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Photoacoustic signal generation by metal nanoparticles relies on the efficient conversion of light to heat, its transfer to the environment and the production of pressure transients. In this study we demonstrate that a dielectric shell has a strong influence on the amplitude of the generated photoacoustic signal, and that silica coated gold nanorods of the same optical density are capable of producing about 3-fold higher photoacoustic signals than nanorods without silica coating. Spectrophotometry measurements and finite difference time domain (FDTD) analysis of gold nanorods before and after silica coating showed only an insignificant change of the extinction and absorption cross-sections, hence indicating that the enhancement is not attributable to changes in absorption cross-section resulting from the silica coating. Several factors including the silica thickness, the gold/silica interface, and the surrounding solvent were varied to investigate their effect on the photoacoustic signal produced from silica-coated gold nanorods. The results suggest that the enhancement is caused by the reduction of the gold interfacial thermal resistance with the solvent due to the silica coating. The strong contrast enhancement in photoacoustic imaging, demonstrated using phantoms with silica-coated nanorods, shows that these hybrid particles acting as "photoacoustic nano-amplifiers" are high efficiency contrast agents for photoacoustic imaging or photoacoustic image-guided therapy. KeywordsPhotoacoustic imaging; silica coated-gold nanorods; photoacoustic nano-amplifiers; medical and biological imaging; contrast agents Photoacoustic imaging is a non-ionizing and noninvasive imaging modality that combines the advantages of both optical and acoustic imaging. [1][2][3][4] In photoacoustic imaging, the intensity modulated electromagnetic radiation, e.g. a beam of pulsed laser light, is directed at the imaging target. The light is absorbed and converted to an outgoing thermoacoustic wave that can be detected by an ultrasound transducer and used to reconstruct images.5 -8 Since light is only used for heating and not for imaging, and acoustic waves are less scattered in optically turbid materials such as tissue, photoacoustic imaging can reach far deeper into turbid materials than purely optical imaging techniques.8 -9 The contrast in photoacoustic * To whom correspondence should be addressed. Telephone: (512) 471-1733. Fax: (512) imaging depends on the optical-to-acoustic conversion (optoacoustic) efficiency, i.e., how many incident photons can be absorbed and converted to heat, and how fast the generated heat can diffuse out from the target during thermoelastic expansion and wave generation. When a uniformly absorbing target is irradiated by pulsed light, the amplitude of the generated photoacoustic signal is proportional to the optical absorption and the thermalacoustic properties of the absorbing medium. In contrast, in a heterogeneous medium such as a weakly absorbing solvent containing plasmonic nanoparticles, the amp...

since being discovered by Alexander Bell, photoacoustics may again be seeing major resurgence in biomedical imaging. Photoacoustics is a non-ionizing, functional imaging modality capable of high contrast images of optical absorption at depths significantly greater than traditional optical imaging techniques. optical contrast agents have been used to extend photoacoustics to molecular imaging. Here we introduce an exogenous contrast agent that utilizes vaporization for photoacoustic signal generation, providing significantly higher signal amplitude than that from the traditionally used mechanism, thermal expansion. our agent consists of liquid perfluorocarbon nanodroplets with encapsulated plasmonic nanoparticles, entitled photoacoustic nanodroplets. upon pulsed laser irradiation, liquid perfluorocarbon undergoes a liquid-to-gas phase transition generating giant photoacoustic transients from these dwarf nanoparticles. once triggered, the gaseous phase provides ultrasound contrast enhancement. We demonstrate in phantom and animal studies that photoacoustic nanodroplets act as dualcontrast agents for both photoacoustic and ultrasound imaging through optically triggered vaporization.

Imaging modalities play an important role in the clinical management of cancer, including screening, diagnosis, treatment planning, and therapy monitoring. Owing to increased research efforts in the past two decades, photoacoustic imaging -a non-ionizing, non-invasive technique capable of visualizing optical absorption properties of tissue at reasonable depth, with spatial resolution of ultrasound -has emerged. Ultrasound-guided photoacoustics is regarded for its ability to provide in vivo morphological and functional information about the tumor within the surrounding tissue. With the recent advent of targeted contrast agents, photoacoustics is capable of in vivo molecular imaging, thus facilitating further molecular and cellular characterization of cancer. This review examines the role of photoacoustics and photoacoustic-augmented imaging techniques in comprehensive cancer detection, diagnosis and treatment guidance.

