Electronic Poster Session - Molecular Imaging
  Studies of Metabolism Using Hyperpolarized 13C - Methods 4290-4311
  Studies of Metabolism Using Hyperpolarized 13C - Metabolism 4312-4334
  Novel & Targeted Contrast Agents 4335-4358
  Cell Tracking & Reporter Genes: Approaches & Acquisitions 4359-4381
     

Studies of Metabolism Using Hyperpolarized 13C - Methods
Click on to view the abstract pdf and click on to view the video presentation. (Not all presentations are available.)
Thursday 10 May 2012
Exhibition Hall  13:30 - 14:30

  Computer #  
4290.   1 In Vivo Magnetic Resonance Imaging of Glucose
Hyla Allouche-Arnon1,2, Trevor Wade3, Rachel Katz-Brull1,2, Lanette Friesen Waldner3, Valentina N. Miller 1, J. Moshe Gomori 1, and Charles A. McKenzie3
1Radiology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel, 2BrainWatch Ltd., Tel-Aviv, Israel, 3Medical Biophysics, The University of Western Ontario, London, Ontario, Canada

 
A new noninvasive approach for glucose imaging using spin hyperpolarization technology and stable isotope labeling is presented. A glucose analog fully labeled with 13C and directly bonded deuterons, was intravenously injected to rats. Hyperpolarized glucose images in the live rat showed time-dependent organ distribution patterns. At 8 s, during bolus injection, the inferior vena cava was demonstrated at angiographic quality. Distribution of hyperpolarized glucose in the kidneys, vasculature, and heart was demonstrated at 12- and 20 s. The heart-to-vasculature intensity ratio at 20 s suggests myocardial uptake.

 
4291.   
2 Real-time in vivo monitoring of pyruvate C1 polarization using C2 integral ratios
Justin Yat Cheong Lau1,2, Albert P. Chen3, Yi-Ping Gu2, Jennifer Barry2, and Charles H. Cunningham1,2
1Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada, 2Imaging Research, Sunnybrook Research Institute, Toronto, Ontario, Canada, 3GE Healthcare, Toronto, Ontario, Canada

 
In order to obtain concentrations of metabolites in physical units from in vivo measurements with hyperpolarized pyruvate, it is necessary to monitor the instantaneous polarization as it decays. We present an empirical model for [1,2-13C2]-pyruvate based on the correlation between the C2 upfield-to-downfield partial integral ratio and the C1 polarization in whole pig blood. Using the blood calibration data, we estimate real-time in vivo C1polarization decay curves from whole pig heart spectroscopic measurements. Polarization estimates obtained by this method are effectively independent of signal amplitude variations due to perfusion and metabolism.

 
4292.   3 Single-shot, 2D and 3D Dynamic Imaging of Hyperpolarized 13C Biomarkers In Vivo at 14.1 Tesla
Subramaniam Sukumar1, Simon Hu1, Peder E. Larson1, Vickie Y. Zhang1, Michael Ohliger1, Robert Bok1, John Kurhanewicz1, and Daniel B. Vigneron1
1Radiology and Biomedical Imaging, UCSF, San Francisco, CA, United States

 
13C imaging using hyperpolarized biomarkers require special pulse sequences to efficiently capture the limited magnetization and to measure the dynamically varying metabolite signals. We developed single shot, 2D and 3D dynamic imaging sequences for selectively observing 13C metabolites at 14.1T. The sequences also address some of the limitations on high field systems, such as, wide spectral width and T2* effects. We have applied these new sequences to acquire dynamic, lactate and alanine images from a mouse cancer model with prostate tumor.

 
4293.   4 Frequency-domain quantification and interpretation of dynamic hyperpolarized 13C signals
Florian Wiesinger1, Oleksandr Khegai1,2, Jonathan I Sperl1, Eliane Weidl2, Axel Haase2, Markus Schwaiger2, and Rolf F Schulte1
1GE Global Research, Munich, Germany, 2Technische Universitaet Muenchen, Munich, Germany

 
In this work an efficient and novel frequency-domain signal quantification framework is presented for the analysis and interpretation of dynamically acquired hyperpolarized 13C data. The method is used to compare simple signal normalization versus apparent rate constant estimation for dynamically-acquired, slice-selective FID spectra and IDEAL spiral CS imaging animal rat experiments.

 
4294.   5 SNR improvement by frequency correction and timepoint addition in dynamic 3D imaging of pre-polarized 13C metabolites
William Dominguez-Viqueira1, Albert P Chen2, and Charles H Cunningham1,3
1Imaging Research, Sunnybrook Research Institute, Toronto, Ontario, Canada, 2GE Healthcare, Toronto, Ontario, Canada, 3Dept. of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada

 
A rapid spectral-spatial echo-planar imaging pulse sequence was developed previously for time-resolved 3D metabolic imaging with correction for the spatial shifts that occur in practice due to field inhomogeneities. In this work, an automated method was developed to create higher SNR images by correcting the spatial shifts and summing k-space data from multiple time points. Higher SNR maps of the hyperpolarized 13C metabolites with excellent contrast were obtained and shown. The tradeoffs between spatial-temporal resolution and image quality inherent in this technique are discussed.

 
4295.   6 Non-CPMG Echo-Train Sequence for T2 Mapping and Large SNR Gain in Hyperpolarized 13C Imaging
Yi-Fen Yen1, Sonal Josan2,3, Lasitha Senadheera4, Jae Mo Park3,5, Atsushi Takahashi1, Taichang Jang6, Milton Merchant6, Priti Balchandani3, James Tropp1, Dirk Mayer2,3, Lawrence Recht6, Lei Xing4, Daniel Spielman3, Ralph Hurd1, and Patrick Le Roux7
1Global ASL, GE Healthcare, Menlo Park, CA, United States, 2Neuroscience Program, SRI International, Menlo Park, CA, United States, 3Dept. of Radiology, Stanford University, Stanford, CA, United States, 4Dept. of Radiation Oncology, Stanford University, Stanford, CA, United States, 5Dept. of Electrical Engineering, Stanford University, Stanford, CA, United States, 6Dept. of Neurology and Neurological Sciences, Stanford University, Stanford, CA, United States, 7Global ASL, GE Healthcare, Palaiseau, France

 
High resolution T2 mapping of hyperpolarized [1-13C]pyruvate and its metabolic products was accomplished by using a novel pulse sequence comprised of a non-CPMG echo train. Approximately 3-fold increase in signal-to-noise ratio (SNR) was obtained by averaging echo-train signals as compared to the SNR of the first spin-echo. This technique was demonstrated in vivo on normal rat liver, mouse prostate cancer model and rat glioma model.

 
4296.   7 Ratiometric analysis of hyperpolarized 13C-NMR data to quantify reaction rate constants
Lin Z Li1,2, Stephen Kadlececk1, Ben Pullinger1, He N. Xu1, Dania Daye3,4, Lewis Chodosh3, and Rahim Rizi1
1Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States, 2Britton Chance Lab of Redox Imaging, Johnson Research Foundation, University of Pennsylvania, Philadelphia, PA, United States, 3Department of Cancer Biology, University of Pennsylvania, Philadelphia, PA, United States, 4Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, United States

 
Various modeling methods have been used to analyze in vivo hyperpolarized 13C-NMR data from the lactate dehydrogenase (LDH) reaction, which converts pyruvate to lactate. However, these models make certain assumptions about transport in the blood, across cell membranes, and/or enzymatic kinetics, and require at least 3 modeling parameters. Here we present a new method which relaxes some of these assumptions and minimizes the modeling parameters. By fitting the lactate/pyruvate ratio in mouse tumor models we quantify both the forward and reverse exchange rate constants of the LDH reaction. First order temporal derivatives of the lactate/pyruvate ratio help to determine the proper time range for fitting.

 
4297.   8 Volumetric quantitation of metabolic kinetics of hyperpolarized [1-13C]pyruvate using multiband RF pulses
Sonal Josan1,2, Tao Xu3, Ralph Hurd4, Adam Kerr3, Yi-Fen Yen4, Dirk Mayer1,2, and Daniel Spielman2,3
1Neuroscience Program, SRI International, Menlo Park, CA, United States, 2Radiology, Stanford University, Stanford, CA, United States, 3Electrical Engineering, Stanford University, Stanford, CA, United States, 4Applied Science Laboratory, GE Healthcare, Menlo Park, CA, United States

 

4298.   9 Differentiation of Flux and Isotopic Exchange using Co-administration of Hyperpolarized [2-13C]Pyr and [1-13C]Lac
Jae Mo Park1,2, Ralph E Hurd3, Sonal Josan2,4, Yi-Fen Yen3, Adolf Pfefferbaum4,5, Dirk Mayer2,4, and Daniel M Spielman1,2
1Electrical Engineering, Stanford University, Stanford, CA - California, United States, 2Radiology, Stanford University, Stanford, CA - California, United States, 3Applied Science Laboratory, GE Healthcare, Menlo Park, CA - California, United States, 4Neuroscience Program, SRI International, Menlo Park, CA - California, United States, 5Psychiatry, Stanford University, Stanford, CA - California, United States

 
Bi-directional metabolic conversion can be estimated by simultaneously injecting both co-polarized substrates. The amount of flux and isotopic exchange can be estimated by the difference in flow of each substrate. We demonstrate the differentiation of flux and isotopic exchange between Pyr and Lac by injecting polarized [2-13C]Pyr and [1-13C]Lac together, and observed increased flux from Pyr to Lac after EtOH infusion.

 
4299.   10 Direct Estimation of Hyperpolarized Metabolites with IDEAL Spiral CSI
Jeremy Gordon1, Sean B. Fain1,2, and Kevin Johnson1
1Medical Physics, University of Wisconsin-Madison, Madison, WI, United States, 2Radiology, University of Wisconsin-Madison, Madison, WI, United States

 
Hyperpolarization dramatically improves signal from 13C labeled molecules; however, the transient polarization must be used efficiently. Highly efficient acquisition trajectories, such as spirals, are well-suited to maximize utilization of hyperpolarization but are limited by off-resonance blurring, forcing short readout duration spirals for imaging. Here, we propose to use 1H data to provide a field-map estimate, reducing reconstruction of chemically-shifted species to a linear problem. A least-squares technique is presented to directly solve for 13C metabolites, generating images corrected for Boinhomogeneity and with minimal off-resonance blurring. This technique permits non-Cartesian acquisitions with longer readouts, greatly increasing 13C spiral CSI efficiency.

 
4300.   11 Switch-Tuned Dual-Frequency Birdcage RF Coil for 13C and 1H Imaging
Heeseung Lim1, Kundan Thind1, Jian-xiong Wang2, Andrew Alejski3, Francisco Martinez3, and Timothy J. Scholl1,3
1Medical Biophysics, University of Western Ontario, London, Ontario, Canada, 2GE Healthcare, Applied Science Laboratory, London, Ontario, Canada,3Imaging Research Laboratories, Robarts Research Institute

 
A novel dual-frequency birdcage RF coil that is electronically switchable between 13C and 1H imaging modes has been developed for molecular imaging with hyperpolarized substances. PIN diodes in parallel with end-ring capacitors were used to switch the resonator between a band-pass (1H: 127.7 MHz) and a low-pass (13C: 32.1 MHz) configuration using a DC bias. The SNR-efficiency of this combined coil has been systematically compared with that of identical single-frequency coils for each nucleus using phantoms. In vivo imaging of pyruvate metabolism in a healthy rat brain has been demonstrated and co-registered with detailed proton morphology.

 
4301.   12 On the use of 13-C labelled anhydrides as chemical precursors of short chain fatty acids for DNP-MRS.
Fabio Tedoldi1, Sonia Colombo Serra1,2, Magnus Karlsson3, Giovanni Battista Giovenzana4,5, Camilla Cavallotti5, Fulvio Uggeri1, and Silvio Aime6
1Centro Ricerche Bracco, Bracco Imaging Spa, Colleretto Giacosa, Torino, Italy, 2Dipartimento di Fisica Sperimentale, Università degli Studi di Torino, Torino, Italy, 3Albeda Research, Copenhagen, Denmark, 4Dipartimento di Scienze Chimiche Alimentari Farmaceutiche e Farmacologiche, Università degli Studi del Piemonte Orientale, Novara, Italy, 5CAGE Chemicals srl, Novara, Italy, 6Dipartimento di Chimica IFM, Università degli Studi di Torino, Torino, Italy

 
Hyperpolarized 13-C labelled butyric and acetic acids are potentially valuable tracers for investigating cardiac metabolism. Unfortunately they can not be polarized as neat compounds, but only after addition of a glass forming agents which could affect their metabolic fate. Symmetric anhydrides are here proposed as chemical precursors, which can be polarized as such and provide, upon dissolution and hydrolysis, a highly concentrated neat solution of the corresponding acid. In addition, tailored lipophilic derivatives of trityl radicals have been investigated and shown to be suitable polarization agents for anhydrides, that can be easily removed by filtration upon dissolution in aqueous media.

