Fast, quantitative, murine cardiac 19F MRI/MRS of PFCE-labeled progenitor stem cells and macrophages at 9.4T

• Published in: PloS one Vol. 13; no. 1; p. e0190558
• Main Authors: Constantinides, Christakis, Maguire, Mahon, McNeill, Eileen, Carnicer, Ricardo, Swider, Edyta, Srinivas, Mangala, Carr, Carolyn A, Schneider, Jurgen E
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 2018; Public Library of Science (PLoS)
• Subjects: Animals; Biology and Life Sciences; Bone marrow; Butterflies; Coils; Confocal; Confocal microscopy; Cytometry; Departments; Feasibility studies; Flow cytometry; Fluorine; Fluorine-19 Magnetic Resonance Imaging - methods; Heart; Heart - diagnostic imaging; Heart diseases; Immunology; In vivo methods and tests; Load limits; Macrophages; Macrophages - cytology; Magnetic resonance; Magnetic resonance imaging; Magnetic resonance spectroscopy; Medicine; Medicine and Health Sciences; Mice; Microscopy; Microscopy, Confocal; Nanoparticles; NMR; Nuclear magnetic resonance; Perfluorocarbons; Phantoms, Imaging; Research and Analysis Methods; Resonance; Software; Spectroscopy; Spectrum analysis; Stem cell transplantation; Stem cells; Stem Cells - cytology; Transfection; Transplants & implants
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0190558

To a) achieve cardiac 19F-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. 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 19F 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. SPGR/SSFP proved favorable imaging sequences yielding good signal-to-noise ratio values. Confocal microscopy confirmed heterogeneity of cellular label uptake in CPCs. 19F 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 19F 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 19F-MRI was demonstrated with SPGR/SSFP and MRS acquisitions spanning 3-5 min, using a butterfly coil. The developed methodologies achieved in vivo cardiac 19F 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.