Although photoacoustic computed tomography (PACT) operates with high spatial resolution in biological tissues deeper than other optical modalities, light scattering is a limiting factor. The use of longer near infrared wavelengths reduces scattering. Recently, the rational design of a stable phosphorus phthalocyanine (P-Pc) with a long wavelength absorption band beyond 1000 nm has been reported. Here, we show that when dissolved in liquid surfactants, P-Pc can give rise to formulations with absorbance of greater than 1000 (calculated for a 1 cm path length) at wavelengths beyond 1000 nm. Using the broadly accessible Nd:YAG pulse laser emission output of 1064 nm, P-Pc could be imaged through 11.6 cm of chicken breast with PACT. P-Pc accumulated passively in tumors following intravenous injection in mice as observed by PACT. Following oral administration, P-Pc passed through the intestine harmlessly, and PACT could be used to non-invasively observe intestine function. When the contrast agent placed under the arm of a healthy adult human, a PACT transducer on the top of the arm could readily detect P-Pc through the entire 5 cm limb. Thus, the approach of using contrast media with extreme absorption at 1064 nm readily enables high quality optical imaging in vitro and in vivo in humans at exceptional depths.

Photoacoustic computed tomography (PACT) holds great promise for biomedical imaging, but wide-spread implementation is impeded by the bulkiness of flash-lamp-pumped laser systems, which typically weigh between 50 -200 kg, require continuous water cooling, and operate at a low repetition rate. Here, we demonstrate that compact lasers based on emerging diode technologies are well-suited for preclinical and clinical PACT. The diodepumped laser used in this study had a miniature footprint (13 × 14 × 7 cm 3 ), weighed only 1.6 kg, and outputted up to 80 mJ per pulse at 1064 nm. In vitro, the laser system readily provided over 4 cm PACT depth in chicken breast tissue. In vivo, in addition to high resolution, non-invasive brain imaging in living mice, the system can operate at 50 Hz, which enabled high-speed cross-sectional imaging of murine cardiac and respiratory function. The system also provided high quality, high-frame rate, and non-invasive three-dimensional mapping of arm, palm, and breast vasculature at multi centimeter depths in living human subjects, demonstrating the clinical viability of compact lasers for PACT.

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While the majority of photoacoustic imaging systems used custom-made transducer arrays, commercially-available linear transducer arrays hold the benefits of affordable price, handheld convenience and wide clinical recognition. They are not widely used in photoacoustic imaging primarily because of the poor elevation resolution. Here, without modifying the imaging geometry and system, we propose addressing this limitation purely through image reconstruction. Our approach is based on the integration of two advanced image reconstruction techniques: focal-line-based three-dimensional image reconstruction and coherent weighting. We first numerically validated our approach through simulation and then experimentally tested it in phantom and in vivo. Both simulation and experimental results proved that the method can significantly improve the elevation resolution (up to 4 times in our experiment) and enhance object contrast.

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