ISMRM 23rd Annual Meeting & Exhibition • 30 May - 05 June 2015 • Toronto, Ontario, Canada

Traditional Poster Session • Molecular Imaging
1877 -1939 Molecular Imaging

Wednesday 3 June 2015
Exhibition Hall 10:00 - 12:00

1877.   Roemer-Optimal Reconstruction of Hyperpolarized 13C Cardiac Images with an 8 Channel Coil
William Dominguez-Viqueira1, Benjamin Geraghty1,2, Justin Y.C. Lau1,2, Albert P Chen3, and Charles H Cunningham1,4
1Imaging Research, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada, 2Medical Biophysics, University of Toronto, Toronto, Ontario, Canada, 3GE Healthcare, Toronto, Ontario, Canada, 4Medical Biophyscis, University of Toronto, Toronto, Ontario, Canada

Roemer-optimal coil combination using a Biot-Savart numerical model of the sensitivity maps coefficients has been successfully used previously in 13C images of the heart. The Biot-Savart numerical estimation method was extended to the 8-channel receiver array that will be used in human studies. Results were compared to a low-pass-filter method and to sum of squares. Estimated coefficients using Biot-Savart resulted in better image quality than using a low-pass-filter of the acquired images. SNR improvements of up to a 100 % in areas closer to the base of the heart were demonstrated by using the Roemer reconstruction, as compared with sum-of-squares.

1878.   19F-Hyperpolarized Structures as Markers for the Improved Detection of Amyloid Plaques
Ute Bommerich1,2, Thomas Trantzschel1, Markus Plaumann1, Denise Lego2, Gerd Buntkowsky3, Grit Sauer3, Torsten Gutmann3, Joachim Bargon4, and Johannes Bernarding1
1Institute for Biometrics and Medical Informatics, Otto von Guericke University Magdeburg, Magdeburg, Saxony-Anhalt, Germany, 2Special Lab Non-invasive Brain Imaging, Leibniz Institute for Neurobiology, Magdeburg, Saxony-Anhalt, Germany, 3Eduard-Zintl-Institute for Inorganic Chemistry, Technical University Darmstadt, Hesse, Germany, 4Institute for Physical and Theoretical Chemistry, University Bonn, North Rhine-Westphalia, Germany

Fluorinated bis(styryl)benzene derivatives can improve the MR detection of amyloid plaques, that are supposed to play an important role in the progression of Alzheimer´s disease. These molecules enable 19F-MRI experiments with optimal contrast only restricted by the concentration of the applied markers. An increase of MR-sensitivity by orders of magnitude makes Parahydrogen Induced Polarization (PHIP) a promising tool. It is demonstrated that hyperpolarization of 19F nuclei in molecules that are structurally closely related to amyloid markers is feasible. This leads to an in-phase signal with improved intensity which could be further increased by a field cycling step.

1879.   PHIP hyperpolarization of linear and branched fluorinated alkanes as well as their interaction with cyclodextrins
Markus Plaumann1, Thomas Trantzschel1, Jan Wüstemann1, Denise Lego2, Grit Sauer3, Torsten Gutmann3, Joachim Bargon4, Gerd Buntkowsky3, Johannes Bernarding1, and Ute Bommerich1,2
1Department for Biometrics and Medical Informatics, Otto-von-Guericke University Magdeburg, Magdeburg, Saxony-Anhalt, Germany, 2Special Lab Non-Invasive Brain Imaging, Leibniz Institute for Neurobiology, Magdeburg, Saxony-Anhalt, Germany, 3Eduard-Zintl-Institute for Inorganic Chemistry, Technical University Darmstadt, Darmstadt, Hesse, Germany, 4Institute of Physical and Theoretical Chemistry, University Bonn, Bonn, North Rhine-Westphalia, Germany

The chemical inertness of fluorinated alkanes makes them ideal for in vivo application, e.g. molecular imaging. Here, the hyperpolarization of four semifluorinated substrates is presented by using the parahydrogen induced polarization (PHIP). 1H,1H,2H-perfluorohexane, 1H,1H,2H-perfluorooctane, 1H,1H,2H-perfluorodecane and perfluoro-(4-methylpentane) are chosen to demonstrate the polarization transfer from protons over a chain of CF2 respectively CF groups to the end-standing CF3 groups, which leads in a nonuniform distribution of the polarization. Additionally studies in presence of cyclodextrin derivatives show a molecular interaction between cyclodextrin and the lipophilic semifluorinated substrate. This allows the transport into an aqueous solution, which is important for biomedical applications.

1880.   Speeding up Dynamic Spiral Chemical Shift Imaging with Incoherent Sampling and Low-Rank Matrix Completion: Application in Hyperpolarized 13C Metabolic Imaging
Stephen DeVience1 and Dirk Mayer1
1Diagnostic Radiology, University of Maryland School of Medicine, Baltimore, MD, United States

While hyperpolarized 13C metabolic imaging permits real-time investigation of metabolism in vivo, it requires fast acquisition schemes. We implemented an iterative reconstruction algorithm based on low-rank matrix completion that exploits spatiotemporal correlations in incoherently undersampled, time-resolved data. The algorithm was applied to both retro- and prospectively undersampled dynamic spiral chemical shift imaging (spCSI) data by pseudo-randomly omitting spatial interleaves and the results were compared to conventional reconstruction. The presented data demonstrate that LRMC reconstruction in combination with incoherent undersampling permits substantial reduction in minimum acquisition time of dynamic spCSI without significantly compromising image quality.

1881.   The Effects of Acute and Chronic Up-Regulation of Pyruvate Dehydrogenase on Myocardial Metabolism
Lucia F Giles1, Vicky Ball1, and Damian J Tyler1
1Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, Oxfordshire, United Kingdom

Pyruvate dehydrogenase (PDH) is a key regulatory enzyme in cardiac metabolism and is activated by dichloroacetate (DCA). The effects of DCA on PDH and glycolytic flux were investigated in vivo and the perfused heart using hyperpolarized [13C]pyruvate and [3H]glucose. PDH flux was enhanced in vivo following acute and chronic DCA treatment. This was accompanied by a decrease in glycolytic flux and lactate production despite the increase in PDH flux. This suggests that either glucose is oxidised more efficiently when coupling between glycolysis and glucose oxidation is enhanced or that increased glucose oxidation leads to inhibition of glycolysis via a negative feedback pathway.

1882.   Generation of hyperpolarized bicarbonate in large concentrations to image pH
Rajat K Ghosh1, Mehrdad Pourfathi1, Stephen J Kadlecek1, and Rahim R Rizi1
1Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States

Synopsis: Hyperpolarized (HP) bicarbonate has been used to image pH in vivo. However, its utilization has been limited by difficulties in generating high polarizations and concentrations. In this work, we describe a new technique for generating HP bicarbonate by de-carboxylating HP pyruvate. HP bicarbonate produced in this manner is then used to image pH in rat lungs at sub-mm resolutions. Production of HP bicarbonate through direct polarization is currently limited to concentrations of ~100mM. In contrast, our indirect decarboxylation approach generates 100-400mM bicarbonate, further increasing signal to allow for high-resolution pH imaging.

1883.   Hyperpolarized [2-13C]Dihydroxyacetone: Monitoring Hepatic Gluconeogenesis in Real-Time
Karlos X Moreno1, Santhosh Satapati1, Ralph J DeBerardinis2, Shawn C Burgess1, Craig R Malloy1, and Matthew E Merritt1
1Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, TX, United States, 2Children's Medical Center Research Institute, UT Southwestern Medical Center, Dallas, TX, United States

Direct observation of hyperpolarized glucose from a gluconeogenic substrate has not previously been observed. Isolated mouse livers perfused in a gluconeogenic or glycogenolytic state were injected with hyperpolarized [2-13C]dihydroxyacetone. In each condition, hyperpolarized glucose signals were observed. Purified effluent glucose confirmed the enrichment. Minimal differences in hyperpolarized glucose signals between the two conditions were observed. Triose intermediates of glycolysis showed large differences, the glycogenolytic condition having greater signals. This is the first study to demonstrate direct gluconeogenesis using hyperpolarization methods.

