Chen- Wei

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.

Enhanced photoacoustic stability of gold nanorods by silica matrix confinement

Photoacoustic tomography (PAT) has garnered much attention for its high contrast and excellent spatial resolution of perfused tissues. Gold nanorods (GNRs) have been employed to further enhance the imaging contrast of PAT. However, the photon fluences typically needed for PA wave induction often also result in GNR shape changes that significantly reduce the efficiency of acoustic wave generation. In this work, we propose, synthesize, and evaluate amorphous silica-coated gold nanorods (GNR-Si) in an effort to improve contrast agent stability and ameliorate efficiency loss during photoacoustic (PA) wave induction. TEM and optical absorption spectra measurements of GNR and GNR-Si show that encasing GNRs within amorphous silica provides substantial protection of nanorod conformation from thermal deformation. PA signals generated by GNR-Si demonstrate considerably greater resistance to degradation of signal intensity with repetitive pulsing than do uncoated GNRs, thereby enabling much longer, high-contrast imaging sessions than previously possible. The prolongation of high-contrast imaging, and biocompatibility and easy surface functionalization for targeting ligands afforded by amorphous silica, suggest GNR-Si to be potentially significant for the clinical translation of PAT.

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 by use of laser-induced shape transitions of gold nanorods.

A quantitative technique for flow measurements based on a wash-in analysis is proposed. The technique makes use of the shape dependence of the optical absorption of gold nanorods and the transitions in their shape induced by pulsed laser irradiation. The photon-induced shape transition of gold nanorods involves mainly a rod-to-sphere conversion and a shift in the peak optical absorption wavelength. The application of a series of laser pulses will induce shape changes in gold nanorods as they flow through a region of interest, with quantitative flow information being derived from the photoacoustic signals from the irradiated gold nanorods measured as a function of time. To demonstrate the feasibility of the technique, a Nd:YAG laser operating at 1064 nm was used for irradiation and a 1 MHz ultrasonic transducer was used for acoustic detection. The flow velocity ranged from 0.35 to 2.83 mm/s. Excellent agreement between the measured velocities and the actual velocities was demonstrated, with a linear regression correlation coefficient of 0.93. This study is a pioneer work on wash-in flow estimation in photoacoustic imaging.

Multiple targeting in photoacoustic imaging using bioconjugated gold nanorods

Cancer cells presented altered surface molecules to encourage their growth and metastasis. Expression of oncogeneic surface molecules also play important roles in the prediction of clinical outcome and treatment response of anti-cancer drugs. It is thus conceivable that imaging of cancer lesions while simultaneously obtaining their pathogenic information at molecular level of as many oncogenic proteins as possible is of great clinical significance. Gold nanoparticles have been used as a contrast agent for photoacoustic imaging. In addition, gold nanoparticles can be bioconjugated to probe certain molecular processes. An intriguing property of gold nanoparticles is its ability to tailor its optical properties. For example, size effects on the surface plasmon absorption of spherical gold nanoparticles have shown that the peak optical absorption red-shifts with the increasing particle size. In addition, the optical absorption spectrum of cylindrical gold nanoparticles (i.e., gold nanorods) exhibits a strong absorption band that is directly related to the aspect ratio. With these unique characteristics, selective targeting can be achieved in photoacoustic molecular imaging. Specifically, gold nanorods with different aspect ratios can be bioconjugated to different antibodies. Multiple targeting and simultaneous detection can then be achieved by using laser irradiation at the respective peak optical absorption wavelength. In this study, photoacoustic multiple targeting using gold nanorods is experimentally demonstrated. We have chosen Her2 and CXCR4 as our primary target molecule as Her2 expression is associated with growth characteristics and sensitivity to Herceptin chemotherapy. On the other hand, CXCR4 expression predict the organ-specific metastatic potential of the cancer cells for clinical intervention in advance. Monoclonal antibody (mAb) against Her2/neu was conjugated to nanorods with several different aspect ratios. The agarose gel is suitable for photoacoustic signal acquisition. A wavelength tunable Ti-Sapphire laser was used for laser irradiation and a 1 MHz ultrasound transducer was used for acoustic detection. The optical wavelength of the laser was tuned between 800 nm and 940 nm, corresponding to gold nanorods of an aspect ratio ranging from 3.7 to 5.9. The results clearly show the potential of photoacoustic molecular imaging with multiple targeting in revealing different oncogene expression levels of the cancer cells.

Polarization-insensitive, 40 Gb/s wavelength and RZ-OOK-to-RZ-BPSK modulation format conversion by XPM in a highly nonlinear PCF

Polarization-insensitive wavelength conversion, as well as the conversion of return-to-zero (RZ) ON-OFF keying (RZ-OOK) to RZ binary phase-shift keying (RZ-BPSK), has been simultaneously achieved at 40 Gb/s for the first time by cross-phase modulation (XPM) in a highly birefringent, nonlinear photonic crystal fiber (PCF). A 10-9-BER receiver sensitivity conversion penalty of < 3 dB was achieved for a polarization scrambled, 40 Gb/s 25%-RZ-OOK pump, when the 40 Gb/s RZ probe was launched at 45 degrees with respect to the birefringence axes of the PCF and when the pump-probe detuning was greater than about 6 nm.

Subband photoacoustic imaging for contrast improvement

Contrast in photoacoustic imaging is primarily determined by optical absorption. This paper proposes a subband imaging method to further enhance the image contrast. The method is based on media with different absorptions generating acoustic waves with different frequency contents. Generally, assuming all other conditions remain the same, a high-absorption medium generates acoustic waves with higher frequency components, and hence the imaging contrast can be enhanced by appropriate selection of the spectral subbands. This study employed both finite-difference, time-domain-based simulations and phantom imaging. The numerical results show that the peak frequencies of the signals for objects with absorption coefficients of 1 and 100 cmM(-1) were 2.4 and 7.8 MHz, respectively. Imaging an agar-based phantom further demonstrated that the contrast between two objects with absorption coefficients of 5.01 and 41.75 cm(-1) can be improved by 4-10 dB when the frequency band was changed from 0-7 to 7-14 MHz. Finally, a method to further enhance the contrast based on optimal weighting is also presented. The proposed method is of particular interest in photoacoustic molecular imaging.

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.

Photoacoustic temperature measurements for monitoring of thermal therapy

Plasmonic photothermal therapy is a new cancer thermotherapy method based on surface plasmon resonance of nanoparticles. It is important to measure the temperature during thermotherapy for safety and efficacy. In this study, we apply a photoacoustic (PA) method for real-time, non-invasive temperature measurements. In particular, this method can be effectively combined with a photothermal therapy system that we developed in parallel. The method is based on the fact that the PA pressure amplitude is linearly related to temperature. To explore its potential, a home-made, 20 MHz PA transducer was used, in which an optical fiber was inserted in its center for emitting laser pulses while the PA signal was simultaneously detected. Continuous wave (CW) laser was used to heat the subject, including both phantoms and mice. The temperature of the region of interest was also measured by a fine-needle thermal couple. Results show that the temperature was linearly proportional to the PA signal with good correlation with the CW laser irradiation. The in vivo study also demonstrated potential of this technique.