ISMRM 21st Annual Meeting & Exhibition 20-26 April 2013 Salt Lake City, Utah, USA

3859 -3882 Molecular Imaging Techniques & Cell Labeling
3883 -3906 Novel Agents & Targeting in Molecular Imaging
3907 -3930 Hyperpolarized 13C & Metabolism
3931 -3954 Hyperpolarization: New Methods, Probes, & Applications

Wednesday, 24 April 2013 (10:00-11:00) Exhibition Hall
Molecular Imaging Techniques & Cell Labeling

  Computer #  
3859.   1 On the Fate of MRI Gd-Complexes in Cells. Evidence for Extensive Degradation of Linear Complexes.
Eliana Gianolio1, Enza Di Gregorio1, Rachele Stefania1, and Silvio Aime1
1Molecular Biotechnologies and Health Sciences, University of Torino, Torino, TO, Italy

The use of highly stable complexes has been an important guide-line in the design of Gd-based contrast agents (Gd-CA). Many pre-clinical studies have been reported addressing the use of Gd-CA in cellular labeling experiments. In this presentation we report, for the first time, results concerning the stability of Gd-CA upon their cellular entrapment. Mass spectrometry was used for assessing the amount of intact Gd-complex inside cells upon time. Insights into the intracellular degradative mechanisms have been gained by analyzing the relaxometric NMRD profiles of cells labeled with the Gd-CA.

3860.   2 Decreased Reticuloendothelial System Clearance and Increased Blood Half-Life and Immune Cell Labeling for Nano- And Micron-Sized MRI Contrast Agents Upon Pre-Treatment with Intralipid
Li Liu1, T Kevin Hitchens1, Qing Ye1, Yijen Wu1, Brent D. Barbe1, Devin E. Prior1, Wendy Fei Li1, Lesley M. Foley1, Frank Fang-Cheng Yeh1, Daniel J. Bain2, and Chien Ho1
1Pittsburgh NMR Center for Biomedical Research and Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, United States,2Department of Geology and Planetary Science, University of Pittsburgh, Pittsburgh, PA, United States

Non-invasive in-vivo MRI of monocytes/macrophages labeled with MRI contrast agents may lead to a better understanding of the pathogenesis of many diseases. MRI contrast agents are taken up by the reticuloendothelial system, in particular by liver Kupffer cells, which often contribute to the major loss of the agents in circulation. Strategies that reduce liver uptake and prolong the circulation residence time of these MRI contrast agents can improve the in-vivo labeling efficiency of monocytes/macrophages and lower the required effective dose. In this study, we found that pre-treatment with Intralipid, FDA approved fat emulsion, can result a ~50% decrease in liver uptake of nano- and micron-sized superparamagnetic iron-oxide based MRI contrast agents, resulting a ~3-fold increase in blood half-life and a 2- to 5-fold increase in the labeling efficiency of monocytes in the peripheral blood.

3861.   3 Expanding Applications of Cellular MRI by Combining Fluorine-19 and Iron-Oxide Techniques
T Kevin Hitchens1,2, Li Liu1, Virgil Simplaceanu1,2, Lesley M. Foley1, Eric T. Ahrens1,2, and Chien Ho1,2
1Pittsburgh NMR Center for Biomedical Research, Carnegie Mellon University, Pittsburgh, PA, United States, 2Department of Biological Science, Carnegie Mellon University, Pittsburgh, PA, United States

Both perfluorocarbon (PFC) and iron-oxide nanoparticles are established reagents for cell labeling and MRI tracking studies. Here we combine these two labels to investigate new applications. We show that 19F MRI can detect PFC-labeled cells in the presence of iron-oxide-labeled cells, opening the possibility of simultaneously tracking two populations of labeled cells. In addition, iron-oxide nanoparticles in the same cell can be used to quench 19F signal from the PFC label. Thus, systemic iron-oxide labeling of macrophages may be used to quench 19F signal taken up from dead PFC-labeled cell transplants, a major limitation to current MRI cell tracking studies.

3862.   4 in vivo Magnetic Resonance Imaging of Activity-Dependent Neural Progenitor Cell Migration
Nikorn Pothayee1, Diana Cummings2, Leonardo Belluscio2, and Alan P. Koretsky1
1Laboratory of Functional and Molecular Imaging, NINDS/NIH, Bethesda, MD, United States, 2Developmental Neural Plasticity Section, NINDS/NIH, Bethesda, MD, United States

Neural progenitor cells (NPCs) are produced throughout life by neural stem cells in the subventricular zone (SVZ). NPCs migrate from the SVZ through the rostral migratory stream (RMS) to the olfactory bulb (OB), where they differentiate into various types of interneurons. Herein, we use cellular MRI to investigate potential role of olfactory sensory input on the rate and pattern of NPC migration.

3863.   5 Multifunctional Fluorocapsules for 19F MRI, Immunoprotection, and Oxygenation of Transplanted Pancreatic Islet Cells.
Dian R. Arifin1,2, Deepak K. Kadayakkara1,2, and Jeff W.M. Bulte2,3
1Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States, 2Cellular Imaging Section, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United States, 3Department of Radiology, Johns Hopkins University, Baltimore, MD, United States

Microencapsulation of pancreatic beta islets may potentially provide immunoprotection for islet grafts in treatment of type I diabetes. Here we demonstrated that co-encapsulation of perfluoropolyether emulsions improved the survival and therapeutic function of islet grafts. Fluorocapsules could be visualized as “hot spots” by 19F MRI with single capsule detection capability in vitro. 19F MRI was also able to distinguish intact versus ruptured fluorocapsules, and hence can be used to monitor the persistence of immunoprotection provided only by intact capsules.

3864.   6 Tracking of Labelled Stem Cells After Traumatic Brain Injury: A Serial, in vivo Magnetic Resonance Imaging Study
Sushanta Kumar Mishra1, Gangenahalli U. Gurudutta2, Rajendra P. Tripathi1, and Subash Khushu1
1NMR Research Centre, Institute of Nuclear Medicine and Allied Sciences (INMAS), Delhi, Delhi, India, 2Stem Cells and Gene Therapy Research Group, Institute of Nuclear Medicine and Allied Sciences (INMAS), Delhi, Delhi, India

Tissue replacement by stem cell transplants is a promising approach to treat various diseases. MRI provides 3D imaging and in vivo cell tracking. Mice mesenchymal stem cells were labelled with T2 contrast agent like Dextran-Fe3O4 nanoparticles and Poly-L-Lysine at a final concentration of 50µg/ml and 1.5µg/ml respectively at an incubation period of 4 hours. Labelled mMSCs were injected intravenously and tracked through 7T MRI up to 2 weeks in traumatic brain injury mice. Decrease in T2/T2* value at the injury site in between day 3 and 7 indicates homing of the stem cells to the site of injury.

3865.   7 Labeling of Macrophages with Novel Gadolinium Oxide Nanoparticles for in vivo Imaging of Inflammation
Gary R. Stinnett1, Minjung Cho2, Huigang Zhu2, Pedersen E. Steen1, Christeen Beeton1, Vicki L. Colvin2, and Robia G. Pautler1
1Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, United States, 2Chemistry, Rice, Houston, Texas, United States

We have developed novel gadolinium oxide contrast agents with an R1 three times higher than Magnevist in a 9.4 T MRI. These agents were used to label macrophages resulting in labeled cells significantly brighter than non-labeled cells.

3866.   8 In Vivo Tracking of Ferritin Over-Expressing Human Neural Progenitor Cells in the Rat Central Nervous System
Ksenija Bernau1, Christina Lewis2, Anna Petelinsek3, Masatoshi Suzuki4, Mary Elizabeth Meyerand1,2, and Clive Svendsen5
1Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, United States, 2Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin, United States, 3Biochemistry, University of Wisconsin-Madison, Madison, WI, United States, 4Comparative Biosciences, University of Wisconsin-Madison, Madison, WI, United States, 5Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States

The development of stem cell therapies for neurodegenerative diseases has made great progress in the past decade. The ability to track engrafted cells in vivowill be an essential tool in research and clinical translation of these methods. This research aims to develop a cell tracking method that is clinically translatable, leaves cell dynamics unaffected, and provides specific information regarding cell location and survival. Over-expression of the iron storage protein ferritin enables human neural progenitor cell detection on GE T2*-weighted images after engraftment in the rat brain.

3867.   9 Glioma Cells Transfected with Mms6 Enhance Cellular Iron Oxide Nanoparticles Uptake and Retention in Vitro
Xiaoyong Zhang1, Brenda Robledo1, Jie Song1, and Xiaoping P. Hu1
1Department of Biomedical Engineering, Emory University, Atlanta, GA, United States

Iron oxide nanoparticles (IONPs) and MR reporter genes are tools used for cell labeling and tracking using MRI. In this work, we hypothesized that expressing mms6 gene with IONPs could enhance cellular IONPs uptake and retention. After culturing with IONPs, compared to mms6-negative tumor cells, mms6-positive tumor cells contained a higher level of intracellular iron and exhibited a higher R2. In addition, mms6-positive cells retained more iron with cell passages. These results indicate that expression of mms6 can potentially enhance cellular uptake and retention of IONPs. This capability of mms6 may allow us to develop a mean for targeted uptake and retention of IONPs for MR molecular imaging.

3868.   10 in vivo Magnetic Resonance Tracking of Endothelial Progenitor Cells Trafficking to Sites of Hepatoma Angiogenesis
Xiao Li Mai1, Hai Jian Fan2, Bing Han3, and bin zhu3
1radiology, Nanjing Drum Tower Hospital,The Affiliated Hospital of Nanjing University Medical School, nanjing, jiangsu, China, 2Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China, 3Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China

Tumors must establish new vascular network to promote growth and metastasis. The dependency of tumors on angiogenesis provides a rationale for anti-angiogenesis therapy of cancer targeted at shutting down the tumor blood-supply. Endothelial progenitor cells (EPCs) are precursors to vascular endothelial cells originating from the bone marrow, which have the ability to form endothelial colonies in vitro, may integrate into the neovasculature of tumors and could promote tumor angiogenesis.EPCs have been detected in the circulation of lymphoma-bearing mice and patients with cancer.

3869.   11 Fluorinated Gas MR Imaging at Ultra Short Echo Time: Initial Results on a 1.5 T Clinical System
Pascal Hagot1, Ludovic De Rochefort1, Jean-Christophe Ginefri1, Rose-Marie Dubuisson1, Marie Poirier-Quinot1, Jean-Pierre Ruaud1, Hongchen Wang1, Xavier Maître1, and Luc Darrasse1
1IR4M(UMR8081), Univ Paris-Sud, CNRS, Orsay, France

Using inert fluorinated gas as sulfur hexafluoride have proven its feasibility without the need of polarizing the gas thanks to its short T1 (few ms) that allows rapid repetition of RF pulse and thus a high number of signal averages. On the other hand, its short T2* ~ 1 ms reduces significantly the available time to acquire NMR signal after an excitation RF pulse. To overcome this constraint, ultra-short echo time sequences can be used. Preliminary UTE experiments using SF6 on a clinical 1.5T scanner and show the significant gain over standard gradient-echo acquisition.

3870.   12 Evaluation of the Concentration of Lanthanide Ions in ex vivo Mouse Tissue Using BMS NMR Spectroscopy
Sandra I. Gonzalez1, Dina V. Hingorani2, and Marty Pagel1,2
1Biomedical Engineering, University of Arizona, Tucson, AZ, United States, 2Chemistry & Biochemistry, University of Arizona, Tucson, AZ, United States

The evaluation of lanthanide-based MRI contrast agents often requires the quantification of concentrations of the agents in ex vivo tissues to validate in vivo results. We have developed a BMS NMR spectroscopy method that can quantify the concentrations of lanthanide-based agents in ex vivo tissues, which has an outstanding yield of 93, excellent precision within ~1 mM, and acceptable sensitivity approaching 0.1 mM.

3871.   13 MRI in Vitro Setup for Studying Contrast Agent Effect in Inhomogeneous Environment
Cyril Samuel Lorenzato1, Chris Oerlemans2, Frank Nijsen2, Chrit T.W. Moonen1, and Clemens Bos1
1Imaging division, University Medical Center Utrecht, Utrecht, Netherlands, 2Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht, Netherlands

Last decade, switchable MR contrast-agent based nanocarriers have been designed to monitor release from nanocarriers. Here, we present an easily manufactured gel which consists of alginate microspheres that could be used to address questions related to quantification and or detection thresholds of switchable MR contrast agents. We investigated how the relaxivities of a commercially available gadolinium chelate (Gadovist) are affected by the presence of enclosed water volumes that simulate a soft tissue environment. It was shown that particularly r2 and r2* were strongly increased by a heterogeneous environment in this in vitro setup.

