Nano-sized particles are widely regarded as a tool to study biologic events at the cellular and molecular levels. However, only some imaging modalities can visualize interaction between nanoparticles and living cells. We present a new technique, pulsed magneto-motive ultrasound imaging, which is capable of in vivo imaging of magnetic nanoparticles in real time and at sufficient depth. In pulsed magneto-motive ultrasound imaging, an external high-strength pulsed magnetic field is applied to induce the motion within the magnetically labeled tissue and ultrasound is used to detect the induced internal tissue motion. Our experiments demonstrated a sufficient contrast between normal and iron-laden cells labeled with ultrasmall magnetic nanoparticles. Therefore, pulsed magneto-motive ultrasound imaging could become an imaging tool capable of detecting magnetic nanoparticles and characterizing the cellular and molecular composition of deep-lying structures.
Background and Objectives
We report on a study to investigate feasibility of utilizing ultrasound imaging to guide laser removal of subcutaneous fat. Ultrasound imaging can be used to identify the tissue composition and to monitor the temperature increase in response to laser irradiation.
Study Design/Materials and Methods
Laser heating was performed on ex vivo porcine subcutaneous fat through the overlying skin using a continuous wave laser operating at 1,210 nm optical wavelength. Ultrasound images were recorded using a 10 MHz linear array-based ultrasound imaging system.
Ultrasound imaging was utilized to differentiate between water-based and lipid-based regions within the porcine tissue and to identify the dermis-fat junction. Temperature maps during the laser exposure in the skin and fatty tissue layers were computed.
Results of our study demonstrate the potential of using ultrasound imaging to guide laser fat removal.
laser therapy; ultrasound imaging; thermal imaging; treatment monitoring; fat removal; body reshaping
Photoacoustic imaging, a promising new diagnostic medical imaging modality, can provide high contrast images of molecular features by introducing highly-absorbing plasmonic nanoparticles. Currently, it is uncertain whether the absorption of low fluence pulsed light by plasmonic nanoparticles could lead to cellular damage. In our studies we have shown that a low fluence pulsed laser excitation of accumulated nanoparticles at low concentration does not impact cell growth and viability, while we identify thresholds at which higher nanoparticle concentrations and fluences produce clear evidence of cell death. The results provide insights for improved design of photoacoustic contrast agents and for applications in combined imaging and therapy.
Previously, pulsed magneto-motive ultrasound (pMMUS) imaging has been introduced as a contrast-agent-assisted ultrasound-based imaging modality capable of visualizing biological events at the cellular and molecular level. In pMMUS imaging, a high intensity pulsed magnetic field is used to excite cells or tissue labeled with magnetic nanoparticles. Then, ultrasound (US) imaging is used to monitor the mechanical response of the tissue to an externally applied magnetic field (i.e., tissue displacement). Signal to noise ratio (SNR) in pMMUS imaging can be improved by using superparamagnetic nanoparticles with larger saturation magnetization. Metal-doped magnetic nanoparticles with enhanced tunable nanomagnetism are suitable candidates to improve the SNR and, therefore, sensitivity of pMMUS imaging, which is essential for in vivo pMMUS imaging. In this study, we demonstrate the capability of pMMUS imaging to identify the presence and distribution of zinc-doped iron oxide nanoparticles in live nude mice bearing A431 (human epithelial carcinoma) xenograft tumors.
A biopsy of the first lymph node to which a tumor drains – the sentinel lymph node (SLN) – is commonly performed to identify micrometastases. Image guidance of the SLN biopsy procedure has the potential to improve its accuracy and decrease its morbidity. We have developed a new stable contrast agent for photoacoustic image-guided SLN biopsy: silica-coated gold nanoplates (Si-AuNPs). The Si-AuNPs exhibit high photothermal stability when exposed to pulsed and continuous wave laser irradiation. This makes them well-suited for in vivo photoacoustic imaging. Furthermore, Si-AuNPs are shown to have low cytotoxicity. We tested the Si-AuNPs for SLN mapping in a mouse model where they exhibited a strong, sustained photoacoustic signal. Real-time ultrasound and photoacoustic imaging revealed that the Si-AuNPs quickly drain to the SLN gradually spreading throughout a large portion of the node.
