 6657-extension trial, the first multi-center trial using magnetic resonance spectroscopy (MRS) in breast cancer, has completed and its initial results have been recently published. This study reports on the quality of the MRS data and identifies technical and logistic factors that contributed to a lower-than-anticipated data yield.

Rajakumar Nagarajan, Maithili Gopalakrishnan, Amir Huda, Melissa Joines, Nanette Debruhl, Michael Thomas

In vivo magnetic resonance spectroscopy (MRS) of the breast can be used to measure the level of choline-containing compounds, which is a biomarker of malignancy. The advantage of  four dimensional (4D) echo-planar correlated spectroscopic imaging (EP-COSI) enables full slice coverage of the breast facilitating recording of multi-voxel based two-dimensional (2D) MRS than the single-voxel based localized correlated spectroscopy (L-COSY). Also in addition to differentiate malignant from benign, EP-COSI can differentiate the healthy fatty from glandular. Decreased ADC values derived from diffusion weighted imaging (DWI) can be correlated with increased choline and decreased lipids quantified by the EP-COSI technique.   

Dominik Weidlich, Andreas Hock, Stefan Ruschke, Daniela Franz, Hans Hauner, Ernst Rummeny, Dimitrios Karampinos

Measuring in vivo blood perfusion within the brown adipose tissue depot of the human supraclavicular fossa is highly relevant in metabolic and obesity research. DW-MRS can probe perfusion properties by measuring the IVIM signal of the water peak. However, DW-MRS of the supraclavicular fossa remains a challenging task due the high sensitivity of the region to motion and the associated poor spectral quality. The present work proposes a DW-MRS methodology with a flow compensated acquisition combining cardiac and respiratory tracking to improve spectral quality. IVIM results for the water peak are shown for the first time in the supraclavicular fossa.

Vincent Boer, Henrik Lundell, Tim Dyrby, Itamar Ronen, Esben Petersen

Diffusion weighted spectroscopy is a technique with inherent long scan times. Here it was implemented in a simultaneous multi-voxel technique. This allows simultaneous assessment of multiple brain locations, and gives possibilities to extend the diffusion schemes with more directions and b-values.

Muhammad Saleh, Georg Oeltzschner, Kimberly Chan, Nicolaas Puts, Mark Mikkelsen, Michael Schär, Ashley Harris, Richard Edden

Hadamard Encoding and Reconstruction of MEGA-Edited Spectroscopy (HERMES) allows the simultaneous, separable editing of GABA and GSH, the two most frequently edited metabolites. Rather than a two-step ON/OFF encoding of MEGA editing, HERMES uses a four-step Hadamard encoding matrix to orthogonally edit multiple metabolites. We demonstrate the method through simulations, phantom and in vivo experiments. HERMES provides excellent separation of GABA and GSH with a two-fold reduction in scan time, while maintaining spectral quality and SNR, compared to sequentially acquired measurements of GABA and GSH using MEGA-PRESS.   

Anouk Marsman, Vincent Boer, Mads Andersen, Esben Petersen

Inhibitory neurotransmitter GABA and antioxidant GSH are suggested to be implicated in psychiatric and neurological disorders. These metabolites can be measured in the human brain in vivo using edited ¹H-MRS. However, traditional MEGA editing can only be performed for one metabolite at a time, whereas Hadamard encoded spectral editing assesses both metabolites in one sequence, thereby reducing total scan time twofold. As the relatively small GABA and GSH signals as well as the Hadamard paradigm are highly susceptible to frequency drift and motion, real-time frequency and motion correction was added to the sequence. 

Chen Chen, Bernard Lanz , Carolina Fernandes, Susan Francis, Penny Gowland, Peter Morris

The challenges in T₂ measurement of lactate (Lac) in healthy brain tissue include J-modulation, signal overlaps and low concentration. To overcome these and characterize Lac T₂ relaxation in normal brain tissue at 7T (for the first time), this study used a MEGA-sLASER sequence with J-refocusing echo time extension. The measured T₂ value of Lac was 182±10 ms in healthy human brain (occipital lobe), which can be used for absolute quantification of Lac. The measured T₂ of NAA (169±8 ms) agrees with previous 7T reports. With high sensitivity, this approach showed its potential in detecting changes in Lac T₂ in pathology. 

Meng Gu, Ralph Hurd, Laima Baltusis, Daniel Spielman

GABA editing with frequency-insensitive macromolecule suppression using improved MEGA-SPECIAL sequence (ImSpecial) has been developed. By using a very frequency-selective editing pulse with a pulse width of 30 ms, macromolecule was suppressed without applying a lysine-symmetric editing. An inter and intra-subject repeatability studies were conducted to evaluate GABA editing with MEGA-PRESS and ImSpecial. Compared with GABA+/Cre levels using MEGA-PRESS, GABA/Cre levels using ImSpecial is about 40% less with lower variations for both inter and intra-subject repeatability studies, demonstrating significant MM suppression achieved using ImSpecial.

Donghyun Hong, Seyedmorteza Rohani Rankouhi, Jan-Willem Thielen, David Norris

GABA is challenging to resolve due to j-couplings and overlapping signals. Previously proposed GABA editing ans short TE approach at UHF make it possible to measure relative GABA concentration. We measured GABA concentration with the interleaved sequence at various brain regions, and found an optimal method to estimate GABA in terms of spectral fitting quality. Occiptal cortex  showed a high GABA concentration, and GABA editing approach gave a reliable spectral fitting quality.

Kimberly Chan, Richard Edden, Peter Barker

In in vivo proton spectra, Creatine (Cr) and phosphocreatine are usually regarded as non-coupled spin systems (1).  This abstract reports on the observation of a small coupling between the creatine CH2 (3.91 ppm) and CH3 (3.02 ppm) groups.  A series of J-difference edited experiments were performed both in a phantom and in the human brain to demonstrate that a coupling exists.  This coupling was found to have a coupling constant of 0.28 Hz in an isotropic phantom and an even greater coupling in a white matter region.

Ralph Noeske

The performance of a J-difference spectral editing technique based on the across vendor implementation of semi-LASER with high bandwidth GOIA-WURST adiabatic gradient modulated refocusing pulses for a GABA+ and macromolecule-suppressed GABA protocol was investigated. Phantom measurements show a T_E dependence of the edited 3ppm GABA signal that allows using the longer T_E of 80ms to implement a macromolecular-suppressed protocol with higher signal compared to a PRESS based implementation.

Jia-Ren Lin, Jhih-Ling Liang, Yi-Ru Lin, Cheng-Wen Ko, Shang-Yueh Tsai

The application of phase cycling scheme in combination with interleaved off-odd switch has been suggested for MEGA-PRESS method in many previous reports but the effect of phase cycling schemes on the spectral shape of GABA peak and on the GABA quantification has not been studied yet. Here, performance of phase cycling by different number of steps were and by modified interleaved scheme were compared. The results show that phase cycling is necessary to be applied prior interleaved on-off switch and minimum shape cycling steps are suggested to minimize subtraction artifacts possibly resulting from on-off frequency drift and motion.

Petr Menshchikov, Tolibjon Akhadov, Il'ya Melnikov, Natalia Semenova

Direct Asp observation using PRESS, STEAM etc. in the human brain is strongly complicated by J-evolution and overlapping with other metabolites. In this work we have adjusted MEGA-PRESS for simultaneous  Asp and Glu estimation. According to Vespa simulation as well as phantoms and in vivo studies TE=115ms was chosen as the best for Asp (2.65 and 2.80 ppm) and Glu (2.13 ppm) quantification without overlapping.  Asp is the main precursor of neuronal marker NAA. NAA have been shown to be reduced in many disorders. Using this method allows accurate investigation of this important metabolic pathway.  

Hidehiro Watanabe, Nobuhiro Takaya

The 2D constant time localized sequence of CT-PRESS with J refocusing was proposed, having features of good peak resolution via ¹H decoupling along F₁ and of J refocusing by a 90-degree pulse at the first echo time. By controlling the time point of J refocusing, shorter constant time delay of T_ct can be achieved. This method was developed on a 4.7 T whole-body MR system. Phantom experiments were demonstrated using brain mixture solutions. Three resonances at 2.28 ppm of GABA C2H, 2.35 ppm of glutamate C4H and 2.44 ppm of glutamine C4H were resolved on the phantom spectra.

Lucas Lindeboom, Robin de Graaf

1H-MRS has been used extensively to measure the total amount of lipids stored in organs like skeletal muscle and liver and it has been found that these so called ectopic fat stores are associated with insulin resistance. The role of the composition of these lipid stores (e.g. saturated vs. unsaturated fatty acids) in metabolic disturbances is unclear. Here we show the feasibility of spectral editing techniques to characterize lipid composition in adipose tissue and skeletal muscle in vivo. Estimations of lipid composition with our approach are in line with invasive biopsy studies.

Birte Schmitz, Andrew Maudsley, Sulaimann Sheriff, Heinrich Lanfermann, Xiao-Qi Ding

Local metabolite concentrations in 60 healthy volunteers were estimated from EPSI data that were analyzed from individual voxel measurements and using spectral integration over a ROI and compared to results from single-voxel acquisitions. Linear regression analysis was used to estimate age-dependence of metabolite concentrations obtained with each of the three different methods. The results were compared with each other for quantitative evaluation of EPSI acquisition at short TE for detection of brain metabolites.