3872.   14 Optimal Field Strength for Molecular MR Imaging : Detection of Targeted Gd-Based Contrast Agents on a Living Cell Monolayer
Nicolas Gargam1, Marie Poirier-Quinot1, Jean-Christophe Ginefri2, Jean-Sebastien Raynaud3, Philippe Robert3, and Luc Darrasse1
1Univ Paris Sud, CNRS, UMR 8081, IR4M, Orsay, France, 2Univ Paris-Sud, Orsay, France, 3Guerbet, Research, Roissy CDG cedex, France

The variation of relaxivity of macromolecular contrast agent as a field function, and the contrast to noise then induced, had already been studied in vitro, but had not yet been highlighted in live cells. The dynamic uptake of a Gd-based nanoemulsion by a cell monolayer is investigated here at 2 field strenghts, 4.7 T to 2.35 T, leading to a signal enhancement of 2.7. That results tends to be in line with in vitro theoretical study showing the efficiency of a paramagnetic nanoemulsion as a field function, raising the question of the optimal field strenght for molecular MR Imaging.

3873.   15 Evaluation of ParaCEST Detection Threshold on Human Stem Cells Under Physiological Constraints
Wen Ling1, Francesca Nicholls1,2, Silvio Aime3, Daniela Delli Castelli3, and Michel Modo1
1Radiology, University of Pittsburgh, Pittsburgh, PA, United States, 2dept of Neuroscience, King's College London, London, London, United Kingdom, 3Dept of Chemistry, University of Torino, Torino, Torino, Italy

Optimal detection conditions were established for paraCEST to detect different cell populations in vitro. The scanning conditions were further verified by the fact that human neural stem cells can withstand up to 5 hrs without significant effects on their viability. The detection threshold was then evaluated in terms of concentration and voxel size.

3874.   16 Investigation of the CEST Effect in Prostate Metabolites
Meer Basharat1, Maysam Jafar1, Nandita M. deSouza1, and Geoffrey Payne1
1CRUK & EPSRC Cancer Imaging Centre, Insitute of Cancer Reaserch, Sutton, Surrey, United Kingdom

Experiments were performed at 11.7T for the first time on solutions of spermine and citrate, to discover whether these two major prostate secretions demonstrate a CEST effect at expected pH and concentration conditions. There was a 42% CEST effect for 10mM spermine at pH 6.0 at 310K, but no considerable CEST effect for 100mM citrate at pH1.8 also at 310K. SpermineCEST was increased with acidity, but decreased with higher citrate and temperature levels. This latter behaviour is not expected, so spermineCEST will be explored with other metabolite concentrations and by performing CEST on the related chemicals putrescine and spermidine.

3875.   17 Modeling the Brownian Relaxation of Nanoparticle Ferrofluids: Comparison with Experiment
Michael A. Martens1, Robert J. Deissler1, Yong Wu1, Lisa Bauer1, Zhen Yao1, Mark A. Griswold2, and Robert W. Brown1
1Physics, Case Western Reserve University, Cleveland, Ohio, United States, 2Radiology, Case Western Reserve University, Cleveland, Ohio, United States

We investigate the ability of current models for magnetic nanoparticles immersed in dilute ferrofluids and external sinusoidal magnetic fields to explain recent experiments in which the relaxation effects are dominated by viscous damping. The Fokker-Planck (FP) equation, appropriate for the nanoparticle magnetic moment distribution corresponding to the underlying stochastic Langevin model, is numerically studied and solutions compared to experimental results. By incorporating the polydisperse properties of the particles into the analysis we obtain good agreement with recent experimental results using ferrofluids containing nanoparticles with average hydrodynamic diameters in the 40-120 nm range.

3876.   18 Magnetic Susceptibility Anysotropy of Oriented Single Walled Carbon Nanotubes Suspensions as Measured by SQUID Induces Water Relaxation Anysotropy as Detected by MRI
Daniel Calle1, Arisbel Cerpa2, Viviana Negri1,3, Elisabetta Agostinelli4, Sebastián Cerdán5, Sara Laureti4, Paloma Ballesteros3, and Gaspare Varvaro4
1Instituto de Investigaciones Biomédicas "Alberto Sols", Madrid, Madrid, Spain, 2Universidad Europea de Madrid, Villaviciosa de Odón, Madrid, Spain,3Universidad Nacional de Educación a Distancia, Madrid, Madrid, Spain, 4Istituto di Struttura della Materia, Monterotondo, Rome, Italy, 5Instituto de Investigaciones Biomédicas - CSIC, Madrid, Madrid, Spain

The relaxation of water molecules induced by classical contrast agents occurs in an isotropic manner, becoming not possible to determine the molecular orientation of the contrast agent molecule from water relaxivity measurements. In this work we report on a novel family of contrast agents endowed naturally with anisotropic relaxivity (1,2) and thus able to reveal the molecular orientation of the contrast agent probe from non invasive, water relaxivity measurements. Single Walled Carbon Nanotubes (SWCNTs) preparations are shown to be useful systems for this purpose since they align along the magnetic field and may depict different magnetic properties in the longitudinal and axial directions. In this communication we report, for the first time to our knowledge, measurements of the directional magnetic susceptibility of SWCNTs suspensions using a SQUID magnetometer and of the resulting anisotropic water relaxivity using an MRI scanner.

3877.   19 A Computational Model of the Time – Independent Bloch NMR Flow Equation for Molecular Imaging
Michael Oluwaseun Dada1 and Bamidele Omotayo Awojoyogbe1
1Physics, Federal University of Technology, Minna, Nigeria, Minna, Niger State, Nigeria

In this study, a new methodology based on the time – independent Bloch NMR flow equations and Hermite equations for detailed studies of tissue processes at molecular level has been developed. We study the flow properties of the equations which describes the dynamics of fluid flow under the influence of rF field as derived in the earlier studies involving the equations. We found out that the solutions only show very clear contrast at very small fluid velocity and the MR signals are incredibly high such that at this molecular level, the possibility of having clear images is very good.

3878.   20 Magnetic Field Simulations for SPIOns
Ricardo Hernandez1, Miguel Mendez-Rojas2, Eric Gutierrez3, and Silvia Hidalgo Tobón4
1Science Faculty, UNAM, DF, DF, Mexico, 2Nanotechnology, UDLAP, Puebla, Puebla, Mexico, 3Medical Physics, UAEM, Toluca, Mexico, Mexico, 4Imagenology, Children Hospital Federico Gomez, Mexico, MExico, Mexico

Introduction: we studied the susceptibility effects of iron oxide (SPIONs) functionalized with triethylenglycol (TREG) and Polyethylen Glycol (PEG), those nanoparticles have the necessary properties to be used in the clinic as contrast media in imaging by MRI. We are considering the behavior of the magnetic field as plane wave to explain the electrical and magnetic field produced by SPIONs.

3879.   21 Experimental and Simulation Studies on the Behavior of Signal Harmonics in Magnetic Particle Imaging
Kenya Murase1, Takashi Konishi1, Yuki Takeuchi1, Ruiciao Song1, Hiroya Suzuki1, Hiroshige Takata1, and Shigeyoshi Saito1
1Medical Physics and Engineering, Osaka University, Suita, Osaka, Japan

Recently, a new imaging method called magnetic particle imaging (MPI) has been introduced that allows for imaging the spatial distribution of magnetic nanoparticles (MNPs) with high sensitivity and spatial resolution. In this study, we investigated the behavior of signal harmonics in MPI under various conditions of drive and selection magnetic fields by experimental and simulation studies. We also investigated the dependency of signal harmonics on the particle size of MNPs by simulation studies based on the particle sizes actually measured. This study will be useful for better understanding, optimization, and development of MPI and for designing MNPs appropriate for MPI.

3880.   22 MRI Pulse Sequence Optimization for Molecular Imaging of the Brain Aneurysm Wall
Imramsjah M.J. van der Bom1, Matthew J. Gounis1, Shaokuan Zheng2, Juyu Chueh1, Anna Luisa Kühn1, and Alexei A. Bogdanov3
1Radiology/NECStR, University of Massachusetts Medical School, Worcester, Massachusetts, United States, 2Radiology/AMRIC, University of Massachusetts Medical School, Worcester, Massachusetts, United States, 3Radiology/Nuclear Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States

To investigate the role of unruptured aneurysm wall inflammation and propensity for rupture, imaging parameters of a motion-sensitized driven-equilibrium black-blood sequence were optimized to suppress signal caused by slow non-linear blood flow within aneurysms while preserving CNR from surrounding tissue. Parameter optimization was performed using a silicone vascular replica and a rabbit aneurysm model. The optimized sequence was used to investigate signal enhancement of inflamed aneurysm walls in rabbits using a MPO-specific contrast agent. Blood signal within the aneurysms was sufficiently suppressed in all rabbits and a significant increase of SNR was observed in the inflamed aneurysms compared to controls.

3881.   23 Value of Wholebody 18F-FDG PET/MRI in the Diagnosis Liver Metastases in Comparison to PET/CT
Karsten Beiderwellen1, Benedikt Gomez2, Verena Hartung-Knemeyer2, Christian Buchbender3, Felix Nensa1, Hilmar Kuehl1, Andreas Bockisch2, and Thomas C. Lauenstein1
1Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, Essen, Germany, 2Clinic for Nuclear Medicine, University Hospital Essen, Essen, Germany, 3Department of Diagnostic and Interventional Radiology, University Hospital Dusseldorf, Dusseldorf, Germany

The purpose of this study was to evaluate the potential of simultaneaously acquired wholebody PET/MRI with 18F-FDG in the diagnosis of liver metastases in comparison to PET/CT. 71 patients with solid tumors received in a whole body PET/CT and subsequently underwent a wholebody PET/MRI (Biograph mMR, Siemens Healthcare). The resulting datasets (PET/CT, PET/MRI) were rated separately by two readers. The criteria comprised scores for lesion detectability and diagnostic confidence. Due to the high soft tissue contrast of MRI significantly higher scores for lesion conspicuity and diagnostic confidence were found in PET/MRI.

3882.   24 Phase Contrast MR Imaging to Image Bacterial Translocation in a Mouse Model for Graft Versus Host Disease
Wilfried Reichardt1,2, Nicoleta Baxan2,3, Robert Zeiser4, Franziska Leonhardt4,5, and Dominik von Elverfeldt2
1Deutsches Konsortium für translationale Krebsforschung (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany, 2Department of Radiology Medical Physics, University Medical Center Freiburg, Freiburg, Germany, 3Bruker BioSpin MRI GmBH, Ettlingen, Germany, 4Division of Hematology and Oncology, Department of Medicine, University Medical Center Freiburg, Freiburg, Germany, 5Department of Biology, Albert-Ludwigs-University-Freiburg, Freiburg, Germany

The aim of this work was using phase contrast MR imaging for the in vivo tracking of bacteria in vivo after total body irradiation (TBI) using SPIO-tagging of bacteria and highly sensitive phase contrast MRI. SPIO+E. coli were injected into the rectum of mice that had received TBI or no treatment. The signals from SPIO+ E. coli creating a dipole-shaped pattern were clearly visible in the tissue surrounding the intestinal wall. SPIO+E. coli were seen significantly more frequently in mice that had received TBI as compared to the untreated group indicating that TBI enhanced transmigration of bacteria through the epithelial layer of the intestinal wall.


Wednesday, 24 April 2013 (11:00-12:00) Exhibition Hall
Novel Agents & Targeting in Molecular Imaging

  Computer #  
3883.   1 Biological Modifiers of Novel Theranostic Metalloporphyrins
Talaignair N. Venkatraman1, Artek Tovmasyan2, Ines Batinic-Haberle2, Ivan Spasojevic2, and Christopher D. Lascola1
1Radiology, Duke University Medical Center, Durham, NC, United States, 2Radiation Oncology, Duke University Medical Center, Durham, NC, United States

This study investigates the potential impact of common biological moieties on the relaxation properties of our two lead candidate MnPs (MnTE-2-PyP5+ and MnTnHex-2-PyP5+). These include the most abundant intracellular redox mediator, ascorbate; (2) the most metabolically relevant counter-anion, citrate; (3) and the most abundant serum protein, albumin. With respect to likely biological redox modifiers, both MnP isoforms showed a systematic reduction in relaxivity in the presence of ascorbate, consistent with the hypothesis that metal center oxidation state will have a significant impact on relaxation properties of MnPs in vivo. Intriguingly, citrate anion does not negatively impact relaxation, and in the case of MnTE2PyP5+, may actually enhance contrast enhancement. These two isoforms of MnP demonstrate impressive relaxation properties that enable MR detection in vivo.

3884.   2 New Lanthanide Agents for BIRDS and CEST Imaging
Yuegao Huang1,2, Daniel Coman1,2, Garry E. Kiefer3, and Fahmeed Hyder1,4
1Diagnostic Radiology, Yale University, New Haven, CT, United States, 2Magnetic Resonance Research Center, Yale University, New Haven, CT, United States, 3Macrocyclics, Dallas, TX, United States, 4Biomedical Engineering, Yale University, New Haven, CT, United States

Temperature mapping has important biomedical applications. Unlike PARACEST agents that provide temperature contrast, the Biosensor Imaging of Redundant Deviation in Shifts (BIRDS) method provides absolute temperature mapping, where directly imaging proton resonances of the lanthanide complexes with 3D CSI is key. Motivated by success of TmDOTMA- with BIRDS for temperature mapping, we designed new agents with methyl groups on different positions of DOTA-based chelates. Comparison with TmDOTMA- shows much higher temperature sensitivities with BIRDS are achieved with the new agents. Moreover, the new agents have strong PARACEST capabilities to allow quantitative molecular imaging by combining with BIRDS.

