Abstract
In vivo monitoring of nanoparticle delivery is essential to better understand cellular and molecular interactions of nanoparticles with tissue and to better plan nanoparticle-mediated therapies. We developed a three-dimensional ultrasound and photoacoustic (PA) imaging system and a spectroscopic PA imaging algorithm to identify and quantify the presence of nanoparticles and other tissue constituents. Using the developed system and approach, three-dimensional in vivo imaging of a mouse with tumor was performed before and after intravenous injection of gold nanorods. The developed spectroscopic PA imaging algorithm estimated distribution of nanoparticle as well as oxygen saturation of blood. Moreover, silver staining of excised tumor tissue confirmed nanoparticle deposition, and showed good correlation with spectroscopic PA images. The results of our study suggest that three-dimensional ultrasound-guided spectroscopic PA imaging can monitor nanoparticle delivery in vivo.
Highlights
Gold nanoparticles have been considered attractive contrast agents for photoacoustic molecular imaging [1,2,3,4], as well as therapeutic agents for photothermal therapy [5,6,7], because of high optical absorption properties, superior biocompatibility [8] and capability of molecular specific targeting of the cells
We present an in vivo spectroscopic PA imaging algorithm as well as a threedimensional (3-D) ultrasound (US) and PA imaging system
The developed spectroscopic PA imaging algorithm based on minimum mean square errors (MMSEs) analysis can reconstruct the concentrations of optical absorbers in the region where Linear least squares (LLS) method fails due to negative concentration of photoabsorbers
Summary
Gold nanoparticles have been considered attractive contrast agents for photoacoustic molecular imaging [1,2,3,4], as well as therapeutic agents for photothermal therapy [5,6,7], because of high optical absorption properties, superior biocompatibility [8] and capability of molecular specific targeting of the cells. The photoacoustic (PA) imaging technique can detect nanoparticles (NPs) based on 2 ways: quantitative changes of PA signals between pre- and post-injection of NPs and spectroscopic methods. Single-wavelength PA imaging has been used to detect contrast agents in live mice based on changes of PA signal intensity [2,11]. Analysis of PA signal at only one wavelength is prone to error because the increase of PA intensity can be caused by the deposition of contrast agents, and by physiological changes (i.e., tumor growth, angiogenesis, etc.). When longitudinal PA imaging is performed, the repeatability of the imaging experiments can be another problem because PA signals are linearly dependent with local laser fluence, which will be changed by tumor growth and re-positioning of the animal between imaging sessions. Multi-wavelength PA imaging (i.e., spectroscopic PA imaging) can be a solution to overcome the problems of single-wavelength PA imaging
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