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

TRADITIONAL POSTER SESSION • MOLECULAR IMAGING
1850 -1913 Molecular & Cellular Imaging
1914 -1937 Hyperpolarized Contrast Agents

TRADITIONAL POSTER SESSION • MOLECULAR IMAGING
Tuesday, 23 April 2013 (16:00-18:00) Exhibition Hall
Molecular & Cellular Imaging

1850.   Tumors Established with Glioma Cells Transfected with the Gene mms6 Produce a Strong Increase in Transverse Relaxivity in Vivo
Brenda Robledo1, Xiaoyong Zhang1, and Xiaoping P. Hu1
1Biomedical Engineering, Emory University/Georgia Institute of Technology, Atlanta, Georgia, United States

 
In magnetotactic bacteria, the gene mms6 expresses a protein thought to initiate magnetite crystal formation. We previously found that transfecting glioma cells with mms6 increased the cells’ ability to uptake iron and increased their spin-spin relaxation rate (R2) in vitro. We hypothesized that tumors established with glioma cells transfected with mms6 would uptake endogenous iron and produce MR contrast. Our results show that mms6-positive tumors exhibit a larger R2 in vivo, likely due to the increased intracellular iron accumulation observed by Prussian staining the tumor. Our results suggest that mms6 may function as an MR reporter gene in cancer studies.

 
1851.   Supercharged Green Fluorescent Proteins as Bimodal Reporter Genes for CEST and Optical Imaging
Amnon Bar-Shir1,2, Yajie Liang1,2, Assaf A. Gilad1,2, and Jeff W.M. Bulte1,2
1Department of Radiology, Johns Hopkins University, Baltimore, MD, United States, 2Institute for Cell Engineering, Johns Hopkins University, Baltimore, MD, United States

 
Positively charged amino acids (mostly lysine and arginine) in peptide and proteins enable their use as CEST-based contrast agents or reporter genes. We show here that superpositively-charged mutants of the green fluorescent protein (GFP) reporter gene can generate superior CEST contrast. The additional, water-exposed, lysine and arginine amino acids of these mutants were found to increase the CEST contrast obtained from the baseline guanidine (arginine) and amide (lysine and arginine) exchangeable protons. These mutant GFPs retained their fluorescence thus making it a bimodal reporter gene.

 
1852.   Mammalian Expression of a CEST Reporter Gene Based on Human Protamine-1
Amnon Bar-Shir1, Guanshu Liu2, Kannie W.Y. Chan2, Michael T. McMahon2, Peter C.M. van Zijl2, Jeff W.M. Bulte1,3, and Assaf A. Gilad1,3
1Radiology, Johns Hopkins University, Baltimore, MD, United States, 2Kennedy Krieger Research Institute, Baltimore, MD, United States, 3Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United States

 
We have developed a novel CEST-MRI reporter gene based on human protamine-1, and demonstrated its expression and detection in mammalian cells, as well as in a three-dimensional cell culture model of immune-isolated cells. Due to its biocompatibility, this humanized reporter gene is expected to have higher cellular tolerance with minimal immune response.

 
1853.   Biosynthesis of Chimeric Magnetoferritin, a Novel MRI Reporter Gene
Marina Radoul1, Batya Cohen2, Moriel Vandsburger2, Dorit Granot2, Eyal Shimoni3, Alon Harmelin4, Raz Zarivach5, and Michal Neeman2
1Radiology, UCSF, San Francisco, CA, United States, 2Biological Regulation, Weizmann Institute of Science, Rehovot, Israel, 3Chemical Research Support, Weizmann Institute of Science, Rehovot, Israel, 4Veterinary Resources, Weizmann Institute of Science, Rehovot, Israel, 5Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel

 
Ferritin is one of the most extensively studied MRI reporter genes. However, compared to iron in magnetite, iron in ferritin demonstrates lower relaxivity and thus lowers sensitivity for detection by MRI. Here we report on a new recombinant fusion protein HA-Ferritin-M6A considerably enhanced r2 relaxivity and cell iron loading which represents a significant advance over existing Ferritin reporter gene strategies.

 
1854.   Hypotonic Swelling: A Soft Route for ex vivo Cellular Labeling with Paramagnetic Complexes
Enza Di Gregorio1, Giuseppe Ferrauto1, Eliana Gianolio1, Daniela Delli Castelli1, and Silvio Aime1
1Molecular Biotechnology & Health Sciences, Molecular Imaging Center, Torino, Italy

 
Different strategies to label cells with paramagnetic MRI contrast agents have been exploited in the last years like pinocytosis, electroporation, receptor/transporter mediated endocytosis, external labeling. Herein we show that hypotonic swelling of cells is a new efficient route to label cells with paramagnetic Gd-complexes. In fact, the cytoplasmatic uptake shifts to much higher loadings the “quenching” effect on the relaxivity observed when the paramagnetic Gd-complexes are compartmentalized into endosomal vesicles.

 
1855.   Gadolinium Oxide Nanoparticles for Positive Contrast MRI of Human Aortic Endothelial Cells at 7 Tesla
Yasir Loai1, Nurus Sakib1, Rafal Janik2, Warren D. Foltz3, and Hai-Ling Margaret Cheng1,4
1The Hospital for Sick Children, Toronto, Ontario, Canada, 2Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada, 3University Health Network, Toronto, Ontario, Canada, 4Medical Biophysics, University of Toronto, Toronto, Ontario, Canada

 
Positive T1 contrast MRI offers improved specificity and spatial delineation over conventional negative-contrast imaging, and gadolinium oxide (Gd2O3) nanoparticles have shown promise as a sensitive T1 agent for labeling. However, it is not known if signal enhancement in labeled cells is maintained at high field strengths, where relaxivity is known to decline. This study explores the potential of Gd2O3 for positive-contrast MRI at 7 Tesla. It is demonstrated in human aortic endothelial cells that large amounts of Gd2O3 were ingested spontaneously and that significant and stable positive T1 contrast on cells was achieved for at least 7 days.

 
1856.   Pharmacokinetics and Biodistribution of Superparamagnetic Nanoparticles Using PEPR in the Mouse: An in vivo, in Vitro and Ex Vivo Validation.
Oliviero Gobbo1,2, Friedrich Wetterling3, Kieran Crosbie-Staunton2, Peter Vaes4, Stephanie Teughels4, Farouk Markos5, Marek Radomski1, Adriele Prina-Mello2, and Yuri Volkov2
1School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin, Ireland, 2School of Medicine, Trinity College Dublin, Dublin, Ireland, 3School of Engineering, Trinity College Dublin, Dublin, Ireland, 4PEPRIC nv, Leuven, Belgium, 5Physiology, University College Cork, Cork, Ireland

 
The biodistribution of superparamagnetic iron oxide nanoparticles (SPIO) was evaluated in a mouse model using MRI measurements and a new analytical technique based on particle electron paramagnetic resonance (pEPR). Additionally, the pEPR results were also compared to inductively coupled plasma mass spectrometry (ICP-MS) iron analysis. Our results indicate that both techniques were equally sensitive. The iron measurements by pEPR in the organs were consistent with signal intensity changes recorded by MRI. Overall the data showed that this new technique is suitable for pharmacokinetic and biodistribution studies of SPIO.

 
1857.   High Contrast, Quantitative Stem Cell Tracking with Magnetic Particle Imaging
Bo Zheng1, Tandis Vazin1,2, Wisely Yang1, Patrick W. Goodwill1, Emine U. Saritas1, Laura R. Croft1, David V. Schaffer1,2, and Steven M. Conolly3,4
1Bioengineering, UC Berkeley, Berkeley, CA, United States, 2Chemical and Biomolecular Engineering, UC Berkeley, Berkeley, CA, United States, 3Bioengineering, University of California, Berkeley, Berkeley, CA, United States, 4Electrical Engineering and Computer Sciences, UC Berkeley, Berkeley, CA, United States

 
Magnetic Particle Imaging (MPI), a new technique that images distributions of superparamagnetic iron oxide nanoparticles by exploiting their nonlinear magnetization, can achieve high positive-contrast and quantitative clinical cell tracking, angiography, and inflammation imaging. Here, we present the first experimental demonstration of stem cell tracking with MPI. We show experimentally that MPI signal has excellent positive contrast, is highly linear with cell number, and is not depth-attenuated or diffused in tissue, in contrast to optical techniques. The detection sensitivity for MPI stem cell imaging is currently 10K cells, with potential for improvement by more than 2 orders of magnitude.

 
1858.   in vivo Imaging T Cells in the Rheumatoid Arthritis with Nano-Sized Iron Oxide Particles by MRI
Chih-Lung Chen1, Cheng-Hung Chou2, Chen-Hsuan Lin1, Wen-Yuan Hsieh1, Shian-Jy Wang1, and Chen Chang2
1Industrial Technology Research Institute, Hsinchu, Taiwan, 2Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan

 
The activation of T-cells correlates with the pathogenesis of rheumatoid arthritis (RA). Understanding the genesis, migration, and distribution of the T-cells provides important perspectives regarding RA. We developed an optimal carboxylated group of iron-oxide particles and adapted it to conjugate with CD3 antibody. We then investigated the labeling efficiency and binding specificity of the nano-sized iron oxide-based contrast agent IOPC and IOPC conjugated CD3 by cellular MRI via intravenous infusion. Specifically, we have detected a migration and accumulation of the T-cells in the arthritis joint in a rat RA model with in vivo MRI by IOPC-CD3.

 
1859.   T Cell Labeling and Tracking by MRI in Mouse Brain During Viral Infection
Tatjana Atanasijevic1, Jasmin Herz1, Dorian McGavern1, and Alan P. Koretsky1
1NINDS, NIH, Bethesda, MD, United States

 
Viral infection of the central nervous system (CNS) is a common cause of inflammatory disease. Anti-viral T cells recruited from the periphery play a critical role in fighting CNS viral infections. The ability to track single T cells in the brain with MRI would help pre-clinical studies and open novel diagnostic possibilities. Here it is demonstrated that T cells can be labeled with MPIOs in short incubation times and sorted for cells that have internalized particles. These cells can be re-introduced into LCMV-infected mice and detected by MRI opening the possibility of tracking single T cells migrating in the brain.

 
1860.   in vivo Tracking of Ferumoxytol Labeled NK Cells Using MRI
Naomi Santa Maria1, Thomas Ng2, Sharon Lin2, Sarah McCaig3, Desiree Crow3, Jianyi Wang3, Andrew Raubitschek3, and Russell E. Jacobs2
1Biology, Caltech, Pasadena, CA, United States, 2Caltech, Pasadena, CA, United States, 3City of Hope, Duarte, CA, United States

 
MRI can provide a noninvasive tool to characterize adoptive NK cell therapy. We aimed to implement MRI-based NK cell tracking methods that could be clinically translatable by using an FDA-approved USPIO cell label on NK cells isolated from human peripheral blood. MRI as a noninvasive in vivo cellular imaging technique could further elucidate optimization of adoptive NK cell transfer as a cancer therapy.

 
1861.   Cell Labeling with Gd-Based MRI Agents: Recent Achievements Using Sonoporation in the Presence of Liposomes.
Giuseppe Ferrauto1, Pierangela Giustetto1, Daniela Delli Castelli1, Marta Ruzza1, Francesca Garello1, Silvio Aime1, and Enzo Terreno1
1Molecular Biotechnology & Health Sciences, Molecular Imaging Center, Torino, Italy

 
The development of innovative strategies for labeling cells with Gd-based MRI agents is an important topic. It has been demonstrated that the ability of a labeling agent to generate a contrast when internalized into a cell is significantly higher if it is localized in the cytosol. Ultrasound stimulation can permeabilize cell membranes, allowing the passage of molecules from the external solution to cytosol. The purpose of this work was to design a proper experimental set-up for optimizing the cell labeling procedure via sonoporation. Furthermore the study was aimed at evaluating the effect of the presence of liposomes on labeling efficiency.

