Conoscopic interferometry is a promising detection technique for ultrafast acoustics. By focusing a probe beam through a birefringent crystal before passing it through a polarizer, conoscopic interferences sculpt the spatial profile of the beam. The use of these patterns for acoustic wave detection revealed a higher detection sensitivity over existing techniques, such as reflectometry and beam distortion detection. However, the physical origin of the increased sensitivity is unknown. In this work, we present a model, describing the sensitivity behavior of conoscopic interferometry with respect to the quarter-wave plate orientation and the diaphragm aperture, which is validated experimentally. Using the model, we optimize the detection sensitivity of conoscopic interferometry. We obtain a maximal sensitivity of detection when placing the diaphragm edge on the dark fringes of the conoscopic interference patterns. In the configurations studied in this work, conoscopic interferometry can be 18 dB more sensitive to acoustic waves than beam distortion detection.

Significance: Physics-based simulations of photoacoustic (PA) signals are used to validate new methods, to characterize PA setups and to generate training datasets for machine learning. However, a thoroughly validated PA simulation toolchain that can simulate realistic images is still lacking.Aim: A quantitative toolchain was developed to model PA image acquisition in complex tissues, by simulating both the optical fluence and the acoustic wave propagation.Approach: Sampling techniques were developed to decrease artifacts in acoustic simulations. The performance of the simulations was analyzed by measuring the point spread function (PSF) and using a rotatable three-channel phantom, filled with cholesterol, a human carotid plaque sample, and porcine blood. Ex vivo human plaque samples were simulated to validate the methods in more complex tissues.Results: The sampling techniques could enhance the quality of the simulated PA images effectively. The resolution and intensity of the PSF in the turbid medium matched the experimental data well. Overall, the appearance, signal-to-noise ratio and speckle of the images could be simulated accurately.Conclusions: A PA toolchain was developed and validated, and the results indicate a great potential of PA simulations in more complex and heterogeneous media.

Conoscopic interferometry is a promising detection technique for ultrafast acoustics. By focusing a probe beam through a birefringent crystal before passing it through a polarizer, conoscopic interferences sculpt the spatial profile of the beam. The use of these patterns for acoustic wave detection revealed a higher detection sensitivity over existing techniques, such as reflectometry and beam distortion detection. However, the physical origin of the increased sensitivity is unknown. In this work, we present a model, describing the sensitivity behaviour of conoscopic interferometry with respect to the quarter-wave plate orientation and the diaphragm aperture, which is validated experimentally. Using the model, we optimize the detection sensitivity of conoscopic interferometry. We obtain a maximal sensitivity of detection when placing the diaphragm edge on the dark fringes of the conoscopic interference patterns. In the configurations studied in this work, conoscopic interferometry can be 8x more sensitive to acoustic waves than beam distortion detection.

Multi-spectral photoacoustic imaging (MSPAI) is promising for morphology assessment of carotid plaques; however, obtaining unique spectral characteristics of chromophores is cumbersome. We used MSPAI and non-negative independent component analysis (ICA) to unmix distinct signal sources in human carotid plaques blindly. The feasibility of the method was demonstrated on a plaque phantom with hemorrhage and cholesterol inclusions, and plaque endarterectomy samples ex vivo. Furthermore, the results were verified with histology using Masson's trichrome staining. Results showed that ICA could separate recent hemorrhages from old hemorrhages. Additionally, the signatures of cholesterol inclusion were also captured for the phantom experiment. Artifacts were successfully removed from signal sources. Histologic examinations showed high resemblance with the unmixed components and confirmed the morphologic distinction between recent and mature hemorrhages. In future pre-clinical studies, unmixing could be used for morphology assessment of intact human plaque samples.

