Traditional Poster Session - Molecular Imaging
  Novel Contrast Agents 1612-1622
  Targeted Contrast Agents 1623-1635
  Molecular Imaging of Cancer 1636-1645
  Cell Tracking & Reporter Genes: Approaches & Acquisitions 1646-1661
  Studies of Metabolism Using Hyperpolarized 13C - Methods 1662-1681
  Studies of Metabolism Using Hyperpolarized 13C - Metabolism 1682-1695

Novel Contrast Agents
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Tuesday 8 May 2012
Exhibition Hall  10:00 - 12:00

1612.   Novel Solid Lipid Nanoparticles (SLNs) Encapsulated with Gd-DOTA for Contrast-Enhanced MRI
Erica Marie Andreozzi1, Marc Dhenain2, and Angelique Louie1
1Biomedical Engineering, University of California, Davis, Davis, CA, United States, 2MIRCen, URA CEA CNRS 2210, Fontenay aux Roses, France

Herein, we report the encapsulation of Gadolinium-DOTA (Gd-DOTA) into solid lipid nanoparticles (SLNs) for use as a stable, long-circulating, biocompatible T1-weighted agent. We have confirmed that these Gd-loaded SLNs are stable in size and Gd content over time, and have previously shown that they have a longer blood half-life in mice compared to free Gd-DOTA. Relaxivity measurements (1.4 T, 37°C) of these Gd-loaded SLNs indicate an r1 value of ~2.5 mM-1sec-1 in vitro, and intracerebral ventricular (ICV) injection of the Gd-loaded SLNs in mice confirms the ability for these particles to provide positive contrast enhancement in vivo using T1-weighted imaging.

1613.   Synthesis and evaluation of a biodegradable macromolecular contrast agent containing macrocyclic Gd(III) chelates for cancer MRI
Zhen Ye1,2, Xueming Wu2, and Zheng-Rong Lu2
1Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT, United States, 2Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, United States

A neutral biodegradable polymeric MRI contrast agent containing macrocyclic Gd chelates, GOLS, were synthesized and evaluated for clinical contrast-enhanced MR imaging. The agent had higher relaxivity than clinical agents, and can be readily degraded. Kinetic stability study showed that this agent had significantly higher stability against transmetallation than polymer based on linear chelates. The contrast-enhancing efficacy of GOLS was evaluated on mice bearing orthotopic 4T1 breast tumor. Significantly higher tumor enhancement was generated by GOLS than clinical agents. This new agent is of great potential as a safe and effective contrast agent in contrast enhanced MRI.

1614.   New Bifunctional Chelates with Optimal Water Residence Times for Molecular Imaging
Erik C. Wiener1, Raghvendra Sengar2, Luce Vander Elst3, Marie-Caline Abadjian4, Curtis E Moore5, Arnold L Rheingold5, and Douglas Grotjahn6
1University of Pittsburgh, Pittsburgh, PA, United States, 2University of Pittsburgh, Johnstown, United States, 3General, Organic and Biomedical Chemistry, University of Mons, Mons, Belgium, 4San Diego State University, United States, 5University of California, San Diego, California, United States, 6San Diego State University, San Diego, California, United States

MRI offers the promise of molecular and cellular imaging by using exogenous or endogenous markers. Using exogenous stains requires suitable concentrations at the desired target by delivery of large numbers of paramagnetic or super paramagnetic ions, or a smaller number of more highly efficient agents. This report presents the syntheses of two new bifunctional Gd(III) chelates, with optimal water exchange rates, that can be coupled to other molecules using either click or peptide coupling chemistry. Nuclear magnetic relaxation dispersion experiments demonstrate 100% higher relaxivities then their slower exchange rate controls. Water residence times are measured using 17O NMR.

1615.   Reversible low-light induced photoswitching of a light sensitive magnetic resonance contrast agent
Klaus Kruttwig1, Diego R. Yankelevich2, Chantal Brueggemann3, Chuqiao Tu1, Erica Andreozzi1, Noelle L'Etoile3, André Knoesen2, and Angelique Y. Louie1
1Department of Biomedical Engineering, University of California Davis, Davis, CA, United States, 2Department of Electrical and Computer Engineering, University of California Davis, Davis, CA, United States, 3Center for Neuroscience, University of California Davis, Davis, CA, United States

The work performed here describes as a long term goal a method to noninvasively map gene expression in deep tissues in vivo by developing magnetic resonance contrast agents (MRI CA) that are responsive to commonly employed luminescent biomarker systems. Photoswitchable spiropyran has been conjugated to the crowned ring system DO3A complexed with the lanthanide ion Gadolinium(III). This leads to a photoresponsive MRI CA that displays an increased spin-lattice relaxation time (T1) upon visible light stimulation. The photo response of this contrast agent to weak light illumination using light emitting diodes was investigated, simulating the emission spectra from Gaussia princeps luciferase.

1616.   Gadolinium- and dysprosium-encapsulated single-walled ultra-short carbon nanotubes as intracellular agents for high field MR microscopy at 11.75 and 21.1 T
Jens T Rosenberg1,2, Micheal L Matson3,4, Brandon T Cisneros3, Michelle Sokoll2, Fabian Calixo-Bejarano1, Lon J Wilson3, 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, 3Department of Chemistry and The Smalley Institute for Nanoscale Science and Technology, Rice University, Houston, TX, United States, 4Natural Sciences, University of Houston-Downtown, Houston, TX, United States

Ultra-short, singled walled carbon nanotubes (US-tubes) that encapsulate gadolinium (Gd) have shown MRI cell tracking capabilities. Their biocompatibility together with a hollow interior and potentially beneficial water access are factors of interest especially at high magnetic fields. In this study, Gd-doped US-tubes are compared to a high field optimized, dysprosium (Dy) variant. Results suggest that doped US-tubes in solution follow theoretical field-dependent changes in relaxation for the two lanthanides. Once incorporated into cells, T1 contrast is quenched while T2 and T2* contrast dominates. Dy-doped US-tubes have overall shorter transverse relaxation times and compares favorably to other Dy-based agents.

Hyperpolarized silicon nanoparticles – Towards 29Si in-vivo imaging
Maja C. Cassidy1, Brandon D. Armstrong1, Henry R. Chan2, Brian D. Ross2, Pratip K. Bhattacharya2, and Charles M. Marcus1
1Harvard University, Cambridge, MA, United States, 2Huntington Medical Research Institutes, Pasadena, CA, United States


1618.   Multifunction nanocomposites based on fluorescent carbon and magnetic nanoparticles: An effective MR/fluorescence imaging probe
Rishi Awasthi1, Sachidanand Srivastava2, Namdeo S Gajbhiye3, Deepak Tripathi4, Mohit Kumar Rai4, Vikas Agarwal4, Vinita Agrawal5, and Rakesh Kumar Gupta1
1Radiodiagnosis, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India, Lucknow, Uttar Pradesh, India, 2Chemistry, Indian Institute of Technology, Kanpur, Lucknow, Uttar Pradesh, India, 3Chemistry, Indian Institute of Technology, Kanpur, Kanpur, Uttar Pradesh, India, 4Immunology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India, Lucknow, Uttar Pradesh, India, 5Pathology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India, Lucknow, Uttar Pradesh, India

A new type of MR/fluorescence multimodal imaging probe has been developed using fluorescent carbon nanomaterials and Fe3O4 (6 nm) magnetic nanoparticles. The prepared nanocomposite satisfies the primary conditions for both MR as well as fluorescence imaging: i.e (i) superparamagnetic nature; & (ii) wavelength tunable fluorescence properties with high fluorescence quantum yield (QY). The obtained results of in-vivo MR and fluorescence imaging strongly suggest that these multimodal imaging probes can be used as MR contrast agent and equally effective fluorescent biomarker. This novel and facile approach opens up a new route to design carbonaceous based multifunctional nanocomposites for various biomedical applications including various types of multimodal imaging as well as effective drug delivery systems and targeting agents.

Jing Huang1, Liya Wang1, Qiqi Yu1, Andrew Wang2, and Hui Mao1
1Radiology and Imaging Sciences, Emory University, Atlanta, GA, United States, 2Ocean Nanotech LLC, Springdale, Arkansas, United States

Milk protein (casein) coated iron oxide nanoparticles (CSIOs) are fabricated and investigated for potential MRI probes in molecular imaging. Due to the specific protein coating, these CSIOs have been demonstrated to have higher T2-weighted MRI contrast enhancement, as well as a wide range pH stability, compared with that of conventional polymer coated iron oxide nanoparticles.

1620.   Rapid dynamic PRF/Capital Greek DeltaT1/T2* monitoring for the characterization of heat-induced USPIO release from thermosensitive liposomes
Cyril Lorenzato1, Alexandru Cernicanu2, Baudouin Denis de Senneville1, Pierre Smirnov1, Marie-Edith Meyre3, Matthieu Germain3, Mario Ries1, and Chrit Moonen1
1Molecular and Functional Imaging: from Physiology to Therapy (IMF), Bordeaux, France, 2Philips Healthcare, Suresnes, France, 3Nanobiotix, Paris, France

Thermosensitive magnetoliposomes (TSM) can be prepared to contain drugs as well as super paramagnetic contrast agent. This would allow heat induced drug release, while detecting the release by simultaneously imaging relaxivity changes. Here, we propose a fast dynamic MRI method to simultaneously monitor temperature, T2*, and T1-changes in a gel doped with USPIO-charged TSM during heating. From a sigmoidal fit to the ∆T1 evolution the half-time of release at each voxel is obtained as well as estimate of the temperature of release, effectively characterizing the heat-induced release of USPIO from the TSM.

1621.   T1 modulation of CEST in a Eu(III)-DOTA-tetraamide-bis(nitroxyl) complex
James S Ratnakar1, Subha Viswanathan1, Matthew E. Merritt1, Chien-Yuan Lin1, A. Dean Sherry1, and Zoltan Kovacs1
1Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, Texas, United States

The CEST properties of a Eu(III)-DOTA-tetraamide complex having two covalently appended TEMPO (2,2,6,6-(tetramethylpiperidin-1-yl)oxyl) units can be turned on under reducing conditions due to the reduction of the paramagnetic TEMPO moieties to its diamagnetic hydroxylamine derivative.

