Andreas Korzowski, Sarah Neumann, Ludwig Dominik, Loreen Ruhm, Mark Ladd, Peter Bachert

³¹P MRS allows the non-invasive observation of high-energy phosphate turnover in vivo. A model incorporating the effects of exchange processes onto the transverse steady-state magnetization was derived, which allows the direct estimation of relaxation rates from signal intensities in MRSI datasets. Multiple ³¹P MRSI datasets with different excitation parameters of four healthy were evaluated. Spatially-resolved turnover rates of high-energy phosphates could be estimated and are in agreement with literature values proving feasibility of the proposed approach.

Yuchi Liu, Bryan Clifford, Chao Ma, Fan Lam, Zhi-Pei Liang, Xin Yu

Dynamic ³¹P-MRSI serves as a non-invasive tool to assess mitochondrial oxidative capacity in skeletal muscle during ischemia-reperfusion or exercise-recovery. However, ³¹P-MRSI with high spatial resolution requires long acquisition times which render dynamic measurements impractical. In this study, we adapted a recently proposed low-rank tensor-based method for high-resolution dynamic ³¹P-MRSI in preclinical studies. We present results from an in vivo ischemia-reperfusion experiment on a rat hindlimb with 15 s nominal temporal resolution and 0.75×0.75×1.6 mm³ nominal spatial resolution, demonstrating the potential of the method for assessing mitochondrial function in different muscle types in small animal models.

Irene van Kalleveen, Jurgen Runge, Wybe van der Kemp, Debra Rivera, Jaap Stoker, Dennis Klomp, Aart Nederveen

The standard evaluation of detecting liver parenchyma is invasive liver biopsy, while MRS is a non-invasive measurement to monitor metabolites. Using ³¹P spectroscopy it is possible to follow metabolic changes in the liver and the functionality of the liver during fructose uptake by measuring ATP levels. Going to ultra-high field strength, we are more sensitive to ATP levels and are able to use more localized MRS sequences (e.g. 3D CSI). We have shown we are able to monitor ATP levels during fructose uptake  in vivo in the liver at 7T and see a decrease in ATP levels during the uptake.

Francesco Santini, Dirk Fischer, Oliver Bieri, Xeni Deligianni

Dynamic 31P spectroscopy of the skeletal muscle can provide useful insight into its energy metabolism. However, in order to see dynamic changes in metabolites, a minimum threshold of physical exercise is necessary. In this work, we present a system that uses electrical muscle stimulation superimposed to volitional muscle contraction in order to enhance the metabolic response of the muscle in the same workload condition. This method can have potential application to patients that are unable to voluntarily exert sufficient work for a dynamic spectroscopy investigation.

Veronika Rackayova, Vladimir Mlynarik, Cristina Cudalbu

Chronic liver disease (CLD) induces irreversible brain alterations, especially in children, probably linked with oxidative stress and energy metabolism perturbations. Our aim was to use combination of NOE enhanced and ¹H-decoupled ³¹P-MRS, ³¹P-saturation transfer experiment (to estimate mitochondrial creatine kinase rate) and ¹H-MRS to study the effect of CLD on developing brain. Our results show significantly reduced k_ATP→PCr and fluctuating NAD⁺/NADH ratio indicating perturbation in mitochondrial function, possibly induced by oxidative stress. In addition, altered phospholipid metabolism was observed. 

Ladislav Valkovic, William Clarke, Lucian Purvis, Matthew Robson, Stefan Neubauer, Christopher Rodgers

Determination of human cardiac intracellular pH using ³¹P-MRS is challenging as the resonance frequency of Pi is concealed by a close resonating 2,3-DPG signal originating from blood. Common short TR and low-flip angle scan used for cardiac ³¹P-MRS increase the effective SNR/time, but can additionally suppress the Pi signal intensity. We have investigated the feasibility of detecting cardiac Pi and calculating intracellular pH of human heart using long TR 3D-CSI examination with adiabatic excitation at 7T. Comparison to short TR acquisition was performed using interleaved TR measurements. We report robust and repeatable detection of Pi signal in 100% of subjects.

Petr Sedivy, Miloslav Drobny, Monika Dezortova, Karel Roztocil, Andrea Nemcova, Vit Herynek, Robert Bem, Helena Cermakova, Jan Peregrin, Milan Hajek

Reduced blood supply limits the oxidative muscle metabolism and causes acidosis due to anaerobic glycolysis. Similar results were found in patients with peripheral artery occlusive disease (PAOD) in which chronic ischemia causes claudication and restricts walking distance. ³¹P MR spectroscopy of calf muscles of healthy controls and patients show that PAOD significantly influences muscular metabolism which is reflected in dynamic parameters of PAOD patients. The effect of diabetes is significantly pronounced in diabetic PAOD patients at rest compared to controls and PAOD patients without diabetes.

Martin Meyerspeer, Albrecht Schmid, Fabian Niess, Georg Fiedler, Sigrun Goluch, Michale Wolzt, Ewald Moser

Alterations in T1 have implications on the physiological interpretation of dynamic high-energy phosphate data. Progressive saturation during rest-exercise-recovery experiments was used to simultaneously quantify PCr depletion, recovery and T1 values. The data were acquired using localised 31P MRS in human gastrocnemius. Apparent T1 values increased from 5.0 ± 0.4 s at rest to an average value of 5.8 ± 0.5 s during exercise, with a peak in early exercise and returning towards baseline values before exercise was ceased. These alterations may be explained by changes in the chemical exchange rates of PCr with ATP and Pi.

Ming Lu, Xiao-Hong Zhu, Yi Zhang, Wei Chen

Decline in NAD⁺ availability is tightly linked to many neurological disorders. Our recent study also revealed age dependences of intracellular NAD⁺, NADH and total NAD concentrations in healthy human brains. Accumulating evidences have shown that the cellular NAD⁺ could serve as a therapeutic target for treating metabolic or age-related neurological diseases and promoting longevity. Therefore, to investigate the effect of exogenous NAD⁺ on intracellular NAD metabolism, the in vivo ³¹P-MRS NAD imaging assay developed in our lab was applied in normal rat brains at 16.4 T. Significant increases of cerebral α-ATP, total NAD and NAD⁺ levels were observed after the intra-peritoneal infusion of exogenous NAD⁺. This study not only demonstrates the feasibility of using exogenous NAD⁺ to enhance cerebral ATP and NAD metabolisms, but also provides an opportunity to better understand the roles of NAD metabolism in health and age-related disease.

Alejandro Santos Diaz, Michael Noseworthy

Very long acquisition times is the most important limitation against performing ³¹P magnetic resonance spectroscopic imaging (MRSI) in clinic environments.  To overcome this limitation we show the feasibility of implementing in vivo highly accelerated ³¹P-MRSI combining flyback echo planar spectroscopic imaging (EPSI) and compressed sensing (CS) achieving a 12x12 matrix over a 24 cm field of view (FOV) in less than 6 minutes.  Due to the denoising nature of CS the resultant SNR was also improved using this approach.

Kai Ludwig, Diego Hernando, Nathan Roberts, Ruud van Heeswijk, Sean Fain

In preclinical applications, the high specificity of quantitative ¹⁹F MRI may be compromised by non-negligible signal contributions from fluorinated anesthetics (e.g. isoflurane). Here, we demonstrate the feasibility of chemical shift encoding (CSE) with multi-resonance fluorine signal modeling and least-squares estimation image reconstruction for ¹⁹F MRI. We optimize noise performance (NSA) and use a 3D spoiled gradient-echo acquisition to separate signal contributions from perfluoro-15-crown-5-ether (PFCE) and isoflurane. The method is tested in mixed PFCE/isoflurane phantoms showing effective signal separation. The CSE reconstruction removes isoflurane signal contributions in ¹⁹F MR images of PFCE in vivo, potentially reducing errors in ¹⁹F concentration quantification.

Henk De Feyter, Kevin Behar, Douglas Rothman, Robin de Graaf

We adopted a 2D heteronuclear single-quantum coherence (HSQC) MR spectroscopy method to detect in vivo ¹³C isotopomers in rat brain through exploiting the high sensitivity of ¹H MRS. This method allows for in vivo detection of unique ¹³C-labeling patterns in brain metabolite pools during simultaneous infusion of different ¹³C-labeled substrates. We demonstrated that high-quality 2D HSQC MR spectra can be acquired in vivo in a time-resolved manner from rat brain during simultaneous infusion of [U-¹³C₆]-glucose and [2-¹³C]-acetate. This method can be used to study with high accuracy neuronal and glial metabolism, and the contribution of alternate substrates to brain energy metabolism. 

