ISMRM 23rd Annual Meeting & Exhibition • 30 May - 05 June 2015 • Toronto, Ontario, Canada

Scientific Session • It's a Polarized World

Tuesday 2 June 2015

Constitution Hall 107

10:00 - 12:00


T.B.A., T.B.A.

10:00 0319.   
Resonance frequency-shifting nitroxide for probing proteolytic activity in vivo using the Overhauser-enhanced MRI technique
Neha KOONJOO1, Gérard Audran2, Lionel Bosco2, Paul Brémond2, Elodie Parzy1, Philippe Massot1, Matthieu Lepetit-Coiffé1,3, Jean-Michel Franconi1, Sylvain R.A Marque2, Eric Thiaudière1, and Philippe Mellet1,4
1Centre de Résonance Magnétique des Systèmes Biologiques, Bordeaux, France, Metropolitan, 2UMR 7273 Aix-Marseille Université, Marseille, France, Metropolitan, 3Siemens, Saint-Denis, France, Metropolitan, 4INSERM, Université de Bordeaux Segalen, Bordeaux, France, Metropolitan

Proteolysis of a line-shifting nitroxide-OMRI probe was visualized in the digestive tract of living mice using Overhauser-enhanced MRI. Upon enzymatic action on the probe, its hyperfine coupling constants are shifted; thus resulting in two detectable electronic excitation frequencies enabling both substrate and end product visualization. High signal enhancements revealed either the substrate or its end product in the stomach. Highly resolved 3D-keyhole OMRI images of resolution 0.5mm3 were obtained with a fully balanced steady state sequence – TrueFISP at 0.2T in 18 seconds. This work is a steppingstone in in vivo pathology-related proteolysis detection.

10:12 0320.   Dynamic in vivo free radical imaging with Overhauser-enhanced MRI
Mathieu Sarracanie1,2, Fanny Herisson3, Najat Salameh1,2, David E J Waddington1,4, Cenk Ayata3, and Matthew S Rosen1,2
1MGH/A.A. Martinos Center for Biomedical Imaging, Charlestown, MA, United States, 2Department of Physics, Harvard University, Cambridge, MA, United States, 3Neurovascular Research Lab, Department of Radiology, Massachusetts General Hospital, Charlestown, United States, 4ARC Center for Engineered Quantum Systems, School of Physics, University of Sydney, Sydney, NSW, Australia

We explore the use of b-SSFP based OMRI to acquire free radical images with sufficient spatial and temporal resolution to probe oxidative stress status via free radical decay dynamics in the rat brain. We present here time-resolved OMRI following a single injection of TEMPOL in healthy living rats. Sixteen full 11 slice OMRI data sets were acquired over 240s at 6.5mT. Free radical contrast is clearly seen in the hemisphere ipsilateral to the injection. The results presented here suggest that temporally resolved OMRI in conjunction with an exogenous free radical agent may allow study the redox status of brain tissue.

10:24 0321.   
Towards Targeted Molecular Imaging of Colorectal Cancer by Hyperpolarized Silicon Particles Functionalized with Mucin Antibody
Jingzhe Hu1,2, Nicholas Whiting3, Pamela Constantinou4, Niki Zacharias Millward3, David Menter5, Daniel Carson4, and Pratip Bhattacharya3
1Bioengineering, Rice University, Houston, TX, United States, 2MD Anderson Cancer Center, Houston, TX, United States, 3Cancer Systems Imaging, MD Anderson Cancer Center, Houston, TX, United States, 4BioSciences, Rice University, Houston, TX, United States, 5Cancer Biology, MD Anderson Cancer Center, Houston, TX, United States

We aim to develop a real-time molecular MR imaging platform to diagnose colorectal cancer with silicon particles functionalized with mucin (MUC1) antibodies. These silicon particles can be hyperpolarized via Dynamic Nuclear Polarization, leading to a potential signal increase of over 10,000 fold. Here, we present preliminary data showing that the antibody functionalization can survive the cryogenic temperature required by DNP (~3.7 K) and the binding affinity was not adversely affected in vitro. We have also successfully imaged hyperpolarized PEGylated-silicon particles in vivo following intraperitoneal injection, paving the way for targeted molecular MRI of orthotopic colon cancer models.

