| SPECIAL INTEREST SESSION |
| In Vivo MR with DNP Polarized Compounds |
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Monday 20 April 2009 |
| Room 315 |
11:00-13:00 |
Moderators: |
Charles Cunningham and John Kurhanewicz |
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11:00 |
51. |
Preclinical Studies in Cancer Models using
Hyperpolarized Carbon-13 MR |
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Daniel B. Vigneron1
1University of California San Francisco |
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11:20 |
52. |
Investigating the Effects of
Hyperthyroidism on Cardiac Metabolism Using
Hyperpolarized Magnetic Resonance |
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Helen J. Atherton1,
Marie A. Shroeder1, Lisa C. Heather1,
Julian L. Griffin2, Kieran Clarke1,
George K. Radda1, Damian J. Tyler1
1Physiology, Anatomy and Genetics, University
of Oxford, Oxford, Oxfordshire, UK; 2Biochemistry,
University of Cambridge, Cambridge, Cambridgeshire,
UK |
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In this study Dynamic
Nuclear Polarization enhanced 13C-MRS was
used to investigate the effects of elevated thyroid
hormone (T3) levels on cardiac metabolism in vivo.
Our study uniquely revealed that pyruvate
dehydrogenase (PDH) flux was reduced by 76 % in rats
administered T3 for 7 days, indicative of an
increased reliance on fatty acid oxidation (FAO) for
ATP production. Metabolically profiling cardiac
tissue ex vivo using 1H-NMR revealed a
concomitant increase in glycolysis, evidenced by
increased lactate and alanine, and decreased
glucose. Together these results suggest that the
hyperthyroid heart can be characterized by increased
FAO and glycolysis, and decreased PDH flux. |
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11:32 |
53. |
Hyperpolarized 13C
MR Spectroscopic Imaging: Application to Brain
Tumors |
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Ilwoo Park1,2,
Peder E. Larson2, Simon Hu1,2,
Robert Bok2, Tomoko Ozawa3,
John Kurhanewicz1,2, Daniel B. Vigneron1,2,
Scott R. VandenBerg3, C David James3,
Sarah J. Nelson1,2
1Bioengineering, University of California, San
Francisco/Berkeley, San Francisco, CA, USA; 2Surbeck
Laboratory of Advanced Imaging, Department of
Radiology and Biomedical Imaging, University of
California, San Francisco, San Francisco, CA, USA;
3Brain Tumor Research Center, Department
of Neurological Surgery, University of California,
San Francisco, San Francisco, CA, USA |
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The purpose of this
study was to explore the feasibility of using
13C MRSI with hyperpolarized 13C1-pyruvate
as a substrate for evaluation of in vivo
brain tumor by comparing hyperpolarized 13C
MRSI data from rats with and without intracranial
human xenograft tumors. Significant differences in
13C metabolic characteristics were found
between tumor and normal brain tissue. The SNR of
lactate, pyruvate and total carbon were observed to
be different between U-251 MG and U-87 MG model, in
a manner that was consistent with the findings of
immunochemical analysis, and the SNR of lactate
showed strong correlation with proliferation marker
(MIB-1). |
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11:48 |
54. |
Real-Time Cardiac Metabolism
in a Pig Model of Cardiac Disease Using
Hyperpolarized 13C MR |
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Angus Zoen Lau1,2,
Nilesh Ghugre2, Albert P. Chen3,
Wilfred W. Lam2, Venkat Ramanan2,
Yuesong Yang2, Graham A. Wright1,2,
Charles H. Cunningham1,2
1Dept. of Medical Biophysics, University of
Toronto, Toronto, ON, Canada; 2Imaging
Research, Sunnybrook Health Sciences Centre,
Toronto, ON, Canada; 3GE Healthcare,
Toronto, ON, Canada |
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Hyperpolarization of spins via DNP has been explored
as a method to non-invasively study real-time
metabolic processes in vivo. In this
abstract, we investigate the use of hyperpolarized
13C MR to study real-time cardiac
metabolism in a pig model of cardiac disease. A
13C-tuned transmit/receive surface coil was
used to acquire cardiac-gated non-localized dynamic
spectra following injection of a hyperpolarized [1-13C]-pyruvate
solution. Pyruvate, lactate, and bicarbonate
resonances were observed. Spatially encoded
breath-held cardiac-gated CSIs were also obtained
displaying the presence of pyruvate in the blood in
the chambers of the heart. |
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12:00 |
55. |
13C-Labeled Malate
as a Treatment Response Marker in a Murine Lymphoma
Model in Vivo |
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Rene in 't Zandt1,
Mikko Kettunen2, Magnus Karlsson1,
Pernille Rose Jensen1, Anna Gisselsson1,
Ferdia Gallagher2,3, De Hu2,
Georg Hansson1, Kevin Brindle2,
Mathilde Lerche1
1Imagnia AB, Malmö, Sweden; 2Cancer
Research UK Cambridge Research Institute and Dept.
