ISMRM 21st Annual Meeting & Exhibition 20-26 April 2013 Salt Lake City, Utah, USA

Hyperpolarized 13C
Thursday 25 April 2013
Room 150 AG  13:30 - 15:30 Moderators: Sean B. Fain, Peder E. Z. Larson

13:30 0652.   Optimal Variable Flip Angle Schemes for Multi-Band Dynamic Acquisition of Hyperpolarized 13C MRSI
Yan Xing1, Galen D. Reed1, John M. Pauly2, Adam B. Kerr2, and Peder E.Z. Larson1
1Radiology and Biomedical Imaging, U of California - San Francisco, San Francisco, CA, United States, 2Electrical Engineering, Stanford University, Stanford, CA, United States

Hyperpolarized [1-13C]pyruvate to lactate conversion can be used to discern cancerous tissues from the healthy ones or to monitor cancer progression. Conventionally, the amount of nonrenewable non-equilibrium polarization rapidly diminishes over the duration of the scan, leading to decreased signal level particularly for dynamic acquisitions. We developed a novel approach with multi-band spectral-spatial RF excitation pulses to account for the metabolic conversion, losses due to RF excitation and T1 relaxation, so that a constant signal level can be maintained. Simulations of two approaches showed signal constancy; in vivo experiments also exhibited improved signal.

13:42 0653.   
Improved Measures of Renal Pyruvate-To-Lactate Conversion Using Diffusion Gradients
Jeremy W. Gordon1, David J. Niles1, Kevin M. Johnson1, and Sean B. Fain1
1Medical Physics, University of Wisconsin-Madison, Madison, WI, United States

Imaging of hyperpolarized 13C is often hampered by partial-volume effects from the large pyruvate signal in the vasculature. Signal from these spins can lead to flow-related artifacts and partial-volume effects with organ voxels, interfering with modeling of kinetic parameters. To mitigate these effects, bipolar gradients were inserted into a spiral sequence to remove the signal contribution from vascular spins. An optimal b-value was experimentally chosen to null flowing spins while minimizing signal attenuation from static spins. Partial-volume and flow related artifacts are substantially reduced while the kinetics are substantially changed, due to the elimination of contaminating vascular signal.

13:54 0654.   
in vivo Single-Scan 13C Spatiotemporally-Encoded Spectroscopic Imaging of Hyperpolarized Metabolites
Rita Schmidt1, Christoffer Laustsen2,3, Jan Henrik Ardenkjaer-Larsen3,4, and Lucio Frydman1
1Chemical Physics, Weizmann Institute of Science, Rehovot, Israel, 2The MR Research Centre, Aarhus University, Aarhus, Denmark, 3Danish Research Centre for Magnetic Resonance, Hvidovre Hospital, Hvidovre, Denmark, 4GE healthcare, Broendby, Denmark

Fast and effective scanning methods are required for the hyperpolarized [1-13C]pyruvate dynamic metabolic imaging due to the short time available before the hyperpolarized signal decays. Recent studies described the potential of single-shot spatiotemporal encoding (SPEN) principles to derive chemical shift images. SPEN acquired signal contains the spatial and spectral information at no extra cost. Sequences with 180° chirp pulses were recently shown to yield single-shot chemical shift images. The present work demonstrates the first in-vivo results using a SPEN sequence; showing [1-13C]pyruvate and the metabolic derivatives in the kidneys after hyperpolarized [1-13C]pyruvate injection to healthy rats at 4.7T.

14:06 0655.   
Differentiation of Pyruvate Flux Versus Exchange in Rat Liver in vivo Using a Three-Site Exchange Model
Jae Mo Park1,2, Ralph Hurd3, Kelvin Bilingsly1, Sonal Josan1,4, Yi-Fen Yen1, Dirk Mayer1,4, and Daniel Spielman1,2
1Radiology, Stanford University, Stanford, California, United States, 2Electrical Engineering, Stanford University, Stanford, California, United States, 3Applied Science Laboratory, GE Healthcare, Menlo Park, California, United States, 4Neuroscience Program, SRI International, Menlo Park, California, United States

We propose an improved three-site exchange model that considers conversion between pyruvate, lactate, and alanine, and measure the ratio of flux and isotopic exchange among them by injecting co-polarized pairs of [2-13C]pyruvate and [1-13C]alanine, and [2-13C]pyruvate and [1-13C]lactate.