10:36 0322.   The tumor exception that proves the rule: Hyperpolarized 13C MRS cannot be used to detect the presence of mutant IDH1 glioma or their responses to Temozolomide therapy
Myriam Marianne Chaumeil1, Marina Radoul1, Pia Eriksson1, Michael D Blough2, Charles Cheneslong2, Russell O Pieper3,4, Joanna J Phillips3,4, J Gregory Cairncross2, and Sabrina M Ronen1,4
1Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, United States, 2Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada, 3Neurological Surgery, University of California San Francisco, San Francisco, CA, United States, 4Brain Tumor Research Center, University of California San Francisco, San Francisco, CA, United States

Recent studies show that 13C MRSI of hyperpolarized (HP) pyruvate can serve as an indicator of response to Temozolomide in primary glioblastoma. However, this imaging method had never been applied to mutant IDH1 gliomas, in which LDH-A is silenced. Here, we show that, in contrast to glioblastoma, mutant IDH1 oligodendrogliomas or oligoastrocytomas cells and tumors do not produce a significant amount of HP lactate, making these tumors virtually invisible by HP 13C MRSI. Furthermore, we demonstrate that TMZ treatment does not affect HP lactate levels in oligodendrogliomas or oligoastrocytomas, highlighting the need for new biomarkers specific to these tumor types.

10:48 0323.   Application of Good’s buffers to pH imaging using hyperpolarized 13C-MRI
Robert R Flavell1, David Korenchan1, Cornelius von Morze1, Mark Van Criekinge1, Renuka Sriram1, Sukumar Subramaniam1, Robert Bok1, Joseph Blecha1, Daniel Vigneron1, Peder Larson1, Kayvan R Keshari2, John Kurhanewicz1, and David M Wilson1
1Radiology and biomedical imaging, University of California, San Francisco, San Francisco, CA, United States, 2Memorial Sloan-Kettering Cancer Center, New York, NY, United States

Solid tumors have numerous mechanisms to export acid into the extracellular space, resulting in a low interstitial pH. In this abstract we report a novel method for imaging this property using hyperpolarized 13C,15N ACES, a commonly used biological buffer. ACES demonstrates remarkable pH dependent chemical shift change over the physiologic range. Application to phantom imaging and preliminary in vivo imaging experiments will be presented. This method combines the large 13C chemical shifts of HP ACES in the physiologic range, with the dramatic signal enhancements afforded by dissolution dynamic nuclear polarization (DNP).

11:00 0324.   Dynamic imaging of hyperpolarized 6Li cerebral distribution at pharmacological concentration - permission withheld
Mor Mishkovsky1, Andrea Capozzi2, Najat Salameh2, Jean-Noel Hyacinthe3, Rolf Gruetter1,4, and Arnaud Comment2
1Laboratory of Functional and Metabolic Imaging, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland, 2Institute of the Physics of Biological Systems, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland, 3Haute Ecole de Santé, University of Applied Sciences Western Switzerland, Geneva, Switzerland, 4Center of biomedical imaging (CIBM), Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland

Hyperpolarization by dissolution dynamic nuclear polarization (DNP) allows enhancing the signal intensity of insensitive nuclear spins such as 6Li. The long in vivo T1 of 6Li makes it an attractive hyperpolarized contrast agent for real-time perfusion imaging. The present study demonstrates the feasibility of imaging in real time the cerebral distribution of hyperpolarized 6Li at pharmaceutical concentration. As lithium salt is used for treating bipolar disorder, this opens new opportunities to assess the effect of Li+ on cerebral function.

11:12 0325.   Effect of Epinephrine on Metabolism of HP [1-13C]pyruvate in Low-flow Myocardial Ischemia
Chalermchai Khemtong1, Wei Chen1, Weina Jiang1, Craig R Malloy1,2, and A. Dean Sherry1,3
1Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, United States, 2Veterans Affairs North Texas Health Care System, Dallas, TX, United States, 3Chemistry, University of Texas at Dallas, Richardson, TX, United States

Adrenergic agents are widely used to assess cardiac conditions. Hyperpolarized (HP) 13C-MRS offers direct assessment of metabolic consequences of adrenergic stimulation rather than assessing metabolism based on mechanical function. We tested whether metabolism of HP-[1-13C]pyruvate is sensitive to adrenergic stimulation or ischemia in perfused hearts. During normal perfusion conditions, epinephrine increased glycolysis and glycogenolysis to lactate, and production of HP-bicarbonate from [1-13C]pyruvate. During ischemia, epinephrine had little effect on the HP-signals after HP-[1-13C]pyruvate, because coronary flow could not increase. HP-pyruvate is preferentially converted to alanine rather than lactate during ischemia after epinephrine, indicating compartmentation of HP-pyruvate metabolism in ischemic heart.

