A Multimodality Investigation of the Dynamics, Trafficking and Properties of Iron Oxide Core High-Density Lipoprotein in Experimental Atherosclerosis
Torjus Skajaa^1,2, David Peter Cormode¹, Peter Jarzyna¹, Courtney Blachford³, Amanda Delshad¹, Edward A. Fisher³, Ronald E. Gordon⁴, Zahi A. Fayad¹, Willem J. M. Mulder^1
1Translational and Molecular Imaging Institute, Mount Sinai School of Medicine, New York, NY, United States; ²Dept. of Cardiology, Clinical Institute, Aarhus University Hospital (Skejby), Aarhus, Denmark; ³School of Medicine, New York University, New York, NY, United States; ⁴Department of Pathology, Mount Sinai School of Medicine, New York, NY, United States

FeO-HDL is a lipoprotein derived nanoparticle platform detectable by MRI, optical imaging and TEM. In the current study FeO-HDL was synthesized, applied to various cell lines in vitro and to apoE-KO and wild type mice in vivo. Characterization of FeO-HDL revealed close resemblance to native HDL. In vitro experiments confirmed the aforementioned and showed excellent biocompatibility. Upon intravenous administration in vivo MRI experiments on apoE-KO mice revealed their uptake in the lesioned vessel wall, which was confirmed histologically. Lipid exchange measurements showed lipid transfer from FeO-HDL to native lipoproteins. Conclusively we have shown that FeO-HDl closely resembles native HDL.

The Effects of Iron Oxide Labelling on the in Vitro Chondrogenic Potential of Three Human Cell Types
Sushmita Saha¹, Steven Frederick Tanner², Jennifer Kirkham¹, David Wood¹, Stephen Curran³, Xuebin B. Yang^1
1Department of Oral Biology, University of Leeds, Leeds, W-Yorkshire, United Kingdom; ²Division of Medical Physics, University of Leeds, Leeds, W-Yorkshire, United Kingdom; ³Smith and Nephew Research Centre, York, United Kingdom

MRI has been used to monitor the distribution of labelled cells in studies related to cell therapy in regenerative medicine.  There has been debate on the effects of the Super-Paramagnetic Iron Oxide (SPIO) label on cellular differentiation along the chondrogenic lineage. Whilst previous studies have employed tissue staining to infer cartilage formation; here we use the quantitative reverse transcription polymerase chain reaction technique to assess the effects of the SPIO label on chondrogenic gene expression. The study has shown that inhibition of gene expression resulting from SPIO labelling is dependent on the target cell used.

Non-Invasive Monitoring of Human Dendritic Cell Migration in the CB17 Scid Mouse by Cellular MRI
Gregory A. Dekaban¹, Xizhong Zhang², Vasiliki Economopoulos³, Jennifer Noad³, Roja Rohani³, Adele Wang⁴, Megan Levings⁴, Ronan Foley⁵, Paula Foster^3
1BioTherapeutics Research Laboratory, Robarts Research Institute, London , Ontario, Canada; ²BioTherapeutics Research Laboratory, Robarts Research Institute, London, Ontario, Canada; ³Imaging Research Laboratories, Robarts Research Institute; ⁴Department of Surgery, University of British Columbia; ⁵Department of Pathology and Molecular Medicine, McMaster University

The successful migration of adequate numbers of in vitro-generated human dendritic cells (DC) from the site of injection to a draining lymph node is a necessary and crucial step in order for a DC-based vaccine to be a successful immunotherapy for cancer and infectious disease.  Currently, less than 5% of injected DC migrate to a draining lymph node. How well a preparation of DC migrates is best assessed by conducting migration assays in vivo.  Here we demonstrated that migration of human DC labeled with superparamagnetic iron oxide nanoparticles can be tracked to  lymph nodes of CB17 scid mice.

