Ruth L O'Gorman¹, Lars Michels¹, Richard Edden², and Ernst Martin^1
1University Children's Hospital, Zürich, Switzerland, ²Russell H Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University, Baltimore, MD, United States

Few studies have examined the normal inter-subject variability in MRS GABA and glutamate (Glu) concentrations with factors like age and gender. This study investigates age- and gender-related differences in GABA and Glu in a group of healthy adults. No significant age effects were seen, but GABA, Glu, and Glx (glutamate+glutamine) levels were significantly higher in the male participants. These significant differences are independent of the grey and white matter fraction in the MRS voxel and emphasize the importance of gender-matching for GABA and Glu MRS studies with mixed-cohort subject groups.

Christopher John Evans¹, Frederic Boy¹, Richard A E Edden², Krish D Singh¹, and Petroc Sumner^1
1CUBRIC, School of Psychology, Cardiff University, Cardiff, Wales, United Kingdom, ²Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University, Baltimore, United States

In this work, we report on the regional differences in human GABA levels, measured with MEGA-PRESS. Six regions were studied - anterior cingulate, dorsolateral pre-frontal cortex, inferior frontal gyrus, supplementary motor area, parietal lobe and occipital lobe. There was a significant effect of region and of voxel grey matter fraction on GABA. The measured differences in GABA not attributable solely to differences in the tissue composition across regions.

Christopher John Evans¹, Frederic Boy¹, Richard A E Edden^2,3, Krish D Singh¹, Masud Husain⁴, and Petroc Sumner^1
1CUBRIC, School of Psychology, Cardiff University, Cardiff, Wales, United Kingdom, ²Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University, Baltimore, United States, ³F.M. Kirby Research Center for Functional MRI, Kennedy Krieger Institute, Baltimore, United States, ⁴UCL Institute of Cognitive Neuroscience & UCL Institute of Neurology, UCL, London, England, United Kingdom

The concentration of inhibitory neurotransmitter GABA has previously been demonstrated to predict participants’ performance in visual behavioural tasks. Here, we demonstrate that GABA concentration correlates with the performance of participants in a motor task closely associated with behavioural inhibition (the Negative Compatibility Effect, NCE). Individual differences in participants' NCE is explained by differences in participants GABA levels in the supplementary motor area, but not correlated with other brain regions.

Mary Charlotte Stephenson¹, Matthew J Brookes¹, Darren Price¹, Antonio Napolitano², Susan T Francis¹, and Peter G Morris^1
1School of Physics and Astronomy, University of Nottingham, Nottingham, Nottinghamshire, United Kingdom, ²Academic Radiology, University of Nottingham, United Kingdom

The peak frequency of stimulus-induced visual -oscillations, measured using magnetoencephalograpy, has been shown to be predicted by the resting concentration of -amino butyric acid (GABA). However, cortical network models show that the oscillatory frequency depends on the balance between excitatory and inhibitory neurotransmitters. In this study we utilize the increased spectral resolution and signal available at 7T to quantify glutamate, glutamine and GABA. Our results indicate a stronger correlation between -frequency and glutamate/GABA than for GABA alone. The strongest correlation was found for glutamine/GABA where the glutamine concentration is thought to be closely related to the glutamate neurotransmitter pool size

Hyeon-Man Baek^1
1Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, Texas, United States

Recently, in vivo 1H-MRS acquired with water suppression has been proven helpful for the detection and therapy response monitoring of breast cancer based on total choline-containing compounds (tCho). However, the role of 1H-MRS acquired without water suppression is less established. The aim of our study was to determine whether quantitative results from the breast cancer can show good agreement between the estimated tCho levels in water-suppressed and unsuppressed spectra. There was a statistically significant correlation between the estimated tCho concentration levels by 1H-MRS with and without water suppression (r2 = 0.462, p =0.001). This result demonstrates the feasibility of in vivo quantitative 1H-MRS without water suppression for the measurement of tCho concentrations from in vivo malignant breast lesions.

Wybe van der Kemp¹, Vincent Boer¹, Peter Luijten¹, Jannie Wijnen¹, and Dennis Klomp^1
1Department of Radiology, University Medical Centre, Utrecht, Netherlands

Here we show for 31P MR spectroscopy that by integrating polarization transfer (BINEPT) and a spin echo (SE) in one repetition time, one can gain extra signal to noise for the BINEPT as compared to spectra from separate BINEPT and SE sequences. The BINEPT signal is hardly affected by the subsequent SE. However, the BINEPT signal has some saturating effect on the SE signal. Alternatively, the integrated sequence can be used to obtain an BINEPT at the same SNR, but with the additional information on metabolite content that direct detection offers.