11:24 0326.   Flow-sensitizing gradients for first-pass perfusion imaging using hyperpolarized 13C urea in the rat heart
Angus Z Lau1,2, Jack J Miller2,3, and Damian J Tyler1,2
1Department of Cardiovascular Medicine, University of Oxford, Oxford, Oxfordshire, United Kingdom, 2Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, Oxfordshire, United Kingdom, 3Department of Physics, University of Oxford, Oxford, Oxfordshire, United Kingdom

We investigate the feasibility of imaging the first passage of a bolus of hyperpolarized 13C urea through the rat heart. We propose to use flow-sensitizing bipolar gradients to null the bright signal within the cardiac chambers. An ECG-gated, golden angle spiral pulse sequence is used to obtain dynamic images of 13C urea in the heart (2.3x2.3x5 mm3 resolution, TR~150 ms). Flow-sensitization results in black-blood contrast that enables direct visualization of hyperpolarized 13C urea within the tissue capillary bed. Our results demonstrate reduced contamination from the cardiac lumen.

11:36 0327.   
Metabolic flux analysis of hepatic mitochondrial oxidation of hyperpolarized [1-13C] and [2-13C] pyruvate in vivo
Emine Can1, Jessica A.M. Bastiaansen2,3, Hikari A.I. Yoshihara1,4, Rolf Gruetter5,6, and Arnaud Comment1
1Institute of Physics of Biological Systems, EPFL, Lausanne, Switzerland, 2Department of Radiology, University Hospital Lausanne (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland, 3Center for Biomedical Imaging (CIBM), Lausanne, Switzerland, 4Department of Cardiology, University Hospital Lausanne (CHUV), Lausanne, Switzerland, 5Laboratory for Functional and Metabolic Imaging, EPFL, Lausanne, Switzerland, 6Department of Radiology, University of Lausanne, University of Geneva, Switzerland

Hepatic 13C MRS studies are challenging due to abundant intracellular lipid resonances, impairing the detection of 13C glutamate labeling commonly used to measure TCA cycle fluxes. The carboxyl resonances typically detected by hyperpolarized 13C MRS do not interfere with lipid resonances. In this study, we assessed hepatic metabolism in vivo in real time using hyperpolarized [2-13C]pyruvate and [1-13C]pyruvate to detect the contributions to mitochondrial metabolism related to pyruvate carboxylase and pyruvate dehydrogenase activities. Using the 13C labeling of TCA cycle intermediates within a single 1-min experiment, TCA cycle fluxes were estimated, enabling comparative studies of different metabolic states.

11:48 0328.   Detection of lung mitochondrial dysfunction using hyperpolarized [1-13C] pyruvate metabolism
Hoora Shaghaghi1, Stephen Kadlecek1, Mehrdad Pourfathi1, Sarmad Siddiqui1, Maurizio Cereda2, Hooman Hamedani1, Harrilla Profka1, Yi Xin1, and Rahim R. Rizi1
1Radiology, University of Pennsylvania, Philadelphia, PA, United States, 2Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, PA, United States

Mitochondrial dysfunction is associated with various forms of lung injury and disease. To address the effect of mitochondrial dysfunction on lung metabolism, HP-Pyruvate metabolism was studied in presence of complex I inhibitor (rotenone) and complex IV activator (TMPD). Rotenone decreased bicarbonate production significantly (49%) and TMPD elevated it about 74% when compared to control. Lactate label exchange significantly increased in treated lungs with rotenone (53%). Enhancement of lactate production of injured lungs could be from presence of inflammatory cells and/or because of mitochondrial dysfunction. But the bicarbonate production is not changed in inflamed lungs and decreased on dysfunction of mitochondria.