Photoacoustic imaging (PAI) is a promising imaging modality due to its high optical specificity. However, the low signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of in vivo PA images are major challenges that prevent PAI from finding its place in clinics. This paper investigates the merit of spatial compounding of PA images in arterial phantoms and the achievable improvements of SNR, when in vivo conditions are mimicked. The analysis of the compounding technique was performed on a polyvinyl alcohol vessel phantom with black threads embedded in its wall. The in vivo conditions were mimicked by limiting the rotation range in ±30°, adding turbid surrounding medium, and filling the lumen with porcine blood. Finally, the performance of the technique was evaluated in ex vivo human carotid plaque samples. Results showed that spatial compounding elevates the SNR by 5-10 dB and CNR by 1-5 dB, depending on the location of the absorbers. This paper elucidates prospective in vivo PA characterization of carotid plaques by proposing a method to enhance PA image quality.

Assessment of microvasculature and tissue perfusion can provide diagnostic information on local or systemic diseases. Photoacoustic (PA) imaging has strong clinical potential because of its sensitivity to hemoglobin. We used a hand-held PA probe with integrated diode lasers and examined its feasibility and validity in the detection of increasing blood volume and (sub) dermal vascularization. Blood volume detection was tested in custom-made perfusion phantoms. Results showed that an increase of blood volume in a physiological range of 1.3% to 5.4% could be detected. The results were validated with power Doppler sonography. Using a motorized scanning setup, areas of the skin were imaged at relatively short scanning times ( < 10 ?? s / cm 2 ) with PA. Three-dimensional visualization of these structures was achieved by combining the consecutively acquired cross-sectional images. Images revealed the epidermis and submillimeter vasculature up to depth of 5 mm. The geometries of imaged vasculature were validated with segmentation of the vasculature in high-frequency ultrasound imaging. This study proves the feasibility of PA imaging in its current implementation for the detection of perfusion-related parameters in skin and subdermal tissue and underlines its potential as a diagnostic tool in vascular or dermal pathologies.

The signal-to-noise ratio (SNR) of photoacoustic (PA) images of carotid arteries is considerably low for in vivo measurements. Compounding of the acquisitions from multiple locations might improve SNR of PA images. In this study, we investigated the effects of spatial compounding based on SNR comparison of PA images of a polyvinyl alcohol (PVA) phantom and an ex vivo carotid plaque, both imaged in an experimental setting. PA and plane wave ultrasound (PUS) data were acquired in a cross-section of each sample. The sample was rotated by 10° and measurements were repeated for 36 angles. Results showed that PA compounding elevated the SNR by 28.7±5.1 dB for the PVA sample and 5.5±2.4 dB for the plaque sample. Additionally, the compounding results for the limited range of rotation as would be feasible in vivo ( −30 to +30) showed an enhancement in SNR of 7.02 ± 2.73 dB. For the future, extra characterization parameters such as resolution, contrast, and sensitivity will be investigated under in vivo conditions.

Abstract. Photoacoustic imaging (PAI) may have the ability to reveal the composition and the anatomical structure of carotid plaques, which determines its mechanical properties and vulnerability. We used PAI and plane wave ultrasound (PUS) imaging to obtain three-dimensional (3-D) images of endarterectomy samples ex vivo and compared the results with histology to investigate the potential of PAI-based identification of intraplaque hemorrhage. Seven carotid plaque samples were obtained from patients undergoing carotid endarterectomy and imaged with a fully integrated hand-held photoacoustic (PA) probe, consisting of a pulsed diode laser (tpulse=130  ns, Epulse=1  mJ, λ=808  nm) and a linear array transducer (fc=7.5  MHz). The samples were rotated 360 deg with 10 deg steps, and data were spatially compounded to obtain complete 3-D images of the plaques. Areas of high absorption in the 3-D datasets were identified and compared to histological data of the plaques. Data in six out of seven endarterectomy samples revealed the presence of intraplaque hemorrhages that were not visible in the PUS images. Due to the noninvasive nature of PAI, this ex vivo study may elucidate preclinical studies toward the in vivo, noninvasive, vulnerability assessment of the atherosclerotic carotid plaque.

