Room 150 AG

13:30 - 15:30

Moderators:

Sean B. Fain, Peder E. Z. Larson

Yan Xing¹, Galen D. Reed¹, John M. Pauly², Adam B. Kerr², and Peder E.Z. Larson^1
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.

Jeremy W. Gordon¹, David J. Niles¹, Kevin M. Johnson¹, and Sean B. Fain^1
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.

Rita Schmidt¹, Christoffer Laustsen^2,3, Jan Henrik Ardenkjaer-Larsen^3,4, and Lucio Frydman^1
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.

Jae Mo Park^1,2, Ralph Hurd³, Kelvin Bilingsly¹, Sonal Josan^1,4, Yi-Fen Yen¹, Dirk Mayer^1,4, and Daniel Spielman^1,2
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.

Stephan Düwel^1,2, Markus Durst^1,3, 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. Menzel^3
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.

Karlos X. Moreno¹, A. Dean Sherry¹, Craig R. Malloy¹, and Matthew E. Merritt^1
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.

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. Ronen^1
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.

Chalermchai Khemtong¹, Nicholas R. Carpenter¹, Lloyd L. Lumata¹, Matthew E. Merritt¹, Karlos X. Moreno¹, Zoltan Kovacs¹, Craig R. Malloy¹, and A. Dean Sherry^1,2
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.

Angus Z. Lau^1,2, Albert P. Chen³, Yiping Gu¹, Jennifer Barry⁴, Nilesh R. Ghugre^1,2, Graham A. Wright^1,2, and Charles H. Cunningham^1,2
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.

Mikko I. Kettunen¹, Brett W.C Kennedy¹, De-En Hu², and Kevin M. Brindle^2
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.