1884.   Partial-Volume Correction for Metabolic Imaging with Hyperpolarised [1-13C]Pyruvate
Rolf F Schulte1, Martin A Janich1, Ulrich Koellisch1,2, Markus Durst1,2, Florian Wiesinger1, Eliane Ferral2, Markus Schwaiger2, Axel Haase2, and Marion I Menzel1
1GE Global Research, Munich, Germany, 2Technical University, Munich, Germany

Hyperpolarised metabolic imaging suffers from low resolution, which can hamper quantification due to partial volume effects. In this work, we implement and evaluate Partial-Volume Correction (PVC), which is a correction method applied in Positron Emission Tomography. It is possible to improve spatial resolution characteristics at the boundaries of the object with PVC.

1885.   Hyperpolarized ketone body metabolism in the in vivo rat heart
Angus Z Lau1,2, Jack J Miller2,3, and Damian J Tyler1,2
1Department of Cardiovascular Medicine, University of Oxford, Oxford, Oxfordshire, United Kingdom, 2Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, Oxfordshire, United Kingdom, 3Department of Physics, University of Oxford, Oxford, Oxfordshire, United Kingdom

Building on previous work in the ex vivo rat heart, we investigate the feasibility observing metabolism of hyperpolarized acetoacetate in the in vivo rat heart. Rats were scanned in the fed and fasted states. Spectra were obtained every 1 s by surface coil localization to the rat heart. We observe conversion of the acetoacetate substrate into acetylcarnitine and interconversion into the ketone body lower case Greek beta-hydroxybutyrate. Decarboxylation of acetoacetate into bicarbonate was observed in the fed state, but not in the fasted state (p<0.05).

1886.   Development of Hyperpolarized 13C-MRS Probes for Oxidative Stress measurement
Arif Wibowo1, Jae Mo Park2, Ralph Hurd3, Graham F Sommer4, Chaitan Khosla5, and Daniel M Spielman6, Stanford, CA, United States, 2Stanford, CA, United States, 3GE healthcare, CA, United States, 4Diagnostic Radiology, Stanford University, CA, United States,5Chemistry and ChEM-H, Stanford University, CA, United States, 6Radiology, Stanford University, CA, United States

In this study, we evaluated the potential of cysteine (Cys), N-acetyl cysteine (NAC), and Mercaptopyruvate (MCP as hyperpolarized 13C substrate for assessing oxidative stress (OS) in vivo. Of these, MCP was identified as a viable substrate for in vitro OS assessment, and we are currently developing large-scale MCP synthesis for testing the potential of this substrate for in vivo OS measurements.

1887.   Quantitative analysis for hyperpolarized 13C-pyruvate imaging: comparison of methods on a clinical system.
Charlie J Daniels1, Mary A McLean2, Nicholas McGlashan1, Martin J Graves1, Fraser J Robb3, David J Lomas1, Rolf F Schulte4, Kevin M Brindle2, and Ferdia A Gallagher1,2
1Department of Radiology, University of Cambridge, Cambridge, United Kingdom, 2Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom,3USA Instruments Inc., Aurora, Ohio, United States, 4GE Global Research, Munich, Germany

Hyperpolarized imaging with 13C-labelled endogenous molecules is on the verge of clinical translation. A simple, robust and objective method of quantitative analysis is required to process hyperpolarized data clinically, however there is currently debate over the best methods to apply. We assessed four quantitative methods by imaging conversion of [1-13C]pyruvate to [1-13C]lactate using a clinical polarizer system at 3 T and a pyruvate concentration predicted for future patient studies. We conclude that extracting data from a single voxel is sufficiently robust and suggest the area under the curve ratio be taken forward as a standardised clinical parameter.

1888.   31P Dynamic Nuclear Polarization Applied to Phosphonates for MRS/MRI Applications.
Roha Afzal1,2, Gary V. Martinez1, and Robert J. Gillies1
1Cancer Imaging and Metabolism, H.Lee Moffitt Cancer Centre, Tampa, Florida, United States, 2Chemical and Biomedical Engineering, University of South Florida, Tampa, Florida, United States

This study demonstrates the first application of 31P Dynamic Nuclear Polarization to the Phosphonates. The experimental conditions (glassing agents, radicals microwave irradiation frequencies, maximum polarization build-up time, etc.) were optimized for the hyperpolarization of Dimethyl Methyl Phosphonate. An in-vivo experiment was then carried out at these optimum conditions and the hyperpolarized 31P image and signal were observed in the animal.

1889.   Hepatic Metabolism of Hyperpolarized [1-13C]Pyruvate in the Zucker Rat
Jian-Xiong Wang1,2, Leila Fidelino3, Karlos Moreno3, A. Dean Sherry3,4, Craig Malloy3,5, and Matthew E Merritt1,6
1AIRC, UT Southwestern Medical Center, Dallas, TX, United States, 2Radiology, UT Southwestern Medical Center, Dallas, TX, United States, 3AIRC, UT Southwestern Medical Center, TX, United States, 4Chemistry, University of Texas at Dallas, TX, United States, 5Internal Medicine, UT Southwestern Medical Center, TX, United States, 6Radiology, UT Southwestern Medical Center, Dallas, United States

Hyperpolarized [1-13C]pyruvate can be metabolized in the liver via flux through pyruvate dehydrogenase (PDH) or pyruvate carboxylase (PC). In normal rats, PDH dominates the generation of [13C]bicarbonate in vivo. The Zucker rat is a model of diabetes that displays high levels of hepatic gluconeogenesis. In fasting, [13C]bicarbonate production is maintained, contrary to the normal animal. Sources of the [13C]bicarbonate production (PDH versus PC) will be identified.

1890.   Low cell number perfusion bioreactor system for hyperpolarized MRS in a MRI setting
Lotte Bonde Bertelsen1, Simon Lauritsen1, Christoffer Laustsen1, Preben Daugaard1, Xiaolu Zhang1, and Hans Stødkilde-Jørgensen1
1The MR Research Centre, Department of Clinical Medicine, Aarhus University, Aarhus University Hospital, Aarhus, Denmark

Development of a MR-compatible bioreactor system for measuring metabolic fluxes in cells grown in scaffold makes it possible to examine various cell types with different hyperpolarized 13C bio-probes. The 3D printed scaffold system facilitates a dynamic cell culture environment with controlled nutrient flow, oxygen supply and a large surface area for growth of adherent cells with minimal disturbance of the cells. Ongoing studies are focusing on evaluation of low cell numbers in scaffold and in suspension in this bioreactor design.

1891.   Investigation of Metabolic Changes in STZ Induced Diabetic Rats with Hyperpolarized [1-13C]Acetate
Ulrich Koellisch1, Christoffer Laustsen2, Thomas S. Nørlinger2, Concetta V. Gringeri3, Marion I. Menzel4, Rolf F. Schulte4, Axel Haase1, and Hans Stødkilde-Jørgensen2
1Institute of Medical Engineering, Technische Universität München, Munich, Germany, 2MR Research Centre, Aarhus University, Aarhus, Denmark, 3Nuklearmedizinische Klinik und Poliklinik, Technische Universität München, Germany, 4GE Global Research, Munich, Germany

In the metabolism of acetate several enzymes are involved, which play an important role for free fatty acid oxidation. Therefore it might serve as a marker for pathological changes of cells' fuel selection in particular in the myocardium. The goal of this study was to investigate whether the ratio of acetylcarnitine to acetate could serve as a marker for myocardial, hepatic and renal metabolic changes under Streptozotocin induced diabetes in vivo.

1892.   19F-MRI applications of PERFECTA at 7T: characterization studies on phantoms and on in vitro fibroblasts and T cells.
Alfonso Mastropietro1, Chiara Cordiglieri2, Ilaria Tirotta3,4, Francesca Baldelli Bombelli3,4, Fulvio Baggi2, Giuseppe Resnati3,4, Pierangelo Metrangolo3,4, Maria Grazia Bruzzone5, and Ileana Zucca1
1Scientific Direction Unit, Fondazione IRCCS Istituto Neurologico C. Besta, Milan, Milan, Italy, 2Neurology IV Unit, Fondazione IRCCS Istituto Neurologico C. Besta, Milan, Italy,3Laboratory of Nanostructured Fluorinated Materials (NFMLab), Department of Chemistry, Materials, and, Politecnico di Milano, Milan, Italy, 4Fondazione Centro Europeo Nanomedicina, Milan, Italy, 5Neuroradiology Unit, Fondazione IRCCS Istituto Neurologico C. Besta, Milan, Milan, Italy

This work aims at the magnetic characterization of a novel superfluorinated 19F MRI contrast agent. Preliminary data on labeled Fibroblasts and T cells using a 7T MRI scanner are presented.

