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A miniature, directional fibre-optic acoustic source is presented that employs geometrical focussing to generate a nearly-collimated acoustic pencil beam. When paired with a fibre-optic acoustic detector, an all-optical ultrasound probe with an outer diameter of 2.5 mm is obtained that acquires a pulse-echo image line at each probe position without the need for image reconstruction. B-mode images can be acquired by translating the probe and concatenating the image lines, and artefacts resulting from probe positioning uncertainty are shown to be significantly lower than those observed for conventional synthetic aperture scanning of a non-directional acoustic source. The high image quality obtained for excised vascular tissue suggests that the all-optical ultrasound probe is ideally suited for in vivo, interventional applications.

We report on simultaneous frequency domain optical-resolution photoacoustic and fluorescence microscopy with sub-µm lateral resolution. With the help of a blood smear, we show that photoacoustic and fluorescence images provide complementary information. Furthermore, we compare theoretically predicted signal-to-noise ratios of sinusoidal modulation in frequency domain with pulsed excitation in time domain.

Acoustic resolution photoacoustic Doppler velocimetry promises to overcome the spatial resolution and depth penetration limitations of current blood flow measuring methods. Despite successful implementation using blood-mimicking fluids, measurements in blood have proved challenging, thus preventing in vivo application. A common explanation for this difficulty is that whole blood is insufficiently heterogeneous relative to detector frequencies of tens of MHz compatible with deep tissue photoacoustic measurements. Through rigorous experimental measurements we provide new insight that refutes this assertion. We show for the first time that, by careful choice of the detector frequency and field-of-view, and by employing novel signal processing methods, it is possible to make velocity measurements in whole blood using transducers with frequencies in the tens of MHz range. These findings have important implications for the prospects of making deep tissue measurements of blood flow relevant to the study of microcirculatory abnormalities associated with cancer, diabetes, atherosclerosis and other conditions.

The feasibility of detecting red blood cell (RBC) aggregation with photoacoustics (PAs) was investigated theoretically and experimentally using human and porcine RBCs. The theoretical PA signals and spectra generated from such samples were examined for several hematocrit levels and aggregates sizes. The effect of a finite transducer bandwidth on the received PA signal was also examined. The simulation results suggest that the dominant frequency of the PA signals from non-aggregated RBCs decreases towards clinical frequency ranges as the aggregate size increases. The experimentally measured mean spectral power increased by ~6 dB for the largest aggregate compared to the non-aggregated samples. Such results confirm the theoretical predictions and illustrate the potential of using PA imaging for detecting RBC aggregation.

The establishment of multiplex photoacoustic molecular imaging to characterize heterogeneous tissues requires the use of a tunable, thermally stable contrast agent targeted to specific cell types. We have developed a multiplex photoacoustic imaging technique which uses targeted silica-coated gold nanorods to distinguish cell inclusions in vitro. This paper describes the use of tunable targeted silica-coated gold nanorods (SiO(2)-AuNRs) as contrast agents for photoacoustic molecular imaging. SiO(2)-AuNRs with peak absorption wavelengths of 780 nm and 830 nm were targeted to cells expressing different cell receptors. Cells were incubated with the targeted SiO(2)-AuNRs, incorporated in a tissue phantom, and imaged using multiwavelength photoacoustic imaging. We used photoacoustic imaging and statistical correlation analysis to distinguish between the unique cell inclusions within the tissue phantom.

We describe 3D single particle tracking of gold nanoparticles (AuNPs) moving along collagen fibers in aqueous environment with two-photon excitation conditions. The photoacoustic effect at the collagen fiber caused by the irradiation with ultrashort, near-infrared laser pulses propels the particles adsorbed to the surface of the collagen fibers. We report the tracking of individual AuNPs in three dimensions with high spatial and temporal resolution, of few nanometers and milliseconds, respectively. Due to the emission signal caused by the interaction between the AuNPs and the weak chromophores in the collagen fiber, the trajectories of individual AuNPs reveal the fiber topography with nanometric resolution. The intensity along the trajectory shows that we are sensitive to the distribution of the weak chromophores on the fiber.

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.

