Cell Tracking I

Hall B                        Monday 14:00-16:00                                                                             Computer 67           

14:00         4166.     Monitoring the Uptake of 19F Nanoparticles and in Vivo Migration of Dendritic Cells Using Magnetic Resonance

Helmar Waiczies1,2, Bettina Erdmann3, Bernd Ittermann1,2, Frank Seifert1,2, Thoralf Niendorf, 2,4, Sonia Waiczies, 2,5

1Physikalisch Technische Bundesanstalt, 10587 Berlin, Germany; 2Berlin Ultrahigh Field Facility, Max-Delbrueck Center for Molecular Medicine, 13125 Berlin, Germany; 3Electron Microscopy, Max-Delbrueck Center for Molecular Medicine, 13125 Berlin, Germany; 4Experimental and Clinical Research Center (ECRC), Charité Campus Buch, Humboldt-University, 13125 Berlin, Germany; 5Department of Hematology and Oncology, Charité Campus Buch, Humboldt-University, 13125 Berlin, Germany

19F cellular magnetic resonance imaging (MRI) provides signal selectivity during cell tracking and a possibility to overlay 19F-labeled cells with anatomic 1H scans. This work investigates the uptake of nanoparticles containing perfluoro-15-crown-5 ether in dendritic cells and their impact on cell function. 19F MR spectroscopy and electron microscopy showed a rapid and efficient uptake of nanoparticles by DC. The 19F signal intensity in these cells was shown to be directly related to 19F nanoparticle size. 19F/1H MRI showed that DC function was not disturbed following 19F-labeling as demonstrated by an efficient migration of these cells into draining popliteal lymph nodes.

14:30         4167.     Long Term Evaluation of the 1.28 Ppm After Transplantation of Purified Neural Progenitor Cells in the Brain

Chiao-Chi V. Chen1, Kuan-Chi Mo1, Ching-Yu Chuang2, Hung-Chih Kuo3, Chen Chang1

1Functional and Micro-magnetic Resonance Imaging Center, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan; 2Institute of Biotechnology, National Taiwan University, Taipei, Taiwan; 3Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan

The present study aimed to use in vivo MRS to track the long term changes and consequences of purified neural progenitor cells (NPCs) in the brain. Following transplantation, there were signal intensity changes over time at the 1.28 ppm along with the NAA signal, which may represent the variations of the functional status of the NPC biomarker.

15:00         4168.     Molecular MR Imaging of Labeled Stem Cells in a Mouse Burn Model in Vivo

Valeria Righi1,2, Ali M. Rad3, Dionyssios Mintzopoulos1, Alan J. Fischman4, A Aria Tzika1,2

1NMR Surgical Laboratory, Department of Surgery, Massachusetts General Hospital and Shriners Burns Institute, Harvard Medical School, Boston, MA, United States; 2Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Athinoula A. Martinos Center for Biomedical Imaging, Boston, MA, United States; 3Division of Burn, Shriners Burn Institute, Harvard Medical School, Boston, MA, United States; 4Division of Burn, Shriners Burns Institute, Harvard Medical School, Boston, MA, United States

Recently, the interest in noninvasive novel methods for molecular imaging using MRI of clinically relevant mouse models using super-paramagnetic iron-oxide (SPIO) nanoparticles as contrast agents has increased. SPIO nanoparticles are commonly used to label cells for cellular imaging. Several methods to generate positive contrast of magnetically labeled cells have been suggested. The scope of this study was to track label stem cells in a burn mouse model using noninvasive positive-contrast MRI methods in vivo. The results have direct implications for monitoring labeled stem cells during wound healing.

15:30         4169.     Use of Balanced SSFP MR Microscopy for Imaging Endogenously Labeled Neuroprogenitor Stem Cells with Linear Combination Steady-State Free Precession (LCSSFP) for Artifact Reduction.

H. Douglas Morris1, James P. Sumner2

1NIH Mouse Imaging Facility, National Institues of Health, Bethesda, MD, United States; 2Laboratory of Functional and Molecular Imaging, National Institues of Health, Bethesda, MD, United States

MRI has become a potent method for tracking cells in situ and in vivo.   Recent techniques can produced endogenously labeled cells that can be for tracking cellular migration.  A complication is the presence of a large amount of magnetic particle label, which adversely affects high-efficiency pulse sequences such as balanced SSFP.  The worst off-resonance artifacts can be mitigated by using a linear combination of SSFP sequences (LCSSFP), which can reduce the artifacts produced by these label caches while preserving the effect detection of the labeled cells.

                                   Tuesday 13:30-15:30                                                                            Computer 67           

13:30         4170.     Relaxometry Vs Artefact Volume Measurements  for Estimating the Number of Iron-Labelled Macrophages:  in Vivo Testing in the Mouse Brain

Jean-Christophe Brisset1,2, Monica Olivia Sigovan1,2, Fabien Chauveau1,2, Adrien Riou1,2, Norbert Nighoghossian1,2, Emmanuelle Canet-Soulas1,2, Yves Berthezene1,2, Marlene Wiart1,2

1University of lyon, Lyon, france, France; 2Creatis-LRMN, CNRS, UMR 5220; Inserm, U 630; Insa de Lyon, Lyon, France

The aim of this study was to compare 4 quantitative methods for estimating the number of iron-labelled cells injected in the mouse brain: T2, T2* relaxometry, and artefact volume measurement using negative and positive contrasts. Eight mice were stereotaxically injected with [500-7,500] iron-labelled cells and imaged at 4.7T. Bland-Altman and scatterplots were used to compare the T2 and T2*-based estimated number of cells, the artefact volumes, and the actual number of iron-labelled cells. T2 and T2* quantification failed to estimate the number of iron-labelled cell in-vivo, while measurement of the artefact volume gave promising results.

14:00         4171.     Detecting the Migration and Accumulation of Macrophages in an Acute Rejection Model of Heart-Lung Transplantation in Rats by in Vivo MRI Using a New Nano-Sized Iron Oxide Particle

Haosen Zhang1, Qing Ye1, Chih-Lung Chen2, Kevin Hitchens1, Wen-Yuan Hsieh3, Li Liu1, Yijen Wu1, Lesley Foley1, Hsin-Hsin Shen2, Jassy Wang2, Chien Ho1

1NMR Center for Biomedical Research, Carnegie Mellon University, Pittsburgh, PA, United States; 2Biomedical Engineering Laboratories, Industrial Technology Research Institute, Hsinchu, Taiwan; 3Material and Chemical Research Laboratories, Industrial Technology Research Institute, Hsinchu, Taiwan

The aim of this study is to detect the migration and accumulation of macrophages by in vivo MRI in a rat heart-lung transplantation model of acute rejection using a sensitive nano-sized iron oxide particle (ITRI-IOP). After infusion of the macrophages labeled in vitro with ITRI-IOP, punctuate spots of hypointensity are observed on the myocardium of the transplant allograft heart 24 hrs later. Ex vivo imaging and immunohistochemistry analysis of the fixed allograft heart shows abundance of punctuated spots of hypointensity that are caused by the iron-loaded macrophages, which is not shown in the native heart of the same rat.

14:30         4172.     1.5T Micro-MRI of Macrophages in Obesity-Associated Inflammation: Feasibility Study

Marie Poirier-Quinot1, Alain Luciani2, Michael Levy3, Jean-Christophe Ginefri1, Nathalie Luciani3, Vanessa Devaux2, Sylvie Manin2, Eric Lancelot4, Luc Darrasse1, Claire Wilhelm3, Florence Gazeau3

1U2R2M - UMR 8081 CNRS/Univ Paris Sud, Orsay, France; 2INSERM U841, Hôpital Henri Mondor, Créteil, France; 3UMR 7057 CNRS/Univ Paris - Diderot, France; 4Guerbet Recherche, Roissy, France

It has been recently shown that obesity-associated inflammation is related to the recruitment of pro-inflammatory macrophages. The present work investigates the feasibility to detect in-vivo macrophages in a murine model of obesity using magnetic resonance microscopy following systemic injection of a new kind of iron-oxide nanoparticles (USPIO). High-resolution 1.5 T MRI combined with a superconducting surface coil and an improved USPIO, for micrometric evaluation of fat tissue, appears to be an efficient way to detect macrophages related to fat inflammation. This approach for the follow-up of animals involved in therapeutic trials aimed at limiting fat inflammation has great potential.