1622.   Maintaining Hyper-CEST performance of a dye-labelled cryptophane cage
Federica Rossella1, Christopher Witte1, and Leif Schröder1
1Leibniz-Institut für Molekulare Pharmakologie (FMP), Berlin, Germany

Xenon biosensors are currently under development as a new type of contrast agent. They contain a molecular cage to temporarily trap the detected hyperpolarized 129Xe. To improve our understanding of their interaction with cells, fluorophore-labelled cages have been proposed. However, attachment of functional units like dyes may influence exchange dynamics and accessibility of the noble gas to its host, thereby potentially hampering the Hyper-CEST signal amplification technique that has been successfully applied to biosensor detection. Here, we present proof that a flexible linker between the cage and the dye ensures full Hyper-CEST performance as a prerequisite for future NMR studies.
Traditional Poster Session - Molecular Imaging

Targeted Contrast Agents
Click on to view the abstract pdf. Click on to view the poster (Not all posters are available for viewing.)
Tuesday 8 May 2012
Exhibition Hall  10:00 - 12:00

Magnetic resonance molecular imaging of atherosclerotic plaque in an atherosclerosis mouse model
Xueming Wu1, Niranjan Balu2, Wen Li1, Yong Chen1, Xin Yu1, Chun Yuan2, and Zheng-Rong Lu1
1Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, United States, 2Department of Radiology, University of Washington, Seatle, Washington, United States

This study designed, synthesized and evaluated a peptide-based low molecular weight MRI contrast agent specific to clotted plasma proteins for molecular imaging of atherosclerotic plaques with MRI. The atherosclerotic plaque imaging effectiveness of the targeted agent was demonstrated by using an atherosclerotic apolipoprotein E–deficient mouse model. Our preliminary results demonstrate that the newly developed targeted MRI contrast agent is promising for noninvasive assessment of plaque progression in an atherosclerotic mouse model.

1624.   Thrombin-Inhibiting Perfluorocarbon Nanoparticles Manifest Versatile Inhibition and Contrast for Thrombosis
Jacob Wheatley Myerson1, Li He2, John Stacy Allen2, Todd A Williams2, Douglas M Tollefsen2, Gregory M Lanza1,2, Shelton D Caruthers1, and Samuel A Wickline1,2
1Biomedical Engineering, Washington University in Saint Louis, Saint Louis, Missouri, United States, 2Medicine, Washington University in Saint Louis, Saint Louis, Missouri, United States

Perfluorocarbon nanoparticles functionalized for thombin inhibition with Bivalirudin or PPACK were tested as an inhibitor of thrombin in vitro and in acute thrombosis models. The particles significantly inhibited occlusive arterial thrombi. Via specific polyvalent binding to activated thrombin, the particles also manifested binding providing magnetic resonance contrast highlighting thrombi.

1625.   First in-vivo application of heparin-polynitroxide derivatives for labeling of vascular wall
Maxim Terekhov1, Kurt Reifenberg2, Alexander Scholz1, Stefan Weber1, Stefan Fischer1, Vasilyi Sen'3, Valery Golubev3, Thomas Münzel4, Andrei L Kleschyov4, and Laura Maria Schreiber1
1Section of Medical Physics, Radiology Department, University Medical Center Mainz, Mainz, Germany, 2Central Animal House, University Medical Center Mainz, Mainz, Germany, 3. Institute of Problems of Chemical Physics, Russian Academy of Sciences, Chernogolovka, Russian Federation, 4II-Department of Medicine, University Medical Center Mainz, Mainz, Germany

Cyclic nitroxides (CNR) are stable free radicals with multiple applications in MRI. Heparin is known to have a high affinity for the vascular extracellular structures. We propose that CNR could be delivered to the vascular wall by means of heparin-polynitroxide (HPR) derivatives where the nitroxide is linked with the heparin macromolecule. The first in-vivo studies show that high molecular HPN exhibits the long-lasting in-vivo life time and bind irreversibly to the inner layer of vascular wall, where they can be visualized both by EPR and MR techniques.

1626.   PECAM-1-targeted MPIO as a molecular MRI contrast agent for detection of vascular remodeling after experimental stroke
Lisette H. Deddens1, Geralda A. F. Van Tilborg1, Annette Van der Toorn1, Willem J. M. Mulder2, Helga E. De Vries3, and Rick M. Dijkhuizen1
1Biomedical MR Imaging and Spectroscopy Group, Image Sciences Institute, University Medical Center Utrecht, Utrecht, Netherlands, 2Translational and Molecular Imaging Institute, Mount Sinai School of Medicine, New York, United States, 3Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, Netherlands

Vascular remodeling is a key process in stroke pathophysiology and plasticity. This abstract reports on a novel targeted contrast agent for MRI-based detection of the expression of the vascular marker PECAM-1. PECAM-1 is constitutively expressed on endothelium and regularly used as a target for histological vessel staining. We demonstrate that PECAM-1 mRNA and protein expression were highly increased in ipsilesional vessels as early as 24h after stroke in mice. MPIO targeted to PECAM-1 bound specifically to murine endothelial cells and significantly shortened the T2 of these cell samples compared to cells incubated with IgG-MPIO. PECAM-1-targeted MPIO may therefore provide a promising molecular MRI contrast agent to detect early stage vascular modifications after stroke.

1627.   Micron-sized particles of iron oxide and gadolinium-containing liposomes as targeted contrast agent for molecular MRI of neuroinflammation after stroke: A comparative study.
Lisette H. Deddens1, Geralda A. F. Van Tilborg1, Annette Van der Toorn1, Leonie E.M. Paulis2, Gustav J. Strijkers2, Gert Storm3, Willem J. M. Mulder4, Helga E. De Vries5, and Rick M. Dijkhuizen1
1Biomedical MR Imaging and Spectroscopy Group, Image Sciences Institute, University Medical Center Utrecht, Utrecht, Netherlands, 2Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands, 3Biopharmacy and Pharmaceutical Technology, Utrecht University, Utrecht, Netherlands, 4Translational and Molecular Imaging Institute, Mount Sinai School of Medicine, New York, United States, 5Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, Netherlands

Molecular imaging of neuroinflammation after stroke is a challenging field. In this abstract we describe the comparison between two multivalent contrast agent platforms targeted to ICAM-1, i.e. gadolinium-loaded liposomes and micron-sized particles of iron oxide. Particles were injected 24h after experimental stroke in mice, and MRI was performed directly after injection and 24h thereafter. Both types of particles effectively targeted ICAM-1 under in vitro and in vivo conditions, but significant in vivo detection with MRI in post-stroke mouse brain was only achieved with ICAM-1-targeted MPIO. Our data advocate the use of targeted MPIO as most effective contrast agent platform for in vivo molecular MRI after stroke.

1628.   Diagnostic Technique of Rheumatoid Arthritis using Angiogenesis Specific MR Contrast Agents
Jang Woo Park1, Hui-jin Song1, Hee-Kyung Kim1, Jee Hye Seo1, Seong-Uk Jin1, Jong Su Baeck1, Moon Han1, Ji-Young Kim2, and Yongmin Chang3,4
1Department of Medical & Biological Engineering, Kyungpook National University, daegu, Korea, 2Department of School of Medicine, Kyungpook National University, daegu, Korea, 3Department of Diagnostic Radiology, Kyungpook National University, daegu, Korea, 4Kyungpook National University, Department of Molecular Medicine, daegu, Korea

Magnetic resonance imaging (MRI) allows the direct visualization of the bone and soft tissues and inflammatory activity. Angiogenesis is known to play a significant role in RA. We researched the inflammatory angiogenesis in RA using angiogenesis specific MR contrast agent, Gd-DOTA-RGD. Arginine-glycine-aspartic (RGD) peptide is well known to have a high specific affinity for ¥áv¥â3-integrin, which is over-expressed in endothelial cells during angiogenesis. Targeting and blocking experiments about ¥áv¥â3-integrin receptors were used to confirm integrin specific contrast enhancement of Gd-DOTA-RG. This study demonstrates the successful application of Gd-DOTA-RGD as a potential molecular MR agent for inflammatory disease such as RA with specificity to ¥áv¥â3-integrin receptor in the inflammatory angiogenesis.

1629.   Multifunctional Anionic Nanoparticles for the Targeted Delivery of Therapeutic Agents to the Brain for the Treatment of Dementias
Gavin D Kenny1,2, Alison Bienemann3, Katharina Welser4, Frederick Campbell4, Aristides D Tagalakis1, Mauro Botta5, Alethea B Tabor4, Ed White3, Mark F Lythgoe2, and Stephen L Hart1
1Molecular Immunology Unit ICH, UCL, London, United Kingdom, 2Centre for Advanced Biomedical Imaging, UCL, London, United Kingdom, 3Functional Neurosurgery Group, University of Bristol, Bristol, United Kingdom, 4Department of Chemistry, UCL, London, United Kingdom, 5Dipartimento di Scienze dell 'Ambiente e della Vita, Università del Piemonte Orientale "Amedeo Avogadro", Alessandria, Italy

Genetic therapies offer great promise for the development of new therapeutics in the CNS. One of the major obstacles to overcome is the inability to effectively bypass the BBB and deliver the therapeutic nucleic acids to the affected region. Nanoparticles are extensively used as delivery vectors for genes due to their biocompatibility and the protection they afford the gene and if administered using convection enhanced delivery the BBB can be circumvented. Here we have investigated the use of anionic nanoparticles, that are MR sensitive, contain labels for fluorescence microscopy/histology, in combination with a targeting peptide to mediate the functional delivery.

1630.   Liver Directing Uridine-based Paramagnetic Amphiphilic T1 MRI Contrast Agent with High Relaxivity
Hyunseung Lee1, Hyeyoung Moon1, Sankarprasad Bhuniya2, Jong Seung Kim2, and Kwan Soo Hong1,3
1Division of MR Research, Korea Basic Science Institute, Cheongwon-gun, Chungcheongbuk-Do, Korea, 2Department of Chemistry, Korea University, Seoul, Korea, 3Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon, Korea

The chelated Gd3+ metal ion improves imaging contrast by increasing the longitudinal relaxation time (T1) of proximal water protons, which appear brighter in the T1-weighted image. Current advanced medical diagnosis techniques stipulate high-resolution images with a high magnetic field scanner; however, current Gd3+-based contrast agents (CAs) ligated with polyamino carboxylate are incapable of meeting requirements as they do not have optimal relaxivity profiles at high magnetic fields.

1631.   Characterization of Heparin or Low Molecular Weight Heparin, Protamine Ferumoxytol Nanocomplexes for labeling of Stem Cells: Implications for translation to the clinic
Esmaeel Reza Dadashzadeh1,2, L. Henry Bryant Jr.3, Dana D. Dean1, Bobbi Lewis1, and Joseph A Frank1,4
1Frank Laboratory, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, Maryland, United States, 2Howard Hughes Medical Scholar, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, Maryland, United States, 3Laboratory of Diagnostic Radiology Research, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, 4Intramural Research Program, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health

A straight-forward method has been developed to label cells with self-assembling nanocomplexes (NC) that form by combining three FDA-approved agents: ferumoxytol (F), heparin (H) or fragmin (Fr), and protamine sulfate (P). HPF or FrPF NC self-assemble and flocculate over time and can be isolated by lyophilization to form solid NC. Lyophilization appears to stabilize NC based on the dynamic polydispersion profile (size and PDI) over the time-course of 24h. Intracerebrally implanted HPFL-labelled neural stem cells migrated to growing metastatic breast cancer in rat brain demonstrating the utility of this family of NC to label cells for use in cellular MRI.