Recently, a dual photoacoustic and ultrasound contrast agent—named photoacoustic nanodroplet—has been introduced. Photoacoustic nanodroplets consist of a perfluorocarbon core, surfactant shell, and encapsulated photoabsorber. Upon pulsed laser irradiation the perfluorocarbon converts to gas, inducing a photoacoustic signal from vaporization and subsequent ultrasound contrast from the resulting gas microbubbles. In this work we synthesize nanodroplets which encapsulate gold nanorods with a peak absorption near 1064 nm. Such nanodroplets are optimal for extended photoacoustic imaging depth and contrast, safety and system cost. We characterized the nanodroplets for optical absorption, image contrast and vaporization threshold. We then imaged the particles in an ex vivo porcine tissue sample, reporting contrast enhancement in a biological environment. These 1064 nm triggerable photoacoustic nanodroplets are a robust biomedical tool to enhance image contrast at clinically relevant depths.
(110.5120) Photoacoustic imaging; (170.7170) Ultrasound; (160.4236) Nanomaterials; (170.3880) Medical and biological imaging; (170.7180) Ultrasound diagnostics
Hybrid nanostructures with unique optical and magnetic properties have attracted considerable interest as effective mediators for medical imaging and therapy. An aqueous-based, self-assembly approach to synthesizing hybrid plasmonic-superparamagnetic nanostructures is presented. The building blocks of the hybrid nanostructure include plasmonic gold nanorods (AuNRs) and superparamagnetic iron oxide nanoparticles (SPIONs). The AuNRs were functionalized via carboxyl-bearing surface ligands, while the SPIONs were kept “bare” after synthesis via a surfactant-free, thermal decomposition reaction in triethylene glycol. Hybrid SPION-studded AuNR nanostructures were produced upon simple mixing of the components due to chemisorption of the AuNRs’ free carboxyl groups to the SPIONs’ surfaces. The reported synthesis strategy is modular in nature and can be expanded to build hybrid nanostructures with a multitude of other plasmonic nanoparticles. With tunable near-infrared absorption peaks and a sufficient number of bound SPIONs, the self-assembled hybrid nanostructures are suitable for biomedical imaging and therapy applications.
Hybrid nanostructures; self-assembly; gold nanoparticles; iron oxide; silica; plasmonic nanoparticles; superparamagnetic nanoparticles
The photothermal stability of plasmonic nanoparticles is critically important to perform reliable photoacoustic imaging and photothermal therapy. Recently, biodegradable nanoclusters composed of sub-5 nm primary gold particles and a biodegradable polymer have been reported as clinically-translatable contrast agents for photoacoustic imaging. After cellular internalization, the nanoclusters degrade into 5 nm primary particles for efficient excretion from the body. In this paper, three different sizes of biodegradable nanoclusters were synthesized and the optical properties and photothermal stability of the nanoclusters were investigated and compared to that of gold nanorods. The results of our study indicate that 40 nm and 80 nm biodegradable nanoclusters demonstrate higher photothermal stability compared to gold nanorods. Furthermore, 40 nm nanoclusters produce higher photoacoustic signal than gold nanorods at a given concentration of gold. Therefore, the biodegradable plasmonic nanoclusters can be effectively used for photoacoustic imaging and photothermal therapy.