 
4302.   13 Multi-side kinetic modeling of 13C metabolic MR using [1-13C]pyruvate
Pedro A Gómez Damian1,2, Jonathan I Sperl1, Oleksandr Khegai1, Stefan Grott1, Eliane Weidl3, Martin A Janich3, Florian Wiesinger1, Steffen J Glaser4, Axel Haase5, Markus Schwaiger3, Rolf F Schulte1, and Marion I Menzel1
1GE Global Research, Munich, Germany, 2Tecnologico de Monterrey, Monterrey, Mexico, 3Nuclear Medicine, Technische Universität München, Munich, Germany, 4Department Chemie, Technische Universität München, Munich, Germany, 5IMETUM, Technische Universität München, Munich, Germany

 
Quantitation of metabolite conversion through a multi-side kinetic model that involves all downstream metabolites present in MR spectroscopy after injection of [1-13C]pyruvate is presented. This method provides more kinetic data than previously existing methods and parameter interdependency allows a more accurate quantitation that can be useful for the monitoring of metabolic activity. The results are compared to kinetic modeling obtained with two-side integral and two-side differential models.

 
4303.   14 Rapid Sequential Injections of Hyperpolarized [1-13C]Pyruvate In Vivo Using a Sub-Kelvin, Multi-Sample DNP Polarizer
Simon Hu1, Peder E Larson1, Mark VanCriekinge1, Andrew M Leach2, Ilwoo Park1, Peter J Shin1, Galen Reed1, Hikari Yoshihara1, Robert A Bok1, Sarah J Nelson1, John Kurhanewicz1, and Daniel B Vigneron1
1Radiology and Biomedical Imaging, University of California, San Francisco, CA, United States, 2Global Research Center, General Electric, Niskayuna, NY, United States

 
Development of hyperpolarized technology utilizing dynamic nuclear polarization has enabled the measurement of 13C metabolism in vivo at very high SNR. Traditionally, consecutive injections of a hyperpolarized compound in an animal have been separated temporally by approximately 1 hour, with the practical minimum time between injections determined by the sample build-up time. The effects of greatly reducing the time separation between injections have not been investigated. In this study, using the new GE SpinLab DNP polarizer with the capability of simultaneously polarizing up to 4 samples, we performed dynamic and 3D echo-planar spectroscopic imaging of [1-13C]pyruvate in normal rats. For each rat, three hyperpolarized scans were performed 5 minutes apart. The results demonstrate the feasibility of detecting the uptake and metabolic conversion of HP-pyruvate within sequential acquisitions with repeat injections with a temporal resolution of 5 minutes. In normal rats this method shows minimal changes, indicating the potential for rapid monitoring of the metabolic effects of treatments and/or physiologic interventions on this time scale.

 
4304.   15 Quantitative Measurement of Pyruvate-Lactate Exchange Rate in Both Directions Using Exchange-Linked Dissolution Agents (ELDA) in Hyperpolarized 13C Metabolic Imaging
Ralph Hurd1, Daniel Spielman2, Sonal Josan3, Jae Mo Park4, Yi-Fen Yen1, Adolf Pfefferbaum3,5, and Dirk Mayer2,3
1GE Healthcare, Menlo Park, CA, United States, 2Radiology, Stanford University, Stanford, CA, United States, 3Neuroscience Program, SRI International, Menlo Park, CA, United States, 4Electrical Engineering, Stanford University, Stanford, California, United States, 5Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, United States

 
In hyperpolarized [1-13C]pyruvate and hyperpolarized [1-13C]lactate metabolic imaging, the pool size of the exchange partner may limit the rate of isotopic mixing. This is especially true for hyperpolarized [1-13C]lactate metabolic imaging, given the small steady-state pyruvate pool. Under conditions where addition of unlabeled exchange partner to the bolus results in a linear increase in rate, absolute values for exchange rate constant (Kexchange) can be determined in both directions. In this study we show that such conditions appear to be true for a bolus of 80mM pyruvate and 40 mM lactate in rat kidney, and use the dynamic imaging data to calculate Kexchange.

 
4305.   16 Thermally-Activated Clustering of Xe Atoms Increases 129Xe T1 in Solid-State DNP Mixtures
Huseyin Kara1,2, Nicholas N. Kuzma2, Philip Manasseh3, Mehrdad Pourfathi2, Stephen J. Kadlecek2, and Rahim R. Rizi2
1Astronomy and Physics, University of Pennsylvania, Philadelphia, PA, United States, 2Radiology, University of Pennsylvania, Philadelphia, PA, United States, 3Department of Chemistry, Earlham College, Richmond, IN, United States

 
In light of 3He shortages, Dynamic Nuclear Polarization (DNP) offers a promising alternative method of producing bulk quantities of hyperpolarized 129Xe for human lung imaging. We studied T1 spin relaxation of 129Xe in typical DNP mixtures (xenon/1-propanol/trytil radical) at 1.43 K and 5 T. Specifics of sample preparation as well as thermal history are shown to promote spontaneous creation of pure xenon clusters in the solid matrix, leading to a wide range (100 min - 35 hours) of 129Xe T1 values.

 
4306.   17 Solid-state 15N polarimetry of hyperpolarized 15N2O based on the modeling of NMR spectral patterns
Nicholas N. Kuzma1, Pär Håkansson2, Rajat K. Ghosh1, Huseyin Kara1,3, Mehrdad Pourfathi1, Stephen J. Kadlecek1, Giuseppe Pileio2, Malcolm H. Levitt2, and Rahim R. Rizi1
1Radiology, University of Pennsylvania, Philadelphia, PA, United States, 2School of Chemistry, Southampton University, Southampton, Hempshire, United Kingdom, 3Astronomy and Physics, University of Pennsylvania, Philadelphia, PA, United States

 
A theoretical model of the solid-state 15N NMR spectrum in an isotropic 15N2O/1-proponal/trityl-radical mixture is presented, which makes it possible to calculate in-situ 15N polarization directly from the powder-spectrum shape of the measured 15N NMR peaks. The model is in excellent agreement with the experimental line shape. The maximum 15N polarization was calculated to be (11plus-or-minus sign4)%.

 
4307.   18 Combined Parallel and Partial Fourier MR Reconstruction for Accelerated Hyperpolarized 13 In Vivo MRSI
Michael Abram Ohliger1, Peder E. Z. Larson1, Robert Bok1, Simon Hu1, Peter Shin1, James Tropp2, Lucas Carvajal1, Sarah J. Nelson1, John Kurhanewicz1, and Daniel Vigneron1
1Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, United States, 2General Electric Healthcare, Fremont, CA, United States

 
We implement a combined partial Fourier and self-calibrating parallel MR reconstruction for acquisition of hyperpolarized 13C spectroscopic imaging in a rat, achieving an added reduction in scan time of 39% when compared with parallel MRI alone. Using an echo planar spectroscopic imaging sequence, we acquire a 30 x 10 x 16 matrix of spectroscopic voxels within 13 s. The shorter scan time is critical to combat signal loss due to T1 decay, metabolism, and RF saturation. In addition, this acquisition enables the time scale and imaging coverage required for human imaging in vivo.

 
4308.   19 Non-invasive quantification of intracellular redox state in tissue by hyperpolarized 13C-NMR
Lin Z Li1,2, He N. Xu1,2, Stephen Kadlececk1, Kavindra Nath1, Kejia Cai1, Hari Hariharan1, Jerry D. Glickson1, and Rahim Rizi1
1Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States, 2Britton Chance Laboratory of Redox Imaging, Johnson Research Foundation, University of Pennsylvania, Philadelphia, PA, United States

 
NAD+ (nicotinamide adenine dinucleotide)-coupled redox potential NAD+/NADH is a key mediator in many biological processes including metabolism, growth, survival, motility and signaling. It is implicated in pathologies of cardiovascular diseases, diabetes, cancer etc. Despite its importance, non-invasive method for measuring NAD+/NADH in tissue has not been developed. This work presents hyperpolarized 13C-NMR detection of pyruvate and lactate in tissue as the first non-invasive method to quantify the intracellular NAD+/NADH in vivo. We quantified cytosolic redox state in human breast cancer mouse xenografts along with intracellular pH measurement by 31P-NMR.

 
4309.   20 Using pyruvic acid as a solvent for dynamic nuclear polarization sample preparation
Albert P Chen1, C.T. Tan2, and Charles H Cunningham3,4
1GE Healthcare, Toronto, ON, Canada, 2Sigma-Aldrich/Isotec, Miamisburg, Ohio, United States, 3Imaging Research, Sunnybrook Health Sciences Centre, Toronto, ON, Canada, 4Medical Biophysics, University of Toronto, Toronto, ON, Canada

 
One of the requirements for obtaining high polarization for organic substrates is that the DNP samples become amorphous solids at low temperature. Although neat pyruvic acid is typically used as the sole substrate in the DNP sample matrix, it may be feasible to use pyruvic acid as the solvent and dissolve other substrates of interest. Not only would this solvent-substrate mixture form a glass at solid state, the safety profile of pyruvate has been determined for administration in humans. In this work, N-acetyl-[1-13C]methionine was used to demonstrate the feasibility of utilizing pyruvic acid as the solvent for DNP sample preparation.

 
4310.   21 Device to minimise cannula dead volume for the injection of hyperpolarised substrate
Steven Reynolds1, Joanne Bluff2, Samira Kazan2, Michael Port3, Emily Wholey2, Gillian Tozer2, and Martyn Paley1
1Academic Unit of Radiology, University of Sheffield, Sheffield, South Yorkshire, United Kingdom, 2Tumour microcirculation group, University of Sheffield, Sheffield, United Kingdom, 3Department of Psychology, University of Sheffield, Sheffield, United Kingdom

 
Dose limitations required for animal well-being restrict the quantity of hyperpolarised substrate that may be administered. Physical constraints for an animal in a MRI scanner can require a long length of cannula for delivery of substrate into the animal, resulting in a significant dead volume. Typically, saline occupies the dead volume of the cannula that constitutes part of the dose but does not contribute to the signal. We have developed an automated flow diverter, which permits the dead volume to be cleared to waste before the desired substrate is injected. We show a significant increase in 13C signal as a result of injecting only hyperpolarised substrate.

 
4311.   22 First MRI of Micro-Fluid Jets with In-bore DNP of 1H at 1.5 T
Maxim Terekhov1, Jan Krummenacker1,2, Vasyl Denisenkov2, Kathrin Gerz1, Thomas Prisner2, and Laura Maria Schreiber1
1Section of Medical Physics, Radiology Department, University Medical Center Mainz, Mainz, Germany, 2Institute of Physical and Theoretical Chemistry, Center for Bimolecular Magnetic Resonance Goethe-University, Frankfurt-am-Main, Germany

 
Dynamic Nuclear Polarization (DNP) is a technique, in which hyperpolarization is achieved by microwave irradiation of electron spins in radicals. The NMR signal enhancement by factor 600 is potentially possible. Typically DNP is achieved in external polarizers at low temperatures. Being optimal for signal enhancements; the requirement to shuttle prohibits the use nuclei with short T1, e.g. 1H. To circumvent these we implemented liquid-state DNP at 1.5T for 1H that allows polarization inside MRI bore close to the imaging objects and continuous-flow delivery of hyperpolarized agent. The fluid micro-jets visualization with resolution of 100 µm was achieved in pilot experiments.
 
Electronic Poster Session - Molecular Imaging

Studies of Metabolism Using Hyperpolarized 13C - Metabolism
Click on to view the abstract pdf and click on to view the video presentation. (Not all presentations are available.)
Thursday 10 May 2012
Exhibition Hall  14:30 - 15:30

  Computer #  
4312.   1 Metabolic Response of Glioma to Dichloroacetate Measured by Hyperpolarized 13C MRSI
Jae Mo Park1,2, Lawrence Recht3, Sonal Josan2,4, Taichang Jang3, Milton Merchant3, Yi-Fen Yen5, Ralph E Hurd5, Daniel M Spielman1,2, and Dirk Mayer2,4
1Electrical Engineering, Stanford University, Stanford, CA - California, United States, 2Radiology, Stanford University, Stanford, CA - California, United States, 3Neurology and Neurological Sciences, Stanford University, Stanford, CA - California, United States, 4Neuroscience Program, SRI International, Menlo Park, CA - California, United States, 5Applied Science Laboratory, GE Healthcare, Menlo Park, CA - California, United States

 
We demonstrate that measuring 13C-Bic is feasible to assess PDH flux and effect of DCA in tumor-bearing rat brain by injecting hyperpolarized [1-13C]Pyr. Lac/Bic gave a better contrast between glioma and normal brain, and reflected both pathways to cytoplasmic and mitochondrial metabolism.