 
1862.   Quantification of Cells Labeled by Superparamagnetic Iron Oxide Particles Using R1, R2, and R2* Mappings: A Comparative Study Using Cell Phantoms
Fang-Cheng Yeh1, Li Liu2, T Kevin Hitchens2, and Chien Ho2
1Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA, United States, 2Pittsburgh NMR Center for Biomedical Research, Pittsburgh, PA, United States

 
We obtained the R1, R2, and R2* maps of a cell phantom created by mixing ultra-small superparamagnetic iron oxide (USPIO) labeled cells with raw cell matrix to simulate the labeling condition. Our analysis shows that R1, R2, and R2* values exhibit a good linear correlation with the number of cells (correlation coefficients > 0.9). Using the iron concentration of 1.25 pg Fe/cell, R2* value gives the best quantification index for cell density, about 107~109 cells per mL, the R2 values for cell density are in the range of 109 cells per mL, and the R1 values for cell density are greater than 1010 cells per mL.

 
1863.   Accumulation of Micron Sized Iron Oxide Particles (MPIOs) in Endothelin-1 Induced Focal Cortical Ischemia in Rats Is Independent of Cell Migration
Dorit Granot1 and Erik M. Shapiro2
1Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel, 2Department of Radiology, Michigan State University, East Lansing, Michigan, United States

 
Endogenous labeling of stem/ progenitor cells via intracerebroventricular injection of MPIOs has become standard methodology for MRI imaging of adult neurogenesis. While this method is well characterized in the naďve rodent brain, it has not been fully investigated in disease models. Here we describe challenges in this methodology that can confound data analysis when this technique is applied to a rat model of stroke.

 
1864.   Detection and Quantification of Magnetically Labeled Single Cells in Live Animals by MRI
Erik M. Shapiro1, Ronen Globinsky2, Xenios Papademetris2, and Margaret F. Bennewitz3
1Department of Radiology, Michigan State University, East Lansing, Michigan, United States, 2Department of Radiology, Yale University School of Medicine, New Haven, Connecticut, United States, 3Department of Biomedical Engineering, Yale University, New Haven, Connecticut, United States

 
In this work, MPIO labeled single MSCs were robustly detected in vitro and in vivo with 3D T2* MRI and quantified using automated image processing techniques. The effect of TE and resolution on spot size and intensity was evaluated within in vitro agarose samples, containing dispersed MPIO labeled single MSCs. MPIO labeled MSCs were injected intracardially to create an in vivo magnetically labeled single cell model in the rat brain, which was again optimized using TE and also TR imaging parameters. The presence of magnetically labeled single cells in the brain was confirmed with histology. For the first time, image processing techniques were used to generate automated counts of MPIO labeled MSCs in the rat brain of live animals from MRI scans.

 
1865.   Improving Fluorine Imaging Through Optimized Acquisitions and Advanced Reconstruction Techniques
Samuel Fielden1, Alexander Klibanov1,2, Frederick H. Epstein1,3, Yaqin Xu1, Brent French1,2, and Craig Meyer1,3
1Biomedical Engineering, University of Virginia, Charlottesville, VA, United States, 2Medicine, University of Virginia, Charlottesville, VA, United States, 3Radiology, University of Virginia, Charlottesville, VA, United States

 
Fluorine-19 (19F) is an attractive second-nucleus for contrast-enhanced MRI. However, for 19F cellular and molecular imaging, in order to achieve useful image resolution in reasonable scan times, methods must be developed to efficiently generate and utilize signal arising from small volumes of contrast agent. Here, we attempt to improve 19F imaging of cardiac inflammation through a 3-pronged approach: First, through pulse sequences optimized to maximize SNR; second, by incorporating side information from proton images in a constrained iterative reconstruction; finally, by exploiting the underlying sparsity of 19F images using model-based image reconstructions.

 
1866.   Metabolomics Reveals in vivo Significant Impact from Iron Oxide Nanoparticle-Labeled, Grafted Cells on the Host Organism
Verena Hoerr1, Harry Parkes2, Kathrin Halama1, Sonja Mertsch1, Volker Senner1, Astrid Jeibmann1, and Cornelius Faber3
1University Hospital Muenster, Muenster, Germany, 2Royal Marsden Hospital, Sutton, United Kingdom, 3University Hospital Münster, Muenster, Germany

 
We investigated in vivo the effect of iron oxide nanoparticles (IONPs) on C6 glioma cells with regards to growth behavior and metabolic pathogenesis by MRI and NMR metabolomics using statistical pattern recognition techniques. While tumor growth was similar for labeled and unlabeled tumors, 1H NMR spectra from urine of mice transplanted with iron labeled C6 glioma cells differed significantly from those of untreated cells and showed significant increase in trans-aconitate, N,N-dimethylglycine and 2-phenylproprionate. Our results indicate that IONPs may have significant impact on cell behavior in vivo which may result in metabolic changes superposing the pathological ones.

 
1867.   Can Chronic Cardiac Allograft Rejection (CCAR) Be Detected Before Irreversible Vascular Changes Occur? Noninvasive Assessment of CCAR by Cellular MR Imaging in a Rat Model
Qing Ye1, Yijen L. Wu1, Lesley M. Foley1, Parker H. Mills1, T Kevin Hitchens1, Fang-Cheng Yeh1,2, Haosen Zhang1, Danielle F. Eytan1, Li Liu1, and Chien Ho1
1NMR Center for Biomedical Research and Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, United States, 2Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA, United States

 
Chronic cardiac allograft rejection (CCAR) remains a major obstacle for long-term heart graft survival. Early identification the disease by noninvasive method is highly desirable. By using cellular MRI, we investigated the characteristics of CCAR progression over time in a rat model. Our preliminary results revealed that CCAR appears heterogeneous in its early stages and the accumulation of iron-labeled cells can be an indicator of the lesion formation prior to irreversible vascular changes occur. Cellular MRI is able to evaluate graft status noninvasively over time, which may be a reliable alternative for assessment of CCAR and potentially translatable to clinical work.

 
1868.   Potential of Newly Developed USPIO P904 in Detecting Lymph Node Metastasis
Yasuo Takehara1, Naoki Kato2, Satoshi Yoshise2, Jean-Sebastien Raynaud3, Philippe Robert3, Claire Corot3, Kazuya Hokamura4, and Harumi Sakahara5
1Radiology, Hamamatsu University Hospital, Hamamatsu, Shizuoka, Japan, 2Guerbet Japan, Chiyoda-ku, Tokyo, Japan, 3Guerbet Research, Roissy CDG, Cedex, France,4Pharmacology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan, 5Radiology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan

 
Under general anesthesia, five VX2 tumor bearing rabbits were examined with contrast enhanced MRI on 3.0T clinical scanner with phased array knee coil. Newly developed USPIO P904 was intravenously administered at a dose of 100 micro mol Fe/kg. Pre and 24 hrs post-contrast MRI was imaged with 3DT2*GRE. Metastatic and non-metastatic popliteal lymph nodes were excised and the specimens were stained with high sensitivity ion stain, macrophage stain and cytokeratin stain. Close histopathological-MRI correlations disclosed that P904 successfully increased the metastatic foci in the lymph node. Newly developed USPIO P904 may be a promising second generation USPIO after ferumoxtran-10.

 
1869.   SPIO-Loaded Unilamellar Polyion Complex Vesicles (SPIO-Cy5-PICsomes) as a High Relaxivity Contrast Agent for Tumor Detection
Daisuke Kokuryo1, Yasutaka Anraku2, Akihiro Kishimura2, Sayaka Tanaka3, Mitsunobu R. Kano4, Nobuhiro Nishiyama3, Tsuneo Saga1, Ichio Aoki1, and Kazunori Kataoka2,3
1Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Chiba, Japan, 2Graduate School of Engineering, The University of Tokyo, Tokyo, Tokyo, Japan,3Graduate School of Medicine, The University of Tokyo, Tokyo, Tokyo, Japan, 4Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Okayama, Japan

 
A newly developed SPIO-loaded and fluorescence dye (Cy5)-labeled polyion complex nanocarrier, termed SPIO-Cy5-PICsome, composed of two biocompatible oppositely charged block copolymers was applied to evaluate its ability to detect small tumors with MRI. In vitro r2 of the SPIO-Cy5-PICsomes was 2.54 times higher than that of free ferucarbotran. In in vivo experiments using subcutaneously xenografted mice, MR signal from the tumor changed during the 3 hours after SPIO-Cy5-PICsome administration. A small tumor was also detected at 24 hours after administration. SPIO-Cy5-PICsomes are a powerful nanocarrier with the potential to detect small and early-stage tumor for early diagnosis.

 
1870.   Development of a Novel Target Moiety of SPIO Contrast Agent for Effectively Targeting to Pancreatic Cancer Cells in Vitro and in vivo
YunMing Wang1, ShouCheng Wu1, and YuJen Chen1
1Department of Biological Science and Technology, National Chiao Tung University, HsinChu, Taiwan

 
We developed an MR/optical imaging contrast agents for the diagnosis and treatment of pancreatic cancer. A highly sensitive and specific T2 weighted MR-optical imaging agent has been synthesized. The results of the experiments show significant negative contrast enhancement in mucin4 positive cell lines. As a result, we demonstrated that the T2 weighted MR-optical imaging agent can specifically target mucin4 and can be potentially used for the detection of pancreatic cancer.

 
1871.   Quantitative 19F MRI and CT Tracking of the Microencapsulated Stem Cells in Peripheral Arterial Disease Model
Guan Wang1,2, Yingli Fu1, Steven M. Shea3, Judy Cook1, and Dara L. Kraitchman1,4
1Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, United States, 2Electrical and Computer Engineering, Johns Hopkins University, Baltimore, Maryland, United States, 3Center for Applied Medical Imaging, Siemens Corporation, Corporate Research and Technology, Baltimore, MD, United States, 4Molecular and Comparative Pathobiology, Johns Hopkins University, Baltimore, MD, United States

 
Microencapsulated stem cell (SC) offers a novel means to transplant mismatched SCs to avoid immunorejection for the treatement of peripheral arterial disease (PAD) that is too extensive for the conventional therapy. We produced dual X-ray/MR-visible microcapsules (XMRCaps) by impregnated the perfluorooctyl bromine (PFOB) to enable cell tracking with non-invasive imaging modalities. Here we first explore quantitative serial cell tracking using c-arm CT and 19F-MRI of XMRCaps in a rabbit PAD model using conventional clinical imaging systems. Results indicate that in vivo XMRCaps volume tracking could be achieved by both CT and MRI, while only MRI demonstrates the XMRCaps degradation.

 
1872.   Preparation and MR Imaging of Giant Vesicles Containing Superparamagnetic Iron Oxide for Cell-Tracking MRI Probe
Taro Toyota1,2, Naoto Ohguri2, Kouichi Maruyama3, Masanori Fujinami2, Tsuneo Saga3, and Ichio Aoki3
1The University of Tokyo, Meguro, Tokyo, Japan, 2Chiba University, Inage, Chiba, Japan, 3National Institute of Radiological Sciences, Inage, Chiba, Japan

 
We describe biodegradable probes made of giant vesicles (GVs; closed lipid membranes with diameters >1 lower case Greek mum) that encapsulate SPIO for use as an MRI contrast agent. These SPIO-containing GVs (SPIO-GVs) exhibited excellent contrast enhancement in the single cell of medaka fish (Oryzias latipes) embryos immediately after their microinjection, and this enhancement disappeared when the GV membranes were destroyed.