(170.5120) Photoacoustic imaging; (170.3880) Medical and biological imaging
The metastasis of cancer is a multistage process involving complex biological interactions and difficult to predict outcomes. Accurate assessment of the extent of metastasis is critical for clinical practice; unfortunately, medical imaging methods capable of identifying the early stages of invasion and metastasis are lacking. Photoacoustic imaging is capable of providing noninvasive, real-time imaging of significant anatomical and physiological changes. indicating the progression of cancer invasion and metastasis. Preclinically, photoacoustic methods have been used to image lymphatic anatomy, including the sentinel lymph nodes, to identify circulating tumor cells within vasculature and to detect micrometastases. Progress has begun toward the development of clinically applicable photoacoustic imaging systems to assist with the determination of cancer stage and likelihood of metastatic invasion.
circulating tumor cells; lymphatic system; medical imaging; metastasis; photoacoustics; sentinel lymph node
We report a highly sensitive method based on phase-stabilized swept source optical coherence elastography (PhS-SSOCE) to measure elastic wave propagation in soft tissues in vivo. The waves were introduced using a mechanical stimulus and were assessed using the phase response of the swept source optical coherence tomography signal. The technique was utilized to measure age-related changes in elastic flexural wave velocity and attenuation in mice cornea in vivo. Results demonstrate that the wave velocity increases with animal age, supporting previous observations that stiffness of mice cornea gradually increases with age. Our studies suggest that the PhS-SSOCE technique could potentially be used to obtain biomechanical properties of ocular tissues in vivo.
optical coherence tomography; phase sensitive; elastography; ocular tissues; biomechanical properties; shear wave; elastic wave; in vivo
Cancer is one of the leading causes of death in the world. Diagnosing a cancer at its early stages of development can decrease the mortality rate significantly and reduce healthcare costs. Over the past two decades, photoacoustic imaging has seen steady growth and has demonstrated notable capabilities to detect cancerous cells and stage cancer. Furthermore, photoacoustic imaging combined with ultrasound imaging and augmented with molecular targeted contrast agents is capable of imaging cancer at the cellular and molecular level, thus opening diverse opportunities to improve diagnosis of tumors, detect circulating tumor cells and identify metastatic lymph nodes. In this paper we introduce the principles of photoacoustic imaging, and review recent developments in photoacoustic imagingas an emerging imaging modality for cancer diagnosis and staging.
Photoacoustic imaging; ultrasound; cancer; diagnosis; staging; exogenous contrast agents; spectroscopy
Spectroscopic photoacoustic imaging has the potential to become a powerful tool that can estimate distributions of optically absorbing chromophores in the body. We have developed an algorithm to select imaging wavelengths for spectroscopic photoacoustics given the spectra of expected chromophores. The algorithm uses the smallest singular value of a matrix constructed from the absorption spectra as a criterion to remove extraneous wavelengths. The method performed significantly better than an approach where evenly spaced wavelengths were used in the presence of noise and wavelength-dependent attenuation of light in tissue. Finally, the algorithm was applied to photoacoustic imaging of a phantom containing indocyanine green dye and silica-coated gold nanorods, demonstrating significant improvements in the ability to estimate relative contrast agent concentrations compared to the case where evenly spaced wavelengths were chosen. In summary, our work provides a versatile framework to select optical wavelengths and evaluate sets of absorbers for spectroscopic photoacoustic imaging.
Spectroscopic photoacoustic imaging; Feature selection; Spectral unmixing; Spectroscopy
Evaluating the regenerative capacity of a tissue-engineered device in a noninvasive and synchronous manner is critical to determining the mechanisms for success in clinical applications. In particular, directly tracking implanted cells in a three-dimensional (3D) scaffold is desirable in that it enables the monitoring of cellular activity in a specific and localized manner. The authors’ group has previously demonstrated that the PEGylation of fibrin results in a 3D scaffold that supports morphologic and phenotypic changes in mesenchymal stem cells that may be advantageous in wound healing applications. Recently, the authors have evaluated adipose-derived stem cells (ASCs) as a mesenchymal cell source to regenerate skin and blood vessels due to their potential for proliferation, differentiation, and production of growth factors. However, tracking and monitoring ASCs in a 3D scaffold, such as a PEGylated fibrin gel, have not yet been fully investigated. In the current paper, nanoscale gold spheres (20 nm) as cell tracers for ASCs cultured in a PEGylated fibrin gel were evaluated. An advanced dual-imaging modality combining ultrasound and photoacoustic imaging was utilized to monitor rat ASCs over time. The ASCs took up gold nanotracers and could be detected up to day 16 with high sensitivity using photoacoustic imaging. There were no detrimental effects on ASC morphology, network formation, proliferation, and protein expression/secretion (ie, smooth muscle α-actin, vascular endothelial growth factor, matrix metalloproteinase-2, and matrix metalloproteinase-9) associated with gold nanotracers. Therefore, utilization of gold nanotracers can be an effective strategy to monitor the regenerative process of a stem cell source in a 3D gel for vascular and dermal tissue engineering applications.