15:00         4173.     Magnetic Resonance MicroImaging of Cell Migration in Porous Biomaterial Scaffolds Designed for Tissue Engineering

Marie Poirier-Quinot1, Claire Wilhelm2, Mohammed Derkaoui3, Jean-Christophe Ginefri1, Nathalie Luciani2, Luc Darrasse1, Didier Letourneur3, Florence Gazeau2, Catherine Le Visage3

1Imagerie par Résonance Magnétique Médicale et Multimodalités (UMR 8081 ), Univ Paris Sud, CNRS, Orsay, France; 2UMR 7057 CNRS/Univ Paris - Diderot, France; 3Inserm U698,  CHU X. Bichat Paris, France

Polymeric scaffolds, involved in tissue engineering, for cell seeded migration and proliferation, are often extremely sensitive. Therefore 3D non-invasive imaging methods are needed to study tissue-engineered constructs. This work has demonstrated the efficiency of high resolution imaging, using a superconducting surface coil at 1.5 T, with efficient medium and cellular contrast agents, for 3D visualization of tissue-engineered constructs. The labeled cell presence was quantified within the entire structure and their spatial distribution was assessed along the privileged orientation of the pores. According to these results, spatial distribution of cells is easily monitored through the complex microstructure of scaffolds.

                                   Wednesday 13:30-15:30                                                                       Computer 67           

13:30         4174.     Application of Ultra-Short Echo Time Imaging for Visualization of SPIO-Loaded Tumor Cells in Brain

Yuanxin Chen1, Jian-Xiong Wang2, Lisa M. Gazdzinski1, Paula J. Foster1, Brian K. Rutt3

1Imaging Research Laboratories, Robarts Research Institute, London, Ontario, Canada; 2Applied Science Laboratory, GE HEALTHCARE, London, Ontario, Canada; 3Department of Radiology, Stanford University, Stanford, CA, United States

There has been increased interest in positive-contrast MRI methods to visualize cells labeled with superparamagnetic iron oxide (SPIO) nanoparticles. Here, we applied the 3D Cones technique for ultra-short echo time (UTE) imaging of SPIO-labelled tumour cells in mouse brain. An intracranial tumour model was created by injection of SPIO labeled GL261 mouse glioma cells into the striata of C57/Bl6 mice. Short-T2-selective UTE imaging with a 3D Cones sequence on a 1.5T MR scanner was accomplished through the subtraction of interleaved, alternating-TE data acquired in an RF-TE1-RF-TE2 scheme. This work shows the feasibility of selectively tracking SPIO-labeled cells with positive-contrast.

14:00         4175.     Immunomodulation and Magnetic Resonance Tracking of Transplanted Human Glial-Restricted Precursor Cells in a Mouse Model of Multiple Sclerosis - not available

Heechul Kim1,2, Piotr Walczak1,2, Naser Muja1,2, James T. Campanelli3, Jeff W.M. Bulte1,2

1Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; 2Cellular Imaging Section, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; 3Q Therapeutics, Inc., Salt Lake City, UT, United States

Magnetically labeled human glial restricted precursor (hGRP) cells were transplanted and tracked in a mouse model of multiple sclerosis. The clinical severity of EAE was attenuated in hGRP-transplanted mice compared with controls. Hypointense MRI signals were detected primarily in the ventricles after transplantation. hGRP cell-treated mice showed a significant decrease in antigen-specific T cell proliferation in response to MOG and concanavalin A, compared to control mice. Based on the above results, we postulate that the signals generated from transplanted GRP cells in the ventricle modulate the systemic immune response.

14:30         4176.     Cellular MRI Assessment of Magnetic Fluorescent Bead Labeled Macrophage Accumulation Following High Intensity Focused Ultrasound (HIFU) Induced Damage in a Murine Model

Hilary Hancock1, Eric M. Gold1, Bobbi K. Lewis1, Melissa Smith1, Victor Frenkel1, Joseph A. Frank1,2

1Radiology and Imaging Sciences, NIH, Bethesda, MD, United States; 2National Institute of Biomedical Imaging and Bioengineering, NIH, Bethesda, MD, United States

This study investigated in vivo labeling of monocytes with SPIO/fluorescent 40nm beads followed by Cellular MRI and fluorescent microscopy to determine the effects of ablative or pulsed high intensity focused ultrasound (HIFU) in a murine model. Pulsed HIFU exposures exhibited smaller regions of edema and hypointense regions, confined to superficial muscle and dermis, on T2*W images with smaller amounts of immune response within tissues compared to ablated tissues.

15:00         4177.     19F MRI Tracking of Dendritic Cells in a Novel Migration Assay

Fernando Bonetto1, Mangala Srinivas1, Bettina Weigelin2, Luis Cruz Ricondo1, Arend Heerschap3, Carl Figdor1, I.J. de Vries1

1Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands; 2Cell Biology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands; 3Radiology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands

Dendritic cell migration is monitored and quantified by using 19F-Chemical Shift Spectroscoypic imaging (CSI) in a novel migration assay. 3D scaffolds specially designed to mimic biological tissue are used in this assay. The particular layered structure of the assay allows to assess cell migration and to perform the control experiment simultaneously. Cells were labeled with a perfluorocarbon compound. Our results demonstrate that 19F-CSI at 7T is suitable to track cell migration in this type of opaque assays. The migration rates obtained in this way are comparable to clinical results suggesting that the proposed migration assays properly mimics in-vivo conditions.

                                   Thursday 13:30-15:30                                                                          Computer 67           

13:30         4178.     19F Imaging Assessment of Labeled Macrophage Accumulation in a Mouse Brain Following Experimental Traumatic Brain Injury

Lesley May Foley1, T Kevin Hitchens2,3, John A. Melick4, Chien Ho2,3, Patrick M. Kochanek4,5

1Pittsburgh NMR Center for Biomedical Research , Carnegie Mellon University, Pittsburgh, PA, United States; 2Pittsburgh NMR Center for Biomedical Research, Carnegie Mellon University, Pittsburgh, PA, United States; 3Department of Biology, Carnegie Mellon University, Pittsburgh, PA, United States; 4Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States; 5Departments of Critical Care Medicine, Pediatrics and Anesthesiolgy, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States

Macrophages may play a role in mediating both early detrimental and delayed beneficial effects of inflammation. Therefore, the ability to detect the macrophage response in vivo after traumatic brain injury (TBI) may lead to a greater understanding of both secondary injury and repair. Here we report the use of an MRI 19F tracer agent that is taken up by macrophages in vivo to detect the response to experimentally induced TBI in a mouse model. Preliminary results indicate presumptive 19F-labeled macrophage infiltration at the site of injury in the brain which corroborated findings from a recent study using iron oxide-labeled macrophages.

14:00         4179.     A Membrane Labeling Agent for MR Tracking of Transplanted Pancreatic Islets

Emily Alexandria Waters1, Ellen Kretzschmar Kohlmeir2, Daniel J. Mastarone1, Ling-Jia Wang3, Dixon Blake Kaufman3, Thomas J. Meade1,2

1Chemistry, Northwestern University, Evanston, IL, United States; 2Biochemistry, Molecular Biology, and Cellular Biology, Northwestern University, Evanston, IL, United States; 3Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, United States

Pancreatic islet transplant is a promising treatment for diabetes, but little is known about the fate of islets after transplant.  We have developed a multimeric MR contrast agent with three macrocyclic Gd(III) chelates attached to a scaffold, with a branched alkyne chain installed to anchor the agent in cellular membranes.  This agent effectively labels islets in a time- and concentration-dependent fashion.  Islets can be detected with MRI after a 4h incubation with 30 μM agent.  Minimal leaching occurs over a 24h period after incubation.  Labeling of islets does not affect cell viability or alter islet morphology.