1893.   Chemical exchange sensitive Spin-lock MRI of 3-O-methyl-D-glucose transport in brain
Hunter Mehrens1, Tao Jin1, and Seong-Gi Kim1,2
1Radiology, University of Pittsburgh, Pittsburgh, PA, United States, 2Center for Neuroscience Imaging Research, Institue for Basic Science, SKKU, Suwon, Korea

Recent studies showed an increase of chemical exchange-sensitive spin-lock (CESL) MRI signal during administration of 2-deoxy-glucose (2DG) with high sensitivity. However, the toxicity of 2DG is a concern for its clinical and preclinical application. 3-O-methyl-D-glucose (3OMG) is a non-metabolizable glucose analogue with minimal toxicity, therefore, it may have better potential as a contrast agent for the study of glucose transport. In this work, we demonstrated that 3OMG has similar chemical exchange properties as 2DG and glucose, and unique advantages relative to 2DG and glucose for in vivo studies.

1894.   New PARACEST MRI Contrast Agents Based on the DOTMA Scaffold
Mojmir Suchy1, Alex X. Li2, Robert Bartha2, and Robert H. E. Hudson1
1Department of Chemistry, University of Western Ontario, London, Ontario, Canada, 2Centre for Functional and Metabolic Mapping, University of Western Ontario, London, Ontario, Canada

A synthetic methodology has been developed for the preparation of Tm(III) complexes derived from DOTMA as new type of PARACEST MRI contrast agent. Agents were identified that possessed CEST peaks at chemical shifts beyond the frequency range of the endogenous macromolecule magnetization transfer. The CEST effects of these agents investigated were found to be sensitive to both temperature and pH.

1895.   Enriching Fluorine Nanoparticles with Saturated Phosphoethanolamines to Improve Dendritic Cell Detection by 19F Magnetic Resonance In Vivo
Sonia Waiczies1, Stefano Lepore1, Min-Chi Ku1, Helmar Waiczies1,2, Conrad Martin1, Susanne Drechsler1, Karl Sydow3, Margitta Dathe3, Andreas Pohlmann1, and Thoralf Niendorf1
1Berlin Ultrahigh Field Facility (B.U.F.F.), Max Delbrück Center for Molecular Medicine, Berlin, Germany, Germany, 2MRI.Tools GmbH, Berlin, Germany, 3Leibniz-Institut für Molekulare Pharmakologie, Berlin, Germany

Magnetic resonance (MR) methods to detect and quantify fluorine nuclei provide the opportunity to study the fate of cellular transplants in vivo. Challenges pertaining to MR signal sensitivity and cell detection exist. This study addresses these issues by examining the uptake mediating potential of nanoparticles enriched with phosphatidylethanolamines to improve dendritic cell detection.

1896.   Detecting Nanodiamonds With DNP
David E J Waddington1,2, Mathieu Sarracanie1,3, Huiliang Zhang3,4, David Reilly2, Ronald L Walsworth3,4, and Matthew S Rosen1,3
1MGH/A.A. Martinos Center for Biomedical Imaging, Charlestown, MA, United States, 2ARC Centre of Excellence for Engineered Quantum Systems, School of Physics, University of Sydney, Sydney, NSW, Australia, 3Department of Physics, Harvard University, Cambridge, MA, United States, 4Harvard-Smithsonian Center for Astrophysics, Cambridge, MA, United States

This work aims to develop a new bio-probe based on the detection and tracking of nontoxic nanoparticles in biological environments. We report the first DNP enhancement of 1H in a nanodiamond/water solution at very low magnetic field. Overhauser-enhanced MRI (OMRI) utilizes the nuclear hyperpolarization of hydrogen to detect paramagnetic species. A –1.36 times enhancement of the 1H signal has been demonstrated in a 10%/wt solution of 100 nm natural nanodiamonds (Microdiamant) and DI water at 6.5 mT. This result will drive further research into the use of OMRI methodologies as a means of tracking nanoparticles in vivo.

1897.   High Relaxivity MRI Contrast Agents based on a closo-borane platform
Shatadru Chakravarty1,2, Lixin Ma1, Lalit N. Goswami1, Satish S. Jalisatgi1, and M. Frederick Hawthorne1
1Radiology, International Institute of Nano and Molecular Medicine-University of Missouri-Columbia, Columbia, MO, United States, 2Radiology, Michigan State University, East Lansing, MI, United States

The signal intensity and the overall detail and clarity of an image obtained in an MRI exam is enhanced spectacularly by the administration of chemical species known as Contrast Agent (CAs). Despite several years of research, the current batch of clinically approved CAs are mostly small molecular weight species that suffer from low relaxivity, poor tissue selectivity and extremely short intravascular half-lives. We herein report a novel class of CAs based on a closo-borane framework with multifold improvements in relaxivity. These multifunctional molecules are based on the novel and unique twelve-fold functionalization of closo-B12(OH)122- with a modified Gd- AAZTA chelate.

1898.   Vesicles assembled from new dendrimeric amphiphiles and their applicative potential as MRI-based theranostic nanocarriers
Miriam Filippi1, Deyssy Patrucco1, Jonathan Martinelli2, Lorenzo Tei2, Mauro Botta2, and Enzo Terreno1,3
1Department of Molecular Biotechnology and Health Sciences, Molecular Imaging Center, University of Turin, Turin, To, Italy, 2Department of Sciences and Technological Innovation, University of Eastern Piedmont 'A. Avogadro', Alessandria, Al, Italy, 3Center for Preclinical Imaging, University of Turin, Colleretto Giacosa, To, Italy

Vesicles composed of newly synthesized amphiphilic dendrimers were investigated to understand their effective applicative potential as theranostic tools, based on their biocompatibility, stability in biological environments and capability to encapsulate Magnetic Resonance Imaging (MRI) agents and drugs. Dendrimeric vesicles revealed to be extremely safe and appropriate for vascular administration, besides displaying a very high membrane water permeability, preserving the Longitudinal Relaxivity of encapsulated paramagnetic MRI probes from undesired quenching effects. Specifically, 3,5-C12-EG-(OH)4–based vesicles were provided with highest stability, becoming interesting candidates for further development as theranostic tools.

1899.   Improved liposomes-based Ca(II) responsive MRI contrast agents
Francesca Garello1, Sandip Vibhute2, Serhat Gunduz2, Nikos K Logothetis2, Goran Angelovski2, and Enzo Terreno1
1University of Torino, Torino, Italy, 2Max Planck Institute for Biological Cybernetics, TŸbingen, Germany

This contribution reports a methodology that enables the preparation of paramagnetic liposomes loaded with an amphiphilic ligand capable to coordinate selectively and sequentially Gd(III) and Ca(II) ions, respectively. The presence of Gd(III) imparts the ability to generate MRI contrast, which is remarkably boosted (ca. 400%) by the coordination of Ca(II), thus improving the calcium responsiveness of the nanoprobes with respect similar agents previously investigated.

1900.   Organic radical contrast agents based on polyacetylenes containing 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO): targeted MR /optical bimodal imaging of folate receptor expressing HeLa tumors in vitro and in vivo
Lixia Huang1, Chenggong Yan1, Danting Cui1, Xiang Liu1, Xiaodan Lu1, Yichen Yan2, Xiangliang Tan1, Jun Xu3, Yingjie Mei4, Xinwei Lu2, Yikai Xu1, and Ruiyuan Liu2
1Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China, 2School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, China, 3Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China, 4Philips Healthcare, Guangzhou, Guangdong, China

Polyacetylenes containing 2,2,6,6-tetramethyl-piperidinooxy and poly(ethylene glycol) conjugated with carboxyl fluorescein and folic acid (FA) are synthesized by metathesis polymerization of corresponding substituted acetylenes for targeted bimodal MRI /optical imaging of tumors. In vitro studies confirm excellent binding specificity and subsequent enhanced cellular internalization of the targeted ORCAs (PA-TEMPO-FI-FA). In vivo T1-weighted MRI and optical imaging demonstrate the active tumor targeting ability of PA-TEMPO-FI-FA to generate specific contrast enhancement in mice bearing HeLa tumors. These results indicate that the multifunctional ORCAs may provide a tumor-targeted delivery platform for further molecular imaging guided cancer therapy.