 
1873.   in vivo Detection of Membrane-Bound Radicals in Mouse Brains with Sepsis Using Molecular MRI and Immuno-Spin-Trapping
Rheal A. Towner1, Nataliya Smith1, Philippe Garteiser1, Debra Saunders1, Florea Lupu2, Robert Silasi-Mansat2, Dario C. Ramirez3, Sandra E. Gomez-Mejiba3, Ronald P. Mason4, Marilyn I. Ehrenshaft4, Fernando Bozza5, Marcus Frenandes de Oliveira6, and Hugo C. Castro Faria-Neto7
1Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States, 2Cardiovascular Biology, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States, 3Laboratory of Experimental and Therapeutic Medicine, National University of San Luis, San Luis, San Luis, Argentina,4Laboratory of Pharmacology & Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, NC, United States, 5Instituto de Pesquisa Clinica Evandro Chagas, Fundaçăo Oswaldo Cruz, Rio de Janeiro, RJ, Brazil, 6Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil,7Instituto de Pesquisa Clinica Evandro Chagas, Fundaçăo Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, Brazil

 
Oxidative stress from free radicals plays a major role in sepsis. A combination of immuno-spin-trapping (IST) and targeted molecular magnetic resonance imaging (mMRI) was used to detect in vivo levels of membrane-bound radicals (MBR) in brain tissues from mice with cecal ligation puncture (CLP)-induced sepsis. The spin trapping compound DMPO (5,5-dimethyl pyrroline N-oxide) was used to trap radicals. An anti-DMPO probe (anti-DMPO antibody covalently bound to an albumin-Gd-DTPA-biotin construct was used to detect MBR in vivo with mMRI. This method can be applied towards any radical-associated pathological condition for the in vivo assessment of membrane-bound protein and/or lipid radical levels.

 
1874.   Combined Molecular MRI and Immuno-Spin-Trapping for in vivo Detection of Membrane-Bound Radicals in Mouse GL261 Gliomas
Rheal A. Towner1, Nataliya Smith1, Debra Saunders1, Patricia Coutinho De Souza1, Leah Henry1, Florea Lupu2, Robert Silasi-Mansat2, Marilyn I. Ehrenshaft3, Ronald P. Mason3, Sandra E. Gomez-Mejiba4, and Dario C. Ramirez4
1Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States, 2Cariovascular Biology, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States, 3Laboratory of Pharmacology & Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, NC, United States, 4Laboratory of Experimental Medicine & Therapeutics, National University of San Luis, San Luis, San Luis, Argentina

 
Free radicals associated with oxidative stress play a major role in cancer. By combining immuno-spin-trapping (IST) and targeted molecular magnetic resonance imaging (mMRI), we detected in vivo levels of membrane-bound radicals (MBR) within tumors of GL261 glioma-bearing mice. The spin trapping agent DMPO (5,5-dimethyl pyrroline N-oxide) traps MBR which can be detected in vivo with a targeted molecular MRI probe that detects DMPO-trapped-MBR. This is the first report regarding the detection of in vivo levels of MBR from a glioma model. This novel non-invasive method can be applied to investigate free radical mechanisms in the pathogenesis of various cancers.

 
1875.   Development of Targeted Paramagnetic Nanoparticle for Non-Invasive Tumor Imaging
Meser M. Ali1, Nadimpalli RS Verma1, Janic Branislava1, James R. Ewing2, Robert A. Knight2, and Ali S. Arbab1
1Radiology, Henry Ford Hospital, Detroit, Michigan, United States, 2Neurology, Henry Ford Hospital, Detroit, Michigan, United States

 
Water soluble membrane peptide (pHLIP) is conjugated with anionic dendrimer-based paramagnetic nanoparticle. pHLIP-tagged nanoparticles bind to and are internalized by breast cancer cells in vitro. Systemic delivery of dendrimer-based nanoparticles lead to accumulation of the nanoparticles in a flank mouse model of breast cancer that are detected by optical and MR imaging.

 
1876.   Curcumin/Gd Loaded Apoferritin: A Novel "Theranostic" Agent to Prevent Hepatocellular Damage in Models of Hepatic Injuries
Simonetta Geninatti1, Juan Carlos Cutrin1, Diana Burgelea1, Dario Livio Longo1, Walter Dastru1, and Silvio Aime1
1Molecular Biotechnology and healt sciences, University of Torino, Torino, TO, Italy

 
Curcumin/Gd loaded Apoferritin is herein proposed as a new theranostic agent able to deliver simultaneously therapeutic and imaging probes to the liver. The incapsulation of curcumin inside the apoferritin cavity increases significantly its stability and bioavailability by maintaining its antioxidant and anti-inflammatory properties. Curcumin/Gd loaded Apoferritin was able to protect hepatocytes by the thiocetamide toxic action generating acute hepatitis injury.

 
1877.   Gd Complexes of DO3A-(Biphenyl-2,2prime or minute-Bisamides) Conjugates as MRI Blood-Pool Contrast Agents
Ki-Hye Jung1, Hee-Kyung Kim2, Min-Kyoung Kang2, Ji-Ae Park3, Eun-Young Jeon4, Seung-Tae Woo5, Joo-Hyun Kim5, Tae-Jeong Kim1, and Yongmin Chang2,6
1Applied Chemistry, Kyungpook National University, Daegu, Korea, 2Medical & Biological Engineering, Kyungpook National University, Daegu, Korea, 3Molecular Imaging Research Center, Korea Institute of Radiological & Medical Science, Seoul, Korea, 4The Advanced Medical Technology Cluster for Diagnosis & Prediction, Kyounpook National University, Daegu, Korea, 5Bayer Healthcare, Medical care, Seoul, Korea, 6Diagnostic Radiology and Molecular Medicine, Kyungpook National University, Daegu, Korea

 
We report the synthesis of DO3A derivatives of 2,2prime or minute- diaminobiphenyl and their Gd complexes of the type [Gd(1)(H2O)]·xH2O (2a,b)for use as new MRI blood-pool contrast agents that provide strong and prolonged vascular enhancement. Pharmacokinetic inertness of 2 compares well with that of structurally related Dotarem, a DOTA-based MRI CA currently in use. They show interaction with HSA to give association constants (Ka) in the order of two (ˇ­102), revealing the existence of the blood-pool effect. The in-vivo MR images of mice obtained with 2 are coherent, showing strong signal enhancement in both heart, abdominal aorta, and small vessels.

 
1878.   ZnDPA-DOTA Targeted Contrast Agents for MRI Detection of Bacteria in a Mouse Model of Infection
Sona Saksena1, Adnan Hirad1,2, Stephen B. Pickup1, Harish Poptani1, Ari D. Goldberg1, Anatoliy V. Popov1, and Edward James Delikatny1
1Radiology, University of Pennsylvania, Philadelphia, PA, United States, 2School of Medicine and Dentistry, University of Rochester, Rochester, New York, United States

 
Bacterial infections, both localized and disseminated (bacteremia), are responsible for significant morbidity and mortality in the community and hospital settings. A robust method to noninvasively identify and localize pathogenic bacterial sources with high sensitivity and specificity would greatly aid in the timely diagnosis and treatment of bacteremia. In an animal model of localized bacterial infection, E. coli exposed to ZnDPA-DOTA-thiourea reduced T1 by a factor of three indicating binding of ZnDPA-DOTA-thiourea to bacteria. We demonstrate that detection of bacteria in an animal model is feasible via changes in T1 relaxation.

 
1879.   DO3A-Benzothiazole Conjugates for Use as Gd-Based Theragnostic Agents
Hee-Kyung Kim1, Ki-Hye Jung2, Min-Kyoung Kang1, Ji-Ae Park3, Eun-Young Jeon4, Seung-Tae Woo5, Joo-Hyun Kim5, Tae-Jeong Kim2, and Yongmin Chang1,6
1Medical & Biological Engineering, Kyungpook National University, Daegu, Korea, 2Applied Chemistry, Kyungpook National University, Daegu, Korea, 3Molecular Imaging Research Center, Korea Institute of Radiological & Medical Science, Seoul, Korea, 4The Advanced Medical Technology Cluster for Diagnosis & Prediction, Kyungpook National University, Daegu, Korea, 5Bayer Healthcare, Medical Care, Seoul, Korea, 6Diagnostic Radiology and Molecular Medicine, Kyungpook National University, Daegu, Daegu, Korea

 
DO3A-benzothiazole conjugates have been prepared as a new family of multifunctional MRI/optical imaging probes with concomitant antitumor activity as well as tumor-specificity. Its R1 relaxivity is 3.84 mM-1sec-1, almost the same values as that of structurally related Dotarem®. The pattern of in vivo MRI enhacement compares well with those of liver-specific MRI CAs. More characteristically, it is to be noted that excretion is made via bile duct, confirming hepatobiliary uptake. T1-weighted MR images of MCF-7 cells incubated with Gd-DO3A-BT, revealing the tumor-specificity of the present series. In addition, antitumor activity of the present system represented as GI50 and TGI values.

 
1880.   Tunable Manganese Porphyrin as Gd-Free T1 Contrast Agents for Broad Applications
Hai-Ling Margaret Cheng1,2, Weiran Cheng3,4, Inga E. Haedicke3,4, Joris Tchouala Nofiele1,2, and Xiao-an Zhang3,4
1Medical Biophysics, University of Toronto, Toronto, Ontario, Canada, 2The Hospital for Sick Children, Toronto, Ontario, Canada, 3Physical and Environmental Sciences, University of Toronto Scarborough, Toronto, Ontario, Canada, 4Chemistry, University of Toronto, Toronto, Ontario, Canada

 
Gadolinium-based contrast agents are less efficient at high fields and are potentially toxic. Recently, the Zhang group developed a new class of T1 contrast agents based on the manganese porphyrin (MnP) structure with improved efficacy and safety. This study investigates MRI properties of two specific versions: a small polar MnP and a larger dimer. In-vitro measurements at 3 Tesla demonstrate high T1 relaxivities and a relatively weak T2 effect. Signal enhancement in rats is significantly greater compared to Gd-DTPA, and biodistribution is specific to each MnP. Potential applications are broad and include cardiac, liver, angiography, and perfusion and permeability imaging.

 
1881.   Water-Soluble Gadolinium Nanoparticles Coated with DO3A-Benzothiazole Conjugate: Synthesis and Application as a Potential Theragnostic Agent
Min-Kyoung Kang1, Hee-Kyung Kim1, Ki-Hye Jung2, Ji-Ae Park3, Seung-Tae Woo4, Joo-Hyun Kim4, Eun-Young Jeon5, Tae-Jeong Kim2, and Yongmin Chang1,6
1Medical & Biological Engineering, Kyungpook National University, Daegu, Korea, 2Applied Chemistry, Kyungpook National University, Daegu, Korea, 3Molecular Imaging Research Center, Korea Institute of Radiological & Medical Science, Seoul, Korea, 4Bayer Healthcare, Medical care, Seoul, Korea, 5The Advanced Medical Technology Cluster for Diagnosis & Prediction, Kyungpook National University, Daegu, Korea, 6Diagnostic Radiology and Molecular Medicine, Kyungpook National University, Daegu, Korea

 
Gadolinium nanoparticles (GdNPs) based perfectly soluble potential theragnostic agents formulated as Gd@SiO2-NHCO-DO3A-BT. The preparation initially requires the formation of Gd@SiO2 through self-condensation of TEOS on the surface of GdNPs. Gd@SiO2-NH2 thus formed was dispersed in diethylen glycol to react with APTES. In order to increase solubility as well as used by potential bimodal contrast agents, Gd@SiO2-NH2 was further conjugated with DO3A-benzothiazole to give the desired product Gd@SiO2-NHCO-DO3A-BT. Gd@SiO2-NHCO-DO3A reveals high MR relaxivity (R1 = 8.29 mM-1s-1) and may be put into a new family of potential multifunctional MRI/optical CAs.

 
1882.   A Novel Targeted MRI Contrast for Glioma Using Interleukin-13 Receptor Conjugated Liposome
Xiaoli Liu1, A.B. Madhankumar1, Patti A. Miller2, Becky Webb1, Kari A. Duck1, James R. Connor1, and Qing X. Yang1,2
1Department of Neurosurgery, The Pennsylvania State University College of Medicine, Hershey, PA, United States, 2Department of Radiology, The Pennsylvania State University College of Medicine, Hershey, PA, United States

 
Previous work demonstrated that inteleukin-13 receptors alpha 2 (IL-13Rlower case Greek alpha2) are highly expressed in glioma cells, but not in the normal cells. Thus, the IL-13Rlower case Greek alpha2 receptor was used as a target for delivering MRI contrast agent specifically to gliomas. In this work, we demonstrated that our targeted liposomes captured infiltrating tumor that were totally absent in Magnevist-enhanced MRI.

