We designed, fabricated and tested the laser optoacoustic imaging system for breast cancer detection (LOIS-64), which fuses optical and acoustic imaging techniques in one modality by utilizing pulsed optical illumination and ultrawide-band ultrasonic detection of resulting optoacoustic (OA) signals. The system was designed to image a single breast slice in craniocaudal or mediolateral projection with an arc-shaped array of 64 ultrawide-band acoustic transducers. The system resolution on breast phantoms was at least 0.5 mm. The single-channel sensitivity of 1.66 mVPa was estimated to be sufficient for single-pulse imaging of 6 to 11 mm tumors through the whole imaging slice of the breast. The implemented signal processing using the wavelet transform allowed significant reduction of the low-frequency (LF) acoustic noise, allowed localization of the optoacoustic signals from tumors, and enhanced the contrast and sharpened the boundaries of the optoacoustic images of the tumors. During the preliminary clinical studies on 27 patients, the LOIS-64 was able to visualize 18 out of 20 malignant lesions suspected from mammography and ultrasound images and confirmed by the biopsy performed after the optoacoustic tomography (OAT) procedure.

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 µL 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 µL 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.

Abstract. We develop a system for three-dimensional whole-body optoacoustic tomography of small animals for applications in preclinical research. The tomographic images are obtained while the objects of study ͑phantoms or mice͒ are rotated within a sphere outlined by a concave arc-shaped array of 64 piezocomposite transducers. Two pulsed lasers operating in the near-IR spectral range ͑755 and 1064 nm͒ with an average pulsed energy of about 100 mJ, a repetition rate of 10 Hz, and a pulse duration of 15 to 75 ns are used as optical illumination sources. During the scan, the mouse is illuminated orthogonally to the array with two wide beams of light from a bifurcated fiber bundle. The system is capable of generating images of individual organs and blood vessels through the entire body of a mouse with spatial resolution of ϳ0.5 mm.

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 ~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 ~100 µm 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.

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