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Abstract
Micrometer-sized iron oxide particles (MPIOs) attract increasing interest as contrast agents for cellular tracking by clinical Magnetic Resonance Imaging (MRI). Despite the great potential of MPIOs for in vivo imaging of labeled cells, little is known on the intracellular localization of these particles following uptake due to the lack of techniques with the ability to monitor the particle uptake in vivo at single-cell level. Here, we show that coherent anti-Stokes Raman scattering (CARS) microscopy enables non-invasive, label-free imaging of MPIOs in living cells with sub-micron resolution in three dimensions. CARS allows simultaneous visualization of the cell framework and the MPIOs, where the particles can be readily distinguished from other cellular components of comparable dimensions, and localized inside the cell.
Highlights
Cell transplantation using, e.g., stem cells, progenitor cells and adult cell lines constitutes a promising approach for treatment of several human diseases [1,2], and has already been tested for clinical treatment of cardiovascular, neurological, and metabolic disorders [1,3,4,5,6]
We present a combination of resonant and nonresonant Coherent anti-Stokes Raman Scattering (CARS) microscopy as a useful tool for the visualization of Magnetic Resonance Imaging (MRI) labels in living cells
A droplet of solution containing 108 particles/mL of MPIOs was left to dry for one hour on a conventional microscope cover slip before imaging with both brightfield and coherent anti-Stokes Raman scattering (CARS) microscopy
Summary
E.g., stem cells, progenitor cells and adult cell lines constitutes a promising approach for treatment of several human diseases [1,2], and has already been tested for clinical treatment of cardiovascular, neurological, and metabolic disorders [1,3,4,5,6]. Substantial effort has been devoted to the development of techniques to image individual cells in live organisms, as monitoring cell transplantation is crucial for the success of the therapy. The outcome of cell transplantation in clinical trials has been investigated via biopsies from the target organ, using visualization by radioisotope imaging [14]. This approach has serious limitations, : it is associated with a risk for the patient due to the invasive procedure and constrained by the fact that only a limited part of the organ can be investigated, and only at limited numbers of moments in time.
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