 
4313.   2 Monitoring changes in tumor perfusion and metabolism following anti-angiogenic therapy using hyperpolarized tracers
Aaron K Grant1, Elena Vinogradov2, Xiaoen Wang1, Rupal Bhatt3, Robert E Lenkinski2, and David C Alsop1
1Department of Radiology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, United States, 2Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, 3Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, United States

 
Anti-angiogenic therapies can dramatically reduce tumor perfusion and vascular permeability. Here we present the use of hyperpolarized 13C labeled tert-butanol for monitoring changes in tumor perfusion resulting from anti-angiogenic therapy in a model of renal cell carcinoma. Dynamic imaging of with balanced SSFP enables quantification of the reduction in blood flow following treatment. In addition, metabolic imaging was performed with hyperpolarized pyruvate to assess changes in metabolism. In a small pilot study, imaging with tert-butanol indicates reductions in blood flow on the order of 70%, while the change in lactate signal following treatment shows more variability.

 
4314.   3 Detection of Early Response to Cyclophosphamide Treatment in a Myc-driven Lymphoma Model Using Hyperpolarized 13C-Pyruvate and FDG-PET
Tiago B. Rodrigues1,2, Mikko I. Kettunen1,2, David Y. Lewis1, Ferdia A. Gallagher1,3, Eva Serrao1,2, Dmitry Soloviev1, and Kevin M. Brindle1,2
1Cambridge Research Institute, Cancer Research UK, Cambridge, United Kingdom, 2Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom, 3Departments of Radiology and Biochemistry, University of Cambridge, Cambridge, United Kingdom

 
Our main goal was to assess if hyperpolarized [1-13C]-pyruvate MRS could detect response within 24 hours of cyclophosphamide treatment in a Myc-driven lymphoma model and to compare it with FDG. Our results showed a 70% reduction in the pyruvate-lactate flux following treatment, whereas a more modest change was seen in FDG-PET. This demonstrates the feasibility of using hyperpolarized 13C-pyruvate to detect early treatment response in a transgenic mouse of lymphoma, being potentially a complement of FDG-PET as a clinical tool.

 
4315.   4 Effects of Tumour Oxygenation on 13C Pyruvate Metabolism
Steven Reynolds1, Samira Kazan2, Joanne Bluff2, Emily Wholey2, Martyn Paley1, and Gillian Tozer2
1Academic Unit of Radiology, University of Sheffield, Sheffield, South Yorkshire, United Kingdom, 2Tumour microcirculation group, University of Sheffield, United Kingdom

 
The influence of tumour oxygenation state was determined by administering hyperpolarised 13C1-pyruvic acid (PA) and determining the conversion rate, kpl, to lactate. The tumour’s oxygenation state was concurrently monitored during MR experiments using invasive Oxylite fluorescent probes. P22 carcinosarcoma-bearing BD1X rats were anaesthetised and femoral cannulations performed for drug administration/blood pressure monitoring. Tumour pO2 was manipulated by supplying either normal air or hypoxia (10% O2, 4% CO2, balance N2). 5ml/kg of hyperpolarised 13C-PA was injected and slice-localised 13C spectroscopic data acquired using a 20mm 13C, 1H surface coil positioned over the tumour in a Bruker 7T MRI system Integral versus time responses curves for pyruvate and lactate were fitted to a one-way exchange model and kpl values extracted. Date for n=6 animals showed that rate of conversion of pyruvate to lactate, kpl, increases under hypoxic conditions.

 
4316.   5 Evaluating Tumor Perfusion with Hyperpolarized HP001 and Comparison with Dynamic Susceptibility Contrast MR Imaging and Pathology Using Orthotopic Human GBM Xenografts
Ilwoo Park1, Cornelius von Morze1, Jan H Ardenkjaer-Larsen2, Janine M Lupo1, Motokazu Ito3, Joydeep Mukherjee3, Joanna J Phillips3, Russell O Pieper3, Daniel B Vigneron1, and Sarah J Nelson1,4
1Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California, United States, 2GE Healthcare, Broendby, Denmark, 3Department of Neurological Surgery, University of California San Francisco, San Francisco, California, United States,4Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, United States

 
We have demonstrated the feasibility of using hyperpolarized HP001 for investigating tumor perfusion in an orthotopic human GBM model. Distinct HP001 characteristics were found between tumor and normal tissues. HP001 data were strongly correlated with the data from the conventional Gd-based DSC imaging and consistent with the findings from immunohistochemical analysis. The results of this study suggest that this technique may provide an alternate way to evaluate tumor perfusion for brain tumors, which could be applied in patient studies.

 
4317.   6 In vivo biochemical imaging of HCC tumor bearing rats using hyperpolarized [1-13C]pyruvate and 18F-FDG
Marion I Menzel1, Eliane Weidl2, Martin A Janich2, Oleksandr Khegai1, Florian Wiesinger1, Axel Haase3, Rolf F Schulte1, and Markus Schwaiger2
1GE Global Research, Munich, Germany, 2Nuclear Medicine, Technische Universität München, Munich, Germany, 3IMETUM, Technische Universität München, Munich, Germany

 
In vivo biochemical imaging using hyperpolarized [1-13C]pyruvate and 18F-FDG PET in HCC tumor rats was compared. Findings for uptake, compartmentalization of signal and overall tumor visibility were correlated with physiological and biochemical data. While all tumors showed high signal in PET, integrated metabolite images shown only 40 % (pyruvate) and 70 % (lactate) of all tumors. Analysis of 13C signal dynamics revealed a statistically higher proportion of pyruvate reaching the gastrointestinal tract (GIT) than the tumors, with tumors exhibiting higher turnover of pyruvate to lactate and alanine than GIT, indicating a compartmentalization effect of [1-13C]pyruvate and its downstream me-tabolites.

 
4318.   7 Comparison of Localized Hyperpolarized 13C-Pyruvate and 13C-Urea Dynamics in Tumor Models
Peder E. Z. Larson1, Kayvan R Keshari2, David M Wilson2, Simon Hu2, Michael Lustig3, Adam B Kerr4, John M Pauly4, John Kurhanewicz2, and Daniel B Vigneron2
1UCSF, San Francisco, California, United States, 2UCSF, 3UC Berkeley, 4Stanford University

 
Copolarization followed by simultaneous injection of [1-13C]-pyruvate (metabolic marker) and 13C-urea (perfusion marker) was combined with a dynamic 3D EPSI acquisition using multiband excitation pulses and compressed sensing to better characterize perfusion and uptake of hyperpolarized agents. Using urea as a separate perfusion marker allowed for improved distinction between perfusion of metabolic products (ie [1-13C]-lactate) and tissue metabolic conversion.

 
4319.   8 Detecting Early Tumor Response of Prostate Cancer to Radiation Therapy using Multi-Parametric 14T 1H and Hyperpolarized 13C MR Imaging
Vickie Zhang1,2, Robert Bok1, Subramaniam Sukumar1, Adam Cunha3, I-C. Hsu3, Jean Pouliot2,3, Daniel B. Vigneron1,2, and John Kurhanewicz1,2
1Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, United States, 2Graduate Program in Bioengineering, University of California, San Francisco - University of California, Berkeley, Berkeley, CA, United States, 3Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA, United States

 
This study used multi-parametric 1H and hyperpolarized 13C MR imaging in the TRAMP model to investigate early response in perfusion, diffusion and metabolism to the impact of increasing dose levels of radiation therapy. TRAMP mouse were treated with a radiation dose distribution from 14Gy to 5Gy within the tumor. Both 1H (t2-weighted, DCE and DWI) and hyperpolarized 13C ([1-13C] pyruvate and 13C urea) imaging was done before treatment and serially after treatment. HP 13C biomarkers correlated with conventional 1H MR markers. Significant dose dependent changes in perfusion and pyruvate-to-lactate flux were observed following radiation therapy.

 
4320.   9 Regulating Myocardial Metabolism by Infusion of Glucose, Insulin and Potassium in Hyperpolarized [1-13C]Pyruvate MRS Studies
Mette Hauge Lauritzen1, Peter Magnusson1, Sadia Asghar Butt1, Lise Vejby Søgaard1, Jan Henrik Ardenkjær-Larsen2, and Per Åkeson1
1Danish Research Centre for Magnetic Resonance (DRCMR) Copenhagen University Hospital, Hvidovre, Denmark, 2GE Healthcare, Hillerød, Denmark

 
Changes in myocardial metabolism play an important role in the etiology of different cardiac diseases. MR Spectroscopy with hyperpolarized [1-13C]pyruvate can visualize myocardial metabolism. However, the usability of the technique can be complicated, because it depends on high myocardial glucose availability, which can be difficult to control during in vivo MR studies. This study demonstrate how infusion of glucose, insulin and potassium can increase the [13C]bicarbonate MRS-signal significantly after injection of hyperpolarized [1-13C]pyruvate in rats. This improves the sensitivity of the technique to assess metabolic changes in the myocardium as a result of disease.

 
4321.   10 Reproducibility of free-breathing dual-gated hyperpolarized 13C imaging measurements of cardiac metabolism
Angus Z. Lau1,2, Albert P. Chen3, William Dominguez-Viqueira2, Yiping Gu2, Jennifer Barry2, Kim A. Connelly4, and Charles H. Cunningham1,2
1Dept. of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada, 2Imaging Research, Sunnybrook Research Institute, Toronto, Ontario, Canada, 3GE Healthcare, Toronto, Ontario, Canada, 4Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael’s Hospital and University of Toronto, Toronto, Ontario, Canada

 
We characterize the reproducibility of hyperpolarized cardiac metabolic measurements in a cohort of normal pigs using a time-resolved, dual respiratory and cardiac-gated, multi-slice, single-shot 13C pulse sequence. The time-resolved nature of the imaging sequence enabled normalization using the first pass of the pyruvate bolus through the heart. Normalization reduced the variability (%CV = mean/SD) for metabolic measurements, with 57% CV for bicarbonate and 29% CV for lactate signals in the heart. Along with increases in LDH activity in ischemia, our results suggest that lactate imaging may be a sensitive marker of metabolic remodeling in ischemic heart disease.

 
4322.   11 In vivo investigation of dicholoroacetate-modulated cardiac metabolism in the rat using hyperpolarized 13C MRS
Sonal Josan1,2, Jae Mo Park3, Yi-Fen Yen4, Ralph Hurd4, Adolf Pfefferbaum1,5, Daniel Spielman2,3, and Dirk Mayer1,2
1Neuroscience Program, SRI International, Menlo Park, CA, United States, 2Radiology, Stanford University, Stanford, CA, United States, 3Electrical Engineering, Stanford University, Stanford, CA, United States, 4Applied Science Laboratory, GE Healthcare, Menlo Park, CA, United States, 5Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, United States

 
Hyperpolarized [1-13C]-pyruvate MRS has been used to measure changes in cardiac pyruvate dehydrogenase (PDH) flux, with up-regulation by dichloroacetate demonstrating an increase in 13C-bicarbonate production. This work investigates the metabolic fate of the corresponding increase in acetyl-CoA generated by the up-regulated PDH flux, using [2-13C]-pyruvate to follow the 13C label into the Krebs cycle. The increase in bicarbonate from [1-13C]-pyruvate was compared to the increase in [5-13C]-glutamate from [2-13C]-pyruvate and provides information about the relative fraction of pyruvate going through PDH that enters the Krebs cycle vs. other metabolic pathways.

 
4323.   12 Assessment of Dichloroacetate Effect on TCA Cycle Metabolism in Rat Brain In Vivo using MRSI of Hyperpolarized [2-13C]Pyruvate
Jae Mo Park1,2, Sonal Josan2,3, Yi-Fen Yen4, Ralph E Hurd4, Daniel M Spielman1,2, and Dirk Mayer2,3
1Electrical Engineering, Stanford University, Stanford, CA - California, United States, 2Radiology, Stanford University, Stanford, CA - California, United States, 3Neuroscience Program, SRI International, Menlo Park, CA - California, United States, 4Applied Science Laboratory, GE Healthcare, Menlo Park, CA - California, United States

 
Although both [2-13C]Pyr and [1, 2-13C]Pyr have been successfully used as substrates to assess mitochondrial function in cardiac metabolism by measuring products such as [5-13C]glutamate (Glu), which is generated from the tricarboxylic acid (TCA) cycle intermediate alpha-ketoglutarate, the application of [2-13C]Pyr in studies of brain metabolism has been limited as Lac was the only metabolic product that could be detected so far. The aim of this work was to exploit the unsaturable component of Pyr transport into the brain by using a high [2-13C]Pyr concentration and measure the effects on brain metabolism when the Pyr dehydrogenase (PDH) flux is up-regulated by dichloroacetate (DCA), a Pyr dehydrogenase kinase (PDK) inhibitor.