Akram Amin, Elena Ackley, Kevin Fotso, Stephen Dager, Stefan Posse

We present a new approach with negligible impact on overall scan time that integrates a short water reference acquisition and navigators into the water suppression module, to spatially and spectrally encode the water signal before suppression. We show that this approach enables quantitative 2D and 3D high-speed MR spectroscopic imaging (MRSI) of brain metabolites, for range of pre-localization techniques (slice-selective, slab-selective or PRESS), at short and long TE, and at different slice locations. This method significantly reduces the acquisition time of volumetric MR spectroscopic imaging and is compatible with a wide range of spectroscopic acquisition methods.

Linqing Li, Li An, Ningzhi Li, Jun Shen

The variation of RF phases may effectively suppress water and lipid coherent signals, as similar effect has been previously demonstrated in GRE MR imaging sequences. We demonstrate a new suppression sequence capable of simultaneous water and lipid suppression with short inter-pulse delay and RF phase spoiling. Monte Carlo analysis showed that the proposed technique can significantly improve both accuracy and precision of metabolite quantification by suppressing lipid contamination.  

Eduardo Coello, Ralph Noeske, Bjoern Menze, Axel Haase, Rolf Schulte

This work proposes an overdiscrete reconstruction for Single Voxel Spectroscopy (SVS). It is demonstrated that in single voxel acquisitions benefit from the SNR and linewidth improvement obtained by correcting for of B₀ inhomogeneities and the optimization of the Spatial Response Function (SRF), as compared to regular signal averaging. This method, enables SV acquisitions in challenging brain areas, i.e. where B₀ shimming is sub-optimal, and corrects for spectral artifacts such as peak aliasing.

Martin Gajdošík, Marek Chmelík, Lorenz Pfleger, Anton Luger, Siegfried Trattnig, Martin Krššák

Liver fat quantification with in vivo ¹H-MR spectroscopy is challenging at ultra-high fields also due to very short T₂ times. Ultra-short TE localized sequence using Gaussian pulses with TE of 3ms was developed and its advantages could be utilized also with ³¹P-MR spectroscopy. Our data showed, that localization was feasible in large homogeneous tissues such as liver providing liver fat measurement with unprecedented precision. The detection of ³¹P signals was feasible and resulted in high spectral resolution in acceptable time.

Dinesh Deelchand, Edward Auerbach, Malgorzata Marjanska

The goal of this study was to compare the apparent transverse relaxation time (T₂) constants of metabolites obtained using LASER and PRESS sequences in the human brain at 3 T.  A 25% higher apparent T₂s of total N-acetyl aspartate, total creatine and total choline were measured with LASER sequence as compared to PRESS while comparable apparent T₂s were measured for strongly coupled metabolites, e.g., glutamate and myo-inositol, with both sequences.

Ralph Noeske, Alessandra Toncelli, Hana Hlavata, Michela Tosetti

A voxel-based implementation of the Bloch-Siegert phase shift method within a semi-LASER 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 resulting in a faster and more reliable calibration procedure to achieve good voxel selection and spectrum quality and avoid additional calibration steps.

Dickson Wong, Amy Schranz, Robert Bartha

At ultra-high field (7T), the quantification of glutamate by ¹H-MRS is more accurate and precise than at lower field strengths. The semi-LASER ¹H-MRS pulse sequence has advantages at high field but requires the use of relatively long radio frequency pulses to reduce power deposition. Typically, the shortest achievable echo times (TE) are sub-optimal for glutamate detection. In this study, the optimal TE for glutamate detection was estimated by time-domain simulation and verified against in-vivo measurements. Using simulations, the optimal TE was found to be 125 ms. In-vivo measurements in one subject produced a result of ~102 ms. Both results suggest that the glutamate signal is greater at longer TEs (100-125 ms) when using semi-LASER at 7T compared to the shortest achievable TEs (40-60 ms).

Morteza Esmaeili, Ovidiu Andronesi

With increasing number of high field 7T MR systems in clinical setting, the potential of using advanced MR modalities such as MR spectroscopy is increasing. Imaging 2-hydroxyglutarate (2-HG) can genotype IDH mutations in gliomas. However, the MR signal of this metabolite is overlapped with other resonances, hampering robust quantification of 2-HG. Here we optimized the timing of LASER sequence for robust detection of 2-HG at high field 7T in the presence of B1 inhomogeneity.

Kofi Deh , Xiangling Mao, Yize Zhao, Guoxin Kang, Pascal Spincemaille, Yi Wang, Dikoma Shungu

As the primary intracellular antioxidant, glutathione (GSH) is involved in free radical reactions in vivo involving paramagnetic iron II/III as catalysts or cofactors, suggesting that findings low tissue GSH by MRS could reflect T₂ signal loss due to differences in iron content, rather than a genuine antioxidant deficit. This study estimated brain iron content using QSM to assess whether GSH deficits previously reported in patients with chronic fatigue syndrome (CFS) were genuine or simply a T₂ signal loss. No iron content differences were found between patients and controls, supporting a genuine GSH deficit in CFS.

Sahar Nassirpour, Paul Chang, Anke Henning

Reliable metabolite mapping of the human brain using ultra-short TE and TR ¹H FID-MRSI is possible at ultra-high fields. However, MRSI studies with high spatial resolutions and brain coverage suffer from long scan times. To make these studies clinically relevant, different acceleration methods are used at the price of losing SNR. The aim of this study is to implement and compare different in-plane acceleration methods: SENSE, GRAPPA and compressed sensing for high-resolution metabolite mapping of the human brain at 9.4T without lipid suppression.

Fan Lam, Yudu Li, Bryan Clifford, Zhi-Pei Liang

This work presents a novel method for macromolecule mapping and quantification. The proposed method integrates an FID-based MRSI acquisition with a generalized series (GS) model based extrapolation scheme. The FID acquisition allows for the use of ultrashort echoes and short repetition times for fast imaging with improved SNR efficiency. The GS model effectively makes use of the spectral priors from single voxel spectroscopy and allows for reformulating the back-extrapolation of metabolite signals as a linear problem (in contrast to conventional nonlinear methods). Results from in vivo experiments demonstrate that MM signals estimated by the proposed method are consistent with an inversion recovery based method and lead to better metabolite quantification.

Zohaib Iqbal, M. Albert Thomas

Chemical shift imaging is a very important method used to investigate several pathologies in vivo. A recent technological development incorporating an echo planar readout, a non-uniform sampling scheme, and an iterative, non-linear reconstruction is the five dimensional echo planar J-resolved spectroscopic imaging (5D EP-JRESI) method. While this technique is capable of obtaining 3 spatial and 2 spectral dimensions in vivo, the indirect spectral dimension has a low spectral resolution, which may hinder accurate metabolite quantitation. In this study, a novel approach using a covariance transformation after reconstruction is assessed and compared to the 5D EP-JRESI method. 

Kexin Deng, Chao Ma, Kui Ying, Georges El Fakhri

It is challenging to remove nuisance water and lipid signals in ¹H-MRSI of body extremities. Strong lipid signals exist both in the subcutaneous layer and bone marrow but also in the muscle, i.e., intramyocellular and extramyocellular lipids.  This work presents a novel minimum-phase Shinnar-Le Roux (SLR) spectral-spatial excitation RF pulse for both water and lipid suppression in 1H-MRSI of body extremities. We have validated the proposed method using Bloch equation simulation, phantom, and in vivo studies.

Kimberly Chan, Georg Oeltzschner, Michael Schär, Peter Barker, Richard Edden

A new approach for simultaneous dual-voxel J-difference spectral editing is described, that uses spatially selective spectral-editing pulses and Hadamard encoding. The theoretical framework for Spatial Hadamard Editing and Reconstruction for Parallel Acquisition (SHERPA) was developed, applying gradient pulses during the frequency selective editing pulses. SHERPA was simulated for GABA, tested in a two-compartment GABA phantom, and applied to the left and right hemispheres of ten normal subjects. SHERPA was successfully implemented with results in close agreement with conventional MEGA-PRESS scans.  Compared to conventional single-voxel single-metabolite J-difference editing, two-fold acceleration is possible without significant loss of SNR using the SHERPA method.

Bryan Clifford, Xi Peng, Yudu Li, Zhi-Pei Liang, Fan Lam

Head motion poses a significant problem in MRSI experiments, especially for 1H-MRSI of the brain performed without water or lipid suppression. In this work we propose a practical method specifically designed to track head motion and correct for its effects on 1H-MRSI data acquired without water suppression. By using the companion spectroscopic water signals, we are able to track head motion with navigators collected in circular and linear trajectories. A specialized data processing scheme is also proposed for processing the navigator data along with the unsuppressed spectroscopic water signals to determine the motion parameters.

Hyeong-Hun Lee, Hyeonjin Kim

Given the issues of chemical shift displacement error, B₁ inhomogeneity and short T₂ at high field, a semi-adiabatic SPECIAL-based MRSI sequence was implemented at 9.4T, which is equipped with a pair of broad-band hyperbolic secant adiabatic full passage pulses for refocusing, and yet, allows a minimum TE of as short as 4.98 ms. In phantom, the effect of the prolonged minimum TE on the J-evolution of coupled spins is negligible. In a rat brain, preliminary quantitative results are in close agreement with the previous results obtained by using single-voxel MRS.

Ipshita Bhattacharya, Ralph Noeske, Baolin Yang, Rolf Schulte, Mathews Jacob

Improved spatial resolution is the need of the hour for MRSI. In this work we propose an algorithm which provides a comprehensive and automatic approach to recover high resolution metabolite maps from highly undersampled acquisitions; the improved spatial resolution translates to improved spectral quality and reduced leakage artifacts. The proposed algorithm is also quite flexible and can be readily used in a variety of sequences, including EPSI, CSI, and spirals acquisition schemes.

