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Optoacoustic imaging emerged in early 1990s as a new biomedical imaging technology that generates images by illuminating tissues with short laser pulses and detecting resulting ultrasound waves. This technique takes advantage of the spectroscopic approach to molecular imaging, and delivers high-resolution images in the depth of tissue. Resolution of the optoacoustic imaging is scalable, so that biomedical systems from cellular organelles to large organs can be visualized and, more importantly, characterized based on their optical absorption coefficient, which is proportional to the concentration of absorbing chromophores. Optoacoustic imaging was shown to be useful in both preclinical research using small animal models and in clinical applications. Applications in the field of molecular imaging offer abundant opportunities for the development of highly specific and effective contrast agents for quantitative optoacoustic imaging. Recent efforts are being made in the direction of nontoxic biodegradable contrast agents (such as nanoparticles made of melanin) that are potentially applicable in clinical optoacoustic imaging. In order to increase the efficiency and specificity of contrast agents and probes, they need to be made smart and capable of controlled accumulation in the target cells. This review was written in recognition of the potential breakthroughs in medical optoacoustic imaging that can be enabled by efficient and nontoxic melanin-based optoacoustic contrast agents., Competing Interests: The authors declare no conflict of interest.

Optoacoustic tomography (OAT), also known as photoacoustic tomography, is an emerging computed biomedical imaging modality that exploits optical contrast and ultrasonic detection principles. Iterative image reconstruction algorithms that are based on discrete imaging models are actively being developed for OAT due to their ability to improve image quality by incorporating accurate models of the imaging physics, instrument response, and measurement noise. In this work, we investigate the use of discrete imaging models based on Kaiser-Bessel window functions for iterative image reconstruction in OAT. A closed-form expression for the pressure produced by a Kaiser-Bessel function is calculated, which facilitates accurate computation of the system matrix. Computer-simulation and experimental studies are employed to demonstrate the potential advantages of Kaiser-Bessel function-based iterative image reconstruction in OAT.

Grüneisen parameter is a key temperature-dependent physical characteristic responsible for thermoelastic efficiency of materials. We propose a new methodology for accurate measurements of temperature dependence of Grüneisen parameter in optically absorbing solutions. We use two-dimensional optoacoustic (OA) imaging to improve accuracy of measurements. Our approach eliminates contribution of local optical fluence and absorbance. To validate the proposed methodology, we studied temperature dependence of aqueous cupric sulfate solutions in the range from 22 to 4 °C. Our results for the most diluted salt perfectly matched known temperature dependence for the Grüneisen parameter of water. We also found that Grüneisen-temperature relationship for cupric sulfate exhibits linear trend with respect to the concentration. In addition to accurate measurements of Grüneisen changes with temperature, the developed technique provides a basis for future high precision OA temperature monitoring in live tissues.

This paper provides a short review of physical principles, technology, biomedical applications and perspectives of the optoacoustic imaging. Ideas that made this rapidly developing field possible include the following: (1) laser pulses may be effectively used to produce acoustic pressure in biological tissues localized to the areas of increased optical absorption, (2) the resulting acoustic (ultrasonic) waves propagate in tissues with minimal distortions and attenuation, (3) 2D and 3D maps (images) of the absorbed optical energy can be reconstructed with high resolution from the detected optoacoustic signals. Modern optoacoustic imaging systems include scanning focused transducers and 2D/3D transducer arrays. The widely accepted 2D arrays are employed either for real-time 2D optoacoustic imaging or for 3D imaging via translational or rotational scanning. A commercial prototype of a 3D OAT system is being developed by TomoWave Labs where major biomedical applications include visualization of specific targeting using exogenous optoacoustic contrast agents and imaging of blood distribution and oxygentaion status can be investigated.

Gold nanorods with a peak absorption wavelength of 760 nm were prepared using a seed-mediated method. A novel protocol has been developed to replace hexadecyltrimethylammonium bromide on the surface of the nanorods with 16-mercaptohexadecanoic acid and metoxy-poly(ethylene glycol)-thiol, and the monoclonal antibody HER2. The physical chemistry properties of the conjugates were monitored through optical and zeta-potential measurements to confirm surface chemistry changes. The efficiency of the modifications was quantified through measurement of the average number of antibodies per gold nanorod. The conjugates were investigated for different cells lines: BT-474, MCF7, MCF10, MDCK, and fibroblast. The results show successful cell accumulation of the gold nanorod HER2 conjugates in cells with HER2 overexpression. Incubation of the complexes in heparinized mouse blood demonstrated the low aggregation of the metallic particles through stability of the spectral properties, as verified by UV/VIS spectrometry. Cytotoxicity analysis with LDH release and MTT assay confirms strong targeting and retention of functional activity of the antibody after their conjugation with gold nanorods. Silver staining confirms efficient specific binding to BT-474 cells even in cases where the nanorod complexes were incubated in heparinized mouse blood. This is confirmed through in vivo studies where, following intravenous injection of gold nanorod complexes, silver staining reveals noticeably higher rates of specific binding in mouse tumors than in healthy liver.The conjugates are reproducible, have strong molecular targeting capabilities, have long term stability in vivo and can be used in pre-clinical applications. The conjugates can also be used for molecular and optoacoustic imaging, quantitative sensing of biological substrates, and photothermal therapy.