of Biochemistry, University of Cambridge, Cambridge,
UK; 3Dept. of Radiology, Addenbrooke’s
Hospital, University of Cambridge, Cambridge, UK |
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Early
measurements of tumor responses to therapy have been
shown to help predict the subsequent treatment
outcome in many tumor cell lines. Previously it has
been shown that the flux of hyperpolarized 13C
label between pyruvate and lactate in a murine
lymphoma model can be used as an early marker of
cell death following chemotherapy both in vitro and
in vivo. This study show that a promising new
tumor biomarker - hyperpolarized [1,4-13C2]fumarate
- can be used in the same model to image the effects
of chemotherapy. |
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12:12 |
56. |
Hyperpolarized
1-[13C]-Ethyl-Pyruvate Metabolic Imaging in
Anesthetized Rat Brain |
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Ralph E. Hurd1,
Yi-Fen Yen1, Dirk Mayer2,3,
Albert Chen4, David Wilson5,
Susan Kohler6, James Tropp1,
Robert Bok5, Daniel Vigneron5,
John Kurhanewicz5, Daniel Spielman2,
Adolf Pfefferbaum3,7
1Applied Science Laboratory, GE Healthcare,
Menlo Park, CA, USA; 2Department of
Radiology, Stanford, Stanford, CA, USA; 3SRI
International, Menlo Park, CA, USA; 4Applied
Science Laboratory, GE Healthcare, Toronto, Ontario,
Canada; 5Department of Radiology, UCSF,
San Francisco, CA, USA; 6Union College,
Schenectady, NY, USA; 7Psychiatry,
Stanford, Stanford, CA, USA |
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Formulation,
polarization and dissolution conditions were
developed to obtain a stable hyperpolarized solution
of 1-[13C]-ethyl-pyruvate. A maximum tolerated dose
and injection rate were determined, and 13C
spectroscopic imaging was used to compare the uptake
of hyperpolarized 1-[13C]-ethyl pyruvate relative to
hyperpolarized 1-[13C]- pyruvate into anesthetized
rat brain. Hyperpolarized 1-[13C]-ethyl pyruvate
metabolic imaging in normal brain is demonstrated in
this feasibility study. |
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12:24 |
57. |
Extending the Utility of Hyperpolarized Compounds by
Storing Polarization in the Singlet State |
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Elizabeth R. Jenista1,
Rosa T. Branca1, Debadeep Bhattacharyya2,
Xin Chen1, Warren S. Warren1
1Department of Chemistry, Duke University,
Durham, NC, USA; 2Oxford Instruments,
Concord, MA, USA |
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Magnetic resonance is
limited as a molecular imaging modality by its poor
sensitivity, due to the small fractional
magnetization achieved in even large magnets.
Hyperpolarization methods have been demonstrated to
increase this sensitivity by orders of magnitude,
but the enhanced signal relaxes away in tens of
seconds in favorable cases, making many imaging
applications problematic. We show theoretically and
experimentally that symmetry protected, true singlet
states can be used to store and retrieve population
in very long lived states, extending the utility of
hyperpolarization techniques. |
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12:36 |
58. |
Measuring Michaelis-Menten Kinetics of
Hyperpolarized 13C1-Pyruvate Metabolism in a Single
Bolus Injection |
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Tao Xu1, Dirk
Mayer2, Meng Gu1, Yi-Fen Yen3,
Edvin Johansson4, Jim Tropp5,
Ralph Hurd3, Daniel Spielman2
1Department of Electrical Engineering,
Stanford University, Stanford, CA, USA; 2Department
of Radiology, Stanford University, Stanford, CA,
USA; 3Global Applied Sciences Laboratory,
GE Healthcare, Menlo Park, CA, USA; 4Medical
Diagnostics R&D, GE Healthcare, Oslo, Norway; 5Global
Applied Sciences Laboratory, GE Healthcare, Fremont,
CA, USA |
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Hyperpolarized MRS of
metabolically active substrates allows the study of
both the injected substrate and downstream metabolic
products in vivo. Nowadays, most dynamic
studies have employed slice-select excitation pulses
with small flip angles to measure the metabolic time
curves following bolus injection of the
hyperpolarized substrate. Constant metabolic
exchange rates are typically assumed throughout the
observation window. We developed a new technique for
measuring Michaelis-Menten kinetics of
hyperpolarized 13C1-pyruvate metabolism in a single
bolus injection. The results clearly demonstrate the
nonlinear relationship between metabolic exchange
rates and pyruvate concentration. |
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12:48 |
59. |
Imaging Brain PH Using
Hyperpolarized 13C-Labeled Bicarbonate |
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Ferdia Aidan Gallagher1,2, Mikko I.
Kettunen2,3, De-en Hu2,3,
Lorna B. Jarvis4, Rebekah L. McLaughlin2,3,
Tim H. Witney2,3, Sam E. Day2,3,
Jan H. Ardenkjaer-Larsen5, Ken G. Smith4,
Kevin M. Brindle2,3
1Radiology, University of Cambridge,
Cambridge, UK; 2CRUK Cambridge Research
Institute, Cambridge, UK; 3Biochemistry,
University of Cambridge, Cambridge, UK; 4Cambridge
Institute for Medical Research, University of
Cambridge, Cambridge, UK; 5GE Healthcare,
Amersham, UK |
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Few imaging biomarkers
can cross an intact blood-brain barrier. We show
here that hyperpolarized 13C-labeled
carbon dioxide can be detected within normal mouse
brain following the injection of hyperpolarized
13C-labeled bicarbonate. The spatial
distribution of the two molecules can also be imaged
and the calculated brain pH was shown to be lower
than the surrounding tissues, in keeping with
previous invasive studies. This method therefore
offers the possibility of a new cerebral imaging
technique which could be applied to imaging brain
function and pathology. |
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