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We present an integrated photoacoustic and ultrasonic three-dimensional (3D) volumetric imaging system based on a two-dimensional (2D) matrix array ultrasound probe. A wavelength-tunable dye laser pumpedby a Q-switched Nd:YAG laser serves as the light source and a modified commercial ultrasound imaging system (iU22, Philips Healthcare) with a 2D array transducer (X7-2, Philips Healthcare) detects both the pulse-echo ultrasound and photoacoustic signals. A multichannel data acquisition system acquires the RF channel data. The imaging system enables rendering of co-registered 3D ultrasound and photoacoustic images without mechanical scanning. The resolution along the azimuth, elevation, and axial direction are measured to be 0.66 mm, 0.91and 0.84 mm for photoacoustic imaging. In vivo 3D photoacoustic mapping of the sentinel lymph node was demonstrated in a rat model usingmethylene blue dye. These results highlight the clinical potentialof 3D PA imaging for identification of sentinel lymph nodes for cancer staging in humans.

We developed a tri-modality imaging system for breast cancer imagingby integrating photoacoustic (PA) and thermoacoustic (TA) imaging techniques into a modified commercial ultrasound scanner. Laser and microwave excitation pulses were interleaved to enable PA and TA dataacquisition in parallel at the rate of 10 frames per second. The performance of the tri-modality imaging system was evaluated in-vitrousing phantom samples. A plastic tube (7 mm inner diameter, 25 mm length) filled with 30 mM methylene blue dye placed at a depth of 8.4cm in chicken breast tissue was successfully detected in PA images with an ultrasonic bandwidth of 1–5 MHz. The SNR at this depth was 15dB after averaging 200 signal acquisitions. Similarly, a plastic tube (7 mm inner diameter, 25 mm length) filled with high concentration salt water placed at a depth of 5.1 cm in porcine fat tissue was successfully detected in TA images. A PA noise-equivalent-sensitivityto methylene blue solution of 260 nM was achieved in chicken tissueat a depth of 3.4 cm and with a laser fluence of 17 mJ/cm2.

Photoacoustic tomography (PAT) is a molecular imaging technology. Unlike conventional reporter gene imaging, which is based on fluorescent proteins, photoacoustic reporter gene imaging is based on opticalabsorption. Using lacZ, one of the most widely used reporter genesin biology, this work demonstrated several key merits of PAT. We proved that the expression of lacZ can be imaged by PAT as deep as 5.0cm in biological tissue with resolutions of ~1.0 mm and ~0.4 mm in the lateral and axial directions, respectively. We further demonstrated non-invasive simultaneous imaging of a lacZ-marked tumor and itssurrounding microvasculature in vivo by dual-wavelength acoustic-resolution photoacoustic microscopy, with a lateral resolution of 45 µmand an axial resolution of 15 µm. Finally, using optical-resolutionphotoacoustic microscopy, we showed sub-cellular localization of lacZ expression, with a lateral resolution of a fraction of a micron.These results suggest that PAT is potentially a complementary tool to conventional optical fluorescence imaging of reporter genes for linking biological studies from the microscopic to the macroscopic scales.