Vulnerability assessment of carotid plaques is vital to prevent atherosclerosis-related mortality and disability. Photoacoustic imaging (PAI) in combination with plane-wave ultrasound (PUS) may have the ability to reveal the composition and the anatomical structure of the plaque, which infers its mechanical properties and vulnerability. In this study, we used PAI and PUS imaging to scan endarterectomy samples ex vivo, targeting intraplaque hemorrhage, and compared the results with those obtained in healthy (porcine) carotids and histology. A fully integrated hand-held photoacoustic probe was used, consisting of a pulsed diode laser (t p = 130 ns, E p = 1 mJ, λ = 808 nm) and a linear array transducer (f c = 7.5 MHz). Three porcine carotid arteries and six carotid plaque samples were obtained from a local slaughterhouse and hospital respectively, and were mounted to the imaging setup. Data of endarterectomy samples revealed that PAI of carotid plaques at 808 nm wavelength is capable of detecting blood clots, which can be extensions of vasculature in the plaque, intra-plaque hemorrhage, or the result of trauma inflicted on the medial vascularization. Due to calcification and the limited optical penetration, imaging depth was mostly limited to the proximal wall of the samples. The porcine carotids revealed no hemorrhaging, which was corroborated by the lack of PAI contrast.

Multispectral photoacoustic (MPA) imaging is a promising tool for the diagnosis of atherosclerotic carotids. Excitation of different constituents of a plaque with different wavelengths of the light may provide morphological information to evaluate plaque vulnerability. Preclinical validation of in vivo photoacoustic (PA) imaging requires a comprehensive phantom study. In this study, the design of optically realistic vessel phantoms for photoacoustics was examined by characterizing their optical properties for different dye concentrations, and comparing those to PA measurements. Four different concentrations of Indian ink and molecular dye were added to a 15 wt% PVA and 1 wt% orgasol mixture. Next, the homogeneously mixed gels were subjected to five freeze - thaw cycles to increase the stiffness of vessel phantoms (r inner 2.51111r1, router 4mm). For each cycle, the optical absorbance was measured between 400 nm 990 nm using a plate reader. Additionally, photoacoustic responses of each vessel phantom at 808 nm were tested with a novel, hand-held, integrated PA probe. Measurements show that the PA signal intensity increases with the optical absorber concentration (0.3 to 0.9) in close agreement with the absorbance measurements. The freeze - thaw process has no significant effect on PA intensity. However, the total attenuation of optical energy increases after each freeze-thaw cycle, which is primarily due to the increase in the scattering coefficient. In future work, the complexity of these phantoms will be increased to examine the feasibility of distinguishing different constituents with MPA imaging.

Ultrasound-based measurements using Doppler, contrast, and more recently photoacoustics (PA), have emerged as techniques for tissue perfusion measurements. In this study, the feasibility of in vitro perfusion measurements with a fully integrated, hand-held, photoacoustic probe was investigated and compared to Power Doppler (PD).Three cylindrical polyvinyl alcohol (PVA) phantoms were made (diameter = 15 mm) containing 100, 200 and 400 parallel polysulfone tubes (diameter = 0.2 mm), resulting in a perfused cross-sectional area of 1.8, 3.6 and 7.1% respectively. Each phantom was perfused with porcine blood (15 mL/min). Cross-sectional PA images (lambda = 805nm, frame rate = 10Hz) and PD images (PRF = 750Hz) were acquired with a MyLab One and MyLab 70 scanner (Esaote, NL), respectively. Data were averaged over 70 frames.The average PA signal intensity was calculated in a region-of-interest of 4 mm by 6 mm. The percentage of colored PD pixels was measured in the entire phantom region. The average signal intensity of the PA images increased linearly with perfusion density, being 0.54 (+/- 0.01), 0.56 (+/- 0.01), 0.58 (+/- 0.01) with an average background signal of 0.53 in the three phantoms, respectively. For PD, the percentage of colored pixels in the phantom area (1.5% (+/- 0.2%), 4.4% (+/- 0.2%), 13.7% (+/- 0.8%)) also increased linearly. The preliminary results suggest that PA, like PD, is capable of detecting an increase of blood volume in tissue. In the future, in vivo measurements will be explored, although validation will be more complex.