Michaël Sdika¹, Yann Le Fur¹, and Patrick J Cozzone^1
1CRMBM, CNRS, UMR 6612, Faculté de Médecine de Marseille, Université de la Méditerranée, Marseille, France

This work addresses the problem of the optimal recombination of multi-coil chemical shift imaging (CSI) data. Eddy current correction is performed using the unsuppressed water signal. Coil sensitivity maps are computed using low resultion images and optimal recombination formula are derived.

Bernd Merkel¹, Markus T. Harz¹, and Horst K. Hahn^1
1Fraunhofer MEVIS, Bremen, Germany

MR Spectroscopy hasn't found the way into clinical routine yet. For one reason, most of the existing devices and software assistants lack of performance or difficult handling. We present the novel research prototype MISSA (MEVIS Imaging and Spectroscopy Software Assistant) for the analysis of single- (in vivo, ex vivo) and multi-voxel (2D, 3D) spectroscopy. All standard processing steps are included, together with different quantification methods, which can be easily extended. Furthermore, 3D-visualization, PACS connection and the possibility of voxel-labeling with export to machine learning algorithms are integrated. Therefore, it is our goal to improve and simplify MRS data analysis.

Tobias Hahn¹, Sebastian Kozerke¹, Werner Schwizer², Michael Fried², Peter Boesiger¹, and Andreas Steingoetter^1,2
1Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland, ²Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland

A combined 19F and 1H MRI framework enabling the co-registration of local intestinal motor function and transit assessed by 19F MRI with anatomical 1H MRI data was implemented and its potential for physiological GI MRI demonstrated. Biologically inert and impermeable 15C5 labeled capsules were developed. Capsule movement and gastric transit upon oral administration of one and two capsules were monitored in real time by a 19F projection imaging sequence using a 3T whole-body system equipped with a dual-channel 19F transmit-receive surface coil. The developed framework was found to be feasible for the non-invasive visualization and quantification of gastrointestinal motor activity.

Elisa Placidi¹, Caroline L Hoad¹, Luca Marciani², Alan C Perkins³, P E Blackshaw³, Robin C Spiller², and Penny A Gowland^1
1SPMMRC, Nottingham, Nottinghamshire, United Kingdom, ²Nottingham Digestive Diseases Centre Biomedical Research Unit, Nottingham, United Kingdom, ³Academic Medical Physics, Nottingham, United Kingdom

A pilot in vivo study measuring gastrointestinal transit with MRI is presented. Purpose built plastic capsules, double labelled with a fluorine agent and a gadolinium solution were given to two volunteers scanned up to 48 hours. The Gadolinium solution gave a very bright signal which could be identified at all time points in the entire GI tract. The fluorine image gave confirmation of their position but the fluorine coil often had to be repositioned after the exact location of the capsules was established. In future it will be possible to perform studies of GI transit using just 1H labelled capsules.

Janet Friedrich¹, Julien Rivoire¹, Maxim Terekhov¹, and Laura Maria Schreiber^1
1Section of Medical Physics, Johannes Gutenberg University Medical Center, Mainz, Germany

High frequency oscillatory ventilation (HFOV) is a protective ventilation method mainly used for patients with acute respiratory distress syndrome (ARDS). To explore gas flow mechanisms during HFOV 19F-MRI of fluorinated gases was performed at 1.5T. With a flow sensitive gradient-echo-sequence velocity profiles during HFOV could be determined and tracked over time with a temporal resolution of 10ms. The signal-to-noise ratio and hence the reliability of velocity information could be improved by skipping the phase encoding gradient. In summary, the present work demonstrates that flow measurement of fluorinated gases is feasible and can also be applied under HFOV.