14:30         4180.     MRI of Vascular Cells Labeled with SPIO-PLL Complexes for Heart Valve Tissue Engineering Studies

Paul A. Schornack1, Sharan Ramaswamy

1Radiology, University of Pittsburgh, Pittsburgh, PA, United States

Noninvasive & nondestructive monitoring of the cellular function within the developing valvular tissue is a critical aspect of implant success.  In-depth study on the longitudinal (temporal) position & migration patterns of   cells during the tissue development process.  This can be achieved through cellular MRI (cMRI) techniques such as with the labeling of cells with superparamagnetic iron oxide (SPIO) particles.  Immediate goal – Conduct efficient, non-toxic, endosomal uptake studies of SPIO particles in endothelial cells (ECs) & smooth muscle cells (SMCs)

15:00         4181.     Pro-Survival Cocktail Improves Bone Marrow Stromal Cells (BMSC) Survival and Homing to Flank Tumors as Demonstrated by Cellular MRI

Aneeka Chaudhry1, Edyta Pawelczyk2, Eric Gold1, Bobbi K. Lewis1, Melissa Brown1, Arun Balakumaran3, Joseph A. Frank1,4

1Clinical Center, NIH, Bethesda, MD, United States; 2Federal Drug Administration, Bethesda, MD, United States; 3National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD, United States; 4National Institute of Biomedical Imaging and Bioengineering, NIH, Bethesda, MD, United States

In-vivo loss of implanted or infused cells is detrimental to stem cell therapies, as it undermines cell homing and therapeutic efficacy.  This study aims to improve the homing and survival of FePro labeled bone marrow stromal cells via incubation with a cocktail of pro-survival and growth factors.

Cell Tracking II

Hall B                        Monday 14:00-16:00                                                                             Computer 68           

14:00         4182.     Efficient Labeling of Multiple Cell Lines with a New SPIO Agent for Cell Tracking by MRI

Catherine Ramsay1, Christiane Mallett1, Paula Foster1

1Imaging, Robarts Research Institute, London, ON, Canada

The purpose of this study was to test a new commercially available SPIO which has a colloidal size of 50 nm, a zeta potential of +31 mV and which is cross-linked with a rhodamine B label. Here we show that a variety of cell lines (lymphocytes, cancer and stem cells) can be labeled with this agent (MoldayION Rhodamine B, BioPal Inc), by simple co-incubation, without the use of transfection agents, at a level that permits their detection by MRI and without affecting cell viability.  This is illustrated using iron staining of cells, fluorescence microscopy, electron microscopy and cellular MRI.

14:30         4183.     Complexation of MPIO with Poly-L-Lysine Greatly Enhances Magnetic Cell Labeling Efficiency

Kevin S. Tang1, Erik M. Shapiro2

1Department of Biomedical Engineering, Yale University, New Haven, CT, United States; 2Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT, United States

Magnetic cell labeling with MPIOs is well established, however, current protocols employ long labeling times. Incubation of negatively charged iron oxide nanoparticles with positively charged transfection agents, such as poly-l-lysine (PLL) increases labeling efficiency. Therefore, it was hypothesized that pre-incubating MPIOs with various quantities of PLL would similarly enhance the rate of magnetic cell labeling. Indeed, it was discovered that MPIO complexation with PLL yielded positive zeta potential. Furthermore, cells labeled with MPIO:PLL complexes were fully labeled after only two hours incubation, whereas negatively charged MPIOs labeled only 20%, even after four hours.

15:00         4184.     Fluorinated Cyclodextrin as a Novel 19F Contrast Agent for Labeling Cells

Florian Schmid1, Maria Becker2, Marc Hotfilder3, Bart-Jan Ravoo2, Cornelius Faber1

1Department for Clinical Radiology, University Hospital Münster, Münster, Germany; 2Organic Chemistry Institute of the Westfälische Wilhelms-Universität Münster, Münster, Germany; 3Department of Pediatric Hematology and Oncology, University Children's Hospital Münster, Münster, Germany

Fluorinated Cyclodextrins are interesting candidates for novel MR contrast agents for cell labelling as they are soluble in water and contain lots of 19F atoms that contribute to a single spectral line. Results from first cell labeling experiments performed on Ewing's sarcoma cells are presented; 19F MR images acquired on a clinical 3T MRI scanner are shown.

15:30         4185.     In Vivo MRI Multicontrast Kinetic Analysis of the Uptake and Intracellular Trafficking of Paramagnetically Labeled Liposomes

Daniela Delli Castelli1, Enzo Terreno1, Walter Dastrů1, Evelina Cittadino1, Francesco Mainini1, Elena Torres1, Michela Spadaro1, Silvio Aime1

1University of Torino, Turin, Italy

The multi-contrast ability of paramagnetically loaded liposomes have been exploited to get a better understanding of their uptake and intracellular trafficking in vivo in a tumor environment.In order to account for the observed MRI data, a kinetic model able to describe the underlying biological processes has been developed. The fit of the data provides a rough estimate of the kinetic constants for each process considered in the model.

                                   Tuesday 13:30-15:30                                                                            Computer 68           

13:30         4186.     Animal Imaging Using L1-Regularized Quantitative Susceptibility Mapping

Ildar Khalidov1, Tian Liu1, Xiaoyue Chen2, Moonso Jin2, Ali S. Arbab3, Quan Jiang3, Martin Prince1, Yi Wang1

1Radiology, Weill Cornell Medical College, NYC, NY, United States; 2Biomedical Engineering, Cornell University, Ithaca, NY, United States; 3Neurology, Henry Ford Hospital, Detroit, MI, United States

Quantitative susceptibility mapping (QSM) is a technique that uses phase data from an MRI image to estimate the susceptibility distribution in the object. It has been demonstrated that QSM is able to correctly estimate the magnetic moment of specimen differing in susceptibility to the surrounding tissue [1]. We would like to exploit this ability to perform quantitative imaging of biomarkers in animal imaging. However, animal imaging presents additional challenges: the need for higher resolution suggests lower SNR; mixes of several tissues can create significant artifacts that impede quantification. In this work, we estimated the susceptibility change induced by SPIO nanoparticles that are targeted to specific cells. In experiment (1), we scan a rat brain after stroke injected with neural progenitor cells (NPCs) incubated in a solution containing a suspension of ferumoxide-protamine sulfate. In experiment (2), we image a mouse injected with SPIO nanoparticles that target the intercellular adhesion molecule ICAM-1, which is induced in response to inflammation. We use total-variation based regularization to circumvent the problems with low SNR and the streaking artifacts.

14:00         4187.     A Dose Dependent Inflammatory Cell Tracking by Micrometer-Sized Iron Oxide Particles-Enhanced MRI in Murine Myocardial Infarction Model

Yidong Yang1,2, Jimei Liu1, Yuhui Yang1, Tom C.-C. Hu1,2

1Department of Radiology, Medical College of Georgia, Augusta, GA, United States; 2Medical Physics Program, Georgia Institute of Technology, Atlanta, GA, United States

Inflammation plays a pivotal role in the cardiac remodeling process following myocardial infarction. Recently, it has been shown that inflammatory cells such as macrophages can be labeled with micrometer-sized iron oxide particles (MPIO) via systemic injection. After myocardial infarction, MPIO-labeled inflammatory-cell infiltration at MI sites can be monitored using T2*-weighted MRI. The purpose of this study is to investigate the relationship between the injected MPIO dose and the signal attenuation therefore to identify an optimal dose. This study will provide a valuable method to track inflammatory cells, which can be applied in either inflammation-related disease monitoring or drug development.

14:30         4188.     Dual Contrast Cellular MRI

Rohan Dharmakumar1, Zhuoli Zhang1, Ioannis Koktzoglou2, Sotirios A. Tsaftaris1,3, Debiao Li1,4

1Radiology, Northwestern University, Chicago, IL, United States; 2Radiology, NorthShore University HealthSystem, Evanston, IL, United States; 3Electrical Engineering and Computer Science, Northwestern University, Evanston, IL, United States; 4Biomedical Engineering, Northwestern University, Evanston, IL, United States

Negative contrast methods utilizing local magnetic susceptibility shifting agents have become one of the most important approaches in cellular imaging research. However, visualizing and tracking labeled cells on the basis of negative contrast is often met with limited specificity and/or sensitivity. Here we report on a cellular MRI method that generates a new contrast with a distinct topology for identifying labeled cells permitting significant improvement in sensitivity and specificity.

15:00         4189.     Cellular Uptake and Imaging Studies of Gadolinium-Loaded Single-Walled Carbon Nanotubes

Annie M. Tang1,2, Jeyarama S. Ananta3, Hong Zhao1, Brandon T. Cisneros3, Edmund Y. Lam4, Stephen T. Wong1, Lon J. Wilson3, Kelvin K. Wong1,5

1The Center for Bioengineering and Informatics and Department of Radiology, The Methodist Hospital Research Institute, Weill Cornell Medical College, Houston, TX, United States; 2Department of Electrical and Electronic Engineering, The University of Hong Kong, Hong Kong, Hong Kong; 3Department of Chemistry, Rice University, Houston, TX, United States; 4Department of Electrical and Electronic Engineering, The University of Hong Kong, Hong Kong,, Hong Kong, Hong Kong; 5Texas Children Small Animal Imaging Facility, Texas Children Hospital, Houston, TX, United States

Single-walled carbon nanotubes (SWCNTs) have recently been proposed as vehicles for efficient delivery of biomolecules such as drugs and genes into targeting sites for therapeutic purposes. In order to monitor the delivery location and efficiency, visualization of these SWCNTs is crucial.  In this study, we investigate the intracellular uptake of gadonolimum-loaded ultra-short carbon nanotubes (gadonanotubes) with MRI and demonstrated single cell visualization in a sparsely distributed cell agarose phantom.