1632.   Development of multimodal imaging probes for neuroanatomical connectivity studies in vivo by means of MRI
Ilgar Mamedov1, Joern Engelmann2, Gisela Hagberg1, Oxana Eschenko1, and Nikos K Logothetis1,3
1Physiology of Cognitive Processes, Max Planck Institute for Biological Cybernetics, Tuebingen, BW, Germany, 2High Field Magnetic Resonance Center, Max Planck Institute for Biological Cybernetics, 3Imaging Science and Biomedical Engineering, University of Manchester, Manchester, United Kingdom

A Gd3+ based paramagnetic dextran conjugate has been developed, which enables the tracking of neuroanatomical connectivity in the brain by both MR and optical imaging. Cell studies demonstrated that the synthesized tracer was efficiently internalized into neuronal cells and transported toward the axons. Furthermore, our preliminary in vivo experiments revealed efficient transportation of the conjugate, thereby proving its applicability for neuroanatomical studies by T1-weighted MRI. Initial in vivo experiments in rodents demonstrated the significant potential of this method.

1633.   Direct in vivo evidence of penetration of the Blood Brain Barrier with Nano-liposomes
Xiaoli X. Liu1, Achuthamangalam B. Madhankumar1, Patti A. Miller2, Kari A. Duck1, James R. Connor1, and Qing X. Yang2
1Neurosurgery, The Pennsylvania State College of Medicine, Hershey, PA, United States, 2Radiology, The Pennsylvania State College of Medicine, Hershey, PA, United States

A formulation liposome has been developed to encapsulate Gd-DTPA (Liposome-Gd) for targeted imaging of glioma. However, it is not clear whether Liposme-Gd is able to cross intact blood brain barrier (BBB) so that it can be used for detecting tumors at early stage when treatment is more effective. Our data obtained from normal mice with intact BBB demonstrated the first and direct evidence that liposome-Gd are capable of crossing BBB, which creates a great potential application in imaging of gliomas.

1634.   A prospective, Randomized, Blinded Study of MultiHance® on 1.5T and 3.0T Strength Field: An Evaluation of Brain, Optic Nerve and Spinal Cord Protocols in Multiple Sclerosis Patients
Robert Zivadinov1, Sara Hussein1, Cheryl Kennedy1, Niels Bergsland1, Christina Brooks2, and Michael G Dwyer1
1Buffalo Neuroimaging Analysis Center, Buffalo, NY, United States, 2Buffalo Neuroimaging Analysis Center

This was prospective, randomized, cross-over, blinded study that included 86 RRMS patients who underwent brain, 53 spinal cord and 40 optic nerve MRI exams at both 1.5T and 3.0T. The same scanning protocol was applied at two scanner field strengths (1.5T and 3.0T) after administration of MultiHance 0.1 mmol/kg body weight (injection, 529 mg/mL) with 5 min delay between injection and scanning. The use of a high relaxivity contrast agent, such as MultiHance at 3.0T field strength increases the diagnostic benefit in detecting enhancing lesions when compared intra-individually to the application of the same agent at 1.5 T.

1635.   Multifunctional Nanoparticles for the Monitoring and Assessment of Therapeutic Delivery
Gavin D Kenny1, Bhavana S Solanky2, Italo A Sanhueza3, Nicholas J Mitchell3, Frederick Campbell3, Katharina Welser3, Mauro Botta4, Alethea B Tabor3, Helen C Hailes3, and Mark F Lythgoe1
1Centre for Advanced Biomedical Imaging, UCL, London, United Kingdom, 2Institute of Neurology, UCL, London, United Kingdom, 3Department of Chemistry, UCL, London, United Kingdom, 4Dipartimento di Scienze dell 'Ambiente e della Vita, Università del Piemonte Orientale "Amedeo Avogadro", Alessandria, Italy

Nanoparticles are widely used as therapeutic delivery vectors in a wide range of diseases, due to their versatility. However, accurate monitoring of distribution is challenging using current techniques. Here, we have investigated the use of a novel fluorinated peptide incorporated into a nanoparticle for the monitoring of distribution and assessment of therapeutic delivery by taking advantage of the lack of endogenous 19F signal
Traditional Poster Session - Molecular Imaging

Molecular Imaging of Cancer
Click on to view the abstract pdf. Click on to view the poster (Not all posters are available for viewing.)
Tuesday 8 May 2012
Exhibition Hall  10:00 - 12:00

1636.   Anti-HER2 Antibody and scFv of EGFR Conjugated ¡°Stealth¡± Magnetic Iron Oxide Nanoparticles for Targeting and Magnetic Resonance Imaging of Breast Cancer
Hongwei Chen1,2, Qiqi Yu1,3, Liya Wang1,2, Weiping Qian4, Zehong Cao4, Lily Yang4, and Hui Mao1,2
1Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, United States, 2Center for Systems Imaging, Emory University School of Medicine, Atlanta, Georgia, United States, 3Center for Systems Imaging, Emory University School of Medicine, Atlanta, GA, United States, 4Surgery, Emory University, Atlanta, GA, United States

Magnetic iron oxide nanoparticles (IONPs) coated with block copolymer poly(ethylene oxide)-block-poly(¦Ã-methacryloxypropyltrimeth oxysilane) (PEO-b-P¦ÃMPS) that exhibit a long blood circulation time (t1/2 = 12 h) in mice and low accumulation in both the liver and spleen. Conjugation of a HER2 antibody, or a single chain fragment (scFv) of antibody against epidermal growth factor receptor (scFvEGFR) to PEO-b-P¦ÃMPS coated IONPs (anti-HER2-IONPs or scFvEGFR-IONPs) results in HER2 or EGFR-targeted IONPS which specifically bind to HER2 over-expressing breast cancer cell line SK-BR-3 or EGFR positive MDA-MB-231 cells. Both antibody-conjugated and non-conjugated IONPs avoid non-specific uptake by mouse macrophages in vitro. Magnetic resonance imaging (MRI) of the mice bearing EGFR positive human breast cancer xenografts 24 h after systemic administration of scFvEGFR-IONPs led to signal reduction in tumors as the result of accumulation of the targeted IONPs and IONP induced transverse relaxation T2 weighted contrast.

1637.   Phytate-Complex as a Novel MRI Agent for Tumor Associated Macrophage (TAM)-specific Image Contrast and Drug Delivery
Hyeonjin Kim1, and Byung-Chul Oh2
1Radiology, Seoul National University Hospital, Seoul, Seoul, Korea, 2Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Korea

Tumor-associated macrophages (TAMs) accumulate in various cancers and promote tumor angiogenesis and progression, and thus might be ideal imaging targets for non-invasive detection of tumors with high specificity. Here, we developed an iron-calcium-phytate complex (ICPC) as an MRI agent that specifically targets TAMs. Beyond the capability of current TAM imaging methods, which is limited to visualization of TAMs, an ICPC variant was also developed by combining ICPC with an anticancer drug, Doxorubicin (Dox@ICPC). Our preliminary data strongly support that the novel antitumor MR agent, Dox@ICPC, may potentially achieve both TAM-specific MR imaging and tumor-specific drug delivery simultaneously.

1638.   CEST imaging of particle-based therapy for cervical tumors
Kannie WY Chan1,2, Tao Yu3, Guanshu Liu1,4, Ming Yang5, Assaf A Gilad1,2, Jeff WM Bulte1,2, Peter CM van Zijl1,4, Justin Hanes3,5, and Michael T McMahon1,4
1Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States, 2Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, Baltimore, MD, United States, 3Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, United States, 4F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, 5Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United States

Nanoparticle-based local drug treatment has potential for chemotherapy for cervical tumors, but there is a need for real time in vivo imaging of the particle delivery to monitor therapeutic efficacy. We are interested in using Chemical Exchange Saturation Transfer (CEST), a molecular MRI contrast mechanism, to monitor the vaginal delivery of drug-loaded nanoparticles to treat local cervical tumors by co-encapsulating CEST contrast agents and drugs within liposomes. The goal is to image the distribution of these particles and to indirectly assess the retention of drugs over the course of treatment.

1639.   Passively masked surface charge of SPIO nanoparticles for specific detection of EGFR expressing tumor cells
Yun-Ming Wang1, Shou-Cheng Wu2, and Jia-Gong Lin3
1Department of Biological Science and Technology, National Chiao Tung University, HsinChu, Taiwan, 2Department of Biological Science and Technology, National Chiao Tung University, Taiwan, 3National Chiao Tung University, Taiwan

In this study, a facile approach for the passive masking of non-conjugated reactive amine groups on the surface of iron oxide nanoparticles is demonstrated. The usefulness of this strategy has been exemplified by EGFR specific MR-optical imaging agent (SPIO-mAb-FITC NPs). The TEM and confocal image shows that the passive masking of reactive groups enhances the targeting efficacy of the imaging agent.

1640.   A hydroxyapatite-targeted gadolinium contrast agent for MRI of breast cancer microcalcifications
Jonathan Marmurek1, Elaine Lunsford2, Elena Vinogradov2,3, Khaled Nasr2, Fangbing Liu2, Ananth J. Madhuranthakam4, John V. Frangioni2,5, and Robert E. Lenkinski3
1Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, United States, 2Beth Israel Deaconess Medical Center, Boston, MA, 3UT Southwestern Medical Center, Dallas, TX, 4Global Applied Science Laboratory, GE Healthcare, Boston, MA, 5Harvard Medical School, Boston, MA

Clinical x-ray mammography cannot delineate hydroxyapatite (HA) and calcium oxalate (CO), the respective forms of microcalcification in malignant and benign breast cancer. We present the first in-vivo MRI of an HA-targeted gadolinium contrast agent. Pre- and post-contrast MRI using ultra-short echo times (UTE) showed that the contrast agent had a 4.3-fold relative specificity for HA over CO when delivered systemically to subcutaneous crystal implants in mice. UTE MRI of a breast cancer model in rats showed that the HA-targeted contrast agent produced a signal intensity enhancement greater than 200% in tumor calcifications.

1641.   A bacteriophage-based hyperpolarized 129Xe MRI contrast agent targeting the EGF receptor in mammalian cells
Richard Matthew Ramirez1,2, Krishnan K Palaniappan1, David E Wemmer1,3, Matthew B Francis1,2, and Alex Pines1,2
1Department of Chemistry, University of California, Berkeley, CA, United States, 2Materials Science Division, Lawrence Berkeley National Laboratory, Berkeley, CA, United States, 3Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, United States

A hyperpolarized Xe molecular sensor capable of targeting specific cell types is presented. The sensor agent is composed of multiple cage-like cryptophane molecules attached to a bacteriophage which can then be targeted. This particular agent incorporated an anti-EGFR moiety and was successfully bound by EGFR-positive MDA-MB-231 cells, but not by Jurkat cells which do not express the EGF receptor. Presence of the agent is detected using a hyperCEST scheme.