1901.   Detection of matrix metalloproteinases using an "on/off" 19F MR probe
Alex John Taylor1, James Lee Krupa2, Huw Williams3, Dorothee P Auer1, Simon R Johnson4, Neil R Thomas2, and Henryk Michael Faas1
1Sir Peter Mansfield Imaging Centre, School of Medicine, University of Nottingham, Nottingham, Nottinghamshire, United Kingdom, 2School of Chemistry, University of Nottingham, Nottingham, Nottinghamshire, United Kingdom, 3Centre for Biomolecular Sciences, University of Nottingham, Nottingham, Nottinghamshire, United Kingdom, 4School of Medicine, University of Nottingham, Nottingham, Nottinghamshire, United Kingdom

A novel chemical sensor is presented which is able to detect matrix metalloproteinases (MMPs) using 19F MR. The contrast mechanism uses an “on/off” principle with paramagnetic gadolinium linked to a fluorine source via an enzyme substrate. Two examples of synthesised sensors are shown; one for MMPs 2 and 9, the other for all types of MMP. Upon addition of MMP 9, both sensors show an increased T1 relaxation time due to enzymatic cleavage which causes an increase in the fluorine-gadolinium distance. Fluorine signal intensity is also increased by a factor of 3.5 after MMP addition.

Ina Vernikouskaya1,2, Alexander Pochert3, Mika Linden3, 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, 3Inorganic Chemistry II, University of Ulm, Ulm, Baden-Wuerttemberg, Germany

19F offers great potential for in vivo quantification without any background signal. Perfluorocarbons (PFC) are typically applied due to their high 19F density. Mesoporous amorphous silica nanoparticles have attracted a lot of interest as drug carriers. However more attractive particle architecture would be hollow spheres with a porous shell that would allow higher PFC loadings per particles. 250nm-sized hollow mesoporous silica spheres (HMSS) are loaded with perfluoro-15-crown-5-ether (PFCE) and evaluated as a new contrast agent. PFCE-HMSS was characterized using MRI. 19F MRS was performed for quantification of the fluorine load. A good fluorine signal localized in the liver and in the brown fat was detected in vivo.

1903.   Multifunctional Gd2O3-loaded nanoprobe for targeted molecular MR imaging
Xiang Liu1, Xiaodan Lu1, Chenggong Yan1, Danting Cui1, Yichen Yan2, Xinwei Lu2, Queenie Chan3, Jun Xu4, Yikai Xu1, and Ruiyuan Liu2
1Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China, 2School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, China, 3Philips Healthcare, HongKong, China, 4Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China

Multifunctional and folate (FA) modified gadolinium oxide (Gd2O3) nanocarriers were developed for targeted molecular MRI of FA receptor positive HeLa tumors. Gd2O3-based nanoparticles were conjugated with 5(6)-carboxyfluorescein (FI) for fluorescence and functionalized with poly(ethylene glycol) (PEG) segments bearing FA group. Enhanced cellular uptake of the targeted Gd2O3 nanocarriers in Hela tumor cells was vitro. Moreover, the targeted Gd2O3 naoparticles showed more remarkable contrast enhancement than the control probes according in vivo MRI. Thus, these Gd2O3 nanoparticles may be a promising nano-platform for combined targeted antitumor drug delivery and molecular MRI cancer diagnosis in future clinical applications.

1904.   Facilitating the EPR Effect and Improving Tumor Penetration and Nanoparticle Delivery with Ultrafine Iron Oxide Nanoparticle as Observed via Its Dual-Contrast Effect
Jing Huang1,2, Liya Wang1,2, Hui Wu1,2, Lily Yang3, and Hui Mao1,2
1Laboratory of Functional-Molecular Imaging and Nanomedicine, Emory University School of Medicine, Atlanta, GA, United States, 2Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, Georgia, United States, 3Surgery, Emory University, Atlanta, GA, United States

Engineered nanoparticles are delivered to the tumor mainly through the enhanced permeability and retention (EPR) effect, which is dependent on and limited by nanoparticle size. Here we report ultrafine iron oxide nanoparticles (uIONPs) with a core diameter of 3.5 nm and dual T1-T2 contrast to facilitate the EPR effect for improved MRI and drug delivery. uIONPs are highly dispersed in circulation but can undergo reversible self-clustering at pH below 7, when entering tumor interstitial space, leading to switching from bright T1 contrast to dark T2 contrast while promoting tumor accumulation by 1.6 fold compared to nanoparticles with larger sizes.

1905.   Theranostic prospects of gadolinium-based mesoporous silica nanoparticle probes for functional MRI
Veronika Mamaeva1,2, Tina Pavlin3,4, Didem Sen Karaman5, Diti Desai5, Melanie Ostermann1, Jessica Rosenholm5, and Emmet McCormack1,2
1Department of Clinical Science, Hematology Section, University of Bergen, Bergen, Norway, 2Department of Internal Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway, 3Department of Biomedicine, Molecular Imaging Center, University of Bergen, Bergen, Norway, 4Department of Radiology, Haukeland University Hospital, Bergen, Norway, 5Laboratory of Physical Chemistry, Åbo Akademi University, Turku, Finland

A novel mesoporous silica nanoparticle MRI probe with theranostic prospects for targeted drug delivery was developed and applied to imaging of subcutaneous tumors in mice. Animals were injected either with Gd-doped MSNPs, pristine MSNPs, or Dotarem, and T1-weighted RARE images were collected pre- and at various time points post contrast injection. We observed a slight, but significant, increase of SI on T1-weighted images of GadoNPs-treated tumors at 24 hours. Conclusion: Gd–doped MSNPs are retained for at least 96 hours in tumor tissue and can be visualized by MRI, suggesting feasibility of using this NP platform for future theranostic applications.

1906.   Brain redox imaging using nitroxide contrast agents in pentylenetetrazol-kindled mice with EPR imaging
Hirotada G Fujii1, Miho C Emoto1, Mayumi Yamato2, and Ken-ichi Yamada2
1Center for Medical Education, Sapporo Medical University, Sapporo, Hokkiado, Japan, 2Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan

Seizure-induced neuronal death is thought to be caused by oxidative stress resulting from generation of reactive oxygen species (ROS). The purpose of this study was to examine the effect of oxidative stress in a pentylenetetrazol (PTZ)-induced seizure mouse model using a redox-sensitive nitroxide, 3-methoxycarbonyl-PROXYL, and to visualize brain redox status by noninvasive EPR imaging. In particular, a remarkable change in redox status in hippocampus of kindled mice was detected by EPR. An in vitro assay showed decreased concentrations of glutathione in the hippocampus after repeated seizures. Both results supported the involvement of ROS generation in epileptic-seizure mouse brain.

1907.   A NIR830-Bevacizumab-Conjugated Iron Oxide Nanoparticle Probe for Vascular Endothelial Growth Factor (VGEF) Targeted MRI
Run Lin1,2, Jing Huang1, Liya Wang1, Yuancheng Li1, Prieto Ventura Veronica E1, Kevin Kim1, and Hui Mao1
1Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, United States, 2Department of Radiology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China

Vascular endothelial growth factor (VEGF) plays a pivotal role in the cascade of development and progression of cancers by promoting angiogenesis. Targeting this biomarker would be a logical strategy for imaging based cancer detection and anti-angiogenesis treatment. Bevacizumab is a recombinant humanized monoclonal antibody directly against VEGF and is currently used in clinic for treating various cancers with VEGF overexpression. In this study, a VEGF targeted molecular imaging probe was developed by conjugating near infrared dye (NIR830) labeled bevacizumab to magnetic iron oxide nanoparticles (IONP) for optical and magnetic resonance (MR) imaging of cancers overexpressing VEGF.