In photoacoustic imaging, the second near infrared (NIR II) window is where tissue generates the least background signal. However, the large size of the few available contrast agents in this spectral range impedes their pharmacokinetics and decreases their thermal stability, leading to unreliable photoacoustic imaging. Here, we synthesize miniaturized gold nanorods absorbing in NIR II that are 5–11 times smaller than regular-sized gold nanorods with a similar aspect ratio. Under nanosecond pulsed laser illumination, small nanorods are about three times more thermally stable and generate 3.5 times stronger photoacoustic signal than absorption-matched large counterparts. These unexpected findings are confirmed using theoretical and numerical analysis, showing that photoacoustic signal is not only proportional to the optical absorption of the nanoparticle solution but also to the surface-to-volume ratio of the nanoparticles. In living tumor bearing mice, these small targeted nanorods display a 30% improvement in efficiency of agent delivery to tumors and generate 4.5 times greater photoacoustic contrast.

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Gold nanoparticles targeting epidermal growth factor receptor via antibody conjugation undergo molecular specific aggregation when they bind to receptors on cell surfaces, leading to a red shift in their plasmon resonance frequency. Capitalizing on this effect, we demonstrate the efficacy of the molecular specific photoacoustic imaging technique using subcutaneous tumor-mimicking gelatin implants in ex-vivo mouse tissue. The results of our study suggest that highly selective and sensitive detection of cancer cells is possible using multiwavelength photoacoustic imaging and molecular specific gold nanoparticles.The developments in the fields of nanotechnology and molecular biology provide a promising platform for detection of cancer at an asymptomatic stage. Bioconjugated nano contrast agents together with imaging techniques can satisfy the compelling need to reliably detect, diagnose and characterize cancer at an early stage. [1][2][3][4][5][6][7] Recently, gold nanoparticles (Au NPs) have gained popularity as nano-sized contrast agents 2,6,[8][9][10][11][12][13][14] for their well-developed bioconjugation protocols, 11,[15][16][17] biocompatibility 18,19 and ease of tuning the optical properties. [20][21][22] Immunotargeted gold nanoparticles have been used to enhance contrast in optical imaging techniques. 6,9,13,14 However, the penetration depth achievable with high resolution optical imaging techniques is limited to a few millimeters. Optical techniques utilizing incoherent light extend the penetration depth to several centimeters while spatial resolution is severely sacrificed. Therefore, an in vivo imaging technique that is sensitive in detecting Au NPs and capable of imaging deep lying structures is desired. Photoacoustic imaging [23][24][25] is a technique that can provide penetration depth on the order of centimeters if near-infrared (NIR) laser light is used. In the photoacoustic phenomenon, 26 electromagnetic energy in the form of light is absorbed and subsequently an acoustic wave is emitted. Using a wideband ultrasound detector the acoustic waves can be detected and spatially resolved to provide an image of the optical absorption properties of the internal tissue structure. [23][24][25] Gold nanoparticles have been used as contrast agents in photoacoustic imaging because of their unique optical absorption properties. 8,10,[27][28][29][30][31] Using three-dimensional (3D) tissue models, we previously demonstrated that highly selective detection of cancer could be achieved using molecular targeted gold nanoparticles and combined photoacoustic and ultrasound imaging. 8,32 In particular, the contrast in the photoacoustic images was attributed to the epidermal growth factor receptor (EGFR) 33,34 leading to plasmon resonance coupling between adjacent gold particles and a red-shift in their absorbance spectra 6,8,9,14 while the nontargeted or isolated gold nanoparticles have absorbance peak at around 520 nm. 8,35,36 In this paper, we demonstrate the efficacy of multiwavelength photoacoustic imagin...

Photothermal stability and, therefore, consistency of both optical absorption and photoacoustic response of the plasmonic nanoabsorbers is critical for successful photoacoustic image-guided photothermal therapy. In this study, silica-coated gold nanorods were developed as a multifunctional molecular imaging and therapeutic agent suitable for image-guided photothermal therapy. The optical properties and photothermal stability of silica-coated gold nanorods under intense irradiation with nanosecond laser pulses were investigated by UV-Vis spectroscopy and transmission electron microscopy. Silica-coated gold nanorods showed increased photothermal stability and retained their superior optical properties under much higher fluences. The changes in photoacoustic response of PEGylated and silica-coated nanorods under laser pulses of various fluences were compared. The silica-coated gold nanorods provide a stable photoacoustic signal, which implies better imaging capabilities and make silica-coated gold nanorods a promising imaging and therapeutic nano-agent for photoacoustic imaging and image-guided photothermal therapy.