Hannes Wiesner, Yi Zhang, Ming Lu, Nanyin Zhang, Xiao-Hong Zhu, Wei Chen

In this study we performed dynamic in vivo ¹⁷O MRS measurements in conscious and isoflurane-anesthetized rat during inhalations of ¹⁷O₂-enriched gas at ultra-high field of 16.4T, ultimately to compare the relation between CMRO₂ and brain condition.

Robert Borowiak, Wilfried Reichardt, Dmitry Kurzhunov, Christian Schuch, Benjamin Görling, Dieter Leibfritz, Jochen Leupold, Thomas Lange, Helge Haas, Jens Timmer, Michael Bock

We studied the chemical exchange kinetics of ¹⁷O-labeled glucose at the C1 and the C6 position with dynamic ¹⁷O-MRS. A profile likelihood analysis is performed to determine identifiability and confidence intervals of the metabolic rate CMR_Glc. The exchange experiments confirm that the C6-¹⁷OH label is transferred via glycolysis exclusively by the enzyme enolase into the metabolic end product H₂¹⁷O, while C1-¹⁷OH ends up in water via direct hydrolysis as well as via glycolysis. From H₂¹⁷O-concentration time-courses cerebral metabolic rates of CMR_Glc = 0.05-0.08 µmol/g/min are obtained which are in of the same order of magnitude as ¹⁸F-FDG PET.

Jason Crane, Ilwoo Park, Marram Olson, Daniel Vigneron, Sarah Nelson

Methods for dynamic spectroscopic imaging of hyperpolarized (HP) ¹³C substrates are rapidly evolving and accessible tools are required for reconstructing the data and for validating quantitative kinetic models. This study presents processing tools for automatic analysis of data from dynamic HP ¹³C experiments.  The methods were implemented in the open-source SIVIC software package and applied to the fitting of data from a human brain tumor trial to derive metabolic K_pl maps.  

Felix Kreis, Jiazheng Wang, Alan Wright, Kevin Brindle

Dissolution Dynamic Nuclear Polarized NMR (dDNP NMR) is a promising new tool for assessing metabolism in vivo. The signals of the hyperpolarized substrate and its downstream metabolites are usually detected by direct ¹³C observation. Here we demonstrate an effective way to repetitively transfer hyperpolarization via indirect couplings from [1-¹³C] to [3,3,3-¹H₃] in [1-¹³C] lactate formed from hyperpolarized [1-¹³C] pyruvate. The changes in the hyperpolarized [3,3,3-¹H₃] lactate peak were fitted to a kinetic model. The method sets the stage for dynamic hyperpolarized ¹H imaging.

Anne-Sophie Hanak, Jacques Stout, Lucie Chevillard, Boucif Djemaï, Patricia Risède, Michel Luong, Eric Giacomini, Joel Poupon, David Barrière, Frank Bellivier, Bruno Mégarbane, Fawzi Boumezbeur

Lithium (Li) is the first-line mood stabilizer to treat bipolar disorder patients. However, its mechanisms of action and transport across the blood-brain barrier remain poorly understood.  In this study, we aimed at mapping ex vivo the cerebral Li distribution of rats treated for 28 days with Li₂CO₃ using ⁷Li-MRI at 17.2 Tesla. Using a phantom replacement approach, MRI-derived Li concentrations were calculated and validated by comparison to inductively coupled plasma-mass spectrometry (ICP-MS) measurements. Lithium distributions were uneven (normalized lithium content ranging from 0.7 to 1.4) and symmetrical with consistently lower concentrations in the metencephalon and higher ones in the cortex.

James Grist, Frank Riemer, Esben Hansen, Mary McLean, Rasmus Tougaard, Joshua Kaggie, Martin Graves, Hans Stodkilde-Jorgensen, Ferdia Gallagher, Christoffer Laustsen

Imaging of the renal system with sodium MRI has gained interest in the past few years, especially in using the technique to quantify, and assess for, changes in the cortio-medullary sodium gradient. 

The main hindrance for previous work has been the lengthy scan time required to obtain sodium images. However, utilizing a 3D cones trajectory, the work presented here shows good detection of the cortio-medullary sodium gradient, in a  clinically feasible scan time, in a sample of six healthy controls. 

Yasmin Blunck, Sonal Josan, Brad Moffat, Roger Ordidge, Jon Cleary, Leigh Johnston

Challenging imaging characteristics (low SNR, fast bi-exponential decay) have so far limited the application of ²³Na-MRI in clinical environments. This work presents 3D Multi-Echo Radial Imaging of ²³NA (3D-MERINA), a time-efficient acquisition protocol from which multiple parameter maps (sodium-density, T₂*_slow and T₂*_fast, free ²³NA) can be derived in a single acquisition. Phantom and in-vivo measurements were analysed for the evaluation of parameter mapping and the inference of tissue characteristic based on decay behaviour. All parameters were acquired in a single sodium-density-weighted acquisition under relatively low SAR. Future investigation will exploit 3D-MERINA for SQF-SNR enhancement and the detection of MQF contrasts.

Yongxian Qian, Tiejun Zhao, Karthik Lakshmanan, Yulin Ge, Yvonne Lui, Timothy Shepherd, Fernando Boada

In human brain, intracellular sodium ions (Na⁺) are in slow and restricted motion due to their binding to negatively-charged macromolecules while their extracellular counterparts are in fast and unrestricted motion. This difference in motion properties leads to changes in bi-exponential transverse decay of free and bound sodium ions, which have been explored previously as a means to separate free and bound sodium. In this study, a new approach is proposed to separate free and bound sodium using single-quantum sodium images, without the SNR and SAR limitations as encountered in the triple-quantum filtering approach.

Nicholas Drachman, Stephen Kadlecek, Rahim Rizi

In this study we use hyperpolarized 13C-NMR to probe the dynamics of the decarboxylation reaction of pyruvate via H2O2, commonly used to produce hyperpolarized bicarbonate. Using this method we are able to observe and quantify the dynamics of the intermediate state, 2-hydroperoxy-2-hydroxypropranoate, which has never before been directly observed at room temperature, as well as characterizing a previously overlooked side reaction between the products and reactants of the decarboxylation reaction. This study serves as a template for how to use hyperpolarized 13C NMR to study the dynamics of innumerable other organic reactions with polarizable substrates.

Tanja Platt, Nicolas Behl, Thomas Fiedler, Armin Nagel, Andreas Bitz, Peter Bachert, Mark Ladd, Mark Wielpütz, Hans-Ulrich Kauczor, Reiner Umathum

Up to now, only a few abdominal ²³Na-MRI studies have been performed at 7T. In this work a ²³Na body coil for 7T was enhanced. To achieve an improved homogeneity in the transmit field and in the receive sensitivity, transmit phase settings were optimized and four separate receive channels were implemented. Field distributions in a phantom were obtained for the original and the enhanced configuration. Both setups were applied to the human chest and abdomen. Transmit and receive homogeneity are markedly improved for the enhanced setup. Improvements for in-vivo image quality are especially visible in the contour of the body.

Jack Miller, Damian Tyler, Vicky Ball, Oliver Rider, Christopher Rodgers

Ferumoxytol is a licensed carbohydrate-coated, superparamagnetic iron oxide nanoparticle indicated in the treatment of anaemia. We show that, in contrast to other agents, it predominantly reduces T₂, is confined to the blood pool for >1 hour post administration, and therefore could improve the efficiency of saturation pulses that aim to remove the 2,3-diphosphoglycerate signal from blood. This proof-of-principle study shows that Ferumoxytol could enable inorganic phosphate detection in vivo, and hence the determination of pH.

Sergey Cheshkov, Ivan Dimitrov, Joseph Rispoli, Jiaming Cui, Mary McDougall, Steve Wright, Stephen Seiler, A. Dean Sherry, Craig Malloy

Upregulated glucose uptake in cancer is often observed and can be monitored with a radiolabeled analogue of glucose, ¹⁸FDG, with detection by PET, however, a well-known constraint is its ionizing radiation. Additionally, except for the trapping of that glucose analogue, PET does not provide information about subsequent glucose metabolism. Here, we demonstrated the feasibility of a simple glucose infusion protocol that allows detection of glucose oxidation in human breast cancer in vivo via 7T ¹³C MRS. The [U-¹³C]glucose infusion is performed outside of the magnet making the protocol significantly more suitable for patients compared to previous approaches that required prolonged ¹³C substrate infusions inside the scanner.