3885.   3 Dendrimeric Paramagnetic Chelates for BIRDS
Yuegao Huang1,2, Meser M. Ali3, Daniel Coman1,2, Garry E. Kiefer4, and Fahmeed Hyder1,5
1Diagnostic Radiology, Yale University, New Haven, CT, United States, 2Magnetic Resonance Research Center, Yale University, New Haven, CT, United States, 3Radiology, Henryford Health System, Detroit, MI, United States, 4Macrocyclics, Dallas, TX, United States, 5Biomedical Engineering, Yale University, New Haven, CT, United States

Temperature mapping using low molecular weight paramagnetic chelates has advantageous sensitivities compared to conventional MRI thermometry methods. 3D temperature maps can be generated with a method called Biosensor Imaging of Redundant Deviation in Shifts (BIRDS), where directly imaging proton resonances of lanthanide complexes with 3D CSI is key. Considering success of BIRDS with low molecular weight individual chelates, in the present work we explore the possibilities to improve BIRDS sensitivity with larger biocompatible molecules, such as dendrimers. The BIRDS detection can be achieved with lower agent dosage when lanthanide chelates are conjugated to the surface of the dendrimers.

3886.   4 An Anovel Multifunctional Dendrimer-Based Nanoparticles for in vivo MRI/CT Dual Modal Molecular Imaging of Breast Cancer
Kangan Li1, Shihui Wen2, Xiangyang Shi2, Guixiang Zhang3, and Andrew C. Larson1
1Department of Radiology, Northwestern University, Chicago, Illinois, United States, 2Chemical Engineering and Biotechnology, Donghua University, Songjiang, Shanghai, China, 3Department of Radiology, Shanghai Jiaotong University, Hongkou, Shanghai, China

A novel multifunctional dendrimer-based gold nanoparticles as a MRI/CT dual modality contrast agent for in vivo molecular imaging of breast cancer.

3887.   5 D-Glucuronic Acid Coated DyEuO3 and HoEuO3 Nanoparticles for Magnetic Resonance Imaging (MRI) and Fluorescence Imaging (FI)
Wenlong Xu1, Krishna Kattel1, Md. Wasi Ahmad1, Badrul Alam Bony1, Tirusew Tegafaw1, Woo Choul Heo1, Cho Rong Kim1, Yongmin Chang2, and Gang Ho Lee1
1Department of Chemistry, Kyungpook National University, Buk-gu, Daegu, Korea, 2Department of molecular medicine, Kyungpook National University, Buk-gu, Daegu, Korea

A dual imaging now emerges as a new and advanced imaging technique in clinical applications. The single-phase mixed DyEuO3 and HoEuO3 nanoparticles are potential candidates for dual imaging experiment. It is expected that it will play a key role to diagnose diseases by replacing conventional single-imaging techniques. For example for MRI-FI dual imaging, the fluorescence imaging can be used to locate a disease and then MRI can be used to obtain high resolution MR images around the disease. We developed a facile synthesis of ultra-small D-Glucuronic acid coated Eu3+ doped Dysprosium oxide nanoparticles and Holmium oxide nanoparticles. The capability of nanoparticles as T2 MRI contrast agent was proved in vivo through T2 MR images of a rat. The fluorescent images were observed in vitro by taking DU145 and NCTC1469 cells. The nanoparticles exhibited no appreciable cytotoxicity up to 100 lower case Greek muM concentrations and in vivo MR experiment showed the negative contrast enhancement on mouse liver and kidneys after the injection of nanocolloid. Hence, it can be used as a fluorescence imaging agent as well as a T1 MRI contrast agent.

3888.   6 Biopolymer Coated Gd2O3 Nanoparticles for MRI Contrast Agent
Md. Wasi Ahmad1, Kattel Krishna1, Badrul Alam Bony1, Wenlong Xu1, Tirusew Tegafaw1, Woo Choul Heo1, Yongmin Chang2, and Gang Ho Lee1
1Chemistry, Kyungpook National University, Daegu, Korea, 2Molecular Medicine School of Medicine, Kyungpook National University, Daegu, Korea

The surface modified Gd2O3 nanoparticles as an active ingredient has a higher relaxation rate compared to currently commercialized MRI contrast agent. The performance of nanoparticles for biomedical applications is highly dependent on the nature and quality of surface coating materials. In particular, the development of functionalized nanoparticles for magnetic resonance imaging (MRI) requires the grafting of hydrophilic and biocompatible polymers, this polymer enhances the steric repulsion and therefore the stability of the colloids

3889.   7 Synthesis of CuO Doped Gd2O3 Nanoparticles as T1 MRI Contrast Agent
Badrul Alam Bony1, Krishna Kattel1, Wenlong Xu1, Woo Choul Heo1, Tirusew Tegafaw Mengesha1, Md. Wasi Ahmad1, Cho Rong KIM1, Yongmin Chang2, and Gang Ho LEE1
1Department of Chemistry, Kyungpook National University, Daegu, Korea, 2School of Medicine, Kyungpook National University, Daegu, Korea

CuO doped Gd2O3 nanoparticles can be used as a MRI contrast agent clinically because of its enhanced relaxivity and less toxicity. The r1 value of CuO doped Gd2O3 nanoparticles is 13.8 mM-1s-1 which is more than double of ordinary Gd2O3 nanoparticles. That is why, CuO doped Gd2O3 nanoparticles can be a novel candidate for T1 MRI contast agent.

3890.   8 Preclinical in Vitro and in vivo Assessment of a Novel Graphene Based MRI Contrast Agent
Shruti kanakia1, Jimmy Toussaint1, Sayan Mullick Chowdhury1, Tanuf Tembulkar1, Terry Button2, Kenneth Shroyer3, William Moore2, and Balaji Sitharaman1
1Biomedical Engineering, Stony Brook Univeristy, Stony Brook, New York, United States, 2Radiology, Stony Brook Univeristy, Stony Brook, New York, United States, 3Pathology, Stony Brook Univeristy, Stony Brook, New York, United States

We report pre-clinical in vitro and in vivo small animal studies of a novel graphene-based MRI CA. The formulation called GNP-Dex consists of monodisperse graphene nanoplatelets (GNPs; small disc-shaped graphene nanoparticles with diameter ~40 nm and thickness ~3-4 nm), intercalated with manganese Mn2+ ions, and water-solubilized with dextran. The results show that the GNP-Dex formulation is safe (LD50 > 500 mg/kg). At potential therapeutic doses (≤100 mg/kg), they show no nephrotoxicity and are more efficacious than clinical MRI CAs Magnevist and Ablavar. The results indicate that GNP-Dex show potential for development as high performance clinical T1 MRI CA.

3891.   9 Visualization of Therapeutic Angiogenesis by a Polymer-Based Magnetic Resonance Contrast Agent
Jun-ichiro Jo1,2, Ichio Aoki1, Tsuneo Saga1, and Yasuhiko Tabata2
1Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Chiba, Japan, 2Department of Biomaterials, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Kyoto, Japan

The objective of this study is to design and prepare a new polymer-based contrast agent of magnetic resonance imaging (MRI) for the evaluation of therapeutic angiogenesis. Diethylenetriaminepentaacetic acid (DTPA), cyclic peptide containing an arginine-glycine-aspartic acid sequence (cRGD), and gadolinium ion (Gd3+) were introduced to dextran to obtain the dextran-based contrast agent (cRGD-dextran-DTPA-Gd). The cRGD-dextran-DTPA-Gd showed a higher longitudinal relaxivity compared with DTPA-Gd. The ischemic-angiogenic region could be clearly detected with MRI by the intravenous injection of cRGD-dextran-DTPA-Gd to mice with hindlimb ischemia. It is concluded that the cRGD-dextran-DTPA-Gd is a promising material to evaluate the therapeutic angiogenesis.

3892.   10 A R2p/R1p Ratiometric Approach with Gd Containing Liposomes for the Imaging of Matrix Metalloproteinases by MRI
Giuseppe Digilio1, Valeria Catanzaro2, Valeria Menchise3, Sergio Padovan3, Martina Capozza4, Linda Chaabane5, and Silvio Aime4
1Università del Piemonte Orientale "A. Avogadro", Alessandria, AL, Italy, 2Istituto di Ricerca Diagnostica e Nucleare SDN, Via Gianturco 113, Napoli, 80143, Na, Italy, 3CNR - IBB, Torino, TO, Italy, 4Department of Chemisty & Center for Molecular Imaging, University of Turin, Torino, TO, Italy, 5Institute for Experimental Neurology - INSpe, San Raffaele Scientific Institute, Milano, MI, Italy

A novel paramagnetic Gd-loaded liposome for the MRI assessment of the activity of Matrix Metalloproteinase-2 is described. It relies on a ratiometric R2p/R1p procedure that is independent of the total concentration of gadolinium.

3893.   11 Super-Relaxive Gd Nanoparticle
Ananth Annapragada1, Eric Tanifum1, Ketan Ghaghada1, and Divya Sabapathy1
1Pediatric Radiology, Texas Childrens Hospital, Houston, TX, United States

Novel presentation of Gd atoms on nanoparticles were tested, to identify the mechanism of hyperrelaxivity of nanoparticle presented Gd. A new lipid construct with dramatically higher relaxivity is described.

3894.   12 Long Longitudinal Relaxation Time Silicon Nanoparticles
Shawn Wagner1,2, Denis Avdic1, Alexander Grunfeld3, and Debiao Li1,2
1Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, United States, 2Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States, 3Life Sciences, UCLA, Los Angeles, California, United States

½ spin nuclei like yttrium (89Y) and silicon (29Si) can have long T1 values. Recent literature has suggested that the T1 value in silicon particles is size dependent because the dominate relaxation is a result of spin diffusion from the surface to the core. In this work, we measured the T1 values of silicon nanoparticles of various sizes to verify whether the hypothesis is true. We found that small nanoparticles have longer than predicted relaxation times and would be suitable for development into molecular targeting agents which could be followed for several hours.

3895.   13 Measuring the Accumulation of Magnetite Labeled Nanoparticles in the Rat Brain
Naira P. Martinez Vera1, Klaus Langer2, Iavor Zlatev2, Robert Wronski3, Manfred Windisch3, Ewald Auer3, Hagen von Briesen4, Sylvia Wagner4, Motti Deutsch5, Claus Pietrzik6, Franz Fazekas1, Reinhold Schmidt1, and Stefan Ropele1
1Department of Neurology, Medical University of Graz, Graz, Styria, Austria, 2Institut für Pharmazeutische Technologie und Biopharmazie, Münster, North Rhine-Westphalia, Germany, 3JSW Life Sciences GmbH, Grambach, Styria, Austria, 4Department of Cell Biology & Applied Virology, Fraunhofer-Institute for Biomedical Engineering, St. Ingbert, Saarland, Germany, 5Physics Department, Schottenstein Center for the Research and Technology of the Cellome, Bar Ilan University, Ramat Gan, Israel, 6Institute of Pathobiochemistry, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Rhineland-Palatinate, Germany

Nanoparticles (NP) have been suggested as a vehicle to selectively transport drugs over the blood brain barrier. In this work we investigated the feasibility of measuring the accumulation of HSA based NP in the rat brain after intravenous injection. The NP were labeled with magnetite in order to achieve a significant T1 relaxivity effect. The measurement of NP concentration was based on a histogram fitting technique which allowed to globally assess T1 changes in gray and white matter. This approach proved to be very sensitive and was validated with results from autofluorescence imaging.

3896.   14 T1 and T2 Mapping of Superparamagnetic Iron Oxide Nanoparticles for the Detection of Breast and Pancreatic Cancer Cells
Dirk Krueger1, Gorka Salas2, Macarena Calero2, Silvia Lorrio González1, Angeles Villanueva2, María P. Morales3, and René M. Botnar1
1Division of Imaging Sciences & Biomedical Engineering, King's College London, London, United Kingdom, 2Instituto IMDEA Nanociencia, Madrid, Spain,3Instituto de Ciencia de Materiales de Madrid, CSIC, Madrid, Spain

The aim of this project is to develop and validate multifunctionalised magnetic nanoparticles (MF-MNP) to selectively target and monitor delivery and treatment response of MNPs to cancer cells by MRI. We assessed eight MNPs on their MR imaging properties and investigated their effects on various cancer cell lines. The investigated 15 nm DMSA-coated MNP shows promising imaging (i.e. r1 and r2 relaxivities) and labelling properties without affecting viability of the cells and thus warrant in-vivo investigation in nude tumour bearing mice (BT474, MDA-MB-231, BxPc-3 PANC-1) to evaluate biodistribution, specificity and suitability for in vivo imaging and therapy.

