Molecular Imaging Agents & Techniques

13:30         3202.     A Novel Targeted Iron Oxide Nanocolloid Agent for T1 and T2* Imaging of Fibrin Using Conventional MR Techniques

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Shelton D. Caruthers¹,², Angana Senpan¹, Dipanjan Pan¹, Mike J. Scott¹, Patrick J. Gaffney³, Christian Stehning⁴, Jochen Keupp⁴, Patrick M. Winter¹, Samuel A. Wickline¹, Gregory M. Lanza¹

¹Washington University, St. Louis, Missouri, USA; ²Philips Medical Systems, Andover, Massachusetts, USA; ³St. Thomas' Hospital, London, UK; ⁴Philips Research Europe, Hamburg, Germany

A novel nanocolloid contrast agent with multiple iron-oxide crystals per nanoparticle (1240 &[mu]g Fe per g of emulsion) has been targeted to fibrin clot phantoms and human endarterectomy specimens in vitro. The agent can be visualized as the typical signal dearth on T2* imaging, but also as bright signal on conventional T1-weighted turbo spin echo imaging.  The agent is constrained by size to the vasculature and is predicted to allow imaging to be performed within minutes post-injection.

14:00         3203.     19F Magnetic Resonance Imaging of Increased VCAM-1 Expression in the Kidneys of ApoE-Null Mice Using Targeted  Perfluorocarbon Nanoparticles

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Richard Southworth¹, Junji Chen², Lei Zhang², Megan Kaneda², Huiying Zhang², Samuel Wickline²

¹King's College London, London, UK; ²Washington University School of Medicine, St. Louis, Missouri, USA

Vascular Cell Adhesion Molecule-1 (VCAM-1) is responsible for the tethering of leukocytes to the vascular lumen in early inflammation.  It has been implicated in the pathogenesis of numerous inflammatory diseases, and therefore represents a potentially useful molecular imaging target.  We have developed unique liquid perfluorocarbon nanoparticles which can be functionalised with homing ligands in their outer lipid layer, allowing us to target them to intravascular biomarkers of disease.  These nanoparticles are capable of delivering a targeted payload of over 50,000 Gd atoms, or by virtue of their high 19F content (98% by volume), providing a quantifiable 19F MR signal. Here, we describe their use in specific visualisation and quantification of VCAM-1 expression in the kidneys of atherosclerotic ApoE-/- mice.

14:30         3204.     First Results of an Ex-Vivo Experiment on Human Plaques Using a Contrast Agent Targeting Activated Platelets

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Dominik Paul¹, Constatin von zur Mühlen¹, Julia Möller¹, Timo Spehl¹, Christoph Bode¹, Karlheinz Peter², Dominik von Elverfeldt¹

¹University Hospital Freiburg, Freiburg, Germany; ²Baker Heart Research Institute, Melbourne, Australia

Targeted MRI contrast agents are gaining importance in clinical diagnostic. Here we present an experimental ex-vivo environment for the evaluation of target specific MRI contrast agents on human plaque tissue. The contrast agent consists of microparticles of iron oxide and single-chain antibodies targeting ligand-induced binding sites on activated glykoprotein IIb/IIIa-receptors. Specific target binding resulted in a clear signal drop in high resolution, high field T2 and T2* imaging and was verified by immunohistochemistry. The experimental setup proves to be a promising tool for pre-clinical research on target specific contrast agents.

15:00         3205.     Towards Dual-Mode Imaging of Vulnerable Plaques [Not Available]

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Ben Jarrett¹, Bjorn Gustafsson¹, Angelique Louie¹

¹UC Davis, Davis, California , USA

We have developed dual-mode imaging agents detectable by both MRI and PET for detection and diagnosis of plaque vulnerability.  The probes are targeted to macrophages, whose density correlates with plaque vulnerability.

13:30         3206.     Characterization of Signal Ehnacement Following the  Intraperitoneal Injection of Gadolinium Based Contrast Agents

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Sharon Portnoy¹, Jonathan Bishop¹, Jun Dazai¹, Shoshana Spring¹, R.M. Henkelman¹,²

¹Toronto Centre for Phenogenomics, Toronto, Canada; ²University of Toronto, Toronto, Canada

The objective of this investigation is to determine the enhancement time-course and dosage requirements in mice for intraperitoneally (IP) administered Gadolinium contrast agents.  Although higher doses are required (~2.5 mmol/kg) and enhancement is slightly delayed, results suggest that IP injection may be an effective method for Gadolinium administration.  The relative simplicity of IP contrast administration compared to traditional tail-vein injection makes this method a convenient alternative, particularly in longitudinal studies and high-throughput imaging of large numbers of mice.

14:00         3207.     Fluorine-19 MRI of the Lung: First Human Experiment

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Ursula Wolf¹, Alexander Scholz¹, Maxim Terekhov¹, Kerstin Muennemann¹, Karl Kreitner¹, Christian Werner¹, Christoph Dueber¹, Wolfgang Guenter Schreiber¹

¹Johannes Gutenberg University, Mainz, Germany

As fluorine-19 MRI of the lung appears to be a promising tool for the diagnosis of obstructive lung diseases such as COPD, efforts have been made to improve image quality and to develop a technique which can be safely and effectively used in humans. Since 1984, a lot of animal experiments have been performed using SF6, C2F6, C4F8, C3HF7, and CF4 as contrast gases. Here, we present the data of the first human experiment using up to 78% SF6. This experiment is an important milestone towards the use of fluorine-19 MRI in patients.