Henk De Feyter, Raimund Herzog, Peter Brown , Douglas Rothman, Robin de Graaf

We present an indirect ¹H-[¹³C] MRS detection method (selective proton-observed, carbon edited (selPOCE) that can be used in the frontal lobe of human brain, allows for separation of overlapping glutamate (Glu) and glutamine (Gln) peaks and provides well-defined spatial localization of the ¹³C-signal. The method was successfully implemented at 4 Tesla and allowed for the selective detection of¹³C-labeling in Glu and Gln in a timely manner (15 min), indicating that the selPOCE can be used for quantitative studies of brain energy metabolism and neurotransmission in a relatively small volume localized in the human frontal lobe. 

Sebastian Niesporek, Reiner Umathum, Jonathan Lommen, Armin Nagel

A dynamic ¹⁷O-MRI inhalation experiment enables localized mapping of the cerebral metabolic rate of oxygen consumption (CMRO₂) in the human brain via H₂¹⁷O quantification. These functional information are tissue viability parameters and can help studying the brain metabolism. In ¹⁷O-MRI, accurate quantification and CMRO₂-determination is severely biased by partial volume effects caused by low spatial resolution and fast transverse relaxation. A human brain-simulation providing realistic dynamic ¹⁷O-data was used to evaluate the performance of a partial volume correction algorithm at different temporal resolution. Findings were then adapted to an in-vivo ¹⁷O-MRI inhalation experiment which was conducted in a healthy volunteer.

Lena Gast, Michael Uder, Armin Nagel

Double quantum filtered sodium (²³Na) MRI represents a way to examine the degree of tissue microstructure but suffers from low signal intensity and therefore long acquisition time. In this work we developed an efficient simultaneous acquisition scheme of single and double quantum images and determined the optimum acquisition parameters for human skeletal muscle. The feasibility of double quantum filtered ²³Na images of human lower leg at 3T was shown. 

Arthur Coste, Fawzi Boumezbeur, Alexandre Vignaud, Guillaume Madelin, Kathrin Reetz, Denis Le Bihan, Cécile Lerman, Sandro Romanzetti

This work presents a new method to measure Sodium concentration in human tissue using the Variable Flip Angle method with optimized acquisition parameters. Healthy volunteers were scanned and measures provided concentration values and T1 values in agreement with litterature values.

Yuchi Liu, Yifan Zhang, Chunying Wu, Junqing Zhu, Charlie Wang, Nicholas Tomko, Mikhail Linetsky, Robert Salomon, Yanming Wang, Xin Yu

This study aimed at developing a 3D dynamic oxygen-17 (¹⁷O) MR imaging method to delineate the kinetics of ¹⁷O-water uptake and washout in mouse brain with glioblastoma at high temporal and spatial resolution. A 3D imaging method using a stack-of-stars golden-ratio-based radial sampling scheme was combined with k-space weighted image reconstruction to improve the temporal resolution with preserved spatial resolution. The proposed method achieved a temporal resolution of 7.56 s with a voxel size of 5.625 μL in mouse brain at 9.4T. It can also be used to image cerebral oxygen consumption rate in ¹⁷O inhalation studies.

Jonathan Lommen, Sebastian Flassbeck, Nicolas Behl, Mark Ladd, Armin Nagel

Sodium imaging is mainly performed with spin-density weighted sequences to quantify tissue sodium concentration. However, relaxation weighting can add additional specific information. We pursue appropriate sampling for low SNR and fast biexponential decay. The accuracy and precision of typical T₂^* measurements is determined for different sampling schemes by simulation and phantom measurements. We developed a dedicated sampling scheme for brain parenchyma employing numerical optimization. The results suggest that averaging is preferable to increase reliability compared to denser temporal sampling. In-vivo comparison confirmed the advantage of the optimized patter with increased separation of the decay components.

Dimitri Welting, Wybe van der Kemp, Ingmar Voogt, Armin Nagel, Mark Ladd, Peter Luijten, Alexander Raaijmakers, Dennis Klomp, Nicolas Behl, Mariska Luttje

This work shows the potential of sodium imaging of the thyroid gland in vivo at 4mm isotropic resolution integrated to ¹H imaging. An optimized setup combined with tuned sequences and B₁ corrections enables quantitative sodium mapping of the thyroid gland and its surrounding tissue. The thyroid gland has the highest concentration of sodium in this part of the neck, estimated to be 64.5 mmol/L in vivo. Sodium imaging might open up the detection of (lymph node) metastases of thyroid cancer, as they are expected to exceed the healthy concentration of sodium detected in the head and neck region.

Nicolas Behl, Armin Nagel, Florian Maier, Peter Bachert, Mark Ladd, Reiner Umathum

²⁵Mg spectroscopy and imaging were performed for the first time in vivo. T₁ and T₂* of ²⁵Mg were evaluated in model solutions and T₂* was additionally estimated in vivo for the human calf. ²⁵Mg spectroscopy of an MgCl₂ model solution exhibits a single resonance attributed to free ²⁵Mg²⁺ ions, while in vivo spectroscopy of a human calf displays an additional resonance possibly attributable to bound ²⁵Mg. Phantom and in vivo ²⁵Mg imaging of the human calf were performed with a voxel size of 25×25×25 mm³.

Nadia Paschke, Wiebke Neumann, Tanja Gaa, Andreas Neubauer, Lothar Schad, Frank Zöllner

Sodium MRI enables to measure tissue sodium content (TSC) non-invasively, which provides additional cellular information and can serve as biomarker e.g. for tumor imaging. Thus, sodium imaging can complement standard clinical protocols. Many clinical routine protocols include perfusion scans with proton contrast agents but the influences on sodium relaxation times and therefore quantification accuracies of TSC are unknown. Our preliminary results showed no significant changes in sodium T₁ and only small reductions of T₂ with clinically relevant concentrations of contrast agents. Therefore, proton contrast agents are not expected to influence the TSC quantification in UTE sodium sequences.

Ruomin Hu, Andreas Neubauer, Matthias Malzacher, Simon Konstandin, Lothar Schad

Chloride Cl^- as the most abundant anion in mammals is a vital component of biophysical regulatory processes. ³⁵Cl MRI has the potential to visualise Cl^- homeostatic changes during stroke, in tumors and in ionic regulatory diseases. This study aimed at demonstrating the advantages of implementing density-adapted k-space sampling to overcome the instrinsically low SNR associated with ³⁵Cl MRI. We showed that density-adapted k-space sampling yielded distinctively visible improvement of image quality as well as quantitative SNR gain in phantoms with very fast bi-exponential T₂* relaxation over conventional radial sampling.

Wieland Worthoff, Aliaksandra Shymanskaya, N. Shah

Sodium imaging delivers valuable information about metabolism and disease. The spin dynamics of sodium are significantly impacted by the environment of the nuclei, multiple quantum coherences might develop via the quadrupole interaction. This allows imaging with multi quantum filters (MQF) to achieve weightings towards different sodium compartments. MQF sodium signals are detected with three consecutive RF pulses, by placing a readout train between the first and second RF pulse, a fully quantitative characterisation of relaxation properties in a two-compartment model is possible from measurements within a single sequence.

Nastaren Abad, Jens Rosenberg, Tangi Roussel, Dillon Grice, Michael Harrington, Samuel Grant

This study evaluates biochemical and metabolic imbalances that may result in a collection of dysfunctional pathways that are distinct in migraineurs. The high sensitivity and spectral dispersion available to ¹H MRS at 21.1 T expanded metabolic profiling in an animal model of migraine to include total creatine (tCr), choline (Cho), N-acetyl-aspartate (NAA), myoinositol (mI),  lactate (Lac), taurine (Tau), aspartate (Asp), Glx, a mixture of glutamate, glutamine and GABA, and Gly, the latter identified as a mixture of glycine, glutamine, and glutamate. For the migraine analogue, Lac, Gly and Tau increased while tCr decreased temporally and in comparison to saline controls.

