Joint Annual Meeting ISMRM-ESMRMB 2014 10-16 May 2014 Milan, Italy



3791-3814 Hyperpolarized Agents, MEMRI & Gene Tracking
3815-3838 Molecular Imaging

Hyperpolarized Agents, MEMRI & Gene Tracking

Tuesday 13 May 2014
Exhibition Hall  10:00 - 11:00

  Computer #  
25 Single-shot Acquisition of [1-13C]Pyruvate and Lactate on a 3T Clinical Scanner
Benjamin J. Geraghty1,2, Justin Y. C. Lau1,2, Albert P. Chen3, and Charles H. Cunningham1,2
1Dept. of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada, 2Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada, 3GE Healthcare, Toronto, Ontario, Canada

Simultaneous acquisition of multiple hyperpolarized 13C metabolites within a single-shot is possible through jointly sampling k-t space with a spiral trajectory that oversamples the field-of-view, and has been demonstrated on a small animal scanner. Due to limited gradient performance in conventional clinical scanners, achieving large oversampling rates while maintaining adequate resolution within a single readout is unfeasible. We relax the oversampling requirement by selectively exciting only two metabolites using a dual-band spectral-spatial pulse. Images are recovered through a model based least squares reconstruction. In vivo feasibility of simultaneous acquisition of hyperpolarized [1-13C]pyruvate and lactate is demonstrated on a healthy rat.

3792.   26 Compensating for Metabolite Dynamics in 13C Chemical Shift Separation
Elena Nasonova1, Markus Durst2,3, Concetta Gringeri3, Eliane V. Farrell4, Michael Friebe1, Axel Haase2, Markus Schwaiger4, and Rolf F. Schulte3
1Chair of Computer Aided Medical Procedures, TU München, Munich, Germany, 2Zentralinstitut für Medizintechnik (IMETUM), Munich, Germany, 3GE Global Research, Munich, Germany, 4Department for Nuclear Medicine, TU München, Munich, Germany

Iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) is a fast and efficient method for separation of 13C species. However, the underlying least squares chemical shift imaging (LSCSI) technique makes use of assumption of constant signal contributions from metabolites within several acquisitions and, therefore, is not consistent with the fast-changing metabolic signal. We attempted to compensate this non-valid assumption in our method. It uses time-dependent correcting factors, obtained from the computed metabolic time courses and inserted into a spectral encoding matrix. Resulting images are then obtained by conventional inversion of this modified matrix and gridding reconstruction.

27 Automated Kinetic Modeling of Perfusion and Metabolism Based on Dynamic Hyperpolarized 13 C Data With Open-Source SIVIC Software
Christine Leon Swisher1,2, Jason C. Crane1, Marram P. Olson1, Cornelius Von Morze1, Daniel B. Vigneron1,2, and Sarah J. Nelson1,2
1Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, United States, 2UC Berkeley-UCSF Graduate Program in Bioengineering, San Francisco, CA, United States

Considerable attention has been dedicated to investigating the dynamics of hyperpolarized signals to detect the underlining pathophysiology4-8. Derivation of kinetics from HP substrates often requires complex, multi-compartment models, which are prone to misinterpretation. Moreover, as the technology moves into the clinic, there is a clear need for standardization, simplification of complicated workflows, and a format compatible with PACS. The SIVIC package processes and quantifies dynamic HP spectroscopic data in two simple steps producing multiple parameters including quantification of dynamics, perfusion, and metabolic reaction rate kinetics. These can then be displayed with ease in SIVIC, a free, open-source software package.

3794.   28 Reconstruction of Carbon-13 Metabolic MR Images Using Constrained Optimisation
Elena Nasonova1, Markus Durst2, Concetta Gringeri3, Eliane V. Farrell4, Michael Friebe1, Axel Haase2, Markus Schwaiger4, and Rolf F. Schulte3
1Chair of Computer Aided Medical Procedures, TU München, Munich, Germany, 2Zentralinstitut für Medizintechnik (IMETUM), Munich, Germany, 3GE Global Research, Munich, Germany, 4Department for Nuclear Medicine, TU München, Munich, Germany

MR spectroscopy with hyperpolarised [1-13C] agents is a novel functional imaging modality that examines natural metabolic reactions. Due to rapid signal decay and challenging experimental settings reconstructed images exhibit low signal-to-noise ratio (SNR) and artifacts. In this work the SNR improvement by 20% at least was achieved with iterative reconstruction with included Tikhonov, total variation (TV), total generalised variation (TGV) regularisation terms as well as anatomy-based support mask. The proposed methods were validated in mathematical simulations and in vivo studies and proved to be advantageous for reconstruction of functional metabolic images.

3795.   29 Spectrally Selective Imaging of Hyperpolarized 13C Pyruvate with Multi-Echo, Multi-Phase Advance Balanced Steady State Free Precession
Gopal Varma1, Xiaoen Wang1, and Aaron K Grant1
1Radiology, Division of MR Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States

Balanced steady-state free precession (bSSFP) offers potential advantages for imaging of hyperpolarized 13C, including high signal-to-noise ratio (SNR) and efficient use of magnetization. Several variants of bSSFP provide spectroscopically selective images, including multi-echo methods and techniques that use a variable RF phase advance. Both approaches have undesirable sensitivity to off-resonance, and poor conditioning of the reconstruction can degrade SNR. Here we describe a multi-echo variable phase advance method that may provide more robust imaging. The technique is applied to phantoms and in vivo imaging of pyruvate and its metabolites, yielding images with 1mm2 in-plane resolution, 4mm slice, and peak lactate SNR~30.

3796.   30 Robust Single-Shot Hyperpolarized 13C Spectroscopic Imaging Utilizing Incoherent k-t spiral Sampling and Low-Rank Matrix Completion
Jeremy W Gordon1, Sean B Fain1,2, David J Niles1, and Kevin M Johnson1,2
1Medical Physics, University of Wisconsin-Madison, Madison, WI, United States, 2Radiology, University of Wisconsin-Madison, Madison, WI, United States

Joint spatial-spectral reconstruction enables highly accelerated 13C spectroscopic imaging but requires high performance gradients to optimally sample k-t space. However, temporal correlations between adjacent timeframes can be exploited by permuting or shifting the TE to reduce gradient requirements while still sampling k-t space sufficiently. Simulations and in-vivo results indicate that by permuting the k-t trajectory via pseudorandom TEs and incorporating low-rank regularization, temporal correlations across timeframes can be incorporated to improve the conditioning of the encoding matrix and reduce noise in low signal metabolite images. The proposed framework reduces gradient requirements and may enable k-t spiral sampling on clinical platforms.

