ISMRM 21st Annual Meeting & Exhibition 20-26 April 2013 Salt Lake City, Utah, USA

Novel Contrast Agents & Reporters
Monday 22 April 2013
Room 255 EF  16:30 - 18:30 Moderators: Assaf A. Gilad, Willem M. Mulder

16:30 0151.   
in-vivo 29Si Magnetic Resonance Imaging of Hyperpolarized Silicon Particles
Maja Cassidy1, Henry Chan2, Pratip Bhattacharya2,3, and Charles Marcus1,4
1Harvard University, Cambridge, MA, United States, 2Huntington Medical Research Institutes, Pasadena, CA, United States, 3Experimental Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, United States, 4University of Copenhagen, Copenhagen, Denmark

We report direct in-vivo imaging of hyperpolarized silicon microparticles by 29Si MRI. Hyperpolarization of the 29Si nuclei is generated by dynamic nuclear polarization using electronic defects that naturally occur at the particle surface, and so no additional radical is required. Applications to gastrointestinal, intravascular, and tumor perfusion imaging at sub-picomolar concentrations are presented.

16:42 0152.   
Imaging Ca2+ Using Fluorine Chemical Exchange Saturation Transfer (19F-CEST)
Amnon Bar-Shir1,2, Assaf A. Gilad1,2, Kannie W.Y. Chan1,3, Guanshu Liu1,3, Peter C.M. van Zijl1,3, Michael T. McMahon1,3, and Jeff W.M. Bulte1,2
1Department of Radiology, Johns Hopkins University, Baltimore, MD, United States, 2Institute for Cell Engineering, Johns Hopkins University, Baltimore, MD, United States, 3F.M. Kirby Research Center, Kennedy Krieger Institute, Baltimore, MD, United States

Although Ca2+ ions are involved in a myriad of biological signaling processes, a non-invasive means of detecting micromolar Ca2+ levels remains a formidable challenge. We present an approach for specifically sensing the presence of Ca2+ ions through its substrate binding kinetics by exploiting the chemical shift change of 19F upon binding of Ca2+ to the fluorinated chelator 1,2-Bis-[2-bis(carboxymethyl)amino-5-19fluorophenoxy]ethane (5-19FBAPTA). Using RF labeling at the bound-19F frequency and detection of label transfer to the free-19F frequency (Δω=5.8ppm) in millimolar concentration substrate, we were able to amplify the signal of Ca2+ with supreme specificity over other divalent cations.

16:54 0153.   
A Novel MR-Visible Persistent Apoptosis Marker Validated with Immunohistochemistry
Firas Moosvi1, Jennifer H.E. Baker1,2, Andrew Yung1, Kenneth Curry3, and Stefan A. Reinsberg1
1Physics and Astronomy, University of British Columbia, Vancouver, BC, Canada, 2Radiation Biology, BC Cancer Research Institute, Vancouver, BC, Canada, 3RF Therapeutics, Vancouver, BC, Canada

We validate an MR-visible, necrosis-avid contrast agent(RF1101) using TUNEL staining and DCEMRI. The agent is injected and binds to areas of apoptosis/necrosis and unbound agent is excreted from the systemic circulation. T1-weighted imaging is performed after approximately 24h to identify areas of contrast agent uptake. Data from a preclinical cancer model is shown with spectacular agreement between histologically identified areas of necrosis and RF1106 uptake.

17:06 0154.   Evaluation of Vanadium-Based Contrast Agents for Detection of Early Murine Colon Cancer Using MRI, X-Ray Fluorescence Microscopy and a Novel Method of Image Co-Registrations
Devkumar Mustafi1, Jesse Ward2, Urszula Dougherty3, Erica Markiewicz1, Marc Bissonnette3, Stefan Vogt2, and Gregory S. Karczmar1
1Radiology, The University of Chicago, Chicago, Illinois, United States, 2Advanced Photon Source - Sector 2, Argonne National Laboratory, Lemont, Illinois, United States, 3Medicine, The University of Chicago, Chicago, Illinois, United States

Targeted contrast agents that specifically enhance early cancers could significantly improve diagnostic accuracy. Here we compare a new vanadium-based (VC) MRI contrast agent that is sensitive to glycolysis to a conventional Gd-based agent in a mouse model of colorectal cancer. A novel method is developed for co-registrations of in vivo MR images with ex vivo histological images using agar-based phantoms. X-ray fluorescence microscopy (XFM) imaging was used to quantify contrast uptake directly and to determine cellular and sub-cellular distributions in situ. Results revealed that VC-based agents preferentially accumulate in cancer cells, offering an advantage over less selective Gd-based agents.

17:18 0155.   
Chemical Doping of Iron Oxide Inside Apoferritin to Form an MRI Contrast Agent with High R1 and Low R2
Maria Veronica Clavijo Jordan1 and Kevin M. Bennett1
1School of Biological and Health Systems Engineering, Arizona State University, Tempe, Arizona, United States

Chemical doping is implemented in order to disrupt magnetic moment coupling within a crystal and render a paramagnetic nanoparticle. Tunstate is introduced inside the apoferritin cavity as a dopant of the iron oxide core. The crystal surface un-coupled moments are in close contact with the surrounding water protons to reduce overall longitudinal relaxation. The paramagnetic apoferritin composite resulted in a particle r1 of 4870mM-1s-1 and r2/r1 of 1.86 making them a sensitive nanoparticle agent for in vivo molecular MRI.