14:30         3208.     In-Vivo Ultra-High Resolution Imaging of Small Vessels Using Improved Sensitivity and Long Circulation Time of FeCo-Graphitic Carbon Shell Nanocrystals

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Jin Hyung Lee¹, Sarah Sherlock¹, Masahiro Terashima¹, Hisanori Kosuge¹, Won Seok Seo¹,², Yoriyasu Suzuki¹, Michael V. McConnell¹, Dwight G. Nishimura¹, Hongjie Dai¹

¹Stanford University, Stanford, California , USA; ²Sogang University, Seoul, Republic of Korea

FeCo-Graphitic Carbon Shell Nanocrystals have been recently reported to have an unprecedented high relaxivity with multi-functional capabilities. In this paper, we demonstrate how the improved sensitivity provided by the high relaxivitiy combined with the long circulation time can be used to generate high-resolution in-vivo vessel images.

15:00         3209.     Development of a New Series of Nitroimidazoles Probes for Oxygen Tension (pO₈) Measurement by ¹H Magnetic Resonance Spectroscopy

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Jesus Pacheco¹,², Paloma Ballesteros², Sebastian Cerdan¹, Pilar Lopez-Larrubia¹

¹Instituto de Investigaciones Biomedicas "Alberto Sols"- CSIC, Madrid, Spain; ²Instituto Universitario de Investigacion - UNED, Madrid, Spain

Hypoxia is known to be an important physiological parameter determining tumour progression and malignancy. In this study, we report the synthesis and in vitro evaluation of a new series of nitroimidazolyl derivatives as quantitative pO₈ markers. The NADPH:cytochrome P450 reductase enzymatic systems was found to reduced the probes only under anoxic conditions. Incubation of one of this derivative with C6 cells under different oxygen concentrations depicted clearly visible changes in the ¹H-NMR spectrum at the probe, which depended on the degree of hypoxia.

13:30         3210.     Targeted MR Imaging of CD44-Positive Breast Cancer Stem-Like Cell Phenotype

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Dmitri Artemov¹, Wenlian Zhu¹, Yoshinori Kato¹, Marie-France Penet¹, Farhad Vesuna¹, Zaver Bhujwalla¹, Venu Raman¹

¹Johns Hopkins University, Baltimore, Maryland, USA

Recently, a subpopulation of highly tumorigenic and drug resistant cancer cells was identified in multiple solid tumors, which is currently referred to as cancer stem-like cells.  In breast cancer, these cells are characterized by high level expression of the cell surface receptor CD44 and decreased expression of another marker, CD24..  Here we have developed a CD44-targeted system for MR imaging of breast cancer stem-like cells and demonstrated the MR imaging of CD44 positive MDA-MB-231 human breast cancer cell in vitro.

14:00         3211.     Nanoglobular Gd-DO3A Conjugates as Highly Effective MRI Contrast Agents

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Todd Kaneshiro¹, Eun-Kee Jeong, Dennis Parker, Zheng-Rong Lu¹

¹University of Utah, Salt Lake City, Utah, USA

Novel macromolecular Gd(III) chelates with well-defined nanosizes and globular morphology were synthesized as highly effective MRI contrast agents.  The nanoglobular MRI contrast agents resulted in significant blood and tumor enhancement at a substantially reduced dose, e.g. 10 µmol-Gd/kg.

14:30         3212.     Manganese-Alginate Gels for Controlled-Release of Mn²⁺

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Christian Brekken¹, Ioanna Sandvig¹, Olav Haraldseth¹, Gudmund Skjåk-Bræk¹, Yrr Mørch¹

¹NTNU, Trondheim, Norway

In the present study we aimed at designing alginate beads for controlled release of Mn2+. Both elemental analysis and swelling studies of the alginate gel beads showed great differences in the ion binding properties of alginate to manganese. Dynamic T1-weighted MRI of single alginate beads immersed into NaCl-solution showed that the Mn2+ release rate differed by a factor of up to ~100% between the 4 differently designed beads imaged. The results indicate that nano-fabrication of Mn-alginates can tailor-make biocompatible manganese delivery systems and hopefully help in introducing MEMRI in targeted contrast-enhanced MRI of otherwise toxicity-limited organs, such as the brain.

15:00         3213.     Novel Receptor-Targeted Nanoparticles for MR Imaging and Specific Delivery of Gene Therapy

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Panagiotis Kyrtatos*¹, Michele Writer*, Anthony N. Price¹, Stephen Hart, Mark F. Lythgoe¹

¹Institute of Child Health and Department of Medicine, University College London, London, UK

Multimodal nanoparticles offer a promising application as MRI contrast agents with therapeutic capabilities. Our group is developing a novel gene therapy vector, which utilises an anti-cancer targeting peptide for specific transfection of tumour cells with therapeutic genes. In addition, a Gd3+ moiety has been incorporated for non-invasive real-time monitoring of the delivery. Here we present a pilot in-vitro tumour cell study investigating the MRI properties of the vector, confirming its potential for both specificity of delivery of DNA to the target cells for gene therapy and also providing evidence of the MR contrast enhancement in targeted cells.