3797.   31 Assessment of acute inflammatory liver injury in a rat CCl4 model using metabolic imaging of hyperpolarized [1-13C]pyruvate
Sonal Josan1,2, Kelvin Billingsley1,3, Juan Orduna2, Jae Mo Park1, Richard Luong4, Srinevas Reddy5, Ralph Hurd6, Adolf Pfefferbaum2,7, Daniel Spielman1, and Dirk Mayer1,8
1Radiology, Stanford University, Stanford, CA, United States, 2SRI International, Menlo Park, CA, United States, 3Chemistry and Biochemistry, San Francisco State University, San Francisco, CA, United States, 4Comparative Medicine, Stanford University, Stanford, CA, United States, 5Surgery, University of Maryland, Baltimore, MD, United States, 6GE Healthcare, CA, United States, 7Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, United States, 8Diagnostic Radiology and Nuclear Medicine, University of Maryland, Baltimore, MD, United States

Numerous studies using hyperpolarized pyruvate (Pyr) have been applied to investigate cancer and heart disease, but very few reports have been published on applications in diseased liver other than cancer. As several liver pathologies are associated with elevated alanine transaminase (ALT) activity, the aim of this work was to investigate the use of dynamic metabolic imaging of hyperpolarized [1-13C]Pyr for the assessment of liver damage induced by administration of carbon tetrachloride (CCl4).

3798.   32 Gradient-Enhanced Effectively Decoupled INEPT (GREEDI)
Daniel Spielman1, Keshav Datta2, Sonal Josan3, Stephen Lynch4, and Ralph Hurd5
1Radiology, Stanford University, Stanord, CA, United States, 2Electrical Engineering, Stanford University, CA, United States, 3Radiology, Stanford University, CA, United States, 4Chemistry, Stanford University, CA, United States, 5GE Healthcare, CA, United States

Polarization transfer methods provide improved detection of 13C nuclei directly bonded to protons. However, efficient in vivo measurements are difficult due to SAR-intensive decoupling requirements. Here we present a modification to the conventional INEPT sequence that eliminates splitting due to short-range 13C-1H J-coupling, while providing a √2 SNR gain, without the need for proton decoupling. The targeted application is enhanced imaging and spectroscopy of [2-13C]Lac and [2-13C]Ala (metabolic products generated by hyperpolarized [2-13C]Pyr), however the approach may also be applicable to detecting C2, C3, and C4 glutamate and glutamine resonances following infusion of thermally polarized 13C-substrates.

3799.   33 Quantitative Perfusion with Hyperpolarized 13C-tert-butanol: Correlation against ASL and Quantitative Immunohistopathology
Leo L Tsai1, Xiaoen Wang1, Gopal Varma1, Benjamin Edelstein1, Rupal Bhatt2, David C Alsop1, and Aaron K Grant1
1Department of Radiology, Beth Israel Deaconess Medical Center, Boston, MA, United States, 2Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, United States

Hyperpolarized C-13-tert-butanol (hC13-tert-butanol) provides a robust and rapid method of tumor perfusion quantification with high SNR, with high translational potential for clinical monitoring of antiangiogenics. Here we show excellent correlation of hC13-tert-butanol perfusion quantification as compared to ASL and direct immunostaining with CD34.

3800.   34 Purely endogenous hyperpolarized [1-13C]Pyruvate solutions for metabolic study in glioblastoma rat models - permission withheld
Mor Mishkovsky1,2, Emine Can3, Tim Eichhorn4, Denis Mario5, Ivan Radovanovic5, Rolf Gruetter1,6, Virginie Clément-Schatlo5, and Arnaud Comment3
1Laboratory for Functional and Metabolic Imaging (LIFMET), Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland, 2Department of radiology, Univesity of Lausanne, Lausanne, Switzerland, 3Institute of Physics of Biological Systems, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland, 4Paul Scherrer Institute (PSI), Villigen, Switzerland, 5Hôpitaux Universitaires de Genčve (HUG), Geneva, Switzerland,6Department of radiology, Univesity of Lausanne and Geneva, Switzerland

Hyperpolarized [1-13C]pyruvate solutions prepared without persistent radicals were used to study brain metabolism in rat model of human glioblastoma. Real time in vivo pyruvate metabolism was acquired with large signal-to-noise ratio that allows studying the kinetic of the LDH-mediated conversion of pyruvate to lactate in the tumor. The use of completely endogenous sample compositions through all the steps of the dissolution DNP experiment can facilitate the clinical application of hyperpolarized pyruvate for tumor diagnostic and treatment response as the filtration step is eliminated.

3801.   35 Measuring polarization using asymmetry of hyperpolarized [1,2-13C]Pyr doublets
Keshav Datta1, Sonal Josan2, and Daniel Spielman2
1Dept. of Electrical Engineering, Stanford University, Stanford, CA, United States, 2Department of Radiology, Stanford University, Stanford, CA, United States

Knowledge of the liquid-state polarization is necessary for absolute quantitation of in vivo hyperpolarized MRS data. In contrast to earlier work suggesting asymmetry of the C2 doublet (aC2) of [1,2-13C]Pyr (1% naturally abundant in a hyperpolarized [1-13C]Pyr sample) can directly be used to compute the instantaneous polarization, we present both analytic expressions and experimental results demonstrating a single measurement of aC2 is insufficient, and polarization calculations also depend on both the delay between the sample exiting the polarizer and the time of measurement as well as knowledge of the T1 decay rates of the individual peaks in the doublet resonance.

3802.   36 Improved dynamic 3D spiral CSI with interleaved spectral band excitation for metabolic imaging of hyperpolarized [2-13C]pyruvate
Sonal Josan1, Jae Mo Park1, Ralph Hurd2, Daniel Spielman1, and Dirk Mayer1,3
1Radiology, Stanford University, Stanford, CA, United States, 2GE Healthcare, CA, United States, 3Diagnostic Radiology and Nuclear Medicine, University of Maryland, Baltimore, MD, United States

There has been growing interest recently in using hyperpolarized [2-13C]pyruvate, to follow the 13C label into metabolic products including glutamate (in exchange with α-ketoglutarate in the TCA cycle), citrate, and acetylcarnitine as well as lactate and alanine. CSI with [2-13C]Pyr is challenging given the wide spectral dispersion of the resonances. This work presents an improved design for 3D CSI with [2-13C]Pyr using spectrally selective excitation of limited frequency bands containing a subset of metabolites, and interleaving different bands to acquire dynamic metabolic data in vivo in rat liver.