Ping-Huei Tsai¹, Alan C Seifert¹, Alexander C Wright¹, Hamidreza S Rad¹, Jeremy F Magland¹, Hee Kwon Song¹, Mary B Leonard², and Felix W Wehrli^1
1Laboratory for Structural NMR Imaging, Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States, ²Center for Clinical Epidemiology and Biostatistics, Children¡¦s Hospital of Philadelphia, Philadelphia, PA, United States

Osteomalacia is characterized by hypomineralization of bone, i.e., low phosphorus concentration, and a noninvasive means to assess bone phosphorus would be desirable. However, 31P MR signals from bone have low SNR due to extremely short T2* and long T1, as well as small gyromagnetic ratio. High-field scanners and 3D radial imaging sequences can mitigate these limitations. The purpose of this study was to design and evaluate the peformance a 3D radial imaging technique and customized RF coils to obtain in-vivo phosphorus images of human cortical bone at the mid-shaft tibia at 7T. Preliminary results demonstrate the method¡¦s feasibility and suggest the potential for quantitative measurements.

Junghwan Kim¹, Bumwoo Park¹, Alessandro Furlan¹, Chanhong Moon¹, Sung-hong Park¹, Tiejun Zhao², and Kyongtae Ty Bae^1
1Department of Radiology, University of Pittsburgh, Pittsburgh, PA, United States, ²MR Research Support, Siemens Healthcare, Pittsburgh, PA, United States

We have developed a dual-tuned proton/sodium knee RF coil at 7T and obtained high-resolution sodium MR imaging and T2 mapping of human knee cartilages within clinically acceptable time. Further studies on coil optimization and reproducibility of sodium concentration measurement should be followed for the clinic application.

Friedrich Wetterling¹, Saema Ansar², Laurant Tritschler², Raffi Kalayciyan¹, Stefan Kirsch¹, Marc Fatar², Stephen Meairs², and Lothar R. Schad^1
1Computer Assisted Clinical Medicine, Heidelberg University, Mannheim, Germany, ²Departmenet of Neuroloy, Heidelberg University, Mannheim, Germany

The aim of this project was to develop a triple resonant 1H/23Na/35Cl coil system for investigations on a rat stroke model without the need to exchange resonators during the measurements. The newly-developed coil system was composed of a linear 1H birdcage resonator and a double-tuned 35Cl/23Na surface coil. 1H imaging capability enabled the use of standard stroke sequences such as diffusion- and T2 weighted MRI. The coil performance was successfully tested on a 1H/35Cl/23Na-phantom. First brain images at 5 days after stroke confirmed the excellent coil performance for in vivo imaging.

Adrian Tsang¹, Rob Stobbe¹, and Christian Beaulieu^1
1Biomedical Engineering, University of Alberta, Edmonton, Alberta, Canada

B0-inhomogeneities may cause regional signal loss on triple-quantum-filtered (TQF) sodium images. Three phase cycling algorithms were proposed recently to rectify this adverse effect with the cost of extensively increasing scan time; however, these were all only verified on small agarose phantoms. The goal of our study is to evaluate the extent of off resonance signal loss and their correction on human brain sodium TQF images and to determine whether the considerable two fold increase in scan time is warranted for in vivo studies.

Victor D. Schepkin¹, Fabian Calixto Bejarano¹, Thomas Morgan², Shannon Gower-Winter², and Cathy W. Levenson^2
1CIMAR/MRI, NHMFL/FSU, Tallahassee, Florida, United States, ²Biomedical Sciences, FSU, Tallahassee, Florida, United States

The diagnostic value of sodium MRI has not been established; however, the evidence of its potential is growing with the availability of high magnetic fields. Rodent glioma therapy by BCNU was thoroughly evaluated by sodium and diffusion MRI. The time courses of tumor responses reveal loss of the tumors’ intracellular sodium gradients early on during therapy, demonstrating it can be part of the in vivo apoptotic process. This finding correlates with multiple evidences already found in vitro. The effect of positive therapy can be detected for each animal individually in a day after initiation of treatment.

Aiming Lu¹, Ian C Atkinson¹, and Keith R Thulborn^1
1Center for MR Research, University of Illinois, Chicago, IL, United States

The sodium MR signal is affected by the local electrical field gradient and exhibits bi-exponential relaxation behavior in brain. The relaxation times not only are critical parameters for optimizing the sequences for quantifying tissue sodium concentration, but also convey information on the local sodium ion environment. However mapping the relaxation times of sodium in biological tissues in vivo is challenging. We demonstrate here with an efficient multiple-echo flexible twisted projection imaging sequence that high quality T2* maps of the sodium MR signal in the entire human brain can be achieved within a reasonable scan time at 3T.