15 High R1 Relaxivity Sub-5 Nm Suprasmall Iron Oxide Nanoparticles (SSIOs) as Intravascular T1-Weighted MRI and Cell Tracking Contrast Agents
Jing Huang1, Liya Wang1, and Hui Mao1
1Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, United States

Superparamagnetic iron oxide nanoparticles (SPIOs) have been widely used as MRI contrast agents both in clinical applications (e.g. liver, lymph nodes imaging) and preclinical models (e.g. cell tracking, molecular imaging). Currently, most SPIOs are fabricated with size larger than 5 nm, therefore exhibit predominant shortening effect on T2, causing signal void in T2-weighted MRI. Here we report a new class of high r1 relaxivity, sub-5 nm, suprasmall iron oxide nanoparticles (sSIOs, ~3.5 nm) as intravascular T1-weighted MRI contrast agents, providing reverse T2 contrast and T1-T2 contrast switch, when taken up by cells and liver, or between labeled and lysed cells.

3898.   16 Characterization of Fe-Co Ferrite Nanoparticles for Contrast Generation and Heat Therapy in Cancer
Sheikh Manjura Hoque1, Yuegao Huang1, Samuel Maritim1, Daniel Coman1, and Fahmeed Hyder1
1Yale University, New Haven, CT, United States

Ferrite nanoparticles are used for contrast, but they also have potential for cancer therapy because nanoparticles can be heated by alternating RF. Since diamagnetic resonances are susceptibility-shifted with nanoparticles, temperature and/or pH mapping with typical MRI/MRS methods are difficult. To generate both tissue contrast and map temperature/pH in presence of nanoparticles, we used a new method called BIRDS, which requires that we detect protons emanating from a temperature/pH probe (e.g., TmDOTP5-) itself, instead of the agent’s effect on water proton relaxation times. Promising in vitro results from a family of Fe-Co mixed ferrite nanoparticles are discussed.

3899.   17 Multi-Modal Imaging to Evaluate the Effects of Novel TLR Agonist Adjuvants in Vaccine-Mediated Tumor Immunity
Deepak K. Kadayakkara1, Hyam I. Levitsky1, and Jeff W.M. Bulte2,3
1Department of Oncology, Johns Hopkins School of Medicine, Baltimore, Maryland, United States, 2Cellular Imaging Section, Institute for Cell Engineering, Johns Hopkins University, Baltimore, Maryland, United States, 3MRI research division, Johns Hopkins School of Medicine, Baltimore, Maryland, United States

We evaluated the effects of novel adjuvants in cancer vaccines using non-invasive imaging. ‘Magnetovaccination’ and MRI were used to evaluate dendritic cell-mediated antigen capture and delivery to regional lymph nodes. The ensuing effector immune response mediated by T cells was studied by antigen-specific transgenic T cells and bioluminescence imaging. We show that, unexpectedly, adjuvants reduced antigen delivery to lymph nodes; however they induced a more effective tumor therapeutic response suggesting an alternate and hitherto unreported pathway for T cell expansion and accumulation.

3900.   18 Magnetic Resonance Imaging(MRI) and X-Ray Computed Tomography(CT) Dual Functionality of Gadolinium Iodate Dihydrate Nanomaterials
Cho Rong Kim1, Eun Jung Lee1, Woo Choul Heo2, Yongmin Chang3, and Gang Ho Lee1
1Chemistry, Kyungpook national university, Daegu, Korea, 2Chemistry, Kyungpook National University, Daegu, Korea, 3School of medicine, Kyungpook National University, Daegu, Korea

We synthesized D-glucuronic acid coated Gd(IO3)3.2H2O nanomaterials and for the first time investigated their magnetic properties, water proton relaxivities, and X-ray phantom images. D-glucuronic acid coated Gd(IO3)3.2H2O nanomaterials were paramagnetic, with very large longitudinal (r1) and transverse (r2) water proton relaxivities of 52.3 and 63.4 s-1mM-1, respectively, both of which were larger than those of commercial Gd-chelates. Hydrated water molecules seem to serve as a reservoir for strong MR signals. The stronger contrast enhancements in X-ray phantom images than those of commercial molecular iodine CT contrast agents were also observed. These results revealed that D-glucuronic acid coated Gd(IO3)3.2H2O nanomaterials should be a potential candidate for a MRI-CT dual contrast agent.

3901.   19 MRI and Fluorescence Imaging with Upconverting Nanoparticles: a New Multimodal Approach for Lung Targeting
Hugo Groult1,2, Andrea Bianchi3, Moreno Zamai4, Jesus Ruiz-Cabello1, Yannick Crémillieux3, and Fernando Herranz-Rabanal1
1Advanced imaging unit, CNIC (centro nacional de investigaciones cardiovasculares), Madrid, Madrid, Spain, 2CIBERES (Centro de Investigacíon biomedica en red Enfermedades Respitorias), Bunyola, Mallorca, Spain, 3Cardio-thoracic Center of Bordeaux, University of Bordeaux Segalen, Bordeaux, Aquitaine, France, 4Microscopy and Dynamic imaging Unit, CNIC (centro nacional de investigaciones cardiovasculares), Madrid, Madrid, Spain

One of the most attractive approaches in molecular imaging is the combination of fluorescence with MRI, providing high sensitivity and resolution together with structural and functional data. We present here the physicochemical characterization and the in vitro and in vivo multimodal study (MR and fluorescence imaging) of a new class of nanoparticles based on UpConverting NanoPhosphors albumin-coated. These nanoparticles present the unique feature of converting low energy near-infrared (NIR) light into higher visible light and/or NIR emission, which allow to overcome all the typical problems of fluorescent probes. At the same time they can be combined to MR imaging modality.

3902.   20 Magnetic Resonance-Fluorescent Dual Imaging of Fluorescein Coated Gd2O3 Nanoparticles
Tirusew Tegafaw Mengesha1, Krishna kattel1, Wenlong Xu1, Badrul Alam Bony1, Woo Choul Heo1, Kim Cho Rong1, Md. Wasi Ahmad1, Yong Min Chang2, and Gang Ho Lee1
1Departement of Chemistry, Kyungpook National University, Daegu, Korea, 2Departement of molecular medicine, Kyungpook National University, Daegu, Korea

MRI is a very useful technique in diagnosing diseases because of its high spatial resolution and good sensitivity. Detection of diseases can be further improved by using MRI contrast agents through contrast enhancement. Fluorescein coated gadolinium oxide nanoparticles are promising candidates as either T1 MRI-CL or MRI-FI dual agents because gadolinium oxide nanoparticles show a longitudinal relaxivity (r1) which is much larger than those of Gd (III) -chelates while dyes generally provide a very strong fluorescent intensity. The enhanced r1 of gadolinium oxide nanoparticles with respect to those of Gd (III) - chelates is due to a high density of probing Gd (III) ions in nanoparticles. Gadolinium oxide nanoparticles must be biocompatible and completely excreted from the body through the renal system to avoid any danger such as nephrogenic systemic fibrosis. Therefore, nanoparticles should be well-coated with water-soluble and biocompatible ligands. In this work, fluorescein is conjugated to hydrophilic and biocompatible polyethyleneimine (PEI) (Mn = y1200 amu) to improve both water-solubility and biocompatibility of fluorescein through the EDC/NHS coupling method. Finally, fluorescein-PEI was conjugated to gadolinium oxide nanoparticles. We demonstrated MRI-CL dual functionality of fluorescein-PEI coated gadolinium oxide nanoparticles both in vivo and in vitro.

3903.   21 pH-Triggered 19F MRI for Lung Cancer Cell A549
Shizhen Chen1, Yuqi Yang1, Qi Wang1, Haidong Li1, and Xin Zhou1
1Wuhan Center for Magnetic Resonance,Wuhan Institute of Physics and Mathematics,CAS, Wuhan, Hubei, China

We developed a novel nanosized and pH-trigged biosensor, which encapsulates high-sensitive 19F MRI contrast agent in gold nanoparticles (AuNPs)-capped mesoporous silica nanoparticles (MSNs) platform,and this biosensor is capable to specifically target to lung cancer cell (A549) for intracellular MRI.

3904.   22 Monitoring Neuroinflammation in vivo with MR Spectroscopy and CEST Imaging
Maria Yanez Lopez1, Marie-Christine Pardon2, Dorothee P. Auer1, and Henryk Faas1
1Radiological and Imaging Sciences, University of Nottingham, Nottingham, Nottinghamshire, United Kingdom, 2School of Biomedical Sciences, University of Nottingham, Nottingham, Nottinghamshire, United Kingdom

This study assesses the short term inflammatory response in the brain to a standard immune challenge, lipopolysaccharide injection, with serial MR Spectroscopy and imaging using Chemical Exchange Saturation Transfer. Results show in vivo MRS changes three hours after lipopolysaccharide administration: increase in the microglial marker myo-inositol and decrease in total choline (both effects absent in controls with PBS administration). They also indicate that CEST can assess, at high spatial resolution, metabolic changes following low dose lipopolysaccharide administration, since CEST images at offset frequencies of 0.5-1, 1.8-2.2 ppm in the z-spectrum, showed a correlation with myo-inositol and total creatine MRS ratios.

3905.   23 MR Imaging of ex-vivo Mouse Joints on a Clinical 3T System with Diagnostic SPION Imaging Using DUTE in an Arthritis Model.
Lindsey Alexandra Crowe1, Frank Tobalem2, Marije Koenders3, Eline Vermeij3, Fons A. van de Loo3, Azza Gramoun1, Jatuporn Salaklang4, Anthony Redgem4, Alke Petri-Fink5, Heinrich Hofmann6, Wim van der Berg3, and Jean-Paul Vallée1
1Radiology / Faculty of Medicine, Geneva University Hospital, Geneva, Switzerland, 2Radiology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, 3Department of Rheumatology, Rheumatology Research and Advanced Therapeutics, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands, 4Adolphe Merkle Institute, Université de Fribourg, Fribourg, Switzerland, 5Adolphe Merkle Institute and Chemistry Departement, Université de Fribourg, Fribourg, Switzerland, 6Institute of Materials, Powder Technology Laboratory, EPFL, Lausanne, Switzerland

Many pre-clinical studies are carried out on clinical MRI systems due to translational possibilities and availability of technology. For small sample sizes, an adapted coil to give high signal intensity is needed. Diagnostic potential of signal loss and positive contrast difference Ultrashort Echo (dUTE) sequences for iron oxide nanoparticle detection (amino-PVA-SPIONs) was compared in a mouse model of antigen induced arthritis. SPION administration routes and doses in arthritic and control knees are compared for synovial uptake with high sample throughput.

3906.   24 Effect of Moderate Hyperthermia on Inflammation Following Experimental Traumatic Brain Injury in Mice
Lesley M. Foley1, Steven L. Shein2,3, Vincent A. Vagni2, T Kevin Hitchens1,4, Chien Ho1,4, and Patrick M. Kochanek2,5
1Pittsburgh NMR Center for Biomedical Research, Carnegie Mellon University, Pittsburgh, Pennsylvania, United States, 2Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States, 3Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States, 4Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania, United States,5Departments of Critical Care Medicine, Pediatrics and Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States

Secondary insults are known to worsen outcome following traumatic brain injury (TBI). Though there is conflicting clinical evidence with regards to hyperthermia, it is generally considered as detrimental and for patients that exhibit pyrexia it is important temperature control. In animal models there is no question about the role of hyperthermia and it’s detrimental effect on outcome. In our study there was a significant increase in macrophage influx to the brain following TBI and moderate hyperthermia.


Wednesday, 24 April 2013 (10:00-11:00) Exhibition Hall
Hyperpolarized 13C & Metabolism

  Computer #  
25 Toward a Hyperpolarized C13 Metabolic Imaging of Human Brain at 3T
Ilwoo Park1, Peder E.Z. Larson1, Jim Tropp2, Lucas Carvajal1, Mark VanCriekinge1, Robert A. Bok3, John Bringas4, Adrian Kells4, Philip Pivirotto4, Krystof Bankiewicz4, Daniel B. Vigneron4, and Sarah J. Nelson1,5
1Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, United States, 2GE Healthcare, Menlo Park, CA, United States, 3Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, United States,4Department of Neurosurgery, University of California, San Francisco, San Francisco, CA, United States, 5Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, United States

We have designed a hyperpolarized 13C metabolic imaging experimental setup for the human brain and demonstrated its feasibility by acquiring in vivo data from a healthy non-human primate brain. 13C coils and pulse sequences were designed and tested using phantom and rats. Dynamic 13C data acquired from a healthy non-human primate brain showed excellent detection of pyruvate and lactate in brain. The metabolite conversion kinetics showed distinctive characteristics between the brain and its surrounding tissues. These results suggest that this technique may provide a unique way to investigate in vivo metabolism in patients with brain tumors.