                                   Wednesday 13:30-15:30                                                                       Computer 68           

13:30         4190.     Poly-L-Lactic Acid (PLLA) Iron Loaded Nanoparticles for MRI Cell Labelling

Gerlinde Schmidtke-Schrezenmeier1, Markus Urban2, Sonu Sharma3, Katharina Landfester2, Hubert Schrezenmeier1, Volker Rasche3

1Institute for Transfusion Medicine, University Hospital of Ulm, Ulm, Germany; 2Max-Planck-Institute for Polymer Research, Mainz, Germany; 3Department of Internal Medicine II, University Hospital Ulm, Ulm, Germany

Different iron-loaded nanocapusles (diameter 110nm to 135nm, zeta-potential -28mV to -55mV) were synthesized by the mini-emulsion process and applied for efficient labeling of MSCs. The MRI efficiency (T2 and T2* relaxation) and kinetics of the particles regarding cell uptake and release as well as its impact on the cell properties were investigated. The visibility of the labeled cells was investigated over a time period of 14days in an agarose gel phantom.

14:00         4191.     In-Vivo Positive Contrast Tracking of Bone Marrow Stem Cells Labeled with IODEX-TAT-FITC Nanoparticles

Philip Lee1, Bingwen Zheng1, George Radda1, Parasuraman Padmanabhan1, Kishore Bhakoo1

1Singapore Bioimaging Consortium, Biomedical Sciences Institute, Singapore, Singapore

In vivo tracking with MRI has become standard in modern therapeutic cell studies. Typically, cells loaded heavily with iron-oxide nanoparticles, are identified as signal voids in T2*-weighted imaging. This raises two issues, namely the detrimental effect of high iron load in terms of cellular function and viability as well as interpretation ambiguities associated with partial volume artifacts and local magnetic field inhomogeneities. TAT-IODEX-FITC nanoparticles offer dual modality detection (MRI and optical) without adverse impact on cellular biology. By utilizing a multiple-echo ultra-short echo-time pulse sequence, we obtain high positive contrast of labeled bone marrow stem cells injected into rats’ striatum in vivo.

14:30         4192.     Quantification of Cell Density of SPIO-Labelled Cell Populations

Bernhard Neumayer1, Clemens Diwoky1, Andreas Reinisch2, Dirk Strunk2, Rudolf Stollberger1

1Institute of Medical Engineering, Graz University of Technology, Graz, Austria; 2Stem Cell Research Unit, Dept. of Hematology, Univ. Clinic of Internal Medicine, Medical University of Graz, Graz, Austria

The use of intracellular contrast agent suffers from quenching effects due to compartmentalization of the contrast medium inside the cell. These effects impede the correct quantification of cell populations. This study presents a simple way to quantify cell density by using inversion recovery measurements and biexponential fitting routines.

15:00         4193.     Magnetic Resonance Imaging of Stem Cells Labeled with Micrometer-Sized Iron Oxide Particles: Applications to Musculoskeletal Tissue Engineering

Karl Saldanha1,2, Kimberly Loo1, Sharmila Majumdar1,2

1Department of Radiology, UCSF, San Francisco, CA, United States; 2Joint Graduate Group in Bioengineering, UC Berkeley/UCSF, San Francisco, CA, United States

To aid in the development and implementation of clinically viable stem cell-based tissue engineering therapies, a technique is needed to monitor implanted cells throughout the course of treatment. Labeling of stem cells with an iron oxide contrast agent prior to implantation has the potential to allow for longitudinal non-invasive in vivo assessment of the bio-distribution of transplanted cells via magnetic resonance imaging (MRI). This study aims to investigate labeling of stem cells with micrometer-sized iron oxide particles to enable MRI detection, and its applications in longitudinal monitoring of stem cell-based musculoskeletal tissue engineering.

                                   Thursday 13:30-15:30                                                                          Computer 68           

13:30         4194.     Characterization of MPIO Labeled Primary Murine Bone Marrow Derived Macrophages

Kevin S. Tang1, Erik M. Shapiro, 1,2

1Department of Biomedical Engineering, Yale University, New Haven, CT, United States; 2Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT, United States

Macrophages are key players in the innate immune response and important markers of local inflammation. Here, we evaluated the effects of MPIO labeling on macrophage functions: cytokine secretion, maintained phagocytosis, and cell migration. Labeling with MPIOs did not, on its own, stimulate the cells to produce TNF-á and IL-12, two important inflammatory cytokines. Furthermore, MPIO labeling did not inhibit macrophages to secrete these cytokines upon activation with LPS. Fluorescence microscopy demonstrates the ability to continue phagocytosis after labeling. Lastly, transwell migration assays showed migration from both unlabeled and labeled macrophages, suggesting no effect on migratory ability by MPIOs.

14:00         4195.     Nanoparticle-Loaded Stem Cells for MR Imaging and Hyperthermia

Lyubov Ostrovska1, Mohammad Hedayati2, Christine Cornejo2, Yoshinori Kato1, Dmitri Artemov1, Theodore L. DeWeese2, Robert Ivkov2

1The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; 2Department of Radiation  Oncology & Molecular Radiation Sciences, The Johns Hopkins University School of Medicine

The goal of this study is to sensitize tumors to radiation therapy with heat generated by magnetic bionized nanoferrite (BNF)-nanoparticles within stem cells that home to hypoxic areas in tumors. Previously, we demonstrated that in mouse models of prostate cancer intravenously injected mesenchymal stem cells migrate to tumors, home to hypoxic areas, and participate in tumor neovasculogenesis. It was also demonstrated that heating of tumor-bearing mice injected with BNF-particles resulted in tumor size reduction and delayed tumor growth. We aim to develop methods for stem cell-based delivery of BNF-nanoparticles to hypoxic areas in tumors for hyperthermic sensitization to irradiation.

14:30         4196.     Differentiation of Multiple Stem Cells Types Labeled  with MPIOs Down Multiple Lineages Is Identical to Unlabeled Cells

Cicely Williams1, Dorit Granot2, Teodor Leahu1, Erin B. Lavik3, Erik M. Shapiro, 1,2

1Department of Biomedical Engineering, Yale University, New Haven, CT, United States; 2Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT, United States; 3Center for Translational Neuroscience, Case Western Reserve University, Cleveland, OH, United States

Critical to the use of magnetic particles for MRI-based cell tracking is that particles not interfere with cellular processes. This is especially the case with stem cells. In this work, we investigated the effect of magnetic cell labeling with various sized MPIOs on differentiation of mesenchymal stem cells and neural progenitor cells, down multiple cell lineages. Neural progenitor cells labeled with MPIOs differentiated into neurons and glia identically to unlabeled cells. Similarly, mesenchymal stem cells labeled with MPIOs were able to differentiate into adipocytes and osteocytes identically to unlabeled cells. Importantly, MPIOs remained intracellular during differentiation.

15:00         4197.     Differences in Clearance of Ferucarbotran and Ferumoxide from the Liver Using Gradient Echo MRI and T2 Measurement in Rat.

Lindsey Alexandra Crowe1, Frederic Ris2, Matthieu Lepetit-Coiffé1, Christian Toso2, Thierry Berney2, Jean-Paul Vallée1

1Department of Radiology, Geneva University Hospital, University of Geneva, Faculty of Medicine, Geneva, Switzerland; 2Cell Isolation and Transplant Center, Department of Surgery, Geneva University Hospital, Geneva, Switzerland

The clearance of two injected iron oxide contrast agents was followed by GRE MRI and T2 decay at 1.5T.  Ferucarbotran (Resovist®) was found to clear from the rat liver significantly faster than ferumoxide (Endorem®). The rate of clearance will affect the choice of contrast agent for serial cell labeling studies where the iron signal from a rejected cell should be cleared as fast as possible after cell death. T1- and T2- weighted images and T2 decay curves return to normal within 10 days for ferucarbotran, but ferumoxide still has a significant effect on the liver after more than 100 days.