Guillaume Madelin¹, Alexej Jerschow², and Ravinder R Regatte^1
1Radiology Department, New York University Medical Center, New York, NY, United States, ²Chemistry Department, New York University, New York, NY, United States

This preliminary work shows the feasibility of sodium T1 and T2* measurements in vivo on 8 healthy volunteers in 4 different regions (patellar, medial, lateral and condyle) of the articular cartilage at 7T and in a reasonable time for the patient (~35 min for each relaxation time). Sodium relaxation maps are calculated and could be useful as information complementary to the sodium concentration maps for assessing early osteoarthritis (OA) in patients, as T2* and T1 are expected to change with cartilage degeneration. Future improvements may include fluid suppression for reducing partial volume effects and a systematic study of OA patients.

Joshua Kaggie¹, Danny Park², Rexford D Newbould³, Glen R Morrell⁴, Brian Hargreaves⁵, Ernesto Staroswiecki^5,6, Gary E Gold⁵, and Neal K Bangerter^2
1Physics, University of Utah, Salt Lake City, UT, United States, ²Electrical & Computer Engineering, Brigham Young University, Provo, UT, United States, ³GSK Clinical Imaging Centre, London, United Kingdom, ⁴Radiology, University of Utah, Salt Lake City, UT, United States, ⁵Radiology, Stanford, Stanford, CA, United States, ⁶Electrical Engineering, Stanford, CA, UT, United States

In this work, we improve upon previously reported values of T1 and T2* for sodium in the breast. Previously, we used a DESPOT1 sequence, whereas we have developed an inversion recovery sequence so that we can measure T1 values more accurately. For our healthy woman volunteer, we measured sodium T1 to be 39.0 ± 4.8 ms, T2long to be 21.0 ± 5.6 ms, and T2short to be 0.8 ± 0.4 ms.

Yi Sui^1,2, Haoyang Xing², Theodore Claiborne², Keith R Thulborn^2,3, and Xiaohong Joe Zhou^2,4
1Department of Bioengineering, University of Illinois at Chicago, Chicago, IL, United States, ²Center for Magnetic Resonance Research, University of Illinois Medical Center, Chicago, IL, United States, ³Department of Radiology, University of Illinois Medical Center, Chicago, IL, United States, ⁴Departments of Radiology, Neurosurgery and Bioengineering, University of Illinois Medical Center, Chicago, IL, United States

In this study, we report multiple techniques to address the challenges of 31P relaxation measurements at 9.4 T. A Look-locker (LL) method was adapted for T1 measurement to shorten the total scan time. A two-tip-angle method was used to address the B1-field non-uniformity problem in the LL sequence. Additionally, quadratic-phase modulated RF pulses were employed to reduce RF peak amplitude without compromising the requirement of broad bandwidth of 31P spectrum at 9.4T. By strategically integrating these techniques, 31P relaxation times in human muscle have been determined accurately at 9.4 T within ~30 min.

Guillaume Madelin¹, Gregory Chang¹, Alexej Jerschow², and Ravinder R Regatte^1
1Radiology Department, New York University Medical Center, New York, NY, United States, ²Chemistry Department, New York University, New York, NY, United States

This study demonstrates the feasibility of quantitative sodium MRI with fluid suppression in vivo in the knee joint at 3T and compares the results with that of 7T on the same 4 asymptomatic healthy volunteers. Two inversion recovery based methods (with a rectangular and an adiabatic pulse) for suppressing the fluids are also compared and show a good agreement at both fields. These preliminary results at 3T, despite their lower SNR and the small number of volunteers in this study, show slightly lower sodium concentration measurements but are still in good agreement with the data at 7T.

Yongxian Qian¹, Tiejun Zhao², Jonathan Weimer³, Hai Zheng³, and Fernando E Boada^1,3
1Radiology, University of Pittsburgh, Pittsburgh, PA, United States, ²R&D, Siemens Medical Solutions USA, Pittsburgh, PA, United States, ³Bioengineering, University of Pittsburgh, Pittsburgh, PA, United States

The 7T scanners produce images of higher signal to noise ratio (SNR) than the 3T scanners and thus have potential to generate sodium images of higher spatial resolutions. This work demonstrates the feasibility of high-resolution (0.86mm) sodium imaging on human brain at 7T.

