In vivo Ultrasound and Photoacoustic Monitoring of Mesenchymal Stem Cells Labeled with Gold Nanotracers

Abstract

Longitudinal monitoring of cells is required in order to understand the role of delivered stem cells in therapeutic neovascularization. However, there is not an imaging technique that is capable of quantitative, longitudinal assessment of stem cell behaviors with high spatial resolution and sufficient penetration depth. In this study, in vivo and in vitro experiments were performed to demonstrate the efficacy of ultrasound-guided photoacoustic (US/PA) imaging to monitor mesenchymal stem cells (MSCs) labeled with gold nanotracers (Au NTs). The Au NT labeled MSCs, injected intramuscularly in the lower limb of the Lewis rat, were detected and spatially resolved. Furthermore, our quantitative in vitro cell studies indicate that US/PA imaging is capable of high detection sensitivity (1×104 cells/mL) of the Au NT labeled MSCs. Finally, Au NT labeled MSCs captured in the PEGylated fibrin gel system were imaged in vivo, as well as in vitro, over a one week time period, suggesting that longitudinal cell tracking using US/PA imaging is possible. Overall, Au NT labeling of MSCs and US/PA imaging can be an alternative approach in stem cell imaging capable of noninvasive, sensitive, quantitative, longitudinal assessment of stem cell behaviors with high spatial and temporal resolutions at sufficient depths.

Imaging Strategies for Tissue Engineering Applications

“…115,116 Linear ultrasound array-based PA imaging is capable of detecting a target at deeper regions than PA microscopy and thus can be applied for a rat model, having been commonly used for tissue regeneration studies. 117,118 For example, it was demonstrated that mesenchymal stem cells labeled with gold nanospheres and delivered within 96 NAM ET AL.…”

“…106,131 Therefore, fusion of ultrasonically acquired structural data and photoacoustically obtained functional and molecular data can provide synergetic benefits for a variety of applications that require noninvasive monitoring of implanted tissue-engineered constructs. 117,118 Novel dual contrast agents for combined ultrasound and PA imaging have recently been developed by indocyanine green loading to perfluorocarbon nanodroplets. 132 Also, hybrid PA imaging is possible with other optical imaging modalities, such as OCT, by sharing a photon delivery system to complement structural information.…”

“…Reprinted with permission from Cai et al 115 (C) Combined ultrasound and spectroscopic photoacoustic imaging of gold nanoparticle-labeled mesenchymal stem cells intramuscularly injected within a PEGylated fibrin hydrogel. Reprinted with permission from Nam et al 118 Color images available online at www.liebertpub.com/teb…”

Cell Tracking Technologies for Acute Ischemic Brain Injury

“…Reduced viability and proliferative capability reduce the potential for translation of this particular radiotracer, since the primary goal of therapeutic stem cells is that they are effective and not that they are of definitive whereabouts. 89 Zr-oxinate 4 has also been shown to reduce cell viability by about 20% during the labelling process, although no further reduction is seen 24 hours later. It is evident that the use of a radioisotope is highly likely to affect cell function and/or toxicity.…”

Array-Based Real-Time Ultrasound and Photoacoustic Ocular Imaging

“…Photoacoustic imaging has been widely reported to be capable of visualizing various biological tissues [6,7]. Compared to other ocular imaging modalities, photoacoustic imaging can achieve relatively deep penetration depth and more functional and cellular information based on photoacoustic signal generation from endogenous contrast agents such as hemoglobin and melanin [8,9].…”