 
1883.   1H MRSI Maps of Tumor Hypoxia Using an Extrinsic Hypoxia Probe
Jesús Pacheco-Torres1,2, Pilar Lopez-Larrubia1, Elena Nieto3, Ramón Alajarín3, Julio Álvarez-Builla3, Paloma Ballesteros2, and Sebastián Cerdán1
1Instituto de Investigaciones Biomédicas - CSIC, Madrid, Madrid, Spain, 2Universidad Nacional de Educación a Distancia (UNED), Madrid, Madrid, Spain, 3Universidad de Alcalá, Alcalá de Henares, Madrid, Spain

 
Measurement of tumor oxygenation has gained importance in the last decades due to the known relationship between tumor hypoxia and tumor aggressiveness, poor outcome and resistance to therapies. Several techniques have been developed for this end (oxygen electrodes, EPR, PET…) but none of them has gained widespread acceptance. 2-Nitroimidazole derivatives (EF5, Pimonidzole, 18F-MISO...) have been extensively used as molecular markers of hypoxia in combination with different techniques as immunohistochemistry, PET or 19F-MRI. Here we evaluate, for the first time to our knowledge, the use of these hypoxia markers in combination with 1H-MRSI to generate oxygenation maps in vivo.

 
1884.   Vascular Permeability Change as an Imaging Biomarker for Disease Progression and Efficacy of Therapeutic Intervention of Rheumatoid Arthritis: DCE-MRI Study
Jang Woo Park1, Hui-jin Song1, Hee-Kyung Kim1, Jeehye Seo1, Seong-Uk Jin1, Jong Su Baeck1, Moon Han1, Yongmin Chang2,3, and Young-Hwan Lee*4
1Medical & Biological Engineering, Kyungpook National University, Daegu, Daegu, Korea, 2Diagnostic Radiology, Kyungpook National University, Daegu, Daegu, Korea, 3Molecular Medicine, School of Medicine, Kyungpook National University, Daegu, Daegu, Korea, 4Radiology, Daegu Catholic University Medical Center, Daegu, Daegu, Korea

 
Magnetic resonance imaging (MRI) can help to diagnose disease progression in rheumatoid arthritis (RA) by measuring potential inflammatory activity from vascular permeability. To calculate permeability value, dynamic contrast enhanced (DCE) MRI and relating pharmacokinetic models which was defined by Tofts and Kermode was used. Vascular permeability reflects angiogenesis and vascular structural changes the blood vessel wall by Rheumatoid arthritis, so this study make vascular permeability map and compare permeability value for each RA progression and the efficacy of therapeutic intervention. This study demonstrates the successful application of vascular permeability for inflammatory disease such as RA, and permeability value form DEC-MRI can be quantitative index of RA diagnose.

 
1885.   An Activatable Manganese-Based MR Contrast Agent for the Imaging of Redox Environment
Shreya Mukherjee1, Galen S. Loving1, and Peter Caravan2
1Department of Radiology, A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts, United States, 2Department of Radiology, Massachusetts General Hospital, Charlestown, Massachusetts, United States

 
Redox reactions are ubiquitous in biochemical activities. However, the lack of suitable redox responsive probes has hindered the non-invasive observation of intracellular redox activities through molecular imaging. We hypothesized that a redox-activated MR probe based on Mn2+/Mn3+ couple would be stable with respect to metal dissociation in both oxidation states, sensitive to biological reductants, and sufficiently reactive to act as an in vivo sensor. Here we report the design and characterization of a potential redox probe. The feasibility of this probe to act as redox responsive MR agents was tested under physiologically relevant reducing conditions. We anticipate that the probe activation would be limited primarily to regions where the normal mechanisms that regulate extracellular redox have been severely impaired.

 
1886.   Kinetics and Mechanism of Bioreduction of Nitrimidazoles as Hypoxia Probes
Jesús Pacheco-Torres1, Paloma Ballesteros2, Pilar Lopez-Larrubia1, and Sebastián Cerdán1
1Instituto de Investigaciones Biomédicas - CSIC, Madrid, Madrid, Spain, 2Universidad Nacional de Educación a Distancia (UNED), Madrid, Madrid, Spain

 
2-Nitroimidazole derivatives have been traditionally used as molecular markers of hypoxia due to their preferential reduction and subsequent trapping in vivo under hypoxic conditions. However, the reduction mechanism and its rate determining steps remained largely unexplored. We show that it is the intracellular redox state (NADP/NADPH, GSSG/GSH), rather than the oxygen tension by itself, what determines the reduction rate of these compounds, the reaction rate being limited mainly by the GSH concentration. This is a general mechanism occurring in all 2-Nitroimidazole derivatives investigated. Also, we report the appearance and the kinetics of new signals belonging to reaction intermediates.

 
1887.   Relaxivity of Amorphous Manganese Oxide at Various Field Strengths
Eveliina Lammentausta1, Gamzegul M. Behrouz2, Elli-Noora Salo3, Ville-Veikko Telkki2, Susanna Ahola2, Jessica M. Rosenholm4, Roberto Blanco Sequeiros1,5, and Miika T. Nieminen3,5
1Department of diagnostic Radiology, Oulu University Hospital, OYS, Oulu, Finland, 2Department of Physics, University of Oulu, Oulu, Oulu, Finland, 3Department of diagnostic Radiology, Oulu University Hospital, OYS, Finland, Finland, 4Center for Functional Materials, Laboratory of Physical Chemistry, Department of Natural Sciences, Ĺbo Akademi University, Turku, Turku, Finland, 5Department of Radiology, University of Oulu, Oulu, Oulu, Finland

 
Novel amorphous manganese oxide (MnOx) nanostructures were examined in various concentrations from 0.01 mM t0 1 mM at four different field strengths (3T, 4.7T, 7.1T and 9.4T) to determine its T1 relaxivity. MnOx displayed substantially higher relaxivities than typical clinically used gadolinium based contrast agents and thus is a very promising candidate for stem cell labeling and dynamic imaging studies.

 
1888.   Thermally Reversible Nanoparticle Aggregation: Modeling T2 Variation with Temperature
Bashar Issa1,2, Ihab M. Obaidat1, Shahnaz M. Qadri2, and Yousef Haik2,3
1Physics, UAE University, Al-Ain, AD, United Arab Emirates, 2UNCG, Greensboro, NC, United States, 3Mechanical Eng., UAE University, Al-Ain, AD, United Arab Emirates

 
Magnetic nanoparticles have been previously used as both MRI contrast and hyperthermia agents. The overall aim is to develop a MRI-based thermal mapping technique for the heated tissue. The first step is the modeling of relaxation times at different temperatures. Echo Limited Regime is used to fit the T2 data using a modified particle size that takes into account the clustering of particles. It is believed that thermally enhanced surface layer spins plays pivotal role in the thermally reversible agglomeration of particles up to a temperature around Curie temperature 43oC. Thermally induced agglomeration can be used as temperature sensor.

 
1889.   Evaluate Morphological Effect on MR Relaxivity for Bifunctional Au-Fe3O4 Heterostructures
Ya-Han Yang1, Fang-Hsin Lin1, Yi-Tzu Lu1, Ruey-An Doong1, and Hsu-Hsia Peng1
1Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan

 
Au-Fe3O4 heterostructures have been used as bifunctional probes for optical imaging and MRI. The aim of this study is to investigate the morphological effect on MRI relaxivity for pure Fe3O4 nanoparticles (NPs), 5 nm Au dumbbell-like NPs (mAu DBNPs), 10 nm Au dumbbell-like NPs (LAu DBNPs), and 10 nm Au flower-like NPs (LAu FLNPs). The mAu DBNPs showed stronger r2 relaxivity than that of LAu DBNPs and LAu FLNPs exhibited higher relaxivity than that of LAu DBNPs, demonstrating the morphological effect on MR relaxivity. Therefore, to manufacture proper configurations of heterostructures are able to enhance T2 contrast in MRI applications.

 
1890.   The Effect of Cryoprotection on the Use of PLGA Encapsulated Iron Oxide Nanoparticles for Magnetic Cell Labeling
Erik M. Shapiro1 and Kevin S. Tang2
1Department of Radiology, Michigan State University, East Lansing, Michigan, United States, 2Department of Biomedical Engineering, Yale University, New Haven, Connecticut, United States

 
The objective of this study was to identify a cryoprotection scheme to enhance redispersion of PLGA encapsulated iron oxide NPs in water and to study the effect this would have on magnetic cell labeling. We discovered that optimal percentage of dextrose for retaining initial particle characteristics was 1% with increasing percentages having little effect on average particle size and distribution and decreasing percentages having increasing degrees of aggregation. We found that for magnetic cell labeling, increasing dextrose cryoprotection decreased labeling efficiency, however all cryoprotectant percentages labeled cells robustly enough to enable single cell detection on MRI.

 
1891.   19F-Lanthanide Complexes: T1 - And T2 - Dependent Signal Gain Using Gradient Echoes
Gisela E. Hagberg1, Aneta Keliris2, Ilgar Mamedov3, Matteo Placidi3, Hellmut Merkle4, Nikos K. Logothetis3, and Klaus Scheffler1,2
1Biomedical Magnetic Resonance, University Hospital Tuebingen, Tuebingen, Germany, 2High-field Magnetic Resonance, Max Planck Institute for Biological Cybernetics, Tuebingen, Germany, 3Physiology of Cognitive Processes, Max Planck Institute for Biological Cybernetics, Tuebingen, Germany, 4LFMI-NINDS, National Institutes of Health, Bethesda, MD, United States

 
19F-labelled compounds have unique benefits for biological applications but are hampered by low sensitivity. Lanthanide-complexes that shorten the 19F T1 and T2 relaxation times can boost the SNR in spoiled gradient echo sequences (FLASH). We investigated the MRI signal systematically for a wide range of T1 and T2 times for FLASH and balanced steady state free precession (tFISP). For long T2 times the tFISP signal is always greater, and for short relaxation times the signal gain depends on the duration of encoding and spoiling. None of the available compounds had ‘ideal’ relaxation times that gives the highest possible signal. Our results can be used to design better 19F contrast agents tailored to a specific MRI sequence.

 
1892.   Trimodality Detection of Magnetic Megaparticles for Simultaneous Tracking of a Large Number of Primary Human Cells Assembled in Collagen Matrices
David P. Cormode1, Willem J M Mulder2, and Erik M. Shapiro3
1Radiology, University of Pennsylvania, Philadelphia, PA, United States, 2Translational and Molecular Imaging Institute, Mount Sinai School of Medicine, New York, NY, United States, 3Radiology, Michigan State University, East Lansing, MI, United States

 
We herein report the development and use of a new type of particle as a contrast agent for MRI-related imaging: a magnetic megaparticle. We will report the synthesis and characterization of the megaparticle, as well as the results of long-term biocompatibility experiments and cell-labeling. The particle could be used for tracking very large numbers of cells using a hand held magnetic device, which we also integrated into an iPhone based imaging system. The particle facilitates optical imaging, as well. The megaparticle will be broadly applicable for the study of a variety of diseases.

 
1893.   in vivo Biodegradation of PLGA Encapsulated Magnetite Nanoparticles
Erik M. Shapiro1 and Michael K. Nkansah2
1Department of Radiology, Michigan State University, East Lansing, Michigan, United States, 2Department of Biomedical Engineering, Yale University, New Haven, Connecticut, United States

 
Magnetic particles are a key technology behind MRI-based cell tracking. We describe the first characterization of in vivo biodegradation rate of a specifically designed magnetic nanoparticle dedicated for magnetic cell labeling. PLGA-encapsulated magnetic nanoparticles, ~ 100 nm @ 84% iron weight were injected intravenously into mice. Inert MPIOs and Feridex, were also injected into additional mice. Serial MRI of the liver over 12 weeks revealed that Feridex was rapidly degraded within two weeks while inert MPIOs exhibited no biodegradation. 2:1 NPs exhibited an intermediate biodegradation rate, with 80% clearance of the iron at the end of 12 weeks.