Namgyun Lee, Vincent Boer, Esben Petersen, Gyunggoo Cho

Estimating a set of coil sensitivity maps that is consistent with the low-resolution SENSE model is challenging in SENSE spectroscopic imaging. Recently, ESPIRiT, an autocalibrating approach to estimate sensitivity maps for MR imaging, that combines both advantages of SENSE and GRAPPA has been developed. In this work, we propose a spectroscopic extension of ESPIRiT, referred to as S-ESPIRiT, to estimate sensitivity maps from Cartesian 2D spectroscopic k-space data.  The proposed method was demonstrated using 2D spectroscopic imaging data of a brain metabolite phantom acquired with a semi-LASER pulse sequence and a 32-channel receive head coil on a 7T MRI scanner.

Peter Adany, In-Young Choi, Phil Lee

The presence lipids of several orders of magnitude higher concentrations than metabolites in the extracranial tissues present significant challenges for the reliable acquisition and quantification of 1H MRSI, especially in the outer perimeter areas of the brain.  We developed a novel spatial lipid reconstruction technique to remove nuisance lipid signals in 1H MRS. We applied lipid reconstruction to MRSI data and performed BASE-SLIM localization on the lipid-subtracted signal. Using this method, high quality compartment spectra of GM and WM could be obtained.

Andres Saucedo, Zohaib Iqbal, Manoj Sarma, M. Albert Thomas

Magnetic Resonance Spectroscopic Imaging (MRSI) is a valuable tool to characterize metabolic concentrations and changes in several spatial locations in a single recording. However, the long acquisition time of conventional three-dimensional (3D) MRSI limits its practical application. Non-uniformly sampled 3D echo planar spectroscopic imaging (EPSI) has been proposed to accelerate the scan time, combined with compressed sensing (CS) to retain reconstruction fidelity.  We apply the novel approach of reconstructing 3D EPSI data by applying TV, Wavelet-$$$\ell_{1}$$$, and TV + Wavelet-$$$\ell_{1}$$$ CS-based regularization on both the combined spectral and two undersampled spatial dimensions. These three reconstruction methods were evaluated in both simulated and in retrospectively undersampled data of a brain phantom. 

Antoine Klauser, Dimitri Van De Ville, Franc¸ois Lazeyras

High resolution MRSI data were acquired with 2D FID-MRSI at 3T and a post-processing including lipid suppression, low-rank approximation and TGV-reconstruction is proposed. The resulting metabolic images of tNAA, tCre, Cho, Ins and Glx showed a substantial gain in quality, CRLB values associated and the SNR. This effect was particularly marked for lower signal metabolite: Ins and Glx. In addition, the proposed post-processing reconstructed efficiently under-sampled data allowing a 2- or 4-fold acquisition acceleration.

Jabrane Karkouri, Fabien Millioz, Magalie Viallon, Rémy Prost, Hélène Ratiney

Magnetic resonance spectroscopic imaging (MRSI) has multiple interests in clinical practice but it faces quite long acquisition time in practice which limits their use in a clinical environment. In this work, a new fast Magnetic Resonance Spectroscopic image acquisition method, based on Compressed Sensing and the a priori known support of the metabolites chemical shift, is introduced and evaluated based on a k-t space spiral sampling.  In the real-world noisy scenario the error in the recovered spectrum highly depends on the acquired samples. We reduce this error to an acceptable level by selecting irregularly the samples using the Sequential Backward Selection algorithm. Our method has been applied on an in vivo 31P acquisition, to prove the feasibility of the proposed approach.

Rebecca Feldman, Priti Balchandani

High field MRI permits us to leverage increased signal-to-noise ratio (SNR) and spectral separation between metabolite peaks for more sensitive metabolite detection at higher spatial resolutions. However, the acquisition of high-resolution spectral grids can be prohibitively time intensive. Accelerated MRSI acquisitions are challenged by the limitations at 7T. We develop a multi-region SPSP excitation pulse and use it to create a novel low power, B₁ insensitive multi-region SASSI sequence with minimal chemical shift to enable accelerated MRSI. 

Yibo Zhao, Chao Ma, Chang Gao, Kui Ying, Jinsong Ouyang, Georges El Fakhri

For brain imaging, even with head restraints, maximum translations in the range of 5-10 mm and rotations of 1-4 degrees are sometimes observed.  The rigid body motion of the subject during MRSI acquisition can degrade both the spatial resolution and spectral quality. In this work, we developed a wireless active marker based method to track and correct motion in MRSI.

Chu-Yu Lee, In-Young Choi, Phil Lee

Data acquisitions for magnetic resonance spectroscopic imaging (MRSI) require a long scan time to increase SNR and for spatial encoding. During the prolonged scan time, maintaining a constant static magnetic field (B0) is important for a robust MRSI measurement. However, frequency drifts occur over time even in advanced MR systems and become larger when high shim currents or rapidly switched gradients are applied. The frequency drift causes broad and distorted spectral lineshapes, reduced SNR, and quantification errors. These effects can be mitigated retrospectively and prospectively. However, in MRSI measurements, these effects can only be mitigated using the prospective frequency correction, because each spectrum is phase-encoded. The prospective frequency correction is typically achieved by incorporating a PRESS-based interleaved reference scan (PRESS-IRS) as a navigator, termed as PRESS-IRS navigator. A small excitation flip angle (10-20°) is used for the PRESS-IRS navigator to reduce the saturation-induced SNR loss on metabolite signals. Nonetheless, the SNR loss remains unavoidable and becomes notable when the imperfect refocusing pulses or a short repetition time (TR) are used in MRSI. In this study, a new prospective frequency correction method is introduced. The new method utilizes the outer volume suppression-localized navigator, termed OVS-localized navigator, resulting in no perturbations of metabolite signals and thus no saturation-induced SNR losses. Meanwhile, a precise measurement of the frequency drift and the effective correction is achieved. The presented method was demonstrated in two-dimensional (2-D) MRSI measurements under the large frequency drift induced by a fMRI experiment.

Lukas Hingerl, Bernhard Strasser, Philipp Moser, Gilbert Hangel, Siegfried Trattnig, Wolfgang Bogner

A density weighted concentrically circular echo-planar trajectories readout scheme is presented for brain MRSI at 7 T. We give an analytic solution for the variable radii distribution in order to intrinsically measure a Hamming weighted k-space. A comparison with post acquisition filtered equidistant concentric circles is done. Invivo metabolic maps and spectra are shown.

Alex Bhogal, Carrie Wismans, Christiaan Vinckers, Peter Luijten, Dennis Klomp, Jannie Wijnen

In this work we attempt to overcome MRSI limitations associated with extra-cranial lipid signal leakage and low SNR at high resolution. We use a dedicated crusher coil for lipid signal removal, in combination with a high density receive array and an  7T MR scanner for boosted SNR. 

Uzay Emir, Brian Burns, Mark Chiew, Peter Jezzard, Albert Thomas

In this study, the feasibility of acquiring and quantifying short-echo (TE = 14 ms), two-dimensional (2D) STEAM MRSI spectra from the motor cortex was demonstrated by utilizing a non-water-suppressed metabolite-cycling technique. The increase in measurement time by the metabolite-cycling is counterbalanced by a time-efficient concentric ring k-space trajectory. High quality spectra were acquired from 36 localized 2mL voxels in 8 minutes. The metabolite spectra and estimated concentrations were in agreement between non-water-suppressed and water-suppressed MRSI techniques.  Findings of this study demonstrate that a non-water-suppressed metabolite-cycling MRSI technique can perform robustly on clinical MRI scanners and within a clinically feasible acquisition time.

Mohammed Goryawala, Andrew Maudsley, Sulaiman Sheriff

Proton MR spectroscopic imaging (MRSI) is complicated by the presence of subcutaneous lipids, which, if not suppressed before Fourier reconstruction, cause ringing in metabolite maps due to limited k-space sampling. In this study inversion recovery (IR) based lipid suppressed acquisition was compared to non-lipid suppressed acquisition combined with two methods for reducing lipid ringing in whole brain MRS imaging. Results indicate non-lipid suppressed acquisition using the l2-regularization or Papoulis-Gerchberg algorithm for reconstruction is possible without significant ringing artifacts, however, can have a detrimental effect on spectral linewidth and baseline, resulting in smaller spatial coverage than IR based lipid-suppressed acquisition.

Rajakumar Nagarajan, Eric Daar, Zohaib Iqbal, Manoj Sarma, Mario Guerrero, Michael Thomas

In vivo proton magnetic resonance spectroscopy studies of HIV-infected humans have demonstrated region-specific changes in brain metabolites including N-acetylaspartate, creatine, choline, glutamate/ glutamine, and myo-inositol. Using a 3D EPSI technique, we examined metabolite ratios with respect to creatine in several regions of brain in 18 HIV adults (mean age 46.2 years) and 15 healthy controls (mean age 43.4 years). We have demonstrated for the first time the feasibility of a novel accelerated 3D EPSI method in HIV-infected adults compared to age matched healthy controls and correlated with CD4 counts and number of years of treatment.