Peter Linz¹, Davide Santoro², Wolfgang Renz^2,3, Jan Ruff³, Jens Titze⁴, Friedrich Luft⁵, and Thoralf Niendorf^2,5
1Department of Nephrology and Hypertension, University Clinic Erlangen-Nuernberg, Erlangen, Germany, ²Berlin Ultrahigh Field Facility, Max-Delbrueck Center for Molecular Medicine, Berlin, Germany, ³Siemens Healthcare, Erlangen, Germany, ⁴Department of Nephrology and Hypertension and Nikolaus-Fiebiger-Center for Molecular Medicine, University Clinic Erlangen-Nuernberg, Erlangen, Germany, ⁵Experimental and Clinical Research Center (ECRC), Charité Campus Buch, Humboldt-University, Berlin, Germany

We propose a dedicated 23Na coil to accomplish the first 23Na-MRI images of the skin with a sub-millimeter in plane resolution.

Robert L. Greenman¹, Xiaoen Wang¹, and Howard A. Smithline^2
1Radiology, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, MA, United States, ²Emergency Medicine, Bay State Medical Center, Tufts University School of Medicine, Boston and Springfield, MA, United States

The structure, blood flow patterns and metabolism have wide spatial variations in healthy individuals and are further modified in disease states and with physical training. Current methods cannot provide a simultaneous assessment of multiple muscle beds in a human limb. To address this need we have evaluated a phosphorus-31 MRI method for measuring the post-exercise recovery time constant of phosphocreatine in all of the muscles in a cross-section of the human leg. The method agrees very closely with the current standard method of phosphorus-31 MR spectroscopy and is highly reproducible.

Benjamin M. Pullinger¹, Stephen J. Kadlecek¹, Helen Chen², Qingwei Chu², Nicholas N. Kuzma¹, and Rahim R. Rizi^1
1Radiology, University of Pennsylvania, Philadelphia, PA, United States, ²Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA, United States

The metabolism of hyperpolarized [1-¹³C]pyruvate was investigated in the isolated perfused mouse liver. Along with the commonly observed conversions to alanine and lactate, we also observed pyruvate dehydrogenase (PDH) and pyruvate carboxylase (PC) activity. The ability to simultaneously measure PC and PDH flux has important implications in the study of insulin resistance. As a proof of concept, we report an increase in PC flux (0.17  0.03 to 0.30  0.06) in fasted livers compared to fed livers.

Mikko I Kettunen¹, Menna R Clatworthy^2,3, Timothy H Witney¹, De-en Hu¹, Brett W. C Kennedy¹, Sarah E Bohndiek¹, Rebeccah J Mathews^2,3, Ferdia A Gallagher^1,4, Ken G Smith^2,3, and Kevin M Brindle^1
1Department of Biochemistry, University of Cambridge & Cancer Research UK Cambridge Research Institute, Cambridge, Cambridgeshire, United Kingdom, ²Cambridge Institute for Medical Research, Cambridge, Cambridgeshire, United Kingdom, ³Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, Cambridgeshire, United Kingdom, ⁴Department of Radiology, Addenbrooke’s Hospital, University of Cambridge, Cambridge, Cambridgeshire, United Kingdom

Acute tubular necrosis (ATN) and glomerulonephritis (GN) are two common clinical forms of acute kidney injury with different treatment requirements. Currently, there is no non-invasive test to differentiate them. Here we exploited the appearance of malate signals following injection of hyperpolarized [1,4-¹³C₂]fumarate to identify folate-induced ATN. Significantly increased malate signals were observed 18h after folate injection indicating increased necrosis. In contrast, malate signals were not increased in GN model despite the presence of proteinuria in both models. The results suggest hyperpolarized [1,4-¹³C₂]fumarate is a potential non-invasive marker for separating ATN and GN.

Aaron Keith Grant¹, Elena Vinogradov¹, Xiaoen Wang¹, Hao Wang¹, Pankaj K Seth², Vikas P Sukhatme², David C Alsop¹, and Robert E Lenkinski^1
1Radiology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, United States, ²Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, United States

13C spectra acquired after administration of hyperpolarized contrast media generally result in a relatively sparse collection of spectra lines. Several strategies that exploit this sparsity have been proposed for fast 13C spectroscopic imaging. Here we show that by acquiring a series of balanced steady-state free precession (bSSFP) images with a variable RF phase advance it is possible to obtain separate images of several metabolites. The method is illustrated using phantoms and in vivo studies with hyperpolarized pyruvate and t-butanol.