 
1894.   In Vitro and in Vivo Characterization of (Albumin-Binding) Dendritic MRI Contrast Agents for Dynamic Contrast-Enhanced MRI
Igor Jacobs1, Siem Wouters1, Henk Keizer2, Henk Janssen2, Eliana Gianolio3, Silvio Aime3, Gustav J. Strijkers1, and Klaas Nicolay1
1Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands, 2SyMO-Chem BV, Eindhoven, Netherlands,3Dipartimento di Chimica & Centro di Imaging Molecolare, Universitŕ degli Studi di Torino, Torino, Italy

 
DCE-MRI is widely used for evaluation of tumor treatment. Macromolecular contrast agents may be preferred for determination of specific pharmacokinetic parameters and treatment-induced vascular changes. In this study (albumin-binding) dendritic contrast agents of various molecular weights were extensively characterized. Albumin-binding (confirmed in vitro) led to increased circulation half-lives, while a size-dependent range of circulation half-lives was observed for the non-albumin-binding dendrimers. Tumor/muscle uptake ratios of the dendrimers were higher than of Gd-DOTA. These findings imply that these agents likely possess a range of tumor wash-in and wash-out rates, making them suitable for investigation of the size-dependency of pharmacokinetic parameters.

 
1895.   Au@Gd Core-Shell Nanoparticles as a CT/MR Bimodal Contrast Agent
Min-Kyoung Kang1, Hee-Kyung Kim1, Ki-Hye Jung2, Ji-Ae Park3, Seung-Tae Woo4, Joo-Hyun Kim4, Eun-Young Jeon5, Tae-Jeong Kim2, and Yongmin Chang1,6
1Medical & Biological Engineering, Kyungpook National University, Daegu, Korea, 2Applied Chemistry, Kyungpook National University, Daegu, Korea, 3Molecular Imaging Research Center, Korea Institute of Radiological & Medical Science, Seoul, Korea, 4Bayer Healthcare, Medical care, Seoul, Korea, 5The Advanced Medical Technology Cluster for Diagnosis & Prediction, Kyungpook National University, Daegu, Korea, 6Diagnostic Radiology and Molecular Medicine, Kyungpook National University, Daegu, Korea

 
Gold/gadolinium core-shell nanoparticles of the formula Au@SiO2@Gd@PEG were synthesized for use as a CT/MR bimodal contrast agent. The preparation initially requires the formation of Au@SiO2 through self-condensation of TEOS on the surface of AuNPs. Au@SiO2 thus formed was dispersed in aqueous alcohol to react with Gd(NO3)3 in the presence of urea, leading to the formation of Au@SiO2@Gd core-shell nanoparticles. In order to increase solubility as well as biocompatibility further coated with PEG. These systems reveal both high CT attenuation and MR relaxivities (R1 = 13.01 mM-1sec-1) so may be put into entry a new class of CT/MR bimodal imaging probes.

 
1896.   Characterization of Gd-Based Contrast Agents Encapsulated in Thermosensitive Liposomes as Potential Tool for MRI Assisted Hyperthermia
Michael Peller1, Martin Hossann2, Zulfiya Syunyaeva2, Rolf D. Issels2, Maximilian F. Reiser1, and Lars H. Lindner2
1Institute for Clinical Radiology, University Hospital Munich, Ludwig-Maximilians University, München, Germany, 2Department of Internal Medicine III, University Hospital Munich, Ludwig-Maximilians University, München, Germany

 
Thermosensitive liposomes (TSL) with encapsulated contrast agents (CA) have been proposed for MRI-assisted thermotherapy in tumors. For such purpose an effective temperature induced r1-relaxivity change and stability in the presence of serum components is needed. Here, temperature induced r1 change of 6 approved Gd-based CAs comprising diverse chemical structures and charges encapsulated in phosphatidyldiglycerol (DPPG2)-TSL were characterized. The shelf life of TSL was also investigated. CAs with nonionic chemical structure were more suitable than those with ionic structure. Of these Gd-DTPA-BMA showed effective r1-change and the highest shelf life

 
1897.   A Novel Hyaluronan Based Contrast Agent for Non-Invasive Detection of Hyaluronidase by MRI
Marina Radoul1, Fortune Kohen2, Hagit Dafni3, Moriel Vandsburger2, Sharon G. G. Wolf4, and Michal Neeman2
1Radiology, UCSF, San Francisco, CA, United States, 2Biological Regulation, Weizmann Institute of Science, Rehovot, Israel, 3Veterinary Resources, Weizmann Institute of Science, Rehovot, Israel, 4Chemical Research Support, Weizmann Institute of Science, Rehovot, Israel

 
One of the most common ECM components is hyaluronan (HA). Hyaluronidase (HYAL) degrades high molecular weight HA into low molecular weight fragments thus altering the ECM to become permissive to angiogenesis. Our goal is to detect HYAL non-invasively by MRI in order to predict the tilt of angiogenic balance within the tumor microenvironment. Here we demonstrate how r1 and r2 relaxivities altered in response to degradation of a novel contrast agent HA-GdDTPA nanoparticles by hyaluronidase secreted by ES-2 ovarian carcinoma cells.

 
1898.   Aminocyclopentane- And Aminocyclophexane-Carboxylic Acid Containing Cyclic RGD-DOTA-Gd Conjugates with High Specific Affinity for lower case Greek alphalower case Greek nulower case Greek beta3 Integrin as MRI Contrast Agents
In Ok Ko1, Ji-Ae Park1, Jung Young Kim1, Wonho Lee1, Sang Moo Lim2, and Kyeong Min Kim1
1Molecular Imaging Research Center, Korea Institute of Radiological & Medical Science, Seoul, Korea, 2Department of Nuclear Medicine, Korea Institute of Radiological & Medical Science, Seoul, Korea

 
We designed two integrin lower case Greek alphalower case Greek nulower case Greek beta3-specific MRI contrast agents, which is an inserted aminocyclopentane (ACP) or amicocyclohexane (ACH)-carboxylic acid into c(RGDK) to improve the binding affinity, and evaluated their tumor targeting efficacy in U87MG tumor bearing mice. Substitution of ACP or ACH in the lead structure c(RGD-ACP-K)-DOTA and c(RGD-ACH-K)-DOTA exhibited much higher binding affinity for lower case Greek alphalower case Greek nulower case Greek beta3 integrin than c(RGDyK). The in vivo MR images of mice obtained with c(RGD-ACP-K)-DOTA-Gd and c(RGD-ACH-K)-DOTA-Gd showed a significant enhancement in the tumor.

 
1899.   Relaxometric Properties of Gadolinium Chelates of DOTA-Like Ligands with Axially Uneven Distribution of Donor Atoms
Miloslav Polasek1 and Peter Caravan2
1Radiology, A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital/Harvard Medical School, Charlestown, Massachusetts, United States, 2Radiology, Massachusetts General Hospital, Charlestown, Massachusetts, United States

 
We explored a novel design of DOTA-like compounds where removal of an acetate arm on N1 is counterbalanced by a donor arm on N7. Surprisingly, presence of a non-coordinating moiety on N1 lowered kinetic stability of the Gd chelates. Choice of the donor arm on N7 influenced both kinetic stability and water exchange rate, the latter could be tuned over 2 orders of magnitude.

 
1900.   A Single Amino Acid Gd-Complex as a Modular Tool for High Relaxivity MR Contrast Agent Development.
Eszter Boros1, Miloslav Polasek1, Zhaoda Zhang1, and Peter Caravan2
1Department of Radiology, Massachusetts General Hospital, Harvard Medical School, The Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, United States,2Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Massachusetts General Hospital, Charlestown, MA, United States

 
We investigated applications of the alanine analogue of Gd(DOTA), Gd(DOTAla). Fmoc protected DOTAla suitable for solid phase peptide synthesis was synthesized and integrated into polypeptide structures containing 1-3 Gd(DOTAla) complexes (GdL1, GdL2, GdL3).GdL3 is superior to commercial contrast agents gadoteridol and gadofosveset /HSA (human serum albumin) at high fields. The modularity of design, the ease of solid phase synthesis, high kinetic inertness (t1/2 = 61±4h) for Gd3, and optimal water exchange rate renders the Gd(DOTAla) scaffold a suitable platform for the development of high field T1 agents based on Gd.

 
1901.   Molecular Imaging Beyond Contrast Generation: Utility of BIRDS
Samuel Maritim1, Daniel Coman2,3, Yuegao Huang2, Majura Hoque2, and Fahmeed Hyder2,4
1Diagnostic radiology, Yale University, New Haven, CT, United States, 2Diagnostic Radiology, Yale University, New Haven, CT, United States, 3Quantitative Neuroscience with Magnetic Resonance (QNMR), Yale University, New Haven, CT, United States, 4Biomedical Engineering, Yale University, New Haven, CT, United States

 
Conventional T1 and T2 contrast agents offer great tissue contrast. To go beyond shades of gray in typical molecular/cellular MRI, we developed a new ultra-high speed 3D chemical shift imaging (CSI) method called Biosensor Imaging of Redundant Deviation in Shifts (BIRDS), which requires that we detect protons emanating from the agent (e.g., TmDOTP5-), itself instead of the agent’s effect on water proton relaxation times. Here we show how resilient BIRDS can be for pH and temperature mapping, specifically when TmDOTP5- is in presence of high concentrations of typical T1 and T2 agents and even when TmDOTP5- inside in liposomes.

 
1902.   Using Ellipsoidal Microshells to Generate Multispectral Contrast
Gary Zabow1,2, Stephen Dodd1, and Alan P. Koretsky1
1NINDS, National Institutes of Health, Bethesda, Maryland, United States, 2Electromagnetics Division, National Institute of Standards & Technology, Boulder, Colorado, United States

 
A new class of microengineered multispectral contrast agent is introduced based on ellipsoidal microshell structures. In principle, the new ellipsoidal geometries allow for higher spectral resolution than previously demonstrated microfabricated multispectral agents, improving detection sensitivity and agent multiplexing potential. This talk discusses the theory behind these new agents, considers ways to fabricate the required microstructure geometries, and presents initial NMR data from the first sets of such agents.

 
1903.   Synthesis of Human Protamine-1 (HPRM1), a Novel CEST Contrast Agent
Nikita Oskolkov1, Kannie W.Y. Chan2, Amnon Bar-Shir2, Peter C.M. van Zijl1,3, Jeff W.M. Bulte2,4, Assaf A. Gilad2,4, and Michael T. McMahon1,3
1Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, 2Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, United States, 3F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, 4Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, Baltimore, MD, United States

 
We have synthesized human protamine-1 (hPRM1), a compound biologically relevant for packing cellular DNA, which is rich in arginine and generates high CEST contrast associated with the exchangeable protons in the guanidyl group. We have also determined how the contrast varies upon binding of hPRM1 to nucleotides, the natural role of this protein, which is relevant to how it might perform in vivo as contrast material. This synthetic approach has resulted in a high yield and retention of the peptide’s ability to bind DNA, potentially enabling use of hPRM-1 as an alternative to recombinant or naturally occurring protamine.

 
1904.   Tuning Histidine Proton Exchange Rates for CEST Contrast Through Peptide Design
Nikita Oskolkov1, Xiaolei Song1, Kannie W.Y. Chan2, Michael Giano3, Jeff W.M. Bulte2,4, Peter C.M. van Zijl1,4, Joel Schneider3, and Michael T. McMahon1,4
1Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, 2Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, United States, 3National Cancer Institute, National Cancer Institute, Frederick, MD, United States, 4F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States

 
Chemical Exchange Saturation Transfer (CEST) is a novel MRI contrast mechanism for detection of water exchangeable protons. We have designed peptides which form hydrogels suitable for use as adjuvants in cell therapy. These peptides are designed to form strong hydrogen bonding networks in order to slow down imino proton chemical exchange. These peptide-based hydrogels possess a wide range of unique properties that make them potentially applicable for different biological studies.