3908.   26 Non-Invasive Identification of Functional Brown Adipose Tissue in Rodents Using Hyperpolarized 13C Imaging
Angus Z. Lau1,2, Albert P. Chen3, Michelle Ladouceur-Wodzak1, Krishna S. Nayak4, and Charles H. Cunningham1,2
1Imaging Research, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada, 2Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada, 3GE Healthcare, Toronto, Ontario, Canada, 4Department of Electrical Engineering, University of Southern California, Los Angeles, California, United States

The recent identification of functional brown adipose tissue (BAT) in humans has implications for the treatment of obesity. In this study, dynamic, spatially resolved hyperpolarized 13C imaging was used to non-invasively identify functional BAT in vivo in a rodent model. BAT was activated using intraperitoneal injection of norepinephrine and detected following infusion of pre-polarized 13C pyruvate. Increases in 13C bicarbonate (3.7-fold) and 13C lactate (3.5-fold) signal in the interscapular region correspond to a known rodent BAT deposit. The radiation-free nature of this imaging exam may potentially facilitate trials of therapeutics targeting BAT activation in humans.

3909.   27 Magnetic Resonance Imaging of Tumor Glycolysis Using Hyperpolarized 13C-Labelled Glucose
Tiago B. Rodrigues1, Eva M. Serrao1, Brett W.C. Kennedy1, De-En Hu1, Kevin M. Brindle1, and Mikko I. Kettunen1
1Biochemistry/CRUK, University of Cambridge, Cambridge, United Kingdom

Tumor cells frequently display high rates of aerobic glycolysis, resulting in increased lactate production and correlating with a poor prognosis and increased tumor aggressiveness and metatasis. We show here that hyperpolarized [U-2H, U-13C]glucose allows real-time monitoring of tumor glycolysis in vivo, through the production of hyperpolarized [U-13C]lactate, and that this flux is substantially reduced in murine EL4 lymphoma tumors by 24 h after etoposide treatment. Although the sensitivity of MR detection of hyperpolarized [U-2H, U-13C]glucose is much lower than PET detection of FDG, it has some significant potential advantages for detecting tumor treatment response.

3910.   28 Mapping Changes in Lactate-To-Pyruvate Signal Ratio Using Hyperpolarized 13C-Pyruvate in Early Radiation Induced Lung Injury Post Conformal Radiotherapy of the Lung
Kundan Thind1,2, Elaine Hegarty1, Albert P. Chen3, Heeseung Lim1,2, Francisco Martinez1, Michael Jensen2, Eugene Wong1,4, Timothy J. Scholl1, and Giles E. Santyr1,5
1Robarts Research Institute, Western University, London, ON, Canada, 2Dept. of Medical Biophysics, Western University, London, ON, Canada, 3GE Healthcare, Toronto, ON, Canada, 4Dept. of Physics and Astronomy, Western University, London, ON, Canada, 5Dept. of Medical Imaging, Western University, London, ON, Canada

Sprague Dawley rats were irradiated using conformal radiotherapy to lower-medial right lung (18.5 Gy) to induce RILI (Radiation Induced Lung Injury). Hyperpolarized 13C-pyruvate was injected and regional lactate-to-pyruvate signal ratio was quantified day 10 and 15 (early RILI) post radiotherapy. Statistically significant increase in lactate-to-pyruvate signal ratio was observed in both left lung and right lung of irradiated animals compared to age matched healthy animals at day 10 and day 15. Onset of inflammation during early RILI was confirmed using histology. Lack of systemic spread of injury was confirmed by measuring blood lactate concentration.

3911.   29 Investigation of Substrate Dose on Rat Cardiac Metabolism in Vivo Using MRS of Hyperpolarized [2-13C]pyruvate
Sonal Josan1,2, Jae Mo Park2, Yi-Fen Yen2, Ralph Hurd3, Adolf Pfefferbaum1,2, Daniel Spielman2, and Dirk Mayer1,2
1SRI International, 2Stanford University, 3GE Healthcare

Hyperpolarized [1-13C]-pyruvate MRS has been used to measure changes in cardiac PDH flux via measurement of 13C-bicarbonate, but may not reflect tricarboxylic acid (TCA) cycle activity. This work investigates the metabolic fate of the corresponding acetyl-CoA produced using [2-13C]-pyruvate to track the 13C label into glutamate and acetyl-carnitine, comparing the response to increased cardiac workload with dobutamine at two different pyruvate doses.

3912.   30 Hyperpolarised [1-13C]-Pyruvate Metabolism in Brown Fat
Lanette J. Friesen-Waldner1,2, Trevor P. Wade1,2, Curtis N. Wiens3, Kundan Thind1,2, Jacqueline K. Harris1, Kevin J. Sinclair1, Colin M. McCurdy1, Albert P. Chen4, Nica M. Borradaile5, and Charles A. McKenzie1,2
1Department of Medical Biophysics, University of Western Ontario, London, Ontario, Canada, 2Imaging Research Labs, Robarts Research Institute, London, Ontario, Canada, 3Department of Physics and Astronomy, University of Western Ontario, London, Ontario, Canada, 4GE Healthcare, Toronto, Ontario, Canada, 5Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada

Brown fat is more metabolically active than white fat. The purpose of this study was to detect metabolism in brown fat using hyperpolarised 13C MRS and CSI. 2D CSI of hyperpolarised [1-13C]pyruvate in the subscapular fat pad of mice showed more metabolism to lactate in brown fat than white fat. The ratio of lactate to total carbon was 53% in brown fat, and 22% in white fat. These results suggest that hyperpolarised [1-13C]pyruvate MRS and CSI can be used to differentiate the metabolic activity of brown fat from white fat.

3913.   31 Towards a More Quantitative Physiological Analysis: Comprehensive Kinetic Modeling of Pyruvate Metabolism in Tumors Via Co-Injection of Hyperpolarized 13C Pyruvate and Urea in Combination with Measurement of Arterial Input Functions
Samira Kazan1, Steven Reynolds2, Tooba Alizadeh1, Adriana Bucur2, Aneurin Kennerley3, Vincent Cunningham4, Martyn Paley2, and Gillian M. Tozer1
1CR-UK/YCR Sheffield Cancer Research Centre, University of Sheffield, Sheffield, South Yorkshire, United Kingdom, 2Academic Unit of Radiology, University of Sheffield, Sheffield, South Yorkshire, United Kingdom, 3Signal Processing in Neuroimaging and Systems Neuroscience, University of Sheffield, Sheffield, South Yorkshire, United Kingdom, 4Aberdeen Biomedical Imaging Centre, University of Aberdeen, Aberdeen, Scotland, United Kingdom

Mathematical models are required to estimate kinetic parameters of [1-13C] pyruvate-lactate interconversion from magnetic resonance spectroscopy data. It has been shown previously that the use of a measured arterial input function provides a robust and more comprehensive analysis of the kinetics compared to using a hypothetical box-car input function. A measured AIF reduces the number of free parameters for fitting and provides physiologically meaningful values not only for the rate constant of conversion of pyruvate to lactate, but also for clearance of pyruvate from the blood to the tissue. This parameter would be of particular relevance if blood flow effects were of interest in a study. Urea has been used previously as a perfusion marker to track the perfusion of pyruvate to the site of interest. In this study, by simultaneous injection of hyperpolarized 13C pyruvate and urea we measured both AIFs in order to compare the clearance/perfusion rates obtained using both methods at a tumor site.

3914.   32 Metabolic Profiling of Experimental Tumors Using Hyperpolarized [1-13C] Pyruvate: Evaluating Cell Type Specificity and Effects of Tumor Environment.
Georgios Batsios1, Divya Vats1, Catherine Germanier1, Michael Batel2, Marcin Krajewski1, and Markus Rudin1,3
1Institute for Biomedical Engineering, ETH and University of Zurich, Zurich, Switzerland, 2Laboratory of Physical Chemistry, ETH Zurich, Zurich, Switzerland, 3Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland

Hyperpolarized 13C magnetic resonance spectroscopy and imaging is a rapidly expanding field with many applications, particularly in the field of cancer. In this study we compare the lactate dehydrogenase (LDH) activity by measuring the conversion of pyruvate to lactate using same type of tumor cells growing at different implantation sites and different genetic background mice and using different tumor cell lines. We show that the pyruvate to lactate conversion depends mostly on the tumor type and not on the tumor environment. This indicates that the pyruvate processing through the LDH reaction reflects an intrinsic property of the tumor cell line.

3915.   33 Comparison of Tumor Perfusion Measured by Hyperpolarized 13C Urea with DCE MR Imaging Prior to and Following Radiation Therapy
Vickie Zhang1,2, Robert A. Bok3, Jessie Lee2, Subramaniam Sukumar1, Adam Cunha4, I-Chow Hsu4, Jean Pouliot4, Daniel B. Vigneron1,2, and John Kurhanewicz1,2
1Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California, United States, 2Graduate Program in Bioengineering, University of California, San Francisco & University of California, Berkeley, Berkeley, California, United States, 3Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California, United States, 4Department of Radiation Oncology, University of California, San Francisco, San Francisco, California, United States

Dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) has shown great clinical potential for assessing prostate cancer presence and aggressiveness prior to and after radiation therapy. Co-polarization of 13C pyruvate and urea also allows the simultaneous assessment of tumor perfusion and metabolism in a single MR acquisition (3,4). However, whether hyperpolarized 13C urea provides the same information as DCE MRI remains to be answered. This study investigated tumor perfusion prior to therapy and following radiation therapy in a transgenic murine model of prostate cancer using both HP 13C urea and DCE-MRI.

3916.   34 Reproducibility of 13C Magnetic Resonance Spectroscopy Measurements with Hyperpolarized [1-13C]pyruvate  -permission withheld
Eva M. Serrao1, Tiago B. Rodrigues1, Mikko I. Kettunen1, Ferdia A. Gallagher1, Brett Kennedy2, De-En Hu3, Keith Burling4, Joan Boren1, Helen Sladen1, and Kevin M. Brindle3
1Cambridge Research Institute CRUK, Cambridge, Cambridge, United Kingdom, 2Biochemistry, Cambridge University, Cambridge, Cambridge, United Kingdom, 3University of Cambridge, Cambridge, Cambridge, United Kingdom, 4Clinical Biochemistry, Addenbrook’s Hospital, Cambridge, Cambridge, United Kingdom

Hyperpolarized [1-13C]pyruvate has shown great promise for clinical oncology, particularly in the assessment of early response to treatment, and has also been the only hyperpolarized substrate to be used in humans. Determination of its reproducibility as a probe and the factors that affect reproducibility are important in order to understand if changes in its metabolism reflect real effects of therapy or changes in mouse physiology. We show that hyperpolarized[1-13C]pyruvate is a reproducible probe, showing relatively little variability when injected into fasted mice, suggesting that the fasted state may be more optimal for performing this technique in humans.

3917.   35 Optimized Sampling of Metabolically Labeled [2-13C]Lactate Following Injection of Hyperpolarized [2-13C]Pyruvate
Ralph Hurd1, Sonal Josan2,3, Jae Mo Park2,4, Yi Fen Yen2, Dirk Mayer2,3, and Daniel Spielman2,4
1GE Healthcare, Menlo Park, CA, United States, 2Radiology, Stanford University, Stanford, CA, United States, 3Neuroscience Program, SRI International, Menlo Park, CA, United States, 4Electrical Engineering, Stanford University, Stanford, CA, United States

With the increased use of hyperpolarized [2-13C]pyruvate in metabolic spectroscopy and imaging, there is an emerging need for optimized sampling of the metabolically labeled [2-13C]lactate. Toward that goal, the T1 of [1-13C]lactate was measured in vivo and used to calculate optimum flip angles for time-resolved spectroscopic data collection. An equimolar mixture of 40 mM [1-13C]pyruvate and 40 mM [2-13C]pyruvate was used to compare the apparent in vivo T1’s and to optimize the time-resolved sampling of [2-13C]lactate with [1-13C]lactate.

3918.   36 Evaluation of Renal Metabolic Response to Partial Ureteral Obstruction with Hyperpolarized 13C MRI
David J. Niles1, Jeremy W. Gordon2, Gengwen Huang3, Kevin M. Johnson1, Arjang Djamali4, and Sean B. Fain1,5
1Medical Physics, University of Wisconsin, Madison, WI, United States, 2Medical Physics, University of Wisconsin-Madison, Madison, WI, United States,3Surgery, University of Wisconsin, Madison, WI, United States, 4Medicine, University of Wisconsin, Madison, WI, United States, 5Radiology, University of Wisconsin, Madison, WI, United States

Congenital obstructive nephropathy is the most common cause of end-stage renal disease in children, and there is a need to improve tools for early diagnosis. In this study we used hyperpolarized 13C MRI to longitudinally and non-invasively assess the hemodynamic and metabolic changes in the kidney following partial unilateral ureteral obstruction. We observed reduced blood flow to the obstructed kidney and a preferential shift toward glycolysis in both kidneys. Our results may contribute to the understanding of the pathogenesis of obstructive nephropathy and to the development of improved approaches for clinical assessment.