3803.   37 Single voxel localization for dynamic hyperpolarized 13C MR spectroscopy
Albert P Chen1 and Charles H Cunningham2,3
1GE Healthcare, Toronto, ON, Canada, 2Imaging Research, Sunnybrook Health Sciences Centre, Toronto, ON, Canada, 3Medical Biophysics, University of Toronto, Toronto, ON, Canada

PRESS technique has been widely used to achieve voxel localization for in vivo 1H MRS acquisitions, but for dynamic hyperpolarized 13C MRS experiments, the transition bands of the refocusing pulses may prematurely saturate the pre-polarized substrate spins moving into the voxel. This limitation may be overcame by designing refocusing pulses that do not perturb the resonance of the hyperpolarized substrate but refocuses the spins of the metabolic products. In this study, a PRESS pulse sequence incorporating spectral-spatial refocusing pulses that have a stop band (‘notch’) at the substrate resonance is tested in vivo using hyperpolarized [1-13C]pyruvate.

3804.   38 Ascorbic Acid Enhances Pyruvate Dehydrogenate Flux In Isolated Perfused Rat Lungs
Hoora Shaghaghi1, Stephen J. Kadlecek1, Sarmad Siddiqui1, Mehrdad Pourfathi1, Profka Harrilla1, and Rahim R. Rizi1
1Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States

Ascorbic acid is a first line pulmonary defense mechanism against endogenous and exogenous oxygen reactive species. As such, we investigated the effect of ascorbate on lung metabolic activity using hyperpolarized [1-13C] pyruvate. The bicarbonate signal significantly increased in the presence of ascorbate. Addition of N,N,N′,N′-tetramethyl-p-phenylenediamine(TMPD), a well-known compound used in electron transfer chain investigations, into the ascorbate-containing perfusate amplifies this enhancement. Since the reaction rate of ascorbate plus TMPD is 30 times faster than that of ascorbate alone, we concluded that the effect of ascorbate on PDH flux is a mitochondrial membrane linked effect.

3805.   39 Interleaved Imaging and Frequency-Selective Spectroscopic Acquisition for in vivo Pyruvate Polarization Monitoring
Justin Y. C. Lau1,2, Albert P. Chen3, Jennifer Barry2, William Dominguez-Viqueira2, and Charles H. Cunningham1,2
1Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada, 2Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada, 3GE Healthcare, Toronto, Ontario, Canada

The feasibility of interleaved imaging and selective spectroscopic acquisition for hyperpolarized 13C is demonstrated in vivo. The asymmetry of the pyruvate C2 doublet has been shown to correlate with the instantaneous polarization. Combined with a calibration-based interpretation of measured C2asymmetry, this investigation is a promising step toward hyperpolarized signal intensity normalization for quantitative in vivo metabolic image analysis.

3806.   40 Effects of acute and chronic dichloroacetate treatment on hyperpolarized 13C pyruvate metabolism, necrosis and tumor volume in P22 sarcoma bearing BDIX rats
Steven Reynolds1, Tooba Alizadeh2, Stephen Metcalf2, Adriana Bucur1, Samira Kazan2, Becky Bibby2, Martyn Paley1, and Gillian M Tozer2
1Academic unit of radiology, University of Sheffield, Sheffield, South Yorkshire, United Kingdom, 2Tumor microcirculation group, University of Sheffield, Sheffield, South Yorkshire, United Kingdom

Hyperpolarized 13C-pyruvate MRS/MRI was used to study the effect of dichloroacetate (DCA), which disrupts pyruvate dehydrogenase kinase, on tumor metabolism. We used acute DCA dosing (30 minutes prior to scanning) and chronic DCA dosing (up to 10 daily doses) in P22 sarcoma-bearing BDIX rats. MR data showed no significant difference between treated and control groups for the pyruvate to lactate rate constant kpl in either the acute or chronic cohorts. There were also no significant differences in tumor growth rate or percentage cell necrosis. However, pyruvate concentration was decreased in tumors treated chronically with DCA versus control.

3807.   41 Carnitine supplementation creates a cardiac reserve of free carnitine to enable buffering of excess acetyl units
Michael S Dodd1, Andrew J Lewis1, Vicky Ball1, and Damain J Tyler1
1Oxford Metabolic Imaging Group, University of Oxford, Oxford, OXON, United Kingdom

Carnitine performs several vital roles in cellular metabolism including facilitating the transport of fatty acids into the mitochondria and buffering acetyl groups from excess acetyl-CoA. Carnitine supplementation has been proposed as a treatment for conditions such as heart failure. In this study, short-term carnitine supplementation in control animals did not alter the metabolism of pyruvate under normal situations. However, during a time of increased acetyl group availability, caused by dichloroacetate infusion, there was evidence of a carnitine reserve which was able to buffer excess acetyl groups into acetylcarnitine, allowing recycling of CoA back into β-oxidation or the TCA cycle.

3808.   42 Axonal transport rate decreased at the onset of optic neuritis in EAE mice
Tsen-Hsuan Lin1, Joong Hee Kim2, Carlos Perez-Torres2, Chia-Wen Chiang2, Kathryn Trinkaus3, Anne H. Cross4,5, and Sheng-Kwei Song2,5
1Physics, Washington University, St. Louis, MO, United States, 2Radiology, Washington University School of Medicine, St. Louis, MO, United States,3Biostatistics, Washington University School of Medicine, St. Louis, MO, United States, 4Neurology, Washington University School of Medicine, St. Louis, MO, United States, 5The Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, United States

Axonal transport plays a crucial role in neurodegenerative diseases. However, few reports have assessed axonal transport rate in MS or in experimental autoimmune encephalomyelitis (EAE). To assess the integrity of axonal transport in EAE, we employed the widely used manganese-enhanced MRI (MEMRI) on EAE mice at the onset of optic neuritis. Our results reveal that the axonal transport rate in EAE mice at the optic neuritis onset was significant decreased compared with the sham mice and correlated well with severity of impaired visual function. Postmortem immunohistochemistry was performed to assess optic nerve pathologies, including axonal injury, demyelination, and inflammation.