 
1905.   Detection of Carboxypeptidase G2 Activity with Chemical Exchange Saturation Transfer Magnetic Resonance.
Yann Jamin1, Thomas R. Eykyn1,2, Evon Poon3, Caroline J. Springer3, and Simon P. Robinson1
1Division of Radiotherapy and Imaging, The Institute of Cancer Research, Sutton, Surrey, United Kingdom, 2Division of Imaging Sciences and Biomedical Engineering, Kings College London, London, United Kingdom, 3Division of Cancer Therapeutics, The Institute of Cancer Research, Sutton, Surrey, United Kingdom

 
The exchange rates of amine protons with bulk water are much faster than those of amide protons. We show here that this property can be exploited using chemical exchange saturation transfer magnetic resonance (CEST-MR) to monitor the activity of the bacterial protein carboxypeptidase G2 (CPG2), an enzyme utilized in cancer gene therapy. We demonstrate that CPG2 activity leads to the “activation” of a concentration-dependent CEST signal at a resonance offset of +3 ppm from the water frequency (GluCEST), induced by the CPG2-mediated release of glutamate (amine) from CPG2 substrates (amides).

 
1906.   Evaluation of a TGase-Responsive PARACEST MRI Contrast Agent: The Influence of Conformations and Non-Covalent Adducts
Dina V. Hingorani1, Edward T. Randtke2, and Marty Pagel3
1Chemistry and Biochemistry, University of Arizona, Tucson, Arizona, United States, 2Chemistry and Biochemistry, University of Arizona, Tucson, AZ, United States,3Biomedical Engineering, University of Arizona, Tucson, AZ, United States

 
We have characterized the CEST effect of a TGase-responsive PARACEST MRI contrast agent that is conjugated to a protein and hydrophilic peptides that include arginine. The appearance of CEST at -11 ppm differs from the appearance of CEST at +4, +11, and +22 ppm after conjugation of the agent a hydrophobic ZQR peptide, which demonstrates outstanding specificity of CEST for different molecular conformations, which may be exploited to design responsive CEST agents. CEST at -11 ppm before TGase-catalyzed conjugation indicated the formation of a non-covalent supramolecular adduct, which may be further exploited to design responsive CEST agents.

 
1907.   
A Dual Fluorescent/Paramagnetic Chemical Exchange-Based MRI Probe for Cell Death Imaging
Jonatan A. Snir1, Mojmír Suchý2,3, Alex X. Li4, Robert H.E Hudson5, Stephen H. Pasternak6,7, and Robert Bartha8
1Department of Medical Biophysics, Robarts Research Institute, London, Ontario, Canada, 2Department of Chemistry, Western University, London, Ontario, Canada, 3Imaging Research Laboratories, Robarts Research Institute, London, On, Canada, 4Imaging Research Laboratories, Robarts Research Institute, London, Ontario, Canada, 5Department of Chemistry, Western University, London, On, Canada, 6Department of Clinical Neurological Sciences, Robarts Research Institute, London, Ontario, Canada, 7Department of Physiology and Pharmacology, Schulich School of Medicine, Western University, London, Ontario, Canada, 8Imaging Research Laboratories, Robarts Research Institute, London, Onta, Canada

 
Programmed cell death (apoptosis) is an important feature for studies of cancer therapy as well as ischemia and neurological pathologies. Recently, we have synthesized a novel MRI and fluorescent contrast agent containing a cleavage site specific to Caspase 3. Prostate cancer cells were either irradiated with ultraviolet radiation or maintained without insult. 24 hour incubation with our contrast agent permitted differentiation of irradiated versus control cells with both confocal microscopy and PARACEST MRI. This work provides a proof-of-principle of PARACEST imaging for the detection of apoptotic cell population following ionizing radiation.

 
1908.   The Hanes-Woolf Linear QUEST Method Provides the Most Accurate Determination of Fast Chemical Exchange Rates for CEST MRI Contrast Agents
Edward T. Randtke1, Liu Qi Chen1, Rene Corrales1, and Marty Pagel2
1Chemistry and Biochemistry, University of Arizona, Tucson, AZ, United States, 2Biomedical Engineering, University of Arizona, Tucson, AZ, United States

 
Most CEST MRI methods fail to accurately determine fast exchange rates (> 20% of the chemical shift difference). We have investigated the accuracies of the Bloch fitting, QUEST, QUESP, omega-plot, and concentration-dependent methods using theoretical simulations and experimental measurements. We have also developed new analysis methods and compared these methods with existing analysis methods. Our results show that the Bloch fitting method is most accurate for determining slow and fast exchange rates, the omega-plot method is acceptable for determining slow exchange rates, and the Hanes-Woolf linear QUESP method is acceptable for determining fast exchange rates.

 
1909.   Using T2-Exchange from Dy3+DOTA-Based Chelates for Contrast-Enhanced Molecular Imaging with MRI
Todd C. Soesbe1,2, S. James Ratnaker1, Zoltan Kovacs1, and A. Dean Sherry1,3
1Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, Texas, United States, 2Department of Radiology, UT Southwestern Medical Center, Dallas, Texas, United States, 3Department of Chemistry, The University of Texas at Dallas, Richardson, Texas, United States

 
Magnetic resonance imaging (MRI) offers superior anatomic resolution and soft tissue contrast compared to x-ray computed tomography, making it an excellent tool for cancer prevention studies. It was recently shown that lanthanide-based Ln3+DOTA chelates (Ln3+ ≠ La3+, Gd3+, Lu3+) create enhanced negative contrast (i.e., darkening) in MRI through the chemical exchange of water molecules. The level of this “T2-exchange” contrast, which adds to the inherent paramagnetic T2 contrast of the Ln3+ ion, reaches a maximum at a specific water molecule exchange rate. It was also recently demonstrated that T2-exchange contrast could be increased by several orders of magnitude through simple linear polymerization of the Ln3+DOTA chelate. We hypothesize that by using these methods a highly sensitive molecule-sized T2 contrast agent can be created. The transverse relaxivity (r2) would be an order of magnitude greater than any currently existing contrast agent (e.g., super paramagnetic iron oxide nanoparticles), while retaining the advantages of using small molecules rather than nanoparticles for improved biological targeting, uptake, and clearing.

 
1910.   A New Type of Responsive MRI Contrast Agents That Modulate T2ex Relaxation: Detection of Nitric Oxide
Iman Daryaei1 and Marty Pagel2
1Chemistry and Biochemistry, University of Arizona, Tucson, AZ, United States, 2Biomedical Engineering, University of Arizona, Tucson, AZ, United States

 
We have developed a MRI contrast agent that changes T2 relaxivity after treatment with nitric oxide. This change in T2 relaxation is attributed to a change in the chemical exchange rate of a proton on the agent, which changes T2 exchange relaxation. The T1 relaxivity does not change after treatment with nitric oxide, so that a ratio of T2- and T1-weighted images can detect nitric oxide in a concentration-independent manner. These results demonstrate that a new class of responsive MRI contrast agents can be developed by changing the chemical exchange rate of an agent and obtaining T2-weighted and T1-weighted images.

 
1911.   Natural D-Glucose as a Biodegradable T2 Contrast Agent for MRI
Nirbhay N. Yadav1,2, Jiadi Xu1,2, Amnon Bar-Shir3,4, Qin Qin1,2, and Peter C.M. van Zijl1,2
1Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States, 2FM Kirby Research Center, Kennedy Krieger Institute, Baltimore, MD, United States, 3Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, United States, 4The Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United States

 
We show that natural D-glucose can be used as an exogenous T2 relaxation agent, particularly at field strengths available for human MRI. Transverse relaxation and diffusion measurements were carried out on D-glucose phantoms at different concentrations, pH, and magnetic field strengths (3 T and 7 T). The results show strong dependence of water transverse relaxivity on glucose concentration, sample pH, and field strength. We show the increased relaxivity is due to the 5 exchangeable hydroxyl protons in glucose and that the greatest relaxivity is observed in the physiological pH range.

 
1912.   Radial K-Space Acquisition Improves Robustness of MR-Based Attenuation Maps for MR/PET Quantification in an Animal Imaging Study of the Abdomen
Jason Bini1,2, Philip Robson1, Claudia Calcagno1, Antoine Millon1,3, Mark Lobatto1,4, and Zahi A. Fayad1,5
1Translational and Molecular Imaging Institute, Mount Sinai School of Medicine, New York, New York, United States, 2Department of Biomedical Engineering, City College of New York, New York, New York, United States, 3Department of Vascular Surgery, University Hospital of Lyon, Lyon, France, 4Department of Vascular Medicine, Academic Medical Center, Amsterdam, Netherlands, 5Department of Radiology, Mount Sinai School of Medicine, New York, New York, United States

 
In this study, we propose a radial k-space MR acquisition sequence designed to redistribute coherent breathing artifacts that result from Cartesian k-space trajectories into incoherent pseudo-noise spread across the image domain. It is proposed that the use of a radial sequence with automatic segmentation, replacing subjective user interaction in image processing, will facilitate more robust segmentation of MR images to generate attenuation maps. The objective of the current study was to then qualitatively and quantitatively evaluate the respective MR-based attenuation maps generated, in addition to their resultant quantitative PET images, to evaluate alternative preclinical MR/PET protocols.

 
1913.   in vivo Evaluation of 68Ga-Labeled Iron Oxide Nanoparticles as a PET/MR Imaging Probe
Renata Madru1, Thuy Tran2, Adnan Bibic3, Sarah Fredriksson4, Freddy Stĺhlberg5, Linda Knutsson5, and Sven-Erik Strand5
1Medical Radiation Physics, Lunds University, Lund, Sweden, 2Lund University BioImaging Centrum, Lund University, Lund, Skane, Sweden, 3Lund University BioImaging Centrum, Lund University, Lund, Sweden, 4Genovis AB, Lund, Sweden, 5Medical Radiation Physics, Lund University, Lund, Sweden

 
The purpose of this study was to develop a new PET/MRI probe to improve the current sentinel lymph node technique used for diagnostic and staging of breast cancer and malignant melanoma. Here we demonstrate the feasibility of labeling the synthetized SPIONs with the generator produced Ga-68 and accumulation of the 68Ga-SPIONs in lymph nodes after subcutanious injection in rats, verified by PET and MRI. The results are encouraging for future clinical applications adding important pre-operative information which may lead to new therapeutic strategies.

 

TRADITIONAL POSTER SESSION • MOLECULAR IMAGING
Tuesday, 23 April 2013 (16:00-18:00) Exhibition Hall
Hyperpolarized Contrast Agents

1914.   Concentric Rings K-Space Trajectory for Hyperpolarized 13C MRSI
Wenwen Jiang1, Michael Lustig2, and Peder Larson3
1UC Berkeley | UCSF Graduate Group in Bioengineering, Berkeley, California, United States, 2Electrical Engineering, University of California, Berkeley, Berkeley, California, United States, 3Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, United States

 
Hyperpolarized 13C MR Spectroscopic Imaging (MRSI) is a novel noninvasive imaging technique which enables spatial mapping of physiological metabolites. But the short-lived effect of hyperpolarization poses severe challenges to develop rapid and robust imaging techniques. The current Echo-Planar Spectroscopic Imaging (EPSI) techniques are slew-rate limited and susceptible to system imperfections. Sampling k-space using concentric rings is advantageous to overcoming these limitations. We provide preliminary data that shows great potential for applying this approach to hyperpolarized 13C MRSI.