Peder Eric Zufall Larson¹, Adam B Kerr², Ralph E Hurd³, John Kurhanewicz¹, John M Pauly², and Daniel B Vigneron^1
1Radiology and Biomedical Imaging, UC - San Francisco, San Francisco, CA, United States, ²Electrical Engineering, Stanford University, Stanford, CA, United States,³Applied Science Laboratory, GE Healthcare, Menlo Park, CA, United States

Stimulated-echoes can be used to provide high sensitivity to diffusion and flow, creating unique contrast, but they inherently suffer from a 50% signal loss. The signal can be improved with a super stimulated-echo, which is more efficient. We have designed a new super stimulated-echo preparation scheme for diffusion and perfusion contrast in hyperpolarized 13C metabolic imaging. These have an expected 60% increase in SNR over a conventional stimulated-echo. By utilizing adiabatic pulse shapes in the preparation, they also have an improved response to B1+ variations. In vivo experiments in transgenic cancer mouse models have shown improved contrast for tumors.

Keita Saito¹, Shingo Matsumoto¹, Nallathamby Devasahayam¹, Sankaran Subramanian¹, Jeeva P Munasinghe², Jan Henrik Ardenkjaer-Larsen³, Herman Douglas Morris², Martin J Lizak², James B Mitchell¹, and Murali C Krishna^1
1National Cancer Institute, Bethesda, Maryland, United States, ²National Institute of Neurological Disorder and Stroke, ³GE Healthcare

MRI using hyperpolarized [1-¹³C]pyruvate is a promising tool for cancer diagnosis, but influences of exogenously injected pyruvate on tumor physiology were not well understood. Here, effects of pyruvate injection on tumor oxygen status were investigated using pulsed electron paramagnetic resonance imaging. Tumor pO₂ was remarkably decreased 30 min after [1-¹³C]pyruvate injection. The pO₂ decrease was transient, and the pO₂ recovered to the pre-injection level 5 h after the pyruvate injection. This transient decrease in the pO₂ influenced effects of X-irradiation: tumor growth suppression by X-irradiation was weakened when [1-¹³C]pyruvate was injected to mice 30 min before X-irradiation.

Jae Mo Park^1,2, Sonal Josan^2,3, Taichang Jang⁴, Milton Merchant⁴, Yi-fen Yen⁵, Ralph Hurd⁵, Lawrence Recht⁴, Daniel Spielman^1,2, and Dirk Mayer^2,3
1Department of Electrical Engineering, Stanford University, Stanford, CA, United States, ²Department of Radiology, Stanford University, Stanford, CA, United States, ³SRI International, Menlo Park, CA, United States, ⁴Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, United States, ⁵Global Applied Science Laboratory, GE Healthcare, Menlo Park, CA, United States

In this work, we measured the kinetics of pyruvate metabolism in a glioma brain tumor model using the hyperpolarized 13C technique with a fast spiral CSI sequence, and compared the metabolic kinetics from three different ROIs: brain tumor, normal brain, and vasculature. Robust dynamic curves of Pyr and Lac were achievable repeatedly with 3 seconds of temporal resolution using the variable RF excitation angle on a single slice. The apparent rate constant of Pyr-to-Lac conversion in the brain tumor was noticeably higher than that in the normal brain and the vasculature.

Lloyd Lumata¹, Richard Martin¹, Ashish Jindal², Zoltan Kovacs¹, Craig Malloy¹, A Dean Sherry¹, Mark Conradi³, and Matthew E Merritt^1
1AIRC, UTSW Medical Center, Dallas, TX, United States, ²UTSW Medical Center, United States, ³Physics, Washington University in St. Louis, St. Louis, MO, United States

In order to produce large volumes of highly polarized imaging agents, a DNP system based on a cryostat placed in an ultra widebore 4.6 T magent has been designed and implemented. The large available space allows a 600 ul sample cup to be used as well as an LN2 shield for the LHe bath. Operating at a 129 GHz ESR frequency and using nitrogen based radicals, samples with sufficient polarization for animal imaging are easily obtained. Total cost of the system was less than $100K, sans the cost of the magnet.

Sonal Josan^1,2, Daniel Spielman², Yi-Fen Yen³, Ralph Hurd³, Adolf Pfefferbaum^1,4, and Dirk Mayer^1,2
1SRI International, Menlo Park, CA, United States, ²Radiology, Stanford University, Stanford, CA, United States, ³GE Healthcare Applied Science Laboratory, Menlo Park, CA, United States, ⁴Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, United States

This work demonstrates time-resolved volumetric metabolic imaging of hyperpolarized [1-13C]-pyruvate using an undersampled spiral MRSI sequence, and applies it to investigate Pyr metabolism modulated by ethanol in rat liver. The dynamic 3D acquisition allows the analysis of spectra from organ-specific regions-of-interest, thus providing improved rate-constant estimates. Ethanol metabolism in the liver leads to accumulation of NADH which is a coenzyme in Pyr-to-Lac conversion. The apparent liver Pyr-to-Lac rate constants increased from pre- to post-ethanol, confirming the hypothesis that NADH levels are rate-limiting for liver Pyr-to-Lac conversion.

