Dissertation/Thesis Abstract

Development and application of a fluorine-19 platform for in vivo MRI: Tracking and quantification of T cells in murine disease models and the effect of immunotherapy on T cell trafficking
by Srinivas, Mangala, Ph.D., Carnegie Mellon University, 2008, 178; 3295598
Abstract (Summary)

We developed a 19F-based Magnetic Resonance Imaging (MRI) technique to fulfil the need for a tool that allows for noninvasive, unambiguous monitoring of cell trafficking in vivo. This novel technology is suitable for both longitudinal cell tracking and dynamic in vivo quantification of cell numbers. The use of a 19F label precludes any background and is exquisitely specific for the labeled cells, while conventional 1H imaging provides anatomic context. Several 19F nanoemulsions were developed and optimized for labeling cells, in particular primary T cells. A novel computational algorithm for quantification allows for accurate determination of total 19F signal, and hence cell numbers, in any region of interest in an MR image. The 19F label was expanded to include a covalently bound fluorescent dye, which was also used for in vivo optical imaging of migrating T cells. We tracked activated T cells in two murine disease models, namely autoimmune diabetes and localized inflammation. The effect of dendritic cell treatment on T cell trafficking in autoimmune disease was also studied. We followed the labeled cells in vivo for up to three weeks in the inflammation model. The technique was supplemented using conventional 19F NMR and flow cytometry. The 19F imaging platform developed is applicable to many cell types and disease models and can potentially be used for monitoring cell therapeutics in the clinic.

A pictorial summary of the project is shown in Fig. 1.1.

Indexing (document details)
Advisor: Ahrens, Eric T.
Commitee:
School: Carnegie Mellon University
School Location: United States -- Pennsylvania
Source: DAI-B 69/03, Dissertation Abstracts International
Source Type: DISSERTATION
Subjects: Biophysics
Keywords: 19F, Cell tracking, Diabetes, Fluorine, Fluorine-based MRI, MRI, Quantification, T cells
Publication Number: 3295598
ISBN: 978-0-549-52028-3
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