1908.   Probing Gq-GPCR Signaling in Rat Primary Motor Cortex with Pharmacogenetic fMRI
Manasmita Das1, Heather K Decot1, Yu-Chieh Kao1, Oyarzabal Esteban1, and Yen-Yu Ian Shih1
1Biomedical Research Imaging Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States

The advent of novel genetic tools has triggered a renaissance in neuroscience research, providing tremendous opportunities to study the neuronal correlates of complex brain function with high spatiotemporal control. This study offers the first, direct evidence of fMRI responses to pharmacogenetic activation of excitatory neurons in rat primary motor cortex (M1) using Gq-coupled Designer Receptors Exclusively Activated for Designer Drugs (DREADDs). This novel technology contributes a potent toolbox for noninvasive mapping of GPCR-mediated cell signaling in vivo, a critical insight of which is necessary to understand various physiological and molecular phenomena and thus broaden the range of new therapeutic interventions.

1909.   Engineering of a MRI Theranostic Agent for Detection and Treatment of Cerebrovascular Amyloid
Jens T Rosenberg1,2, Kristen MJ Ahlschwede3,4, Edward K Agyare5, Geoffery L Curran4, Samuel C Grant1,2, and Karunya K Kandimalla3,4
1National High Magnetic Field Laboratory, Florida State University, Tallahassee, FL, United States, 2Chemical & Biomedical Engineering, Florida State University, Tallahassee, FL, United States, 3Pharmaceutics and Brain Barriers Research Center, University of Minnesota, Minneapolis, MN, United States, 4Neurology, Neuroscience and Biochemistry/Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN, United States, 5College of Pharmacy and Pharmaceutical Science, Florida A&M University, Tallahassee, FL, United States

This work demonstrates a novel MRI-detectable multifunctional nanoparticle targeting cerebrovascular amyloids by conjugating Gd-DTPA with the amyloid antibody Ig 4.1 while at the same time providing drug delivery capabilities. This theranostic nanovehicle shows hypointense contrast for targeted cerebrovascular amyloids on MR microimages acquired at the ultrahigh field of 21.1 T. The approach potentially can provide a heretofore sought after diagnostic and therapeutic tool for cerebral amyloid angiopathy.

1910.   An EDB fibronectin specific contrast agent for molecular imaging of cancer metastasis
Zheng Han1, Zhuxian Zhou1, Maneesh Gujrati1, and Zheng-Rong Lu1
1Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, United States

This work uses ZD2-(HP-DO3A), a peptide-based targeting agent, for MRI molecular imaging of cancer metastasis. Accuracy and sensitivity of cancer metastasis imaging can be improved due to the sensitive targeting of this imaging agent to EDB fibronectin.

1911.   Improving Tumor Targeting and MRI of Pancreatic Cancer Using IGF-1R Targeted "Stealth" Iron Oxide Nanoparticles
Yuancheng Li1,2, Hongyu Zhou3, Run Lin1,2, Liya Wang1,2, Jing Huang1,2, Hui Wu1,2, Lily Yang3, and Hui Mao1,2
1Laboratory of Functional-Molecular Imaging and Nanomedicine, Emory University School of Medicine, Atlanta, Georgia, United States, 2Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, Georgia, United States, 3Department of Surgery, Emory University School of Medicine, Atlanta, Georgia, United States

Biomarker-targeted pancreatic tumor imaging has been investigated by MRI using the anti-biofouling iron oxide nanoparticle (IONP) previously developed in our group. This nanomaterial demonstrated an excellent anti-biofouling effect to prevent the formation of protein corona and the non-specific cellular uptake. As a consequence of the excellent anti-biofouling property, PEG-b-AGE coated IONP conjugated with targeting ligands showed significantly improved targeting specificity and efficiency by reducing off-target and non-specific interactions with biological media. After systemic administration of IGFR targeted IGF-IONP and non-targeted BSA-IONP, in vivo MRI showed 44% and 21% signal intensity drop in pancreatic tumor.

1912.   Paramagnetic micelles targeting VCAM-1 receptors for imaging inflamed endothelium by MRI
Amerigo Pagoto1, Rachele Stefania2, Francesca Garello2, Francesca Arena2, Giuseppe Digilio3, Silvio Aime2, and Enzo Terreno2
1University of Torino, Torino, Italy, 2University of Torino, Italy, 3University of Eastern Piedmont, Italy

Imaging inflammation is still a hot topic for its relevance in both diagnosis and therapeutic fields. To overcome the poor sensitivity in the detection of MRI contrast agents, we target the intravascular inflammation-associated receptors VCAM-1 (Vascular Cell Adhesion Molecule-1) that are involved in the recruitment of immune cells from blood to the inflammation site. To further increase sensitivity, micellar nanoparticles containing a high number of Gd(III) complexes were prepared. Such micelles, which exposed the MRI agents, a specific peptide targeting VCAM-1, and a fluorescent dye for histological validation, were successfully tested on mouse models of peripheral, and brain inflammation.

1913.   Functional Brain Mapping in ADHD Rats using Manganese-enhanced MRI
Chieh-Yin Chang1, Chi-Ru Lai1, Bor-Show Tzang2, Vincent Chin-Hung Chen3, Yeu-Sheng Tyan1,4, and Jun-Cheng Weng1,4
1School of Medical Imaging and Radiological Sciences, Chung Shan Medical University, Taichung, Taiwan, 2Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan, 3Department of Psychiatry, Chung Shan Medical University Hospital, Taichung, Taiwan, 4Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung, Taiwan

The spontaneously hypertensive rat (SHR) is the best-validated animal model of attention-deficit hyperactivity disorder (ADHD) based on behavioral, genetic, and neurobiological data. The symptoms of this common disorder include difficulty controlling behavior and over-activity. Manganese-enhanced MRI (MEMRI) uses manganese ion (Mn2+) as the contrast agents by shortening the spin-lattice relaxation time constant (T1) and entering the voltage-gated calcium channels in active neurons. It enables visualization of neuronal tracks, and enhance the capacity of MRI to provide functional information of the localization of brain activity. In the study, we tried to establish a working protocol to map the motor cortex of ADHD rats, and compared the functional brain mapping between ADHD and normal Wistar-Kyoto (WKY) rats by MEMRI method. In the results, we have mapped ADHD motor cortex using MEMRI and have shown the difference of the manganese enhanced cortical and thalamic regions between ADHD and WKY rats.

1914.   Manganese Accumulations in Brain and Toenails reflect Different Time Periods of Exposure
Chien-Lin Yeh1,2, Eric Ward1, Sandy Snyder1, Frank Rosenthal1, and Ulrike Dydak1,2
1School of Health Sciences, Purdue University, West Lafayette, Indiana, United States, 2Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana, United States

High exposure to manganese (Mn) causes motor impairments closely resembling Parkinson’s disease. Using R1 relaxation rate mapping we investigated the relationship between Mn deposition in the brain of welders with Mn accumulation in toenails. A significant correlation was found between R1 and Mn exposure in the past 3 months, but no correlation was found between toenail Mn and R1. Since toenail Mn is known to best reflect exposure 7-12 months ago, our results demonstrate that R1 in certain brain regions and toenail Mn accumulation may both serve as biomarkers of exposure to Mn, reflecting different time periods of exposure.

1915.   Adult Neurogenesis and Olfactory Activity Regulate Olfactory Bulb Volume
Nikorn Pothayee1, Diana Cummings2, Timothy Schoenfeld3, Heather Cameron3, Leonardo Belluscio2, and Alan Koretsky1
1Laboratory of functional and molecular imaging, NINDS, NIH, Bethesda, MD, United States, 2Developmental neural plasticity section, NINDS, NIH, Bethesda, MD, United States,3Neuroplasticity Section, NIMH, NIH, Bethesda, MD, United States

Olfactory bulb displays remarkable plasticity and its volume changes have been implicated in many CNS pathologies such as Alzheimer’s and Parkinson’s diseases. Understanding factors that play role in regulating the OB and its size may yield insights into the OB plasticity. In this work, we utilize longitudinal cellular MRI in combination with transgenic animal model of adult neurogenesis to study interplaying effects of olfactory input level and neurogenesis on the dynamic volume changes of the olfactory bulb.