 
4324.   13 In vivo real time cardiac metabolism using hyperpolarized acetate
Jessica A M Bastiaansen1, Tian Cheng1, Rolf Gruetter1,2, and Arnaud Comment3
1Laboratory of Functional and Metabolic Imaging, Ecole Polytechnique Federale de Lausanne, Lausanne, Switzerland, 2Department of Radiology, Universite de Lausanne and Geneva, Lausanne and Geneva, Switzerland, 3Institute of Physics of Biological Systems, Ecole Polytechnique Federale de Lausanne, Lausanne, Switzerland

 
Following the infusion of hyperpolarized [1-13C]acetate, we measured the real-time metabolic conversion of acetate to acetylcarnitine and citrate in vivo in rat hearts. A kinetic model allowed us to determine quantitative conversion rates inside the myocardium. Our study supports the role of acetylcarnitine as a shuttle for acetyl groups across the mitochondrial membrane.

 
4325.   14 Investigating pharmacological modification of cardiac pyruvate metabolism using hyperpolarized magnetic resonance
Lydia M Le Page1, Michael S Dodd1, Daniel R Ball1, Vicky Ball1, Huw B Jones2, Edvin Johansson3, and Damian J Tyler1
1University of Oxford, Oxford, United Kingdom, 2AstraZeneca, Alderley Park, Macclesfield, United Kingdom, 3AstraZeneca, Mölndal, Sweden

 
Increasing flux through the pyruvate dehydrogenase (PDH) enzyme has been considered as a potential treatment for type 2 diabetes, as it should lead to reduced blood glucose levels. In this study the ability to assess pharmacologically stimulated increases in PDH flux, both in vivo and ex vivo, has been demonstrated using hyperpolarized [1-13C]pyruvate in combination with magnetic resonance spectroscopy. The generic PDH kinase inhibitor, dichloroacetate, was seen to significantly increase PDH flux both in vivo and ex vivo, whilst the PDH kinase 2 specific inhibitor, AZD7545, did not result in changes to PDH flux in either situation.

 
4326.   
15 Detection of hyperpolarized 13C labeled ketone bodies in vivo
Brett William Clive Kennedy1,2, Mikko Iivari Kettunen1,2, De-En Hu1,2, Sarah Elizabeth Bohndiek1,2, and Kevin Michael Brindle1,2
1Department of Biochemistry, University of Cambridge, Cambridge, England, United Kingdom, 2Cambridge Research Institute, Cancer Research UK, Cambridge, England, United Kingdom

 
The aim of this study was to use hyperpolarized 13C labeled ketone bodies to examine metabolism in vivo. Despite high polarization (~25%) and long T1 values (~35s), little in vivo metabolism was observed in our current models. Nevertheless, we hope these molecules may still have important roles to play in our understanding of mitochondrial redox state in vivo.

 
4327.   16 In vivo enzymatic assay of carnitine acetyl transferase and acetylCoA synthetase using hyperpolarized acetate
Jessica A M Bastiaansen1, Tian Cheng1, Mor Mishkovsky1,2, Arnaud Comment3, and Rolf Gruetter1,4
1Laboratory of Functional and Metabolic Imaging, Ecole Polytechnique Federale de Lausanne, Lausanne, Switzerland, 2Department of Radiology, Universite de Lausanne, Lausanne, Switzerland, 3Institute of Physics of Biological Systems, Ecole Polytechnique Federale de Lausanne, Lausanne, Switzerland, 4Department of Radiology, Universite de Lausanne and Geneva, Lausanne and Geneva, Switzerland

 
Hyperpolarized MR allows for the characterization of fast biochemical reactions in vivo. Here we studied the metabolic conversion of acetate to acetylcarnitine, a buffer for excess acetylCoA and transporter of acetyl groups. A two-compartment model was used to determine the kinetic rate constants for several substrate concentrations which allowed for the determination of Michaelis-Menten kinetic parameters related to acetate transport and metabolism.

 
4328.   17 In vivo measurement of ALDH2 activity in rat liver ethanol model using dynamic MRSI of hyperpolarized [1-13C]-pyruvate
Sonal Josan1,2, Tao Xu3, Yi-Fen Yen4, Ralph Hurd4, Julio Ferreira5, Che-Hong Chen5, Adolf Pfefferbaum1,6, Dirk Mayer1,2, and Daniel Spielman2,3
1Neuroscience Program, SRI International, Menlo Park, CA, United States, 2Radiology, Stanford University, Stanford, CA, United States, 3Electrical Engineering, Stanford University, Stanford, CA, United States, 4Applied Science Laboratory, GE Healthcare, Menlo Park, CA, United States, 5Chemical and Systems Biology, Stanford University, Stanford, CA, United States, 6Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, United States

 
Aldehyde dehydrogenase-2 (ALDH2) enzyme is important for eliminating toxic aldehydes that accumulate in several diseases. It is also used in ethanol metabolism in the liver, producing NADH in the process. This work investigates using hyperpolarized [1-13C]-pyruvate MRSI for in vivo measurement of ALDH2 activity. Two different doses of ALDH2 inhibitor disulfiram were used to reduce ALDH2 activity in two groups with another group acting as control. Using ethanol metabolism to modulate the NADH availability in rat liver, the resulting change in pyruvate-to-lactate conversion was measured with 13C MRSI and correlated with ALDH2 enzyme activity.

 
4329.   18 Relaxation behaviour of hyperpolarized pyruvate in solution and in whole blood at 7 T
Justin Yat Cheong Lau1,2, Albert P. Chen3, William Dominguez-Viqueira2, Gang Wu4, and Charles H. Cunningham1,2
1Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada, 2Imaging Research, Sunnybrook Research Institute, Toronto, Ontario, Canada, 3GE Healthcare, Toronto, Ontario, Canada, 4Department of Chemistry, Queen's University, Kingston, Ontario, Canada

 
In this work, we characterize longitudinal relaxation of hyperpolarized [1-13C], [2-13C], and [1,2-13C2] pyruvate in solution and in pig blood at 7 T. We show that single-labelled pyruvate in solution exhibits shorter T1 at 7 T as compared to 3 T while dual-labelled pyruvate exhibits comparable T1 at 3 T and 7 T in solution and in blood. We argue that experiments with dual-labelled pyruvate may benefit from a greater chemical shift dispersion at 7 T with minimal T1 penalty. Results from this work may further the understanding of relaxation mechanisms that affect hyperpolarized pyruvate.

 
4330.   19 Assesment of diabetic nephropathy with Hyperpolarised [1-13C]Pyruvate
Christoffer Laustsen1,2, Jakob Appel Østergaard3, Rikke Nørregaard4, Steffen Ringaard1, Niels Chr. Nielsen5, Allan Flyvbjerg3, Michael Pedersen1, Per Åkeson2, and Jan Henrik Ardenkjaer-Larsen6,7
1The MR Research Centre, Institute of clinical Medicine, Aarhus University, Aarhus N, Denmark, 2DRCMR, Hvidovre Hospital, Hvidovre, Denmark,3Department of Endocrinology and Internal Medicine, Aarhus University, Aarhus, Denmark, 4Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark, 5Center for Insoluble Protein Structures (inSPIN), Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Denmark, 6GE Healthcare, Denmark, 7Department of Electrical Engineering, Technical University of Denmark, Kgs Lyngby, Denmark

 
A type-1 STZ induced diabetic nephropathy rat model is investigated with hyperpolarized [1- 13C]pyruvate, to allow early diagnosis and monitoring of decreased kidney function, with increased diabetes. We here show the metablic profile of the type 1 diabetic rat, from early diabetes to late diabetes, with a significant altered profile over the time course, showing the decreasing kidney function. The method show great promise for accurate non-invasive metabolic profiling of diabetic patients, with different stages of reduced kidney function.

 
4331.   20 Use of Dichloroacetate to Aid the Investigation of Krebs Cycle Metabolism In Vivo in Normal Rat with Hyperpolarized [1-13C]Pyruvate and [2-13C]Pyruvate
Simon Hu1, Hikari Yoshihara1, Robert A Bok1, John Kurhanewicz1, and Daniel B Vigneron1
1Radiology and Biomedical Imaging, University of California, San Francisco, CA, United States

 
Development of hyperpolarized technology utilizing dynamic nuclear polarization has enabled the measurement of 13C metabolism in vivo at very high SNR. In vivo mitochondrial metabolism can, in principle, be monitored with pyruvate, which is catalyzed to acetyl-CoA via pyruvate dehydrogenase (PDH). The purpose of this work was to determine if the compound sodium dichloroacetate (DCA) could aid the study of mitochondrial metabolism with hyperpolarized pyruvate. DCA stimulates PDH by inhibiting its inhibitor, pyruvate dehydrogenase kinase (PDK). In this work, hyperpolarized [1-13C]pyruvate and [2-13C]pyruvate were used to probe mitochondrial metabolism in normal rats. In the case of [1-13C]pyruvate, increased bicarbonate was observed after DCA was given. In the case of [2-13C]pyruvate, increased acetoacetate and acetylcarnitine were detected.

 
4332.   21 The use of fatty acids with hyperpolarized pyruvate to study cardiac substrate metabolism in the isolated perfused heart
Daniel Ball1, Ben Rowlands1, Rhys Evans1, Kieran Clarke1, and Damian Tyler1
1Physiology, Anatomy and Genetics, Oxford University, Oxford, Oxfordshire, United Kingdom

 
The isolated perfused heart, in combination with dynamic nuclear polarization, has proven to be an excellent model for the study of cardiac metabolism. However this model ideally requires the use of fatty acids to achieve a more physiological preparation. Previous work has shown that using bovine serum albumin to solubilise long chain fatty acids reduces the signal observed from hyperpolarized metabolites. The aim of this study was therefore to find alternative ways of providing the heart with fatty acids without compromising hyperpolarized signal intensity.

 
4333.   22 Dynamic spectroscopy and modeling of response to 2-deoxyglucose using hyperpolarized [1-13C]-pyruvate
James A Bankson1, Vlad C Sandulache2, Matthew E Merritt3, Andrew M Elliott1, Yunyun Chen4, Waldemar Priebe5, Dawid Schellingerhout6, Stephen Y Lai4, Charles A Conrad7, and John D Hazle1
1Department of Imaging Physics, UT MD Anderson Cancer Center, Houston, TX, United States, 2Bobby R. Alford Department of Otolaryngology, Baylor College of Medicine, Houston, TX, United States, 3Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, TX, United States,4Derpatment of Head & Neck Surgery, UT MD Anderson Cancer Center, Houston, TX, United States, 5Department of Experimental Therapeutics, UT MD Anderson Cancer Center, Houston, TX, United States, 6Department of Diagnostic Radiology, UT MD Anderson Cancer Center, Houston, TX, United States, 7Department of Neuro-Oncology, UT MD Anderson Cancer Center, Houston, TX, United States

 
Metabolic imaging using hyperpolarized [1-13C]pyruvate can provide new insights into cancer and therapies that target or affect metabolism. Strategies for acquisition, reconstruction, and analysis must be designed to extract reproducible quantitative biomarkers within a limited window of time. We have dynamically monitored the chemical fate of hyperpolarized pyruvate in murine models of cancer to investigate temporal dynamics and inform on the design of robust acquisition and analysis strategies. Preliminary results indicate, as expected, that multiple processes can modulate the behavior of hyperpolarized tracers in vivo, and that the effects of these processes can be modeled to clarify data interpretation.

 
4334.   23 Simultaneous 13C MR spectroscopy measurements of hyperpolarized [1-13C] pyruvate in two cancer bearing mice
Georgios Batsios1, Catherine Germanier1, Marcin Krajewski1, Michael Batel2, Kilian Weiss1, Andreas Sigfridsson1, and Markus Rudin1,3
1Instute for Biomedical Enginnering, ETH and University of Zurich, Zurich, Switzerland, 2Laboratory of Physical Chemistry, ETH, Zurich, Switzerland,3Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland

 
Hyperpolarized 13C magnetic resonance spectroscopy and imaging is a rapidly expanding field with many applications, in particular in the field of cancer. Due to a variety of reasons preclinical cancer studies are commonly carried out in nude mice, which put limits to the total amount of solution that can be administered intravenously. However, the amount of compounds polarized by commonly used polarizers is significantly larger. To make efficient use of this amount, in the present work we demonstrate the feasibility of parallel monitoring pyruvate metabolism in two animals using a single MR transceiver coil in combination with slice selective excitation.
 
Electronic Poster Session - Molecular Imaging

Novel & Targeted Contrast Agents
Click on to view the abstract pdf and click on to view the video presentation. (Not all presentations are available.)
Thursday 10 May 2012
Exhibition Hall  13:30 - 14:30

  Computer #  
4335.   25 Hexamethyldisiloxane-based dual-modality dual-functional nanoprobes for cellular and molecular imaging
Jyothi Menon1,2, Praveen Gulaka1, Madalyn McKay2, Sairam Geethanath1, and Vikram D Kodibagkar1,3
1Joint program in biomedical engineering, UT Arlington/UT Southwestern Medical Center, Dallas, Texas, United States, 2Radiology, UT Southwestern medical center, Dallas, Texas, United States, 3School of Biological and Health Systems Engineering, Arizona State University, Tempe, Arizona, United States

 
An emerging need for evaluation of promising cellular therapies is a non-invasive method to track and image the movement and health of cells following transplantation into the subject. Multi-modal imaging strategies are becoming more popular in recent times because of their improved sensitivity, higher resolution and structural/functional visualization. This study aims at formulating hexamethyldisiloxane (HMDSO) based dual modality (MRI / Fluorescence), dual-functional (oximetry/detection) nanoprobes for cellular and molecular imaging. Studies using CRI Maestro and PISTOL imaging confirmed that these nanoprobes could be used to detect changes in oxygen tension and for fluorescence imaging.