Chi-Hyeon Yoo, Kyu-Ho Song, Song-I Lim, Do-Wan Lee, Dong-Cheol Woo, Bo-Young Choe

The chronic forced swimming stress (CFSS) depression-like animal model has been widely used to investigate the pathophysiology of depression focusing on the monoamine system. The goal of this study was to investigate the CFSS-induced metabolic effects in the prefrontal cortex (PFC) of animals showing depression-like behavior using high-field and short echo time (TE) in vivo proton magnetic resonance spectroscopy (1H MRS). The results suggest that high-field and short TE in vivo 1H MRS can reliably quantify the key metabolites involved in depression and CFSS-induced behavioral despair and metabolic alterations similar to those found in human patients with depressive disorders.

Francois Lazeyras, Maria Toms, Antoine Klauser

The aim of this study is to obtain normative reference 1H-MRSI data on the ratio of total NAA to total Cho in healthy subjects for subsequent use for clinical diagnosis of epileptic patients. Furthermore, we studied the effect of voxel content, primarily white matter and regional gray matter on metabolic levels.

Hoby Hetherington, Anne VanCott, Victor Yushmanov, Jodilyn Roberts, Daniela Mejia, Monique Kelley, Jullie Pan

Following mild traumatic brain injury (mTBI) many veterans continue to experience persistent symptoms despite an absence of significant findings on conventional MRI. In this study we acquired MRSI and volumetric data from veterans with a history of mTBI and PTSD, healthy age matched controls and veterans with PTSD without a history of mTBI. Data was acquired from the hippocampus (single slice MRSI) and cingulate (multiband MRSI). Significant declines in NAA/Ch were seen in the hippocampal formation in comparison to healthy controls and veterans with PTSD. Further, reductions in hippocampal NAA/Ch were statistically correlated with reductions in NAA/Ch from the cingulate

Sai Man Cheung, Ehab Husain, Yazan Masannat, Klaus Wahle, Steven Heys, Jiabao He

Breast cancer is associated with increased lactate production in tumour, known as Warburg effect, that is postulated to enhance cancer cell survival advantage and invasiveness. However, current evidence, mainly based on xenografted animal models or biopsy results, remains controversial, where non-identical biological environments are compared to humans, or partial sampling error may play a role. We therefore examined the role of lactate concentration in whole human breast tumour, and hypothesised that there is a difference in lactate concentration between grade II and III breast cancer. To extract lactate under overwhelming lipid signal, MQC MRS was optimised for robust measurement.

Chao Ma, Yen-Lin Chen, Kyung-Wook Jee, Ruth Lim, Ivan Chebib, Muge Oner Tamam, Shuang Hu, Georges El Fakhri

As the recent rapid development of radiation therapy techniques glowingly facilitate an individualized adaptive radiation therapy (RT), the roles of imaging as a tool to assess the early treatment response to RT or to tailor the treatment volume are becoming important. Conventional structural MR images have limited specificities in delineating and differentiating between residual/recurrent tumor and treatment effects (e.g., edema, inflammation, and radiation necrosis). This work presents a pilot study to assess response to RT in soft tissue sarcoma (STS) patients using a recently proposed rapid high-resolution MRSI method: SPectroscopic Imaging by exploiting spatiospectral CorrElation (SPICE). 

Kelley Swanberg, Hetty Prinsen, Robert Fulbright, David Pitt, Katherine Destefano, Mary Bailey, Christoph Juchem

Multiple sclerosis (MS) is an autoimmune disease that damages the central nervous system and affects an estimated 2.3 million people worldwide. One potential key to understanding MS is investigating the metabolic distinctions between its relapsing-remitting (RR-MS) and progressive courses (P-MS). We obtained single-voxel metabolic ¹H spectra at 7 Tesla from the frontal cortex of RR-MS and P-MS patients and controls to explore the effects of disease state on concentrations of brain metabolites like glutathione, GABA, glutamate, and N-acetyl aspartate (NAA). Our results suggest an age- and disease-related decrease in glutamate, as well as a disease-related decrease in NAA, in patients with P-MS relative to RR-MS and controls without MS. No disease-related changes in GSH or GABA were found. Our data underscore the importance of continued investigation into the potential physiological distinctions among various MS subtypes. 

Aaron Urquhart, Sharon Del Vecchio , Keng Ng, Hemamali Samaratunga, Graham Galloway, Peter Malycha, Simon Wood, Glenda Gobe, Carolyn Mountford

Small renal masses, such as non-clear cell renal carcinoma (non-ccRCC), can be monitored rather than resected as morbidity is unlikely. The distinction between malignant clear cell RCC (ccRCC) from indolent RCC subtypes and benign renal tumour is not possible by imaging thus some patients undergo unnecessary surgery¹. Using 2D COrrelated SpectroscopY we report that normal renal tissue, non-ccRCC and ccRCC each has different chemical profile. ccRCC differs from normal tissue with cholesterol and lipid increased by 572% and 481% (P=0.001); decreased alanine 51% (P=0.001); valine 57% (P=0.003) and lysine 46% (P=0.005). When comparing ccRCC to the non-ccRCC there are increases in valine 48% (P=0.004) and lysine 40% (P=0.04). 

Hitoshi Kubo, Takenobu Murakami, Masafumi Harada, Noboru Oriuchi, Seiichi Takenoshita, Shoji Yabuki, Yoshikazu Ugawa

To evaluate longitudinal neurochemical modulation induced by rTMS, we used ultra-short TE STEAM MRS. Glx, GABA and 15 other metabolites were measured using 3T MR equipment longitudinally and LCModel was used to calculate these concentrations quantitatively. QPS was employed as rTMS and left M1 was stimulated in each subject. Five healthy male volunteers participated in this study. The long-term depression intervention induced Glx increment, and the long-term potentiation intervention induced GABA decrement. The present results suggested a usefulness of the ultra-short TE STEAM MRS in evaluation of the longitudinal neurochemical modulation induced by rTMS.

Alireza Abaei, Francesca Rizzo, Dinesh K Deelchand, Tobias M. Böckers, Volker Rasche

Proton MRS is employed to assess the effect of systemic administration of aripiprazole and riluzole on the neurochemical profile of distinct functional regions in juvenile rat brain non-invasively in vivo. In this study, a dedicated optimized STEAM sequence with single-shot phase and frequency correction, and image-based shimming was applied to quantify subtle changes in the brain metabolites concentration during drug treatment in an ADHD rat model.

Sunitha Thakur, Olivia Sutton, Samuel Briggs, Ralph Noeske, Andrei Holodny, Ingo Mellinghoff, Robert Young

Cancer-associated mutations in IDH results in overproduction of 2-hydroxyglutarate (2HG). A few studies have evaluated the use of MR spectroscopy (MRS) technology to noninvasively determine IDH mutation status by measuring 2HG concentrations. However, it is unknown how factors such as signal-to-noise ratio (SNR), spectral apodization, and Cramér–Rao Lower Bounds (CRLB) can influence MRS sensitivity and specificity for 2HG detection in gliomas. This study seeks to define the ideal method to define optimal thresholds of CRLB and spectral filtering resulting in improved 2HG detection sensitivity without a drop in MRS specificity. 
 

Ryan Larsen, Borjan Gagoski, Marie Drottar, Thea Francel, Alana Matos, Clarisa Carruthers, Catherine Vu, Jonathan Litt, Bradley Sutton, Ellen Grant

We report measurements of GABA concentration in infants without sedation using the MEshcher-Garwood (MEGA) sequence.  Single-voxel measurements were performed in 114 infants at approximately one month and/or three months of age.  Quantification is performed with water scaling, and concentration values are reported in units of mM of NMR-visible water in the brain.   For the two scan times, we found the inter-subject coefficient of variation (CV) of GABA to be 8% and 9%, respectively.  Average GABA concentration values are 7% higher for the 3 month scan than the 1 month scan, indicating a gradual increase in GABA concentration after birth.  

Andrew Wright, Ruoyun Ma, Tom Hummer, Michael Francis, Andrew Visco, Nikki Mehdiyoun, Ulrike Dydak, Alan Breier

This study followed early stage schizophrenia patients undergoing treatment with single voxel MRS in the frontal lobe. Patients were split into a placebo (sugar pills) and treatment (N-acetylcysteine (NAC)) group and followed over the course of a year where they participated in 2-3 MRS scans at regular intervals. Patients show significantly elevated concentrations of Cre and Glx when compared to controls. This significance remained throughout the longitudinal study in intra- and inter-patient comparisons. This unchanged elevation of Glx and Cre contradicts the hypothesis that NAC will work to normalize these metabolite concentrations.