3919.   37 Hyperpolarised 13C MRS on a 3T Clinical Platform: Kinetic Modelling of Pyruvate-Lactate Exchange Provides a Sensitive Measure of Response to Dichloroacetate in HT29 Xenografts
Deborah K. Hill1, Jessica K.R. Boult1, Rafal Panek1, Harold G. Parkes1, Matthew R. Orton1, Anne-Christine L.F. Wong Te Fong1, Maysam Jafar1, Simon P. Robinson1, Martin O. Leach1, Thomas R. Eykyn1,2, and Yuen-Li Chung1
1CR-UK and EPSRC Cancer Imaging Centre, The Institute of Cancer Research and Royal Marsden NHS Trust, Sutton, Surrey, United Kingdom, 2Division of Imaging Sciences and Biomedical Engineering, Kings College London, St Thomas Hospital, London, United Kingdom

Clinical MR platforms offer superior hardware advances, larger available field of view and clinically relevant field strengths. The lower field strengths are particularly advantageous for Dynamic Nuclear Polarisation studies, where hyperpolarised signals decay more slowly, increasing the time available for data acquisition. In this study we have developed and acquired apparent hyperpolarised [1-13C]pyruvate-[1-13C]lactate exchange rates from subcutaneous xenografts in mice on a 3T clinical platform. Full kinetic modelling provided a sensitive assay to detect significant treatment response induced by the PDK inhibitor, dichloroacetate, which exemplifies this technique as a superior analysis method when handling data from small animal cohorts.

3920.   38 Preliminary Study of Hypoxic Ischemic Rat Pup Model Using Hyperpolarized 13C Spectroscopy
Duan Xu1, Zinaida Vexler2, Subramaniam Sukumar1, Robert A. Bok1, John Kurhanewicz1, and Xiaoliang Zhang1
1Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, United States, 2Department of Neurology, University of California San Francisco, San Francisco, CA, United States

Hypoxic-ischemic injury occurs in approximately 25,000 live births in the US every year. Injuries evolve over days to weeks, with some neurons rapidly undergoing necrotic cell death while others suffer delayed impairment in energy metabolism and die more slowly. Animal studies involving rats have shown that average diffusivity is reduced on diffusion weighted imaging, lactate is increased on proton MRS, and ratio of phosphocreatine (PCr) to inorganic phosphate (Pi) is increased during hypoxic-ischemic insult. This preliminary study is designed to test the ability of using hyperpolarized 13C metabolic imaging to assess tissue metabolism after ischemic insult.

3921.   39 Ratio of Lactate-To-Pyruvate Apparent Diffusion Coefficients Is an Indicator of Necrosis in Tumor Cells
Franz Schilling1,2, Stephan Düwel1,2, Ulrich Köllisch1,3, Markus Durst1,3, Steffen J. Glaser2, Axel Haase1, Marion I. Menzel3, and Angela M. Otto1
1Institute of Medical Engineering, Technische Universität München, Garching, Germany, 2Department of Chemistry, Technische Universität München, Garching, Germany, 3GE Global Research, Garching, Germany

Using a modified pulsed gradient spin echo sequence, we analyzed MCF-7 tumor cell spheroids under detrimental conditions by measuring ADCs of hyperpolarized 13C-metabolites. Such conditions were given by treating cells with Triton X-100 to gradually permeabilize the cell membrane to mimic a necrotic process. The ADClac/ADCpyr ratio increased with time. Fluorescent staining showed that an increase of the ADClac/ADCpyr ratio correlates to an increase in the fraction of dead cells. As a new technique, 13C-metabolite ADCs are indicators of necrosis in tumor cells potentially making them useful tools for monitoring the pathological state of tumors in-vivo.

3922.   40 Alternating Acquisition for Quantification of Pyruvate Metabolism in Hyperpolarized 13C Studies
Seungwook Yang1, Joonsung Lee1, Yoonho Nam1, Eunhae Joe1, Jae-Eun Suk2, Ho-Taek Song2, and Dong-Hyun Kim1
1Electrical and Electronic Engineering, Yonsei University, Seoul, Korea, 2Department of Radiology, College of Medicine, Yonsei University, Seoul, Korea

A method for accurate quantification of hyperpolarized pyruvate and the product lactate in in vitro experiment is described. By using a narrow-band RF excitation pulse with alternating acquisition at every TR, metabolic product can be selectively excited with a higher flip angle for increased SNR while the hyperpolarized magnetization of the substrate can be minimally perturbed with a low flip angle. Also, baseline signals from neighboring resonances can be suppressed to accurately quantify the metabolism kinetics. Furthermore, with the modified version of the two-site exchange model that is also presented, calculation of the rate constants associated with the conversion is also possible.

3923.   41 3D Whole-Heart Cardiac Metabolic Imaging with [1-13C]pyruvate Using IDEAL Spiral CSI
Ulrich Köllisch1, Rolf F. Schulte2, Markus Durst1, Jan Henrik Ardenkjaer-Larsen3, Francesca Frijia4, Luca Menichetti5, Massimo Lombardi4, Axel Haase1, and Florian Wiesinger2
1Institute of Medical Engineering, Technische Universität München, Garching, Germany, 2GE Global Research, Garching, Germany, 3GE Healthcare, Brøndby, Denmark, 4Fondazione CNR-Regione Toscana G.Monasterio, Pisa, Italy, 5Institute of Clinical Physiology of CNR, Pisa, Italy

Metabolic imaging with hyperpolarized [1-13C]pyruvate has high potential for examination of myocardial viability. In this work a 3D cardiac sequence for imaging the metabolism of hyperpolarized [1-13C]pyruvate over the whole porcine heart is presented. Therefore a multiband pulse was implemented using the polarization very efficiently. The results demonstrate, that the presented acquisition scheme is feasible for [1-13C]pyruvate metabolic imaging by accurately depicting pyruvate lactate and bicarbonate distributions over the entire left ventricle.

3924.   42 Apparent Rate Constant Mapping Using Hyperpolarized [1-13C]Pyruvate
Oleksandr Khegai1,2, Rolf F. Schulte2, Martin A. Janich2, Marion I. Menzel2, Eliane Farrell3, Angela M. Otto4, Jan Henrik Ardenkjaer-Larsen5,6, Steffen J. Glaser1, Axel Haase4, Markus Schwaiger3, and Florian Wiesinger2
1Department of Chemistry, Technische Universität München, Munich, Germany, 2GE Global Research, Munich, Germany, 3Institute of Nuclear Medicine, Technische Universität München, Munich, Germany, 4Institute of Medical Engineering, Technische Universität München, Munich, Germany, 5MST-ASL MR, GE Healthcare, Copenhagen, Denmark, 6Department of Electrical Engineering, Technical University of Denmark, Copenhagen, Denmark

Hyperpolarization of [1-13C]pyruvate in solution enables dynamic imaging of pyruvate metabolism using MRS methods. In this work, we present methods for the quantification of dynamic hyperpolarized 13C signals, with an emphasis on spatially resolved apparent rate constant mapping. This novel type of quantitative contrast comprehensively visualizes metabolic activity of underlying tissues and organs. In comparison to individual metabolite images, apparent rate constant maps emphasize metabolically active tissues and suppress regions of high perfusion but low conversion (e.g. blood vessels). Based on high metabolic activity of the tumor, its location can be clearly identified from the apparent rate constant maps.

3925.   43 A Relationship Between Hyperpolarized 13C Pyruvate Metabolism and Tumour Volume in a Chronic Study of Oral Dichloroacetate Treatment of P22 Bearing BDIX Rat
Steven Reynolds1, Tooba Alizadeh2, Becky Bibby2, Matthew Fisher2, Adriana Bucur1, Samira Kazan2, Martyn Paley1, and Gillian M. Tozer2
1Academic Radiology, University of Sheffield, Sheffield, South Yorkshire, United Kingdom, 2Department of Oncology, University of Sheffield, Sheffield, South Yorkshire, United Kingdom

There has been recent interest in using hyperpolarised 13C1-pyruvate for studying cancer metabolism. The methodology has been used to study the effect of dichloroacetate (DCA) on tumour metabolism which disrupts pyruvate dehydrogenase kinase (PDK). However, these studies have been acute treatments up to 24h. In this study we examine the effect of chronic oral DCA dosing on P22 bearing BDIX rats over 17 days. The data showed a strong negative linear correlation between conversion of pyruvate to lactate and tumour volume and that there was a significant difference in the slope of the correlation between control and DCA treated rats.

3926.   44 Detecting and Characterizing Therapeutic Response to Radio- & Chemotherapies with Hyperpolarized [1-13C] Pyruvate in Rat Glioma Model
Heeseung Lim1, Kundan Thind1, Timothy Pok Chi Yeung1,2, Francisco M. Martinez-Santiesteban1, and Timothy J. Scholl1,3
1Medical Biophysics, Western University, London, Ontario, Canada, 2London Regional Cancer Program, LHSC, London, Ontario, Canada, 3Imaging Research Laboratories, Robarts Research Institute, Western University, London, Ontario, Canada

This study monitors the effects of radio- and chemotherapy on glioblastoma multiforme in a rat model through chemical-shift imaging of hyperpolarized [1-13C]pyruvate. Preliminary results suggest that both radiotherapy and chemotherapy alter tumor metabolism (determined by the observed lactate-to-pyruvate ratio) as early as 2 days after treatment. Seven days after treatment, the lactate-to-pyruvate ratio in tumors was similar to healthy tissue. Response to therapy was more immediate for tumours receiving radiotherapy. Further animal studies will better quantify the time course of therapeutic response and to investigate the effects of combined therapies.

3927.   45 Hyperpolarization of Biologically Relevant Compounds Which Are Important in the GABA Metabolism
Markus Plaumann1, Ute Bommerich2, Thomas Trantzschel1, Denise Lego2, Sonja Dillenberger3, Joachim Bargon4, Gerd Buntkowsky3, and Johannes Bernarding5
1Department of Biometry and Medical Informatics, Otto-von-Guericke-University Magdeburg, Magdeburg, Saxony-Anhalt, Germany, 2Special Lab Non-Invasive Brain Imaging, Leibniz Institute for Neurobiology, Magdeburg, Saxony-Anhalt, Germany, 3Eduard-Zintl-Institute for Inorganic Chemistry, Technical University Darmstadt, Darmstadt, Hesse, Germany, 4Inst. of Physical and Theoretical Chemistry, University Bonn, Bonn, North Rhine-Westphalia, Germany, 5Department of Biometry and Medical Informatics, Otto von Guericke University, Magdeburg, Saxony-Anhalt, Germany

GABA is one of the most important inhibitory neurotransmitter in the central nervous system. Knowledge of changes in the GABA metabolism can help to understand different disease pattern. Therefore, the ParaHydrogen Induced Polarisation can be used to enhance signals for MR studies. In this contribution we described a new method to hydrogenate unsaturated organic amines in aqueous solution and present first spectra of hyperpolarized vigabatrin, allylglycine and GABA. All spectra were detected at 7 T. This new approach opens the way to hyperpolarize further biologically important molecules which were inaccessible to PHIP until now, like amino acids and peptides.

3928.   46 Using [1-13C]lactic Acid for Hyperpolarized 13C Cardiac Studies
Albert P. Chen1 and Charles H. Cunningham2,3
1GE Healthcare, Toronto, ON, Canada, 2Imaging Research, Sunnybrook Health Sciences Centre, Toronto, ON, Canada, 3Dept. of Medical Biophysics, University of Toronto, Toronto, ON, Canada

Preparation of hyperpolarized [1-13C]lactate in solution was demonstrated in this study using neat [1-13C]lactic acid as the DNP sample. Hyperpolarized [1-13C]lactate was also compared to [1-13C]pyruvate for in vivo investigation of cardiac PDH flux at the same dose in the same subjects. Hyperpolarized [1-13C]lactate may provide non-invasively assessment of cardiac PDH flux with minimal perturbation of the enzymes involved in this metabolic pathway.

3929.   47 Towards Real-Time Metabolic and Molecular Imaging of Cancer by Three Different Modalities of Hyperpolarization
Niki Zacharias1, Maja Cassidy2, Mark Lingwood3, Napapon Sailasuta4, Nicholas Whiting1, Jingzhe Hu5,6, Song-I Han3, Brian Ross4, Charles Marcus2,7, and Pratip Bhattacharya8
1Experimental Diagnostic Imaging, The University of Texas, M.D. Anderson Cancer Center, Houston, TX, United States, 2Harvard University, Cambridge, MA, United States, 3Department of Chemistry and Biochemistry, University of California, Santa Barbara, Santa Barbara, CA, United States, 4Enhanced MR Laboratory, Huntington Medical Research Institutes, Pasadena, CA, United States, 5Experimental Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, United States, 6Bioengineering Department, Rice University, Houston, TX, United States, 7University of Copenhagen, Copenhagen, Denmark, 8Experimental Diagnostic Imaging, University of Texas, Houston, TX, United States

Hyperpolarized magnetic resonance is a non-toxic, non-radioactive method for assessing tissue metabolism and other physiologic properties. Hyperpolarization allows for over 10,000-fold signal enhancement relative to conventional magnetic resonance imaging (MRI) or spectroscopy (MRS). My laboratory has worked on three different modalities of hyperpolarization, both on technique development as well as advancing novel in vivo applications. The research described here is focused on the different in vivo applications of Parahydrogen Induced Polarization (PHIP) (and subsequent transfer to 13C), continuous flow Dynamic Nuclear Polarization (DNP) of water (1H), and long lived DNP hyperpolarized signal of Silicon nanoparticles (29Si) as molecular imaging agents.