13:30         3214.     MR Imaging of Breast Cancer Using the Folate-Receptor Targeted Contrast Agent P1133

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Reinhard Meier¹,², Tobias D. Henning¹, Sophie Boddington¹, Sidhartha Tavri¹, Sandeep Arora¹, Claire Corot³, Ernst J. Rummeny², Heike E. Daldrup-Link¹

¹University of California San Francisco, San Francisco, California , USA; ²Technical University Munich, Klinikum Rechts der Isar, Munich, Germany; ³Guerbet, Paris, France

The purpose of this study was to assess the uptake of the new FR-targeted USPIO P1133 in breast cancers. In vivo studies demonstrated a progressive enhancement of central tumor areas with the FR-targeted USPIO P1133 in FR-positive MDA-MB-231 breast cancers. Corresponding SNR data were significantly higher for P1133 compared to P904B, indicating at least a component of FR-specific enhancement with P1133. The P1133 tumor uptake was not significantly inhibited by FFA in vivo, most likely due to the rapid FFA metabolism in the liver. Thus, the FR-targeted USPIO P1133 provides a significant and specific enhancement of FR-positive MDA-MB-231 breast cancers.

14:00         3215.     Synthesis and Characterization of a Redox- And Light-Responsive MRI Probe [Not Available]

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Chuqiao (Tom) Tu¹, Ryan Ngao¹, Angelique Louie¹

¹UC Davis, Davis, California , USA

We have previously developed a gadolinium contrast agent that reversibly changes relaxivity properties in response to irradiation by different wavelengths of light.  We here demonstrate that the contrast agent can also be modulated by reduction/oxidation.  The mechanism for the relaxivity effects in response to redox appear to differ from the light induced response.

14:30         3216.     Quantitative Molecular Imaging with a Combined Fluorescence Diffuse Optical Tomography and MRI System

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yuting lin¹, Orhan Nalcioglu², Gultekin Gulsen²

¹University of California, Irvine, California , USA; ²University of California, Irvine, California , USA

An ideal molecular imaging technique should have both high sensitivity for molecular probes and also provide high-resolution images. Our solution to this demanding requirement is to employ a multimodality imaging strategy. In this study, we show the feasibility of using a combined MRI and optical fluorescence imaging approach to quantitatively resolve the fluorescence contrast agent concentration. The true fluorophore concentration was recovered only if the MRI anatomical information was employed.

15:00         3217.     Real-Time Feedback Paradigm for Functional and Metabolic Imaging Using a Combined PET/MR Scanner: Proof of Concept

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Thomas Sheung Chee Ng¹,², Daniel Procissi¹, Andrey Demyanenko¹, Yibao Wu³, Ciprian Catana⁴, Simon R. Cherry³, Andrew A. Raubitschek⁵, Russell E. Jacobs¹

¹California Institute of Technology, Pasadena, California, USA; ²University of Southern California, Los Angeles, California , USA; ³University of California,  Davis, Davis, California , USA; ⁴Massachusetts Gener

Positron Emission Tomography (PET) and Magnetic Resonance (MR) offer complementary functional and anatomic information that provide unique windows into biological processes. As well as integrating images in space and time, the combined PET/MR scanner offers the potential to perform real time analysis of multi-modal data that can feedback to direct further studies in a single imaging session. We demonstrate the feasibility of this paradigm. Mice implanted with tumor cells were imaged simultaneously with PET/MR. Functional data derived from the PET was used as a basis for 1H-MR spectroscopy studies, demonstrating metabolic heterogeneity within a tumor cell mass.

MRS of Cells, Body Fluids

13:30         3218.     [3-¹³C]Pyruvate: Useful Alternative to Labeled Glucose for in Vitro Metabolic Studies in Primary Mouse Hepatocytes

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Sven Gottschalk¹, Michaela Hohnholt², Dieter Leibfritz², Marc Bilodeau¹, Claudia Zwingmann¹

¹University of Montréal, Montréal, Canada; ²University of Bremen, Bremen, Germany

Application of stable isotope labeling in vitro is a powerful method to study metabolic pathways and fluxes. We applied [3-¹³C]pyruvate on primary mouse hepatocyte cultures to establish labeled pyruvate for metabolic studies and flux analysis in this cellular model. Our results show: [3-¹³C]pyruvate was metabolized by lactate dehydrogenase, alanine-/aspartate-aminotransferase, PC, PDH and subsequent metabolic pathways through the TCA-cycle. Considering that almost no ¹³C-NMR studies in isolated hepatocytes have been performed so far, labeled pyruvate will provide an important physiological substrate to assess hepatocellular pathways and the de novo synthesis of metabolites in these cells under normal and pathological conditions.

14:00         3219.     A Versatile NMR-Compatible Bioreactor for Alginate-Encapsulated Liver Cells

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Rex Errol Jeffries¹, Kayvan R. Keshari, Chris Seagle, Peter Pediaditakis, Michael P. Gamcsik, John Kurhanewicz, Jeffrey M. Macdonald

¹University of North Carolina, Chapel Hill, USA

Synopsis: A remodeled NMR-compatible bioreactor was used with electrostatic alginate encapsulation of hepatocytes to create a bioartificial liver ultimately designed for metabolomic studies. The 500 μm diameter spherical encapsulates are well perfused and permit the use of 20% oxygen rather than the standard 95% oxygen. The 31P NMR spectra from a rat liver cell line, JM1, and primary rat hepatocytes were compared to oxygen uptake rates for bioenergetics.