Comparison of Rate of Islet Loss in Syngeneic, Allogeneic and Xenogeneic Grafts in Rat Using Quantification of Iron Oxide Labeled Islet Cells by 3D Radial UTE MRI
Lindsey Alexandra Crowe¹, Frederic Ris², Sonia Nielles-Vallespin³, Peter Speier³, Michel Kocher⁴, Solange Masson², Christian Toso², Domenico Bosco², Thierry Berney², Jean-Paul Vallée^1
1Department of Radiology, Geneva University Hospital, University of Geneva, Faculty of Medicine, Geneva, Switzerland; ²Cell Isolation and Transplant Center, Department of Surgery, Geneva University Hospital, Geneva, Switzerland; ³Siemens AG Medical Solutions, Erlangen, Germany; ⁴Biomedical Imaging Group, School of Engineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Vaud, Switzerland

In-vivo 3D difference ultra-short echo time (dUTE) imaging gives quantitative positive contrast images for serial examination by automatic segmentation of iron oxide labeled islet cell clusters transplanted into the liver. Coverage of the whole liver in the absence of cardiac and respiratory motion artifact, and isotropic resolution is obtained with uniform background suppression. Three types of grafts: syngeneic, allogeneic and xenogeneic, were studied over time in rat, with success of islet graft, effect of magnetofection and rate of islet loss measurably different.  The method shows promise for robust long term tracking of cell rejection in patients.

Long-Term MR Imaging of Immunocompetent and Immunodeficient Mice Reveals Distinct Differences in Contrast Clearance in the Brain - not available
Stacey Marie Cromer Berman^1,2, Assaf A. Gilad^1,2, Jeff W. M. Bulte^1,2, Piotr Walczak^1,2
1Russell H. Morgan Dept. of Radiology and Radiological Science, Division of MR Research, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; ²Cellular Imaging Section, Vascular Biology Program, The Johns Hopkins University School of Medicine, Baltimore, MD, United States

One important obstacle for correct interpretation of long-term MRI cell tracking is the possibility of persisting hypointense signal even after death of transplanted cells. In order to evaluate this challenge, SPIO-labeled neural stem cells were allografted into the brains of immunocompetent Balb/C mice, inducing cell rejection (dead cells) and immunodeficient Rag2 mice, with no cell rejection (live cells). The transplanted cells were monitored in vivo by MRI for 93 days. Unexpectedly, the MR hypointensities cleared more rapidly in non-rejecting Rag2 mice than in rejecting Balb/C mice, indicating that cell proliferation and migration may dominate clearance of MR signal.

MRI Tracking of Endogenous Neural Precursors Odor Induced Accumulation in the Mitral Cell Layer of the Rodent Olfactory Bulb
James P. Sumner¹, Der-Yow Chen¹, Stephen Dodd¹, Elizabeth Wayne^1,2, Yun Chen^1,3, Dragan Maric¹, Alan P. Koretsky^1
1National Institutes of Health, Bethesda, MD, United States; ²University of Pennsylvania, United States; ³National Institute of Standards and Technology, Boulder, CO, United States

In the adult mammals, neural progenitor cells (NPCs) migrate to the olfactory bulb and differentiate into neurons.  These cells are believed to be involved in processing olfactory signals.  Here we demonstrate that high resolution MRI can be utilized to evaluate the affects of odor enrichment on new neurons in the olfactory bulb with anatomical layer specificity.  We found that amyl acetate enrichment resulted in the accumulation of NPCs in the mitral cell layer.  This in vivo method illustrates the advantages of using high resolution anatomical imaging in combination with cell tracking.

Using ¹⁹F MR to Monitor Delivery and Engraftment of Therapeutic Stem Cells in Vivo: Accuracy Evaluation
Yibin Xie¹, Steven M. Shea², Yingli Fu³, Wesley D. Gilson², Tina Ehtiati², Ronald Ouwerkerk⁴, Dorota Kedziorek³, Meiyappan Solaiyappan³, Gary Huang³, Steffi Valdeig³, Frank Wacker³, Dara L. Kraitchman^3
1Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, United States; ²Center for Applied Medical Imaging, Siemens Research Corporate, Inc., Baltimore, MD, United States; ³Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, United States; ⁴National Institutes of Health, Bethesda, MD, United States