Xiaorui Su, Weina Wang, Qiyong Gong, Qiang Yue

In order to explore the changes of metabolites in the amygdala and the anterior cingulate of PTSD after earthquake, MR spectroscopy was applied. MRS showed higher ml and NAA levels in ACC, higher NAA levels in the right amygdala of PTSD group as compared to healthy controls. Besides, both in PTSD and healthy controls, NAA+NAAG levels were higher in the left amygdala than the right. And our results indicate there are some metabolic changes in amygdala and ACC of PTSD subjects. Whether combining depressive disorders, cause of PTSD and types of traumatic causes may have contributed to the inconsistency.

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

The purpose of the study was to evaluate neurochemical changes in the prefrontal cortex of rats during time-dependent sensitization in the single prolonged stress (SPS) model that reveals pathogenetic neurometabolites characteristic of posttraumatic stress disorder by using in vivo and ex vivo proton magnetic spectroscopy. After the time-sensitization period, Glu and Cr levels were reduced and Cho and Lac levels were increased in SPS group in comparison with control group. These indicate that SPS induced sustained adaptation of the glutamatergic activity in PFC.

Mingming Huang, Xiaobao Li, Guiquan Shen, Hui Yu

1H-MRS technology combined with Lcmodel software were used to quantitative the concentration of metabolites of posterior cingulate gyrus (PCC) in Parkinson’s disease patients with(PDCI) and without cognitive impairment(PDN), and  MMSE and MOCA tests were also performed. Compared with controls, the concentration of total creatine (tCr), N-acetylaspartate(NAA), myo-Inositol(mI), Glutathione (GSH), as well as glycerophosphocholine + phosphocholine (tCho) were found significantly decreased in PCC in PDCI group , but no changes were found in PDN. Additionally, correlations between concentration of tCr, GSH, tCho, NAA and MMSE (MoCA) scores can also be found . These results may indicate that the metabolites abnormalities in PCC might be used as a biomarker to track cognitive decline in Parkinson's disease in a clinical setting.

Jay Hennessy, Jamie Near

Previous fMRS studies at 7T have shown changes in brain metabolite levels elicited by different stimuli. This 3T study employed a modified version of PRESS to effectively measure neurochemical changes generated by a finger tapping task during the MRS scan. The results show lactate in the motor cortex increased approximately 11%, while glutamate and aspartate trend toward a 2% increase and 3% decrease respectively. More subjects are required for further validation.  

Kayla Ryan, Krzysztof Wawrzyn, Joseph Gati, Blaine Chronik, Neil Duggal, Robert Bartha

Transcranial direct current stimulation (tDCS) is a form of non-invasive brain stimulation that has been used to treat numerous cognitive and motor disorders.  However, its mechanism of action is poorly understood, resulting in controversy over its effectiveness.  The current study used ultra-high magnetic field (7 Tesla) magnetic resonance spectroscopy to determine if metabolite ratios were altered after the application of tDCS. In this preliminary study of 8 subjects, we found no differences in metabolite ratios in the motor cortex immediately following stimulation.

JY-KANG LIOU, Tun-Wei Hsu, Wei-Ta Chen, Chien-Yuan Lin, Jiing-Feng Lirng

We apply MEGA-PRESS MRS to measure brain metabolite level of Fibromyalgia patients and healthy controls at anterior cingulate cortex. The results show higher levels of GABA in Fibromyalgia than healthy controls but no significant difference was found in glutamine and glutamate levels.

Emmanuelle Flatt, Cristina Cudalbu, Olivier Braissant, Stefanita Mitrea, Valérie McLin, Dario Sessa, Rolf Gruetter

Hepatic encephalopathy (HE) is a severe complication of chronic liver disease (CLD). Treatments for HE have focused on reducing plasma ammonia levels implicated in HE pathogenesis. The antibiotic rifaximin reduces the production of gut ammonia which is considered to be the main toxin in CLD-induced HE. Rifaximin is commonly used in the treatment of HE and has been shown to reduce the frequency of HE episodes, but the molecular mechanisms behind this effect are unknown. We assessed, in vivo and longitudinally, the effect of rifaximin on brain metabolites in bile duct ligated rats using high-field proton Magnetic Resonance Spectroscopy.

Benita Tamrazi, Marvin Nelson, Stefan Bluml

Atypical Teratoid Rhabdoid Tumors (AT/RT) are highly malignant pediatric brain tumors distinguished from other primitive/embryonal tumors by alterations of the SMARCB1 gene. Recently, two molecular subtypes have been described for AT/RTs.  We have reviewed MR spectra of AT/RT patients and identified two distinct clusters in respect to their metabolic profiles. Should a correlation with genetic subtypes be confirmed, in vivo MRS could potentially play a key role in the initial stratification of patients diagnosed with AT/RT.

Dirk Cleppien, Bernd Lecher, Christian Kempe, Markus Sack, Anja Meier, Max Kullack, Wolfgang Weber-Fahr, Alexander Sartorius

Glycolysis is fundamental for cerebral energy metabolism. The current glycolysis pathway gives direct information about the local cellular health. To investigate hippocampal glycolysis in living rats, we established an experimental setup combining MRS and laser spectroscopy. It provides the opportunity to observe the behavior to the involved substances (glucose, lactate, NADH) for different glycolytic pathways. Under hyperglycemic conditions, blood oxygen limits glucose consumption leading to drops in NADH and lactate. In contrast, NADH and lactate concentrations increase under anaerobic conditions. This corresponds well with known literature and demonstrates the power of the presented setup to characterize hippocampal glycolysis in vivo.

Ivan Tkac, Igor Nestrasil, Steven Le, Jakub Tolar, Patricia Dickson

Mucopolysaccharidosis type I (MPS I) is an autosomal lysosomal storage disease caused by deficiency of α-L-iduronidase enzyme, which results in glycosaminoglycans accumulation within the lysosomes. MPS I leads to progressive loss of cognitive function and substantial physical disease in children. Abnormal myelin composition and reduced expression of myelin-related genes has been recently reported in a canine model of MPS I. The purpose of this study was to demonstrate whether demyelination of the corpus callosum can be detected also in a mouse model of MPS I using in vivo ¹H MRS at 9.4 T.

Rama Jayasundar, Aruna Singh

With increasing interest in the role of taste related fatty acids in food, pharmacology, health and diseases, objective study of this chemosensory parameter has assumed importance. The potential of NMR metabolomics to fingerprint chemosensory properties has been explored in the context of non-polar phytocompounds in this study. Non-polar fractions obtained by dual phase (chloroform-methanol/water) extraction of select dietary plants (n=24) were studied using proton NMR spectroscopy. Partial Least Squares Discriminant Analysis of the spectral data showed distinct chemosensory based clustering. NMR based chemosensory studies of non-polar phytocompounds could open new applications in sensorial sciences related to lipids and fatty acids.

Mark Mikkelsen, Maiken Brix, Pieter Buur, Kim Cecil, Kimberly Chan, David Chen, Alexander Craven, Koen Cuypers, Niall Duncan, Ulrike Dydak, David Edmondson, Gabriele Ende, Lars Ersland, Ian Greenhouse, Ashley Harris, Stefanie Heba, Tun-Wei Hsu, Jacobus Jansen, R. Lebel, Chien-Yuan Lin, Jy-Kang Liou, Jiing-Feng Lirng, Ruoyun Ma, Celine Maes, Scott Murray, Sean Noah, Ralph Noeske, Michael Noseworthy, Georg Oeltzschner, James Prisciandaro, Nicolaas Puts, Timothy Roberts, Markus Sack, Napapon Sailasuta, Muhammad Saleh, Michael-Paul Schallmo, Nicholas Simard, Stephan Swinnen, Martin Tegenthoff, Peter Truong, Hans-Jörg Wittsack, Vadim Zipunnikov, Helge Zöllner, Richard Edden

In this large multi-vendor, multi-site study, we seek to better understand the factors that impact quantitative outcomes of GABA-edited MR spectroscopy. Data from 187 participants from 19 research sites acquired on scanners from the three major vendors were pooled and analyzed using a standard pipeline. Coefficients of variation for GABA measurements acquired on each scanner platform and across the entire cohort were less than 11%. Multilevel linear modelling showed that most of the variance was accounted for by participant-level differences, while vendor-level differences accounted for comparatively more proportional variance than site-level differences.