Rajakumar Nagarajan, Eric Daar, Ebrahim Haroon, Zohaib Iqbal, Neil Wilson, Sathya Arumugam, Mario Guerrero, Michael Thomas

In this work, we have successfully evaluated the accelerated 5D EP-JRESI sequence in 16 adult HIV-infected  patients and 15 healthy subjects. Compared to healthy subjects, significant neurochemical changes were observed in HIV+ patients on ART: elevated Ch/Cr ratios in frontal gray, right frontal white and right basal ganglia locations, decreased Glx ratios in the left frontal white, right basal ganglia, occipital gray and white and right insular cortical regions. There was also decreased NAA/Cr in the left basal ganglia and right occipital white regions. In the HIV+ patients, a positive correlation was recorded between the left basal ganglia NAA/Cr and the number of years of ART treatment (r=0.58, p<0.02).

Ruoyun Ma, Sandy Snyder, Ann-Kathrin Stock, Wolfgang Bogner, Ovidiu Andronesi, Christian Beste, Ulrike Dydak

This pilot study on manganese (Mn) neurotoxicity investigates the association between deficits in response selection and GABA and Glx levels in basal ganglia structures using MEGA-LASER 3D MRSI. Using a novel automated brain-structure-specific quantification approach for GABA+ and Glx, we studied three basal ganglia structures and the thalamus in Mn-exposed welders and controls. A modified Simon task was used to measure selection inhibition. GABA+ and Glx in putamen and globus pallidus were associated with response times in the most complicated experimental scenario in Mn-exposed subjects; whereas thalamic Glx levels were associated with response time for all subjects.

Marram Olson, Jason Crane, Peder Larson, Sarah Nelson

The evaluation of MRSI data is complex because data files are encoded with vendor specific file formats and there is a lack of standardized tools for reconstruction. A standard way to describe raw MRSI data is necessary for the reconstruction of sequences utilizing parallel and non-Cartesian sampling strategies. In this work we are developing a vendor neutral data format to define MRSI sequences with arbitrary k-space trajectories that can be used by reconstruction software to understand the data acquisition scheme. This file format is XML-based and uses the ISMRMRD header as a basis for its scheme.

Dinesh Deelchand, Edward Auerbach, Malgorzata Marjanska

This abstract reviews and highlights the various properties and advantages of the LASER pulse sequence 

A. Dean Sherry, Qiang Li, Mark Jeffrey, Shawn Burgess, Craig Malloy

A MatLab-based program is presented for predicting ¹³C NMR spectra and mass ¹³C isotopomer data of various tissue metabolites in a ¹³C tracer experiments.  The program is useful for predicting changes in ¹³C multiplet patterns in NMR spectra and changes in mass isotopomer ratios in mass spectral data as a tissue responds to changes in flux of various substrates through completing pathways involving mitochondrial metabolism.   The program tcaSIM₂ (copies available free of charge) is also valuable for teaching metabolism and analysis of ¹³C NMR data and mass spec data in metabolic tracer experiments.

Alexander Lin, Benjamin Rowland, John Griffiths

Magnetic resonance spectroscopy (MRS) is an ideal tool for therapeutic monitoring in clinical trials although its role has not been formally examined.  An initial search in a clinical trials database showed 488 studies; however the results were cross-referenced with the scientific literature to yield 61 studies demonstrating the use of MRS in clinical trials.  It is most frequently used to study hepatic lipid content, followed by studies of skeletal muscle, and finally the brain, which surprisingly was only 15% of the MRS studies.  A review is provided to assess its importance as a non-invasive and quantitative biomarker for disease.

Petr Sedivy, Miloslav Drobny, Monika Dezortova, Irena Hejlova, Monika Cahova, Pavel Trunecka, Milan Hajek

Liver transplantation (TxL) is a treatment that rapidly improves the clinical status of patients. However, side effects due to long-term immunosuppressive therapy may negatively influence the function of certain organs and metabolism. ³¹P MRS and MRI are suitable methods for the clinical examination of muscles and abdomen fat volume in transplanted patients. Our pilot results show that TxL leads to an improvement of resting muscle metabolism in especially in diabetic patients and an increase of volume visceral fat in a short term (six months) after transplantation.

Simona Nikolova, Shauna Stark, Craig Stark

Structures in the medial temporal lobe (MTL) like the hippocampus play a critical role in memory. Functional disruptions of the MTL (typically studied with BOLD fMRI) are present in a range of disorders and diseases. The relative and indirect nature of BOLD makes it difficult to interpret findings such as the hippocampal “hyperactivity” that has been tied to age-related cognitive decline and the progression to Alzheimer’s Disease. In this work, “functional” MR spectroscopy is combined with simultaneous BOLD during memory tasks to investigate the relationship between the two.  While task-related activity is observed in both, there are points of departure. 

Leslie Mazuel, Ursule Dumont, Noël Pinaud, Vanessa Zhendre, Silvia Rizzitelli, Jordy Blanc, Hélène Roumes, Anne-Karine Bouzier-Sore, Yannick Crémillieux

The role of lactate in neuronal activation is central in the hypothesis of the astrocyte-to-neurons lactate shuttle. In this work, we implement highly sensitive 1H-MRS on brain microdialysate in order to monitor online the lactate fluctuations during neuronal activation in the S1BF area. The custom-made microcoil used in this study was shown to be sensitive enough for measuring a 40% increase in lactate concentration during brain stimulation.

Kavindra Nath, Jeffrey Roman, David Nelson, Andrew Butterworth, Stephen Pickup, Dennis Leeper, Jerry Glickson

We seek to understand the pH-dependent physicochemical changes of lonidamine (LND), an antineoplastic drug, particularly to locate the sites of ionization. LND samples at pH 2, 7, and 13 were analyzed using ¹H and ¹³C NMR. The results indicate that there is a noticeable change in the chemical shifts for a few atoms in LND from neutral to alkaline pH. These changes demonstrate that LND is ionized at its imidazole α-nitrogen. In addition, the expected ionization of the carboxyl group of LND at acid pH is not directly observed, and this may be due to a rapid-exchange phenomenon.

Kyle Sexton, David Reiter, Hasan Celik, Kenneth Fishbein, Tariq Nayfeh, Richard Spencer

One-dimensional transverse relaxometry has proven to be an effective method for characterizing macromolecular compartments in cartilage. Two-dimensional studies extend the capabilities of these types of experiments, providing characterization of tissue compartments in terms of correlated relaxation times and providing a means of probing intercompartmental exchange.  We provide results of T₂-T₂ and T₁-T₂ relaxometry experiments on human articular cartilage, indicating that exchange between tissue compartments may be augmented in degraded tissue.

Ali Özen, Mazin Jouda, Jan Korvink, Michael Bock

Concurrent Excitation and Acquisition (CEA) offers fundamental advantages for NMR such as 100% signal acquisition efficiency, true zero echo time, reduction of acoustic noise, and decreased peak RF power. Bandwidth of the excitation in CEA is independent of the RF power, allowing detection very broad resonances. In this work, a CEA system is introduced with a full digital cancellation. The system uses a lock-in amplifier combined with an arbitrary signal generator. Preliminary results for NMR of various samples are represented and discussed.

Hirotada Fujii, Miho Emoto, Yuta Matsuoka, Ken-ichi Yamada

EPR imaging has been used to visualize redox status in oxidative brain diseases, but the role of cerebral glutathione (GSH) is not clear. In this study, using the mouse model of GSH depletion with diethylmaleate (DEM), the role of GSH in brain redox status was examined. The remarkable change in redox status in DEM-treated mouse brain was visualized with EPR imaging, and in vitro assay showed decrease in the level of GSH. ME-MRI clearly visualized blood-brain barrier dysfunction in DEM-treated mice. Results indicate that GSH plays an important role in the maintenance of both brain redox status and BBB integrity.

Shivanand Pudakalakatti, Ashvin Jaiswal, Prasanta Dutta, Michael Curran, Pratip Bhattacharya

The cancer immunotherapy has brought new ray of hope in cancer patients with its capability of curing cancer with less side effects. However not all patients responds to therapy. In this study we have employed Nuclear Magnetic Spectroscopy (NMR) and in vivo hyperpolarized 1-13C pyruvate magnetic resonance spectroscopy (MRS) to differentiate immunotherapy responding from immunotherapy resisting melanoma. 

Sarah Calvert, Steven Reynolds, Martyn Paley, Allan Pacey

¹H MRS was used to examine good and poor sperm populations to identify biomarker differences between them. Spectra were binned to 0.02ppm and two-way ANOVA with Bonferroni correction, Wilcoxon match rank test and ROC curve analyses were used to find bins with significant differences between good and poor sperm. All three statistical methods identified the bins at 1.24-1.32ppm which correlates with overlapping lipid and lactate peaks. Differences in these peaks may result from metabolic differences between the two sperm populations and this may give a useful insight into the pathology of sperm dysfunction.

Uma Sharma, Deepti Upadhyay, Prasenjit Das , Siddhartha Gupta , Govind Makharia, Naranamangalam Jagannathan

Potential celiac disease (CeD) patients have immunological abnormalities similar to CeD but unlike CeD, their duodenum displays normal histology. In-vitro proton NMR study of small intestinal mucosa of these patients demonstrated metabolic abnormalities associated with the intestinal inflammation. Both potential CeD and CeD patients had lower concentration of histidine compared to controls while lower glycine was seen only in CeD. Since, both amino acids exert anti-inflammatory effects; their reduced levels suggested compromised cytoprotective mechanism. Significantly higher level of glycerophosphocholine seen in potential CeD compared to CeD might have contributed for renewal of enterocytes and thus to normal small intestine histology.