3809.   43 Not All Brain Regions Are Created Equal: Insights From Longitudinal Imaging of Early Postnatal Mouse Brain Development.
Kamila U Szulc1,2, Jason P Lerch3, Brian J Nieman3, Benjamin B Bartelle1,4, Edward J Houston1, Giselle A Suero-Abreu1,2, Miriam Friedel3, Charles Watson5, Alexandra L Joyner6, and Daniel H Turnbull1,7
1Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine, NYU School of Medicine, New York, NY, United States,2Biomedical Imaging Graduate Program, NYU School of Medicine, New York, NY, United States, 3Mouse Imaging Centre, Hospital for Sick Children, Toronto, ON, Canada, 4Molecular Biophysics Graduate Program, NYU School of Medicine, New York, NY, United States, 5The Australian Mouse Brain Mapping Consortium, The University of Queensland, Brisbane, QLD, Australia, 6Developmental Biology Program, Sloan-Kettering Institute, New York, NY, United States, 7Departments of Radiology and Pathology, NYU School of Medicine, New York, NY, United States

Lacking among the currently available set of MRI techniques has been an imaging approach that would allow for 3D noninvasive, longitudinal studies of brain development in individual mice. The goal of this project was to develop and optimize a Mn-enhanced MRI (MEMRI) imaging approach and to create a comprehensive database of normal mouse brain development to serve as a reference for future studies of mouse models of neurodevelopmental disorders. Through this work we were able to show that different brain regions are characterized by unique growth rates and patterns, which are accompanied by brain-region specific changes in MEMRI signal intensity.

3810.   44 In vivo molecular imaging using a dual-imaging reporter gene for verifying the role of HOXA gene subfamily in gastric cancer development and therapeutic monitoring
Chiao-Yun Chen1,2, Twei-Shiun Jaw1,2, Deng-Chyang Wu2,3, Yun-Ming Wang4, Gin-Chung Liu1,2, Kazunari K. Yokoyama2, and Yaw-Bin Huang2
1Kaohsiung Medical University Hospital, Kaohsiung, TAIWAN, Taiwan, 2Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, TAIWAN, Taiwan, 3Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, TAIWAN, Taiwan, 4National Chiao Tung University, Hsinchu, TAIWAN, Taiwan

We established a high penetration, high sensitivity infrared-fluorescent protein(IFP) for fluorescent imaging and synthesized the relatively high temporal and spatial resolution MR sensing contrast agent (SCA):Ł]-galactosidase(Ł]-gal) MR probe for producing the MR molecular imaging with a dual-imaging reporter animal model. The modality was used to verify the role of HOXA gene subfamily in gastric cancer development .It might also be useful in evaluating the effects of various therapeutic approaches. Because of the advantages offered by a combination of optical and MR images, it is hopeful that this technique will move quickly from in vitro and animal study to clinical trials.

3811.   45 Pyruvate Decarboxylase as a Reporter Gene for Magnetic Resonance Spectroscopic Imaging (MRSI)
Piotr Dzien1, Sui-Seng Tee1, Mikko Kettunen1, Timothy Larkin1, Scott Lyons1, Kerstin Timm1, De-En Hu1, Tiago Rodrigues1, Eva Serrao1, Elizabeth Mannion1, Paula D'Santos1, and Kevin Brindle1
1Biochemistry, University of Cambridge, Cambridge, Cambridgeshire, United Kingdom

A reporter gene that could be used with MRI would allow exploitation of the advantages of this imaging technique - spatial and temporal resolution and the penetration depth necessary for in vivo imaging. DNP increases the signal-to-noise ratio sufficiently to allow direct detection of the 13C tracer in real time and presents a novel approach for developing MR reporter genes. Here we report a proof of concept study in which we use inducible expression of a bacterial gene encoding the enzyme, pyruvate decarboxylase (PDC), as a marker for DNP MRSI.

3812.   46 19F MRI for non-invasive imaging of treatment failure in microencapsulated pancreatic cell therapy
Dian R. Arifin1,2, Deepak Kadayakkara1,2, and Jeff W.M. Bulte1,2
1Russell H. Morgan Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States, 2Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United States

We developed fluorine-labeled alginate microcapsules (fluorocapsules) for protection of transplanted pancreatic cells against immunorejection. Our goal is to assess the feasibility of 19F MRI to non-invasively visualize the degradation of fluoroencapsulated cell grafts, and therefore the impending failure of cell therapy in the case of capsule rupture. We successfully demonstrated that the release and dissipation of the fluorine agent upon capsule rupture could be detected as a reduction in 19F MR signal. This corresponded to a decrease in cell viability, indicating that 19F MRI can be used as a surrogate marker to predict therapeutic success or failure.

3813.   47 Sequential and Time-lapse MRI Monitoring of Peripheral Macrophage Recruitment and Migration in Mouse Brain
Yuki Mori1,2, Ting Chen1, Koji Ohno3, Shinichi Yoshida4, Yoshiyuki Tago4, Tetsuya Fujisawa5, Yuuto Kashiwagi1, Masaki Fukunaga1,2, Yutaka Komai6, Yutaka Hata5, and Yoshichika Yoshioka1,2
1Biofunctional Imaging, Immunology Frontier Research Center (IFReC), Osaka University, Suita, Osaka, Japan, 2Center for Information and Neural Networks (CiNet), National Institute of Information and Communications Technology (NICT) and Osaka University, Suita, Osaka, Japan, 3Institute for Chemical Research, Kyoto University, Uji, Kyoto, Japan, 4Frontier Biochemical and Medical Research Laboratories, Kaneka Corporation, Takasago, Hyogo, Japan, 5Graduate School of Engineering, University of Hyogo, Himeji, Hyogo, Japan, 6Single Molecule Imaging, IFReC, Osaka University, Suita, Osaka, Japan

Combination of MRI and nanoparticles has a possibility for visualizing the dynamics of cells in mouse brain. In this study, we focused on peripheral macrophages and attempted to track them noninvasively. We also attempted to monitor dynamic behaviors of cell migration with time-lapse MRI movie. MRI can successfully monitor the recruitment of peripheral macrophages into CNS even in normal as well as abnormal condition such as systemic inflammation or brain ischemia. Time-lapse MRI movie may reveal critical insights into cell behaviors that are not readily evident by microscopy. Our technique could contribute to reveal the mechanisms of neuro-immune crosstalk.