1642.   Development and In-vivo Magnetic Resonance Imaging of Polymer Micelles Targeted to the Melanoma-Specific Marker MC1R
Natalie M Barkey1, Christian Preihs2, Heather H Cornnell1, Gary Martinez3, Kevin N Sill4, Adam Carie4, Josef Vagner5, Jonathan L Sessler2, Robert J Gilles1, and David L Morse1
1Molecular and Functional Imaging, Moffitt Cancer Center, Tampa, FL, United States, 2Department of Chemistry and Biochemistry, University of Texas at Austin, Austin, TX, United States, 3Small Animal Molecular Imaging, Moffitt Cancer Center, Tampa, FL, United States, 4Intezyne Technologies, Inc, Tampa, FL, United States, 5The Bio5 Institute, University of Arizona, Tuscon, AZ, United States

Rationally-designed, polymer-based micelle carriers offer a promising approach to the delivery of therapeutic and/or diagnostic payloads. We have described the synthesis and characterization of MC1R targeted triblock polymer micelles with encapsulated Gd-texaphyrin and Fe(III) crosslinking for stabilization. These micelles selectively target MC1R-expressing melanoma xenograft tumors in vivo. Tumor uptake is not observed with untargeted or unstabilized control micelles. These agents biodegrade and clear systemically without retention in kidney or liver. To the best of our knowledge, this represents the first report of a targeted micelle system that selectively accumulates in the tumor relative to other tissues.

1643.   MR/optical image-guided two-component nano-delivery systems targeting Her2/neu overexpressing cancer cells
Sudath Hapuarachchige1, Wenlian Zhu2, Yoshinori Kato2, and Dmitri Artemov3
1Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, 2The Johns Hopkins University School of Medicine,3Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MARYLAND, United States

The overexpression of Her2/neu leads to the poor prognosis in human breast cancer. The affinity of the cancer therapeutics can be increased by the synergistic drug delivery by controlled internalization. The mouse models were injected with modified herceptin, followed by secondary component. T1 images were and optical images of the mice were obtained. In vivo optical shows the retention of cargo-carrier on tumor-site due to the "click" chemistry (followed by possible internalization) with respect to the control, without PEG4-Az on Herceptin). MRI imaging exhibits the drop of T1, showing the possible non-invasive image-guided prognosis and translational cancer therapy.

1644.   I/125I-RGD-DOTA-Gd as a Potential lower case Greek alphalower case Greek nulower case Greek beta3 -integrin Targeting Dual MRI/SPECT Agent
Ji-Ae Park1, Jung Young Kim1, Wonho Lee1, In Ok Ko1, Sang-Keun Woo1, Jong Guk Kim1, Joo Hyun Kang1, Sang Moo Lim2, Yongmin Chang3, Tae-Jeong Kim4, and Kyeong Min Kim1
1Molecular Imaging Research Center, Korea Institute of Radiological & Medical Science, Seoul, Nowon-gu, Korea, 2Department of Nuclear Medicine, Korea Institute of Radiological & Medical Science, 3Department of Medical & Biological Engineering, Kyungpook National University, 4Department of Applied Chemistry, Kyungpook National University

We report tumor targeting RGD conjugate Gd complex for MRI/SPECT dual imaging based on isostructural I/125I-RGD-DOTA-Gd to be a potential multimodal imaging probe. To develop a MR/SPECT dual imaging probe, YKRGD amino acids were modified with iodo-tyrosine, resulting in (iodo)YKRGD. For MR imaging agent, Gd-DOTA conjugates to (iodo)YKRGD of the type I-YKRGD-DOTA-Gd have been prepared. For SPECT imaging radioisotope, I-125, was labeled to tyrosine resulting in 125I-YKRGD-DOTA-Gd. The chemical and structural equivalence of I-YKRGD-DOTA-Gd and 125I-YKRGD-DOTA-Gd can be confirmed by HPLC. In vivo MR and SPECT imaging of tumor-bearing mice, these complexes show high specificity for ¥á¥í¥â3 receptor. These result revealed that the I/125I-RGD-DOTA-Gd would be an attractive entry into tumor-targeting dual MRI/SPECT agent.

1645.   Development of multifunctional magnetic nanoparticles for specific and early diagnosis of pancreatic cancer
Yun-Ming Wang1, Shou-Cheng Wu2, and Gyan Singh3
1Department of Biological Science and Technology, National Chiao Tung University, HsinChu, Taiwan, 2Department of Biological Science and Technology, National Chiao Tung University, Taiwan, 3National Chiao Tung University, Taiwan

A highly sensitive and specific dual modality T2 weighted MR-optical imaging agents (SPIO-mAb-Cy777 NPs) has been synthesized. The SPIO NPs and Cy777 serves as MR enhancer and NIR optical imaging dye respectively. The anti-MUC4 mAb has been used as targeting moiety to target MUC4 receptor which is exclusively expressed in pancreatic cancer. An ex-vitro and in vitro experiments shows significant negative contrast enhancement in MUC4 positive cell line, on the contrary contrast enhancement was not observed in MUC4 negatively expressed cell. Therefore, we can conclude that the SPIO-mAb-Cy777 NPs can specifically target MUC 4 receptor and can be potentially used as tool for the detection of pancreatic cancer with high specificity and sensitivity.

Traditional Poster Session - Molecular Imaging

Cell Tracking & Reporter Genes: Approaches & Acquisitions
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Tuesday 8 May 2012
Exhibition Hall  10:00 - 12:00

1646.   Genetically encoded biosensor for detecting Protein Kinase A (PKA) activity using CEST MRI
Raag D. Airan1,2, Amnon Bar-Shir1,2, Guanshu Liu1,3, Michael T. McMahon1,3, Galit Pelled1,3, Peter C.M. van Zijl1,3, Jeff W.M. Bulte1,2, and Assaf A. Gilad1,2
1Department of Radiology and Radiological Sciences, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States, 2Cellular Imaging Section, Institute for Cell Engineering, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States, 3F.M. Kirby Research Center for Functional Imaging, Kennedy Krieger Institute, Baltimore, Maryland, United States

Protein kinases, such as Protein Kinase A (PKA), underlie myriad clinically important signaling pathways. We developed a genetically encoded molecular MRI biosensor for detecting real-time PKA activity dynamics. This biosensor uses chemical exchange saturation transfer (CEST) MRI and its advantages over traditional molecular imaging techniques for detecting organic metabolite activity dynamics. We find that PKA phosphorylation of the biosensor resulted in a >50% modulation of its baseline CEST contrast, with near 250 µM discrimination sensitivity and minutes temporal resolution in vitro. CEST contrast change with phosphorylation likely results from coordination of CEST-contrast generating residues by the negatively-charged phosphate group.

Tracking stem cells in a inherently regenerative environment
Henrik Lauridsen1, Casper Foldager2, Mette Hagensen3, Tobias Wang4, and Michael Pedersen5
1MR-Research Centre, Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark, Denmark, 2Department of Othopaedics, Aarhus University, Denmark, 3Department of Cardiological Mecicine, Aarhus University, Denmark, 4Department of Biological Sciences, Aarhus University, Denmark, 5MR-Research Centre, Institut of Clinical Medicine, Aarhus University, Denmark

Tissue regenerative capacity in humans is very limited. However, there exist model animals in zoology expressing impressive regenerative potential inspiring for future breakthroughs in regenerative medicine. One such model organism is the axolotl, capable of regenerating various tissues, organs and even whole appendages. This study incorporates the expanding field of super paramagnetic iron oxide particle (SPIO) guided MRI evaluation of stem cells therapies with an intrinsic regenerative environment, the regenerating axolotl limb. This has the potential both to allow for a better regenerative model for development of SPIO’s for non-invasive use as well as revealing the mechanisms behind axolotl regeneration.

1648.   Ferritin-N6A as an improved reporter gene for MRI
Marina Radoul1, Batya Cohen1, Moriel Vandsburger1, Raz Zarivach2, and Michal Neeman1
1Biological Regulation, Weizmann Institute of Science, Rehovot, Israel, 2Department of Life Sciences, Ben Gurion University, Israel

Ferritin is a main iron storage intracellular protein which has recently proposed as MRI reporter gene due to paramagnetic ferrihydrate in its core. However, it has low R2 relaxivity and thus provides relatively low sensitivity. In this study, we have designed a recombinant fusion ferritin-N6A to facilitate conversion of ferrihydrate into magnetite and by this induce MRI contrast.

1649.   Visualization of SPIO labeled mesenchymal stem cells in knee joints by R2* mapping
Ramon Van der Werf1, Gerben M. Van Buul1, Henk Smit1, Gavin C. Houston2, Gabriel P. Krestin1, Stefan Klein3, Gerjo J.V.M. Van Osch4, Monique R. Bernsen1, and Gyula Kotek1
1Radiology, Erasmus Medical Centre, Rotterdam, Zuid Holland, Netherlands, 2General Electric Healthcare, Hoevelaken, Gelderland, Netherlands, 3Medical Informatics, Erasmus Medical Centre, Rotterdam, Zuid Holland, Netherlands, 4Orthopaedia, Erasmus Medical Centre, Rotterdam, Zuid Holland, Netherlands

Tracking of stem cells is highly desirable to obtain insight into mechanisms of stem cell based therapies. In the region of the knee, tracking of SPIO labeled cells is hampered by low hydrogen spin density. We show a voxel-based R2* mapping method to visualize a single voxel broad layer of stem cells attached to several structures in knee joints (voxelsize: 26 x 26 x 500 lower case Greek mum3) that are not detectable by looking at signal voids employing conventional MR methods.

1650.   Study on the Single Cell Detectability as the Concentration of Contrast Agent
Jee-Hyun Cho1,2, Janggeun Cho1,2, Sangdoo Ahn2, and Chulhyun Lee1
1Magnetic Resonance Research, Korea Basic Science Institute, Ochang, Cheongwon, Korea, 2Chemistry, Chung-Ang University, Seoul, Korea

In this study, to numerically evaluate how to change the detectability and image-contrast depending upon the concentration of contrast agents, we systematically compared the fractional signal losses of iDQC, EPI, and GE images of single cells labeled with different iron concentrations. The iDQC images visualized labeled cells more effectively and with a higher contrast-to-noise ratio than conventional EPI and GE images, especially at low resolutions and low iron concentration in cell.

1651.   In vivo Molecular MRI of GFP/Ferritin Dual Gene Expression
Xiang Nan1,2, Anna V Naumova3, Jianmin Wei2, Qian Wan1, Lin Gao1, Xin Liu1, and Bensheng Qiu1,3
1Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedical and Health Enginee, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, China, 2Inner Mongolia Agricultural University, Huhhot, Inner Mongolia, China, 3Radiology, University of Washington School of Medicine, United States

In this study, we aimed to develop a reliable method to monitor the gene expression or therapy in vivo, non-invasively. We first utilized optical imaging to assess EP-mediated transgene expression in vitro, and then we next constructed a dual mammalian expression vector also carrying a murine ferritin gene, the vector can provide us to monitor the gene expression in vivo by magnetic resonance imaging scanner. DNA was transfected into mouse muscle by electroporation. We succeeded in imaging transgene expression of marine ferritin reporter gene by MR, and further study is going on.