Santosh Bharti, Flonné Wildes, Chien-Fu Hung, TC Wu, Zaver Bhujwalla, Marie-France Penet

Malignant ascites occurs in approximately 37% of terminal ovarian cancer patients. It significantly contributes to poor quality of life and mortality. Advances in understanding malignant ascites formation and finding new therapeutic options are urgently needed.  High-resolution proton magnetic resonance spectroscopy provides opportunities to characterize biofluid metabolites and can be easily translated to the clinic. Here, we are investigating the metabolic profile of ascites obtained in two different experimental models of ovarian cancer. To further understand the differences observed between both models, we completed our study by analyzing the metabolic profiles of those cells in culture and their corresponding conditioned media.

Santosh K Bharti, Paul T Winnard Jr., Yelena Mironchik, Anirban Maitra, Zaver M Bhujwalla

Cachexia is a poorly understood metabolic syndrome characterized by cancer-induced tissue wasting and weight loss.  Cachexia occurs with the highest frequency and severity in pancreatic ductal adenocarcinoma (PDAC).  To further understand this syndrome, here we used ¹H MRS to analyze liver metabolites in mice with and without cachexia-inducing PDAC. We detected profound liver weight loss in cachectic mice. ¹H MR spectra identified significant depletion of lactate, glucose and glutathione in cachectic mice that provide new insights into the syndrome and may present novel strategies to prevent or reduce cachexia-induced weight loss and the morbidity and mortality associated with the syndrome. 

Bahareh Behzadnezhad, Jian Dong, Nader Behdad, Alan McMillan

This study describes a very low-cost EPR spectrometer that can be feasibly constructed using general purpose laboratory equipment combined with the use of 3D electromagnetic design and additive manufacturing. We demonstrate a functioning, homebuilt, low-cost continuous wave EPR spectrometer operating at 115 MHz. The development of a low-cost spectrometer has applications in education and for other general laboratory purposes. 

Santosh K Bharti, Michael Goggins, Zaver M Bhujwalla

The dismally poor 5 year survival rate of less than 6% in pancreatic ductal adenocarcinoma (PDAC) increases to ~50% with early stage PDAC making early detection critically important.  Metabolic characterization of patient plasma samples provides a unique opportunity to identify biomarkers to assist in routine screening to detect of PDAC.  Here, in a preliminary study, we have characterized the metabolic profiles of plasma samples from normal, benign, and PDAC patients.  Even with a limited sample we identified a significant increase in β-hydroxybutyrate, acetate, acetoacetate, lactate and pyruvate in PDAC compared to normal plasma. 

Sui-Seng Tee, Izabela Suster, Sangmoo Jeong, Roozbeh Eskandari, Valentina Di Gialleonardo, Kristin Granlund, Vesselin Miloushev, Steven Truong, Kayvan Keshari

Cell-line tumor spheroids or patient-derived organoids are 3D structures that self-organize when grown in a suitable extracellular matrix. As they mirror in vivo physiology and biology well, these structures have been used as surrogates for clinical trials. This study describes the ability to grow spheroids in NMR-compatible scaffolds that metabolize hyperpolarized [1-13C] pyruvate. These spheroids are also sensitive to AKT inhibition that manifest in significantly decreased lactate production. Histological analysis confirms on-target inhibition, demonstrating that hyperpolarized magnetic resonance spectroscopy can be used to probe treatment response in spheroids that can mimic human disease. 

Suruchi Singh, Tanushri Chatterji, Manodeep Sen, Ishwar Dhayal, Raja Roy

This study presents the metabolic perturbation in serum and urine samples while comparing Urosepsis with negative and positive controls. It explores the metabolic differentiation of serum samples with sepsis and urine samples with urinary tract infection (UTI) (considered as positive controls), and healthy controls (considered as negative controls) respectively. The serum and urine metabolic profile mainly depicted changes occurring due to severity and spread of infection. The statistical Partial Least Square Discriminant Analysis (PLS-DA) model was robust enough to differentiate the three groups distinctively in both serum and urine samples.

Gaelle Diserens, Damian Hertig, Martina Vermathen, Balazs Legeza, Christa E. Flueck, Jean-Marc Nuoffer, Peter Vermathen

Advanced NMR measurements of biological samples may take several hours. Preanalytical issues may impact the metabolite content, potentially leading to misinterpretation. Our aim was to investigate by ¹H HR-MAS NMR the impact of different cell handling preparation protocols (lysis with and without heating) on the stability of the cell metabolome over the measurement time. In lysed fibroblasts and adrenal-cells, metabolism was ongoing over-time, contrary to a stable metabolite content of the lysed-heated cells. Therefore, to minimize metabolome modifications over the measurement time, it is suggested to use cell lysis in combination with heat inactivation for extended HR-MAS NMR measurements. 

Santosh Bharti, Ellen Tully, Edward Gabrielson, Zaver M Bhujwalla

Lung cancer is a leading cause of cancer associated death in United States and worldwide. Non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancer cases in the United States. Use of metformin is associated with improved cancer treatment outcomes, reduction in cancer incidence and decreased mortality, and because of a higher potency, phenformin may be a more promising anti-cancer agent. Here, we have used 1H MRS of cell extracts to investigate the effect of phenformin on A549 cells.  Significant metabolic changes were observed following phenformin treatment

Ram Khattri, Farhad Dastmalchi, James Rocca, Maryam Rahman, Matthew Merritt

We use ¹H NMR metabolomics to measure the impact of immunotherapy intended to target glioblastoma multiforme in a murine model. Cellular immunotherapy is a promising new platform for cancer treatment. Analysis of the urine of C57Bl6 mice revealed a set of metabolites associated with changes in glycolysis after immunotherapy treatment.

Ashish Gupta, Sudeep Kumar, Shiridhar kashyap, Deepak Kumar, Aditya Kapoor

To address the shortcomings of the conventional biochemical approach for the precise identification of myocardial infarction (MI), and differentiation from chronic stable angina (CSA), and normal coronary (NC) subjects, we applied filtered serum based metabolomics using 1H NMR spectroscopy. The study comprises filtered sera from CAD [CSA (n=88, MI (n=90)], and NC (n=55) subjects. NMR-measured metabolites and clinical evaluation data were examined separately using chemometric approach to probe the signature descriptors for each cohort. This approach reveals that filtered serum based metabolic profiling can differentiate not only NC from CSA and MI but also CSA from MI.   

Candace Fleischer, Xiaodong Zhong, Hui Mao

Parallel imaging and spectroscopy are facilitated by multi-channel phased array coils. An important step is the combination of individual data from each channel, yet the effect of the non-uniformity of array coils on signal-to-noise ratio (SNR) is poorly characterized. Here, we present a systematic framework for identifying vulnerabilities in phased array coils for MRS. We demonstrate the importance of voxel position and coil proximity on overall SNR in a phantom and human subject, with significant SNR improvements after selectively filtering individual spectra based on pre-determined SNR thresholds which must be optimized for each phased array coil and volume of interest.

Chathura Kumaragamage, Dan Madularu, Axel Mathieu, Henk De Feyter, Natasha Rajah, Jamie Near

Carbon-13 (13C) magnetic resonance spectroscopy (MRS) remains to be the only noninvasive method capable of measuring neuroenergetics and neurotransmitter cycling in the brain in vivo [1]. However, 13C MRS is a challenging technique to implement, and suffers from low sensitivity. In this study we investigated a short TE (12.6 ms) PRESS localized proton observed carbon edited 13C MRS utilizing a volumetric resonator for proton excitation. The designed platform demonstrates high sensitivity to 1H signals, provides excellent localization, and high resolution 1H and 1H-[13C] spectra for in vivo rat brain imaging.

Arthur Coste, Nicolas Chauffert, Fawzi Boumezbeur, Alexandre Vignaud, Philippe Ciuciu, Guillaume Madelin, Kathrin Reetz, Denis Le Bihan, Cécile Rabrait-Lerman, Sandro Romanzetti

In this work we explored different aspects that could benefit to in vivo Sodium concentration measurements in order to reduce Acquisition Time to improve patient comfort and an reduce risk of motion artifacts. We studied two Non Cartesian image reconstruction methods and explored subsampling.

Xian-Feng Shi, Young-Hoon Sung, Douglas Kondo, Colin Riley, Perry Renshaw

The aim of the present study was to test a novel method for improving the subcortical tissue segmentation results, of the anatomical brain images acquired using a 31P/1H dual-tuned coil.  When a dual-tuned 31P/1H coil is utilized to perform phosphorus-31 magnetic resonance spectroscopy studies of subcortical brain regions, the resulting anatomical images suffer from both low signal-to-noise ratio, and from reduced image contrast. By registering this volume image on a second anatomical image acquired using a single-tuned, 12 channel 1H head coil, we found that the subcortical tissue segmentation accuracy was significantly improved.

Guillaume Donati, Rolf Gruetter

The inherent low sensitivity of ¹³C-MRS makes detection of natural abundance metabolites in human brain challenging. We aimed to demonstrate that double-tuned array coils are particularly well-suited for ¹³C-MRS studies in vivo, as they provide high sensitivity and high transmit efficiency over a large FOV. To further enhance the SNR, DEPT sequence was used to transfer polarization from ¹H to ¹³C, as well as WALTZ-16 ¹H-decoupling, all within FDA guidelines. Natural abundance metabolites such as glutamate, glutamine, NAA and creatine were successfully detected and decoupled in 30 minutes acquisition time, showing strong efficiency and sensitivity of our measurement setup.

