ISMRM 21st Annual Meeting & Exhibition ○ 20-26 April 2013 ○ Salt Lake City, Utah, USA
SCIENTIFIC SESSION
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 -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 -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 -KG to assess IDH status in orthotopic GBM tumors at clinical field strength. Following injection of hyperpolarized -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 -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 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.