We present a non-metallic interferometric silica optical fiber ultrasonic wideband sensor for optoacoustic imaging applications. The ultrasonic sensitivity of this sensor has been characterized over the frequency range from 1 to 10 MHz. A comparative analysis has been carried out between this sensor and an array of piezoelectric transducers using optoacoustic signals generated from an optical absorbent embedded in a tissue mimicking phantom. Also, a two dimensional reconstructed image of the phantom using the fiber interferometric sensor is presented and compared to the image obtained using the Laser Optoacoustic Imaging System, LOIS-64B. The feasibility of our fiber optic based sensor for wideband ultrasonic detection is demonstrated., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Photoacoustic tomography (PAT) also referred to as optoacoustic tomography (OAT) is a hybrid imaging modality that employs nonionizing optical radiation and ultrasonic detection. Here, we describe the application of a new class of optical contrast agents based on mesoscopic hollow gold nanospheres (HAuNS) to PAT. HAuNS are approximately 40 nm in diameter with a hollow interior and consist of a thin gold wall. They display strong resonance absorption tuned to the near-infrared (NIR) range, with an absorption peak at 800 nm, whose photoacoustic efficiency is significantly greater than that of blood. Following surface conjugation with thiolated poly(ethylene glycol), the pegylated HAuNS (PEG-HAuNS) had distribution and elimination half-lives of 1.38 +/- 0.38 and 71.82 +/- 30.46 h, respectively. Compared with PAT images based on the intrinsic optical contrast in nude mice, the PAT images acquired within 2 h after intravenous administration of PEG-HAuNS showed the brain vasculature with greater clarity and detail. The image depicted brain blood vessels as small as approximately 100 mum in diameter using PEG-HAuNS as contrast agents. Preliminary results showed no acute toxicity to the liver, spleen, or kidneys in mice following a single imaging dose of PEG-HAuNS. Our results indicate that PEG-HAuNS are promising contrast agents for PAT, with high spatial resolution and enhanced sensitivity., (Copyright 2009 Elsevier Ltd. All rights reserved.)

An interferometric sensor based on nonmetallic silica optical fiber is presented as an ultrasonic wideband transducer for optoacoustic imaging applications. We have characterized the sensitivity of the optical fiber sensor by detecting optoacoustic signals from an optically absorbing object embedded in a tissue-mimicking phantom and have compared the signals recorded with those detected from the same phantom using an array of piezoelectric transducers. The optical fiber sensor was also scanned along the phantom surface in order to reconstruct two-dimensional optoacoustic images of the phantom. These images have been compared with images obtained using the Laser Optoacoustic Imaging System, LOIS-64B, demonstrating the feasibility of our fiber-optic sensor as a wideband ultrasonic transducer.

We present a physical model that explains several sequential stages of the conversion of optical to acoustical energy when irradiating diluted suspensions of metal nanoparticles with laser pulses. Optical absorption and scattering of a single particle driven by plasmon resonance interactions in an aqueous medium are considered. Thermal effects produced by laser-irradiated nanoparticles, dynamics of vapor bubble formation, and acoustic signals from expanding bubbles formed around heated nanoparticles are calculated. Stochastic features of the pressure magnitude emitted as a result of low-fluence irradiation of suspensions are also discussed. The probabilistic distribution of pressure magnitude from individual bubbles was found to obey Zipf's law for low concentrations of nanoparticles, while increasing their concentration brings the pressure magnitude distribution into conformance with the Gaussian law.

The development of a contrast agent for a laser optoacoustic imaging system (LOIS) can significantly widen preclinical and clinical applications of this imaging modality for early detection of cancerous tumors. Gold nanorods were engineered to enhance the contrast for optoacoustic imaging. Under in vivo conditions, 25 microL of gold nanorods solution at a concentration of 1.25 pM were injected into nude mice and detected using a single-channel acoustic transducer. LOIS was used to visualize the distribution of gold nanoparticles at a concentration of 125 pM in vivo when 100 microL of solution of gold nanoparticles was delivered subcutaneously. Our results suggest that LOIS can be used for in vivo detection of gold nanorods at low concentrations and the nanoparticles can be engineered to enhance the diagnostic power of optoacoustic imaging.

We describe novel ex vivo method for elimination of tumor cells from cell suspension, Laser Activated Nanothermolysis and propose this method for purging of bone marrow and blood transplants. K562 and human lympholeukemia cells were eliminated in experiments by laser-induced micro-bubbles that emerge inside individual target cells around selectively formed clusters of light-absorbing gold nanoparticles. Pretreatment of tumor cells with specific monoclonal antibodies and Ig-conjugated 30-nm gold particles allowed the formation of clusters of 10-20 on the surface of cell membrane. Electron microscopy found the nanoparticulate clusters inside the cells. Total (100%) elimination of K562 cells targeted with specific antibodies was achieved with single laser pulses with optical fluence of 5J/cm(2) at the wavelength of 532 nm without damage to the same cells targeted without specific antibodies. Total elimination of human lymphoblasts from suspension of normal stem cells was achieved by a single laser pulse with the optical fluence of 1.7J/cm(2), while the damage level of normal cells was 16%.