Recent Advances in Molecular Imaging

Hall B                        Monday 14:00-16:00                                                                             Computer 69           

14:00         4198.     Hollow Structured Mesoporous Silica Coated MnO Nanoparticles as Highly Efficient T1 Contrast Agents and Their Applications in MR Tracking of Transplanted Mesenchymal Stem Cells

Taeho Kim1,2, Eric Momin3, Jonghoon Choi1,4, Hasan Zaidi3, Jaeyun Kim1,2, Mihyun Park2, Michael T. McMahon1,5, Taeghwan Hyeon2, Alfredo Quinones-Hinojosa3, Jeff W. M. Bulte1, Assaf A. Gilad1

1Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; 2Chemical & Biological Engineering, Seoul National University, Seoul, Korea, Republic of; 3Department of Neurological Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; 4CSTL, National Institute of Standards and Technology, Gaithersburg, MD, United States; 5F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States

New MnO nanoparticles, which have "hollow" structures in a mesoporous silica coating were designed and successfully synthesized. We have demonstrated improved T1 and T2 contrast with these nanoparticles. These nanoparticles showed high cellular uptake with the use of electroporation and were detected with magnetic resonance imaging (MRI) both in vivo and in vitro. Thus, these novel MnO nanoparticles represent an efficient alternative to label and track transplanted cells with MRI.

14:30         4199.     In Vivo Tracking of Gastric Stem Cell by MRI Using a Newly Synthesized Iron-Based Contrast Agent, MnFe2O4-PEG

Chiao-Yun Chen1,2, Gin-Chung Liu3,4, Deng-Chyang Wu5,6, Yun-Ming Wang7, Pei-I Liu8, Ting-Jung Chen, 23, Twei-Shiun Jaw3,4, Yu-Ting Kuo3,4

1Department of Medical Imaging, Kaohsiung Medical University Hospital , Kaohsiung, Taiwan; 2Kaohsiung Medical University, Kaohsiung, Taiwan; 3Department of Medical Imaging, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 4Kaohsiung Medical University , Kaohsiung, Taiwan; 5 Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 6Department of Internal Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University , Kaohsiung, Taiwan; 7Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan; 8Department of Radiology, Pingtung Pao Chien Hospital, Pingtung, Taiwan

We have successfully synthesized and characterized a novel iron-based MR contrast agent, MnFe2O4-PEG, for labeling gastric stem cell, CS12, in vitro. Its carcinogenetic potential was well preserved following MR contrast labeling. In addition, tumor growth from the labeled CS12 cell and the T2* effect can be efficiently detected over three weeks with in vivo MRI. We believe that this molecular imaging technique may contribute further understanding of carcinogenesis induced by gastric stem cell and it may be also beneficial to help gene or cellular therapy in the future.

15:00         4200.     Alternative Labels for Visualization of Pancreatic Islets

Vít Herynek1,2, Zuzana Berková3, Daniel Horák4, Michal Babic4, Daniel Jirák1,2, František Saudek3, Milan Hájek1

1MR-Unit, Department of Radiodiagnostic and Interventional Radiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic; 2Center for Cell Therapy and Tissue Repair, Second Medical Faculty, Charles University, Prague, Czech Republic; 3Pancreatic Islet Laboratory, Diabetology Clinic, Institute for Clinical and Experimental Medicine, Prague, Czech Republic; 4Institute of Macromolecular Chemistry, Czech Republic

Visualization of transplanted islets using MRI requires labeling of islets by a suitable contrast agent. We successfully tested alternative superparamagnetic iron oxide nanoparticles with improved biological and physical properties, which represent alternative to commercially available dextran coated contrast agents. Modified coating of the nanoparticles ensures higher efficiency at lower concentrations and no adverse effects on islet viability or insulin secretion.

15:30         4201.     Characterisation of a Liposomal Contrast Agent for Delivery of SiRNA

Gavin David Kenny1, Leigh Pauline Brody1, Nazila Kamaly1,2, Tammy Louise Kalber1, Andrew David Miller2, Jimmy David Bell1

1Metabolic and Molecular Imaging Group, Imperial College, London, United Kingdom; 2Genetic Therapies Centre, Imperial College, London, United Kingdom

This studies aim was to characterise the ability of a liposome encapsulating siRNA to act as a contrast agent for MRI. Liposomes were formed with and without encapsulation of siRNA and size, encapsulation percentage and r1 determined. Encapsulation of siRNA in liposomes had no effect on the size or r1 of the liposomes and was found to be stable for approximately 5 days. This shows that encapsulation of siRNA has no effect on the ability to act as a contrast agent and that liposomes should be used within 5 days, meaning liposomes can be tested without wasting expensive siRNA.

                                   Tuesday 13:30-15:30                                                                            Computer 69           

13:30         4202.     Detection of Spontaneously Occuring Amyloid Plaques in a Primate Model of Alzheimer's Disease

Anne Bertrand1, Adrien Pasquier1, Alexandra Petiet1,2, Christopher Wiggins2, Sebastien Meriaux2, Audrey Kraska1, Olene Dorieux1,3, Nelly Joseph-Mathurin1, Philippe Hantraye1, Fabienne Aujard3, Nadine Mestre-Frances4, Marc Dhenain1,2

1CEA, I2BM, MIRCen-URA2210, Fontenay aux Roses, France; 2CEA, I2BM, Neurospin, Gif-sur-Yvette, France; 3UMR CNRS/MNHN 7179, Brunoy, France; 4INSERM U710- EPHE- Université Montpellier 2, Montpellier, France

Amyloid deposits are one of the characteristic lesions of Alzheimer's disease. Their sizes range from 50 µm to 200 µm. These lesions can be detected in transgenic mouse model of Alzheimer's disease by MRI, however, amyloid deposits in mice are very different than those occurring spontaneously in aged primates or humans with Alzheimer's disease. Here, we show that a protocol based on the staining of amyloid plaques with a non targeted Gadolinium contrast agent allows to detect spontaneously occurring amyloid plaques in aged mouse lemur Primates.

14:00         4203.     Acoustic Relaxation Enhancement in MRI

Christian Höhl1, Nouri Elmiladi1, Fahimeh Jahanbakhsh1, Felix Repp1, Peter Wolf1, Karl Maier1

1Helmholtz-Institut für Strahlen- und Kernphysik (HISKP), Rheinische Friedrich-Wilhelms-Universität, Bonn, Germany

A contrast mechanism which is selective to the binding of a magnetic nanoparticle has been successfully observed in an NMR spectrometer. There are, however, difficulties to achieve compatibility with a standard MRI device. We present first experiments on how to realize this contrast mechanism in an open tomography system.

14:30         4204.     Paramagnetic PH Sensitive Liposomes with Improved MRI  Properties

Elena Torres1, Enzo Terreno1, Roberta Cavalli2, Franco Fedeli3, Francesco Mainini1, Roberta Napolitano1, Silvio Aime1

1Department of Chemistry and Molecular Imaging Center, University of Torino, Torino, Italy; 2Department of Drug Science and Technology, University of Torino, Italy; 3Bioindustry Park of Canavese, Italy

Liposomes occupy a leading role in biomedical field being successfully used since a long time as drug-delivery systems. These nanovesicles can be properly formulated in order to release the entrapped material as a consequence of a specific endogenous stimulus (e.g. acidification, change in redox potential or concentration of specific enzymes) that characterizes the early asymptomatic stage of many diseases. In this contribution, a novel class of paramagnetic pH sensitive liposomes with improved formulations are presented and their basic MRI properties evaluated both in vitro and in vivo on tumor animal model on mice.

15:00         4205.     Gadolinium Chelate Functionalized Gold Nanoparticles for Targeted NIR Laser Heating

Steve Huntz Fung1,2, Edward S. Hui1, Feng Li1, Guoting Qin1, Diana U. Lo1, Rongmin Xia1, Zheng X. Li1,2, Brian E. O'Neill1,2, King C. Li1,2

1Department of Radiology, The Methodist Hospital, Houston, TX, United States; 2Department of Radiology, Weill Cornell Medical College, New York, United States

We have developed gadolinium-chelate functionalized gold nanoparticles (Gd-Au NP) as theranostic agents that can be detected by MRI to guide NIR laser therapy. By tuning the optical properties of Gd-Au NP to absorb in NIR, where tissue penetration of light is optimal, one can selectively heat tumor tissue that contain nanoparticles. We have taken into consideration expected spectral shift of surface plasmon resonance (SPR)-associated absorption from surface functionalization, and designed a good NIR absorber that doubles as a very good T1-contrast agent. In the design process, a new Gd-DTPA-based chelate-linker for conjugation to Au NP is proposed that has two thiol-Au binding sites and a longer linker segment than ones proposed in existing literature, which should allow for better immobilization and increased number of Gd-chelate conjugation to Au NP for better T1-relaxivity. MR relaxivity, UV-visible-NIR spectroscopy, and NIR laser heating data are presented.