The delivery and engraftment of therapeutic stem cells can be monitored by both ¹⁹F MRI and c-arm CT using alginate-poly-L-lysine-alginate microcapsules loaded with perfluorooctylbromide (APA-PFOB). MR tracking is advantageous for high sensitivity and absence of ionizing radiation. However it suffers from lower resolution. This study evaluates accuracy of tracking encapsulated mesenchymal stem cells using ¹⁹F MRI relative to c-arm CT. Results show a high identification and agreement in the spatial locations and volumes of the injection sites between MRI and CT demonstrating that MRI provides an accurate alternative to CT for tracking of encapsulated stem cells in vivo.

Surprising Results in the Use of MPIOs to Label Bone-Marrow Resident Monocytes for Immune Cell Tracking by MRI
Bradley Hann^1,2, Kevin S. Tang³, Kevin M. Bennett², Erik M. Shapiro^3,4
1Biological Health System Engineering, Arizona State College, Tempe, AZ, United States; ²School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ, United States; ³Department of Biomedical Engineering, Yale University, New Haven, CT, United States; ⁴Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT, United States

The accumulation and presence of MPIOs in bone marrow was studied over seven days. High-resolution, serial in-vivo MRI was performed on mice injected with various quantities of MPIOs. MRI signal changes were monitored in bone marrow and muscle to study MPIO trafficking. In vivo labeling efficiency of bone marrow-resident monocytes was then quantified using flow cytometry. Unexpected results were obtained. It was found that MPIOs did not label monocytes in marrow. An alternative explanation for the success of MPIOs in immune cell trafficking is presented, centered around re-entrance of MPIOs into the circulation long after initial clearance from the vasculature.

MRI Visualization of Anatomical Connections in Vivo Using a Gadolinium Chelated Neural Tracer
Carolyn W. H. Wu^1,2, Ning Liu³, Der-Yow Chen², Vasalatiy Olga⁴, Alan P. Koretsky², Gary L. Griffiths⁴, Roger B. Tootell^3,5, Leslie G. Ungerleider^3
1NeuroSpin, CEA de Saclay, Gif sur Yvette, Ile-de-France, France; ²NINDS, NIH, Bethesda, MD, United States; ³NIMH, NIH, Bethesda, MD, United States; ⁴IPDC/NHLBI, NIH, Rockville, MD, United States; ⁵MGH, Harvard University, Charlestown, MA, United States

A shortcoming of conventional neuroanaomy approaches to study neuronal circuitry is that it requires visualizing transported tracer in the post-mortem tissue. The goal of the study is to expand the MRI contrast media available for in vivo target-specific, mono-synaptic, neuronal tract tracing, by testing a new compound that conjugates conventional neuro-anatomical tracer CTB with GdDOTA. We show that CTBGdDOTA is a MRI neural tracer that allows in vivo visualization of mono-synaptically connected brain circuits, that is target-specific, bi-directional, very reproducible, and stable over a relatively long period of time. This agent opens the possibility for repetitive, chronic, and longitudinal studies.

In Vivo Monitoring of Bacterial Infections Using High-Field MR Microscopy
Volker Sturm¹, Tobias Hertlein², Thomas Basse-Lüsebrink¹, Daniel Haddad³, Knut Ohlsen², Peter Jakob^1,3
1Experimental Physics 5, University of Würzburg, Würzburg, Germany; ²Institute for Molecular Infection Biology, University of Würzburg, Würzburg, Germany; ³Research Center for Magnetic Resonance Bavaria e.V., Würzburg, Germany

In vivo monitoring of bacterial infection allows effective testing of potential new drugs and active compounds. Therefore we investigate native (T2) and marker (19F) based MRI methods for those requirements. Here the T2 maps have been proved to be able to visualize the inflammation formation in a mouse muscle abscess model at even early stages (day 2), while the 19F- marker accumulate in the area of infection. The latter has the potential to deliver new insights into the process of host-pathogen interaction, even though the exact mode of accumulation had to be investigated further.