 
4336.   26 Novel Manganese Porphyrins as Potential MR Contrast Agents for Diagnostic Evaluation of Myocardial Perfusion and Viability
Talaignair N Venkatraman1, Haichen Wang2,3, Artak G Tovmasyan4, Ines Batinic-Haberle4, and Chris D Lascola1
1Radiology, Duke University Medical Center, Durham, North Carolina, United States, 2Neurology, Duke University Medical Center, 3Duke University Medical Center, 4Radiation Oncology, Duke University Medical Center

 
In this study, we present initial results investigating the use of two novel, water-soluble, lipophilic manganese-based porphyrins with remarkably high T1 relaxation properties and strong avidity for cardiac mitochondria. We present initial results investigating the use of two novel, water-soluble, lipophilic manganese-based porphyrins (MnTMOHex-PyP and MnTButOE-PyP) with remarkably high T1 relaxation properties and strong avidity for cardiac mitochondria. In vitro and in vivo quantitative MR imaging experiments demonstrate the potential of a novel class of manganese-based porphyrins for diagnostic characterization of myocardial perfusion and viability. The time course of myocardial enhancement and washout, as determined both qualitatively and quantitatively using a novel 3D variable flip angle steady state acquisition technique, would allow for the use of physiological rather than pharmaceutical stress, and also offer the possibility of quantitation at high isotropic resolution.

 
4337.   27 Liposomes Loaded with Paramagnetic Mn SOD Mimetic: Characterization, Relaxometry, and MR Imaging After Systemic Administration
Mohammed Salman Shazeeb1, Giancarlo Feula1,2, and Alexei Bogdanov1,3
1Department of Radiology, University of Massachusetts Medical School, Worcester, MA, United States, 2Worcester Polytechnic Institute, Worcester, MA, United States, 3Department of Cell Biology, University of Massachusetts Medical School, Worcester, MA, United States

 
M40403 is a synthetic manganese based superoxide dismutase (SOD) mimetic that has been extensively studied in vivo and found to have a catalytic activity rate which approaches that of the native Mn SOD enzyme. Here we compared the kinetics of liposome encapsulated M40403 and found that in addition to catalyzing superoxide dismutation in vitro, M40403 also doubled as a paramagnetic contrast agent in vivo, causing enhancement of mouse brain after systemic administration. Thus liposome encapsulated M40403 is an ideal candidate for development as a theranostic compound useful for MR imaging of SOD activity and disease treatment.

 
4338.   28 Magnetosomes, a new class of highly sensitive superparamagnetic contrast agents for MR molecular imaging
Benjamin Marty1, Nicolas Ginet2, Christopher Lefevre2, Daniel Garcia2, Franck Lethimonnier1, Denis Le Bihan1, Sébastien Mériaux1, and David Pignol2
1CEA/DSV/I2BM/NeuroSpin, Gif sur Yvette, France, 2CEA/DSV/IBEB/Laboratoire de Bioénergétique Cellulaire, Saint-Paul-lez-Durance, France

 
In this study we present a new class of superparamagnetic nano-particles, produced naturally by magnetotactic bacteria, and which regroup different characteristics of interest for biomedical applications: a perfectly crystalline and regular nanocrystal of magnetite, a natural lipid bilayer coating the nanoparticles, ensuring their solubilization and a possible functionalization of the lipid surface with biological functions for cellular targeting or in situ enzymatic catalysis. Transverse relaxivity of magnetosomes was measured at high magnetic field (17.2T) and preliminary experiments were performed on mice demonstrating the high in vivo sensivity of such contrast agents.

 
4339.   29 Synthesis, Characterization, In vitro and In vivo MR Studies of Dy(OH)3 Nanostructures for T2 MRI Contrast Agent
Krishna Kattel1, Ja Young Park1, Wenlong Xu1, Badrul Alam Bony1, Woo Choul Heo1, Tirusew Tegafaw Mengesha1, and Gang Ho Lee1
1Department of Chemistry, Kyungpook National University, Daegu, Korea

 
Dy-compounds are promising candidates for MRI contrast agent. Dy3+ has the shortest electronic relaxation time and highest magnetic moment (10.6 ¥ìB) which induce water proton relaxation that primarily affect T2. It increases significantly with the external magnetic field, and is proportional to the square of the magnetic moment of the Dy3+ ion. Dy(OH)3 nanostructures were examined for their possible use in MR imaging and tracking of cells by investigating their cytotoxic behaviors.

 
4340.   30 Non-emulsion clinical gadolinium/perfluorocarbon nanoparticles for 19F MRI
Mangala Srinivas1, Houshang Amiri2, Fernando Bonetto3, Javier L Cruz4, Eric van Dinther2, Jeanette Pots2, Arend Heerschap5, Carl Figdor1, and Jolanda de Vries1
1Tumor Immunology, RUNMC, Nijmegen, Gelderland, Netherlands, 2Tumor Immunology, RUNMC, Netherlands, 3INTEC-CONICET, Argentina, 4Molecular Imaging, UMC Leiden, Leiden, Netherlands, 5Radiology, RUNMC, Nijmegen, Gelderland, Netherlands

 
Gadolinium has previously been used to enhance the relaxativity of perfluorocarbons for more efficient 19F MRI. However, the poor interaction between hydrophilic Gd chelates and hydrophobic perfluorocarbons is problematic. We overcome this issue using polymeric nanoparticles encapsulating both Gd chelates and perfluorocarbon, thereby forcing close interaction. These particles are synthesized using clinically-approved components, and are stable for at least 6 months. We demonstrate frequency and concentration dependence of the 19F longitudinal relaxation time. Finally, we show that labeling has minimal effect on cell function and viability when used to label primary human dendritic cells, as currently used in cancer vaccines.

 
4341.   31 Novel Magnetic Properties of Gd Substituted Mn-Zn Ferrites Nanoparticles: Modeling T2 Variation with Temperature
Bashar Issa1,2, Ihab Obaidat1, Shahnaz Qadri2, and Yousef Haik2,3
1Physics, UAE University, Al-Ain, AD, United Arab Emirates, 2CREN, UNCG, Greensboro, NC, United States, 3Mech Eng, UAE University, Al-Ain, AD, United Arab Emirates

 
The magnetic and NMR relaxation properties of Gd-substituted Mn-Zn ferrite nanoparticles are studied at different temperatures. Magnetization data yielded a decrease in the saturation magnetization with temperature while the average magnetic moment of the particle increased. We propose that heating the particles increased the particle volume and hence its magnetic moment, with larger expansion at the surface shell layer than at the core of the particle. Only when temperature dependent particle size and magnetization are taken into account a close agreement between T2 data and model can be obtained. This enables correct characterization of contrast agent effect on MR images.

 
4342.   32 The effect of intracellular clustering on the stability and contrast generating properties of SPIOs: a comparison between PEGylated SPIOs and liposome SPIOs
Jesse Trekker1,2, Michel Hodenius3, Stefaan Soenen3, Wim Van Roy2, Marcel De Cuyper3, Liesbet Lagae2,4, and Uwe Himmelreich1
1Radiology / BioNMR unit, K.U.Leuven, Leuven, Belgium, 2imec, Leuven, Belgium, 3Lab of BioNanoColloids, IRC, K.U.Leuven Campus Kortrijk, Kortrijk, Belgium, 4Solid State Physics and Magnetism, K.U.Leuven, Leuven, Belgium

 
To study the effect of intracellular clustering on the stability and contrast generation properties of SPIOs we prepared non-clustering PEGylated-SPIOs and clustering liposome-SPIOs. Both SPIOs were taken up by mesenchymale stem cells and showed no to limited toxicity. Intracellular studies showed a difference in clustering between both SPIOs, however no difference in contrast could be detected. On the other hand the intracellular stability of the clustered SPIOs seemed to increase.

 
4343.   33 Assessment of the uptake of magnetite labeled nanoparticles in the rat using MRI
Naira P. Martínez Vera1, Klaus Langer2, Lavor Zlatev2, Robert Wronsky3, Manfred Windisch3, Hagen von Briesen4, Sylvia Wagner4, Motti Deutsch5, Claus Pietrzik6, Reinhold Schmidt1, and Stefan Ropele1
1Department of Neurology, Medical University of Graz, Graz, Styria, Austria, 2Institut für Pharmazeutische Technologie und Biopharmazie,WWU Münster, Germany, 3JSW Life Sciences GmbH, Grambach, Austria, 4Department of Cell Biology & Applied Virology, Fraunhofer-Institute for Biomedical Engineering, St. Ingbert, Germany, 5Physics Department, Schottenstein Center for the Research and Technology of the Cellome, Bar llan University, Israel, 6Institute of Pathobiochemistry, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany

 
Nanoparticles (NP) are expected to allow a more effective application of therapy by facilitating transport of drugs over the blood brain barrier (BBB). This experimental study focused on the development and in vivo testing of magnetite labeled NP. Following the optimization of the R1 relaxivity of different NP formulas in phantoms, the NP were administered intravenously in rats. The distribution and uptake then was assessed by T1 mapping and T1 weighted sequences. Most pronounced NP accumulations were observed in the liver and spleen. Using a histogram analysis, also a small but significant uptake was observed in the brain

 
4344.   34 Ferumoxytol as an intravenous contrast agent for relative cerebral blood volume (rCBV) measurements by MRI in rats at 9.4 Tesla
Andreas Pohlmann1, Babette Wagenhaus1, and Thoralf Niendorf1,2
1Berlin Ultrahigh Field Facility, Max Delbrueck Center for Molecular Medicine, Berlin, Berlin, Germany, 2Experimental and Clinical Research Center (ECRC), a joint cooperation between the Charité Medical Faculty and the Max-Delbrück-Center, Berlin, Berlin, Germany

 
Monitoring changes in blood volume with the use of intravascular contrast agents is of great interest for rodent studies of cerebrovascular diseases, fMRI and cerebrovascular reactivity. Ferumoxytol is a new intravenous iron preparation for treatment of the anemia of chronic kidney disease. It is a carbohydrate-coated USPIO and can also be used as a MRI contrast agent. In this study we investigated the use of ferumoxytol as a T2/T2* based MRI contrast reagent in rats at 9.4T. Its very slow wash-out and narrow, unvarying particle size distribution suggest that it may be well suited for rCBV quantification and rCBV-based fMRI.

 
4345.   35 Enhanced cellular uptake of aminosilane coated superparamagnetic iron oxide nanoparticles in mammalian cell lines
Xiao-Ming Zhu1, Ken Cham-Fai Leung2, Siu-Fung Lee3, Da-Wei Wang3, Feng Zhao1, Josie M. Y. Lai4, Chao Wan4, Christopher H. K. Cheng4, and Yi-Xiang Wang1
1Dept Imaging & Interventional Radiology, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, 2Institute of Creativity and Department of Chemistry, The Hong Kong Baptist University, Kowloon Tong, KL, Hong Kong, 3Department of Chemistry, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, 4School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, NT, Hong Kong

 
It was shown aminosilane (SiO2-NH2) coated SPIO (SPIO@SiO2-NH2) had higher labeling efficiency for rabbit mesenchymal stem cells (MSCs) than SiO2 coated SPIO (SPIO@SiO2). This study compared the intracellular uptake of SPIO@SiO2-NH2 with SPIO@SiO2, bare SPIO, and dextran coated SPIO (SPIO@dextran) in RAW 264.7, L929, HepG2, PC-3, U-87 MG cells, and mouse MSCs. All these six mammalian cell lines showed the highest cellular uptake for SPIO@SiO2-NH2. For SPIO@SiO2, bare SPIO and SPIO@dextran, there were variations of labeling efficiency among different cell lines, with SPIO@SiO2 tended to rank as the second, and bare SPIO and SPIO@dextran tended to have lower labeling efficiency.