14:18 0656.   
Simultaneous Examination of Metabolism and Perfusion of Embolized Hepatocellular Carcinoma in Rats by Hyperpolarized Fumarate and Copolarization of Pyruvate and Urea
Stephan Düwel1,2, Markus Durst1,3, Concetta V. Gringeri3, Yvonne Kosanke4, Claudia Gross4, Martin A. Janich3, Markus Schwaiger5, Axel Haase1, Steffen J. Glaser2, Rolf F. Schulte3, Rickmer Braren4, and Marion I. Menzel3
1Institute of Medical Engineering, Technische Universität München, Garching, Germany, 2Chemistry, Technische Universität München, Garching, Germany, 3GE Global Research, Garching, Germany, 4Institute of Radiology, Klinikum rechts der Isar, Technische Universität München, München, Germany, 5Institute of Nuclear Medicine, Klinikum rechts der Isar, Technische Universität München, München, Germany

Real-time in-vivo studies of energy metabolism can be realized through 13C MRSI of hyperpolarized pyruvate and its metabolites. Simultaneously, tumor perfusion can independently be investigated by the injection of hyperpolarized urea, whereas cell necrosis can be studied by the production of malate from hyperpolarized fumarate. We compared the perfusion information given by hyperpolarized [1,4-13C2]fumarate, [1-13C]pyruvate and [13C,15N2]urea in a group of five rats exhibiting HCC before and after TAE. We have shown that hyperpolarized urea, pyruvate and fumarate all provide consistent information on tumor perfusion. This was quantified by calculating the structural similarity index between images of different substances.

14:30 0657.   The Fate of Hyperpolarized [1-13C]Pyruvate During Substrate Competition Reveals Increased Bicarbonate as a Potential Biomarker for Decreased Fatty Acid Oxidation
Karlos X. Moreno1, A. Dean Sherry1, Craig R. Malloy1, and Matthew E. Merritt1
1Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, United States

The effect of hepatic substrate utilization on hyperpolarized (HP) pyruvate metabolism was examined in isolated mouse livers. Livers were perfused with four different solutions varying in pyruvate, lactate and octanoate content, to potentially modulate hepatic pyruvate metabolism. After perfusion to steady-state with (10:1) lactate:pyruvate, a 3-fold increase in bicarbonate intensity was observed, compared to other solutions, upon administration of 4 mM HP-pyruvate. Carbon-13 isotopomer analysis of liver extracts confirms the increase was due to increased PDH flux. The remaining octanoate-containing solutions had no effect on bicarbonate intensity. These results reflect a possible biomarker for identification of deficient fatty acid oxidation.

14:42 0658.   
In Vivo Assessment of IDH Status in Glioblastoma Using 2D 13C Dynamic CSI of Hyperpolarized lower case Greek alpha-Ketoglutarate
Myriam Marianne Chaumeil1, Peder E.Z. Larson1, Hikari A. I. Yoshihara1, Daniel B. Vigneron1, Sarah J. Nelson1, Russell O. Pieper2, Joanna J. Phillips2, and Sabrina M. Ronen1
1Radiology, University of California, San Francisco, San Francisco, CA, United States, 2Neurological Surgery, University of California, San Francisco, San, CA, United States

We previously showed that hyperpolarized lower case Greek alpha-KG was a promising probe to inform on isocitrate dehydrogenase (IDH1) mutational status in cell lysates and live perfused cells. In this study, we translated our methods in vivo and evaluated the potential of hyperpolarized lower case Greek alpha-KG to assess IDH status in orthotopic GBM tumors at clinical field strength. Following injection of hyperpolarized lower case Greek alpha-KG, hyperpolarized 2-hydroxyglutarate formation was detected in IDH-mutant tumors, but not in in IDH wild-type, using 2D 13C dynamic CSI. This initial study demonstrates that HP lower case Greek alpha-KG can inform on IDH mutational status in vivo through the dynamic assessment of its metabolism.