Matthias Malzacher, Ruomin Hu, Jorge Chacon-Caldera, Andreas Neubauer, Lothar Schad

Chloride (Cl^-) is next to the cations Na⁺ and K⁺ the most abundant non-organic anion in the mammals.  Assessment of chlorine’s (³⁵Cl) concentration in tissue could provide further insights into tissue viability in addition to tissue sodium concentration. Yet, low Signal-to-Noise ratio (SNR) is challenging for the RF hardware components. To overcome these challenges, a Transmit-only-Receive-only (ToRo) system for ³⁵Cl MRI/MRS at 9.4T was developed comprised of an actively-decoupled linearly-driven 16 leg low-pass Birdcage transmitter coil combined with two different receiver coils. Substantial SNR gain was reached using receive-only elements compared to the Birdcage coil in TxRx mode.

Hao Chen, Henk De Feyter, Peter Brown, Douglas Rothman, Robin de Graaf

A wide range a direct ¹³C and indirect ¹H-[¹³C] MR detection methods exist to probe dynamic metabolic pathways in the human brain. Choosing an optimal detection method is difficult as sequence-specific features regarding spectral resolution, power requirements and sensitivity complicate a straightforward comparison. Here we combine density matrix simulations with experimentally determined values for intrinsic ¹H and ¹³C sensitivity, T₁ and T₂ relaxation and transmit efficiency to allow selection of an optimal ¹³C MR detection method for a given application and magnetic field.

Hannes Wiesner, Dávid Balla, Klaus Scheffler, Kamil Ugurbil, Xiao-Hong Zhu, Wei Chen, Kamil Uludag, Rolf Pohmann

In this study, we exploit the feasibility of the ¹⁷O MRSI technique for simultaneous measurement of the metabolic rates of oxygen in brain and surrounding muscle based on ROI analysis of dynamics of tissue H₂¹⁷O time courses acquired at 16.4T with 3D ¹⁷O MRSI. An established three-phase model originally developed for brain application was extended with certain assumptions applied to the resting temporalis muscle of rats.

Keika Saito, Mitsuhiro Takeda, Sosuke Yoshinaga, Hiroaki Terasawa

α-Synuclein (α-Syn) is an abundant protein in neurons, and changes to a neurotoxic α-helical oligomer in vitro. The goal of our study is to investigate the structure of the α-Syn oligomer in vivo, by delivering ¹³C-labeled α-Syn into mouse brains and performing a ¹³C CEST experiment. We report the MRS detection of the ¹³C signals of the α-Syn monomer in an agarose gel phantom, mimicking a physiological environment. We also report that the in vitro oligomerization rate of α-Syn varies, depending on buffer conditions. We envisage that the CEST effect will be detected by adjusting the oligomerization kinetics of α-Syn.

Gokce Hale Hatay, Muhammed Yildirim, Esin Ozturk-Isik

This study aims at investigating the effects of compressed sensing data acquisition and reconstruction factors for accelerated phosphorus MR spectroscopic imaging (³¹P-MRSI). Simulated ³¹P MRSI datasets containing healthy and tumor regions were created based on the metabolite information of brain tumor patient ³¹P-MRSI acquired at 3T. k-space data were randomly undersampled with three different reduction factors while preserving the central portion for different noise levels, reduced datasets were reconstructed using compressed sensing by combining eleven different total variation and L1-norm penalties. Findings showed that data acquisition pattern and reconstruction parameters have a significant effect on the resultant ³¹P-MRSI spectral quality. 

Xeni Deligianni, Tanja Haas, Patricia Hafner, Simone Schmidt, Vanya Gocheva, Francesco Santini, Oliver Bieri, Dirk Fischer

This study was focused on comparing the metabolism of triceps surae muscles on postpoliomyelitis patients and age-matched healthy volunteers through dynamic 31P spectra acquisition at 3T magnetic field. It has been suggested previously that in postpolio patients, metabolic changes are secondary to neurogenic pathways, but may influence Pi/PCr ratios. Here, it was shown that baseline PDE/PCr ratios were higher in patients. During exercise, controls performed significantly higher work and the change of Pi/PCr ratios was lower than in patients. Investigation of the correlation of Pi/PCr with the degree of the disease could be a promising clinical direction.

Lucian Purvis, Ladislav Valkovic, Matthew Robson, Christopher Rodgers

Calculation of in vivo concentrations requires knowledge of the B₁ field. A common solution to this problem has been to use field maps measured in phantoms, but this becomes increasingly difficult at high field. The size of the effect of material and B₀ field strength determining B₁ in the liver using phosphorus (³¹P) phantoms was investigated at 1.5, 3, and 7T using CST simulations. The effect of concentration differences at 7T was demonstrated using 15 and 30mM phosphate phantoms. At 1.5T, using phosphate phantoms with concentrations between 5-40mM give an error of less than 3%. This increases to 10% at 3T, and 20-114% at 7T. 

Jonathan Lommen, Nicolas Behl, Peter Bachert, Mark Ladd, Armin Nagel

Sodium (²³Na) is connected to tissue physiology and can be spatially resolved by MRI. Low in-vivo concentrations and short relaxation times render a quantitative determination challenging. We present a simulation method which allows synthesizing realistic ²³Na MRI raw data. Thereby, most effects in typical quantification experiments on the basis of an external concentration reference can be studied. To establish a reference accuracy level, we investigate the influence of T₂^* decay, undersampling, TE, and TR on ²³Na quantification. The presented simulations can be used for the testing and evaluation of quantitative reconstruction methods as well as to test significance in clinical studies.

Mark Bydder, Armin Nagel, Adil Maarouf, Jeremy Verneuil, Patrick Viout, Maxime Guye, Jean-Philippe Ranjeva, Wafaa Zaaraoui

The study aimed to provide values of the short and long T2* sodium components of the human brain at 7T using a multi-echoes 23Na MRI approach (n=24 TE). These results may help improving sodium quantification at 7T.

Nikolaos Dikaios, Charlie Daniels, Ferdia Gallagher, James O’Callaghan, David Atkinson, Shonit Punwani

Metabolic processes monitored by MRS precede the micro-structural changes visualised by MRI. It is well-recognised that cancer cells reprogram their metabolic pathways to meet their energy demands for abnormal proliferation.  Pyruvate is produced through the breakdown of glucose in glycolysis, and is essential for providing cellular energy. Histological studies have shown increased exchange of pyruvate to lactate in prostate cancer, demonstrating a positive correlation with more aggressive disease. In regions of up-regulation of glucose metabolism, [1-13C]pyruvate is more readily converted to [1-13C]lactate, providing added value for diagnostic imaging.  This work aims to robustly quantify the exchange rates between pyruvate and lactate using Bayesian Inference algorithms.

Andreas Neubauer, Matthias Malzacher, Victor Schepkin, Jorge Chacon-Caldera, Ruomin Hu, Eric Gottwald, Cordula Nies, David Thiele, Lothar Schad

Sodium multi quantum (MQ) spectroscopy was used to record single (SQ) and triple quantum (TQ) resonances from a 3D cell culture implanted in a MRI compatible bioreactor under the strophanthin induced inhibition of the sodium-potassium pump (Na-/K-ATPase) at 9.4T. The results show a clear alteration in the ratio TQ/SQ under strophanthin influence. Due to the high control of physiological parameters the bioreactor provides, this alteration can be directly linked to the inhibition of the Na-/K-ATPase. 

Fabian Niess, Georg Fiedler, Albrecht Schmid, Sigrun Goluch, Roberta Frass-Kriegl, Michael Wolzt, Ewald Moser, Martin Meyerspeer

The distribution of workload between GM and SOL during plantar flexion exercise is strongly linked to the knee angle. This work investigates the differences in muscle activation of GM and SOL during plantar flexion with multiple knee angles.  Time series spectra of both muscle groups were acquired simultaneously with high time resolution using dynamic multi-voxel 31P MRS. A linear correlation was found between knee angle and 31P MRS parameters related to muscle activation (PCr depletion, pH, PCr recovery time), confirming predominant involvement of GM with a straight knee, and increasing contributions of SOL with a bent knee.

Nurul Fadhlina Ismail, Steven Reynolds, Sarah Calvert, Allan Pacey, Martyn Paley

One in five young men has poor semen quality, including low motility. Studying energy metabolism may provide better understanding of sperm motility. We acquired ¹³C Magnetic Resonance spectra of sperm incubated with ¹³C-glucose with different concentrations of inhibitors: malonate, oxaloacetate, succinate, and 2-deoxy-D-glucose. This study examined the effect of these inhibitors on sperm lactate production and vitality, with a secondary aim to observe Krebs cycle intermediates in the MR spectrum. Glucose signal significantly decreased with increasing oxaloacetate concentration. Malonate and oxaloacetate and 2DG significantly decreased in lactate production. These inhibitors did not lead to observable ¹³C labelled Krebs cycle intermediates.

Andrei Manzhurtsev, Olga Vasyukova, Victoria Sergeeva, Tolibjon Akhadov, Ilia Mel'nikov, Olga Bozhko, Natalia Semenova

This study is aimed to reveal the effects of hyperbaric oxygenation on human brain phosphate metabolites using ³¹P MRS. At first, ³¹P MRS study was conducted, after that the subjects took a session in hyperbaric chamber (1.2 atmosphere, 100% O₂) and then ³¹P MRS study was repeated. The increase of α-ATP peak intensity was revealed after hyperbaric oxygenation, while other peak intensities and pH remained unchanged. This phenomenon is likely to happen because of [NAD(H)] increase, that might confirm the positive effect of hyperbaric oxygenation on human brain metabolism.