1652.   Anysotropic relaxivity measurements of solubilized multiwall carbon nanotubes suspensions reveal molecular orientation.
Daniel Calle1, Viviana Negri2, Arisbel Cerpa3, Pilar López-Larrubia1, Paloma Ballesteros2, and Sebastián Cerdán1
1Departamento de Modelos Experimentales Humanos, Instituto de Investigaciones Biomédicas "Alberto Sols", CSIC, Madrid, Madrid, Spain, 2Laboratory of Organic Synthesis and Molecular Imaging by Magnetic Resonance, Faculty of Sciences, UNED, Madrid, Madrid, Spain, 3Universidad Europea de Madrid, Madrid, Madrid, Spain


1653.   Assessment of Early Vascular Response Under Abraxane Therapy Using DCE-MRI and 18F-FPPRGD2 PET
Xilin Sun1, Dan Wang1, and Baozhong Shen1
1The Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang, China

The mechanism of action of Abraxane is complex, and some reports exist that Abraxane triggers reactionary angiogenesis. Our previous studies had shown some alterations of tumor vessels from immature to mature in morphological and molecular characteristics by Abraxane, and the integrin-specific PET tracer 18F-FPPRGD2 (investigational new drug 104150) can noninvasive monitoring the integrin avb3 level. The purpose of this study is to further investigate a comprehensive vascular response (molecular level and functional such as permeability and penetration) during Abraxane therapy with combined dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and 18F-FPPRGD2 PET.

1654.   A matrigel-based lipopolysaccharide release model to evaluate the versatility of different MRI approaches for detection of inflammation
Sebastian Temme1, Christoph Jacoby1, Zhaoping Ding1, Florian Bönner1, Nadine Borg1, Jürgen Schrader1, and Ulrich Flögel1
1Molecular Cardiology, Heinrich Heine University, Düsseldorf, NRW, Germany

In the present study, we developed a standardized matrigel-based LPS-release model of local inflammation suitable for MRI approaches. We demonstrate that matrigel itself can be visualized by conventional 1H MRI and that LPS induced inflammation resulted surprisingly in a decreased T2-relaxation time in the matrigel plug. Furthermore, inflammation in the plug was specifically detected by 19F MRI and the intensity of the 19F signal correlated with the LPS dose. These findings suggest that the matrigel-LPS model is a reproducible and quantitative method for evaluation of specificity and sensitivity of MRI methods used for imaging of inflammation in vivo.

1655.   Quantitative Molecular Imaging of Fluorinated Agents: 19F Flip Angle Calibration Using 1H Power Settings
Matthew J Goette1, Gregory M Lanza1, Samuel A Wickline1, and Shelton D Caruthers1
1School of Medicine, Washington University in St. Louis, St. Louis, MO, United States

This study presents a strategy to more accurately quantify the sparse 19F signal from perfluorocarbon nanoparticle emulsions through flip angle calibration utilizing the abundant 1H signal. We hypothesize that the RF power settings optimized for 1H can be used to determine the correct RF power settings for the 19F signal acquired with19F/1H dual-tuned coils on a 3 T clinical scanner. Flip angle sweep experiments using two types of dual-tuned coils were performed, which showed that a coil-specific, but spatially-independent calibration value can be determined to set the correct 19F power settings using the 1H signal.

1656.   Evaluation of lung metastatic tumor using Dextran-DTPA-Mn nanoprobes with ultra-short echo-time imaging
Daisuke Kokuryo1, Jun-ichiro Jo1, Tsuneo Saga1, and Ichio Aoki1
1Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Chiba, Japan

A newly developed manganese-nanoprobe (Dextran-DTPA-Mn) and three-dimensional ultra-short echo-time (UTE) imaging was applied to evaluate a lung metastatic tumor model. Comparison was made with a conventional Gd-DTPA contrast-agent as a control. The Dextran-DTPA-Mn signal in the lung parenchyma increased immediately after administration and was thereafter maintained for 24 hours. The tumor region in lung parenchyma was enhanced by the accumulation of Dextran-DTPA-Mn. The Dextran-DTPA-Mn with UTE imaging will allow optimized chemotherapy using tumor-targeting nanoprobes.

1657.   Towards MRI Measurement of Magnetic Particle Spacing at Micron Dimensions
Stephen Dodd1, Gary Zabow1, and Alan Koretsky1
1Laboratory of Functional and Molecular Imaging, NINDS, National Insitutes of Health, Bethesda, MD, United States

A method to measure the distance between two magnetic particles at high spatial resolution is presented. Microfabrication is used to make an array of particles at different separations with high precision. Gradient-echo MR images are acquired with 4x higher spatial resolution in the direction of the particle spacing and using phase maps the distance between particles can be measured down to the level of a pixel.

1658.   Phase Contrast MR Microscopy to Study Glioma Invasion in Vivo at High Field
Nicoleta Baxan1, Stella Maria Carro2, Roberto Ferrarese2, Dominik von Elverfeldt1, Markus Bredel2,3, and Wilfried Reichardt1
1Department of Radiology, University Medical Center Freiburg, Freiburg, BW, Germany, 2Department of Neurosurgery, University Medical Center Freiburg, Freiburg, BW, Germany, 3Department of Radiation Oncology, University of Alabama, Birmingham, United States

As the brain is composed of a variety of cell type that vary strongly according to their anatomical location, an accurate assessment of the implantation site plays an important role in the investigation of growth characteristics and physiology of tumors. This study was performed to determine to what extend high-resolution MR microscopy enables to accurately determine the early fate of implanted glioma cells and the injection tract under in vivo conditions. The presented approach based on the MR signal phase can be an efficient alternative to replace the need of cell labeling that might potentially alter cellular characteristics.

1659.   B1 Correction for Quantitative in vivo 19F Magnetic Resonance Imaging with Surface Coils
Philipp Böhm-Sturm1, Eberhard D. Pracht1, Markus Aswendt1, Nadine Henn1, and Mathias Hoehn1
1In-Vivo-NMR, Max-Planck-Institute for Neurological Research, Cologne, Germany

19F MRI has recently received much attention, especially in the field of cell tracking. One of the main advantages of 19F MRI is that it is possible to quantify the number of cells. However, this only holds for the use of volume coils with a homogeneous B1 field for both transmission and reception. Here we present a workflow that allows quantitative 19F MRI with surface coils by mapping the B1 field on the 1H channel and subsequent correction of 19F data by post-processing. Our work may resolve an inherent conflict of sensitivity vs. quantification in coil design for 19F MRI.

1660.   Heteronuclear proton MRI: In vivo detection of Tm-DOTMA labeled HT-1080 cells using ultra-short echo time imaging (UTE)
Klaus Strobel1, Rabecca Schmidt1, Carsten Höltke1, and Cornelius Faber1
1University Hospital Münster, Münster, Germany

Unambiguous MRI detection of labeled cells often uses 19F, because fluorine has no natural background in the images. However, 19F MRI requires dedicated hardware. Alternatively, Tm-DOTMA, which has twelve methyl protons with a chemical shift of 100 ppm, may be used to obtain background free proton images. In this work, we have implemented an ultra-short echo time (UTE) imaging sequences to obtain optimal SNR-efficiency with labeled HT-1080 cells that were injected subcutaneously into the flank of mice. We show that Tm-DOTMA labeled cells can be imaged in vivo without significant water background signal.

1661.   In vivo magnetic resonance imaging beyond the MT window using SWIFT-CEST and a Tb-based PARACEST contrast agent
Todd C. Soesbe1, Federico A. Rojas-Quijano1, and A. Dean Sherry1,2
1Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, TX, United States, 2Department of Chemistry, The University of Texas at Dallas, Dallas, TX, United States

We have recently shown for Eu3+-based PARECEST agents that the same water molecule exchange that enables the CEST effect can also facilitate severe bulk water line broadening via the T2-exchange (T2ex) mechanism. T2ex can significantly reduce the bulk water T2 (i.e. negative contrast) even without spin saturation, causing the PARACEST agent to behave like a susceptibility or T2 agent. This makes “Off” minus “On” imaging of PARACEST agents difficult since the regions of uptake appear dark in both images. We have also recently shown that the ultra-short TE times (<10 μs) used in the Sweep Imaging with Fourier Transform (SWIFT) pulse sequence can reclaim the loss in signal due to T2ex to enable fast and sensitive in vivo PARACEST imaging using simple “Off” minus “On” image subtraction. Here, we use the same SWIFT-CEST method to image a Tb3+-based PARACEST agent in vivo.
Traditional Poster Session - Molecular Imaging

Studies of Metabolism Using Hyperpolarized 13C - Methods
Click on to view the abstract pdf. Click on to view the poster (Not all posters are available for viewing.)
Tuesday 8 May 2012
Exhibition Hall  10:00 - 12:00

Frequency-specific SSFP imaging of hyperpolarized 13C compounds at 14.1T
Cornelius von Morze1, Subramaniam Sukumar1, Galen Reed1, Peder E Larson1, John Kurhanewicz1, and Daniel B Vigneron1
1Department of Radiology and Biomedical Imaging, UCSF, San Francisco, California, United States

The spectral selectivity of SSFP in the low flip angle regime enables frequency-specific imaging of hyperpolarized 13C compounds. Through simulations, we optimized the acquisition parameters for dynamic frequency-specific SSFP imaging of co-polarized [1-13C]pyruvate and [13C]urea, which is useful for studying tumor metabolism and perfusion in vivo. We implemented the methods as a dynamic frequency-cycled bSSFP pulse sequence on a 14.1T animal MRI scanner. We performed thermal and hyperpolarized phantom studies to test the acquisition, and performed in vivo dynamic imaging of a normal mouse kidney.

1663.   Saturation-Recovery Metabolic Exchange Rate Imaging with Hyperpolarised [1-13C]Pyruvate using Spectral-Spatial Excitation
Rolf F Schulte1, Jonathan I Sperl1, Eliane Weidl2, Marion I Menzel1, Martin A Janich1,3, Oleksandr Khegai1,3, Markus Durst1,4, Jan Henrik Ardenkjaer-Larsen5,6, Steffen J Glaser3, Axel Haase4, Markus Schwaiger2, and Florian Wiesinger1
1GE Global Research, Munich, Germany, 2Nuclear Medicine, TU Munich, Germany, 3Chemistry, TU Munich, Germany, 4IMETUM, TU Munich, Germany, 5GE Healthcare, Copenhagen, Denmark, 6Electrical Engineering, Technical University of Denmark, Copenhagen

Hyperpolarised [1-13C]pyruvate is enzymatically converted into lactate, alanine and bicarbonate. In this work, a metabolic exchange rate mapping approach is presented for quantifying metabolic activity. It based on a spectral-spatial excitation of the metabolites combined with a saturation of the downstream metabolites and subsequent recovery due to fresh conversion from pyruvate. Various improvements were made to the spectral-spatial pulse design, the spiral readout and other sequence parameters. The saturation-recovery metabolic exchange rate imaging approach was demonstrated in four rats bearing subcutaneous MAT B III tumours.