14:30         3220.     Metabolism of Colonic Mucosa in Patients with Ulcerative Colitis (UC) and Crohn’s Disease (CD): An NMR Study

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B Krithika¹, S Kumar¹, R R. Singh¹, Uma Sharma¹, V Ahuja¹, G K. Makharia¹, N R. Jagannathan¹

¹All India Institute of Medical Sciences, New Delhi, India

In vitro NMR spectroscopy demonstrated significant differences in the concentration of amino acids (isoleucine/leucine/valine, glutamic acid + glutamine, alanine), membrane components (choline, glycerophosphorylcholine, myoinositol), glycolytic product (lactate) in patients with active state of ulcerative colitis (UC) and Crohn’s disease (CD) compared to controls indicating a decreased protein and carbohydrate metabolism.  In the remission state, levels of most of the metabolites were similar to controls. A significant difference in the concentration of formate was observed between patients with active states of UC and CD suggesting its potential as a biomarker for distinguishing UC and CD.

15:00         3221.     Cellular Metabolism and Apoptosis – Dexamethasone, a Promising New Candidate to Intervene on the Metabolic Level

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Sven Gottschalk¹, Michaela Hohnholt², Dieter Leibfritz², Claudia Zwingmann¹, Marc Bilodeau¹

¹University of Montréal, Montréal, Canada; ²University of Bremen, Bremen, Germany

We have recently shown that the initial phase of the apoptotic process is associated with alterations in specific glucose metabolic pathways. The synthetic glucocorticoid Dexamethasone is known for its anti-apoptotic effects and impact on glucose metabolism (in particular, anaplerosis and gluconeogenesis). We therefore characterized the effects of Dexamethasone on hepatocellular metabolism with multinuclear NMR-measurements. Our results further support the strong relationship noted between changes in cellular metabolism and apoptosis. This paves the way toward the therapeutic modulation of cell metabolism in order to influence upon cell survival/death particularly in the context of liver injury.

Cell Labelling & Tracking

13:30         3222.     In Vivo Imaging of Endogenous Neural Stem Cells Labelled with a Ferumoxide-Polycation Complex Using a Low Field System

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Rachael Dobson¹,², Patrizia Ferretti¹, Mark Lythgoe¹

¹University College London, London, UK

Adult neural stem cells (NSC) migrate towards the olfactory bulb and differentiate into neurons. Ferumoxide-based contrast agents have been used to track the migration of exogenously-labelled NSC, there are limited methods that allow for longitudinal tracing of endogenous neural stem cells using MRI. In this study, two MRI contrast agents were used to label the endogenous population of NSC and neuroblasts in situ in the subventricular zone.  Cell labelling and T2* contrast were assessed up to 28 days post-labelling using a low-field system.  Cell migration was observed in vivo and ex vivo, and histology confirmed labelling of migrating neuroblasts.

14:00         3223.     Quantification of Cell Trafficking in Vivo Using Magnetically Sensitive Histograms

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Christopher M. Long¹, Hyam I. Levitsky¹, Jeff W.M. Bulte

¹Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

Quantification of dendritic cell migration to lymph nodes in vivo is critical for evaluating the efficacy of tumor vaccines.  We developed a new method based on magnetically sensitive histograms and cell-cell transfer of SPIO particles in vivo.   It was found to correlate exceptionally well with ex vivo cell counts after magnetically activated cell sorting  The method may be used to monitor the biological variability associated with cancer vaccination and to evaluate the efficacy of immunoadjuvants.

14:30         3224.     In Vivo Stem Cell Tracking Using Magnetic Resonance Imaging in the Rat Genitalia of a Radical Prostatectomy Model
[Not Available]

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Young Taik Oh¹, Jang Hwan Kim¹, Yong-Min Huh¹, Myeong-Jin Kim¹, Jin-Suck Suh¹

¹Yonsei University College of Medicine, Seoul, Republic of Korea

Erectile dysfunction is a major complication after radical prostatectomy for prostate cancer. There have been vigorous trials for improving erectile dysfunction but no satisfying method until now. Previous reports have shown that stem cell injection improved erectile function in a rat model erection dysfunction. However, they used the immunohistochemical stain for the evaluation of stem cell. A reliable in vivo imaging method to localize transplanted cells and monitor their restorative effects will enable a systematic investigation of cell therapy. Our results showed that in vivo stem cell tracking using MR imaging in a rat model of radical prostatectomy was feasible.

15:00         3225.     Comparison of Different Iron-Oxide Agent Detection Methods Using a Single Dataset

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Gopal Varma¹, Richard Tavare¹, Hannes Dahnke², Stephen Keevil¹, Tobias Schaeffter¹

¹King's College London, London, UK; ²Philips Research Laboratories, Hamburg, Germany

Detection of super-paramagnetic iron oxide can be achieved at varying sensitivities through its inherent negative contrast or by positive contrast methods. A single multi-echo dataset is used to compare T₈* weighted imaging, R₈* mapping, and positive contrast methods. In our study this includes inversion recovery on-resonance (IRON), gradient dephasing (“white marker”), and susceptibility gradient mapping (SGM). T₈* images are found to be most sensitive to the smaller concentrations at short echo times (TEs), but high sensitivity of SGM and T₈* imaging suggests a combination of these two methods is ideal. Data acquired for T₈* images and SGM at 2 different TEs to address different concentrations would provide a more sensitive differentiation to the background.