Optical stimulation of the inner ear, the cochlea, is discussed as a possible alternative to conventional cochlear implants with the hypothetical improvement of dynamic range and frequency resolution. In this study nanosecond-pulsed optical stimulation of the hearing and non-hearing inner ear is investigated in vivo over a wide range of optical wavelengths and at different beam delivery locations. Seven anaesthetized guinea pigs were optically stimulated before and after neomycin induced destruction of hair cells. An optical parametric oscillator was tuned to different wavelengths (420 nm-2150 nm, ultraviolet to near-infrared) and delivered 3-5 ns long pulses with 6 µJ pulse energy via a multimode optical fiber located either extracochlearly in front of the intact round window membrane or intracochlearly within the scala tympani. Cochlear responses were measured using registration of compound action potentials (CAPs). With intact hair cells CAP similar to acoustic stimulation were measured at both locations, while the neomycin treated cochleae did not show any response in any case. The CAP amplitudes of the functional cochleae showed a positive correlation to the absorption coefficient of hemoglobin and also to moderate water absorption. A negative correlation of CAP amplitude with a water absorption coefficient greater than 5.5 cm(-1) indicates additional phenomena. We conclude that in our stimulation paradigm with ns-pulses the most dominant stimulation effect is of optoacoustic nature and relates to functional hair cells.

In this paper, we report our latest progress on proving the concept that ultrasonic phased array can improve the detection sensitivity and field of view (FOV) in laser-scanning photoacoustic microscopy (LS-PAM). A LS-PAM system with a one-dimensional (1D) ultrasonic phased array was built for the experiments. The 1D phased array transducer consists of 64 active elements with an overall active dimension of 3.2 mm × 2 mm. The system was tested on imaging phantom and mouse ear in vivo. Experiments showed a 15 dB increase of the signal-to-noise ratio (SNR) when beamforming was employed compared to the images acquired with each single element. The experimental results demonstrated that ultrasonic phased array can be a better candidate for LS-PAM in high sensitivity applications like ophthalmic imaging.

We developed a high-resolution photoacoustic microscopy (PAM) system with a near-infrared (NIR) laser to noninvasively monitor the distribution of gold nanostar (GNS) in blood vessels, liver and spleen in mice. Photoacoustic images of organs at deep depths were continuously acquired in vivo every 30 minutes after a single dose of GNS by tail vein injection. The experimental results showed that GNS accumulated significantly in both liver and spleen from blood circulation after administration, which was qualitatively validated by fluorescence imaging. Our studies demonstrate that PAM might be potentially used for noninvasive tracing the kinetics of exogenous nanoparticles in biological system.

Modulated tone-burst light was employed to measure non-radiative relaxation time of fluorophores with biomedical importance through photoacoustic effect. Non-radiative relaxation time was estimated through the frequency dependence of photoacoustic signal amplitude. Experiments were performed on solutions of new indocyanine green (IR-820), which is a near infrared dye and has biomedical applications, in two different solvents (water and dimethyl sulfoxide (DMSO)). A 1.5 times slower non-radiative relaxation for the solution of dye in DMSO was observed comparing with the aqueous solution. This result agrees well with general finding that non-radiative relaxation of molecules in triplet state depends on viscosity of solvents in which they are dissolved. Measurements of the non-radiative relaxation time can be used as a new source of contrast mechanism in photoacoustic imaging technique. The proposed method has potential applications such as imaging tissue oxygenation and mapping of other chemophysical differences in microenvironment of exogenous biomarkers.

We have developed a novel, hybrid imaging modality, Transient Absorption Ultrasonic Microscopy (TAUM), which fuses photoacoustic microscopy with non-linear microscopy. Photoacoustic microscopy is well known for its ability to image chromophores deep (> 1 mm) in scattering media with spatial resolutions in the 10s of microns. Non-linear microscopy is well known for its exquisite spatial resolution in three dimensions. This superior spatial resolution is attributed to the fact that the collected signal has a non-linear dependence on the light intensity. This dependence confines the signal to a very small focal volume, producing optically resolved voxels. Transient absorption is a non-linear process often used to map the excited state lifetimes of molecules exhibiting low fluorescence quantum efficiency. This sensitivity to non-radiative transitions makes transient absorption an attractive process to combine with photoacoustic imaging. We have built a prototype transient absorption ultrasonic microscope, implementing off-axis photoacoustic detection to allow the use of a high-quality, high numerical aperture objective. This high-quality, commercial lens is required to provide the tight focusing needed to optimize non-linear effects. We have demonstrated the increased spatial resolution of TAUM by imaging Rhodamine 6G in a capillary tube. The capillary cross-section is fully resolved, suggesting an axial resolution of < 10 microns. A 6 MHz transducer was used in this experiment, which results in an axial resolution of ~ 400 microns when used in a traditional photoacoustic microscope. Boasting the superior penetration depth and absorption contrast offered by photoacoustic emission and complemented by spatial resolutions comparable to confocal microscopy, we believe that Transient Absorption Ultrasonic Microscopy has excellent potential for producing volumetric images with cellular/subcellular resolution in three dimensions deep inside living tissue.