                                   Wednesday 13:30-15:30                                                                       Computer 69           

13:30         4206.     NMR Relaxation of Mn0.5Zn0.5GdxFe(2-X)O4 Hyperthermia Nanoparticles: Effects of Coating

Bashar Issa1, Ihab M. Obaidat1, Shahnaz Qadri2, Basil al-Ramadi3, Yousef Haik2,4

1Physics, UAE University, Al-Ain, Abu Dhabi, United Arab Emirates; 2Mechanical Eng., UAE University, Al-Ain, Abu Dhabi, United Arab Emirates; 3Medicine, UAE University, Al-Ain, Abu Dhabi, United Arab Emirates; 4Center of Research Excellence in Nanobiosciences, Univ. of North Carolina-Greensboro, United States

We studied the of 1/T1 and 1/T2 behaviour and effect of PEG coating for a new class of magnetic nanoparticles (MNPs) Mn0.5Zn0.5GdxFe(2-x)O4 with Gd concentration x = 0.02. MNPs were dispersed in gel with a range of concentrations (in mM of Fe per kg) from 0.0 to 0.3. At 1.5 T, T1 and T2 were measured at temperatures 26 oC. The measured 1/T1 and 1/T2 show linear dependence on concentrations. Variation of R1,2 with concentration is larger for the uncoated than for the coated particles due to smaller distance separating the protons from MNPs. These nanoparticles have already been used as hyperthermia agents and we are investigating the extension of their use as MRI contrast agents.

14:00         4207.     Dual MR-PET Probe for Quantitative, Noninvasive High Resolution PH Mapping

Luca Frullano1, Ciprian Catana1, Thomas Benner1, A. Dean Sherry2,3, Peter Caravan1,4

1A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States; 2Chemistry, University of Texas at Dallas, Dallas, TX, United States; 3Advanced Imaging Research Center, UT Southwestern, Dallas, TX, United States; 4Radiology, Harvard Medical School, Charlestown, MA, United States

In vivo application of activatable contrast agents is limited by the inability to determine both probe concentration and relaxivity.  One approach to this problem is simultaneous MR-PET using a dual MR-PET probe, where PET provides quantification of probe concentration and MR signal can then be related to relaxivity.  We describe synthesis and characterization of a fluorine-18 labeled, gadolinium-based probe with pH dependent relaxivity.  Simultaneous MR-PET imaging indicates a strong correspondence between pH calculated from the joint image analysis and pH measured by electrode.

14:30         4208.     Nuclear Magnetic Relaxation Dispersion Studies of MR Sensor Agents for Myeloperoxidase Imaging

Yuanxin Chen1, John A. Ronald2, Elisenda Rodriguez3, John W. Chen3, Kem A. Rogers4, Brian K. Rutt2

1Imaging Research Laboratories, Robarts Research Institute, London, Ontario, Canada; 2Department of Radiology, Stanford University, Stanford, CA, United States; 3Center for Systems Biology and Department of Radiology, Massachusetts General Hospital, Boston, United States; 4Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario, Canada

Bis-5-hydroxytryptamide-diethylenetriamine-pentaacetate gadolinium [bis-5HT-DTPA(Gd)] is a highly sensitive and specific magnetic resonance reporter of myeloperoxidase (MPO) activity in vivo. In this study, we measured water proton T1 nuclear magnetic relaxation dispersion (NMRD) profiles for bis-5HT-DTPA(Gd) solutions and of the aortic specimen excised from atherosclerotic rabbits 2 hours after injection of bis-5HT-DTPA(Gd).  When activated by MPO, bis-5HT-DTPA(Gd) exhibits a significant relaxivity increase over the entire range of magnetic fields up to 0.93 T. Similarly, the NMRD profiles of atherosclerotic aorta showed increased relaxivity enhancement compared to aortic specimen from control rabbits. This supports our in vivo MRI results that bis-5HT-DTPA(Gd) targets of MPO and identifies active inflammation in experimental atherosclerosis.

15:00         4209.     Quantitative CEST with BIRDS

Daniel Coman1,2, Garry Kiefer3, Douglas L. Rothman, 2,4, Dean A. Sherry5,6, Fahmeed Hyder, 2,4

1Diagnostic Radiology, Yale University, New Haven, CT, United States; 2Quantitative Neuroscience with Magnetic Resonance (QNMR), Yale University, New Haven, CT, United States; 3Macrocyclics, Dallas, TX, United States; 4Diagnostic Radiology and Biomedical Engineering, Yale University, New Haven, CT, United States; 5Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, United States; 6Radiology and Chemistry, University of Texas Southwestern Medical Center, Dallas, TX, United States

Biosensor Imaging of Redundant Deviation of Shifts (BIRDS) represents another alternative to CEST imaging, using resonances from paramagnetic lanthanide-based contrast agents (CAs). Although spatial resolution is high, CEST data are qualitative because the signal attenuation remains relative unless the CA concentration, temperature and pH are known. A typical BIRDS experiment uses high-speed CSI because of favorable relaxation times for CAs. A europium-based CA, EuDOTA-(gly) 4-, exhibits enhanced CEST characteristics while still retaining high sensitivity to temperature variations specific to BIRDS. Here, we illustrate the principles of combining CEST and BIRDS to obtain optimal temperature measurements with improved spatial resolution.

                                   Thursday 13:30-15:30                                                                          Computer 69           

13:30         4210.     Controlling the Dissolution of MnO Nanocrystals for Time-Dependent T1 MRI Contrast Agents

Yi-Cheng Lee1, Der-Yow Chen2, Stephen J. Dodd2, Nadia Bouraoud2, Alan P. Koretsky2, Kannan M. Krishnan1

1MSE, University of Washington, Seattle, WA, United States; 2NINDS, National Institutes of Health, Bethesda, MD, United States

Manganese based nanoparticles have potential as agents that can be "activated" when taken into cells. It would be advantageous to be able to control the rate of dissolution of Mn based nanoparticles to control T1 contrast signals, in vivo with time. To this end, five different coatings on MnO nanocrystals have been tested to study the release rate of the Mn2+ ions and change in relaxivity at pH 7 compared to pH 5. The MnO@SiO2 particles show the best potential for delaying the release of MRI contrast until specific biological processes have occurred, such as endocytosis.

14:00         4211.     Reduced Glutathion Concentration Limits the Reduction Rate of Nitoimidazol Derivatives in Vitro
Jesus Pacheco-Torres1, Paloma Ballesteros2, Pilar Lopez-Larrubia1, Sebastian Cerdan1

1Instituto de Investigaciones Biomédicas "Alberto Sols" - CSIC, Madrid, Spain; 2Laboratory of Organic Synthesis and Molecular Imaging, UNED, Madrid, Spain

We investigate the mechanism of reduction of commercially available misonizazol or pimonidazol and the newly synthesized NIMAC hypoxia probe. We followed by in vitro 1H NMR the P-450 reductase dependent reduction of solutions containing NADPH and the different hypoxia probes in the presence or not of reduced glutathione, either under the air oxygen tension or under anoxic conditions. We found that the oxygen content of the solution had only a small effect of the different reduction rates, the rate limiting step being in all cases the presence or not of reduced glutathione, independently of the oxygen tension achieved.

14:30         4212.     MRI Probes for Sensing the Extracellular Redox State

Giuseppe Digilio1, Valeria Menchise2, Eliana Gianolio3, Franco Fedeli3, Concetta Gringeri1, Roberta Napolitano3, Carla Carrera3, Valeria Catanzaro3, Silvio Aime3

1DISAV, University of Eastern Piedmont, Alessandria, AL, Italy; 2Institute for Bioimages and Biostructures, CNR, Naples, Italy; 3Department of Chemistry IFM, University of Turin, Turin, Italy

Exofacial protein thiols exposed on the cell surface are responsive to the redox state of the extracellular milieu. They can be exploited as anchorage points for suitably designed Gd-based MRI probes, allowing for the visualization of hypoxic tumor regions.