 
4346.   36 MRI investigation of an iron contrast agent in a mouse model of myocardial ischaemia reperfusion
Andrea Protti1, Xuebin Dong2, Marcelo E. Andia3, Bin Yu2, Kate Dokukina2, Sanjay Chaubey2, Maria G. Vizcay-Barrena3, Alkystis Phinikaridou3, Matthias Taupitz4, Ajay M. Shah2, and Rene Botnar3
1Cardiovascular Division and Division of Imaging Sciences and Biomedical Engineering, King’s College London British Heart Foundation Centre of Excellence, London, United Kingdom, 2Cardiovascular Division, King’s College London British Heart Foundation Centre of Excellence, London, United Kingdom, 3Division of Imaging Sciences and Biomedical Engineering, King’s College London, London, United Kingdom, 4Charite Berlin, Department of Radiology, Berlin, Germany

 

4347.   37 Comparison of three mri molecular imaging modalities: application to angiogenesis imaging in a brain tumor mouse model
Céline Giraudeau1, Benjamin Marty1, Julien Flament1, Françoise Geffroy1, Christelle Médina2, Philippe Robert2, Caroline Robic2, Marc Port2, Denis Le Bihan1, Julien Valette1, Sébastien Mériaux1, Fawzi Boumezbeur1, and Franck Lethimonnier1
1NeuroSpin, I2BM, Commissariat à l'Energie Atomique, Gif-sur-Yvette, France, 2Guerbet, Research Division, Roissy-Charles de Gaulle, France

 
In the present work, three different contrast agents (CA) are evaluated: Gd-based emulsion, LipoCEST and fluorine emulsion. A comparison of the three modalities sensitivity and specificity is performed on a mouse model of brain tumor using CA grafted with RGD peptides to specifically target lower case Greek alphalower case Greek nulower case Greek beta3 integrins over-expressed in angiogenic vessels. CA are detected with a sub-nanomolar sensitivity by the three modalities. A higher contrast is systematically observed for RGD contrast agents inside the tumor. Each modality provides additional information, promising for multimodal investigation of brain diseases.

 
4348.   38 ‘MultiPaw’: High throughput MR imaging of ex-vivo AIA mouse joints with injected SPIONs on a clinical 3T system.
Lindsey A Crowe1, Eline A Vermeij2, Marije I Koenders2, Fons A J van de Loo2, Frank Tobalem1, Thomas Goget1, Azza Gramoun1, Wim B Van den Berg2, and Jean-Paul Vallée1
1Faculty of Medicine/Department of Radiology, University of Geneva, Geneva, Switzerland, 2Rheumatology Research and Advanced Therapeutics, Radboud University Nijmegen Medical Centre, Nijmengen, Netherlands

 
We investigate a ‘MultiPaw’ imaging protocol for optimizing small sample scanning at high-resolution in a clinical MRI. An antigen induced mono-arthritis model in mouse knees with/without intra-venous or intra-articular SPION injection is presented to show the diagnostic potential. Pre-clinical studies may use clinical MRI systems due to translational possibilities and availability of the technology. For small sample sizes, an adapted coil to give high signal intensity is needed, though the initial obvious choice of the smallest coil may not be the best. Signal-to-noise is optimized with small, adapted coils, but a longer scan using a larger coil with greater signal homogeneity can be efficient.

 
4349.   39 Assessing the potential of Hexabrix as an ionic x-ray contrast agent to be used as an agent for chemical exchange saturation transfer (CEST) MR imaging at 3 T and 7 T
Benjamin Schmitt1, Pavol Szomolanyi2, Toshiyuki Shiomi3, and Siegfried Trattnig2
1Centre for High-Field MR, Medical University of Vienna, Vienna, Austria, 2Medical University of Vienna, 3Osaka University Graduate School of Medicine

 
The study was performed to assess if the ionic X-ray contrast agent Hexabrix® can be used as an agent for CEST MRI. In-vitro solutions with different concentrations of Hexabrix® were examined with CEST imaging on 3 T and 7 T whole-body MR scanners. Results showed signals, which are attributed to exchangeable amide protons of Hexabrix®. These signal seem to be well suited for CEST imaging as they showed dependency on agent concentration. Using an approved X-ray contrast agent could facilitate the usage as a designated agent for CEST MRI targeting, e.g., biomolecules with surface charge

 
4350.   40 Fuctionalized Magnetoliposomes for visualization of Hepatocytes in vitro and in vivo
Ashwini A. Ketkar-Atre1, Tom Struys2, Tineke Notelaers3, Michel Hodenius4, Philip Roelandt3, Tom Dresselaers2, Marcel De Cuyper4, Catherine Verfaillie3, and Uwe Himmelreich1
1Biomedical NMR unit, KU Leuven, Leuven, Vlaams Brabant, Belgium, 2Biomedical NMR unit, KU Leuven, Leuven, Belgium, 3Interdepartmental Stem Cell Institute, Leuven, Belgium, 4Lab Of BioNano Colloids, KULeuven, Leuven, Belgium

 
In diseases like liver cirrhosis or hepatitis where hepatocytes are damaged and healing is difficult, it is necessary to isolate hepatocytes from mixed population of endo- and mesodermal cells differentiated from stem cells. We labelled differentiated mESCs into hepatocyte like cells with Cationic MLs (unspecific uptake), Anionic MLs (negative control) and Lac MLs (specific uptake) with galactose-terminal entities which are recognized by asialoglycoprotein receptors (ASGPR)present on hepatocytes. Higher specificity in uptake was observed with Lac MLs. And In vivo experiments revealed the potential use of Lac MLs as a contrast agent for non-invasive evaluation of liver function.

 
4351.   41 Concentration dynamic response assessment for intra-articular injected iron-oxide nanoparticles.
Lindsey A Crowe1, Frank Tobalem1, Wolfgang Wirth2, Azza Gramoun1, Benedicte M A Delattre1, Kerstin Grosdemange1, Jatuporn Salaklang3, Anthony Redjem3, Alke Petri-Fink3, Felix Eckstein2, Heinrich Hofmann4, and Jean-Paul Vallée1
1Faculty of Medicine/Department of Radiology, University of Geneva, Geneva, Switzerland, 2Institute of Anatomy & Musculoskeletal Research, Paracelsus Medical University, Salzburg, Austria, 3Adolphe Merkle Institute, University of Fribourg, Fribourg, Switzerland, 4Powder Technology Laboratory, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland

 
Nanoparticle technology, including SPIONs, is of emerging importance for monitoring onset, progression and treatment of inflammatory diseases such as arthritis and drives quantitative imaging. Conventional signal loss in SPION-containing tissues saturate at medium concentrations and show non-linear/non-proportional intensity/concentration profiles due to competing T1/T2 effects. Intra-articular injected SPIONs were compared to phantom calibrations using dUTE (difference-Ultrashort TE) with positive, unambiguous signal characteristics and monotonic increasing concentration response over a wide range in a phantom and a rat model, opening possibilities for quantification. A further advantage of dUTE is the distinction of synovial iron signal intensity from tissues (muscle, bone) and noise.

 
4352.   42 Synergistic Targeting-Imaging Approaches for Sensitive Virus and Tumor Detections
Yung-Ya Lin1, Chaohsiung Hsu1, Zhao Li1, and Lian-Ping Hwang2
1Chemistry and Biochemistry, UCLA, Los Angeles, CA, United States, 2Chemistry, National Taiwan University, Taipei, Taiwan

 
Sensitive in vivo MR imaging of virus (especially the ability to quantify virus concentrations and type/subtype) and tumors (especially at early stages) are important and challenging for medical development and clinical applications. For this purpose, synergistic targeting-imaging approaches were developed and demonstrated. Computer simulations and in vitro H5N2 images suggest 4-10 times of improvements in imaging sensitivity to virus concentrations can be achieved by this this targeting-imaging approach over conventional methods. (ii) In vivo mouse images of colon cancers targeted by SPIO suggest this targeting-imaging approach can provide enhanced, robust, and positive contrast for sensitive tumor detection.

 
4353.   43 Semi-quantification of lipoCEST CA in vivo. Application to molecular imaging of lower case Greek alphalower case Greek nulower case Greek beta3 integrins expressed during angiogenesis using targeted lipoCEST CA in a tumor mouse brain model
Julien Flament1, Françoise Geffroy1, Christelle Médina2, Caroline Robic2, Philippe Robert2, Marc Port2, Gilles Bloch1, Denis Le Bihan1, Franck Lethimonnier1, and Fawzi Boumezbeur1
1CEA/DSV/I²BM/NeuroSpin, Gif-sur-Yvette, France, 2Guerbet Research, Roissy-Charles de Gaulle, France

 
LipoCEST are promising contrast agents for molecular imaging which can be functionalized to target specific biomarkers. Although in vivo detection is complicated by to endogenous MT effects, several studies have already shown feasibility. Still, quantification remains very challenging. Here, we used a 4-pools model which takes into account both endogenous and exogenous MTRasym effects as well as field inhomogeneities in order to establish in vivoquantitative maps. This model was evaluated in a tumor mouse brain model with a functionalized RGD-lipoCEST which targets lower case Greek alphalower case Greek nulower case Greek beta3 integrins expressed during tumor angiogenesis.

 
4354.   44 Towards novel contrast agents for bowel imaging based on 19F compounds
Rolf Lamerichs1,2, Marije van der Paardt2, Aart Nederveen2, Jaap Stoker2, and Raquel Diaz-Lopez1,3
1Philips Research, Eindhoven, Netherlands, 2Academic Medical Center, Amsterdam, Netherlands, 3VU University Medical Center, Amsterdam, Netherlands

 
Contrast agents based on fluorine (19F) compounds have several advantages over T1 or T2 based contrast agents. Here we show the use of non-targeted polymeric microcapsules for bowel imaging. These microcapsules contain perfluoro-octylbromide (PFOB). For the detection of the fluorine signal we used the Fluorine ultrafast Turbo Spectroscopic Imaging (F-uTSI) sequence. This sequence can be applied to any PFC compound. The data show that the polymeric microcapsules can be developed into promising 19F-MRI contrast agents for bowel imaging using 19F spectroscopic imaging methods. The bowel transit time of these agents is around 10 hrs in black mice.

 
4355.   45 DYNAMIC UPTAKE OF A TARGETED Gd-CHELATE NANOEMULSION BY A lower case Greek alphavlower case Greek beta3 EXPRESSING CELL LAYER FOLLOWED-UP WITH A MICRO-MRI SET-UP
Nicolas Gargam1, Marie Poirier-Quinot1, Caroline Robic2, Jean-Frédéric Salazar2, Jean-Sébastien Raynaud2, Philippe Robert2, and Luc Darrasse1
1IR4M - UMR 8081 - CNRS - Université Paris Sud XI, Orsay, France, 2Guerbet Research, Paris, France

 
In this work, we demonstrate by micro-MRI the dynamic uptake of a RGD-targeted Gd-loaded emulsion by a HUVEC cell monolayer expressing the áíâ3 integrin, which is a promising target for molecular imaging due to its high level of expression during tumor angiogenesis. The signal enhancement observed on the cell monolayer indicates a 3-fold higher uptake of the targeted emulsion by the HUVEC cells when compared to the control emulsion. This in vitro molecular imaging model approach can be useful prior to in vivo experiments on animals, particularly to assess the specificity and characterize the binding kinetics of targeted CAs.

 
4356.   46 Stageing of Atherosclerotic Plaques by a Vascular Cell Adhesion Protein-1 Targeted Contrast Agent
Brigit den Adel1, Carmen Burtea2, Sophie Laurent2, Ernst Suidgeest3, Robert E. Poelmann1, Robert N. Muller2, and Louise van der Weerd3,4
1Anatomy & Embryology, Leiden University Medical Center, Leiden, Netherlands, 2Université de Mons-Hainaut, Mons, Belgium, 3Radiology, Leiden University Medical Center, Leiden, Netherlands, 4Human Genetics, Leiden University Medical Center, Leiden, Netherlands

 
We identified a highly specific peptide with nanomolar affinity for human VCAM-1. High resolution MRI performed 1.5 hours after i.v. injection of VCAM-1 targeted USPIOs in aged ApoE-/- mice with advanced plaques showed enhanced uptake of the contrast agent. Young ApoE-/- mice with a collar around the carotid artery, showed an increased uptake of the iron particles, particularly in early plaque stages when VCAM-1 expression is highest. Histology showed co-localisation of VCAM-1 positive endothelial cells and iron deposits in the vessel wall.

 
4357.   47 Diagnostic activity of a new targeted theranostic agent for the peri-infarct region in stroke
Jesús Agulla1, David Brea1, Barbara Argibay1, Miguel Blanco1, José Castillo1, and Pedro Ramos-Cabrer1
1Clinical Neuriosciences Research Laboratory, Department of Neurology, University Clinical Hospital, University of Santiago de Compostela, Santiago de Compostela, Spain

 
In this work we report the development of a theranostic molecule containing Gadolinium based imaging probes, targeted to cells of the peri-infarct region in stroke. The molecular marker used as target for peri-infarct tissue was found by proteomic and immunohistological studies. Fluorescence microscopy and MRI were used to test the diagnostic capacity of the theranostic molecule, allowing the identification of cells of the peri-infarct region.

