In vivo photoacoustic molecular imaging with simultaneous multiple selective targeting using antibody-conjugated gold nanorods.

The use of gold nanorods for photoacoustic molecular imaging with simultaneous multiple targeting is reported. Multiple targeting is done by utilizing the tunable optical absorption property of gold nanorods. This technique allows multiple molecular signatures to be obtained by simply switching laser wavelength. HER2 and EGFR were chosen as the primary target molecules for examining two cancer cells, OECM1 and Cal27. Both in vitro and in vivo mouse model imaging experiments were performed, with contrast enhancement of up to 10 dB and 3.5 dB, respectively. The potential in improving cancer diagnosis is demonstrated.

Photoacoustic imaging of multiple targets using gold nanorods.

Photoacoustic (PA) imaging has been used mainly for anatomical and functional imaging. Although functionalized nanoparticles also have been developed for PA molecular imaging, only single targeting has been demonstrated. In this study, PA imaging of multiple targets using gold nanorods is demonstrated experimentally using HER2 and CXCR4 as target molecules. The two corresponding monoclonal antibodies were conjugated to two types of gold nanorod with different aspect ratios. Gold nanorods with mean aspect ratios of 5.9 and 3.7 exhibited peak optical absorptions at 1000 and 785 nm, respectively. Appropriate selection of laser irradiation wavelength enhances PA signals by 7-12 dB and allows signals from gold nanorods corresponding to specific bindings to be distinguished. This approach potentially allows the expression levels of different oncogenes of cancer cells to be revealed simultaneously.

Nanorod-based flow estimation using a high-frame-rate photoacoustic imaging system.

A quantitative flow measurement method that utilizes a sequence of photoacoustic images is described. The method is based on the use of gold nanorods as a contrast agent for photoacoustic imaging. The peak optical absorption wavelength of a gold nanorod depends on its aspect ratio, which can be altered by laser irradiation (we establish a wash-in flow estimation method of this process). The concentration of nanorods with a particular aspect ratio inside a region of interest is affected by both laser-induced shape changes and replenishment of nanorods at a rate determined by the flow velocity. In this study, the concentration is monitored using a custom-designed, high-frame-rate photoacoustic imaging system. This imaging system consists of fiber bundles for wide area laser irradiation, a laser ultrasonic transducer array, and an ultrasound front-end subsystem that allows acoustic data to be acquired simultaneously from 64 transducer elements. Currently, the frame rate of this system is limited by the pulse-repetition frequency of the laser (i.e., 15 Hz). With this system, experimental results from a chicken breast tissue show that flow velocities from 0.125 to 2 mms can be measured with an average error of 31.3%.

Photoacoustic flow measurements with gold nanoparticles.

The hypothesis that quantitative blood flow measurements are feasible with the time-intensity based method in photoacoustic imaging using gold nanoparticles as contrast agent is experimentally tested. The in vitro results show good linearity between the measurements and the theory, thus suggesting the potential of relative photoacoustic flow measurements with gold nanoparticles.

Simulations of optoacoustic wave propagation in light-absorbing media using a finite-difference time-domain method.

Optoacoustic (OA) imaging is an emerging technology that combines the high optical contrast of tissues with the high spatial resolution of ultrasound. Taking full advantage of OA imaging requires a better understanding of OA wave propagation in light-absorbing media. Current simulation methods are mainly based on simplified conditions such as thermal confinement, negligible viscosity, and homogeneous acoustic properties throughout the image object. In this study a new numerical approach is proposed based on a finite-difference time-domain (FDTD) method to solve the general OA equations, comprising the continuity, Navier-Stokes, and heat-conduction equations. The FDTD code was validated using a benchmark problem that has an approximate analytical solution. OA experiments were also conducted and data were in good agreement with those predicted by the FDTD method. Characteristics of simulated OA waveforms and OA images were discussed. The simulator was also employed to study wavefront distortion in OA breast imaging.