gold nanoparticles; adipose-derived stem cells; fibrin; ultrasound and photoacoustic imaging; angiogenesis; tissue engineering
As applications of nanoparticles in medical imaging and biomedicine rapidly expand, the interactions of nanoparticles with living cells have become an area of active interest. For example, intracellular trafficking of nanoparticles – an important part of cell-nanoparticle interaction, has been well studied using plasmonic nanoparticles and optical or optics-based techniques due to the change in optical properties of the nanoparticle aggregates. However, magnetic nanoparticles, despite their wide range of clinical applications, do not exhibit plasmonic-resonant properties and therefore their intracellular aggregation cannot be detected by optics-based imaging techniques. In this study, we investigated the feasibility of a novel imaging technique – pulsed magneto-motive ultrasound (pMMUS), to identify intracellular trafficking of endocytosed magnetic nanoparticles. In pulsed magneto-motive ultrasound imaging a focused, high intensity, pulsed magnetic field is used to excite the cells labeled with magnetic nanoparticles, and ultrasound imaging is then used to monitor the mechanical response of the tissue. We demonstrated previously that clusters of magnetic nanoparticles amplify the pMMUS signal in comparison to signal from individual nanoparticles. Here we further demonstrate that pMMUS imaging can identify interaction between magnetic nanoparticles and living cells, i.e. intracellular aggregation of nanoparticles within the cells. The results of our study suggest that pMMUS imaging can not only detect the presence of magnetic nanoparticles but also provides information about their intracellular trafficking non-invasively and in real-time.
Pulsed magneto-motive ultrasound imaging; superparamagnetic iron-oxide nanoparticles; macrophage; endocytosis; intracellular trafficking
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.
Importance of the field
Photoacoustic imaging is an imaging modality that derives image contrast from the optical absorption coefficient of the tissue being imaged. The imaging technique is able to differentiate between healthy and diseased tissue with either deeper penetration or higher resolution than other functional imaging modalities currently available. From a clinical standpoint, photoacoustic imaging has demonstrated safety and effectiveness in diagnosing diseased tissue regions using either endogenous tissue contrast or exogenous contrast agents. Furthermore, the potential of photoacoustic imaging has been demonstrated in various therapeutic interventions ranging from drug delivery and release to image-guided therapy and monitoring.
Areas covered in this review
This article reviews the current state of photoacoustic imaging in biomedicine from a technological perspective, highlights various biomedical and clinical applications of photoacoustic imaging, and gives insights on future directions.
What the reader will gain
Readers will learn about the various applications of photoacoustic imaging, as well as the various contrast agents that can be used to assist photoacoustic imaging. This review will highlight both pre-clinical and clinical uses for photoacoustic imaging, as well as discuss some of the challenges that must be addressed to move photoacoustic imaging into the clinical realm.
Take home message
Photoacoustic imaging offers unique advantages over existing imaging modalities. The imaging field is broad with many exciting applications for detecting and diagnosing diseased tissue or processes. Photoacoustics is also used in therapeutic applications to identify and characterize the pathology and then to monitor the treatment. Although the technology is still in its infancy, much work has been done in the pre-clinical arena, and photoacoustic imaging is fast approaching the clinical setting.
