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Fast, quantitative, murine cardiac (19)F MRI/MRS of PFCE-labeled progenitor stem cells and macrophages at 9.4T
PURPOSE: To a) achieve cardiac (19)F-Magnetic Resonance Imaging (MRI) of perfluoro-crown-ether (PFCE) labeled cardiac progenitor stem cells (CPCs) and bone-derived bone marrow macrophages, b) determine label concentration and cellular load limits, and c) achieve spectroscopic and image-based quantif...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5764257/ https://www.ncbi.nlm.nih.gov/pubmed/29324754 http://dx.doi.org/10.1371/journal.pone.0190558 |
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author | Constantinides, Christakis Maguire, Mahon McNeill, Eileen Carnicer, Ricardo Swider, Edyta Srinivas, Mangala Carr, Carolyn A. Schneider, Jurgen E. |
author_facet | Constantinides, Christakis Maguire, Mahon McNeill, Eileen Carnicer, Ricardo Swider, Edyta Srinivas, Mangala Carr, Carolyn A. Schneider, Jurgen E. |
author_sort | Constantinides, Christakis |
collection | PubMed |
description | PURPOSE: To a) achieve cardiac (19)F-Magnetic Resonance Imaging (MRI) of perfluoro-crown-ether (PFCE) labeled cardiac progenitor stem cells (CPCs) and bone-derived bone marrow macrophages, b) determine label concentration and cellular load limits, and c) achieve spectroscopic and image-based quantification. METHODS: Theoretical simulations and experimental comparisons of spoiled-gradient echo (SPGR), rapid acquisition with relaxation enhancement (RARE), and steady state at free precession (SSFP) pulse sequences, and phantom validations, were conducted using (19)F MRI/Magnetic Resonance Spectroscopy (MRS) at 9.4 T. Successful cell labeling was confirmed using flow cytometry and confocal microscopy. For CPC and macrophage concentration quantification, in vitro and post-mortem cardiac validations were pursued with the use of the transfection agent FuGENE. Feasibility of fast imaging is demonstrated in murine cardiac acquisitions in vivo, and in post-mortem murine skeletal and cardiac applications. RESULTS: SPGR/SSFP proved favorable imaging sequences yielding good signal-to-noise ratio values. Confocal microscopy confirmed heterogeneity of cellular label uptake in CPCs. (19)F MRI indicated lack of additional benefits upon label concentrations above 7.5–10 mg/ml/million cells. The minimum detectable CPC load was ~500k (~10k/voxel) in two-dimensional (2D) acquisitions (3–5 min) using the butterfly coil. Additionally, absolute (19)F based concentration and intensity estimates (trifluoroacetic-acid solutions, macrophages, and labeled CPCs in vitro and post-CPC injections in the post-mortem state) scaled linearly with fluorine concentrations. Fast, quantitative cardiac (19)F-MRI was demonstrated with SPGR/SSFP and MRS acquisitions spanning 3–5 min, using a butterfly coil. CONCLUSION: The developed methodologies achieved in vivo cardiac (19)F of exogenously injected labeled CPCs for the first time, accelerating imaging to a total acquisition of a few minutes, providing evidence for their potential for possible translational work. |
format | Online Article Text |
id | pubmed-5764257 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-57642572018-01-23 Fast, quantitative, murine cardiac (19)F MRI/MRS of PFCE-labeled progenitor stem cells and macrophages at 9.4T Constantinides, Christakis Maguire, Mahon McNeill, Eileen Carnicer, Ricardo Swider, Edyta Srinivas, Mangala Carr, Carolyn A. Schneider, Jurgen E. PLoS One Research Article PURPOSE: To a) achieve cardiac (19)F-Magnetic Resonance Imaging (MRI) of perfluoro-crown-ether (PFCE) labeled cardiac progenitor stem cells (CPCs) and bone-derived bone marrow macrophages, b) determine label concentration and cellular load limits, and c) achieve spectroscopic and image-based quantification. METHODS: Theoretical simulations and experimental comparisons of spoiled-gradient echo (SPGR), rapid acquisition with relaxation enhancement (RARE), and steady state at free precession (SSFP) pulse sequences, and phantom validations, were conducted using (19)F MRI/Magnetic Resonance Spectroscopy (MRS) at 9.4 T. Successful cell labeling was confirmed using flow cytometry and confocal microscopy. For CPC and macrophage concentration quantification, in vitro and post-mortem cardiac validations were pursued with the use of the transfection agent FuGENE. Feasibility of fast imaging is demonstrated in murine cardiac acquisitions in vivo, and in post-mortem murine skeletal and cardiac applications. RESULTS: SPGR/SSFP proved favorable imaging sequences yielding good signal-to-noise ratio values. Confocal microscopy confirmed heterogeneity of cellular label uptake in CPCs. (19)F MRI indicated lack of additional benefits upon label concentrations above 7.5–10 mg/ml/million cells. The minimum detectable CPC load was ~500k (~10k/voxel) in two-dimensional (2D) acquisitions (3–5 min) using the butterfly coil. Additionally, absolute (19)F based concentration and intensity estimates (trifluoroacetic-acid solutions, macrophages, and labeled CPCs in vitro and post-CPC injections in the post-mortem state) scaled linearly with fluorine concentrations. Fast, quantitative cardiac (19)F-MRI was demonstrated with SPGR/SSFP and MRS acquisitions spanning 3–5 min, using a butterfly coil. CONCLUSION: The developed methodologies achieved in vivo cardiac (19)F of exogenously injected labeled CPCs for the first time, accelerating imaging to a total acquisition of a few minutes, providing evidence for their potential for possible translational work. Public Library of Science 2018-01-11 /pmc/articles/PMC5764257/ /pubmed/29324754 http://dx.doi.org/10.1371/journal.pone.0190558 Text en © 2018 Constantinides et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Constantinides, Christakis Maguire, Mahon McNeill, Eileen Carnicer, Ricardo Swider, Edyta Srinivas, Mangala Carr, Carolyn A. Schneider, Jurgen E. Fast, quantitative, murine cardiac (19)F MRI/MRS of PFCE-labeled progenitor stem cells and macrophages at 9.4T |
title | Fast, quantitative, murine cardiac (19)F MRI/MRS of PFCE-labeled progenitor stem cells and macrophages at 9.4T |
title_full | Fast, quantitative, murine cardiac (19)F MRI/MRS of PFCE-labeled progenitor stem cells and macrophages at 9.4T |
title_fullStr | Fast, quantitative, murine cardiac (19)F MRI/MRS of PFCE-labeled progenitor stem cells and macrophages at 9.4T |
title_full_unstemmed | Fast, quantitative, murine cardiac (19)F MRI/MRS of PFCE-labeled progenitor stem cells and macrophages at 9.4T |
title_short | Fast, quantitative, murine cardiac (19)F MRI/MRS of PFCE-labeled progenitor stem cells and macrophages at 9.4T |
title_sort | fast, quantitative, murine cardiac (19)f mri/mrs of pfce-labeled progenitor stem cells and macrophages at 9.4t |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5764257/ https://www.ncbi.nlm.nih.gov/pubmed/29324754 http://dx.doi.org/10.1371/journal.pone.0190558 |
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