1916.   Distinction between pro and anti-inflammatory macrophages using MRI relaxometry and quantitative susceptibility mapping
Wassef Khaled1, Benjamin Leporq1, Jing Hong Wan1, Philippe Garteiser1, Simon Auguste Lambert1, Nathalie Mignet2, Bich-Thuy Doan2, Simona Manta2, Sophie Lotersztajn1, and Bernard Edgar Van Beers1
1Center of research on inflammation, Paris 7 University; INSERM U1044, Paris, France, 2Chemical, Genetic and Imaging Pharmacology Laboratory; CNRS UMR 8151; INSERM U1022, Faculty of Pharmacy, Paris Descartes University, Sorbonne Paris Cité, Chimie-ParisTech, Paris, France

This work aims at distinguishing pro and anti-inflammatory (M1 and M2) macrophages with relaxometry and QSM using the degree of phagocytosis of gadolinium liposomes and superparamagnetic iron oxide particles as imaging biomarker. At relaxometry and QSM, M1 macrophages showed higher R2*and susceptibility, indicating higher particle uptake, as confirmed by confocal microscopy. These results show that it is feasible to distinguish between M1 and M2 macrophages with relaxometry and QSM, making phagocytosis of magnetic particles a potential MRI biomarker of inflammation.

1917.   A Novel Assay for the in vivo Detection of Reactive Oxygen Species Using MRI
Gary Stinnett1, Kelly Ann Moore1, Errol Loïc Samuel2, Ming Ge3, Brett Graham3, James Tour2, and Robia G Pautler1
1Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, United States, 2Department of Chemistry, Rice University, Houston, Texas, United States,3Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States

Due to their paramagnetic properties, increased production of superoxide and hydroxyl radicals can cause decreases in T1 relaxation. Animals with increased superoxide and hydroxyl radical production will have lower T1 values in the liver compared to wild type controls. To determine that T1 reduction is due specifically to increased superoxide and hydroxyl radicals, animals were then treated with superoxide scavenging PEG-HCCs. These particles rendered the superoxide and hydroxyl anions inert, increasing T1 values to that of wild type controls. We therefore demonstrate that it is possible to use MRI in conjunction with PEG-HCCs to measure in vivo ROS levels.

1918.   Non-invasive analysis of the degree of inflammatory areas by in vivo time course MRI using long circulating nanoparticles in myocardial inflammation rat model
Hyeyoung Moon1, Jongeun Kang2, Hyunseung Lee1, and Kwan Soo Hong1,2
1Division of MR research, Korea Basic Science Institute, Cheongju, Chungcheongbuk-do, Korea, 2Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon, Korea

In our study, we investigated whether MNP-enhanced MRI could distinguish between the severe inflammatory sites, weak inflammatory sites, and normal tissues within 12 h after injection of MNPs having long blood-circulation time using myocardial inflammation induced rat models.

1919.   Morphological and Quantitative Imaging of Iron Using MP-RAGE and UTE Sequences
Wen Hong1, Qun He2, Hongda Shao2, and Jiang Du2
1Radiology, China-Japan friendship hospital, Beijing, Beijing, China, 2Radiology, UC, San Diego, San Diego, CA, United States

The purpose of this study was to compare 3D-MP-RAGE and UTE sequences for morphological and quantitative imaging of iron.3D MP-RAGE sequence can be used to generate high contrast for lower iron concentration (0.1 to 10 mM), while IR-UTE, especially 3D IR-Cones sequences can be used to imaging iron with higher concentration (0.1 to 30 mM) .

1920.   Characterization of Perfluorocarbon Relaxation Times and Optimization of Fluorine-19 MRI at 3 Tesla
Roberto Colotti1,2, Christine Gonzales3, Juerg Schwitter3, and Ruud B. van Heeswijk1,2
1Department of Radiology, University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland, 2Center for Biomedical Imaging (CIBM), Lausanne, Switzerland,3Division of Cardiology and Cardiac MR Center, Department of Internal Medicine, University Hospital of Lausanne (CHUV), Lausanne, Switzerland

The relaxation times of a perfluoropolyether perfluorocarbon (PFC) that is used for fluorine-19 MRI were determined on a 3T clinical scanner under different physiological conditions. The results were used in Bloch equation simulations to optimize a turbo spin echo (TSE) pulse sequence and to evaluate the loss of acquisition efficiency due to the varying relaxation times observed under different physiological conditions.

1921.   Disentangling different Gadolinium concentrations: a comparison between High Field and Very Low Field MRI.
Allegra Conti1, Massimo Caulo1,2, Angelo Galante3, Vittorio Pizzella1,2, Gian Luca Romani1,2, and Stefania Della Penna1,2
1Department of Neuroscience, Imaging and Clinical Sciences, G. D'Annunzio Univ. of Chieti and Pescara, Chieti, CH, Italy, 2Institute for Advanced Biomedical Technologies (ITAB), G. D'Annunzio Univ. of Chieti and Pescara, Chieti, CH, Italy, 3MESVA, Department of Life, Health & Environmental Sciences, L'Aquila University, L'Aquila, AQ, Italy

Gadolinium based Contrast Agents are routinely used in MRI to improve the diagnostic accuracy of brain pathologies. Recently, Very and Ultra Low Field-MRI scanners have been developed, and the advantages of these system in the study of tissue contrast have been suggested. Here we show how the contrast of T1-weighted images of different concentrations of MultiHance and Gadovist changes varying the applied field (8.9 mT, 0.2 T, 1. 5 T ,3 T). Results demonstrate that signal contrast does not improve at high field strengths, and that longitudinal relaxation rate-maps at ULF are the best instruments to distinguish different Gd-concentrations.

1922.   Design of Implantable alginate MRI pH sensors for cell transplantation
Nikita Oskolkov1,2, Xiaolei Song1,2, Kannie W.Y. Chan1,2, Jeff W.M. Bulte1,2, and Michael T. McMahon1,2
1The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins School of Medicine, Baltimore, Maryland, United States, 2F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland, United States

Cell transplantation is an important strategy for treating otherwise incurable diseases, with numerous clinical trials now ongoing all over the world. Various biocompatible materials have been designed to support transplanted cells and protect them from the immune system. Our previous study showed that alginate-based hydrogels could be used for non-invasive monitoring of hepatocytes cell death in vivo using pH sensitive CEST magnetic resonance imaging (MRI) technique. In this study we were interested in redesigning these for use on lower field scanners, through incorporating salicylic acid (SA)-based pH-nanosensors into the biomaterial through dispersing SA-liposomes through alginate capsules. These SA agents display CEST contrast at high-frequency-offsets. In this abstract we show how these can be used for non-invasive MRI imaging of encapsulated cells.

1923.   Iron Retention in Nonproliferative Cancer Cells Allows for Tracking by MRI: An In Vivo Assay for Studying Cancer Cell Dormancy
Donna H Murrell1,2, Fiona Dickson1, Amanda M Hamilton1, and Paula J Foster1,2
1Imaging, Robarts Research Institute, London, Ontario, Canada, 2Medical Biophysics, Western University, London, Ontario, Canada

Monitoring the fate of dormant cancer cells is important because these provide a reservoir of viable cells that contribute to relapse, even after treatment appears successful. Here, we demonstrate that iron-based MRI cell tracking can be used to study nonproliferative cancer cells in metastatic and primary cancer models. We present 3D MRI of the mouse brain illustrating persisting signal voids over time and show these represent nonproliferative cancer cells. This work shows varying dormancy profiles in cancer, and the ability for nonproliferative cells to persist through therapy. Understanding this dormant cell population is vital to prevent tumor recurrence in patients.

1924.   Tracking and quantification of T-cells labelled with iron oxide nanoparticles using positive contrast
Jinjin Zhang1, Sidath C. Kumarapperuma2, Katie Hurley3, Hattie L. Ring3, and Michael Garwood1
1Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota, Minneapolis, MN, United States, 2Department of Medicinal Chemistry, University of Minnesota, MN, United States, 3Department of Chemistry, University of Minnesota, MN, United States

Cell-based therapies have received much attention as novel therapeutics for the treatment of cancer and autoimmune disease. In this study, T-cells labeled with superparamgnetic iron oxide nanoparticles (SPION) at different concentrations were quantified using the SWIFT Look-Locker T1 mapping method. The longitudinal relaxation rate constant (R1) measured by SWIFT showed a linear dependence on the concentration of SPION in T-cells. These preliminary results indicate a potential role for positive contrast from SWIFT as a means to quantify the distribution of SPION-labeled cells, provided the cells are incubated at a constant SPION concentration.