Atherosclerosis; cancer; contrast agents; drug delivery; molecular imaging; nanoparticles; optoacoustics; photoacoustics; therapy; ultrasound
In both photoacoustic (PA) and ultrasonic (US) imaging, overall image quality is influenced by the optical and acoustical properties of the medium. Consequently, with the increased use of combined PA and US (PAUS) imaging in preclinical and clinical applications, the ability to provide phantoms that are capable of mimicking desired properties of soft tissues is critical. To this end, gelatin-based phantoms were constructed with various additives to provide realistic acoustic and optical properties. Forty-micron, spherical silica particles were used to induce acoustic scattering, Intralipid® 20% IV fat emulsion was employed to enhance optical scattering and ultrasonic attenuation, while India Ink, Direct Red 81, and Evans blue dyes were utilized to achieve optical absorption typical of soft tissues. The following parameters were then measured in each phantom formulation: speed of sound, acoustic attenuation (from 6 to 22 MHz), acoustic backscatter coefficient (from 6 to 22 MHz), optical absorption (from 400 nm to 1300 nm), and optical scattering (from 400 nm to 1300 nm). Results from these measurements were then compared to similar measurements, which are offered by the literature, for various soft tissue types. Based on these comparisons, it was shown that a reasonably accurate tissue-mimicking phantom could be constructed using a gelatin base with the aforementioned additives. Thus, it is possible to construct a phantom that mimics specific tissue acoustical and/or optical properties for the purpose of PAUS imaging studies.
(110.3000) Image quality assessment; (160.4760) Optical properties; (170.5120) Photoacoustic imaging; (170.7170) Ultrasound; (290.5820) Scattering measurements
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.
(170.5120) Photoacoustic imaging; (110.7170) Ultrasound; (170.3880) Medical and biological imaging
Brachytherapy seed therapy is an increasingly common way to treat prostate cancer through localized radiation. The current standard of care relies on transrectal ultrasound (TRUS) for imaging guidance during the seed placement procedure. As visualization of individual metallic seeds tends to be difficult or inaccurate under TRUS guidance, guide needles are generally tracked to infer seed placement. In an effort to improve seed visualization and placement accuracy, the use of photoacoustic (PA) imaging, which is highly sensitive to metallic objects in soft tissue, was investigated for this clinical application. The PA imaging properties of bare (i.e., embedded in pure gelatin) and tissue-embedded (at depths of up to 13 mm) seeds were investigated with a multi-wavelength (750 to 1090 nm) PA imaging technique. Results indicate that, much like ultrasonic (US) imaging, an angular dependence (i.e., seed orientation relative to imaging transducer) of the PA signal exists. Despite this shortcoming, however, PA imaging offers improved contrast, over US imaging, of a seed in prostate tissue if sufficient local fluence is achieved. Additionally, although the PA signal of a bare seed is greatest for lower laser wavelengths (e.g., 750 nm), the scattering that results from tissue tends to favor the use of higher wavelengths (e.g., 1064 nm, which is the primary wavelength of Nd:YAG lasers) when the seed is located in tissue. A combined PA and US imaging approach (i.e., PAUS imaging) shows strong potential to visualize both the seed and the surrounding anatomical environment of the prostate during brachytherapy seed placement procedures.
(170.5120) Photoacoustic imaging; (170.7170) Ultrasound; (170.1610) Clinical applications; (170.7230) Urology; (170.3660) Light propagation in tissues; (110.0113) Imaging through turbid media
In ultrasound strain and elasticity imaging, an accurate and cost-effective sub-pixel displacement estimator is required because strain/elasticity imaging quality relies on the displacement SNR, which can often be higher if more computational resources are provided. In this paper, we introduce an autocorrelation-based method to cost-effectively improve sub-pixel displacement estimation quality. To quantitatively evaluate the performance of the autocorrelation method, simulated and tissue-mimicking phantom experiments were performed. The computational cost of the autocorrelation method is also discussed. The results of our study suggest the autocorrelation method can be used for a real-time elasticity imaging system.