Chang-Hoon Choi, Suk-Min Hong, YongHyun Ha, N. Jon Shah

A double-tuned ¹H/¹⁹F coil using PIN-diode switches was developed and evaluated its performance on a 9.4T preclinical MRI scanner. This proposed design uses an inductor rather than a capacitor in series with the PIN-diode so that the resonance frequency is shifted in the opposite direction compared to the conventional method. This is a key difference from the previous developments and in this way we can maintain the SNR or image quality of the X-nuclei (therefore ¹⁹F); the SNR is nearly as good as a single-tuned ¹⁹F coil. 

Mark J. van Uden, Tom H. Peeters, Tom W.J. Scheenen, Arend Heerschap

³¹P MRS of the brain can reveal changes in energy and lipid metabolism in healthy and diseased brain. In this abstract we compare ³¹P MRS measurements with and without NOE and/or ¹H-decoupling. Adding nuclear Overhauser enhancement (NOE) and ¹H-decoupling to a ³¹P MRS measurement at 3T increases spectral resolution to that at 7T and improves sensitivity so that the theoretical difference with 7T is partly compensated for. At relatively short repetition times both ¹H-decoupling and NOE have to be taken into account for proper quantification.

Chu-Yu Lee, In-Young Choi, Jean Dinh, William Brooks, J. Leeder, Phil Lee

19F MRS allows assessment of fluorine containing anti-psychotic drugs in the brain. However, the reliable quantification remains challenging due to low drug concentrations and MR characteristics of the drugs are not well understood. This study aimed to characterize MR properties of four anti-psychotic drugs: pimozide, paliperidone, risperidone, and racemic fluoxetine, in phantoms at 9.4 T. Our results demonstrated that pimozide, paliperidone and risperidone showed over 50 ppm differences in chemical shifts and over 200 ms differences in T1 and T2 relaxation times compared with racemic fluoxetine. These different MR characteristics may have important implications for the 19F MRS technique development.

Lisa Leroi, Arthur Coste, Ludovic de Rochefort, Mathieu Santin, Romain Valabrègue, Franck Mauconduit, Marie-France Hang, Edouard Chazel, Jérémy Bernard, Michel Luong, Eric Giacomini, Denis Le Bihan, Cyril Poupon, Fawzi Boumezbeur, Cécile Rabrait-Lerman, Alexandre Vignaud

Quantifying physical properties of sodium could be of benefit to assess more specifically changes in cellular homeostasis accompanying neuroinflammatory or neurodegenerative diseases. This work aimed at adapting for ²³Na MRI at 7 Tesla the Quantitative Imaging using Configuration States (QuICS) method, primarily developped for ¹H MRI. We demonstrate the possibility to not only estimate accurately the T₁, T₂, FA, M₀ and ADC simultaneously for ²³Na at physiological concentration at UHF, but to acquire 3D maps for all of them.

Mark Bydder, Wafaa Zaaraoui, Lothar Schad, Maxime Guye, Jean-Philippe Ranjeva

In this abstract we develop and validate an MRI acquisition/reconstruction method to derive the temporal dynamics of 23Na within a 20 min scan.

Inok Ko, Ki-Hye Jung, Kyung Jun Kang, Kyo Chul Lee, Yong Jin Lee, Jung-Young Kim, Sang Moo Lim, Ji-Ae Park

Distinguishing between FLT(fluorothymidine) and FLT-MP(flruorothymidine - monophosphate) by imaging methods is important for evaluating the tumor cell proliferation rate. The aim of this study is to develop and validate a suitable ¹⁹F MR Spectroscopy for measuring TK1 activity via quantitation of FLT and FLT-MP in vivo. We observed the good correlations between SNR and FLT concentration (r2= 0.94). In phantom study, the locations of FLT and FLT-MP was -175.99, -175.24 ppm, respectively. In vivo study, FLT spectrum in mouse tumor was observed in 25 min after injection, whereas FLT-MP spectrum occurred in 90 min after injection. This result shows that ¹⁹F MR Spectroscopy is suitable for monitoring of FLT-MP generation in in vivo.

Marianne Cleve, Alexander Gussew, Gerd Wagner, Jürgen Reichenbach

Possible associations between BOLD and left insular GABA+/tCr and Glx/tCr levels were investigated by conducting whole brain fMRI measurements and ¹H MEGA-PRESS MRS at 3 T in healthy subjects prior to and during acute pain stimulation. A significant negative correlation between insular resting state GABA+/tCr levels and BOLD response was obtained in the supplementary motor area with transition to the mid-cingulate cortex. Furthermore, insular ΔGlx revealed a significant positive association with BOLD signal in the left anterior and right posterior insula. These findings suggest interregional interrelations between metabolite levels and stimulus induced BOLD response in the pain processing network.

Linda Chang, Sara Hayama, Steven Buchthal, Chathura Siriwardhana, Daniel Alicata, Zachary Pang, Tricia Wright, Jon Skranes, Thomas Ernst

In prior studies, children with prenatal methamphetamine-(PME) or tobacco-exposure (PTE) showed elevated brain metabolites levels.  The current study evaluated infants with PME and PTE during the first 5 months of life and found abnormal developmental trajectories of metabolites in the frontal white matter, with abnormally lower levels of total creatine [tCr], N-acetylaspartate [NAA], and glumate+glutamine [Glx] at baseline, and steeper developmental trajectories that resulted in normal or elevated levels after 2-months old. Furthermore, the trajectories of basal ganglia-[NAA] and corticospinal tract-[tCr] further contributed to the slower muscle tone development in PME infants, especially the males. 

Song-I Lim, Kyu-Ho Song, Chi-Hyeon Yoo, Dong-Choel Woo, Bo-Young Choe

In this study, we investigated the neurochemical alterations in mouse hippocampus using in vivo proton magnetic resonance spectroscopy. We also examine the effect of high-fat diet on the levels of abdominal fat, plasma leptin, and corticosterone. The decrease in mIns concentration seen in HF diet mice without corresponding Gln-Glu alternation may reflect changes in glial function. In addition, the observed total choline levels indicate attenuated membrane turnover in HF diet mice. We therefore suggest that diets rich in saturated fats induce a stress-related response through metabolic disturbance and HPA axis dysfunction, which may indicate a relationship between obesity and depression.

Antoine Cherix, Brodier Laurent, Jean-Marc Matter, Rolf Gruetter

¹H-MRS was used to study the metabolic changes associated with development of the neural tissue in vivo longitudinally. Different tissues (yolk, eye and vitreous body) of developing chickembryos were scanned at three different stages (E3, E6 and E8) for metabolic quantification. As expected, results indicate that a critical juncture appears between stages E3 and E6 in terms of energetic status of the embryo.

Elodie Boudes, Rachelle Loo, Kari Parsons, Gareth Barker, David Lythgoe, Richard Edden, R Marc Lebel, Martin Wilson, Ashley Harris

Mixed glutamate/glutamine (GLX) signal contributes to spectra acquired for GABA editing, both as a co-edited peak in the difference spectrum and in the OFF subspectrum. GLX results are often included in GABA studies, but the reliability of these metrics has received little attention. In this study, we examine the relationship between GLX measures, using a short-TE PRESS as a “gold standard”, and comparing GLX measured from the co-edited peak and the OFF subspectrum from typical GABA+ and macromolecule-suppressed GABA acquisitions.

Emmanuel Amabebe, Steven Reynolds, Victoria Stern, Graham Stafford, Martyn Paley, Dilly Anumba

Accurate identification of pregnant women with symptoms of preterm labor (PTL) most likely to deliver prematurely soon after presentation/assessment is crucial for prompt clinical decision making and allocation of scarce resources by minimizing unnecessary hospitalizations and treatments, as well as by triaging patients to the centers with optimal care facilities.  We determined the predictive capacity of cervicovaginal fluid (CVF) acetate/glutamate ratio in pregnant women presenting with symptoms of threatened PTL using ¹H-NMR. The ratio of CVF acetate to glutamate demonstrated better prediction of delivery within 2 weeks of symptomatic presentation, compared to either acetate or glutamate alone.  

Bernhard Neumayer, Thomas Widek, Chris Boesch, Eva Scheurer

The different relaxation times of the water and the fat compartment in human lumbar vertebrae make it necessary to determine these values for a correct calculation of the fat fraction, which is used as a biomarker for various applications. This study investigates the reproducibility of relaxometry in human lumbar vertebrae to serve as a basis for future studies. Furthermore, factors like age, sex, and physique are investigated for their influence on the derived T₁ and T₂ values to investigate whether relaxation times of the fat and water compartments can serve as biomarkers in addition to the fat fraction.

Michal Považan, Eva Heckova, Gilbert Hangel, Bernhard Strasser, Stephan Gruber, Assunta Dal-Bianco, Fritz Leutmezer, Siegfried Trattnig, Wolfgang Bogner

Multiple sclerosis (MS) is a disease of the central nervous system associated with demyelination and glial activation affecting large areas of white matter. ¹H-MRSI may detect the metabolic changes induced by MS and facilitate the differentiation between MS lesions. Our study aimed to detect and map the signal of macromolecules in healthy controls and MS patients. 2D FID-based ¹H-MRSI was used with measurement time under 6 minutes. We found increased macromolecules in the perilesional region and decreased macromolecules in most of the lesions. However, in some lesions, macromolecules were increased, which may be possibly related to pathological activation of lesion.