1925.   Labeling of human peripheral blood mononuclear cells with a Fluorine-19 perfluorocarbon agent permits their in vivo detection using cellular MRI and allows for cancer vaccine formulation comparisons
Corby Fink1,2, Jeffrey Gaudet2,3, Paula Foster2,3, and Gregory Dekaban1,2
1Microbiology and Immunology, Western University, London, Ontario, Canada, 2Robarts Research Institute, London, ON, Canada, 3Medical Biophysics, Western University, London, ON, Canada

A critical aspect of cell-based therapies involving engineered primary cells is knowledge of the location, number and persistence of therapeutic cells following injection. With respect to antigen presenting cell-based cancer vaccines, tracking and quantification of their in vivo migration to a secondary lymphoid organ can be used to not only assess the effectiveness of the vaccine, but also to compare the effectiveness of different vaccine formulations. Our laboratory has efficiently labeled human peripheral blood mononuclear cells with a Fluorine-19 perfluorocarbon cell-labeling agent, which permits their in vivo detection and quantification in a mouse model.

1926.   MR molecular imaging of homing of Integrin-linked kinase-overexpressing mesenchymal stem cells after transplantation via coronary in Swine acute myocardial infarction model
Dan Mu1, Hong Ming Yu2, Bin Zhu3, Biao Xu4, and Wei Bo Chen5
1Drum Tower Hospital, Nanjing, Jiangsu, China, 2Drum Tower Hospital, Jiangsu, China, 3Radiology, Drum Tower Hospital, Nanjing, Jiangsu, China, 4cardiology, Drum Tower Hospital, Jiangsu, China, 5Philips Healthcare, Shanghai, China

The present study in vivo detect the homing and migration ability of MSCs overexpressing ILK (ILK-MSCs) after transplantation via coronary in swine model of AMI using MR molecular imaging technique.

1927.   MRI detection of brain metastases labeled with iron oxide nanoflowers
Emily Alexandria Waters1, Luke Vistain2, Liang Mu3, Madhavi Puchalapalli4, Chad Haney1, Basma El Haddad4, Brandon Parker3, Thomas Meade5, and Jennifer Koblinski4
1Center for Advanced Molecular Imaging, Northwestern University, Evanston, IL, United States, 2Interdisciplinary Biological Sciences Program, Northwestern University, Evanston, IL, United States, 3Northwestern University, IL, United States, 4Pathology, Virginia Commonwealth University, Richmond, VA, United States, 5Chemistry, Northwestern University, Evanston, IL, United States

Though improved treatment of primary breast cancers has increased patient survival, those diagnosed with brain metastases typically survive only 2-16 months. Understanding mechanisms of breast cancer metastasis to the brain should improve patient outcomes. We modeled metastasis in mice with intracardiac injection of bioluminescent breast cancer cells that had been labeled with iron oxide nanoflowers. We used IVIS to screen for successful cell delivery to the brain and then MRI to track the labeled cells for 7 days after their arrival in the brain.

1928.   In vivo quantification of human natural killer cells by 19F MRI
Kai D. Ludwig1, Myriam Bouchlaka2, Jeremy Gordon1, Christian Capitini2, and Sean B. Fain1,3
1Medical Physics, University of Wisconsin-Madison, Madison, WI, United States, 2Pediatrics and Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, United States, 3Radiology and Biomedical Engineering, University of Wisconsin-Madison, WI, United States

A current unmet need in cellular-based immunotherapies is longitudinal tracking and quantification of cells after infusion into a patient. Previously, human natural killer (hNK) cells have successfully been intracellularly labeled with a perfluoropolyether (PFPE) enabling in vivo detection and longitudinal tracking by 19F MRI. Here, a labeling concentration of 4mg/mL PFPE resulted in hNKs with 3.6plus-or-minus sign0.5multiplication sign1011 19F/cell. A minimum detection limit was extrapolated to be 1.2multiplication sign105 hNKs/voxel at 4.7 T. In vivo quantification on a tumor-bearing mouse showed intratumorally localized 19F signal over 7 days with 60-70% of the initially injected hNK cells being detected at all time points.

1929.   Tracking iron labeled stem cells in bone injury model using MRI
May A Taha1, Roman Krawetz2, Derrick E Rancourt2, John R Matyas3, and Jeff F Dunn1
1Department of Radiology, Calgary, Alberta, Canada, 2Department of Biochemistry & Molecular Biology, Alberta, Canada, 3Department of Comparative Biology and Experimental Medicine, Faculties of Medicine and Veterinary Medicine, University of Calgary, Alberta, Canada

Stem cell therapies show significant promise for stimulating healing of bone injury, but nothing is known of how stem cells migrate after implant. We developed a successful iron labeling protocol for embryonic stem cells. We proved it is possible to track ESC’s using 9.4T MRI in a mouse bone injury model and showed that cells migrated to the marrow and to a second injury site. We are the first to image ESC migration in bone injury and, as we did this in mice, it opens the possibility of using the range of mouse models available to study bone injury

1930.   Comparison of Iron-related MR Susceptibility and Transverse Relaxation Rates in the P19 Cell Model
Linshan Liu1,2, Neil Gelman1,2, Rebecca McGirr1, R. Terry Thompson1,2, Frank S Prato1,2, Lisa Hoffman1,2, and Donna E Goldhawk1,2
1Imaging program, Lawson Health Research Institute, London, Ontario, Canada, 2Medical Biophysics, Western University, London, Ontario, Canada

MRI-based cell tracking techniques play an important role in developing cellular therapy. To improve these detection methods, we have examined MR measures of iron contrast in the P19 cell model. We measured the changes in apparent susceptibility (χa) and transverse relaxation rates (R2*, R2', R2) in cells cultured in the presence and absence of iron supplementation. Cellular iron content was determined using inductively-coupled plasma mass spectrometry and normalized to the amount of protein. The change in transverse relaxation rates showed a stronger correlation to iron levels than did the change in apparent susceptibility.

1931.   Fluorine-19 labelling of stromal vascular fraction cells for clinical imaging applications
Laura C Rose1, Guan Wang1, Brooke M Helfer2, Charles F O'Hanlon2, Amnon Bar-Shir1, Dara L Kraitchman1, Ricardo L Rodriguez3, and Jeff WM Bulte1
1Johns Hopkins University, Baltimore, MD, United States, 2Research & Development, Celsense Inc, PA, United States, 3CosmeticSurg LLC, Luthersville, MD, United States

Labeling cells with perfluorinated carbons allows tracking with 19F-MRI in vivo. As part of clinical trial NCT02035085 and FDA IND submission, we labeled adipose-derived stromal vascular fraction (SVF) cells and determined uptake in cell subtypes. The majority (87-92%) of CD31+ and CD34+ stem cells were labeled but only 47% of CD45+ cells, highlighting SVF cell heterogeneity. With a 3T clinical set-up and 19F content of 1012 atoms/cell, 2x106 cells were detected in a breast phantom 5mm below the surface. With 1x108 SVF cells for breast reconstruction, this sensitivity will be sufficient to track transplanted SVF cells in breast cancer survivors.