Ioannis-Angelos Giapitzakis, Anke Henning

In this abstract, we evaluated the Carr-Purcell behavior of semi-LASER sequence  at 9.4T and we studied the influence of different relaxation times between the different moieties of NAA and NAAG using in-vivo acquired from occipital lobe and simulated spectra. The results indicate that differences in the relaxation time between different moieties can affect the fitting results and the metabolites levels. Moreover, an estimated value for the relaxation time of NAA-aspartate moiety is given. This work indicates that more measurements and investigation should be done, studying more metabolites and brain regions.    

Muhammad Saleh, Georg Oeltzschner, Mark Mikkelsen, Nicolaas Puts, Richard Edden

Initially conceived as a MATLAB-based batch-processing tool for GABA-edited MRS data acquired with MEGA-PRESS, Gannet 3.0 has been extended to provide new functionalities that can reconstruct data acquired using accelerated editing techniques of multiple metabolites and regions, perform frequency-and-phase correction (FPC), and perform fitting for GSH-edited spectra. We have demonstrated optimal FPC for MEGA-PRESS, MEGA-PRIAM and HERMES data, and fitting for GSH-edited spectra, rendering Gannet 3.0 a suitable post-processing tool for both conventional and accelerated editing. 

Malgorzata Marjanska, J McCarten, Dinesh Deelchand, Laura Hemmy, Melissa Terpstra

The resonances originating from high-molecular weight macromolecules (MM) underlie those of metabolites in brain ¹H NMR spectra. In humans, MM content and MM pattern have been shown to depend on age of the subject.  In this project, the influence of age-specific MM pattern on MR quantification was investigated. The age-associated differences in the MM pattern have a major influence on the quantification of metabolite concentrations in the aging brain which might lead to different interpretation of the data. This important finding suggests that the age-specific MM spectrum should be used in the basis set to obtain accurate concentrations of metabolites.

Tamás Borbáth, Ioannis Angelos Giapitzakis, Saipavitra Venkateshwaran Murali Manohar, Anke Henning

In this abstract, we present an adapted version of the ProFit-V2 fitting software to fit J-resolved semi-LASER data at 9.4T. Simulated basis sets with ideal pulses show the need to reduce the echo time to account for the spin locking effect of the adiabatic pulses. Further, a comparison of the fitting error estimations using correlation matrices and Cramer-Rao Lower Bounds with a metabolite cycled semi-LASER fitted with LCModel is done.

Malgorzata Marjanska, Dinesh Deelchand, Melissa Terpstra

To understand how linewidth impacts the current best practice of quantification, the novel approach was used to measure spectra of several linewidths from each subject in contrast to the traditional approach of mathematically broadening one reference spectrum. Mathematical broadening of an in vivo spectrum reproduced the lowering of tCr concentration reported in the past. In contrast, tCr concentrations measured from broader spectra obtained using suboptimal shims tended to be higher than those measured using ideal shims. Further inquiry into the exact source of these artifacts is likely to lead to corrective approaches.

Jan Willem van der Veen, Stefano Marenco, Karen Berman, Jun Shen

Recent high field susceptibility imaging experiments have revealed significant differences in water frequency in different tissue types. We studied the frequency distribution of choline, creatine, NAA, myo-inositol, glutamate, glutamine and GABA from gray matter- and white matter-dominant voxels. Based on data acquired from 135 normal subjects it was found that the best fit frequency of at least several metabolites are significantly dependent on tissue type composition.

Marianne Cleve, Martin Krämer, Alexander Gussew, Jürgen Reichenbach

We present an automatic routine for alignment of GABA ¹H MEGA-PRESS spectra to reduce subtraction artefacts which can compromise reliable GABA quantitation. The algorithm iteratively optimizes relative frequency and phase offsets between the edited and non-edited ¹H MEGA-PRESS spectra by minimizing the sum of the magnitude of the difference spectrum. The proposed method was applied to simulated spectra with preset frequency and phase errors and in vivo MEGA-PRESS data and compared to spectral registration, an alignment method implemented in the open source FID-A toolbox¹. Difference optimization demonstrated robust performance without requiring limitation of the input data range or user intervention.

Andre Doering, Victor Adalid Lopez, Chris Boesch, Roland Kreis

A recently described non-water suppressed diffusion-weighting MR spectroscopy sequence was applied in 13 healthy volunteers. The method uses the large water signal to compensate motion-related signal drop for the metabolite signals. 2D signal modeling with FiTAID allows for implementation of different prior knowledge constraints in order to prevent non-physical solutions or to restrict the number of unknown diffusion constants. In gray matter, highly significant differences for ADCs of several metabolites (faster diffusion for glutamate than NAA or myo-inositol) were found and their dependence on prior knowledge constraints investigated.

Simona Nikolova, Robert Nikolov, Craig Stark

There exist several partial volume correction methods in the literature that often produce similar results. However, various tissue fractions can lead to substantial differences in estimated concentrations. These deviations are greater at longer TEs and greater cerebrospinal fluid contributions. In instances with a 75% WM fraction and no gray matter, the deviations can be up to 37% for TE of 135 ms at 3.0 T. These corrections were then applied to common regions of interest (ROI) in an MRS study involving 5 participants at 3T. By understanding where these methods deviate one can better make cross study comparisons.

Kelley Swanberg, Hetty Prinsen, Daniel Coman, Robin de Graaf , Christoph Juchem

The tripeptide glutathione (L-γ-glutamyl-L-cysteinyl glycine or GSH) is an endogenous antioxidant implicated in many neurological conditions, including multiple sclerosis. Its precise quantification by proton magnetic resonance spectroscopy is, however, hampered by its uncertain T₂. Here, we present a method for the quantification of GSH T₂ in the human brain at 7 Tesla using optimized echo time extension delays and variable refocusing selectivity and symmetry to maximize the intensity and specificity of J-difference-edited GSH signals predicted by a full density matrix description of signal behavior. Using this method, we measured a GSH T₂ of 144.2 ± 5.5 ms that is considerably shorter than that calculated for either of two common reference metabolites NAA (221.9 ± 10.3 ms) or creatine (155.3 ± 5.9 ms), emphasizing the importance of considering T₂ relaxation differences in the spectroscopic measurement of these metabolites at long echo times.

Oun Al-Iedani, Karen Ribbons, Jameen ARM, Jeannette Lechner-Scott, Saadallah Ramadan

 

Our major aim of this study was to to evaluate diurnal effects on two key MR metrics; total brain volume and neurometabolite profiles. Repeated 3D-MPRAGE and 1D-MRS were undertaken over a 10-hour period on 10 healthy subjects (aged 36.1±7.7 years). Volumetric analysis, using vendor segmentation software, did not reveal any statistically significant effect of time of day or sex on total brain volume. Spectral data processing and analysis using LCModel showed a mild increase in glycerophosphocholine and total choline levels between 7am and 12pm. Our study suggested a lack of significant diurnal effect on these parameters.

Jack Miller, Lowri Cochlin, Damian Tyler, Kieran Clarke

In vivo MR spectroscopy is often characterised by a spectral signal-to-noise ratio (SNR) that varies highly between experiments, particularly when investigating non-proton nuclei. A common design for spectroscopic studies is to compare the ratio of two spectral peak amplitudes between groups, e.g. individual PCr/$$$\gamma$$$-ATP ratios in phosphorus MRS, or bicarbonate-to-pyruvate ratios in hyperpolarized $$$^{13}$$$C MRS. The uncertainty on this ratio is often neglected. We show that the correct propagation of this uncertainty improves statistical power.

Jack Miller, Angus Lau, Damian Tyler

Hyperpolarised [1-¹³C]pyruvate forms an effective probe of metabolism in vivo and has been used extensively to diagnose and prognosticate cancer. Commonly, [1-¹³C]pyruvate metabolism is quantified by either total metabolite-to-pyruvate integral ("AUC") ratios, or by fitting metabolic models by least-squares methods. Here, we use a modified Markov Chain Monte Carlo (MCMC) method with adaptive sampling and delayed rejection to fit models to hyperpolarised datasets of the healthy rat brain generated by a spectral-spatial EPI imaging sequence . The method is able to statistically discriminates between signal and noise, and returns quantitatively bounded maps of rate constants of interest, such as $$$k_{\text{Pyruvate}\rightarrow\text{Lactate}}$$$.