Preclinical validation of non-invasive photoacoustic imaging of carotid artery atherosclerosis requires vessel phantoms that imitate optical, acoustic and mechanical properties of vascular tissue. Polyvinyl alcohol (PVA) phantoms that are widely used as ultrasound phantoms due to their elastic properties are also promising for photoacoustics. This study contributes to the field by quantifying the optical and acoustic properties of PVA gel, and aims at the characterization of realistic phantoms for future studies. In this study, we investigated the relation between acoustic scatterers and optical absorbers to quantify optical and acoustic properties of the PVA phantoms. Four different concentrations of orgasol acoustic scatterers, and varying concentration of Indian ink and molecular dye absorbers were added to a 15 wt% PVA solution. Samples were subjected to 1 to 5 freeze-thaw cycles and were examined after each cycle to quantify the effect on the optical and the acoustic properties. Optical attenuation was measured between 400 nm and 990 nm using a plate reader. Additionally, pulse-echo plane wave ultrasound was used for acoustic characterization. Changing the concentration of orgasol between 0.5 wt% and 4 wt% increased the mean optical attenuation of PVA by 35% after the first freeze thaw cycle. Likewise, each freeze-thaw cycle increased the optical attenuation due to scattering of light by the microstructure of PVA. The absorbance of pure PVA increased 40% between the first and second cycle and 3% between the fourth and fifth cycle. While the orgasol concentration and the freeze-thaw cycles altered the acoustic speed and attenuation, the ink and the dye inclusions did not significantly affect the acoustic properties of PVA.

Photoacoustic microscopy, as an imaging modality, has shown promising results in imaging angiogenesis and cutaneous malignancies like melanoma, revealing systemic diseases including diabetes, hypertension, tracing drug efficiency and assessment of therapy, monitoring healing processes such as wound cicatrization, brain imaging and mapping. Clinically, photoacoustic microscopy is emerging as a capable diagnostic tool. Parameters of lasers used in photoacoustic microscopy, particularly, pulse duration, energy, pulse repetition frequency, and pulse-to-pulse stability affect signal amplitude and quality, data acquisition speed and indirectly, spatial resolution. Lasers used in photoacoustic microscopy are typically Q-switched lasers, low-power laser diodes, and recently, fiber lasers. Significantly, the key parameters cannot be adjusted independently of each other, whereas microvasculature and cellular imaging, e.g., have different requirements. Here, we report an integrated fiber laser system producing nanosecond pulses, covering the spectrum from 600 nm to 1100 nm, developed specifically for photoacoustic excitation. The system comprises of Yb-doped fiber oscillator and amplifier, an acousto-optic modulator and a photonic-crystal fiber to generate supercontinuum. Complete control over the pulse train, including generation of non-uniform pulse trains, is achieved via the AOM through custom-developed field-programmable gate-array electronics. The system is unique in that all the important parameters are adjustable: pulse duration in the range of 1-3 ns, pulse energy up to 10 μJ, repetition rate from 50 kHz to 3 MHz. Different photocoustic imaging probes can be excited with the ultrabroad spectrum. The entire system is fiber-integrated; guided-beam-propagation rendersit misalignment free and largely immune to mechanical perturbations. The laser is robust, low-cost and built using readily available components.

In this work, Fourier transform based analytical solution to photoacoustic wave equation is obtained for an optically absorbing spherical object warmed up by a pulsed laser for rectangular and Gaussian radial profiles by treating the temporal profile of the laser as Gaussian. The photoacoustic signal is investigated as a function of time for different locations outside the spherical object. An expression including the dependency of the laser parameters on the photoacoustic signal is presented.