3814.   48 Feasibility of accurately determining cell number by 19F MRI and the impact of cellular rejection, inflammation and transfer of label
Jeff M Gaudet1,2, Emeline J Ribot3, Yuhua Chen1, Kyle Gilbert4, and Paula Foster1,2
1Imaging Research Laboratories, Robarts Research Institute, London, Ontario, Canada, 2Medical Biophysics, University of Western Ontario, London, Ontario, Canada, 3Centre de Resonance Magnetique des Systemes Biologiques, Universite Bordeaux, France, 4Centre for Functional and Metabolic Mapping, Robarts Research Institute, London, Ontario, Canada

Stem cell therapy has the potential to revolutionize modern medicine and clinical trials are already underway. Still, questions persist concerning which parameters (implantation method, size of transplant, timing) produce the best clinical outcomes. Fluorine-19 (19F) MRI provides an excellent tool to address these issues because of the potential for unambiguous detection and accurate quantification. In this study we correlate the change in 19F-signal quantification over time with fluorescence microscopy and immunohistochemistry. Our results indicate that accurate quantification of the cellular number is possible under some conditions and that 19F –labeling of bystander macrophages can confuse interpretation in certain cases.


Molecular Imaging

Tuesday 13 May 2014
Exhibition Hall  11:00 - 12:00

  Computer #  
3815.   49 Noninvasive Imaging of Angiogenesis with a lower case Greek alphalower case Greek nulower case Greek beta3 Integrin-targeted Multi-modality Nanoprobe in Myocardial Infarction Model
Di Chang1
1Department of Radiology, Jiangsu Key Laboratory of Molecular and Functional Imaging, Zhongda Hospital, Southeast University, Nanjing, Jiangsu, China

Angiogenesis is defined as blood vessel formation from a pre-existing vasculature, the formation of which can promote the recovery of cardiac blood flow after myocardial infarction. Proliferating endothelial cells highly express a number of integrins associated with angiogenesis, of which ¦Á¦Í¦Â3 has been shown to be particularly important. Cyclic peptide containing an arginine-glycine-aspartic acid (cyclic RGD) sequence has a high affinity to ¦Á¦Í¦Â3 integrin. The objective of this study was to design and develop a novel cyclic RGD probe based multi-modality imaging for evaluation of angiogenesis in myocardial infarction model.

50 Safety and Efficacy Evaluation Of A Novel Graphene-Based Nanoparticles As An MRI Blood Pool Agent
Shruti Kanakia1, Dung Minh Hoang2, Jimmy Toussaint1, Sayan Mullick Chowdhury1, Stephen Lee1, Kenneth R Shroyer3, William Moore4, Balaji Sitharaman1, and Youssef Zaim Wadghiri2
1Biomedical Engineering, Stony Brook University, Stony Brook, NY, United States, 2Radiology, Bernard & Irene Schwartz Center for Biomedical Imaging, NYU School of Medicine, New York, NY, United States, 3Pathology, Stony Brook University, Stony Brook, NY, United States, 4Radiology, Stony Brook University, Stony Brook, NY, United States

We report pre-clinical in vivo small animal safety and efficacy studies of a novel graphene-based blood pool MRI CA. The formulation called Mn-GNP-Dex (disk-shaped, thickness=3-4 nm, diameter ~100 nm) consists of graphene nanoparticles intercalated with manganese Mn2+ ions, are water-solubilized with dextran and have r1 relaxivity 92 mM-1S-1. The results show that the Mn-GNP-Dex formulation is safe, does not show any toxic effect in the animals with renal insufficiency, remains in blood for up to 2 hours and is more efficacious than clinical blood pool CA Ablavar®. Hence, Mn-GNP-Dex has great potential for development as high performance T1 blood pool MRI CA.

3817.   51 Ultrafast 129Xe Hyper-CEST
Céline Boutin1, Estelle Léonce2, Thierry Brotin3, Alexej Jerschow4, and Patrick Berthault2
1IRAMIS, SIS2M, UMR CEA/CNRS 3299, CEA Saclay, Gif-sur-Yvette, Gif sur Yvette, France, 2IRAMIS, SIS2M, UMR CEA/CNRS 3299, CEA Saclay, Gif sur Yvette, France, 3Laboratoire de Chimie, CNRS, Ecole Normale Supérieure de Lyon, Lyon, France, 4Chemistry Department, New York University, New York, NY, United States

129Xe biosensors have been demonstrated to provide sensitive probes of biological events. Very sensitive detection thresholds can be reached with the HyperCEST approach. We report herein the use of ultra-fast Z-spectroscopy as a powerful means to detect low concentrations of 129Xe NMR-based sensors in a single shot. This experiment enables a multiplexed detection of several sensors, as well as the extraction of the exchange buildup rate constant in a single-shot fashion. The ultrafast method makes it possible to provide ultra-fast and high-throughput sampling of biomarker mixtures.

3818.   52 Targeting radiation-induced neuroinflammation using ICAM-MPIO
Benedicte Descamps1, Sara Neyt2, Caroline Dumolyn2, Elke Decrock3, Julie Bolcaen4,5, Ingeborg Goethals4,5, Tom Boterberg6,7, Filip De Vos2, Christian Vanhove1,8, and Karel Deblaere4,9
1Infinity - Medisip - iMinds, Ghent University, Ghent, Belgium, 2Radiopharmacy, Ghent University, Ghent, Belgium, 3Basic Medical Sciences, Ghent University, Ghent, Belgium, 4Radiology and Nuclear Medicine, Ghent University, Ghent, Belgium, 5Nuclear Medicine, Ghent University Hospital, Ghent, Belgium, 6Radiotherapy and Experimental Cancer Research, Ghent University, Ghent, Belgium, 7Radiotherapy, Ghent University Hospital, Ghent, Belgium, 8GROUP-ID, Ghent University, Ghent, Belgium, 9Radiology and Medical Imaging, Ghent University Hospital, Ghent, Belgium

Iron oxide-based contrast agents can be labeled with antibodies to image selectively targeted molecular processes using MRI. Intercellular adhesion molecule (ICAM1) plays a key role in the early inflammatory cascade following brain irradiation. This protein mostly expresses on the luminal surface of the endothelium of brain venules and capillaries and promotes the recruitment and migration of leukocytes. We show that micron-sized particles of iron oxide (MPIO) labeled with anti-ICAM1 antibodies are a useful tool to selectively image the local upregulation of endothelial ICAM1 expression in an animal model of early radiation injury using T2*w MRI.

