Cell Tracking
Tuesday 4 May 2010
Room A5 10:30-12:30 Moderators: Paula J. Foster and Erik M. Shapiro

10:30 206

A Multimodality Investigation of the Dynamics, Trafficking and Properties of Iron Oxide Core High-Density Lipoprotein in Experimental Atherosclerosis
Torjus Skajaa1,2, David Peter Cormode1, Peter Jarzyna1, Courtney Blachford3, Amanda Delshad1, Edward A. Fisher3, Ronald E. Gordon4, Zahi A. Fayad1, Willem J. M. Mulder1
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.

10:42 207. 

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. Yang1

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.

10:54 208

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 Foster3
BioTherapeutics 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.

11:06 209.  

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 Vallée1
Department 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.

11:18 210.

Long-Term MR Imaging of Immunocompetent and Immunodeficient Mice Reveals Distinct Differences in Contrast Clearance in the Brain - not available
Stacey Marie Cromer Berman1,2, Assaf A. Gilad1,2, Jeff W. M. Bulte1,2, Piotr Walczak1,2
Russell 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.

11:30 211

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 Wayne1,2, Yun Chen1,3, Dragan Maric1, Alan P. Koretsky1
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.

11:42 212

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. Kraitchman3
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.

11:54 213

Surprising Results in the Use of MPIOs to Label Bone-Marrow Resident Monocytes for Immune Cell Tracking by MRI
Bradley Hann1,2, Kevin S. Tang3, Kevin M. Bennett2, Erik M. Shapiro3,4
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.

12:06 214.

MRI Visualization of Anatomical Connections in Vivo Using a Gadolinium Chelated Neural Tracer
Carolyn W. H. Wu1,2, Ning Liu3, Der-Yow Chen2, Vasalatiy Olga4, Alan P. Koretsky2, Gary L. Griffiths4, Roger B. Tootell3,5, Leslie G. Ungerleider3
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.

12:18 215

In Vivo Monitoring of Bacterial Infections Using High-Field MR Microscopy
Volker Sturm1, Tobias Hertlein2, Thomas Basse-Lüsebrink1, Daniel Haddad3, Knut Ohlsen2, Peter Jakob1,3
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.



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