1664.   Producing radical-free hyperpolarized solutions for in vivo magnetic resonance
Tian Cheng1, Mor Mishkovsky2,3, Matthias Junk4, Dariush Hinderberger4, Kerstin Münnemann4, and Arnaud Comment1
1Institute of Physics of Biological Systems, École Polytechnique Fédérale de Lausanne, Lausanne, VD, Switzerland, 2Department of Radiology, Université de Lausanne, Lausanne, VD, Switzerland, 3Laboratory for Functional and Metabolic Imaging, École Polytechnique Fédérale de Lausanne, Lausanne, VD, Switzerland, 4Max Planck Institute for Polymer Research, Mainz, Germany

Dissolution dynamic nuclear polarization allows achieving tremendous gain in signal-to-noise ratio in nuclear magnetic resonance experiments. Once the polarized sample is dissolved, the stable radicals used as polarizing agents become undesirable since their presence is an additional source of nuclear spin relaxation and their toxicity might be an issue. We demonstrate here that by using spin-labeled thermoresponsive hydrophilic polymer networks it is possible to prepare hyperpolarized solutions free of stable radicals immediately after dissolution. We applied this method to hyperpolarize 13C-labeled tert-butanol which has been recently shown to be a promising contrast agent for perfusion imaging.

1665.   Parallel Spiral Chemical Shift Imaging for Metabolic Imaging with Hyperpolarised 13C
Markus Durst1,2, Rolf F. Schulte2, Franz Schilling1, Eliane Weidl3, Oleksandr Khegai2,4, Martin A. Janich2,4, Jonathan I. Sperl2, Ulrich Koellisch1, Florian Wiesinger2, Markus Schwaiger3, and Axel Haase1
1IMETUM, Technische Universität München, Munich, Bavaria, Germany, 2GE Global Research, Munich, Bavaria, Germany, 3Department for Nuclear Medicine, Technische Universität München, Munich, Bavaria, Germany, 4Department of Chemistry, Technische Universität München, Munich, Bavaria, Germany

Imaging hyperpolarised compounds requires rapid acquisition methods due to irreversible T1 decay of the magnetisation. In this work, parallel imaging is used to improve the spatial resolution and spectral width of spiral chemical shift images of healthy rats in-vivo after injection of hyperpolarised [1-13C]pyruvate. An interleaved spiral PMRI sequence specifically designed for the requirements of hyperpolarised chemical shift imaging is presented. The results are in good agreement with a proton GRE anatomical reference image and the metabolic images show high SNR and similar distribution of metabolites as compared to a fully sampled reference measurement from a second injection.

1666.   Cluster Formation in Solid-state Mixtures Restricts DNP of 129Xe
Nicholas N. Kuzma1, Huseyin Kara1,2, Mehrdad Pourfathi1, Philip Manasseh3, Jan H. Ardenkjær-Larsen4, Stephen J. Kadlecek1, and Rahim R. Rizi1
1Radiology, University of Pennsylvania, Philadelphia, PA, United States, 2Astronomy and Physics, University of Pennsylvania, Philadelphia, PA, United States, 3Department of Chemistry, Earlham College, Richmond, IN, United States, 4GE Healthcare, Brøndby, Denmark

At 1.5K and 5T, 129Xe NMR spectra of a homogeneous xenon/1-propanol/trityl-radical mixture exhibit a single 1H-broadened peak. Another peak appears upon 4-hour annealing at 125K. Its characteristic width and chemical shift indicate spontaneous formation of pure Xe clusters. Microwave irradiation can bring both peaks to either positive or negative polarization. Time evolution of DNP in pure Xe clusters can be understood in terms of spin diffusion and T1 relaxation. Our data can be used to evaluate major DNP parameters in situ, revealing a severe spin-diffusion bottleneck at the cluster boundaries and a significant sample overheating due to microwave irradiation.

1667.   Improved evaluation of (Hyper-)CEST images using the spectral dimension
Jörg Döpfert1, Christopher Witte1, Martin Kunth1, Michael Beyermann1, and Leif Schröder1
1Leibniz-Institut für Molekulare Pharmakologie (FMP), Berlin, Germany

Chemical Exchange Saturation Transfer (CEST) is typically quantified by subtracting an on resonant saturation image from an off resonant reference image. When performing single-shot Hyper-CEST imaging with low signal from dissolved xenon this approach has serious problems as the low SNR is further decreased by the image subtraction. Here, we propose two alternative methods based on least squares fitting and principal component analysis, which exploit the information of a series of CEST images with a range of different saturation frequencies. Both presented methods lead to a significant gain in SNR and strongly improve the visualization of the agents.

1668.   Extension of the singlet state lifetime of N2O via alteration of temperature and viscosity of dissolving solvent
Rajat K. Ghosh1, Stephen J. Kadlecek1, Nicholas N. Kuzma1, Jan Henrik Ardenkjaer-Larsen2,3, Giuseppe Pileio4, Malcolm H. Levitt4, and Rahim R. Rizi1
1Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States, 2Electrical Engineering, The Technical University of Denmark, Lyngby, Denmark, 3GE Healthcare, Broendby, Denmark, 4University of Southampton

The utility of hyperpolarized tracers is limited by polarization lifetime. Transferring spin order to a singlet state can significantly increase polarization lifetimes in nitrous oxide dissolved in a liquid solvent. The longitudinal relaxation of nitrous oxide is largely dominated by the spin-rotation interaction. In this work we formulate a model to describe the relaxation of nitrous oxide dissolved in various solvents, and avenues to lengthen the singlet lifetime by altering the characteristics of the dissolving solvent. We experimentally investigate the effect of altering the temperature of the solvent, as well as the effect of varying viscosity and hydrodynamic radius.

1669.   A Method for Simultaneous Echo Planar Imaging of Hyperpolarized Compounds
Galen D. Reed1, Peder E.Z. Larson1, Cornelius von Morze1, Robert Bok1, Michael Lustig2, Adam B. Kerr3, John M. Pauly3, John Kurhanewicz1, and Daniel B. Vigneron1
1Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California, United States, 2Electrical Engineering and Computer Sciences, University of California Berkeley, 3Electrical Engineering, Stanford University

An echo planar imaging sequence for simultaneous dynamic imaging of multiple hyperpolarized 13C compounds is presented. Frequency separation was achieved by spatial mis-registration in the phase-encoded direction by the appropriate choice of echo spacing. Suppression of the pyruvate-hydrate and alanine resonances was achieved using an optimized spectral-spatial RF waveform. Dynamic imaging was demonstrated in a transgenic mouse cancer model. Images of pyruvate and lactate were acquired after hyperpolarized pyruvate infusion. Images of lactate and HP001 were acquired after simultanous infusion of hyperpolarized pyruvate and HP001.

1670.   Non-Cartesian Calibrationless Parallel Imaging Reconstruction: Application to Hyperpolarized 13C Imaging
Markus Durst1,2, Ulrich Koellisch1, Jonathan I. Sperl2, Eliane Weidl3, Florian Wiesinger2, Axel Haase1, and Rolf F. Schulte2
1IMETUM, Technische Universität München, Munich, Bavaria, Germany, 2GE Global Research, Munich, Bavaria, Germany, 3Department for Nuclear Medicine, Technische Universität München, Munich, Bavaria, Germany

Due to the irreversible T1-decay of the magnetization, scan time is crucial for hyperpolarized 13C MRI. In contrast to existing autocalibrated parallel MRI algorithms, calibrationless parallel imaging does not require a fully sampled k-space region as used in existing autocalibrated methods, and therefore yields a further reduction of acquisition time. The basic idea is to reconstruct the data with low-rank matrix completion. This existing approach was succesfully adopted to hyperpolarized 13C spiral imaging. Simulations were performed as well as a reconstruction of in-vivo rat data, results were comparable to existing autocalibrated parallel MRI methods, nevertheless allowing a faster acquisition.

1671.   Determination of the pKa of a Hyperpolarized H13CO3- pH Probe
Thomas C Booth1,2, Mikko I Kettunen1,2, Ferdia A Gallagher1,2, Brett WC Kennedy1,2, Tiago B Rodrigues1,2, Sarah E Bohndiek1,2, and Kevin M Brindle1,2
1Biochemistry, University of Cambridge, Cambridge, United Kingdom, 2Cambridge Research Institute, Cancer Research UK, Cambridge, United Kingdom

Tissue pHe can be determined using 13C MRS and hyperpolarized 13C-labelled bicarbonate. Using an assumed pKa, the H13CO3- and 13CO2 signal intensities allow pH determination using the Henderson-Hasselbalch equation. We compared pH derived by DNP NMR with direct potentiometric measurement of H+ activity using a glass electrode. Using pKa’ = pH – log ([H13CO3]/[ 13CO2]), we assigned the pH determined potentiometrically as the standard and determined whether the 13C MRS derived pKa diverges when there is alteration of ionic strength, pH, temperature and protein concentration within a clinically relevant range of values. Additionally, the pKa in human blood was determined.

1672.   Dynamic nuclear polarization of doubly-labeled 15N2O
Nicholas N. Kuzma1, Huseyin Kara1,2, Mehrdad Pourfathi1, Philip Manasseh3, Rajat K. Ghosh1, Stephen J. Kadlecek1, Giuseppe Pileio4, Pär Håkansson4, Malcolm H. Levitt4, and Rahim R. Rizi1
1Radiology, University of Pennsylvania, Philadelphia, PA, United States, 2Astronomy and Physics, University of Pennsylvania, Philadelphia, PA, United States, 3Department of Chemistry, Earlham College, Richmond, IN, United States, 4School of Chemistry, Southampton University, Southampton, Hempshire, United Kingdom

This is the first report of dynamic nuclear polarization (DNP) of doubly-labeled 15N2O. Sample polarization during DNP at 1.5 K and 5 T was monitored in-situ by solid-state NMR as a function of microwave frequency in the range 140.04 - 140.16 GHz. The fastest initial polarization rate occurred at 140.063 and 140.130 GHz microwave frequencies, corresponding to positive and negative polarizations of the nuclear spin system. Polarization levels of (11plus-or-minus sign4)% were achieved in the frozen sample.

1673.   A Low Field Dual Channel Heteronuclear RF Probe For Hyperpolarized Magnetic Resonance Imaging At 0.0475 T
Aaron M. Coffey1,2, Roman V. Shchepin1, Ken Wilkens1, Kevin W. Waddell1, and Eduard Y. Chekmenev1
1Vanderbilt University Institute of Imaging Science, Vanderbilt University, Nashville, TN, United States, 2Biomedical Engineering, Vanderbilt University, Nashville, TN, United States

A low field MR imaging system for heteronuclear hyperpolarized contrast agents in vivo is under development to demonstrate utility for human scale. Hyperpolarization reopens examination of low field imaging leveraging multi-turn inductors. A 206 turn 13C single layer solenoid coil was used to polarize by PASADENA and detect in situ hyperpolarized 1-13C-succinate-d2 (P = 15%, 13C SNR = 500, FWHM = 22 Hz). Comparison with identical phantom and polarization yielded SNR = 120 with FWHM = 6 Hz for a Doty volume coil (4.7 T) with the solenoid coil (0.0475 T) yielding SNR = 30 with FWHM = 25 Hz.