13:30         3226.     Stem Cell Treatment for Peripheral Arterial Disease - Comparison of Plain and Encapsulated X-Ray Visible Mesenchymal Stem Cell Transplants

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Dorota A. Kedziorek¹, Wesley D. Gilson², Kenyatta Cosby¹, Matthias Stuber¹, Bradley P. Barnett¹, Royston C. Boston³, Grigorios Korosoglou⁴, Bernard E. Kohl¹, Gary Huang¹, Brady Sieber¹, Aravind Arepally¹, Jeff W.M. Bulte¹, Lawrence V. Hofmann⁵, Dara L. Kraitchman¹

¹Johns Hopkins University, Baltimore, USA; ²Siemens, Baltimore, USA; ³University of Pennsylvania, Kennet Square, USA; ⁴University of Heidelberg, Heildelberg, Germany; ⁵Stanford University, USA

The resented work comapares plain and encapsulated Mesenchymal Stem Cell therapy in Peripheral Arterial Disease model. Non-invasive imaging demonstrated a more robust angiogenic response with encapsulated MSCs, while "naked" MSCs can incorporate into the vessel walls.

14:00         3227.     Micrometer-Sized Particles of Iron Oxide (MPIOs) Enhanced Cardiac Imaging to Potentially Monitor Inflammatory Cells Infiltration in a Murine Model of Myocardial Infarction

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Yidong Yang¹,², Ben Waghorn¹,², Yuhui Yang¹, Brianna Klein¹, Nathan Yanasak¹, Tom C-C. Hu¹,²

¹Medical College of Georgia, Augusta, Georgia, USA; ²Georgia Institute of Technology, Atlanta, Georgia, USA

Inflammatory process plays an important role in myocardial injury and the subsequent recovery. In this study, we examined cell mobilization due to myocardial infarction post injection of micrometer-sized particles of iron oxide (MPIOs). MRI was performed to potentially visualize the migration and trafficking of inflammatory cells as well as to provide quantitative information. This technique indicates potential to track disease progression in a preclinical model of myocardial injury.

14:30         3228.     In Vitro MR Thermometry on Magnetically Heated Iron Oxide Labeled Stem Cells

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Daniel Haddad¹, Jochen Lorenscheit², Markus Hildenbrand¹, Meike Weber², Regina Ebert², Peter Michael Jakob¹,²

¹MRB Research Center Magnetic-Resonance-Bavaria, Würzburg, Germany; ²University of Würzburg, Germany

Iron-oxide nanoparticles are commonly used as MR markers to label and track (stem) cells. Magnetic particle heating (magnetic field hyperthermia) can be used to heat the iron-oxide particles and thus the iron labeled stem cells. A proof-of-principle in vitro study shows that MR thermometry can be used to visualize the spatial and temporal heat distribution with high accuracy in the vicinity of iron-oxide labeled stem cells that were heated outside the MR spectrometer via magnetic particle heating. Since the heating capacity depends on the composition and structure of the material of interest, different types of iron-oxide particles yield different heating rates. The heating rates can also be controlled by varying the amount of iron-oxide incorporated in the cells.

15:00         3229.     Tracking of Spio Labeled Natural Killer Cells to Epcam Positive Prostate Cancer with Mr Imaging

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Reinhard Meier¹,², Sidhartha Tavri¹, Tobias D. Henning¹, Winfried S. Wels³, Rick Baehner¹, Ernst J. Rummeny², Heike E. Daldrup-Link¹

¹University of California San Francisco, San Francisco, California , USA; ²Technical University Munich, Klinikum Rechts der Isar, Munich, Germany; ³Chemotherapeutisches Forschungsinstitut, Frankfurt, Germany

Development and optimization of a technique for labeling of human natural killer (NK) NK-92 cells and genetically engineered NK-92-scFv(MOC31)-zeta cells, targeted to the Ep-CAM (epithelial cell adhesion molecule) on prostate cancer cells, with superparamagnetic iron oxides (SPIO). SPIO labeled NK cells were injected intravenously into rats with implanted Ep-CAM positive prostate cancers and the accumulation of the SPIO labeled NK cells in prostate tumors could be monitored with a non-invasive magnetic resonance (MR) imaging technique.

13:30         3230.     Study on the Magnetic Relaxation of Superparamagnetic Nanotubes as Magnetic Resonance Imaging Contrast Agent

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xia Bai¹, sang jun Son¹,², shixiong Zhang¹, wei Liu³, elaine k. Jordan⁴, joseph a. Frank⁴, Thirumalai Venkatesan¹, Sang Bok Lee¹

¹university of maryland college park, college park, Maryland, USA; ²Kyungwon University, Republic of Korea; ³Philips Research North America, Briarcliff Manor, New York, USA; ⁴National Institutes of Health, Bethe

This work describes the synthesis of magnetic nanotubes (MNTs) which is silica nanotube (SNT)/magnetic iron oxide nanoparticle (MION) composite with MIONs loaded in SNTs. This unique structure combines the easy chemistry for differential functionalization of the inner and outer surfaces of SNTs with the superparamagnetic characteristics of MIONs. The MNTs had well-controlled dimensions and retained a high saturation magnetization. It was proved that MNTs worked as an effective T2 magnetic resonance (MR) contrasting agent. The in vitro cell labeling was effective without showing significant cytotoxicity. Our results indicate that MNTs could be an ideal candidate for image-guided drug delivery.