Xian-Feng Shi, Perry Renshaw, Deborah Yurgelun-Todd

The aim of the present study was to examine possible gender differences in 1H brain metabolite concentrations in male and female college basketball players. Decreased total N-acetylaspartate/N- acetylaspartylglutamate (tNAA) levels within white matter tissue were observed in female basketball players with symptoms of depression or anxiety (p = 0.0256 /p = 0.0112). 

Manoj Sarma, Margaret Keller, Tamara Welikson, Sathya Arumugam , David Michalik, Irwin Walot, Karin Nielsen-Saines, Jaime Deville, Andrea Kovacs, Eva Operskalski, Joseph Ventura, M. Albert Thomas

A recently implemented 5D echo-planar J-resolved spectroscopic sequence using 8x acceleration and compressed sensing reconstruction was evaluated in 7 perinatally infected and 8 healthy youths. Selected metabolite ratios with respect to Cr were detected bilaterally in the basal ganglia, anterior insular cortex, posterior insular cortex, frontal white and occipital/frontal gray regions of the two groups. Statistically significant differences were found between metabolite ratios (/Cr) of HIV-infected youing adults and healthy control subjects in the occipital gray N-acetylaspartate, right basal ganglia glutamine/glutamate, left anterior insular cortex choline, and left posterior insular cortex. Also, our pilot findings suggest a possible difference in energy metabolism between perinatally HIV-infected young adults and controls without HIV. The metabolite ratios correlated with neuropsychological test scores showing cognitive impairment as result of HIV-infection and/or long term ART.

Katarzyna Pierzchala, Nicolas Kunz, Rolf Gruetter

The number of patients diagnosed with cancer is increasing. Therefore the ability to predict tumor response to therapeutic agents remains a major challenge. Tumor cell metabolism is currently examined by 1H MRS with the aim of getting more insight into the differences between normal and neoplastic tissues, characterize their metastatic potential/finding prognostic markers, and monitoring the effect of therapies. In this study we demonstrate the feasibility of characterizing in-vitro living cells and present changes in the metabolic profile of WM793 and T24 cells lines subjected to chemotherapy. These results show promise for more personalized treatment protocols for cancer patients. 

Liangjie Lin, Yanqin Lin, Dan Tian, Hongyi Yang, Zhiliang Wei, Peter Barker, Kai Zhong, Zhong Chen

Conventional localized ¹H MRS pulse sequences, such as PRESS and STEAM, generally suffer from J coupling modulations which can aggravate attenuation of multiplet resonances during echo times. Here, the “perfect echo” module combined with an optimized localization scheme is utilized for in-phase single-voxel in vivo MRS at 9.4 T. The relative signal intensities of multiplet to singlet resonances acquired at short and moderate echo times increase substantially in comparison with those at PRESS spectra. Therefore, direct MRS quantification of many important metabolites, such as glutamine, glutamate, γ-aminobutyrate, aspartate, and myo-inositol, may be improved.

Margot Thiaucourt, Polina Shabes, Natalie Schloss, Markus Sack, Ulf Baumgaertner, Christian Schmahl, Gabriele Ende

We present single voxel MEGA-PRESS MRS data from the posterior insula of 20 healthy women demonstrating a significant association of GABA and the subjective pain thresholds. These findings are in good agreement with the postulated role of the posterior insula for pain information processing. In this region pain is first processed and the sensory aspects of pain perception is elaborated and then conveyed to the anterior insula where it is related to emotional and cognitive aspects of pain perception. The data corroborate that GABA levels seem to be an important mediator for pain perception.

Fei Gao, Guangbin Wang, Bin Zhao, Fuxin Ren, Weibo Chen

In this study, we used J-difference edited MRS and resting-state fMRI to investigate correlation between intrinsic neuronal activity and GABA levels in the auditory cortex of patients with presbycusis. Our results indicated that abnormalities in GABAergic neurotransmission may underlie resting-state functional deficits in presbycusis. 

Jia-Ren Lin, Yi-Ru Lin, Shang-Yueh Tsai

Recent studies have reported metabolic change during visual and motor stimulation using MRS at 7T MRI system. We think there is potential to perform fMRS experiments at 3T system. Visual stimuli were given with block design consisting of 2 black-white movie clips and 3 rest sections. Our preliminary results showed that Glu concentrations in visual cortex increases by 1.39% during watching movie, while NAA and Cre have no significant change. The observed Glu change was comparable to previous study performed at 7T.

Yousef Mazaheri, Amita Shukla-Dave, Debra Goldman, Chaya Moskowitz, Victor Reuter, Oguz Akin, Hedvig Hricak

The aims of our study were to retrospectively measure metabolite ratios and apparent diffusion coefficient values for benign and malignant PZ tissue at 3T, develop statistically-based rules for classifying benign and malignant PZ tissue, and assess the rules’ performance, using whole-mount step-section pathology as the reference standard.

Sunitha Thakur, Robert Young, Robin Fatovic, Ralph Noeske, Martin Janich, Andrei Holodny, Ingo Mellinghoff

2-hydroxyglutarate in IDH1/2 mutated tumors is of clinical interest and can be measured in-vivo by magnetic resonance spectroscopy. Goal of this work was to compare results obtained using the standard reduced flip angle refocusing pulses with results using broadband refocusing pulses. Sensitivity improvement was observed in phantoms and demonstrated in vivo.

 

Sadhana Kumari, Senthil Kumaran, Vinay Goyal, SN Dwivedi, Achal Srivastava, Naranamangalam Jagannathan

Proton metabolic profile of serum samples in 20 patients with Parkinson’s disease (PD) and 10 healthy controls (HC) was studied using 700 MHz NMR spectrometer. Data were processed using MestReNova software (version: 10.0) and integral values were evaluated. PLS-DA multivariate analysis was performed to compare the metabolic differences between PD patients and HC using MetaboAnalyst (version: 3.0) software. We found elevated levels of glucose, fatty acid, glutamine, lactate, choline, creatine and acetate in PD patients in comparison with HC (on t-test, p<0.05), indicating disturbances in lipid metabolism, fatty acid oxidation and mitochondrial damage leading to dopaminergic deficiency in Parkinson's disease.

Graham Galloway, Scott Quadrelli, Aaron Urquhart, Katie Trickey, Peter Malycha, Theresa Keane, Carolyn Mountford

This pilot study reports clear deregulation in the neurochemistry  of defense personnel exposed to repeated blast. The changes  recorded are different to those reported for mTBI, PTSD and chronic pain. No differences between blast exposed and healthy were recorded by MRI sequences T1WI, FLAIR or SWI. In vivo neuro 2D spectroscopy  recorded deregulation with PC and GPC, NAA and GABA all decreased compared to the healthy non exposed brain. We we did not observe any changes in the fucosolated glycans, which are reflective of pain, repetitive brain injury  and/or cognitive deficit.

Jong-Hee Hwang, In-Young Lee, Jung-Hyun Kim, Jae Seung Kim

Repetitive and noninvasive MR examinations of fat content can provide indispensable information for longitudinal metabolic studies. It is of great interest to understand how obesity in youth affects the fat metabolism later in life. Thus we longitudinally examined mice with/without a high-fat diet [HFD] for 8 weeks from 13 to 67 weeks old using MRI and 1H MRS.  As a result, visceral fat restored normalcy in 10 weeks after the termination of HFD, subcutaneous and liver fat returned to normalcy in ~ 16 - 20 weeks as compared to controls.  

Mona Mohamed, Peter Barker, Richard Skolasky, Ned Sacktor

Higher magnetic field such as 7T provides increased sensitivity, better signal to noise ratio and more reliable measure of the metabolite concentrations. In this study, 7T MRS was used to measure brain metabolites in HIV+ patients in 5 brain regions. Our study showed impaired neuronal integrity across the white and gray matter as well as possible impaired astrocyte osmoregulation in patients with symptomatic cognitive impairment. In conclusion, 7T MRS brain metabolites measurement can be used as reliable biomarkers for the assessment of cognitive status in HIV+ patients.

Francesca Branzoli, Bélen Díaz-Fernández , Malgorzata Marjanska, Edward Auerbach, Romain Valabrègue, Itamar Ronen, Stéphane Lehéricy, Charlotte Rosso

Diffusion-weighted ¹H magnetic resonance spectroscopy (DW-MRS) probes the diffusion properties of metabolites, which are differentially compartmentalized in brain tissue and are thus more specific than water molecules to the intra-cellular environment. The aim of this study was to measure water and metabolite diffusion in the human brain in the acute, sub-acute and choronic stage of ischemic stroke, in order to better characterize the microstructural dynamic changes ongoing at different stages of the disease, in both infarcted and periferal regions, by disentangling neuronal, glial and extra-cellular pathological processes.

Jameen ARM, Karen Ribbons, Jeannette Lechner-Scott, Kate Skehan, Shiami Luchow, M. Albert Thomas, Saadallah Ramadan

The detection of weak neurometabolites such as g-aminobutyric acid (GABA), glutathione (GSH), glycerophosphocholine (GPC), phosphorylethanolamine (PE) with 2D L-COSY can be challenging due to lower concentrations. Moreover, the standard initial echo time (TE_initial) of 30ms yields suboptimal SNR due to shorter T2*. In this study, we compared short TE_initial of 20ms vs 30ms to evaluate improved detection of low concentration metabolites. Our results show a significant increase in SNR with TE_initial of 20ms compared to 30ms. Short TE_initial of 20ms has increased potential in the detection of peaks from weak neurometabolites.