 
4358.   48 Molecular MRI-based Detection of an Alpha-1A Receptor Agonist Treatment for Ischemia-Induced Cardiac Apoptosis
Rajesh Dash1, Justin Lam1, Ildiko Toma1, Yongquan Gong2, Robert C. Robbins2, Paul C. Simpson3,4, and Phillip C. Yang1
1Cardiovascular Medicine, Stanford University Medical Center, San Francisco, CA, United States, 2Cardiac Surgery, Stanford University Medical Center,3Medicine / Cardiology, UCSF Medical Center, San Francisco, CA, United States, 4Cardiology, San Francisco VA Medical Center, San Francisco, CA, United States

 
A novel anti-apoptotic alpha-adrenergic agonist preserves left ventricular ejection fraction in mice following myocardial infarction. This therapeutic effect is able to be detected and quantified non-invasively, using T2* signal loss assessment of an Annexin-SPIO molecular apoptosis probe.
 
Electronic Poster Session - Molecular Imaging

Cell Tracking & Reporter Genes: Approaches & Acquisitions
Click on to view the abstract pdf and click on to view the video presentation. (Not all presentations are available.)
Thursday 10 May 2012
Exhibition Hall  14:30 - 15:30

  Computer #  
4359.   25 Rescue of LV Dysfunction in a Pig Ischemia-Reperfusion Injury Model By Human Amnion-derived Mesenchymal Stem Cells Tracked by Manganese-Enhanced MRI
Rajesh Dash1, Ildiko Toma1, Fumiaki Ikeno1, Jennifer K. Lyons1, Shahriar Heidary1, Marie-Claude Parent1, I-Ning E. Wang1, Xiaohu Ge1, Justin Lam1, Jaehoon Chung2, Paul J. Kim1, Kaori Nakagawa1, Svetlana Lyalina1, Grace Do1, Robert C. Robbins3, Michael V. McConnell1,4, Alan C. Yeung1, Phillip Harnish5, and Phillip C. Yang1
1Cardiovascular Medicine, Stanford University Medical Center, STANFORD, CA- CALIFORNIA, United States, 2Medicine / Cardiology, University of Illinois-Chicago, Chicago, IL, United States, 3Cardiac Surgery, Stanford University Medical Center, 4Electrical Engineering, Stanford University, 5Eagle Vision Pharmaceutical Corporation, Downington, PA, United States

 
Human Amnion-derived Mesenchymal Stem Cells (hAMSCs) were transplanted into the infarct and peri-infarct regions of a pig ischemia-reperfusion model. The hAMSC therapy improved cardiac systolic function post-MI, compared to control animals, and Cardiac MRI with Manganese-Enhanced MRI (MEMRI) was able to detect increased CNR from live populations of hAMSCs within infarct and peri-infarct zones, as confirmed by human nuclear antigen (hNA) immunostaining.

 
4360.   26 Improved Identification of Ferritin-Tagged Grafts in Mouse Heart at Higher Magnetic Field Strength
Anna V Naumova1,2, Vasily L Yarnykh1,2, Niranjan Balu1,2, Hans Reinecke2,3, Charles E Murry2,3, and Chun Yuan1,2
1Radiology, University of Washington, Seattle, WA, United States, 2Center for Cardiovascular Biology, University of Washington, Seattle, WA, United States, 3Pathology, University of Washington, Seattle, WA, United States

 
Mouse skeletal myoblasts were genetically modified to overexpress ferritin, a natural iron storage protein. T2 relaxivity of ferritin-tagged cells dramatically increased with increase of the magnetic field strength; thus improves MRI graft identification and assessment of the graft size. Transgenic grafts overexpressing ferritin decreased MRI signal intensity by 30% at the 3T magnetic field strength and by 50% at the 14T magnetic field strength. Unlabeled cells transplanted to the mouse heart did not cause MRI signal intensity change and were indistinguishable from host tissue.

 
4361.   27 MAGNETIC RESONANCE IMAGING OF STEM CELL VIABILITY USING DUAL POSITIVE (T1) AND NEGATIVE (T2*) CONTRAST AGENTS IN A MOUSE BRAIN INJURY MODEL
Ethel Ngen1, Yoshinori Kato1, Wenlian Zhu1, and Dmitri Artemov1
1Russell H. Morgan Department of Radiology and Radiological Sciences, ICMIC Program, Johns Hopkins University, School of Medicine, Baltimore, Maryland, United States

 
Given the current need to non-invasively monitor transplanted stem cell viability and integration in vivo, we evaluated the ability of a novel MRI stem cell tracking technique to monitor cell viability in vivo. Stem cells were labeled with both high molecular weight negative and low molecular weight positive contrast agents, then implanted contra-laterally to a cerebral lesion in both immunodeficient and immunocompetent mice. Following graft rejection in immunocompetent mice, T1 enhancement was observed in the surrounding site. These results suggest that T1 changes in the surroundings of transplanted stem cells could be used to track, their viability in vivo.

 
4362.   28 MRI of Intracoronary Local Delivery of Motexafin Gadolinium: Towards Molecular MRI-Guided Gene Therapy
Yanfeng Meng1, Jinnan Wang2, Jihong Sun1, Feng Zhang1, Patrick Willis1, Jiakai Li1, Han Wang1, Tong Zhang1, Stephanie Soriano1, Bensheng Qiu1, and Xiaoming Yang1
1Radiology, University of Washington, Seattle, WA, United States, 2Clinical Sites Research Program, Philips Research North America

 
This study was to develop a new technique, using molecular MRI to monitor local agent delivery to coronary artery walls for potential MRI-guided prevention of in-stent restenosis. The study was divided into three phases. For the in vitro confirmation, we determined the optimum dose of Motexafin Gadolinium (MGd), a multifunctional intracellular T1 MR contrast/anti-atherosclerotic agent. For ex vivo and in vivo study, we infused MGd/trypan blue the coronary arterial walls under MRI, which were correlated with histology confirmation. This study initially demonstrates the possibility of using MRI to monitor the local agent delivery and distribution in the coronary arterial walls.

 
4363.   29 Stearic-Polyethylenimine Modified SPIO Nanoparticles for MRI of Gene Delivery to Liver
lin Gao1, zhiyong Wang1, lisi Xie2, xiaojing Long1, zhiying Chen3, and bensheng Qiu1,4
1Paul C Lauterbur Research Center for Biomedical Imaging, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, China, 2Faculty of Chemical Engineering and Light Industry, Guangdong University of Technology, Gaungzhou, Guangdong, China, 3Gene and Cell Engineering Center, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, China, 4Department of Radiology, University of Washington School of Medicine, Seattle, Washington, United States

 
An amphiphilic polymer, stearic-polyethylenimine (PEI600) was synthesized and used for modified hydrophobic supermagnetic iron oxide (SPIO) nanocrystals via self-assemble progress in aqueous phase. The nanocomposite system is novel magnetic imaging contrast agents and capable to bind and deliver plasmid DNA for gene transfection. In vivo, it was observed that MR signal decreased significantly via a clinical 3.0T MRI scanner. The histochemistry of tissue sections of liver results showed that this nanoparticle gene delivery system provided a safe and efficient method for gene delivery with non-invasive imaging monitoring capability.

 
4364.   30 Tracking of mesenchymal stem cells in a rat stroke model using a novel multimodal, plasmid-functionalized nanoparticle
Jens T Rosenberg1,2, Megan Muroski3, Tom Morgan4, Cathy Levenson4, Geoffrey Strouse3, and Samuel Colles Grant1,2
1Center for Interdisciplinary Magnetic Resonance, The National High Magnetic Field Laboratory, Tallahassee, FL, United States, 2Chemical & Biomedical Engineering, The Florida State University, Tallahassee, FL, United States, 3Chemistry and Biochemistry, The Florida State University, Tallahassee, FL, United States, 4Biomedical Sciences, The Florida State University, Tallahassee, FL, United States

 
Mesenchymal stem cells (MSCs) have demonstrated significant potential for use in the treatment of nervous system injuries, mainly through the secretion of protective proteins rather than direct regeneration. The transport, secretory profile and ultimate fate of MSCs are still areas of active research. The current study reports on a fluorescein and DNA plasmid functionalized iron oxide nanoparticle that has been instituted successfully in MSCs. Used in an animal stroke model, the nanoparticle imparts multimodal MR and optical imaging capabilities as well as genetically modifies MSCs to express in vivo mCherry fluorescence, a precursor to other manipulations of MSC protein expression.

 
4365.   31 MR Contrast and Biological Impacts of Intracellular Superparamagnetic Iron Oxides on Human Mesenchymal Stem Cells with Hypoxic Ischemic Exposure
Jens T Rosenberg1,2, Katelyn Sellgren2, Michelle A Baird3, Micheal W Davidson3,4, Teng Ma2, and Samuel Colles Grant1,2
1Center for Interdisciplinary Magnetic Resonance, The National High Magnetic Field Laboratory, Tallahassee, FL, United States, 2Chemical & Biomedical Engineering, The Florida State University, Tallahassee, FL, United States, 3The National High Magnetic Field Laboratory, Tallahassee, FL, United States,4Department of Biological Science, The Florida State University, Tallahassee, FL, United States

 
Labeling of human mesenchymal stem cells (hMSCs) with superparamagnetic iron oxides (SPIOs) have been demonstrated but few studies have investigated biological impacts or long term tracking capability, especially under stroke conditions. This study shows that hMSCs display dose dependent SPIO uptake and progressive decreases in contrast over extended culture mimicking the maximum expected transplant duration. Though other biological effects were impacted minimally by SPIOs, hypoxic ischemic conditions increased cytotoxicity significantly, with vulnerability related to SPIO exposure. This finding needs to be considered when introducing intracellular contrast agents for cellular based regenerative therapies in an ischemic, low oxygen environment.

 
4366.   32 Monitoring of Iron-PLLA Loaded MSCs after Silicone Carrier Application @ 11.7T
Ina Vernikouskaya1,2, Natalie Fekete3, Alexander Erle3, Hubert Schrezenmeier3, and Volker Rasche1,2
1Internal Medicine II, University Hospital of Ulm, Ulm, Baden-Wuerttemberg, Germany, 2Small Animal MRI, University of Ulm, Ulm, Baden-Wuerttemberg, Germany, 3Institute of Clinical Transfusion Medicine and Immunogenetics, University Hospital of Ulm, Ulm, Baden-Wuerttemberg, Germany

 
The objective of this study was to use chemically defined silicone carrier as an delivery aid of the iPLLA-labeled MSCs to the skin wounds for further monitoring of the cell trafficking using MRI. The magnetic properties of iPLLA nanoparticles were investigated at 3T and at 11.7T. In vitro imaging of a silicone carrier with attached labeled MSCs allowed to determine the amount of cells which could be good visualize and still remains attached to the carrier. In vivo imaging showed the attraction of the labeled MSCs to the skin wound and demonstrated that silicone carriers could be used as a vehicle for the application of MSCs to surface wounds.

 
4367.   33 Consistency Conditions in MRI-based Attenuation Correction for Hybrid PET/MRI scanners
Zhengyi Yang1, Viktor Vegh1, Ian Turner2, and David Reutens1
1Center for Advanced imaging, The University of Queensland, Brisbane, Queensland, Australia, 2School of Mathematical Sciences, Queensland University of Technology, Brisbane, Queensland, Australia

 
Attenuation correction in PET/MRI imaging is a challenging task because the attenuation map is difficult to be calculated due to the lack of information on tissue classification in MRI image. Consistency conditions on PET emission data contain useful information on the attenuation map and can be employed to regularize the creation of MRI-based attenuation map. In this study, the efficacy of consistency conditions were validated on simulated images of normal brain and brain with lesion. The results indicated these conditions are insensitive to brain lesions in finding the attenuation coefficients of each tissue class.

 
4368.   34 Measuring T1 in the presence of very high iron concentrations with SWIFT
Ryan Chamberlain1, Michael Etheridge2, Djaudat Idiyatullin1, Curt Corum1, John Bischof2, and Michael Garwood1
1Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, United States, 2Department of Mechanical Engineering, University of Minnesota, Minneapolis, MN, United States

 
Iron oxide magnetic nanoparticles (MNPs) are widely used in MRI as a T2- and T2*-shortening contrast agent. Quantifying high concentrations of MNPs is crucial in magnetic fluid hyperthermia for cancer therapy. Efforts to quantify MNP concentration have relied on T2* mapping; however, signal loss is a severe obstacle to quantifying high concentrations of MNPs based on traditional MRI methods. Here we use the SWIFT pulse sequence to accomplish T1 measurement of solutions with very high iron concentration and show how the measured T1 value may be used in place of T2* to quantify high concentrations of MNPs.

 
4369.   35 Mass spectrometry detection of loss of structural integrity of Gd-DTPA entrapped in J774 machrophages
Eliana Gianolio1, Enza Di Gregorio1, Rachele Stefania1, and Silvio Aime1
1Chemistry IFM & Molecular Imaging Center, University of Torino, Torino, Italy, Italy

 
Herein we report a mass spectrometric method for accurate detection and quantification of a Gd-complex after its internalization in living cells. This method allowed to determine if, and how Gd-complexes endowed with different thermodynamic stability can be transformed once entrapped into living cells.