1674.   Safety concept, experimental design and quality assurance for parahydrogen in a clinical setting
Jan-Bernd Hövener1, Robert Borowiak1, Sebastien Bär1, Jochen Leupold1, Jürgen Hennig1, and Dominik von Elverfeldt1
1Medical Physics, Dep. of Radiology, Medical Center, University of Freiburg, Freiburg, BW, Germany

While the methodology of pH2 production is known for decades (flow through catalyst at 20 K), its implementation in a clinical setting is rare (none is known to us), but key if pH2 hyperpolarization is to enter life sciences. Here, we present the safety concept, experimental setup and quality assurance to run a pH2 production unit in hospital.

1675.   Hybrid Proton/Carbon Constrained Image Reconstruction for Hyperpolarized Metabolic Imaging
Andreas Sigfridsson1, Kilian Weiss1, and Sebastian Kozerke1
1Institute for Biomedical Engineering, University and ETH Zurich, Zürich, Switzerland

Cardiac metabolic imaging after injection of hyperpolarized pyruvate is inherently limited by resolution due to the short acquisition time available. The low resolution may result in signal contamination from the blood pools into myocardial regions, which can compromise analysis of metabolic processes. Here, an approach that uses high-resolution spatial information obtained from proton images to constrain the reconstruction of the carbon images is presented. The technique is evaluated both in simulations and in-vivo, and the results indicate that the signal contamination may be reduced.

1676.   Sensitivity of hyperpolarized 13C kinetic modeling to flip angle and number of temporal samples
Matthew Smith1, Jeremy Gordon1, Dave Niles1, Kevin Johnson1, and Sean Fain1,2
1Medical Physics, University of Wisconsin, Madison, Wisconsin, United States, 2Radiology, University of Wisconsin, Madison, WI, United States

Dynamic imaging of hyperpolarized 13C with MRI provides metabolic kinetics with spatial localization in-vivo but is challenging because both T1 and RF decay reduce the hyperpolarized signal throughout the experiment. A low flip angle is typically used to mitigate RF decay and enable acquisition of many images by sacrificing image SNR. The simulations presented in this study investigate the kinetic modeling accuracy for a variety of flip angles and number of acquired images using a centric Cartesian trajectory and provides a target SNR for dynamic images.

1677.   Fast and Selective MRI of Xenon Biosensors
Martin Kunth1, Jörg Döpfert1, Christopher Witte1, Federica Rossella1, and Leif Schröder1
1Leibniz-Institut für Molekulare Pharmakologie (FMP), Berlin, Germany

Concepts of biosensor detection by MRI are of actual interest, since its non-ionizing radiation property. This study demonstrates single-shot localization of functionalized129Xe as used in specific biosensors in low concentration. Cryptophane-A was used in different surroundings to simulate two different types of biosensors at concentrations of 10µM each, seperated by 1.2 ppm. Our technique employs presaturation and EPI encoding on hyperpolarized (HP) 129Xe. This fast imaging limits the Hyper-CEST technique to the HP Xe delivery process to the cryptophane-A cages and turns out to be promising for biosensor detection even in the nanomolar range.

1678.   Synthesis of hyperpolarized Ethanol via PHIP
Thomas Trantzschel1, Ute Bommerich2, Markus Plaumann1, Denise Lego2, Torsten Gutmann3, Tomasz Ratajczyk3, Sonja Dillenberger3, Gerd Buntkowsky3, Joachim Bargon4, and Johannes Bernarding1
1Dep. for Biometry and medical Informatic, Otto-von-Guericke University Magdeburg, Magdeburg, Germany, 2Leibniz Institute for Neurobiology, Magdeburg, Germany,3Technical University Darmstadt, Germany, 4University Bonn, Germany

Parahydrogen Induced Polarization (PHIP) gains much attention as it is already used for metabolic studies in MR. Because of keto-enol tautomerism, molecules with a hydroxyl group next to double or triple bonds are not accessible via PHIP e.g. vinyl alcohol which is precursor for ethanol. Our study presents the first time an approach to generate PHIP hyperpolarized ethanol that is probably the mostly used psychoactive drug. Based on the offered pathway, PHIP could be extended on biological relevant compounds, such as serine, malate, adrenaline, glucose, or related structures.

1679.   Continuous hyperpolarization of water via Overhauser DNP for MRI applications
Sandro Ebert1, Andrea Amar1, Christian Bauer1, Michael Kölzer1, Peter Blümler2, Dariush Hinderberger1, Hans W. Spiess1, and Kerstin Münnemann1
1Max Planck Institute for Polymer Research, Mainz, Germany, 2Johannes Gutenberg University, Mainz, Germany

Despite its wide applicability in natural science, NMR and MRI still suffers from its inherently low sensitivity. This could be overcome by hyperpolarization via dynamic nuclear polarization (DNP) which result in enhanced NMR signals. In DNP, the use of toxic radicals and microwave irradiation becomes crucial with regard to medical applications. We implemented a flow system into a mobile DNP polarizer, which overcomes both obstacles. Acquired images demonstrate, because of enhanced and due to dipolar coupling inverted signals, that hyperpolarized water can be an excellent and authentic MRI contrast agent.

1680.   Hyperpolarization of hyperbranched polymers for molecular imaging
Kerstin Münnemann1, Björn C Dollmann1, O Neudert1, Andrew K Whittaker2, and Kristofer J Thurecht2
1Max Planck Institute for Polymer Research, Mainz, Germany, 2Australian Institute for Bioengineering and Nanotechnology and Centre for Advanced Imaging, The University of Queensland, St Lucia, Queensland, Australia

The first hyperpolarization of biocompatible hyperbranched polymers using parahydrogen induced polarization (PHIP) and Dynamic Nuclear Polarization (DNP) is reported. 1H NMR signal enhancements of 1500-fold could be obtained via PHIP whereas 19F Overhauser DNP resulted in an enhancement of -37 for the fluorine containing moieties in the molecules. These results open up new possibilities for designing dual-modal molecular MR imaging agents that combine highly sensitive PHIP or DNP enhancements for measuring relatively fast biological processes with an additional imaging mechanism that is likely much less sensitive (normal 19F MRI), but which would provide contrast over a longer time-scale.

1681.   Optimization of polarization transfer sequence timing for parahydrogen induced polarization
Dirk Graafen1,2, Michael Ryan Hansen2, Laura Maria Schreiber1, and Kerstin Münnemann2
1Section of Medical Physics, Johannes Gutenberg University Medical Center, Mainz, Germany, 2Max Planck Institute for Polymer Research, Mainz, Germany

The aim of the study was to optimize the timing of a PH-INEPT+ sequence for 13C1-Hydroxyethylproprionate (HEP) to enable optimal polarization transfer from hyperpolarized protons using parahydrogen induced polarization (PHIP) to Carbon-13. Spin dynamics simulations showed the different sequence timing behavior of a thermally polarized and a PHIP polarized molecule. In comparison, for this molecule the optimal lower case Greek tau1 delay of the PH-INEPT+ sequence is ~4ms for the thermal polarization whereas it is ~27.5ms for the hyperpolarized state. Experiments in a 7T spectrometer reproduce the simulation results adequately.
Traditional Poster Session - Molecular Imaging

Studies of Metabolism Using Hyperpolarized 13C - Metabolism
Click on to view the abstract pdf. Click on to view the poster (Not all posters are available for viewing.)
Tuesday 8 May 2012
Exhibition Hall  10:00 - 12:00

1682.   Detection of Radiation Response of Prostate Cancer in TRAMP with Hyperpolarized 13C MRSI
Lasitha Senadheera1, Dirk Mayer2,3, Sonal Josan2,3, Yi-Fen Yen4, Moses Darpolor3, Jae Mo Park3, Ralph E. Hurd4, Richard Luong5, Lei Xing1, and Daniel M. Spielman3
1Radiation Oncology, Stanford University, Stanford, CA, United States, 2Neuroscience Program, SRI International, Menlo Park, CA, United States, 3Radiology, Stanford University, Stanford, CA, United States, 4Global Applied Science Laboratory, GE Healthcare, Menlo Park, CA, United States, 5Comparative Medicine, Stanford University, Stanford, CA, United States

Radiation-induced metabolic response of TRAMP prostate tumor was investigated with 13C MRSI of hyperpolarized [1-13C]Pyruvate. The pyruvate metabolism in the tumors of two groups of mice, x-ray treated and untreated, was assessed in terms of Lactate/Pyruvate ratio. The Lactate/Pyruvate ratio was uncorrelated with the tumor size but was significantly (P < 0.05) lower in the treated group than the untreated. Our preliminary data suggest the feasibility of using 13C MRSI for detecting therapeutic response of prostate cancer to radiation in TRAMP mice.

1683.   Compartmentation of MCF-7 tumour cell metabolites characterised by hyperpolarised 13C diffusion-weighted spectroscopy
Franz Schilling1,2, Stephan Düwel1,2, Markus Durst1,3, Ulrich Köllisch1,3, Jan Henrik Ardenkjaer-Larsen4, Pedro A. Gómez Damián3, Markus Schwaiger5, Rolf F. Schulte3, Steffen J. Glaser2, Axel Haase1, Angela Otto1, and Marion I. Menzel3
1Zentralinstitut für Medizintechnik, Technische Universität München, Garching, Germany, 2Department of Chemistry, Technische Universität München, Garching, Germany,3GE Global Research, Munich, Germany, 4GE Healthcare, Copenhagen, Denmark, 5Department of Nuclear Medicine, Technische Universität München, Munich, Germany

Understanding tumour metabolism is a central issue in diagnosis of tumours. Using magnetic resonance spectroscopy, hyperpolarized [1-13C]pyruvate and its metabolites can be detected to characterise the stage of a tumour. The signal of each metabolite emanates from both extra- and intracellular compartments. In this work, we show for the first time, using real-time direct detection, that diffusion coefficients of [1-13C]pyruvate and its metabolites in tumour cell spheroids can be determined. We foresee many new applications of hyperpolarized 13C diffusion-weighted spectroscopy e.g. to separate intra- and extracellular compartments of tumours, and to separate metabolic conversion from perfusion by large diffusion weightings.

1684.   Distinguishing Sensitive and Resistant Early Therapy Response of Pancreatic Tumor Xenografts Using 13C-MRS of Hyperpolarized Pyruvate
Prasanta Dutta1, G V Martinez1, N V Rajeshkumar2, A Le2, A Maitra2, C V Dang2, R A Gatenby1, and R J Gillies1
1Imaging, Moffitt Cancer Center & Research Institute, Tampa, FL, United States, 2School of Medicine, Johns Hopkins University, Baltimore, MD, United States

In this work, we have evaluated the efficacy of a small molecule drug (a potent LDH-A inhibitor,FX11) treatment to human pancreatic xenograft tumors via assessing the metabolic conversion of lactate from pyruvate using 13C magnetic resonance spectroscopy. Measurement of hyperpolarized 13C label flux between pyruvate and lactate is used to detect early response to therapy before differences in tumor volume were observed.