17:30 0156.   
Using Magnetization Transfer Contrast as a Surrogate Marker for the Occurrence of a Foreign Body Reaction in Hydrogel-Based Cell Therapy -permission withheld
Kannie W.Y. Chan1,2, Guanshu Liu1,3, Peter C.M. van Zijl1,3, Jeff W.M. Bulte2,4, and Michael T. McMahon1,3
1Russell H. Morgan Department of Radiology and Radiological Science, The 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, 3F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, 4Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, United States

Hydrogels are used to enhance cell transplantation therapies by providing immunoprotection and physical support. A non-invasive imaging technique that allows monitoring of successful engraftment and lack of fibrosis is needed. In particular at an early stage where cell infiltration is commonly found, imaging is necessary to assess if adjustments are required to enhance cell survival. Here, we are interested in monitoring if cell infiltration is occurring in the region of the transplanted hydrogels using magnetization transfer imaging. We found that the MTR values increased with cell infiltration, which can be used as a surrogate marker for the occurrence of FBR.

17:42 0157.   Macrophage Tracking with Heteronuclear Proton MRI
Cornelius Faber1, Rebecca Schmidt1, Nadine Nippe2, Klaus Strobel1, Max Masthoff1, Carsten Höltke1, Olga Reifschneider3, Daniela Delli Castelli4, Silvio Aime4, and Christoph Bremer1
1Department of Clinical Radiology, University Hospital Münster, Münster, NRW, Germany, 2Department of Dermatology, University Hospital Münster, Münster, NRW, Germany, 3Institute of Inorganic and Analytical Chemistry, University of Münster, Münster, NRW, Germany, 4Department of Molecular Biotechnologies and Health Sciences, University of Torino, Torino, Italy

We have used Tm-DOTMA to label bone marrow-derived macrophages and track their migration after i.v. administration in a mouse model of local inflammation. The strongly shifted methyl resonance of Tm-DOTMA can be detected efficiently with short-TR 3D UTE MRI, avoiding signal losses due to fast relaxation. Labeled cells were detectable over eight days and the detection limit was estimated to be below 10,000 cells. Our approach may be an alternative to fluorine cell tracking, which does not require a dedicated rf coil.

17:54 0158.   Imaging Oncolytic Virotherapy Delivery Using a CEST Reporter Gene
Christian Thomas Farrar1, Jason S. Buhrman2, Guanshu Liu3,4, Assaf A. Gilad3,4, Michael T. McMahon3,4, and Giulia Fulci2
1Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, United States, 2Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, United States, 3F. M. Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, 4Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States

One of the major challenges in treating glioblastoma is the poor efficiency of drug delivery. Oncolytic viruses (OVs) that can selectively replicate in tumor cells and target the infiltrating margins of the tumor represent a promising new tool in cancer therapy. However, the lack of a means to detect the OV in a non-invasive fashion limits the evaluation of such treatments. Here we demonstrate the use of a lysine-rich protein reporter for imaging oncolytic viral delivery using chemical exchange saturation transfer (CEST) MRI that may for the first time provide a tool for the in vivo monitoring of oncolytic virotherapy.

18:06 0159.   
Bioengineering a Reporter System That Combines a Highly Sensitive CEST and Fluorescence Imaging Probe
Amnon Bar-Shir1,2, Yoshinori Kato1, Arvind P. Pathak1, Jeff W.M. Bulte1,2, and Assaf A. Gilad1,2
1Department of Radiology, Johns Hopkins University, Baltimore, MD, United States, 2Institute for Cell Engineering, Johns Hopkins University, Baltimore, MD, United States

The Drosophila melanogaster 2’-deoxynucleoside kinase (Dm-dNK) enzyme phosphorylates a wide range of nucleoside analogs, including the fluorescent nucleoside pyrrolo-2’-deoxycytidine (pyrrolo-dC). We show here that the NH proton of the pyrrolo-dC generates high CEST contrast when a saturation pulse is applied at 5.8ppm from the water protons. The formation of the pyrrolo-dC monophosphate by recombinant Dm-dNK resulted in accumulation of the probe selectively in the cytoplasm of Dm-dNK-expressing cells since its negative charge prevents cellular export. Hence, pyrrolo-dC can be used for monitoring the reporter gene Dm-dNK expression with CEST MRI.

18:18 0160.   
A Bright Multi-Imaging Modality Gene Reporter
P. Stephen Patrick1,2, Jayne Hammersley2, Louiza Loizou2, Mikko I. Kettunen1, Tiago B. Rodrigues1, De-En Hu2, Sui Seng Tee2,3, Robin Hesketh2, Scott K. Lyons1, Silvio Aime4, Sandra M. Fulton2, and Kevin M. Brindle1,2
1Cancer Research UK, University of Cambridge, Cambridge, Cambridgeshire, United Kingdom, 2Department of Biochemistry, University of Cambridge, Cambridge, Cambridgeshire, United Kingdom, 3School of Medicine, University of Stanford, Palo Alto, California, United States, 4Molecular Biotechnology Centre, University of Turin, Turin, Piedmont, Italy

A new reporter gene for MRI is described that gives rapid, intense, and reversible T1-weighted contrast enhancement. We have achieved this through the expression of Oatp1, which is a transporter for the clinically approved contrast agent gadoxetate. R1 was enhanced by over four fold in reporter expressing tissue 5 hours post intravenous gadoxetate injection, while R1 for control tissue was not significantly different than before injection. This system therefore has the potential to allow detection of gene expression with higher sensitivity and resolution than was previously possible using MRI.