3819.   53 In vivo cellular MRI monitoring of FeO Labeled DC-based cancer vaccine for immunotherapeutic treatment of pancreatic cancer
Zhuoli Zhang1, Andrew Christian Gordon1, Weiguo Li1, Yang Guo1, Elias Gounaris1, Alexander Sheu1, Jodi Robin Nicolai1, Daniele Procissi1, and Andrew Larson1
1Radiology, Northwestern University, Chicago, Illinois, United States

In this work we demonstrate that iron-oxide labeled Dendritic Cells (DC), loaded with antigens, can be effectively tracked as they “home in” on the lymph nodes using MRI. We also correlate therapeutic response to successful targeting of DC as measured with MRI. The potential of the methods described can provide additional tools to develop DC based cancer vaccines.

3820.   54 Specificity of Multimodal molecular MR and US imaging applied to kidney tumor xenografts
Marie Poirier-Quinot1, Ludovic de Rochefort1, Ingrid Leguerney1,2, Sandra Robin1,2, Xavier Violas3, Luc Darrasse1, Rose-Marie Dubuisson1, Stéphanie Pitre-Champagnat1, Philippe Robert3, and Nathalie Lassau1,2
1Univ Paris Sud, CNRS, UMR 8081, IR4M, Orsay, France, 2IRCIV Gustave Roussy, Villejuif, France, 3Guerbet, Research, Roissy CDG Cedex, France

Evaluation of the specificity of multimodal molecular protocol, with two different imaging techniques, US and MRI, involving contrast agents (µbubbles and iron oxide nanoemulsion) both of them functionalized to target the same integrin (ανβ3) in mouse xenograft tumor model of kidney cancer is presented here. The protocol allows to quantify the tumor size, the dynamic contrast-enhanced DCE-US, the diffusion, the dynamic susceptibility contrast DSC-MR during 1 hour after injection. This methodological study could be used to follow-up treatment response.

3821.   55 Anti-angiogenic therapy follow-up in mice brain glioma model with P04000, a new molecular imaging avb3-nanoemulsion of iron oxide.
VIOLAS Xavier1, ROBERT Philippe2, NAIN DIT DUCRET Martine2, ROBIC Caroline2, BALLET Sebastien2, and COROT Claire2
1Guerbet, Aulnay sous bois, France, 2Guerbet, France

A new iron oxide nanoparticle based USPIO (P04000) is evaluated in terms of specificity and capacity to monitor antiangiogenic treatment in a brain tumor model in mice. The high affinity rgd vectored contrast agent who targets avb3 allows, with a basic Multi Gradient Echo sequence, to specifically enhance the tumor 2 hours post injection. The uptake of this agent is reduced to zero in the bevacizumab treated group before the tumor regression. This MR contrast agent is able to early demonstrate the effect of anti-angiogenic therapy with feasible MRI sequence and data post processing in humans.

3822.   56 In-Vivo Temperature Measurement using ParaCEST MRI Contrast Agents at 9.4T
Nevin McVicar1,2, Alex X Li2, Mojmir Suchy3, Robert H Hudson3, and Robert Bartha1,2
1Medical Biophysics, University of Western Ontario, London, Ontario, Canada, 2Centre for Functional and Metabolic Mapping, Robarts Research Institute, London, Ontario, Canada, 3Chemistry, University of Western Ontario, London, Ontario, Canada

Tissue temperature is measured in-vivo in mouse leg muscle following intramuscular injection of a paraCEST contrast agent using magnetic resonance imaging (MRI). Tissue MRI properties including relaxation time constants, diffusion coefficients and magnetization transfer effects were measured before and after paraCEST injection. Significant changes in tissue MR properties were observed between pre- and post-injection data. Only apparent diffusion coefficient correlated with measured tissue temperature. The paraCEST tissue temperature measurements were in agreement with true tissue temperature. Therefore, in-vivo tissue temperature measurements made using paraCEST contrast agents following direct injection are accurate despite changes in tissue relaxation properties.

3823.   57 Assessment of the size window of tumor vascular permeability using dextran-based CEST MRI
Yuguo Li1,2, Kannie Chan1,2, Yuan Qiao3, Jiadi Xu2, Jeff Bulte1, Bert Vogelstein3, Michael McMahon1,2, Shibin Zhou3, Peter van Zijl1,2, and Guanshu Liu1,2
1Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States, 2FM Kirby center, Kennedy Krieger Institute, Baltimore, MD, United States, 3Ludwig Center, Howard Hughes Medical Institute and Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, United States

Assessing tumor vascular permeability has important applications in clinical diagnosis and for the development of personalized nanoparticulate therapeutics. Here, we explored dextran as a potential Chemical Exchange Saturation Transfer (CEST) imaging agent by utilizing the CEST contrast originating from OH protons on the glucose units. Contrast was studied for particle sizes ranging from 4-60 nm. Dextrans of different molecular weights could be readily detected using CEST MRI. The differential permeability of an experimental tumor to dextrans sized at 4 and 14 nm was detected and renal clearance of the agents was also monitored.

3824.   58 Generating Positive Contrast from Magnetic Nanoparticles Using a SubShortTE Method with Conventional Spin Echo Sequences
Xiaodong Zhong1, Liya Wang2,3, Jing Huang2,3, and Hui Mao2,3
1MR R&D Collaborations, Siemens Healthcare, Atlanta, GA, United States, 2Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, United States, 3Center for Systems Imaging, Emory University School of Medicine, Atlanta, GA, United States

This study demonstrates a new method of SubShortTE, i.e. subtraction of a later echo signal from an earlier echo signal, with widely available SE/TSE sequences for generating positive contrast from magnetic nanoparticle contrast agents. This approach was evaluated with theoretical simulation and phantom imaging using iron oxide nanoparticles (IONP) with different sizes and concentrations. The results demonstrated that positive contrast could be obtained in IONP phantoms using this approach. SubShortTE could potentially provide a robust alternative method to the other positive contrast methods for molecular imaging and cell tracking applications without the need of any special sequences.

3825.   59 Infarct size and extracellular matrix remodelling quantification using an elastin specific contrast agent (ESMA) in a model of permanent coronary ligation
Andrea Protti1, Xuebin Dong1, Ajay Shah1, and Rene Botnar1
1King’s College London British Heart Foundation Centre of Excellence, London, UK, United Kingdom

Dynamic contrast-enhanced MRI (DCE-MRI) plays an increasingly important role in cardiac imaging . The dynamics of contrast agent uptake and distribution have shown high sensitivity and specificity for many pathological changes that are not detectable by anatomical imaging. Magnevist Gd-DTPA is one of the most used clinically approved contrast agents able to differentiate areas of burden from healthy after myocardial infarction (MI). Despite being an optimal tool to delineate the extent of infarction areas, Magnevist does not provide any insight about remodeling processes. For this reason, the albumin contrast agent gadofosveset, trade name Vasovist (from Ablavar), is used in this work to evaluate similarities and advantages to Magnevist in an MI mouse model at 7T.