 
1915.   Feasibility of Rapid and Direct Detection of DNP Hyperpolarised Betaine Synthesis
Hyla Allouche-Arnon1, Lanette J. Friesen-Walder2,3, Ayelet Gamliel1, Jacob Sosna1, J Moshe Gomori1, and Rachel Katz-Brull1,4
1Radiology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel, 2Medical Biophysics, University of Western Ontario, London, Ontario, Canada, 3Robarts Research Institute, London, Ontario, Canada, 4BrainWatch Ltd., Tel-Aviv, Israel

 
The purpose of this study was to determine if the prolonged T1 of 13C nuclei in choline due to deuteration would allow monitoring of choline oxidase activity using hyperpolarised 13C MRI/S. In vitro thermal equilibrium spectra showed oxidation of choline by choline oxidase from Alcaligenes to betaine aldehyde hydrate and betaine. Deuteration of the choline resulted in decreased enzymatic reaction yield, but the prolonged T1 was required for hyperpolarised 13C studies. Hyperpolarised [1,1,2,2-D4,2-13C]choline was mixed with choline oxidase and dynamic spectra were acquired at 3T. Build-up of the metabolic products, [1,2,2-D3,2-13C]betaine aldehyde hydrate and [2,2-D2,2-13C]betaine was clearly detected.

 
1916.   Hyperpolarized Singlet State of Nitrous Oxide
Rajat Kumar Ghosh1, Stephen J. Kadlecek1, Nicholas N. Kuzma1, Mehrdad Pourfathi1, and Rahim Rizi1
1Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States

 
MRI/NMR signals can be acquired in real time at mM level concentrations by using techniques of Dynamic nuclear polarization to increase nuclear polarization by a factor of over 100,000. However, the utility of the technique is severely limited due to short polarization lifetimes on the order of the T1 time. In this work we hyperpolarize doubly 15N labeled nitrous oxide to the ~15-20% level. Additionally we extend the spin lifetime by over an order of magnitude by transferring the hyperpolarized longitudinal spin order to the singlet state. This may enable applications for perfusion imaging, or for cerebral blood flow measurements.

 
1917.   High Polarization of Nuclear Spins Mediated by Nanoparticles at Millikelvin Temperatures
David G. Gadian1, David T. Peat2, Kelvin Goh2, Anthony J. Horsewill2, and John R. Owers-Bradley2
1UCL Institute of Child Health, London, United Kingdom, 2School of Physics & Astronomy, University of Nottingham, Nottingham, United Kingdom

 
Our goal was to use the ‘brute-force’ approach (exposure to low temperature and high magnetic field) to achieve high polarizations of nuclei such as 13C and 15N, with a view to using pre-polarized 13C- or 15N-labelled agents to probe tissue metabolism in vivo. We explored the possibility that selected nanoparticles (including metallic nanoparticles) might act as low temperature relaxation agents. We found that with the use of copper nanoparticles we were able to achieve very high (>10%) 13C polarization levels in realistic periods of time. This methodology will enable us to generate and store large-scale quantities of highly polarized materials.

 
1918.   On SNR Performance of Sequence Designs for Dynamic Imaging of Hyperpolarized 13C Compounds
Kilian Weiss1, Andreas Sigfridsson1, and Sebastian Kozerke1
1Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland

 
Hyperpolarized metabolically active substances provide a promising approach to investigating in vivo metabolism in real time. However, due to the transient life time of hyperpolarization and fast metabolic conversion of injected substances such as 13C labeled pyruvate, suitable fast dynamic spectroscopic imaging sequences. Several methods have been proposed for efficient spatiotemporal encoding for dynamic imaging of hyperpolarized compounds. The current work presents a theoretical framework based on a compartmental signal model and three frequently used pulse sequence designs for 13C labeled pyruvate are compared in terms of signal-to-noise ratio performance.Spatial and spectral selective excitations are found to be most optimal for signal-to-noise performance. Data acceleration techniques were found to be beneficial for signal-to-nose performance if data acquisitions are limited by technical constraints.

 
1919.   Hyperpolarization Quenching in 13C Nuclei Bound to Fast Relaxing Quadrupolar 14N Mediated by Scalar Coupling Relaxation in Amide Groups Exposed to Earth's Magnetic Field
Enrico Chiavazza1,2, Eugen Kubala2,3, Concetta V. Gringeri2,4, Stephan Düwel2,5, Markus Durst2,5, Rolf F. Schulte2, and Marion I. Menzel2
1Chemistry, University of Turin, Turin, Italy, 2GE Global Research, Munich, Germany, 3Johannes Kepler University, Linz, Austria, 4Klinik im Klinikum Rechts der Isar, Technische Universität München, Munich, Germany, 5Institute of Medical Engineering, Technische Universität München, Munich, Germany

 
Working on hyperpolarized [5-13C]glutamine, a fast liquid-state polarization quenching during the transfer to the MRI scanner has been observed. This behavior can be explained with a substantial 13C T1 shortening caused by scalar coupling relaxation contribution (type II) of the quadrupolar 14N in the amide group. This contribution is effective only low magnetic fields <800lower case Greek muT, impairing the use of 13C-amides as hyperpolarized MRS/MRI probes. It is shown that high hyperpolarization level can be retained either using 15N labeled amide or applying a sustained magnetic field during the transfer of the sample from the polarizer to the MRI scanner.

 
1920.   Lanthanides as Low Temperature Relaxation Switches
David G. Gadian1, David T. Peat2, Angel J. Perez Linde3, Anthony J. Horsewill2, Walter Kockenberger3, and John R. Owers-Bradley2
1UCL Institute of Child Health, London, United Kingdom, 2School of Physics & Astronomy, University of Nottingham, Nottingham, United Kingdom, 3Sir Peter Mansfield MR Centre, School of Physics & Astronomy, University of Nottingham, Nottingham, United Kingdom

 
We report a series of longitudinal relaxation studies designed to evaluate the effectiveness of certain lanthanides as low temperature relaxation agents. This could be of value in the context of pre-polarizing 13C- or 15N-labelled agents that could then be used, following warming and dissolution, to probe tissue metabolism in vivo. We find that dysprosium-DTPA and holmium-DTPA offer scope for acting as relaxation switches, in the sense of enhancing relaxation at low temperatures without causing undue enhancement of relaxation on returning to room temperature.

 
1921.   MRI of 1H Long-Lived States Originated from ParaHydrogen Induced Polarization in Cs-Symmetric Molecules Using a Clinical MRI System
Dirk Graafen1,2, María Belén Franzoni2, Kerstin Münnemann2, Hans Wolfgang Spiess2, and Laura Maria Schreiber1
1Department of Radiology, Johannes Gutenberg University Medical Center, Mainz, Germany, 2Max Planck Institute for Polymer Research, Mainz, Germany

 
The singlet state originated from parahydrogen induced polarization (PHIP) was stored inside the MRI scanner for minutes. After that time, it was converted to observable magnetization by generating singlet-triplet conversion. For this purpose, the Cs-symmetric molecule dimethyl maleate was used. In the present report it is shown that singlet-triplet conversion can be performed inside the observation field by applying a chemical shift scaling pulse sequence. The pulse sequence comprises of 80 cycles of eight 180° pulses and two characteristic delays. Moreover, a proton image was detected by using this conversion sequence prior every k-space line acquisition of a GRE sequence.

 
1922.   High Speed 3D Overhauser-Enhanced MRI Using Combined B-SSFP and Compressed Sensing
Brandon Dean Armstrong1,2, Mathieu Sarracanie1,2, Jason P. Stockmann1,2, and Matthew Rosen1,2
1Physics, Harvard University, Cambridge, MA, United States, 2Martinos Center for Biomedical Imaging, Boston, MA, United States

 
We present a new sequence for Overhauser-enhanced MRI based on balanced steady state free precession. In contrast to other OMRI techniques that use a pre-polarization step, the electron spin saturation is embedded directly into the phase encode gradient step. This significantly reduces the acquisition time as there is no need to refresh the hyperpolarized signal every T1. Undersampling k-space strategies are also employed to further increase the temporal resolution. We present images with 1x1x3.5 mm resolution on a 256x64x32 matrixaquired in 65 s.

 
1923.   Nuclear Spin Properties of Hyperpolarized Solid-State MRI Agents.
Maja Cassidy1, Henry Chan2, Jingzhe Hu3, Nicholas Whiting3, Charles Marcus1,4, and Pratip Bhattacharya2,5
1Harvard University, Cambridge, MA, United States, 2Huntington Medical Research Institutes, Pasadena, CA, United States, 3The University of Texas MD Anderson Cancer Center, Houston, TX, United States, 4University of Copenhagen, Copenhagen, Denmark, 5University of Texas, Houston, TX, United States

 
We present measurement of the nuclear spin properties of hyperpolarized silicon nanoparticles suitable for targeted imaging of gastrointestinal disease. The nuclear polarization dynamics are unaffected by surface functionalization, particle tumbling or the in-vivo environment. Increasing the polarization time results in an increase in 29Si signal together with longer depolarization times. Single shot 29Si images can be obtained up to 90 min after delivery to the imaging magnet, and down to concentrations of 5mg/mL, corresponding to sub-picomolar SiNP concentrations.

 
1924.   Earth’s Field MRI Using Continuous SABRE Hyperpolarization
Niels Schwaderlapp1, Thomas Lickert1, Sebastien Baer1, Jürgen Hennig2, Dominik v. Elverfeldt1, and Jan-Bernd Hövener1
1Department of Radiology, Medical Physics, University Hospital Freiburg, Freiburg, Germany, 2Department of Radiology, Medical Physics, University Medical Center Freiburg, Freiburg, Germany

 
The method of hyperpolarization of signal amplification by reversible exchange (SABRE) is used to acquire images in the earth’s field. The polarization field of an EFMRI system is applied prior to each measurement and utilized here to continuously hyperpolarize a liquid sample. This allows the observation of a substance hyperpolarized by SABRE for long term (>10 min) and thereby allows imaging with a simple spin echo sequence without the need of moving the sample. This technique can be used to promote EFMRI of hyperpolarized targeted molecules.

 
1925.   Method and System for Dynamic Nuclear Polarization of Frozen Gases
Nicholas N. Kuzma1, Mehrdad Pourfathi1, Hoora Shaghaghi1, Rajat Kumar Ghosh1, Stephen J. Kadlecek1, and Rahim Rizi1
1Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States

 
We describe a new general approach for producing highly spin-polarized frozen gases, such as 129Xe, 13CO2, and 15N2O, for magnetic resonance imaging. Each gas is liquefied and mechanically mixed with a free radical (trityl) dissolved in a liquid glassing agent (1-propanol) at a specific temperature and pressure. Molecular diffusion both in the liquid and in the solid state can cause self-segregation of these mixtures into pure frozen-gas clusters surrounded by the well-mixed matrix. We report the effects of the annealing temperature during the sample preparation on the subsequent T1 relaxation times and on the efficiency of the DNP process in the 15N2O system and contrast these new findings with our earlier 129Xe results.

 
1926.   On the Accuracy of AUC Ratio Method for Detecting Treatment Changes with Hyperpolarised 13C Dynamic Spectra
Deborah K. Hill1, Matthew R. Orton1, Martin O. Leach1, Yuen-Li Chung1, and Thomas R. Eykyn1,2
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

 
Signal enhancement from Dynamic Nuclear Polarisation allows estimation of apparent enzymatic rates in vivo in real-time. We have previously described a method for calculating metrics that are sensitive to treatment induced changes in the apparent forwards rate constant, based on AUC ratios of injected and generated metabolites (e.g. pyruvate and lactate). This AUC ratio approach is simpler and more robust than curve fitting using the modified Bloch equations, but suffers from bias. This theoretical abstract explores the assumptions required for the AUC ratio approach to be valid, and shows that the bias is less than 10% in a representative example.