3930.   48 Exploring Detection Limits of Cardiac Ischemia Using Dynamic Imaging of Hyperpolarized 13C Pyruvate
Erika Mariotti1, Kilian Weiss2, Sebastian Kozerke1,2, and Thomas R. Eykyn1,3
1Division of Imaging Sciences and Biomedical Engineering, King's College London, London, United Kingdom, 2Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland, 3CRUK and EPSRC Cancer Imaging Centre, Royal Marsden NHS Trust, The Institute of Cancer Research, Sutton, Surrey, United Kingdom

Using dynamic spatial-spectral imaging techniques,heterogeneity of myocardial metabolism can be studied and ischemic regions identified. Kinetic information on the underlying metabolic activities can be obtained by fitting the metabolite time series with kinetic models. In this work, we considered the detection limit of hyperpolarized 13C metabolic imaging in identifying local myocardial ischemia depending on ischemic transmurality, SNR and image resolution. A numerical signal model was implemented to simulate in vivo hyperpolarized 13C dynamic images with a range of SNRs and spatial resolutions and a kinetic model of the conversion of pyruvate to bicarbonate was used to extract enzymatic reaction rates


Wednesday, 24 April 2013 (11:00-12:00) Exhibition Hall
Hyperpolarization: New Methods, Probes, & Applications

  Computer #  
3931.   25 Frequency Band-Selective Spiral CSI: Application to Imaging Cardiac Metabolism with Hyperpolarized [2-13C]pyruvate
Sonal Josan1,2, Ralph Hurd3, Yi-Fen Yen2, Adolf Pfefferbaum1,4, Daniel Spielman2, and Dirk Mayer1,2
1SRI International, Menlo Park, CA, United States, 2Radiology, Stanford University, Stanford, CA, United States, 3GE Healthcare, 4Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, United States

Spectroscopic imaging with hyperpolarized 13C substrates has been widely used to measure metabolic processes in real time in vivo. There has been growing interest recently in using hyperpolarized [2-13C]pyruvate, to follow the 13C label into metabolic products including glutamate (in exchange with α-ketoglutarate in the TCA cycle), citrate, acetyl-carnitine and acetoacetate as well as lactate and alanine. CSI with [2-13C]Pyr is challenging given the wide spectral dispersion of the resonances. This work uses a spectrally selective excitation to perform 3D CSI of spectral sub-bands containing metabolites of interest. Dynamic data is acquired from multiple sub-bands alternately in vivo in rat heart.

3932.   26 Quantitative Characterization of a Catalyzed PHIP Reaction
Shawn Wagner1,2, Jose Agraz3, and Debiao Li1,2
1Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, United States, 2Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States, 3Bioengineering, UCLA, Los Angeles, California, United States

Hyperpolarization by field cycling and RF transfer utilizing parahydrogen requires a fast addition of hydrogen to preserve the spin alignment of the parahydrogen. To effectively utilize PHIP to produce the highest hyperpolarization, characterization of the reaction kinetics is required. The purpose of this research is to demonstrate how to systematically characterize the reaction kinetics to calibrate and evaluate instrument performance using a common PHIP standard, 2-hydroxyethyl acrylate (HEA). We demonstrate for HEA, catalyst concentration has the greatest contribution to reaction rate.

3933.   27 Branched-Chain Amino Acid Metabolism in Prostate Cancer: Hyperpolarized [1-13C]-Ketoisocaproate as a Novel Molecular Probe
Kelvin Billingsley1, Sonal Josan1,2, Jae Mo Park1,3, Yi-Fen Yen1, Ralph Hurd4, Dirk Mayer1,2, Dwight G. Nishimura3, James Brooks5, and Daniel Spielman1,3
1Department of Radiology, Stanford University, Stanford, CA, United States, 2Neuroscience Program, SRI International, Menlo Park, CA, United States,3Department of Electrical Engineering, Stanford University, Stanford, CA, United States, 4Applied Science Laboratory, GE Healthcare, Menlo Park, CA, United States, 5Department of Urology, Stanford University, Stanford, CA, United States

This work investigates a new biomarker, branched-chain amino transaminase (BCAT) activity, in prostate cancer. In addition, the feasibility of imaging the metabolism of hyperpolarized [1-13C]-KIC in human prostate cancer cell line-derived xenografts is explored.

3934.   28 Cerebral Perfusion Imaging with Hyperpolarized 13C-Tert-Butanol at 9.4 Tesla: Long Relaxation at High Fields
Leo L. Tsai1, Xiaoen Wang1, Gopal Varma1, David C. Alsop1, and Aaron K. Grant1
1Department of Radiology, Beth Israel Deaconess Medical Center, Boston, MA, United States

Hyperpolarized 13C-tert-butanol is a freely diffusible agent which allows for high SNR cerebral perfusion imaging. At 9.4 Tesla, we demonstrate relatively long in-vivo cerebral relaxation times (T2 = 0.71 ± 0.03 s and T1 = 78 ± 26 s), demonstrating feasibility for high-field imaging and spectroscopy with this agent.

3935.   29 Hyperpolarized [1,4-13C]-Diethylsuccinate: A Potential DNP Substrate for in vivo Metabolic Imaging
Kelvin Billingsley1, Sonal Josan1,2, Jae Mo Park1,3, Sui Seng Tee1, Yi-Fen Yen1, Ralph Hurd4, Dirk Mayer1,2, and Daniel Spielman1,3
1Department of Radiology, Stanford University, Stanford, CA, United States, 2Neuroscience Program, SRI International, Menlo Park, CA, United States,3Department of Electrical Engineering, Stanford University, Stanford, CA, United States, 4Applied Science Laboratory, GE Healthcare, Menlo Park, CA, United States

This work explores the synthesis, development and application of [1,4-13C]-diethylsuccinate ([13C]-DES) via DNP polarization. These studies provide a reassignment of the metabolites observed in previous reports and a reexamination of the role of the TCA cycle in processing [13C]-labeled diethylsuccinate probes.

3936.   30 Simultaneous Imaging of 13C Metabolism and 1H Structure for Improved Co-Registration and Off-Resonance Correction
Jeremy W. Gordon1, David J. Niles1, Kevin M. Johnson1, Matthew Smith1, Krishna N. Kurpad1, Eric Peterson1, and Sean B. Fain1,2
1Medical Physics, University of Wisconsin-Madison, Madison, WI, United States, 2Radiology, University of Wisconsin-Madison, Madison, WI, United States

Proton data can be used to aid in the reconstruction of hyperpolarized 13C metabolites, but motion between scans diminishes reconstruction fidelity. This works seeks to improve 13C reconstruction by utilizing simultaneously acquired 1H data, which are inherently registered both spatially and temporally. A simultaneous acquisition scheme was implemented in spiral and Cartesian sequences to demonstrate the feasibility and utility of concurrently acquired 1H data. Metabolite images show excellent registration with the underlying anatomy, while phase related artifacts were mitigated when 13C data was reconstructed with simultaneously acquired field maps, as compared to a field map acquired prior to simultaneous imaging.

3937.   31 Hyperpolarized Singlet Lifetimes of Pyruvate in Human Blood and in Mouse
Irene Marco-Rius1,2, Michael C. D. Tayler3, Mikko I. Kettunen1,2, Eva M. Serrao1,2, Timothy J. Larkin1,2, Tiago B. Rodrigues2, Kerstin N. Timm1,2, Giuseppe Pileio3, Malcolm H. Levitt3, and Kevin M. Brindle1,2
1Biochemistry, University of Cambridge, Cambridge, Cambridgeshire, United Kingdom, 2Cancer Research UK, Cambridge, Cambridgeshire, United Kingdom,3Chemistry, University of Southampton, Southampton, Hampshire, United Kingdom

Hyperpolarized NMR is a promising technique for non-invasive imaging of tissue metabolism in vivo. However, the range of reactions that can be investigated is limited by the fast T1-dependent decay of the nuclear spin order. In metabolites with coupled nuclear spin-1/2 pairs, polarization may be maintained for a longer time by exploiting the non-magnetic singlet (spin-0) state of the pair. We show here that the 13C singlet lifetime of [1,2-13C2]pyruvate is longer than T1 in human blood and in a mouse in vivo at low field, albeit shorter than its T1 in high magnetic field.

3938.   32 Fast 3D Spiral Chemical Shift Imaging of Mitochondrial Metabolism in Brain with C6 Glioma Using Hyperpolarized [2-13C]Pyruvate
Jae Mo Park1,2, Sonal Josan1,3, Taichang Jang4, Milton Merchant4, Ronald D. Watkins1, Yi-Fen Yen1, Ralph Hurd5, Lawrence Recht4, Daniel Spielman1,2, and Dirk Mayer1,3
1Radiology, Stanford University, Stanford, California, United States, 2Electrical Engineering, Stanford University, Stanford, California, United States,3Neuroscience Program, SRI International, Menlo Park, California, United States, 4Neurology and Neurological Science, Stanford University, Stanford, California, United States, 5Applied Science Laboratory, GE Healthcare, Menlo Park, California, United States

We developed a fast volumetric chemical shift imaging sequence for imaging of hyperpolarized [2-13C]Pyruvate and its products, without suffering chemical shift displacement artifact due to the large spectral dispersion of [2-13C]Pyruvate and its products, and applied it to measuring brain metabolism in healthy and C6 glioma-bearing rats.

3939.   33 Laplace Inversion for Kinetic Analysis of Hyperpolarized 13C Data Without a Priori Knowledge Using a Hybrid Maximum Entropy Method (MEM)/ Non-Linear Least Square (NLS)
Erika Mariotti1, Fiona Shaughnessy1, Rodolfo A. Medina1, Joel T. Dunn1, Richard Southworth1, and Thomas R. Eykyn1,2
1Division of Imaging Sciences and Biomedical Engineering, King's College London, London, United Kingdom, 2CRUK and EPSRC Cancer Imaging Centre, Royal Marsden NHS Trust, The Institute of Cancer Research, Sutton, Surrey, United Kingdom

To obtain information on the underlying metabolic activities, hyperpolarized data are usually fit using kinetic models to derive rates. In this work, we show the feasibility of analysing hyperpolarized data without prior assumptions of a model and, at the same time, overcoming the “multiple local minimum” problem by applying a hybrid Maximum-Entropy/NonLinear-Least-Squares (MEM/NLS) method4 to hyperpolarized 13C data both in vitro in whole blood and ex vivo in the isolated rat heart.

3940.   34 Hyperpolarization of Drugs Using Signal Amplification by Reversible Exchange (SABRE)
Haifeng Zeng1, Jiadi Xu2, Joseph Gillen1,2, Michael T. McMahon1,2, Dmitri Artemov1, Jean-Max Tyburn3, Joost Lohman4, Ryan Mewis5, Kevin Atkinson5, Simon Duckett5, and Peter C.M. van Zijl1,2
1Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States, 2F.M.Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, 3Bruker BioSpin GmbH, Silberstreifen, Rheinstetten, Germany, 4Bruker UK Limited, Banner Lane, Coventry, United Kingdom, 5Department of Chemistry, University of York, Heslington, York, United Kingdom

Here we investigated the possibility to use SABRE to polarize several drugs used daily in the clinic. These are isoniazid and pyrazinamide used for treating tuberculosis (TB) and temozolomide for treating brain tumors.

3941.   35 A Flexible Multi-Sample DNP System for Rapid Sequential Dissolutions
Marcin Krajewski1, Michael Batel2, Kilian Weiss1, Andreas Bjoern Joakim Sigfridsson1, Georgios Batsios1, Matthias Ernst2, and Sebastian Kozerke1
1Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland, 2Laboratory of Physical Chemistry, ETH Zurich, Zurich, Switzerland

A new DNP polarizer device suitable for laboratory or small animal imaging applications is be presented. In order to facilitate construction and operation of such a system, a greatly simplified design is introduced here permitting polarization of up to four samples for rapid sequential dissolution with less than 10 min latency in-between. Basic design criteria and performance measurements are presented.

3942.   36 Spectroscopically Selective Imaging of Hyperpolarized Pyruvate and Its Metabolites Using a Single-Echo Variable Phase Advance Method in Balanced SSFP
Gopal Varma1, Xiaoen Wang1, David C. Alsop1, Rupal Bhatt2, and Aaron K. Grant1
1Radiology, Division of MR Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States, 2Medicine, Beth Israel Deaconess Medical Center, Boston, MA, United States

Balanced steady-state free precession (bSSFP) is a fast, signal efficient sequence for imaging of hyperpolarized 13C. By exploiting the dependence of the bSSFP signal on the chemical shift, or, equivalently, the phase advance between successive RF excitation pulses, it is possible to extract chemical shift selective images of multiple metabolites. The method is illustrated in phantoms and for imaging of pyruvate and its metabolites in a mouse model of renal cell carcinoma.