3826.   60 Ultrasmall gadolinium manganese oxide nanoparticles as MRI contrast agent
Badrul Alam Bony1, Wenlong Xu1, Tirusew Tegafaw Mengesha1, Chorong Kim1, Sung June Kim1, Md. Wasi Ahmad1, and Gang Ho Lee1
1Chemistry, Kyungpook National University, Daegu, Korea

Biocompatible and water soluble D-glucuronic acid coated ultrasmall GdMnO3 nanoparticles were synthesized through a straight forward one step route for the first time. In vivo and in vitro images confirmed that, this nanoparticles can be applicable as a potential MRI contrast agent.

3827.   61 Comparison of standardized uptake values in normal structures and breast cancer metastases using PET/CT and PET/MRI
Akshat C Pujara1, Carolyn Wassong1, Roy A Raad1, James Babb1, Linda Moy1, and Amy Melsaether1
1New York University School of Medicine, New York, NY, United States

Validation of MR attenuation correction (MRAC) is required for comparison of SUVs derived from PET/CT with those derived from PET/MRI. The current study demonstrates that SUVmax generated from MRAC correlates well with SUVmax generated from PET/CT for normal structures and breast cancer metastases, and can thus be used for quantification of FDG activity. Interestingly, the metabolic activity of breast cancer metastases during the interval between PET/CT and PET/MRI differed depending on the site of spread. Further investigation is needed to evaluate the potential role of SUV measurements in tailoring imaging protocols to the metabolic activity of organ-specific metastases.

3828.   62 Sub-5 nm Ultrafine Iron Oxide Nanoparticles for Tumor Imaging: Novel Contrast and Improved Tumor Uptake
Liya Wang1,2, Jing Huang1,2, Xiaodong Zhong3, Hui Wu1,2, Lily Yang4, and Hui Mao1,2
1Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, Georgia, United States, 2Center for System Imaging, Emory University School of Medicine, Atlanta, Georgia, United States, 3MR R&D Collaborations, Siemens Healthcare, Atlanta, Georgia, United States, 4Surgery, Emory University School of Medicine, Atlanta, Georgia, United States

This study demonstrated the application of novel sub-5 nm ultra-fine iron oxide (UFIO) nanoparticles in imaging of xenograft tumors. The results showed higher tumor uptake of UFIO nanoparticles comparing to iron oxide nanoparticles (IONPs) with larger sizes, suggesting that the penetration and accumulation of IONPs in tumor tissue is size dependent. The transition from T1 contrast in the tumor vasculature in the early phase of post-injection to the T2 contrast at later phase, i.e., 24 hours after the injection of UFIO nanoparticles may provide a novel capability for following a dynamic process of delivery of UFIO probes to the tumor.

3829.   63 Image-guided Pro-angiogenic Therapy in Diabetic Stroke Mouse Model with a Multi-modal Nanoprobe
Ying-Ying Bai1 and Shenghong Ju1
1Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospita, Nanjing, Jiangsu, China

This study demonstrated that the neovasculature targeted nanoprobe can specifically evaluate angiogenesis in ischemic stroke. Molecular imaging demonstrated impaired angiogenesis in the diabetic mice and revealed the pro-angiogenic effects of EPC, the precursor cell of endothelial cell. While current clinical techniques for monitoring therapeutic efficacy, such as blood flow measurements, are capable of detecting large caliber vessels that form at the late stages of revascularization, molecular imaging with targeted contrast agents can map the early signatures of angiogenesis. In clinical practice, earlier detection of therapeutic response could be invaluable for guiding therapies, including determining effective drug doses and evaluating new treatment strategies.

3830.   64 Interleaved Magnetic Steering and MR imaging of USPIO Particles in One Dimension: Early Results
Hsin-Jung Yang1, Ke Cheng1, Ryan middleton1, Ivan Cokic1, Avinash Kali1, Louis Bouchard2, Eduardo Marban1, and Rohan Dharmakumar1
1Cedars Sinai Medical Center, Los Angeles, California, United States, 2UCLA, Los Angeles, California, United States

Retention of cells within regions of interest following their delivery is a known obstacle in the field of regenerative medicine. Recent studies have demonstrated that magnetic field gradient of bar magnets can be used to couple with the dipole moment of the cells labeled with iron oxide can be used to enhance retention and therapeutic regeneration. In this work, we investigated whether a Maxwell coil, which can be positioned within the MR scanner, would be able to deliver sufficient one-dimensional force on USPIO particles and the effect of this resultant force can be captured on the basis of T2* MRI.

3831.   65 A theranostic approach based on the use of a dual boron/Gd agent to improve the efficacy of Boron Neutron Capture Therapy in the pulmonary metastasis treatment.
Simonetta Geninatti1, Diego Alberti2, Antonio Toppino2, Annamaria Deagostino2, Stefania Lanzardo2, Nicoletta Protti3, Silva Bortulussi3, Saverio Altieri3, and Silvio Aime2
1Molecular Biotechnology and health sciences, University of Torino, Torino, TO, Italy, 2University of Torino, TO, Italy, 3University of Pavia, PV, Italy

A new dual agent targeted to pulmunary metastasis via Low Density Lipoprotein transporters has been proposed as an efficient and selective carrier of Boron and Gadolinium for MRI guided Boron Neutron Capture Therapy.

3832.   66 Evaluation of the novel SPIO GEH121333 for monitoring changes in tumor vascularity and vascular permeability after anti-angiogenic treatment using susceptibility contrast and T1-mapping
Else Marie Huuse1,2, Jana Cebulla2, Dan E Meyer3, Karina Langseth4, Siver Andre Moestue2, and Tone Frost Bathen2
1Department of medical Imaging, St. Olavs University Hospital, Trondheim, Norway, 2MI lab and Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway, 3Biomedical Imaging & Physiology Laboratory, GE Global Research Center, Niskayuna, NY, United States, 4GE Healthcare AS, Oslo, Norway

Preclinical-phase iron oxide particles (GEH121333), with a relatively large diameter and a high r1/r2 rate was used for monitoring vascular response to bevacizumab treatment in ovarian xenografts. Changes in T2 and T2* relaxation rate was used for calculation marker for the blood vessel density Q=Capital Greek DeltaR2/(Capital Greek DeltaR2*2/3) and post contrast tissue T1 after clearance of iron particles from the blood pool was used as a measure for changed tumor vessel permeability. The results suggest that the novel GEH121333 particles can be used to detect vascular changes after anti-angiogenic therapy and that their magnetic properties allow evaluation of changes both in T1 and susceptibility imaging, attributable to underlying changes in permeability and blood vessel density, respectively.