Angus Zoen Lau^1,2, Albert P Chen³, and Charles H Cunningham^1,2
1Medical Biophysics, University of Toronto, Toronto, ON, Canada, ²Imaging Research, Sunnybrook Health Sciences Centre, Toronto, ON, Canada, ³GE Healthcare, Toronto, ON, Canada

Precise determination of transmit RF power (B₁⁺) for ¹³C MR is challenging due to limited natural abundance of ¹³C in vivo. The phase-based Bloch-Siegert shift provides a B₁ mapping method independent of M_z, making it possible to encode B₁ in an image of hyperpolarized magnetization. Bloch-Siegert B₁ mapping was implemented in a multi-slice interleaved ¹³C imaging pulse sequence. This study demonstrated the feasibility of simultaneously acquiring a B1 map and images of hyperpolarized [1-¹³C]pyruvate,¹³C bicarbonate, and [1-¹³C]lactate following a single tracer bolus of pre-polarized [1-¹³C]pyruvate and is anticipated to provide improved quantitative measurements of¹³C metabolism in vivo.

Helen J Atherton^1,2, Michael S Dodd¹, Lisa C Heather¹, Marie A Schroeder¹, Julian L Griffin², George K Radda¹, Kieran Clarke¹, and Damian J Tyler^1
1Department of Physiology, Anatomy & Genetics, University of Oxford, Oxford, United Kingdom, ²Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom

Hyperthyroidism, caused by an elevated level of thyroid hormones, leads to an increase in heart rate, contractility and cardiac output. Cardiac hypertrophy is another effect of hyperthyroidism and, although the hypertrophy is initially beneficial, it can lead to heart failure. The aim of this work was to determine whether alleviating the known inhibition of pyruvate dehydrogenase (PDH) in the hyperthyroid heart using dichloroacetate (DCA) would affect the response to hyperthyroidism. Using hyperpolarized MRS and CINE MRI, we found that DCA treatment increased PDH flux by 134% and significantly reduced the level of hypertrophy observed in the hyperthyroid rat heart.

Albert P Chen¹, Ralph E Hurd², Marie A Schroeder^3,4, Angus Z Lau^4,5, Yi-Ping Gu⁴, Wilfred W Lam⁴, and Charles H Cunningham^4,5
1GE Healthcare, Toronto, ON, Canada, ²GE Healthcare, Menlo Park, CA, United States, ³Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom, ⁴Imaging Research, Sunnybrook Health Sciences Centre, Toronto, ON, Canada, ⁵Deptartment of Medical Biophysics, University of Toronto, Toronto, ON, Canada

To improve the robustness of pH measurement using hyperpolarized H¹³CO₃^- and ¹³CO₂ signals in presence of carbonic anhydrase activity, the ¹³CO₂ resonance was excited independently with a chemically selective RF pulse of larger tip-angle (to achieve higher SNR), while the other resonances of interest were acquired with a smaller tip angle. Accurate pH measurement could still be obtained even with repeated tipping (for temporally and/or spatially resolved data), since the ratio between the two pools was rapidly restored by the enzyme mediated exchange. This method was demonstrated in phantom and in vivo in pig heart.

Peter Otto Magnusson¹, Sadia Asghar Butt¹, Mette Hauge Lauritzen¹, Jan Henrik Ardenkjær-Larsen², Per Åkesson¹, and Lise Vejby Søgaard^1
1Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark, ²GE Healthcare, Hillerød, Denmark

Efficient and rapid utilization of available magnetization is of greatest importance in hyperpolarized 13C MR since the in vivo decay time constant of the hyperpolarized signal is less than one minute. Here we demonstrate the potential of a multi-echo single-shot RARE sequence (FSEME) for rapid spectroscopic imaging of cerebral metabolism using HP [1-13C]Pyruvate. A FSEME-sequence was implemented and optimized and in vivo rat head 13C-scanning was conducted. Identification of cerebral sub-structures in metabolite maps from hyperpolarized [1-13C]Pyruvate in the rat brain was for the first time demonstrated using the rapid FSEME spectroscopic imaging sequence.