Petr Bednarik, Ivan Tkac, Lynn Eberly, Silvia Mangia

Sex is a critical biological factor that needs to be factored into study designs and analyses. In the present work, we sought to quantify sex-related differences of neurochemical profiles, utilizing 1H MRS data from the visual cortex of 22 healthy females (age 24±6 years) and 27 males (age 26±6 years) acquired at 7 T. Whereas there was a trend of sex-related differences for few metabolites, no statistically significant differences were observed above the attained metabolite sensitivity threshold of 0.2 µmol/g. The results indicate that sex is not a major confounding variable for MRS experiments performed on the visual cortex of young subjects.      

Kevin Moll, Alexander Gussew, Maria Nisser, Martin Krämer, Jürgen Reichenbach

Due to specific training orientations athletes adapt with different metabolic responses to a given exercise. We used a 31P MR multi-slice sequence allowing a non-invasive investigation of high energy changes in two muscles. Different metabolic adaptations were shown within two muscles of different trained athletes. This may help to characterize training specific effects  on energy metabolism.

Thao Tran, Marie Csete, Brian Ross, Elizabeth Geesaman, John Wilkes, Dan Buzatu

Pediatric mild traumatic brain injury data is necessary to understanding and predicting recovery of cognitive and psychiatric sequelae as pediatric subjects may take longer to recover than adults. Our study presents MR spectroscopy data acquired in five different brain regions of concussed and non-concussed high school athletes. Data were analyzed utilizing linear discriminant in combination with principal component analysis. Initial results demonstrate reasonable separation of mTBI subjects compared to normal controls. In addition, data from multiple time-points after injury demonstrate a return toward normal pattern and can be used to predict recovery and return-to-play times. 

Bhanu Prakash KN, Sanjay Verma, Suresh Sadananthan, Venkatesh Gopalan, Jadegoud Yaligar, Sankar Seramani, Andrew Maudsley, Sendhil Velan S

Whole brain temperature mapping is of great interest for investigating traumatic brain injuries.    Single-voxel-spectroscopy (SVS) and CSI approaches provides limited spatial coverage in the brain, whereas 3D Echo-planar spectroscopic imaging (EPSI), covers the entire brain for investigating temperature and metabolism in traumatic brain injury  and other studies .  Our study focuses on calibration and validation of the temperature measurement in brain phantoms using EPSI and SVS at pre-clinical and clinical scanners, to study and analysis of whole brain temperature in rodents and humans.

Miloslav Drobny, Petr Sedivy, Tereza Blahova, Katerina Zemankova, Monika Dezortova, Jan Kovar, Milan Hajek

    Liver fat content is an important parameter characterizing clinical status of the liver. Steatosis can be measured by magnetic resonance spectroscopy and imaging techniques non-invasively. The group of healthy volunteers was examined by MRS and MRI on three occasions after fat load, fat load with glucose and during whole-day fasting.

     Obtained results show that both used MR techniques are suitable for fat content measurements in the liver during dietary intervention. The pilot study results suggest that concentration of NEFA in systemic circulation is a critical factor that determines whether fat accumulates in the liver during the day in healthy insulin sensitive subjects.

Michael Dacko, Thomas Lange

For the detection and quantification of lactate (Lac) and β-hydroxybutyrate (bHB) via 1H-MRS, difference editing methods such as MEGA-PRESS have been proposed. Since MEGA-PRESS suffers from substantial signal loss due to large chemical shift displacement, we propose MEGA-sLASER for simultaneous detection of the two metabolites at 3T. It is demonstrated that the signal-to-noise ratio of the target resonances in the difference spectrum is increased by a factor of two compared to MEGA-PRESS and that quantification accuracy can thus be substantially improved, enabling the robust detection of Lac and bHB in healthy brain.

Zhongxu An, Vivek Tiwari, Sandeep Ganji, Changho Choi

Reliable detection of GABA is important for studies in neuro-psychiatric diseases.  In vivo 1H GABA resonances are extensively overlapped with the neighboring resonances including glutamate and glutamine. We present a new triple-focusing 1H MRS method which can fully resolve GABA 2.29-ppm and Glu 2.35 ppm signals at 3T. 

Peter Lally, Alan Bainbridge, Sudhin Thayyil

In this study, we aim to reduce the bias inherent in fitting short echo time spectra by performing a two-point saturation recovery experiment. At both points lipid and macromolecule magnetisation is excited from an approximately fully relaxed state and so this signal component is unchanged, thus the fitting model can be constrained. We show that this may be an advantageous strategy in comparison to other common techniques, reducing bias where fitting spectra with narrow linewidths.

Pallab Bhattacharyya, Mark Lowe, Ovidiu Andronesi

GABA spectroscopy is performed at 7T in vitro and in vivo using MEGA-PRESS and MEGA-LASER sequences. MEGA-LASER is shown to be much less sensitive to B1 inhomogeneity, and having higher signal intensity than MEGA-PRESS. Relative inter- and intra-sequence variabilities with respect to B1 inhomogeneity and regional variation are reported. Higher signal intensity in MEGA-LASER is attributed to reduced chemical shift displacement artifact and less signal loss resulting from spatial effects in phase evolution of J-coupled GABA.

Seyedmorteza Rohani Rankouhi, Hadrien Dyvorne, Donghyun Hong, Priti Balchandani, David Norris

Conventional sLASER sequence has different Chemical Shift Displacement Error (CSDE) in one of the three slice selection directions. In this work, a short TE matched CSDE sLASER sequence (MASE-sLASER) has been implemented using the novel MASE pulses for single voxel spectroscopy at 7T. The matched low CSDE of this sequence in all three directions provides more exact representation of the metabolites in the imaged voxel. The short duration of the MASE pulses with acceptable bandwidths have made it possible to achieve a TE as short as 28 ms for the MASE-sLASER sequence despite having one more RF pulse than the conventional sLASER sequence.

Seyedmorteza Rohani Rankouhi, David Norris

The most commonly used editing MRS method for measuring GABA is MEGA which works at TE=68 ms and any odd multiples thereof. Here we present a J-difference editing method which makes it possible to measure GABA signal at variable TEs independent of the effect of J-evolution by preserving the two side peaks of GABA in antiphase states at any echo time above 34ms. We also show an application of this editing technique to be measurement of T2 relaxation time of GABA in vivo.

Saipavitra Venkateshwaran Murali Manohar, Ioannis Angelos Giapitzakis, Tamas Borbath, Matti Gaertner, Anke Henning

J-resolved semi-LASER with maximum-echo sampling is optimized at 9.4T and compared with the same implementation at 3T in terms of SNR and spectral resolution. SODA scheme is appreciated for the sequence rather than the MC scheme. SNR at 9.4T (t₁ steps: 85) was approximately 5.8 times greater than at 3T (t₁ steps: 100) and strongly coupled peaks are well-resolved. However, the trade-off between SNR and spectral resolution is explained as lactate (1.32 ppm), a weakly-coupled metabolite, is better resolved at 3T.  Higher band-width AFP pulses helped in almost vanishing the J-refocused peaks which made the J-resolved peaks clearly distinguishable. A few interesting downfield peaks and the doublet of NAA (7.82ppm) are observed.

Kimberly Chan, Muhammad Saleh, Georg Oeltzschner, Peter Barker, Richard Edden

It has previously been shown that the HERMES method (‘Hadamard Encoding and Reconstruction of MEGA-Edited Spectroscopy’) can be used to simultaneously edit two metabolites (1).  Examples of pairs of metabolites edited include N-acetyl-aspartate (NAA) and N-acetyl aspartyl glutamate (NAAG), or glutathione and GABA (2).  Here, we demonstrate that HERMES can acquire simultaneously and then separate three overlapping edited signals, for the example of NAA, NAAG and Aspartate (Asp).  We optimize this sequence using simulations, and show its feasibility in phantoms and in vivo. We also explore the echo time modulation of the aspartate spin system using simulations and phantom experiments.

Ariane Fillmer, Ioannis Giapitzakis, Ralf Mekle, Semiha Aydin, Anke Henning, Bernd Ittermann, Florian Schubert

This work presents the combination of metabolite cycling with a non-water-suppressed SPECIAL localization scheme in order to enable improved averaging coherence for very short echo time MRS in small voxels or voxels that suffer otherwise from low SNR or frequency instabilities.