Plasmonic metal nanoparticles are used in photoacoustic imaging as contrast agents because of their resonant optical absorption properties in the visible and near-IR regions. However, the nanoparticles could accumulate and result in long-term toxicity in vivo, because they are generally not biodegradable. Recently, biodegradable plasmonic gold nanoclusters, consisting of sub-5 nm primary gold nanoparticles and biodegradable polymer stabilizer, were introduced. In this Letter, we demonstrate the feasibility of biodegradable nanoclusters as a photoacoustic contrast agent. We performed photoacoustic and ultrasound imaging of a tissue-mimicking phantom with inclusions containing nanoclusters at various concentrations. The results indicate that the biodegradable gold nanoclusters can be used as effective contrast agents in photoacoustic imaging.
An ultrasound-based method to locally assess the shear modulus of a medium is reported. The proposed approach is based on the application of an impulse acoustic radiation force to an inhomogeneity in the medium and subsequent monitoring of the spatio-temporal response. In our experimental studies, a short pulse produced by a 1.5-MHz highly focused ultrasound transducer was used to initiate the motion of a rigid sphere embedded into an elastic medium. Another 25 MHz focused ultrasound transducer operating in pulse-echo mode was used to track the displacement of the sphere. The experiments were performed in gel phantoms with varying shear modulus to demonstrate the relationship between the displacement of the sphere and shear modulus of the surrounding medium. Because the magnitude of acoustic force applied to sphere depends on the acoustic material properties and, therefore, cannot be used to assess the absolute value of shear modulus, the temporal behavior of the displacement of the sphere was analyzed. The results of this study indicate that there is a strong correlation between the shear modulus of a medium and spatio-temporal characteristics of the motion of the rigid sphere embedded in this medium.
Intravascular photoacoustic (IVPA) imaging is a catheter-based, minimally invasive, imaging modality capable of providing high-resolution optical absorption map of the arterial wall. Integrated with intravascular ultrasound (IVUS) imaging, combined IVPA and IVUS imaging can be used to detect and characterize atherosclerotic plaques building up in the inner lining of an artery. In this paper, we present and discuss various representative applications of combined IVPA/IVUS imaging of atherosclerosis, including assessment of the composition of atherosclerotic plaques, imaging of macrophages within the plaques, and molecular imaging of biomarkers associated with formation and development of plaques. In addition, imaging of coronary artery stents using IVPA and IVUS imaging is demonstrated. Furthermore, the design of an integrated IVUS/IVPA imaging catheter needed for in vivo clinical applications is discussed.
Atherosclerosis; contrast agent; imaging catheter; intravascular photoacoustic (IVPA) imaging; intravascular ultrasound (IVUS) imaging; molecular imaging; stent; vulnerable plaque
Stem cells can differentiate into multiple cell types, and therefore can be used for cellular therapies, including tissue repair. However, the participation of stem cells in tissue repair and neovascularization is not well understood. Therefore, implementing a noninvasive, long-term imaging technique to track stem cells in vivo is needed to obtain a better understanding of the wound healing response. Generally, we are interested in developing an imaging approach to track mesenchymal stem cells (MSCs) in vivo after delivery via a polyethylene glycol modified fibrin matrix (PEGylated fibrin matrix) using MSCs loaded with gold nanoparticles as nanotracers. The objective of the current study was to assess the effects of loading MSCs with gold nanoparticles on cellular function.
In this study, we utilized various gold nanoparticle formulations by varying size and surface coatings and assessed the efficiency of cell labeling using darkfield microscopy. We hypothesized that loading cells with gold nanotracers would not significantly alter cell function due to the inert and biocompatible characteristics of gold. The effect of nanoparticle loading on cell viability and cytotoxicity was analyzed using a LIVE/DEAD stain and an MTT assay. The ability of MSCs to differentiate into adipocytes and osteocytes after nanoparticle loading was also examined. In addition, nanoparticle loading and retention over time was assessed using inductively coupled plasma mass spectrometry (ICP-MS).
Our results demonstrate that loading MSCs with gold nanotracers does not alter cell function and, based on the ICP-MS results, long-term imaging and tracking of MSCs is feasible. These findings strengthen the possibility of imaging MSCs in vivo, such as with optical or photoacoustic imaging, to understand better the participation and role of MSCs in neovascularization.
neovascularization; gold nanoparticles; cell tracking; stem cells; fibrin gel; optical imaging