This proposal has a technology development component and a basic immunobiological component. It consists of three Specific Aims: (1) development of novel intracellular MRI agents and associated cell labeling protocols, and measurement of the cell labeling efficiency and lifetime; (2) biological characterizations via quantitative cytotoxicity, proliferation, and immunological assays of labeled immune cells, such as dendritic cells (DCs) and macrophages; and (3) in vivo studies where labeled immune cells will be injected into NOD mice and imaged using extremely-high field (11.7 T) MRI. We will visualize the biodistribution of the labeled cells following intravenous inoculation and the time-lapse cell migration following focal injection into specific tissue sites. We will test the hypothesis that different subsets of DCs have different migratory patterns in vivo based on their maturation state. Using the NOD mouse we will test the hypothesis that the ability of mature DCs to prevent diabetes is dependent, in part, on their migratory capacity. A long-term application of this technology is monitoring the trafficking of cellular therapeutics in vivo. The proposed research project is highly interdisciplinary, and we have assembled a diverse team of investigators in the Pittsburgh area with expertise in in vivo magnetic resonance microscopy (Ahrens), immunology (Morel) and biological reagent design (Ernst/Waggoner).

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Research Project (R01)
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Study Section
Medical Imaging Study Section (MEDI)
Program Officer
Zhang, Yantian
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Carnegie-Mellon University
Schools of Arts and Sciences
United States
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Mills, Parker H; Hitchens, T Kevin; Foley, Lesley M et al. (2012) Automated detection and characterization of SPIO-labeled cells and capsules using magnetic field perturbations. Magn Reson Med 67:278-89
Hitchens, T Kevin; Ye, Qing; Eytan, Danielle F et al. (2011) 19F MRI detection of acute allograft rejection with in vivo perfluorocarbon labeling of immune cells. Magn Reson Med 65:1144-53
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Morel, Penelope A; Srinivas, Mangala; Turner, Michael S et al. (2011) Gene expression analysis of dendritic cells that prevent diabetes in NOD mice: analysis of chemokines and costimulatory molecules. J Leukoc Biol 90:539-50
Srinivas, Mangala; Heerschap, Arend; Ahrens, Eric T et al. (2010) (19)F MRI for quantitative in vivo cell tracking. Trends Biotechnol 28:363-70
Kadayakkara, Deepak K; Beatty, Pamela L; Turner, Michael S et al. (2010) Inflammation driven by overexpression of the hypoglycosylated abnormal mucin 1 (MUC1) links inflammatory bowel disease and pancreatitis. Pancreas 39:510-5
Kadayakkara, Deepak K K; Janjic, Jelena M; Pusateri, Lisa K et al. (2010) In vivo observation of intracellular oximetry in perfluorocarbon-labeled glioma cells and chemotherapeutic response in the CNS using fluorine-19 MRI. Magn Reson Med 64:1252-9
Srinivas, Mangala; Turner, Michael S; Janjic, Jelena M et al. (2009) In vivo cytometry of antigen-specific t cells using 19F MRI. Magn Reson Med 62:747-53
Janjic, Jelena M; Ahrens, Eric T (2009) Fluorine-containing nanoemulsions for MRI cell tracking. Wiley Interdiscip Rev Nanomed Nanobiotechnol 1:492-501

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