14:00         3231.     MRI Detection of the Migrating Neuronal Precursors in Normal and Hypoxic-Ischemic Neonatal Rat Brain by in Vivo Cell Label with MPIO

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Jian Yang¹,², Jian Xin Liu³, Gang Niu², Yong Liu³, Ed X. Wu⁴

¹Department of Electrical and Electronic Engineering, The University of Hong Kong , Hong Kong, People's Republic of China; ²The First Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China; ³The School of

In this study,10-day-old normal rats (n=6) and hypoxic-ischemic (H-I) neonatal rats (n=6) were injected with the micronsized iron oxide particles (MPIOs) into the anterior lateral ventricle. 2D and 3D gradient echo MRI was performed with a 7T animal scanner in hour 3, day 3, day 7 and day 14 after the MPIOs injection. Then animals were sacrificed for double staining with iron and mature neurons. In normal neonatal rat brain, the migrating pathway of the endogenous neural progenitor cells (NPCs) with MPIO is mainly along the rostral migratory stream to the olfactory bulb. In H-I neonatal rat brain, the migration of endogenous NPCs with MPIO is mainly toward injured boundary. MRI can facilely detect the above migrations in 2 weeks. Therefore, in vivo magnetic cell labeling of endogenous NPCs with MPIO and subsequently non-invasive, serial MRI monitoring should open up a new approach to probe into the mechanism of cell migration in the developmental brain under physiological and pathologic states.

14:30         3232.     Quantitative Assessment of Magnetically Labeled Luciferase Positive Cells Using Multimodality Imaging

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April M. Chow¹,², Kwan Man¹, Jerry S. Cheung¹, Tracy Y. Chow¹, Ed X. Wu¹

¹The University of Hong Kong, Pokfulam, Hong Kong

Cellular imaging using magnetically labeled luciferase positive cells with multimodality imaging has found numerous biological applications. However, studies only involve imaging dual-labeled cells, tracking their migrations without quantification of local density of the dual-labeled cells. Quantitative analysis of cells after transplantation may allow more accurate assessment of cell delivery and subsequent distribution and migration, which can lead to more effective monitoring and optimization of therapeutic paradigms. In this study, we demonstrated that dual-labeled cells exhibited excellent linear correlations between cell concentration with photon flux and &[Delta]R2* in vitro, illustrating that quantitative assessment of dual-labeled cells can be achieved.

15:00         3233.     Comparison of 2 Different Tumor Cell Labeling Techniques for in Vitro MRI Characterization with New Iron Oxide Particles

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Olaf Saborowski¹, Francesco Santini², Melpomeni Fani³, Philippe Robert⁴, Sebastien Ballet⁴, Jean Sebastien Raynaud⁴, Robin Santus⁴, Johannes Froehlich³, Klaus Scheffler², Georg Bongartz³, Helmut R. Maecke³

¹University Hospital Basel, Basel , Switzerland; ²University Basel/University Hospital, Basel, Switzerland; ³University Hospital Basel, Basel, Switzerland; ⁴Guerbet Group, Aulnay-Sous-Bois, France

Iron oxide particles (SPIO and USPIO) are widely used for MRI-based cell labeling and tracking because they can be loaded on cells by simple protocols and provide high image contrast due to their large susceptibility effect. We compared 2 different cell labeling models (AGAR and Ficoll) in human KB cells. Both presented cell labeling methods (AGAR and Ficoll model) are feasible for in vitro MR characterization of KB tumor cells at 1.5, 2.35 and 3T. Ficoll method is easier to perform because it does not need a heating procedure for preparation without air bubbles as compared to AGAR method.

13:30         3234.     Longitudinal Tracking and Quantification of T Cells Using in Vivo 19F MRI [Not Available]

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Mangala Srinivas¹, Michael S. Turner², Penelope A. Morel², Jelena M. Janjic¹, David H. Laidlaw³, Eric T. Ahrens¹,⁴

¹Carnegie Mellon University, Pittsburgh, Pennsylvania, USA; ²University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA; ³Brown University, Providence, USA; ⁴Pittsburgh NMR Center for Biological

¹⁹F MRI was used to track T cells in a murine model of acute inflammation for up to 21 days. Quantification of total ¹⁹F signal in the DLN, and hence apparent cell numbers, from the in vivo data showed 2.1x10⁶ ± 9x10⁵ apparent cells at day 2 and 3.6x10⁶ ± 9x10⁵ at day 7 post-transfer in the draining lymph node. The murine inflammation model can be applied to study the effect of therapeutics on T cell trafficking. The in vivo ¹⁹F platform developed can readily be extended to other cells types including, immunotherapeutics or stem cells.

14:00         3235.     A Novel Bimodal Fluorescent and Paramagnetic Lipid for Cell Labelling and Tumour Magnetic Resonance Imaging

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Nazila Kamaly¹, Tammy Louise Kalber¹, Jimmy D. Bell¹, Michael R. Jorgensen¹, Andrew David Miller¹

¹Imperial College London, London, UK

A novel bimodal fluorescent and paramagnetic lipid, Gd.DOTA.Rhoda.DSA was synthesised. Cationic and neutral PEGylated bimodal liposomes were formulated for cell labelling and tumour imaging respectively. Effective IGROV-1 (human ovarian carcinoma) cell labelling was demonstrated in vitro post incubation of cells with the cationic liposome formulations containing Gd.DOTA.Rhoda.DSA. The enhanced permeation and retention (EPR) effect of tumour tissue was exploited post-injection of the neutral PEGylated liposomes in mice to image IGROV-1 xenografts. Tumour T1 values were reduced 14-24 h post-injection of the bimodal liposomes by a substantial 65%. These MRI findings were supported by fluorescence findings co-validating the presence of the bimodal liposomes/lipid within tumour tissue.