1932.   RRx-001 Oxidation of Redox Sensitive Protein Thiols in Tumors Measured by Gd-LC7-SH Enhanced MRI In Preclinical Tumor Models
Natarajan Raghunand1, Jan Scicinski2, Bryan Oronsky2, Bhumasamudram Jagadish3, Eugene A Mash3, and Ronald L Korn4
1Cancer Imaging & Metabolism, Moffitt Cancer Center, Tampa, Florida, United States, 2RadioRx Pharmaceuticals, Mountain View, California, United States, 3Dept. of Chemistry & Biochemistry, The University of Arizona, Tucson, Arizona, United States, 4Imaging Endpoints LLC, Scottsdale, Arizona, United States

We have investigated the kinetics of T1-shortening produced in 3 pre-clinical tumor xenograft models by Gd-LC7-SH, a DOTA-thiol complex of gadolinium. Mice were imaged before and at multiple time points following treatment with RRx-001, a novel anticancer agent that perturbs tumor redox status. Gd-LC7-SH spontaneously binds to macromolecular thiol targets following i.v. administration, producing prolonged shortening of tumor T1 in untreated animals. Following treatment with RRx-001 the washout of Gd-LC7-SH from tumors was markedly faster, consistent with the proposed glutathione-depleting mechanism of action of the drug. Use of Gd-LC7-SH-enhanced MRI as a pharmacodynamic marker of RRx-001 action is discussed.

1933.   Non-invasive assessment of hyperthermic ultrasound enhanced tumor drug delivery with CE-MRI
Nadia Rose Ayat1, Rebecca Schur1, and Zheng-Rong Lu1
1Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, United States

Utilizing mild hyperthermia (40-42°C ) has the potential to increase blood flow into tumors, and thus overcome some of the barriers to drug delivery. This study utilizes MRI to determine the effect of ultrasound-induced mild hyperthermia on the uptake of a paramagentically labeled polymer conjugate. The results of this study show that contrast enhancement increased two-fold upon the induction of hyperthermia in the tumor periphery. A five-fold increase in contrast enhancement was also seen in the tumor intersitium. This work suggests that mild hyperthermia has the potential to enhance the therapeutic efficacy of drugs in development for cancer treatment.

1934.   Eight channel Tx/Rx RF coil array for 1H/19F MR of the Human Knee and Fluorinated Drugs at 7.0 T
Yiyi Ji1, Helmar Waiczies1,2, Lukas Winter1, Pavla Neumanova1, Daniela Hofmann1, Jan Rieger1,2, Ralf Mekle3, Sonia Waiczies1, and Thoralf Niendorf1,4
1Berlin Ultrahigh Field Facility (B.U.F.F.), Max Delbrück Center for Molecular Medicine, Berlin, Germany, 2MRI.TOOLS GmbH, Berlin, Germany, 3Medical Physics, Physikalisch-Technische Bundesanstalt, Berlin, Germany, 4Experimental and Clinical Research Center, a joint cooperation between the Charité Medical Faculty and the Max Delbrück Center, Berlin, Germany

The sensitivity limit for 19F detection constitutes an impediment for translational research and clinical applications of in vivo 19F MR. This limitation could be overcome by sensitivity gain at UHF. This work proposes a double-tuned 1H/19F Tx/Rx RF coil array tailored for knee imaging to examine the feasibility of human 1H/19F MR at 7.0 T. The suitability of the proposed approach for 19F MR following topical application of a fluorinated drug is demonstrated.

1935.   Initial Evaluation of an MR-Hyperthermia Activated Thermosensitive Drug Delivery System
Matthew Tarasek1, Amanda Aleong2,3, Jinzi Zheng2,3, Yannan Dou4, Christine Allen3,4, David Jaffray3,4, Tom Foo1, and Desmond T.B. Yeo1
1MRI, GE Global Research, Niskayuna, NY, United States, 2Princess Margaret Cancer Centre, Toronto, Canada, 3Techna Institute, University Health Network, Toronto, Canada,4University of Toronto, Toronto, Canada

Current innovations in the field of advanced drug delivery are focused on the development of new systems that can (i) trigger drug release at the tumor sites, (ii) avoid drug deposition in non-target tissues, and (iii) allow for quantitative measurement of drug dose to the target tissue. Here we report a pilot evaluation of a novel MR image-guided radiofrequency (RF) hyperthermia-mediated drug delivery platform. Results indicate that the MR body coil provides adequate image quality for monitoring drug release in the current setup, despite its inherent limitations in image acquisition speed and SNR when compared to surface-coil arrays.

1936.   Functionalized Mesoporous Silica Iron Oxide Nanoparticles for Thermal Therapy and T1 Contrast
Hattie L. Ring1,2, Katie R. Hurley2, Michael Etheridge3,4, Jinjin Zhang1,5, Nathan D. Klein2, Connie Chung3,4, Qi Shao4, John C. Bischof3,4, Christy L. Haynes2, and Michael Garwood1,6
1Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, United States, 2Chemistry, University of Minnesota, Minneapolis, MN, United States,3Mechanical Engineering, University of Minnesota, Minneapolis, MN, United States, 4Biomedical Engineering, University of Minnesota, Minneapolis, MN, United States, 5Physics, University of Minnesota, Minneapolis, MN, United States, 6Radiology, University of Minnesota, Minneapolis, MN, United States

Iron oxide nanoparticles (IONPs) have great potential as diagnostic and therapeutic agents in cancer and other diseases; however, their utility is limited by biological aggregation and a short T2. We implement the incorporation of a functionalized mesoporous silica (ms) shell combined with sweep imaging with Fourier transform MRI. This enables the practical use of IONPs as a T1 contrast agent in vitro and in vivo, which is demonstrated in lymph node carcinoma of prostate cells and tumors. Colloidal stability and minimal non-specific cell uptake allowed for effective heating in biological suspensions and strong signal enhancement in MRI in vivo.

1937.   Quantitative treatment response mapping in asthma patients using 3He ventilation MRI
Felix C Horn1, Helen Marshall1, Richard Kay2, Christopher E Brightling3, Juan Parra-Robles1, and Jim M Wild1
1Academic Radiology, Sheffield University, Sheffield, South Yorkshire, United Kingdom, 2Novartis, Switzerland, 3University of Leicester, United Kingdom

Sensitive regional methods to assess efficacy of respiratory therapeutics are urgently needed. A method using hyperpolarized 3He ventilation imaging is introduced to calculate quantitative treatment response maps. Ventilation images from before and after bronchodilator treatment are used to quantify ventilation changes and are masked by a baseline variability calculated from two ventilation images acquired before treatment. The technique is compared to percentage ventilated volume (%VV) and forced expiratory volume (FEV1). In this cohort all tests showed significant differences before and after treatment, nevertheless TRM displayed a tighter clustering and clearer separation of positive from negative response.

1938.   NanoIron Phantom to Validate In-Vivo Iron Mapping
Stephen E. Russek1, Kathryn E. Keenan1, Karl Stupic1, Michael A. Boss1, Zydrunas Gimbutas1, Andrew M. Dienstfrey1, and Robert J. Usselman2
1NIST, Boulder, CO, United States, 2University of Montana, Bozeman, MT, United States

We investigated several materials for use in a nano-iron phantom including Fe chelates, hemoglobin, recombinant human ferritin, horse spleen ferritin (HSF), Feraheme, Molday ion, nanoComposix iron oxide, textured (chained) nanoparticles. The range of concentrations was selected to match brain iron concentrations in healthy and diseased tissue (100-200 ppm). A key advance was to develop recombinant human ferritin by obtaining H-chain DNA sequences, amplifying with PCR, splicing them into pET30a(+) plasmids, and transfecting E. Coli. Various mineralization techniques were applied to mimic pure phase, healthy, and pathologic forms of human ferritin. These materials were incorporated into phantoms and characterized using multiparameter mapping to assess ability to measure concentration and form in-vivo.

1939.   Machine learning and computer vision based quantification of cell number in MRI-based cell tracking
Muhammed Jamal Afridi1, Matt Latourette2, Margaret F Bennewitz3, Arun Ross1, Xiaoming Liu1, and Erik M Shapiro2
1Department of Computer Science and Engineering, Michigan State University, East Lansing, MI, United States, 2Department of Radiology, Michigan State University, East Lansing, MI, United States, 3Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, United States

MRI detection of single cells is an underutilized advancement in MRI-based cell tracking. One reason for its underutilization has been a lack of methods for quantifying information in these images. For example, single cell detection enables quantification of cell numbers and accurate cell localization. To achieve single cell detection by MRI, cells are labeled with superparamagnetic iron oxide particles allowing their detection as punctate hypointensities in T2*-weighted MRI. We have developed a machine learning and computer vision based strategy for the generalizable detection and quantification of MRI-based single cell detection. Our approach can detect spots with an accuracy of 99.8%.