Neha KOONJOO¹, Gérard Audran², Lionel Bosco², Paul Brémond², Elodie Parzy¹, Philippe Massot¹, Matthieu Lepetit-Coiffé^1,3, Jean-Michel Franconi¹, Sylvain R.A Marque², Eric Thiaudière¹, and Philippe Mellet^1,4
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.

Mathieu Sarracanie^1,2, Fanny Herisson³, Najat Salameh^1,2, David E J Waddington^1,4, Cenk Ayata³, and Matthew S Rosen^1,2
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.

Jingzhe Hu^1,2, Nicholas Whiting³, Pamela Constantinou⁴, Niki Zacharias Millward³, David Menter⁵, Daniel Carson⁴, and Pratip Bhattacharya^3
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.

Myriam Marianne Chaumeil¹, Marina Radoul¹, Pia Eriksson¹, Michael D Blough², Charles Cheneslong², Russell O Pieper^3,4, Joanna J Phillips^3,4, J Gregory Cairncross², and Sabrina M Ronen^1,4
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.

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 Wilson^1
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).

Mor Mishkovsky¹, Andrea Capozzi², Najat Salameh², Jean-Noel Hyacinthe³, Rolf Gruetter^1,4, and Arnaud Comment^2
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.

Chalermchai Khemtong¹, Wei Chen¹, Weina Jiang¹, Craig R Malloy^1,2, and A. Dean Sherry^1,3
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.

Angus Z Lau^1,2, Jack J Miller^2,3, and Damian J Tyler^1,2
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.

Emine Can¹, Jessica A.M. Bastiaansen^2,3, Hikari A.I. Yoshihara^1,4, Rolf Gruetter^5,6, and Arnaud Comment^1
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.

Hoora Shaghaghi¹, Stephen Kadlecek¹, Mehrdad Pourfathi¹, Sarmad Siddiqui¹, Maurizio Cereda², Hooman Hamedani¹, Harrilla Profka¹, Yi Xin¹, and Rahim R. Rizi^1
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.