15:00         4213.     Integrating MR with 3D Gene Expression Data in the Mouse Brain

Christopher Lau1, Lydia Ng1, Chihchau Kuan1, Changkyu Lee1, Mallar Chakravarty1, Allan Jones1, George Allan Johnson2, Michael Hawrylycz1

1Allen Institute for Brain Science, Seattle, WA, United States; 2Center for In Vivo Microscopy, Duke University

The Allen Brain Atlas (ABA) adult C56BL/6J mouse brain database of over 20,000 in situ gene expression patterns was registered with a set of multispectral 21.5 micron resolution target MR volumes (T1, T2, and T2*). We developed a 3D viewing application that enables comparison of gene expression patterns with MR data. The application can search for genes expressing in regions of interest defined in MR images, and co-visualize gene expression or histology with MR. This application forms a bridge between the transcriptome and MR data in the mouse brain.

Contrast Agents

Hall B                        Monday 14:00-16:00                                                                             Computer 70           

14:00         4214.     Validation of Optical Tomography in Vivo

Yuting Lin1, Mehmet B. Unlu1, Brian Grimmond2, Anup Sood2, Egidijus E. Uzgiris3, David Thayer1, Han Yan1, Orhan Nalcioglu1, Gultekin Gulsen1

1Center for Functional Onco-Imaging, University of California, Irvine, CA, United States; 2GE Gobal Research, Niskayuna, NY, United States; 3Rensselaer Polytechnic Institute,, Troy, NY, United States

Multi-modality imaging is becoming a trend in developing new generation in vivo imaging techniques for diagnosis. Recently, our group has developed a high temporal resolution dynamic MRI/DOT multi-modality imaging system. In such a multi-modality system, each modality measures a different parameter set, which make it difficult to cross-validate the parameters measured by different modalities. An alternative solution is using a bi-functional contrast agent that provides contrast for both optical and MRI simultaneously. Here, our in vivo small animal study is the first to validate a true multi-modality system with a true multi-modality contrast agent.

14:30         4215.     Novel Cross-Linked Liposomal Chemical Saturation Transfer or CEST Agents

Aristarchos Papagiannaros1, Valeria Righi1,2, George Dai2, A Aria Tzika1,2

1NMR Surgical Laboratory, Department of Surgery, Massachusetts General Hospital and Shriners Burns Institute, Harvard Medical School, Boston, MA, United States; 2Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Athinoula A. Martinos Center of Biomedical Imaging, Boston, MA, United States

Liposomal CEST agents are a novel class of contrast agents that demonstrate excellent imaging capacity in phantoms and ex vivo, but their instability is preventing their use in imaging inflammation or cancer. We present cross-linked liposomal CEST agents that efficiently separated the bulk water from the intra-liposomal water signal, while offer increased stability for in vivo applications.

15:00         4216.     Novel Metalloporphyrins as Molecular MR Contrast Agents

Talaignair Venkatraman1, Ines Batinic-Haberle2, Vladimir Mouraviev2, Haichen Wang2, Chris lascola2

1Radiology, Duke University Medical Center, Durham, NC, United States; 2Duke University Medical cener

We have investigated a new class of therapeutic metalloporphyrins for their potential as molecular MR imaging probes for prostate cancer detection. Mn(III)TE-2-Pyp5+ (meso-tetrakis(N-ethyl-2-prydil)porphyrin) and Mn(III)TnHex-2-PYP5+ (meso-terakis(N-n-hexyl-2-pyridyl)porphyrin are powerful superoxide dismutase mimics with low toxicity and antineoplastic activity. In phantom experiments, we observe unusually high T1 relaxivity. In vivo, we observe selective accumulation of these probes in prostate tumor xenografts following a single dose of either compound. Relaxation changes in prostate tumors is 10-11 fold greater than in normal prostate gland, suggesting these compounds may be particularly effective at detecting multifocal disease in situ.

15:30         4217.     Controlled-Release and Magnetic Resonance Imaging of Doxorubicin-Conjugated Magnetic Nanoparticles from 3D Poly(Propylene Fumarate) Scaffolds

Jonghoon Choi1,2, Kyobum Kim3, Taeho Kim4, Taeghwan Hyeon4, Mike T. McMahon1, Jeff WM Bulte1, John P. Fisher3,5, Assaf A. Gilad1

1Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States; 2Biochemical Science, National Institute of Standard and Technology, Gaithersburg, MD, United States; 3Chemical and Biomolecular Engineering, University of Maryland, College Park, MD, United States; 4Chemical Engineering, Seoul National University, Seoul, Korea, Republic of; 5Fischell Department of Bioengineering, University of Maryland, College Park, MD, United States

Three-dimensional PPF (poly(propylene fumarate)) scaffolds carrying cancer drug-coated nanoparticles showed controlled release of drug nanoparticles and bimodal imaging (fluorescence and magnetic resonance) capabilities. This novel biopolymer matrix could be used for many biomedical applications, including MR-guided implantation, as a drug-carrying vehicle, and as a tumor treatment because of the persistent release of drugs in the vicinity of a malignancy.

                                   Tuesday 13:30-15:30                                                                            Computer 70           

13:30         4218.     Transition to MRI – Guided Interventions: First Multimodal Embolization Particles Being Visible in MRI and X-Ray/CT

Sönke H. Bartling1, Johannes Budjan1, Hagit Aviv2, Henrik J. Michaely1, Wolfhard Semmler3, Stefan O. Schönberg1, Steffen Diehl1, Shlomo Margel2, Maliha Sadick1

1Clinical Radiology and Nuclear Medicine, University Medical Center, Mannheim, Baden-Württemberg, Germany; 2Dept. of Chemistry, Bar-Ilan University, Ramat-Gan, Israel; 3Dept. of Medical Physics in Radiology, German Cancer Research Center, Heidelberg, Germany

MRI guidance of interventions is a goal. Current embolization particles cannot be detected by an imaging modality (clinical) or only by CT/X-ray (research). Here, we developed and tested the first multimodal embolization particles being visible within MRI and CT/x-ray. An animal model was used. Post embolization imaging confirmed dual-modality contrast as embolized areas could be detected by CT and MRI. Histology confirmed results. The particles consist of two clinically approved substances: polymerized Iodine and USPIO. Once introduced into clinical routine, improvements of embolization therapy can be expected, because both CT and MRI could be used for treatment control.

14:00         4219.     On the Effect of Contrast Agent Internalization in a Two Compartment Diffusion Model

Thomas Kampf1, Christian Herbert Ziener1, Peter Michael Jakob1,2, Wolfgang Rudolf Bauer3

1Experimental Physics 5, University of Wuerzburg, Wuerzburg, Bavaria, Germany; 2Research Center for Magnetic Resonance Bavaria (MRB), Wuerzburg, Bavaria, Germany; 3Medical Clinic and Polyclinic 1, University of Wuerzburg, Wuerzburg, Bavaria, Germany

Contrast agents (CA) are commonly used to alter the contrast in MR data. Thus, profound knowledge of the CAs influence on the MR signal is important. In this work the effect of CA internalization is studied numerically. The simulations show that the simple linear relationship between the concentration of the CA and the relaxation rate is not preserved  if the CA is internalized in a small part of the volume. This leads to a decreased apparent relaxivity. Furthermore an upper limit for the averaged relaxation rate was observed for a given volume fraction and size of the CA containing compartment.

14:30         4220.     Prolonged and Homogenous Delivery of Gd Chelates to the Rat Brain with an Osmotic Pump

Paul A. Schornack1

1Radiology, University of Pittsburgh, Pittsburgh, PA, United States

The purpose of this study is to demonstrate the very prolonged, chronic delivery of neutral & negatively charged Gd-chelates, in addition to the positively charged Mn2+ ion, directly to rat brain interstitium by direct infusion into CSF of the lateral ventricles using an osmostic pump.  The main goal of this work is to develop a framework for delivering molecular imaging agents of interest, such as pH reporting agents, to the brain in a consistent & predictable manner.

15:00         4221.     Indirect Sensitive MR Detection of Aβ Plaques with USPIO in Alzheimer Transgenic Mice

Jean-Sebastien Raynaud1, Gaelle Louin1, Olivier Rousseaux1, Isabelle Raynal1, Claire Corot1

1Research, Guerbet, Roissy CdG Cedex, France

The aim was to evaluate the potentiality of an USPIO to increase the sensitivity to indirectly detect, via microglial phagocytic activity, Ab plaques, in Alzheimer transgenic mice. P904-Rhodamine was iv administrated in trangenic mice. MRI was performed at 2.35T and 7T. Microglia (CD45), iron (Perl's), Ab (Congo Red) and Rhodamine were analyzed on histological slices. Post P904 injection, several susceptibility artefacts were observed as focal spots all over the mouse brain. Iron, microglia, amyloid plaques et fluorescence were colocalized. These results suggest that P904 could be a very sensitive tool for Alzheimer disease diagnostic and prognostic.