14:30         3236.     Bimodal Intracellular Nanoparticles Based on Quantum Dot Technology for High Field MR Microscopy at 21.1 T

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Jens Thorvald Rosenberg¹,², Joshua M. Kogot¹, Goeffery F. Strouse¹, Samuel Colles Grant¹

¹The Florida State University, Tallahassee, USA

A bimodal contrast agent for the intracellular transfection of mammalian cells has been optimized for high magnetic field MR imaging at 21.1 T. With a fluorescent InP/ZnS quantum dot as a substrate, a peptide-bound lanthanide (Dy³⁺) component has been added to generate MR contrast. The CAAKA–DOTA-Ln³⁺-Qdot agent displays strong MR contrast enhancement for all relaxation mechanisms, but the strongest contrast for intracellular loading is seen with T2/T2* weighting. Utilizing this agent, Chinese Hamster Ovary (CHO) cells were transfected, with MR and confocal images displaying contrast enhancement and the intracellular localization of nanoparticles.

15:00         3237.     ¹⁹F NMR Molecular Imaging: Cell Labeling With Emulsified Perfluoro-15-Crown-5-Ether

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Samir Mulla-Osman¹, Henrike Goetze², Ute Bommerich³, Johannes Bernarding

¹University of Magdeburg, Magdeburg, Germany; ²University of Magdeburg, Germany; ³Leibniz Institute for Neurobiology, Germany

Monitoring ¹⁹F-labelled cells is an important new technique to evaluate in vivo the fate of implanted cells such as in stem cell therapy. The use of ¹⁹F-marker substances such as perfluorocarbons (PFC) has been explored by ¹⁹F spectroscopy and magnetic resonance imaging (MRI) for cell tracking. We present first results of single volume selective spectroscopy of fibroblasts, which have been labeled with perfluoro-15crown-5-ether (PFCE) emulsion.

MRS Methodology

13:30         3238.     MEGA-Editing of  Spermine/Spermidine in Healthy Human Prostates Using External Phased-Array Coil Assembly

Computer 25

Michael Albert Thomas¹, S.Sendhil Velan², Saadalah Ramadan³,⁴, Nagarajan Rajakumar¹, Daniel J. Margolis¹, Maria Ana Gomez¹, Steve S. Raman¹, Carolyn E. Mountford³,⁴

¹UCLA, Los Angeles, California , USA; ²West Virginia University, Morgantown, West Virginia, USA; ³Brigham and Women's Hospital, Boston, Massachusetts, USA; ⁴Harvard Medical School, Boston, Massachusetts, USA

Polyamines such as spermidine and spermine play a critical role in cell proliferation and differentiation in cancer. Overlap of metabolite resonances is a major concern in conventional one-dimensional (1D) MR Spectroscopy (MRS), hence spectral-editing techniques either based on signal subtraction or multiple-quantum filter have been proposed and tested in human brain in vivo. A goal of this work was to implement a MEGA-based spectral editing sequence on a 3T MRI scanner, to optimize the technique using prostate phantom, and to evaluate the feasibility of detecting spermine/ spemidine in healthy human prostates using an external phased-array matrix coil assembly.

14:00         3239.     Optimized MRS of Neurotransmitters: How Far Do You Need to Go?

Computer 25

Paul Mullins¹,², Hongji Chen², Jing Xu², Arvind Caprihan², Charles Gasparovic²,³

¹Bangor University, Bangor, UK; ²The MIND Research Network, Albuquerque, New Mexico, USA; ³University of New Mexico, Albuquerque, New Mexico, USA

Standard and optimized MRS sequences for the detection of Glutamate and other neurotransmitters are compared for test re-test reliability.

14:30         3240.     High Speed Multi-Voxel Thermography with Free Induction Decay Echo Planar Chemical Shift Imaging

Computer 25

Matthew A. Neimark¹, Scott Henneman², Yingli Yang², Jae Choi², Angelos Aristeidis Konstas³, Melvyn B. Ooi, Hamed Mojahed², Andrew F. Laine², John Pile-Spellman², Truman R. Brown²

¹Columbia University, New York, New York, USA; ²Columbia University, New York, USA; ³Massachusetts General Hospital, Boston, USA

In this study, we present a fast method of performing spectroscopic imaging using free induction decay echo planar chemical shift imaging (FID EP-CSI).  This technique was performed on a phantom made up of Ringer’s lactate and 10 mM NAA.  The phantom was cooled from 38 to 29°C while temperature was continuously monitored, and 13 FID EP-CSI acquisitions were performed.  Each acquisition was 28 seconds.  This is 12 times faster than conventional CSI. For voxels in a central region, the overall regression for  NAA-H₈O difference (δ_NAA-H8O)  vs. temperature (±95% confidence intervals) was T=(100.67±1.07)δ_NAA-H8O+300.36±2.86 (R2=0.9967; rms=0.16°C).

15:00         3241.     Fully Automated Shimming for High Lipid Regions Using Phased Arrays at 3T

Computer 25

Gamaliel Isaac¹, Jeremy jeremy.magland@upenn.edu Magland, Hoby Patrick Hetherington²

¹University of Pennsylvania, Philadelphia, Pennsylvania, USA; ²Yale University, New Haven, Connecticut, USA

We have developed a robust fully automated method for shimming regions of the body with high lipid content which is compatible with phased array detection. The method utilizes multi evolution delay B0 maps to generate high accuracy while retaining a large bandwidth for poor starting homogeneity. The method includes an embedded Dixon image to identify fat and water content such that the chemical shift due to lipid is corrected for allowing for the use of arbitrary evolution times. To demonstrate the method we have applied it to shim the human calf at 3T on a Siemens Trio system.