 
4370.   36 Simultaneous and quantitative tracking of distinct cell populations using 19F MRI
Mangala Srinivas1, Fernando Bonetto2, Jurjen Tel1, Gerty Schreibelt1, Javier Cruz3, Arend Heerschap4, Carl Figdor1, and Jolanda de Vries1
1Tumor Immunology, RUNMC, Nijmegen, Gelderland, Netherlands, 2INTEC-CONICET, Argentina, 3Molecular Imaging, UMC Leiden, Leiden, Netherlands,4Radiology, RUNMC, Nijmegen, Gelderland, Netherlands

 
The use of 19F MRI for cell tracking is a relatively new field. We demonstrate the tracking of two distinct primary human dendritic cell subsets, as used in clinical trials, using distinct 19F resonances. Typically, such multispectral analyses are done using chemical shift imaging (CSI); here we use a modified gradient echo sequence to image both cell populations simultaneously, quantitatively and efficiently (several fold faster than CSI). We use clinically applicable nanoparticle labels, with distinct fluorescent dyes to enable multimodal imaging. We find that labeling has minimal effect on cells, in terms of viability, maturation and migration.

 
4371.   37 Automated workflow for MR-PET attenuation correction in a tri-modality system using Dixon fat-water imaging based tissue classification
Dattesh D Shanbhag1, Sheshadri Thiruvenkadam1, Sandeep Kaushik1, Rakesh Mullick2, Scott D Wollenweber3, and Florian Wiesinger4
1Medical Image Analysis Laboratory, GE Global Research, Bangalore, Karnataka, India, 2GE Global Research, Biosignatures & Signal Processing, Bangalore, Karnataka, India, 3GE Healthcare, PET Clinical Science, Waukesha, WI, United States, 4Diagnostics & Biomedical Tech Laboratory, GE Global Research, Garching b. Munchen, Germany

 
We have demonstrated an automated workflow for generation of the attenuation map for body Dixon-based MRI for PET attenuation correction. The use of a tri-modality system with dedicated patient transporter results in minimal degree of motion between PET-CT and MRI scans and thereby improves the validation accuracy of attenuation correction of MR-PET system with gold standard PET-CT system.

 
4372.   38 Age-dependent sodium content in human calf skin measured with sub-millimeter spatial resolution 23Na-MRI at 7.0 T
Peter Linz1, Davide Santoro2, Wolfgang Renz3, Jan Ruff3, Michael Deimling3, Dominik N. Müller4,5, Jens Titze1,4, Friedrich C Luft5, and Thoralf Niendorf2
1Department of Nephrology and Hypertension, University Clinic Erlangen, Erlangen, Germany, 2Berlin Ultrahigh Field Facility, Max-Delbrueck Center for Molecular Medicine, Berlin, Germany, 3Siemens Healthcare, Erlangen, Germany, 4Nikolaus-Fiebiger-Center for Molecular Medicine, University Erlangen-Nuernberg, Erlangen, Germany, 5Experimental and Clinical Research Center (ECRC), Max-Delbrueck Center for Molecular Medicine, Berlin, Germany

 
Intake of sodiumchloride (NaCl) contributes to hypertension and target-organ damage. Na is stored in the interstitial compartment of the skin but little is known about Na-metabolism in humans. Skin-Na contents in nine healthy men (25-68 years) were measured with 0.9mm X 0.9mm in-plane resolution 23Na-MRI at 7.0T using an optimized surface-coil and a 10min gradient-echo sequence. Intra-subject variability was found to be below 6%. High tissue concentrations up to 60mmol/L were measured. Skin-Na content increased with age comparable to the probability of becoming hypertensive. Best correlations were achieved with a Boltzmann-fit and a maximum slope at 38±5 years.

 
4373.   39 Characterization of lung tumor cell lines by amide proton transfer (APT) imaging in in-vitro system
Kim Kangasniemi1, Koji Sagiyama1, Boning Gao2, Chunxian Huang2, John Minna3, and Masaya Takahashi1
1Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, TX, United States, 2Hamon Center for Therapeutic Oncology, Pharmacology, University of Texas Southwestern Medical Center, UT Southwestern Medical Center, Dallas, TX, United States, 3Hamon Center for Therapeutic Oncology, Internal Medicine, Pharmacology, UT Southwestern Medical Center, Dallas, TX, United States

 
The proton exchange between amide groups in mobile proteins/peptides and free water in two different human cancer cell lines and normal cell line were studied. Amide proton transfer (APT) imaging is one of the chemical exchange saturation transfer (CEST) imaging methods was utilized to differentiate between the tumors. A comparison in magnetization transfer between cell tumor lines showed a difference in APT signal, suggesting that tumor type characterization can be done by in-vivo APT imaging.

 
4374.   40 Improvement of positive contrast dUTE using susceptibility-weighted phase image information applied to iron-labelled cells
Lindsey A Crowe1, Sophie Borot2, Sonia Nielles-Vallespin3, Christian Toso2, Domenico Bosco2, Thierry Berney2, and Jean-Paul Vallée1
1Faculty of Medicine/Department of Radiology, University of Geneva, Geneva, Switzerland, 2Islet Isolation and Transplantation Center, Visceral Surgery Department, Geneva University Hospital, Geneva, Switzerland, 3Royal Brompton Hospital, London, United Kingdom

 
dUTE positive contrast MRI images can be further improved using susceptibility-weighting information from the long echo phase image to enhance contrast and further suppress background to homogeneous near-zero values for the UTE-TE(2) difference image. In-vivo MR imaging of iron-labelled islet cells in the liver are used to illustrate the technique.

 
4375.   
41 Monitoring therapeutic response on GBM in chemotherapy by amide proton transfer (APT) imaging in mice
Koji Sagiyama1, Osamu Togao1, Tomoyuki Mashimo2,3, Kim Kangasniemi1, Vamsidhara Vemireddy3,4, Kimmo J. Hatanpaa5, Melissa A. Maddie3,4, Robert M. Bachoo3,4, Elizabeth A. Maher2,3, A. Dean Sherry1, and Masaya Takahashi1
1Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, Texas, United States, 2Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, United States, 3Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, Texas, United States, 4Department of Neurology, UT Southwestern Medical Center, Dallas, Texas, United States, 5Departement of Pathology, UT Southwestern Medical Center, Dallas, Texas, United States

 
Amide proton transfer (APT) imaging shows increasing interest in characterization of the brain tumor. The objective of our study is to investigate whether APT imaging can be used for monitoring treatment responses of the brain tumor in chemotherapy. In the present study, we compared the temporal changes of APT ratio in glioblastoma multiforme (GBM) in a mouse model with and without chemotherapy by Temozolomide which is widely used for the treatment of GBMs.

 
4376.   42 NOn-transferred MAgnetization Ratio (NOMAR) Filtering: A New Technique to Create Tissue Selective CEST contrast maps
Guanshu Liu1,2, Kannie WY Chan2,3, Xiaolei Song2,3, Jiangyang Zhang2,4, Assaf A Gilad2,3, Jeff WM Bulte2,3, Peter CM van Zijl2,4, and Michael T McMahon2,4
1F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Instittute, Baltimore, Maryland, United States, 2Department of Radiology, Johns Hopkins University School of Medicine, baltimore, maryland, United States, 3Cellular Imaging Section, Institute for Cell Engineering, Johns Hopkins University School of Medicine, baltimore, maryland, United States, 4F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, baltimore, maryland, United States

 
Signal contamination and partial volume effects significantly influence in vivo CEST quantification. To improve upon this, we propose a simple magnetization transfer (MT) based segmentation method based on adding two MT weighted images at offsets of -12.5 and -50 ppm to CEST acquisitions. These are used to calculate a NOrmalizedMAgnetization Ratio (NOMAR) allowing pixels containing fat or fluids to be separated from target tissues using a global threshold determined by histogram analysis. As a first application, we demonstrate that this technique can significantly improve the detection of DIACEST liposomes injected into live mice.

 
4377.   43 Temporally flexible tracking of Neuro-progenitor stem cells using Golden Angle incremented Linear combination Steady-State Free Procession (LCSSFP) imaging for artifact reduction.
H. Douglas Morris1, and J. Andrew Derbyshire2
1NIH Mouse Imaging Facility, National Institutes of Health, Bethesda, MD, United States, 2Laboratory for Cardiac Energetics, National Institues of Health, Bethesda, MD, United States

 
Rapid individual cell tracking of endogenously labeled stem cells is shown using high-field MRI and balanced Steady-State Free Procession sequences. We present a field artifact suppression technique based on the Golden Angle progression for the RF phase cycle as a modification to Linear Combination SSFP (LCSSFP). The use of golden-angle LCSSFP yields a temporally flexible acquisition scheme that can yield continuous progression of resulting images that do not overlap in pulse-band artifacts. This resulting method can yield very high resolution images quickly with few global artifacts while still tracking magnetic particles.

 
4378.   
44 Accelerated In Vivo Cell Tracking Using Fluorine-19 MRI with Compressed Sensing
Jia Zhong1,2, Parker H Mills1,2, T Kevin Hitchens1,2, and Eric T Ahrens1,2
1Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, United States, 2The Pittsburgh NMR Center for Biomedical Research, Carnegie Mellon University, Pittsburgh, PA, United States

 
Compressed sensing (CS) has been used to significantly reduce acquisition times in a variety of MRI applications. In the current study, we describe a 3D CS method for accelerated 19F MRI and signal quantification that is suitable for cell tracking using perfluorocarbon (PFC) labels. The method’s utility was demonstrated in a localized inflammation mouse model, where the quantification of PFC 19F spins in macrophages was performed at the inflammatory site. The 3D CS method displays great potential in advancing in vivo 19F MRI cell tracking to different applications including longitudinal tracking of 19F-labeled cells and in vivo cytometry.

 
4379.   45 DCE-MRI to study vascular dependency of radiolabelled nano-graphene oxide nanoparticle delivery
Bart Cornelissen1, Veerle Kersemans1, Philip Allen1, Sarah Able1, Sean Smart1, and Katherine Vallis1
1Department of Oncology, University of Oxford, Oxford, OXON, United Kingdom

 
A poly-ethylene-glycol conjugated (PEGylated) form of nano-graphene oxide (NGO) was shown to target tumour xenografts, but its mechanism of tumour targeting is not elucidated yet. Here, we show that DCE-MRI proved a valuable tool to study the biodistribution and tumour delivery characteristics of radiolabelled nano-graphene oxide. Taken together, these results suggest that the tumour uptake of NGO-PEG depends heavily on tumour vascular density and permeability.

 
4380.   46 Big Hope from Small Particles: Challenges in Alzheimer's Disease
Houshang Amiri1,2, Morteza Mahmoudi3, Valerio Zerbi1,4, and Arend Heerschap1
1Department of Radiology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands, 2Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands, 3National Cell Bank, Pasteur Institute of Iran, Tehran, Iran, 4Department of Anatomy, Donders Centre for Neurosciences, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands

 
We have given a comprehensive overview of the current developments in Alzheimer's disease (AD) and focused on the most recent advances in the theranosis strategies using magnetic nanoparticles (MNPs). Functionalized MNPs also have been introduced as smart drug delivery systems. Finally we have discussed state-of-the-art in MRI to track MNPs over time with a special emphasis on the molecular/cellular imaging technique.

 
4381.   47 19F Magnetic Resonance Imaging: Technical Aspects
Houshang Amiri1,2, Mangala Srinivas2, Carl Figdor2, Jolanda de Vries2, and Arend Heerschap1
1Department of Radiology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands, 2Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands

 
We introduce 19F MRI and its advantages. We focus on the use of 19F MRI for molecular and cellular imaging and 19F signal quantification. The effect of hardware and RF coils; software, acquisition sequences and imaging parameters, on sensitivity are discussed. In particular we focus on the optimization of signal to noise acquired per unit time. The possible clinical application of 19F MRI will be addressed, together with safety concerns. This educational review endeavours to make the technical aspects of MRI, particularly 19F MRI, understandable to biologists and medical researchers.
 
4381A. 48 Molecular imaging in cell therapy: monocyte tracking and real-time evaluation of angiogenesis in ischemic limb by high resolution MRI
Jelena Kolosnjaj-Tabi1,2, Jose Vilar2, Nathalie Luciani1, Claire Wilhelm1, Gwennhael Autret2, Daniel Balvay2, Jean-Sebastien Silvestre2, Florence Gazeau1, and Olivier Clément2
1Paris-Diderot University, Laboratoire Matière et Systèmes Complexes, Paris, Ile de France, France, 2Paris Cardiovascular Research Center-PARCC / Paris-Descartes University, Paris, Ile de France, France

 
The effects of cellular therapy have been recognized long ago. However only recent advances in molecular imaging allow approaches that enable assessment of distribution and evaluation of regenerative effects of cells in vivo in real time. Here we describe a high-resolution MRI method performed at 4.7 T with a cryogenic probe, that allows detection and concomitant quantification of infiltration of magnetically labelled monocytes to ischemic murine paws and quantification of pro-angiogenic action of administered cells.