                                   Wednesday 13:30-15:30                                                                       Computer 70           

13:30         4222.     Gadolinium-Stained Brains Reveal Amyloid Plaques in Live Alzheimer's Transgenic Mice

Alexandra Petiet1,2, Anne Bertrand2,3, Christopher J. Wiggins3, Fanny Petit2, Diane Houitte2, Thomas Debeir1, Thomas Rooney1, Philippe Hantraye2, Marc Dhenain2,3

1CNS, sanofi-aventis, Vitry-sur-Seine, France; 2MIRCen, CEA-CNRS URA 2210, Fontenay-aux-Roses, France; 3DSV/I2BM/Neurospin, CEA, Gif-sur-Yvette, France

Beta-amyloid (Aβ) plaques, one of the hallmarks of Alzheimer's disease (AD), are the targets of many pharmacological trials. MRI can be used to image these microscopic lesions (50–200μm) in mouse models but their in vivo detection is very challenging. We propose here a protocol based on the use of a gadolinium contrast agent injected directly in the brain of live mice to detect amyloid plaques. We show that Aβ plaques can be identified in APP/PS1 mice aged from 6 to 20 months and that the plaque load measured with MR correlates with histological measurements.

14:00         4223.     Targeting of Tumor Cells with Glutamine Containing Carriers

Simonetta Geninatti-Crich1, Rachele Stefania1, Lorenzo Tei2, Alessandro Barge1, Ibolya Szabo1, Stefania Lanzardo1, Carlotta Bianco1, Silvio Aime1

1University of Torino, Torino, Italy; 2University of piemonte orientale, Alessandria, Italy

Efficient routes to accumulate imaging probes in tumor cells may be found by exploiting the up-regulation of trans-membrane transporting systems. In fact, rapidly growing tumors require an increased and continuous supply of aminoacids and other nutrients.  Glutamine appears an interesting candidate as it is considered the main source of nitrogen for tumor cells. Thus tumor cells have been targeted with MR imaging probes bearing glutamine residues as targeting vectors.

14:30         4224.     19F MRI of Trifluoroacetic Acid Encapsulated Into Liposomes

Mirko Meißner1, Germaine Loredana Truisi2, Constantin von zur Mühlen2, Gerhard Pütz3, Dominik von Elverfeldt1

1Dept. of Diagnostic Radiology / Medical Physics, University Hospital Freiburg, Freiburg, Germany; 2Dept. of Cardiology and Angiology, University Hospital Freiburg, Freiburg, Germany; 3Dept. of Clinical Chemistry, University Hospital Freiburg, Freiburg, Germany

Gd-liposomes had been synthesized with a novel dual asymmetric centrifugation technique. Using MRI we examined the in vitro T1-Relaxivity at 9.4 T and could show the influence of the internal Gd-concentration on the in vitro relaxivity of liposome encapsulated Gd-DTPA.

15:00         4225.     Fluorinated Contrast Agents with Cation Depending T1 Sensitivity

Markus Plaumann1, Dieter Leibfritz1

1Institute of Organic Chemistry, University of Bremen, Bremen, Germany

The synthesis of metal ion sensitive MR-contrast agents is important for many medical studies, i.e. neuronal processes. Eight fluorinated Gd3+ complexes were synthesized to study the effect of different metal ions to the relaxation time. 1H-T1 measurements of the synthesized complexes show a strong dependence of relaxivity in presence of diamagnetic metal ions (i.e. Na+, K+, Ca2+, Mg2+) and additionally Mn+-concentration. Furthermore, relaxation times depend on temperature and pH-value. The molecular structure and length of the side chain of the synthesized complexes is very important for sensitivity to metal ions and changes in T1 times.

                                   Thursday 13:30-15:30                                                                          Computer 70           

13:30         4226.     Positive Contrast and Quantitative Imaging of Magnetic Nanoparticles and Cancer Cells with Biomarker Targeted RGD-Nanoparticle Conjugates Using T1 Weighted Ultrashort Echo Time (UTE) Imaging

Xiaodong Zhong1, Longjiang Zhang2,3, Liya Wang2, Hongwei Chen2, Julie Yeh2, Andrew Wang4, Hui Mao2

1MR R&D Collaborations, Siemens Healthcare, Atlanta, GA, United States; 2Department of Radiology, Center for Systems Imaging, Emory University, Atlanta, GA, United States; 3Department of Radiology, Jinling Hospital, Nanjing University College of Clinical Medicine, Nanjing, Jiangsu, China; 4Ocean NanoTech, LLC, Springdale, AR, United States

Negative contrast of magnetic nanoparticles (MNPs) on conventional T2 weighted images may suffer from poor contrast to noise ratio (CNR). This study demonstrated that positive T1 contrast from MNPs can be obtained using ultrashort echo time (UTE) imaging, resulting higher CNR than that of conventional T2 weighted imaging. Signal intensity of MNPs in UTE images has a linear correlation with core size and concentration of MNPs used in this study. Cell imaging with the UTE method also demonstrated potential applications of UTE imaging of biomarker targeted MNPs with contrast enhancement associated to the binding of cell targeted MNP.

14:00         4227.     MR Lymphography with Fe3O4 Nanoparticles in Rabbits: In Vivo Investigation of Metabolism of Fe3O4 Nanoprobes

Rong Rong1, Wang Ruixue2, Wang Xiaoying1, Zhang Jue2, Song Yujun2

1Department of Radiology, 1st Hospital of Peking University, Beijing, China; 2Department of Biomedicine, Peking University, Beijing, China

The metabolism of magnetic nanoprobes for MRI was investigated in vivo in order to determinate optimized diagnosis time for the most contrast imaging and to discover nidus. After injection of these nanoprobes into rabbits, a significant darkening effect on the liver epithelial net lymph tissue was observed in 20 min, with about 20% reduce of the spin-spin relaxation time T2. The metabolism study on these nanoparticles indicated that they did not show any weak toxicity to organs detected and finally entered into the hematopoietic organ ¨C spleen without obvious retention in any related organs after recycling for 3 days.

14:30         4228.     Ultrasmall Particle of Iron Oxide – RGD Peptidomimetic Conjugate as Novel MRI Contrast Agent

Sophie Laurent1, Carmen Burtéa1, Vincent Rerat2, Jacqueline Marchand-Brynaert2, Luce Vander Elst1, Robert N. Muller1

1Université de Mons, Mons, Belgium; 2Université catholique de Louvain, Louvain-la-Neuve , Belgium

In this work, we describe the grafting of a home-made RGD peptidomimetic on ultrasmall particles of iron oxide (USPIO) coated with 3,3’-bis(phosphonate)propionic acid, and the determination of the grafting rates by X-ray photoelectron spectroscopy (XPS). The USPIO-g-Mimic have been characterized by photon correlation spectroscopy (PCS); their magnetometric and relaxometric profiles, and their capacity to target leukemic cells were also analyzed.

15:00         4229.     Cracked Iron Oxide Nanoprticles as T2 Contrast Agents for Magnetic Resonance Imaging

Sung Lan Jeon1, Min Kyung Chae, Eun Ju Jang, Jee-Hyun Cho, Kwan Soo Hong, Gyunggoo Cho, Chulhyun Lee

1Korea Basic Science Institute, Cheongwon-gun, Chungcheongbuk-do, Korea, Republic of

Nanoparticles with small size and large surface provide magnetic resonance image with high sensitivity and specificity at low imaging-agent concentration. Metal oxide nanoparticles with hollow spheres can incorporate therapeutic agents into their payloads, enabling simultaneous MRI diagnosis and delivery of drugs to targeted sites. Herein, we report a facile synthesis of nontoxic cracked iron oxide nanoparticles (CIONPs) from hydrophobic FeO nanoparticles (HIONPs) via 3 steps. With complex surface structure, CIONPs showed improved r2 relaxivities compared to hydrophobic FeO nanoparticles (HIONPs). We expect that CIONPs have the potential application as a drug or chemical delivery vehicle because of their cracked spheres. In addition, cellular and in vivo MR imaging study with CIONPs will be tested.