14:54 0659.   
Detection of Sudden Changes in Cardiac Metabolism by Hyperpolarized 13C MRS
Chalermchai Khemtong1, Nicholas R. Carpenter1, Lloyd L. Lumata1, Matthew E. Merritt1, Karlos X. Moreno1, Zoltan Kovacs1, Craig R. Malloy1, and A. Dean Sherry1,2
1Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, United States, 2Department of Chemistry, University of Texas at Dallas, Richardson, TX, United States

DNP hyperpolarization of 13C-enriched substrates now allows detection of real-time metabolism in isolated perfused organs and in tissues in vivo. Due to the highly improved NMR sensitivity achieved by dynamic nuclear polarization (DNP), metabolism of HP 13C-enriched pyruvate through the citric acid (TCA) cycle by NMR and MRI has been plausible. Here, we report a hyperpolarized13C-MRS technique as a tool to detect sudden changes in cardiac metabolism in perfused hearts as a result of cardiac drug stimulation. In perfused rat hearts receiving hyperpolarized [1-13C]pyruvate, a rapid increase in the signal intensity of [1-13C]lactate occurs after stimulation of cardiac function by isoproterenol. This results in the appearance of a second apex in the 13C NMR spectrum of HP-lactate derived from HP-pyruvate. No changes were observed in the kinetic appearance of other metabolite resonances derived from HP-pyruvate. This unusual feature was later traced to a rapid increase in the pool size of lactate as a result of glycogenolysis and subsequent glycolysis stimulated by isoproterenol. These results demonstrate the feasibility of using HP13C MRS as a tool to detect rapid changes in cardiac metabolism in response to exposure to cardiac drugs.

15:06 0660.   
Non-Invasive Assessment of Cardiac Metabolic Alterations Following LAD Occlusion Using Hyperpolarized 13C Imaging
Angus Z. Lau1,2, Albert P. Chen3, Yiping Gu1, Jennifer Barry4, Nilesh R. Ghugre1,2, Graham A. Wright1,2, and Charles H. Cunningham1,2
1Imaging Research, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada, 2Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada, 3GE Healthcare, Toronto, Ontario, Canada, 4Imaging Research, Sunnybrook Research Institute, Toronto, Ontario, Canada

Accurate assessment of myocardial viability early following myocardial infarction is a critical challenge in cardiology. In this study, dynamic, spatially resolved hyperpolarized 13C imaging was used to monitor longitudinal cardiac metabolic changes following AMI of different severities (45 and 90 minute LAD occlusion) in vivo in a porcine ischemia-reperfusion model. Within the region exhibiting delayed gadolinium enhancement, the 45 minute group showed a modest decrease in bicarbonate at day 2, which resolved at 7 days, while the 90 minute group showed strongly attenuated bicarbonate at both time points.

15:18 0661.   Spin Echo Measurements of the Extravasation and Tumor Cell Uptake of Hyperpolarized [1-13C]lactate and [1-13C]pyruvate -permission withheld
Mikko I. Kettunen1, Brett W.C Kennedy1, De-En Hu2, and Kevin M. Brindle2
1Department of Biochemistry, University of Cambridge & Cancer Research UK Cambridge Research Institute, Cambridge, Cambridgeshire, United Kingdom, 2Department of Biochemistry, University of Cambridge, Cambridge, Cambridgeshire, United Kingdom

We have investigated whether the increase in the echo/FID ratio in a spin echo experiment, where the FID is the signal acquired immediately following the excitation pulse, could report on [1-13C]lactate and [1-13C]pyruvate transport into the tumor cells in vivo. Apparent diffusion coefficients and T2 relaxation times of these metabolites were also measured. Inhibition of the monocarboxylate transporters decreased the echo/FID ratio to some extent, showing that some of the increase was due to transport, however, under the signal acquisition conditions employed, most of the increase was due to movement of metabolites between the vascular and interstitial pools.