Petr Bednarik, Ivan Tkac, James Joers, Alena Svatkova, Gulin Oz, Dinesh Deelchand

Despite advancements in single-voxel hippocampal ¹H MR spectroscopy, low abundant and J-coupled metabolites, which are critically involved in neuro-energetics, memory and excitation/inhibition balance, are still poorly quantified at 3T. Hippocampal ¹H MRS at 7T may benefit from higher SNR and better spectral dispersion. Thus, the precision and test-retest reproducibility of quantification achieved at 7T using semi-LASER sequence was compared to the outcome of a similarly designed 3T study. The higher SNR at 7T relative to 3T allowed using smaller voxel for more precise selection of hippocampal gray matter while demonstrating improved quantification of J-coupled and/or low abundant metabolites.

Georg Oeltzschner, Karim Snoussi, Nicolaas Puts, Mark Mikkelsen, Ashley Harris, Subechhya Pradhan, Kyrana Tsapkini, Michael Schär, Peter Barker, Richard Edden

Macromolecule-suppressed J-difference-edited MRS of GABA is extremely sensitive to B₀ offsets. Relatively small frequency shifts (~10 Hz) may cause unwanted co-editing of macromolecules, to the extent that the edited ‘GABA’ signal appears negative in-vivo. We demonstrate an approach to measure transient field shifts arising from gradient-related eddy currents, and present a way to minimize these effects in order to restore correct editing.

Chris Hanstock, Dana Cobzas, Christian Beaulieu

Few studies have focused on metabolite diffusion using ¹H-MRS, compared to the vast number observing water diffusion by DWI/DTI. These MRS studies are lengthy, therefore difficult to implement clinically, and use up to three b-values to yield the diffusion spectra. Single exponential signal loss is assumed for metabolites, neglecting the possibility of non-linear decay at high b-values, as has been observed for water. Our goals are: (i) Characterize the metabolite signal decay versus b-value in human white matter to determine the non-linear region. (ii) Develop a rapid diffusion tensor spectroscopy method that can be executed in a clinically useful time.

Nienke Sijtsema, Arjan Hendriks, Peter Luijten, Dennis Klomp, Petra Pouwels, Catalina Arteaga de Castro

A 4-dimensional spatially and spectrally selective spin echo sequence was developed for prostate 1H MRSI at 7T. This sequence has intrinsic water and lipid suppression properties due to the limited spectral bandwidth, so only prostate metabolites are measured. The low peak power of the pulses also leads to lower SAR deposition and RF duty cycles. Phantom experiments showed an average water suppression of 99.99% at short TE, with low SAR and RF duty cycle values compared to adiabatic pulses routinely used at higher field strengths. Combined, these properties enable fast prostate MRSI acquisitions without water and lipid artifacts.

Young Woo Park, Dinesh Deelchand, James Joers, Brian Soher, Peter Barker, HyunWook Park, Gülin Öz, Christophe Lenglet

In this study, we present the implementation and outcome of a scheme for automatic voxel placement in single-voxel spectroscopy. The scheme is based on transfer of voxels prescribed on an atlas to the subject images during the scanning session and allows fast and reliable placement of voxels for spectroscopy measurements. 1H spectra of three different volumes of interest (VOIs) from multiple subjects were measured with a Siemens 3T scanner following automated and manual VOI placements. MRS data acquired using automatic placement produced spectral quality comparable to manual placement, while yielding better cross-subject spatial consistency than manual placement. 

Eric Woodcock, Muzamil Arshad, Dalal Khatib, Jeffrey Stanley

Single-voxel magnetic resonance spectroscopy (MRS) provides quantification of brain metabolite levels in vivo. However, MRS studies suffer from an often overlooked source of error variance:  inconsistent voxel placement. It is well-established that metabolite levels vary by brain region and voxel tissue composition. Thus, inconsistent voxel placement increases likelihood of Type I and II errors. To address this problem, we developed and evaluated a novel and automated method of prescribing voxel placements at the time of scanning. Results demonstrated a significant improvement in prescribing accurate and reliable voxel placements between and within subjects compared to manual placement and published methods. 

Georg Oeltzschner, Nicolaas Puts, Kimberly Chan, Vincent Boer, Peter Barker, Richard Edden

A twofold acceleration of MEGA-edited spectroscopy, using Parallel Reconstruction In Accelerated Multivoxel (MEGA-PRIAM) to simultaneously acquire data in two separate locations, is demonstrated. PRIAM separates the signals from two dualband-excited voxels using spatial receiver-coil sensitivity profiles. Phantom experiments show that MEGA-PRIAM separates GABA- and glutathione-edited spectra with low crosstalk between the voxels. In-vivo experiments establish that dual-voxel MEGA-PRIAM increases signal-to-noise ratio (SNR) 40% compared to sequentially acquired single-voxel MEGA-PRESS measurements with the same total duration. GABA and glutathione estimates are consistent between dual-voxel MEGA-PRIAM and single-voxel MEGA-PRESS acquisitions.

Kelsey Meinerz, Tianzhe Li, Scott Beeman, Joel Garbow, Joseph Ackerman

Crosslinked bovine serum albumin phantoms are used as tissue biexponential relaxation surrogates/mimics to investigate the potential of R₁-based tissue-O₂ quantification and to characterize the influence of physiologically relevant variations of temperature and protein concentration on such determinations. The relaxation-rate constant for the rapidly relaxing apparent water population is dominated by magnetization transfer and is insensitive pO₂. The relaxation-rate constant for the slowly relaxing apparent water population is linearly related to pO₂ and provides the basis for a possible MR-Oximetry protocol.

Miho Emoto, Hideo Sato-Akaba, Hirotada Fujii

Electron paramagnetic resonance (EPR) imaging is a noninvasive imaging method for visualizing the brain redox status using nitroxide compounds as imaging probes. A digital imaging system for three-dimensional continuous-wave EPR imaging of small animals was developed using a high-speed analog-to-digital converter, digital-to-analog converters and field programmable gate array integrated circuits to improve the signal-to-noise ratio (SNR) and visualize the precise brain redox status in mice. Compared to an analog EPR imager, the digital EPR imager obtains a higher SNR of a phantom and produces images with sufficient quality to create a more accurate brain redox map of the mouse head.

Niki Zacharias Millward , Christopher McCullough, Sriram Shanmugavelandy, Jaehyuk Lee, Youngbok Lee, James McHenry, Lawrence Jones , Pratip Bhattacharya

To understand and image how metabolism changes in prostate cancer (PCa), we determined both extracellular and intracellular metabolic profile of four PCa cell lines with varying degrees of aggressiveness.  Differences in metabolism and mechanistic link were further explored using carbon-13 glucose and glutamine feeding studies and  hyperpolarized pyruvate metabolic imaging trials with subcutaneous xenograft PC3 and PC3M animal models. We found increased glutamine utilization in the more metastatic cell line PC3M and this increased dependence on glutamine leads to reduction in cell proliferation and ATP when cells are treated with glutaminase inhibitor CB-839. No reduction is seen in PC3 line.

Tanushri Chatterji, Suruchi Singh, Ajai Singh, Manodeep Sen, Raja Roy

The chemical composition of cerebrospinal fluid (CSF) in central nervous system (CNS), varies during onset of meningitis, neurodegenerative disorders and in traumatic cases.The study attempted to observe the metabolic variation in meningitis cases, negative controls and positive controls. Further differentiation among the groups was carried out using Principal Component Analysis (PCA) followed by Partial Least Square Discriminant Analysis (PLS-DA).On the basis of metabolic profile it was found that negative control CSF samples are more appropriate for differentiation of meningitis than positive control CSF samples.The biomarkers identified were ketone bodies, amino acids, propylene glycol, citrate and creatine/creatinine.

Gaelle Diserens, Martina Vermathen, Chiara Sartori, Marie-Gabrielle Zurich, Peter Vermathen

3D rat brain aggregate model is an excellent tool for mechanistic studies including OMICS analysis. However, their metabolic profile have not been yet fully investigated. The aim was to investigate by ¹H-HR-MAS NMR the metabolic fingerprint of 3D brain cell cultures at different maturation stages to establish a developmental profile of metabolic changes. Chemometric analysis revealed a clear separation of samples from the different maturation days. Metabolite concentration evolutions could be followed and revealed strong and various metabolic alterations. The strong metabolite evolution emphasizes the brain modelling complexity during maturation, possibly reflecting physiological processes of brain tissue development.