In Vivo MR with DNP Polarized Compounds
Monday 20 April 2009
Room 315 11:00-13:00


Charles Cunningham and John Kurhanewicz

11:00  51.

Preclinical Studies in Cancer Models using Hyperpolarized Carbon-13 MR

    Daniel B. Vigneron1
University of California San Francisco
11:20 52. Investigating the Effects of Hyperthyroidism on Cardiac Metabolism Using Hyperpolarized Magnetic Resonance
    Helen J. Atherton1, Marie A. Shroeder1, Lisa C. Heather1, Julian L. Griffin2, Kieran Clarke1, George K. Radda1, Damian J. Tyler1
Physiology, Anatomy and Genetics, University of Oxford, Oxford, Oxfordshire, UK; 2Biochemistry, University of Cambridge, Cambridge, Cambridgeshire, UK
    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.
11:32 53.   Hyperpolarized 13C MR Spectroscopic Imaging: Application to Brain Tumors
    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
Bioengineering, 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
    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).
11:48  54. Real-Time Cardiac Metabolism in a Pig Model of Cardiac Disease Using Hyperpolarized 13C MR
    Angus Zoen Lau1,2, Nilesh Ghugre2, Albert P. Chen3, Wilfred W. Lam2, Venkat Ramanan2, Yuesong Yang2, Graham A. Wright1,2, Charles H. Cunningham1,2
Dept. of Medical Biophysics, University of Toronto, Toronto, ON, Canada; 2Imaging Research, Sunnybrook Health Sciences Centre, Toronto, ON, Canada; 3GE Healthcare, Toronto, ON, Canada
    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.
12:00 55.  13C-Labeled Malate as a Treatment Response Marker in a Murine Lymphoma Model in Vivo
    Rene in 't Zandt1, Mikko Kettunen2, Magnus Karlsson1, Pernille Rose Jensen1, Anna Gisselsson1, Ferdia Gallagher2,3, De Hu2, Georg Hansson1, Kevin Brindle2, Mathilde Lerche1
Imagnia 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
    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.
12:12 56.     Hyperpolarized 1-[13C]-Ethyl-Pyruvate Metabolic Imaging in Anesthetized Rat Brain
    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
Applied 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

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.

12:24 57.  

Extending the Utility of Hyperpolarized Compounds by Storing Polarization in the Singlet State

    Elizabeth R. Jenista1, Rosa T. Branca1, Debadeep Bhattacharyya2, Xin Chen1, Warren S. Warren1
Department of Chemistry, Duke University, Durham, NC, USA; 2Oxford Instruments, Concord, MA, USA
    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.
12:36 58. 

Measuring Michaelis-Menten Kinetics of Hyperpolarized 13C1-Pyruvate Metabolism in a Single Bolus Injection


Tao Xu1, Dirk Mayer2, Meng Gu1, Yi-Fen Yen3, Edvin Johansson4, Jim Tropp5, Ralph Hurd3, Daniel Spielman2
Department 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

    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.
12:48 59.     Imaging Brain PH Using Hyperpolarized 13C-Labeled Bicarbonate

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
Radiology, 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

    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.