Yuen-Li Chung¹, Gigin Lin¹, Helen Troy¹, Anne-Christine Wong Te Fong¹, L E Jackson¹, Deborah K Hill¹, Matthew Orton¹, Dow-Mu Koh¹, Simon P Robinson¹, Ian R Judson², John R Griffiths³, Martin O Leach¹, and Thomas R Eykyn^1
1CR-UK & EPSRC Cancer Imaging Centre, Institute of Cancer Research and Royal Marsden Hospital, Sutton, Surrey, United Kingdom, ²CR-UK Centre for Cancer Therapeutics, Institute of Cancer Research and Royal Marsden Hospital, Sutton, Surrey, United Kingdom, ³Li Ka Shing Centre, CR-UK Cambridge Research Institute, Cambridge, United Kingdom

Autophagy is a cellular degradation response to starvation or stress whereby cellular proteins, organelles and cytoplasm are engulfed, digested and recycled to sustain cellular metabolism. We have investigated the effects of autophagy on TCA cycle activation using 1-13C-pyruvate DNP 13C-MRS. Autophagy was induced in three cancer cell lines by starvation, dichloroacetate and PI103 treatment. A significant reduction in the rate of labelled [1-13C] pyruvate to lactate exchange (and unpolarised lactate production) was associated with autophagy, rather than apoptosis or necrosis. A reduction in lactate production as measured by DNP 13C-MRS, and unchanged NAD+, may provide a non-invasive surrogate biomarker of autophagy.

Cornelius von Morze¹, Peder E Larson¹, Simon Hu¹, Robert Bok¹, Hikari Yoshihara¹, Andrei Goga², Jan Henrik Ardenkjaer-Larsen³, and Daniel B Vigneron^1
1Department of Radiology and Biomedical Imaging, UCSF, San Francisco, CA, United States, ²Department of Medicine, Division of Hematology / Oncology, UCSF, San Francisco, CA, United States, ³GE Healthcare, Hillerød, Denmark

The addition of perfusion information to metabolic information obtained by spectroscopic imaging of hyperpolarized [1-¹³C]pyruvate would be of great value in exploring links between perfusion and metabolism in cancer. We performed both dynamic imaging of the perfusion compound HP001, and co-polarized spectroscopic imaging of urea and pyruvate in preclinical murine cancer models. Spatially heterogenous perfusion was observed in the tumor tissues. A correlation between the urea and HP001 data confirmed the value of co-polarizing urea with pyruvate for simultaneous assessment of perfusion and metabolism.

Steven Reynolds¹, Samira Kazan², Leigh Williams², Aneurin Kennerley³, Jason Berwick³, Gillian Tozer², and Martyn Paley^1
1Academic unit of Radiology, Medical school, University of Sheffield, Sheffield, S. Yorkshire, United Kingdom, ²Department of Oncology, Medical school, University of Sheffield, Sheffield, S. Yorkshire, United Kingdom, ³Department of Psychology, University of Sheffield, Sheffield, S. Yorkshire, United Kingdom

Using the sensitivity enhancement of DNP we are using hyperpolarised pyruvate as a biomarker for changes in tumour oxygenation. To improve our model of the pyruvate metabolic flux we have measured the arterial input function (AIF) using the hyperpolarised 13C pyruvate signal from the carotid artery of a BDIX rat. Since AIF is dependent upon the injection condition there was a requirement to provide an automated, rapid, injection system. We have developed an automated injector that can be used close the bore of an unshielded 7T magnet.

Francesca Reineri¹, Alessandra Viale¹, Silvano Ellena¹, Tommaso Boi¹, Roberto Gobetto¹, and Silvio Aime^1
1University of Torino, Torino, IT, Italy

Para-Hydrogen Induced Polarization (PHIP) has been recently exploited for the preparation of hyperpolarized ¹³C contrast agents for MRI. For the observation of large PHIP effects the use of homogeneous hydrogenation catalysts is generally required. The catalyst and (if present) the organic solvent must then be removed in order to obtain non-toxic formulations of the hyperpolarized agents. Here we report the para-hydrogenation of an unsaturated activated substrate, maleic anhydride, in chloroform, followed by rapid hydrolysis to form a water-soluble derivative, succinic acid, which can be extracted in water to yield a pure aqueous solution of the hyperpolarized molecule.