13:30         3242.     SVD 8-Channel Coil Combine for 2D Chemical Shift Imaging (CSI) MRI

Computer 26

Mithun Diwakar¹, Mingxiong Huang¹,², Roland R. Lee¹,², Rebecca J. Theilmann¹

¹UCSD, La Jolla, California , USA; ²VA San Diego Healthcare System, San Diego, California , USA

This work describes a novel method for combining 2D Chemical Shift Imaging (CSI) data recorded by 8 independent phased array coils (8-channel GE head coil).  Singular Value Decomposition (SVD) is a form of dominant mode analysis that can be used to combine time decay signals.  The work was carried out on a phantom containing physiologic concentrations of key metabolites found in the brain (NAA, Ch, Cr). The advantages of SVD over conventional methods of combining signals from multiple coils include preservation of phase-information, automatic zero-order phasing, and no need of a priori information.

14:00         3243.     Improved Spectral Quality Through Enhanced Shimming on a Clinical Platform at 3T and 7T

Computer 26

Ralf Mekle¹,², Giulio Gambarota¹, Vladimir Mlynarik¹, Rolf Gruetter¹,³

¹Ecole Polytechnique Federale de Lausanne, Lausanne, Switzerland; ²University of Lausanne, Lausanne, Switzerland; ³Universities of Lausanne and Geneva, Lausanne and Geneva, Switzerland

Reliable localized shimming is an essential prerequisite for obtaining high-quality MR spectra, especially at higher fields (≥3T). For the first time, the fast automatic shimming technique by mapping along projections (FASTMAP) and its descendant FASTESTMAP were implemented on a clinical platform of a 3T and a 7T system. In vivo proton spectra from various brain regions were acquired and showed excellent quality due to the enhanced local field homogeneity resulting from improved shimming with FASTMAP/FASTESTMAP that translated into reduced water and metabolite linewidths at both field strengths.

14:30         3244.     Application of Forward Linear Prediction Method to High-Resolution NMR Spectra in Inhomogeneous Fields

Computer 26

Hai Feng¹,², Zhiwei Chen¹, Shuhui Cai¹, Xiaohong Wang¹, Ji Feng³, Zhong Chen¹

¹Xiamen University, Xiamen, People's Republic of China; ²Institute of Physics, Chinese Academy of Sciences, Beijing , People's Republic of China; ³Institute of Physics, Chinese Academy of Sciences, Beijing, People's Republ

The forward linear prediction (LP) method was applied to deal with 2D intermolecular double quantum coherence spectra from inhomogeneous fields. The results show that compared to normal discrete Fourier transform, the use of forward LP extrapolation can shorten sampling time by a factor of eight or more at the same level of sensitivity and resolution. It can effectively extend the data sets acquired from inhomogeneous fields even for shorter data records and lower signal-to-noise ratio.

15:00         3245.     High-Quality MR Spectroscopy of the Human Brain with Full Signal Intensity at Echo Times Below 6 Ms on a Clinical Platform at 3T and 7T

Computer 26

Ralf Mekle¹,², Vladimir Mlynarik¹, Giulio Gambarota¹, Martin Hergt³, Gunnar Krueger³, Rolf Gruetter¹,⁴

¹Ecole Polytechnique Federale de Lausanne, Lausanne, Switzerland; ²University of Lausanne, Lausanne, Switzerland; ³Siemens Medical Solutions-CIBM, Lausanne, Switzerland; ⁴Universities of Lausanne and Geneva, Lau

The implementation of the spin echo full intensity acquired localized (SPECIAL) spectroscopy technique on a clinical platform was taken to the next level by combining interleaved water suppression (WS) and outer volume saturation (OVS), optimized sequence timing, and large B1 fields producing coils in addition to improved shimming. High-quality single voxel spectroscopy (SVS) data of the human brain were acquired at TEs below 6 ms on 3T and 7T systems. The high SNR of the spectra enabled reliable metabolite quantitation at both field strengths. Moreover, the enhanced sensitivity at the higher B0 field allowed a twofold reduction in scan time.

13:30         3246.     Automating Brain Tumour Classification Using High Resolution Magic Angle Spinning Data

Computer 27

Jean-Baptiste Poullet¹, Daniel Monleon², M. Carmen Martinez-Bisbal³,⁴, Bernardo Celda³,⁴, Sabine Van Huffel⁵

¹Katholieke Universiteit Leuven , Leuven, Belgium; ²Fundación Investigación Hospital Clínico Universitario Valencia, Valencia, Spain; ³University of Valencia, Spain; ⁴Networking Research Center on Bioengineering

The limited success of in vivo MRS to classify some brain tumor types tends to encourage the use of other data types. Thanks to their narrow line widths and their large signal-to-noise ratios, high resolution magic angle spinning (HR-MAS) data provides much more information than in vivo MRS. Since biopsy extraction is a routine procedure in the clinical practice, incorporating HRMAS in the decision system is a reasonable solution to improve brain tumor diagnosis. This study propose a fully automated procedure to classify HR-MAS spectra.

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