1685.   Hyperpolarized 13C-pyruvate MRI for evaluating metabolic changes in SCC tumor by X-irradiation
Keita Saito1, Shingo Matsumoto1, H Douglas Morris2, Martin J Lizak2, Jeeva P Munasinghe2, Nallathamby Devasahayam1, Sankaran Subramanian1, James B Mitchell1, and Murali C Krishna1
1Radiation Biology Branch, National Cancer Institute, Bethesda, Maryland, United States, 2National Institute of Neurological Disorder and Stroke, Bethesda, Maryland, United States

We investigated effects of X-irradiation on pyruvate metabolism in squamous cell carcinoma (SCC) implanted in mice leg using 13C-MRI with hyperpolarized [1-13C]pyruvate. [1-13C]lactate to [1-13C]pyruvate ratio (Lac/Pyr) in the SCC tumors increased as tumor grew in non-irradiated control mice. 10 Gy irradiation to SCC tumors slightly suppressed the increase of Lac/Pyr, but there was no significance compared with the control. However, Lac/Pyr significantly droped after three 10 Gy irradiations (10 Gy/day, total dose 30 Gy). So, X-irradiation suppressed increase of LDH activity in SCC tumor, and lactate formation from pyruvate would become a useful marker for tumor response to radiotherapy.

1686.   Real-Time In-vivo Metabolic Characterization in Spontaneous Hepatocellular Carcinoma Using a Novel Transgenic Mouse Model

By incorporating a human hepatitis-B transgene and inducing mutagenesis via a sleeping-beauty-transposon system, a sophisticated liver cancer model has been created to study human hepatocellular carcinoma in mice. To understand changes in metabolic fuel demand as the disease progresses, hyperpolarized carbon-13 technology was utilized to study pyruvate metabolism in-vivo. We observe a reduction in the oxidative decarboxylation of pyruvate, with slight increases in transamination to alanine and reduction to lactate. Biochemical assay of liver extracts suggests an elevated dependence on glutamine as an anaplerotic carbon source. Metabolic imaging of downstream products such as lactate and alanine provides a map of tumor energetics.

1687.   Ovarian Cancer Detection Using Hyperpolarized 13C-Pyruvate with MR Imaging and Spectroscopy
Mehrdad Pourfathi1,2, Stephen J. Kadlecek1, Harrilla Profka1, Hoora Shaghaghi1, Moses Darpolor1, Kiarash Emami1, Nicholas N. Kuzma1, Jan H. Ardenkjær-Larsen3, Rahim R. Rizi1, and Janet A. Sawicki4
1Radiology, University of Pennsylvania, Philadelphia, PA, United States, 2Electrical and Systems Engineering, University of Pennsylvania, Philadelphia, PA, United States, 3GE Healthcare, Brøndby, Denmark, 4Lankenau Institute for Medical Research, Wynnewood, PA, United States

Lactate dehydrogenase (LDH), shown to be unregulated in ovarian cancer, may result in elevated lactate concentrations in the tumors. Using [1–13C] pyruvic acid (hyperpolarized via DNP), we sought to infer elevated LDH levels by detecting a more rapid approach to the equilibrium lactate:pyruvate ratio. The data was acquired by slice-selective spectroscopy of ovarian area from six mice and fitted to a simple model incorporating (a) the forward and backward conversion of pyruvate/lactate in steady-state metabolism and (b) spin-lattice relaxation of pyruvate polarization over time. We observed higher levels of LDH activity (in both directions) associated with ovarian-tumor-bearing animals.

1688.   Myocardial pyruvate dehydrogenase flux in long-chain acyl-CoA dehydrogenase knock-out mice
Adrianus J. Bakermans1, Michael S. Dodd2, Klaas Nicolay1, Jeanine J. Prompers1, Sander M. Houten3, and Damian J. Tyler2
1Biomedical NMR, Eindhoven University of Technology, Eindhoven, Netherlands, 2Cardiac Metabolism Research Group, University of Oxford, Oxford, United Kingdom,3Laboratory Genetic Metabolic Diseases, Academic Medical Center, Amsterdam, Netherlands

Glucose oxidation may be unable to compensate sufficiently to maintain myocardial energy homeostasis in patients affected by fatty acid lower case Greek beta-oxidation disorders. The flux through the pyruvate dehydrogenase (PDH) complex was studied using hyperpolarized 13C-MRS of [1-13C]pyruvate in the in vivo heart of long-chain acyl-CoA dehydrogenase knock-out (LCAD KO) mice and controls in fed and fasted conditions. PDH flux was normal in fed LCAD KO mice. However, after fasting PDH flux decreased to a lesser extent in LCAD KO mice when compared to controls, suggesting a compensatory role for glucose metabolism in fasted LCAD KO mice to maintain myocardial energy homeostasis.

1689.   The Application of Hyperpolarized 13C-MRS in a Cardiac Specific Fumarate Hydratase Knockout Mouse
Michael Dodd1,2, Vicky Ball1, Beat Schuler1, Daniel Ball1, Houman Ashrafian2, Hugh Watkins2, Kieran Clarke1, and Damian Tyler1
1Department of Physiology, Anatomy and Genetics, Oxford University, Oxford, OXON, United Kingdom, 2Department of Cardiovascular Medicine, Oxford University, Oxford, OXON, United Kingdom

The advent of cardiac hyperpolarized 13C-MRS has enabled a greater understanding of the in vivo metabolic changes seen as a consequence of heart disease. This work demonstrates the application of hyperpolarized 13C-MRS in the in vivo mouse heart and shows the sensitivity of the technique to detect changes in pyruvate dehydrogenase (PDH) flux caused by fasting and dichloroacetate. Further, the ability of the technique to study transgenic mouse models of cardiac disease is also demonstrated with application in the fumarate hydratase knockout mouse.

1690.   Application of 13C metabolic imaging for the assessment of ischemia in the perfused heart
Daniel Ball1, Rachel Cruickshank1, Carolyn Carr1, Daniel Stuckey2, Kieran Clarke1, and Damian Tyler1
1Physiology, Anatomy and Genetics, Oxford University, Oxford, Oxfordshire, United Kingdom, 2Imperial College, London, United Kingdom

The aim of this work was to demonstrate the use of a combined dynamic nuclear polarization and chemical shift imaging protocol in the isolated perfused heart to image metabolism in the setting of both acute and chronic myocardial ischemia. The imaging protocol was successfully applied in both models, and in the acute ischemia model, metabolic disturbances could be clearly visualised. Future work will focus on the translation of these techniques into in vivo models of ischemia.

1691.   In vivo real-time metabolic studies in mice at physiological concentrations following 1-13C lactate injection
Yuhei Takado1, Mor Mishkovsky1,2, Tian Cheng1,3, Rolf Gruetter1,2, and Arnaud Comment1,3
1LIFMET, EPFL, Lausanne, 1015, Switzerland, 2Department of Radiology, University of Lausanne, Lausanne, Switzerland, 3Institute of Physics of Biological Systems, EPFL, Lausanne, Switzerland
The real-time metabolic transformation of lactate in the mouse head was monitored following the injection of hyperpolarized 1-13C lactate at physiological doses. The results were compared with metabolic studies performed with hyperpolarized 1-13C pyruvate at similar blood concentration. From the observation that the lactate to alanine ratio was nearly identical following both the pyruvate and the lactate injections, we concluded that the substrate and its metabolites can be detected in real time at physiological concentrations after the injection of lactate.

1692.   Brain metabolism under different anesthesia using hyperpolarized [1-13C]-pyruvate
Malgorzata Marjanska1, Alexander Shestov1, and Pierre-Gilles Henry1
1Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, United States

The low sensitivity of 13C spectroscopy can be enhanced using hyperpolarization techniques such as dynamic nuclear polarization. Detection of [1-13C]pyruvate and its metabolic products including bicarbonate have been reported in the brain. In this work, we investigate the ability to detect bicarbonate under different anesthesia and modeling of that signal to determine value of rate constants of bicarbonate production.

1693.   Evaluation of the progression of obstructive nephropathy in a UUO mouse model using BOLD, hyperpolarized 13C, and DCE MRI
David J Niles1, Jeremy W Gordon1, Matthew R Smith1, Shannon Reese2, Arjang Djamali2, Elizabeth A Sadowski3, and Sean B Fain1,3
1Medical Physics, University of Wisconsin, Madison, WI, United States, 2Medicine, University of Wisconsin, Madison, WI, United States, 3Radiology, University of Wisconsin, Madison, WI, United States

Obstructive nephropathy is the most common cause of end-stage renal disease in children. Currently we have a poor understanding of its pathogenesis, prognosis, and the best course of treatment. Non-invasive, non-radioactive diagnostic approaches are desirable. In this study we used MRI to monitor renal function during obstructive nephropathy in a 14-day unilateral ureteral obstruction (UUO) mouse model. Blood oxygen level-dependent (BOLD), dynamic contrast-enhanced (DCE), and hyperpolarized [1-13C] pyruvate (13C) MRI were used to assess renal oxygenation, perfusion, and pyruvate metabolism, respectively. The results show the potential of using functional MRI, particularly 13C MRI, to track the progression of obstructive nephropathy.

1694.   Metabolism of Hyperpolarized [1-13C]Pyruvate in the Isolated Perfused Rat Lung – An Ischemia Study
Stephen Kadlecek1, Benjamin Pullinger1, Kiarash Emami1, Harrilla Profka1, Masaru Ishii2, and Rahim Rizi1
1Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States, 2Otolaryngology-Head and Neck Surgery, Johns Hopkins University, Baltimore, MD, United States

Difficulties with NMR studies of lung arising from low tissue density and air-tissue interfaces can be partially overcome using 13C-DNP NMR. This experiment studies the evolution of the [1-13C] lactate signal in isolated, perfused rat lungs after injection of pyruvate under normoxic and ischemic conditions in order to understand changes in lung oxidative state, central to ischemia-reperfusion injury, transplantation, and metabolic changes in cancer. A 25-minute period of ischemia is associated with both a ~5x elevated rate of pyruvatelactate conversion and a similar increase in the endogenous lactate pool as measured by proton NMR; both changes are reversible after reperfusion. 31P confirms previously published changes to the ATP and PCr pools during ischemia.

1695.   Rapid Transmembrane Exchange of Hyperpolarized 13C-Urea: Pathology-Methods Development Using Erythrocytes
Guilhem Pages1, Yee Ling Tan1, and Philip William Kuchel1
1Mechanistic Systems-biology NMR Group, Singapore Bioimaging Consortium, A*STAR, Singapore, Singapore, Singapore

Dynamic Nuclear Polarization (DNP) has opened up new avenues to characterize metabolism; we have extended it to study rapid membrane transport of a solute. We used hyperpolarized 13C-urea in the presence of urease in erythrocyte suspensions. We designed an extensive kinetic model, taking into account all chemical and transport reactions of the hyperpolarized urea and its products to extract estimates of rate constants of the reactions. The systems urea/urease and urea/erythrocytes were fully characterized with the detection of all chemical species. The success of this in vitro study albeit on a simple cell-type augurs well for similar in vivo experiments.