3833.   67 Evaluation of the reversibility of the binding between a targeted CA and its receptor by in vitro micro-MRI
Nicolas Gargam1, Luc Darrasse1, Philippe Robert2, Jean-Christophe Ginefri1, Jean-Sébastien Raynaud2, and Marie Poirier-Quinot1
1IR4M - UMR 8081, Université Paris Sud XI, Orsay, France, 2Imaging and Biological Research, Guerbet, Paris, France

In this study, we introduce an in vitro set-up that allows to control the binding of a targeted CA to its receptor by micro-MRI. Experiments inspired by the BIAcore system were realized and allowed to know the kinetics of a CA towards its receptor. This new technique could help optimizing the in vivo protocols especially for the optimal time between the injection of the CA and the imaging acquisition.

3834.   68 Molecular MRI and DCE-US to evaluate anti-angiogenic therapies in kidney tumor xenografts
Ludovic de Rochefort1, Ingrid Leguerney1, Marie Poirier-Quinot1, Sandra Robin1, Xavier Violas2, Rose-Marie Dubuisson1, Stéphanie Pitre-Champagnat1, Luc Darrasse1, Philippe Robert2, and Nathalie Lassau1
1IR4M, Univ. Paris-Sud, CNRS, UMR 8081, Orsay, France, 2Experimental Imaging, MRI unit, Research Division, Guerbet, Aulnay-sous-bois, France

A multimodal molecular MRI and DCE-US protocol was applied in kidney tumor xenograft in mice to follow up the response to anti-angiogenic treatments. Imaging was performed at D0 and D3 after monoclonal anti-body, tyrosine kinase inhibitor and m-Tor inhibitor administration. Tumor growth, perfusion (US), diffusion, first pass enhancement (1 min) and late enhancement (1 hour) of a targeted áíâ3 contrast agent (MRI) were quantified. Tumor growth was reduced with treatments. Differences were observed in apparent diffusion coefficient, targeted contrast agent clearance and fixation in the different groups after treatment.

3835.   69 Soluble Gd(III)DOTA adducts with Multiwalled Carbon Nanotubes as novel contrast agents for Diffusion Tensor Imaging
Viviana Negri1,2, Daniel Calle3, Piedad Ros4, Sebastian Cerdán3, and Paloma Ballesteros2
1CSIC, Instituto de Investigaciones Biomédicas "A.Sols"-CSIC, Madrid, Madrid, Spain, 2Laboratorio de Síntesis Orgánica e Imagen Molecular por Resonancia Magnética, Facultad de Ciencia, UNED, Madrid, Madrid, Spain, 3Departamento de Modelos Experimentales de Enfermedades Humanas, CSIC, Instituto de Investigaciones Biomédicas "A.Sols"-CSIC, Madrid, Madrid, Spain, 4Departamento de Farmacia y Biotecnología, Universidad Europea de Madrid, Madrid, Madrid, Spain

We describe a new generation of highly soluble, paramagnetically labeled multiwall CNTs (MWCNTs) with Gd(III)DOTA monoamide-like functionalized with a pyrene moiety, linked to the CNT through lower case Greek pi-lower case Greek pi stacking interactions. In particular, we report on the synthesis, MRI studies (ADC, T1, T2) and fluorescence emission spectra of these lower case Greek pi-lower case Greek pi stacking MWCNTs-pyrene DOTAma adducts. We synthesized two different lower case Greek pi-lower case Greek pi stacking adducts MWNTs-Gd(III)DOTAmaPyrene and MWNTs-Gd(III)DOTAmaEtDiaminePyrene, shown to be highly water soluble and to induce anisotropic diffusion of water, due to alignment of the magnetic nanotubes along the B0 axis. These derivatives are also potential fluorescence probes yielding a novel multimodal imaging platform.

3836.   70 Dual magnetic resonance imaging (MRI)-fluorescent imaging (FI) agents : ultrasmall mixed lanthanide oxide nanoparticles
Sung June Kim1, Wenlong Xu1, and Gang Ho Lee1
1Chemistry, Kyungpook National University, Daegu, Korea

We demonstrated that mixed lanthanide oxide nanoparticles should be potential dual T2 MRI-FI agents by using three systems of ultrasmall mixed lanthanide (Dy/Eu, Ho/Eu, and Ho/Tb) oxide nanoparticles. Appreciable r2 values at 1.5 tesla MR fields and appreciable fluorescence in visible region were observed in all samples.

3837.   71 Contrast agents with chelated lanthanoid ions for 19F MR imaging
Vít Herynek1, Marie Martinisková2, Andrea Gálisová1, Jan Kotek2, Daniel Jirák1, and Milan Hájek1
1Institute for Clinical and Experimental Medicine, Prague, Czech Republic, 2Faculty of Science, Charles University, Prague, Czech Republic

19F MRI is potentially an interesting tool for diffusion or perfusion measurements, and for cell tracking. It requires biocompatible and non-toxic contrast agents with high fluorine ion concentration with suitable relaxation times. We synthesized and tested both in vitro and in vivo probes based on DOTP chelates with 12 equivalent fluorine ions and a lanthanoid ion, which substantially shortens relaxation times. Measuring sequences were optimized for each chelated lanthanoid.

3838.   72 Comparison of 3T and 14T MRI in a rat antigen-induced arthritis model.
Lindsey Alexandra Crowe1, Nicolas Kunz2, Iris Friedli1, Azza Gramoun1, Kerstin Grosdemange1, Lionel Maurizi3, Geraldine Coullerez3, Marie-Gabrielle Beuzelin3, Rolf Gruetter2, Heinrich Hofmann3, and Jean-Paul Vallée1
1Radiology, Geneva University Hospitals, Geneva, Switzerland, 2Laboratory of Functional and Metabolic Imaging, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, 3Powder Technology Laboratory, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland

The use of iron oxide nanoparticles in MRI is leading development of image acquisition and analysis techniques to accurately localize uptake and persistence of such contrast agents. Detailed localization of the SPION and its contrast to other structures that are also hypointense is important. We explore the advantages of high field and high resolution MRI to assess inflammation, macrophage uptake and bone erosion in an antigen-induced arthritis (AIA) model.