 
1927.   PHIP-Enhanced Natural Abundance 13C Imaging in a Clinical MRI System Via 1H/13C Polarization Transfer
Dirk Graafen1,2, Jan Falk Dechent1,2, Michael Ryan Hansen2, Kerstin Münnemann2, Hans Wolfgang Spiess2, and Laura Maria Schreiber1
1Department of Radiology, Johannes Gutenberg University Medical Center, Mainz, Germany, 2Max Planck Institute for Polymer Research, Mainz, Germany

 
Aim of this study was to realize transfer of 1H hyperpolarization to 13C in a clinical MRI system utilizing parahydrogen induced polarization (PHIP). The transfer was achieved by a modified refocused INEPT sequence (PH-INEPT+) which was sequentially transmitted since most clinical MRI systems are only equipped with a single RF transmitter channel. The generated hyperpolarized 13C state for natural abundance hydroxyethylpropionate was used for MRI employing the RARE sequence with 64 images acquired in the echo train. A single acquisition of an image yielded an SNR of 13 that could be increased to 40 by averaging in the echo train.

 
1928.   Radial Golden Angle Fast Spin Echo: A Hyperpolarized 13C Multi Contrast Metod
Christoffer Laustsen1,2, Steffen Ringgard1, Henrik Birn3, Michael Pedersen1, and Jan Henrik Ardnekjaer-Larsen4,5
1MR Research Centre, Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark, 2Danish Research Centre for Magnetic Resonance, Hvidovre Hospital, Hvidovre, DK, Denmark, 3Department of Biomedicine, Faculty of Health Sciences, Aarhus University, Aarhus, Denmark, 4GE healthcare, Broendby, Denmark, 5Department of Electrical Engineering, Technical University of Denmark, Kgs. Lyngby, Denmark

 
We here present a new multi contrast MRI sequence for 13C-labeled hyperpolarized agents, for angiographic, perfusion and relaxation mapping, with reduced motion artifacts. Radial imaging using the golden angle, 111.25°, has been utilized for free breathing MR and has successfully been used for 3He MR of lungs, where the longitudinal T1 relaxation and RF calibration yields quantitative difficulties. Hyperpolarized pulse sequences should be designed to utilize the magnetization especially efficient. In this study we employ a slice selective radial fast spin echo (FSE) sequence to show the urea transport in the kidney cortex. Further, we used the center of k-space readout for RF self-calibration and T2 mapping.

 
1929.   Chemical Shift of 129Xe Is Dependent on Red Blood Cell Oxygenation
General Leung1, Graham Norquay1, Jan Wolber2, and Jim M. Wild1
1Department of Cardiovascular Science, University of Sheffield, Sheffield, South Yorkshire, United Kingdom, 2GE Healthcare, Chalfont St Giles, Buckinghamshire, United Kingdom

 
Hyperpolarised 129Xe dissolves into various biological tissues and has a change in resonance frequency that is sensitive to its environment. The resonance frequency has previously been shown to be sensitive to red blood cell oxygen saturation and its use as an exogenous probe for MR oximetry is of interest. Here, we develop we develop a robust, quantitative relationship between oxygen saturation and chemical shift in vitro.

 
1930.   Advanced Single-Shot Parallel Imaging Strategies for Hyperpolarized 13C Chemical Shift Imaging
Markus Durst1,2, Ulrich Köllisch1,2, Francesca Frijia3, Luca Menichetti4, Maria Filomena Santarelli5, Massimo Lombardi3, Titus Lanz6, Matthias Müller6, Jan Henrik Ardenkjaer-Larsen7, Marion I. Menzel2, Axel Haase1, and Rolf F. Schulte2
1Institute of Medical Engineering, Technische Universität München, Garching, Germany, 2GE Global Research, Garching, Germany, 3Fondazione CNR-Regione Toscana G.Monasterio, Pisa, Italy, 4Institute of Clinical Physiology of CNR, Pisa, Italy, 5CNR Institute of Clinical Physiology, Pisa, Italy, 6Rapid Biomedical, Rimpar, Germany, 7GE Healthcare, Brřndby, Denmark

 
Metabolic imaging of the heart following injection of hyperpolarised pyruvate could allow new methods for diagnosis and characterisation of heart disease. However, fast and efficient imaging sequences are required to adequately encode the information due to the rapidly decaying signal. Therefore, parallel imaging could be highly beneficial for in vivo metabolic imaging to speed up the acquisition process. In this work, an efficient autocalibrated single-shot spiral parallel imaging sequence for metabolic imaging of hyperpolarised compounds is presented. It is demonstrated that parallel imaging enables single-shot dynamic hyperpolarised imaging of the pig heart, which is an important step towards human studies.

 
1931.   Multiband Excitation Pulses for Treatment Response Studies with Hyperpolarised 13C Fumarate
Markus Durst1, Stephan Düwel1, Concetta V. Gringeri2, Yvonne Kosanke3, Claudia Gross3, Rickmer Braren3, Axel Haase1, Marion I. Menzel2, and Rolf F. Schulte2
1Institute of Medical Engineering, Technische Universität München, Garching, Germany, 2GE Global Research, Garching, Germany, 3Institute of Radiology, Klinikum rechts der Isar, Technische Universität München, München, Germany

 
13C-labeled fumarate is a promising candidate for hyperpolarised in-vivo applications because it could allow the early detection of necrosis. The goal of this work was to design and implement an efficient sequence for the in-vivo quantification of fumarate and its metabolite. The sequence combines a multiband excitation pulse specifically tailored to the spectrum of fumarate and malate with IDEAL spiral imaging. Saturation recovery spectra are acquired for malate to analyse the metabolic kinetics. First measurements in an orthotopic rat tumour model were performed before and after transcatheter arterial embolisation to validate the effectiveness of the method.

 
1932.   Metabolic Spectroscopy and Imaging of Lung Inflammation Using Hyperpolarized 1-13C Pyruvate
Sarmad Siddiqui1, Hoora Shaghaghi1, Stephen J. Kadlececk1, Harrilla Profka1, and Rahim Rizi1
1Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States

 
It is generally accepted that inflammatory cell activity, particularly that of neutrophils, may contribute to, or even exacerbate existing lung injury. In this study, the uptake of hyperpolarized [1-13C] pyruvate is investigated as a potential marker for inflammation in lung tissue. Excised lungs from a bleomycin-exposed inflammatory rat model were used to study changes in hyperpolarized pyruvate uptake and it’s conversion to lactate and alanine. Chemical shift imaging was also performed to generate metabolite maps for excised lungs. Significant differences in the production of hyperpolarized lactate were found between the disease inflammatory model and control rats.

 
1933.   Towards the Implementation of Hyperpolarized, Functionalized Silicon Nanoparticles as in vivo Colorectal Molecular Imaging Agents
Nicholas Whiting1, Jingzhe Hu1,2, Maja Cassidy3, Marc Ramirez1, James A. Bankson1, Niki Millward1, David Menter1, Marsha Frazier1, Charles Marcus3,4, and Pratip Bhattacharya5
1The University of Texas MD Anderson Cancer Center, Houston, TX, United States, 2Bioengineering Department, Rice University, Houston, TX, United States, 3Harvard University, Cambridge, MA, United States, 4University of Copenhagen, Copenhagen, Denmark, 5University of Texas, Houston, TX, United States

 
We describe 29Si magnetic resonance spectroscopy and imaging of hyperpolarized silicon nanoparticles ranging from 20 nm to 2um. The enhanced detection sensitivity, long hyperpolarization decay times (T1 ~40 minutes), and amenable surface chemistry as well as biocompatibility and biodegrability of these nanoparticles make them potentially well-suited as cancer targeting agents. We discuss optimizations to the nanoparticle size, porosity, and surface functionalization with regard to polarization dynamics. Future studies will investigate the viability of functionalized silicon nanoparticles as in vivo targeting agents for the early detection of colorectal polyps and tumors on murine models.

 
1934.   Metabolic Exchange Rate Imaging with Hyperpolarised [1-13C]Pyruvate
Rolf F. Schulte1, Oleksandr Khegai1,2, Eliane Ferral2, Martin A. Janich1, Marion I. Menzel1, Axel Haase3, Markus Schwaiger2, and Florian Wiesinger1
1GE Global Research, Munich, Germany, 2TUM, Munich, Germany, 3Technische Universität München, Munich, Germany

 
Metabolic imaging with hyperpolarised [1-13C]pyruvate and its downstream metabolites requires quantitative methods in order to relate image intensities to the underlying physiological processes. In this work, we improve and compare two different approaches for metabolic exchange rate imaging: saturation-recovery and frequency-domain metabolic modelling. The comparison of the different methods acquired during two separate injections in four rats bearing subcutaneous MAT B III tumours show an excellent agreement with each other, both yielding exchange rates in the tumour of kPL=0.08 s-1.

 
1935.   Multi-Compound Hyperpolarized 13C Perfusion Imaging
Cornelius von Morze1, Robert A. Bok2, Galen D. Reed1, Jan Henrik Ardenkjaer-Larsen3,4, John Kurhanewicz1, and Daniel B. Vigneron1
1Dept. of Radiology and Biomedical Imaging, UC San Francisco, San Francisco, California, United States, 2Dept. of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California, United States, 3GE Healthcare, Frederiksberg, Denmark, 4Dept. of Electrical Engineering, Technical University of Denmark, Lyngby, Denmark

 
We demonstrate simultaneous hyperpolarization and imaging of three non-toxic 13C-labeled perfusion MRI tracers with dissimilar molecular structures (urea, hydroxymethyl cyclopropane aka “HP001”, and t-butanol) and variable physiological characteristics. Due to varying bilayer permeability, these agents may be valuable in cancer imaging for isolating vascular and perfused tissue compartments, and separating vascular permeability and perfusion. Rapid dynamic imaging was by bSSFP with ramped flip angles and multi-band frequency encoding. These methods were applied to transgenic mice with prostate cancer. We modeled the data for absolute quantification of blood flow, and parameters were on the order of expected values.

 
1936.   Hyperpolarized [1-13C]acetylcarnitine as a Tracer for Cardiac Metabolism
Jessica A. M. Bastiaansen1, Tian Cheng1,2, Rolf Gruetter3,4, and Arnaud Comment5
1Laboratory of Functional and Metabolic Imaging, EPFL, Lausanne, Switzerland, 2Institute of Physics of Biological Systems, EPFL, Lausanne, Switzerland, 3Laboratory of Functional and Metabolic Imaging, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, 4Department of Radiology, University of Lausanne and Geneva, Lausanne and Geneva, Switzerland, 5Institute of Physics of Biological Systems, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland

 
Acetylcarnitine transports acetylgroups across mitochondrial membranes, buffers excess acetylCoA and is an intermediate for acetate oxidation. In hearts,hyperpolarized acetate is converted to acetylcarnitine, acetylCoA and citrate which appear with a time delay and decay with T1. This study explored the use of hyperpolarized acetylcarnitine as a tracer,skipping two enzymatic reactions needed for acetate oxidation and to elucidate the backflux to acetylCoA to describe the entire system of enzymatic reactions. Glutamate formation was detected and one additional metabolite which was not observed previously. These findings highlight the intricate relationship between reaction, transport and relaxation rates in the choice of hyperpolarized substrates.

 
1937.   
Continuous Proton Hyperpolaritzation Via SABRE and Hollow Fiber Membranes
Jan Falk Dechent1,2, Louise A. R. Highton3, Gary G. R. Green4, Simon B. Duckett3, Hans Wolfgang Spiess2, Laura Maria Schreiber1, and Kerstin Münnemann2
1Radiology / Medical Physics, University Medicine, Mainz, Germany, 2Max Planck Institute for Polymerresearch, Mainz, Germany, 3Department of Chemistry, University of York, York, United Kingdom, 4York Neuroimaging Centre, York, United Kingdom

 
Despite the interesting applications of hyperpolarized contrast agents, all suffer from their limited T1 time (hetero and proton nuclei) and most techniques can only be applied to small sample volumes in a batch mode. Here, a combination of the SABRE – proton hyperpolarization method (Signal Amplification By Reversible Exchange) together with the use of hollow fiber membranes is presented. The circular flow setup allows for a continuous generation of proton hyperpolarization and a fast transport from the membrane module into the detection chamber. Large signal enhancements can be observed over a period 12 hours.