3943.   37 An Extra-Mitochondrial Domain Rich in Carbonic Anhydrase Activity Improves Myocardial Energetics
Marie A. Schroeder1, Mohammad Ali1, Alzbeta Hulikova1, Claudiu T. Supuran2, Kieran Clarke1, Richard D. Vaughan-Jones1, Damian J. Tyler1, and Pawel Swietach1
1Physiology, Anatomy and Genetics, University of Oxford, Oxford, Oxon, United Kingdom, 2University of Florence, Florence, Italy

CO2 is produced in vast quantities by cardiac mitochondria and efficient means of its venting are required to support metabolism. A range of metabolic and physiological adaptations for improving energy provision has been identified1, yet little is known about mechanisms for improving CO2 venting. Carbonic anhydrases (CAs), expressed at various sites in ventricular cardiomyocytes, may affect mitochondrial CO2 clearance by catalyzing CO2 hydration (to H+ and HCO3−) and changing trans-membrane [CO2]-gradients for diffusion. In this study, we demonstrated that mitochondrial CO2 venting is facilitated by concentrating CA activity near (but not within) mitochondria, and that this distribution improves myocardial energetics.

3944.   38 Spectrally Interleaved Multi-Echo Sequence for Measurement of Hyperpolarized [1-13C]pyruvate Metabolism
Jae Mo Park1,2, Yi-Fen Yen1, Priti Balchandani1,3, Sonal Josan1,4, Ralph Hurd5, Dirk Mayer1,4, and Daniel Spielman1,2
1Radiology, Stanford University, Stanford, California, United States, 2Electrical Engineering, Stanford University, Stanford, California, United States, 3Radiology, Mount Sinai School of Medicine, New York, New York, United States, 4Neuroscience Program, SRI International, Menlo Park, California, United States, 5Applied Science Laboratory, GE Healthcare, Menlo Park, California, United States

We exploit the long T2 of [1-13C]-labeled pyruvate and metabolic products by developing a spectrally interleaved multi-echo sequence using spectral-spatial RF pulses to increase SNR of the labeled metabolites.

3945.   39 Optimal Control Singlet State Storage for Clinical MR Systems
Christoffer Laustsen1,2, Sean Bowen3, Mads Sloth Vinding4, Niels Christian Nielsen4, and Jan Henrik Ardenkjaer-larsen3,5
1The MR Research Centre, Aarhus University, Aarhus, Denmark, 2Danish Research Centre for Magnetic Resonance, Hvidovre Hospital, Hvidovre, Denmark,3Department of Electrical Engineering, Technical University of Denmark, Lyngby, Denmark, 4Center for Insoluble Protein Structures (inSPIN), Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Aarhs, Denmark, 5GE healthcare, Broendby, Denmark

Hyperpolarized compounds has so far been limited by the T1 decay of the magnetization. Recently the novel method magnetization-to-singlet order (M2S) and singlet order-to-magnetization (S2M), has been shown applicable on pre-clinical MRI systems, extending the hyperpolarized life time several orders of magnitude. However, several limitations are imposed by clinical MRI systems with typical hardware constraints such as low maximum B1 amplitude and lower static magnetic field B0. The large B1 and B0 inhomogenties combined with T2 relaxation impose severe limitations on the efficiency of the method. Here we show a possible solution via optimal control theory, finding pulses with maximum efficiency even under clinical conditions.

3946.   40 Filterable Free Radical Polarizing Agents for Dissolution DNP-NMR Spectroscopy
Lloyd L. Lumata1, Matthew E. Merritt1, Craig R. Malloy1, A. Dean Sherry1,2, Johan van Tol3, Likai Song3, and Zoltan Kovacs1
1Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, TX, United States, 2Department of Chemistry, University of Texas at Dallas, Richardson, TX, United States, 3National High Magnetic Field Laboratory, Florida State University, Tallahassee, FL, United States

We demonstrate the efficiency of stable free radicals BDPA, DPPH, and galvinoxyl as polarizing agents for dissolution dynamic nuclear polarization (DNP) NMR spectroscopy. Large NMR signal enhancements were achieved for biologically important labeled substrates such as [1-13C]pyruvic acid and [15N]choline. In addition, these hydrophobic free radicals can be easily filtered out in aqueous hyperpolarized liquids using a simple mechanical filtration process.

3947.   41 A 16 Channel Cardiac Array for Accelerated Hyperpolarised 13C Metabolic Imaging on Pigs at 3T
Titus Lanz1, Markus Durst2,3, Matthias Müller1, Francesca Frijia4, Giulio Govanetti5, Luca Menichetti5, Massimo Lombardi4, Jan Henrik Ardenkjaer-Larsen6,7, and Rolf F. Schulte2
1Rapid Biomedical, Rimpar, Germany, 2GE Global Research, Munich, Germany, 3Technical University Munich, Munich, Germany, 4Fondazione G. Monasterio CNR-Regione Toscana, Pisa, Italy, 5Institute of Clinical Physiology of CNR, Pisa, Italy, 6GE Healthcare, Copenhagen, Denmark, 7Danish Technical University, Copenhagen, Denmark

We show a setup for doing 13C imaging on hyperpolarised media in pigs on a clinical 3 T MR system. A 16 channel 13C Rx array is combined with a Tx birdcage, allowing the MR system's body coil for 1H imaging. Due to the low frequency the array is not sample noise dominated, but allows accelerated 13C imaging which is essential for efficient usage of the hyperpolarised magnetisation. First results of metabolic imaging on the pig heart are shown.

3948.   42 Projection Acquisitions for Dynamic Hyperpolarized 13C MRI
Marc S. Ramirez1, Jaehyuk Lee1, Vlad Sandulache2, Christopher M. Walker1, Yunyun Chen3, Stephen Y. Lai3, and James A. Bankson1
1Department of Imaging Physics, The University of Texas M.D. Anderson Cancer Center, Houston, TX, United States, 2Department of Otolaryngology Head and Neck Surgery, Baylor College of Medicine, Houston, TX, United States, 3Department of Head and Neck Surgery, The University of Texas M.D. Anderson Cancer Center, Houston, TX, United States

The use of multislice projection acquisitions for hyperpolarized 13C MRI is evaluated, where dynamic time courses and spatial images from multiple metabolites may be simultaneously derived from one acquisition. This strategy reduces the high preparation costs and injected tracer volume associated with separate spatial and dynamic hyperpolarized acquisitions. Projection acquisition strategies based on echo-planar spectroscopic imaging (EPSI) and multiband frequency encoding (MBFE) MRI are compared and used to extract vascular input functions and conversion kinetics of hyperpolarized pyruvate and lactate in mice bearing anaplastic thyroid tumors.

3949.   43 A Device for Accurate and Automated Injection of Hyperpolarization Substrate with Minimal Dead Time and Arbitrary Volumes
Steven Reynolds1, Adriana Bucur1, Michael Port2, Tooba Alizadeh3, Samira Kazan3, Gillian M. Tozer3, and Martyn Paley1
1Academic Radiology, University of Sheffield, Sheffield, South Yorkshire, United Kingdom, 2Biological Services Unit, University of Sheffield, Sheffield, South Yorkshire, United Kingdom, 3Department of Oncology, University of Sheffield, Sheffield, South Yorkshire, United Kingdom

Modelling of hyperpolarized pyruvate to lactate conversion can be improved upon with consistent and reliable injections using an automated system. We have improved upon our previously designed injector by using a completely MR compatible direct drive peristaltic pump with a stepper motor and microcontroller. The new injector allows faster injections, no syringe filling, and arbitrary injection volumes. We show excellent correlation between demand and delivered volumes in the range 0.100-10.00ml and faster delivery of hyperpolarized pyruvate into a test phantom.

3950.   44 Polarization Loss from Magnetic Field Noise
Shawn Wagner1,2, Jose Agraz3, Alexander Grunfeld4, and Debiao Li1,2
1Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, United States, 2Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States, 3Bioengineering, UCLA, Los Angeles, California, United States, 4Life Sciences, UCLA, Los Angeles, California, United States

Hyperpolarization by RF irradiation spin transfer utilizing parahydrogen requires low magnetic fields. These fields have been created with solenoids using current to determine the field strength. This abstract is intended to show how noise in the current results in magnet field noise, leading to sporadic loss of polarization in echo sequences. The loss in temporal refocusing is a crucial issue in the reliability of RF irradiation spin transfer PHIP hyperpolarization, since the last part of such sequences contains an echo period in the transverse plane.

3951.   45 Parallel Acquisition of Hyperpolarized 13C1 Pyruvate Metabolism: Multi-Chamber MR Compatible Bioreactor
Adriana Bucur1, Steven Reynolds1, Samira Kazan2, Tooba Alizadeh2, Michael Port3, Gillian M. Tozer2, and Martyn Paley1
1Academic Radiology, University of Sheffield, Sheffield, United Kingdom, 2Department of Oncology, University of Sheffield, Sheffield, United Kingdom, 3Biological Services Unit, University of Sheffield, Sheffield, United Kingdom

In vivo tumour models are the most relevant for comparison with human disease models. However, they are costly, time consuming and have ethical limitations. Additionally, hyperpolarisation experiments require long waits between injections. Using bioreactors provides useful information of cellular metabolism and response to treatment. We developed a multiple chamber MR compatible bioreactor to simultaneously acquire up to 4 datasets with identical hyperpolarised metabolite concentration and polarisation. The throughput increases by four times and consequently reduces the experimental time, by the efficient use of hyperpolarised PA in MR/DNP studies on cells, a possible important step in drugs effects investigation in animals.

3952.   46 Xenon DNP in Inhomogeneous Solid-State Mixtures: Elucidation of the Spin-Diffusion Bottleneck
Mehrdad Pourfathi1, Nicholas N. Kuzma1, Rajat Kumar Ghosh1, Stephen J. Kadlececk1, and Rahim Rizi1
1Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States

Dynamic Nuclear Polarization (DNP) of 129Xe lags far behind that of [1-13C]pyruvate under similar experimental conditions. Understanding the interplay between DNP, spin diffusion and nuclear relaxation at the microscopic scale requires theoretical modeling as well as experimental probes of the local DNP parameters. We use the recently reported measurements in micro-clustered 129Xe/1-propanol/trityl solid mixtures to validate our first-principles theory of the observed spin-diffusion bottleneck at the cluster boundaries. In our self-contained model, the factor of ~ 30 apparent drop in the local 129Xe polarization at the cluster boundary is obtained analytically across a thin “insulating” layer of the matrix immediately surrounding the cluster, in good agreement with the measurements. We estimate cluster size, intrinsic temperature, and T1 relaxation rates by fitting the model to the data. These findings have enabled us to increase the achievable 129Xe polarization from 5% to 21%.

3953.   47 Continuous Flow 1.5T In-Bore Overhauser DNP for 1H and 13C Hyperpolarization: Quantification of Polarization Build-Up to Optimize the MR-Imaging Efficiency
Maxim Terekhov1, Kathrin Gerz1, Jan Krummenacker2, Vasyl Denysenkov2, Thomas Prisner2, and Laura Maria Schreiber1
1Department of Radiology, Section of Medical Physics, Johannes Gutenberg University Medical Center Mainz, Mainz, Germany, 2Institute of Physical and Theoretical Chemistry, Center for Bimolecular Magnetic Resonance, Goethe-University Frankfurt-am-Main, Frankfurt-am-Main, Germany

Dynamic Nuclear Polarization is a technique to achieve the polarization of MRI agents over that at thermal equilibrium by microwave irradiation of electron spins. The liquid-state “Overhauser DNP” (ODNP) allows placing the polarizer core inside MRI magnet close to the imaging objects and delivery of hyperpolarized agent in continuous flow mode . The net efficiency of ODNP-polarizer is a complicated trade-off for which, to our knowledge, no theoretical model exists. We performed the study to establish a method of ODNP-magnetization build-up quantification in order to optimize the SNR of the MR-images obtained with hyperpolarization of 1H and 13C nuclei.

3954.   48 Multi-Resonance 3D Spin-Echo EPI With Chemical Separation For Fast Hyperpolarized 13C MRI
Peter J. Shin1, Peder E.Z. Larson1, Martin Uecker2, Michael Lustig2, and Daniel B. Vigneron1
1Radiology and Biomedical Imaging, UCSF, San Francisco, California, United States, 2Electrical Engineering and Computer Science, UC Berkeley, Berkeley, California, United States

In hyperpolarized 13C experiments, data acquisition window is limited by the rapid metabolism and T1 relaxation of the hyperpolarized signal. This necessitates fast imaging schemes such as echo planar imaging (EPI). In this project, we developed a fast 3D EPI sequence for rapid 13C data acquisition and an accompanying multi-channel chemical separation method based on joint estimation of coil sensitivities and images of different molecules.