Photoacoustic Waves Research Articles

Photoacoustic radiation force on a microbubble.

We investigate the radiation force on a microbubble due to the photoacoustic wave which is generated by using a pulsed laser. In particular, we focus on the dependence of pulsed laser parameters on the radiation force. In order to do so, we first obtain a new and comprehensive analytical solution to the photoacoustic wave equation based on the Fourier transform for various absorption profiles. Then, we write an expression of the radiation force containing explicit laser parameters, pulse duration, and beamwidth of the laser. Furthermore, we calculate the primary radiation force acting on a microbubble. We show that laser parameters and the position of the microbubble relative to a photoacoustic source have a considerable effect on the primary radiation force. By means of recent developments in laser technologies that render tunability of pulse duration and repetition frequency possible, an adjustable radiation force can be applied to microbubbles. High spatial control of applied force is ensured on account of smaller focal spots achievable by focused optics. In this context, conventional piezoelectric acoustic source applications could be surpassed. In addition, it is possible to increase the radiation force by making source wavelength with the absorption peak of absorber concurrent. The application of photoacoustic radiation force can open a cache of opportunities such as manipulation of microbubbles used as contrast agents and as carrier vehicles for drugs and genes with a desired force along with in vivo applications.

Exploring a photo-acousto-optic effect for noncontacting photoacoustic sensing.

To avoid the use of ultrasound transducers and coupling gel in photoacoustic microscopy (PAM), we propose photo-acousto-optic tomography (PAOT) for noncontact photoacoustic (PA) sensing. The process consists of two parts. The first portion is the same as typical PAM, which employs a pulsed laser to induce acoustic waves. The difference from typical methods lies in the second part of the process, which applies a DC beam, rather than a conventional transducer, to sense the PA signal. A two-beam optical microscope system was designed to verify the PAOT effect, whereby an AC spot acted as the source to induce a PA signal, while a DC beam is applied to induce the acousto-optic effect for detection of the acoustic wave. We demonstrated the preliminary result that 5-100 Hz AC radiation could derive PA waves in a water-like medium along with detection sensitivity as high as 4.9%-10.0%; besides, the signal waveform could be detected by a DC spot 10-100 μm away for noncontact sensing with detection sensitivity of about 3.7%-10.4%. Without the need for a transducer or coupling gel, PAOT has the potential to modify conventional PAM into a pure optical system, which could make PA imaging more promising in practical applications.

In vivo optically encoded photoacoustic flowgraphy.

We present an optically encoded photoacoustic (PA) flow imaging method based on optical-resolution PA microscopy. An intensity-modulated continuous-wave laser photothermally encodes the flowing medium, and a pulsed laser generates PA waves to image the encoded heat pattern. Flow speeds can be calculated by cross correlation. The method was validated in phantoms at flow speeds ranging from 0.23 to 11 mm/s. Venous blood flow speed in a mouse ear was also measured.

Photoacoustic phasoscopy super-contrast imaging

Phasoscopy is a recently proposed concept correlating electromagnetic (EM) absorption and scattering properties based on energy conservation. Phase information can be extracted from EM absorption induced acoustic wave and scattered EM wave for biological tissue characterization. In this paper, an imaging modality, termed photoacoustic phasoscopy imaging (PAPS), is proposed and verified experimentally based on phasoscopy concept with laser illumination. Both endogenous photoacoustic wave and scattered photons are collected simultaneously to extract the phase information. The PAPS images are then reconstructed on vessel-mimicking phantom and ex vivo porcine tissues to show significantly improved contrast than conventional photoacoustic imaging.

Coherent photoacoustic-ultrasound correlation and imaging.

Both photoacoustics and ultrasound have been researched extensively but separately. In this letter, we report an initial study on the coherent correlation between pulsed photoacoustic wave and pulse-echo ultrasound wave. By illuminating an object with a pulsed laser and external ultrasound sequentially, both the endogenous photoacoustic wave and pulse-echo ultrasound wave are received and coherently correlated, demonstrating enhanced signal-to-noise ratio. Image contrast of the proposed coherent photoacoustic-ultrasound imaging is also demonstrated to be improved significantly on vessel-mimicking phantom, due to fusion of the optical absorption and ultrasound reflection contrasts by coherent correlation of either conventional laser-induced photoacoustic imaging or pulse-echo ultrasound imaging separately.

Generation of photoacoustic transients from optically induced thermal gradients

Irradiation of an absorbing surface in contact with a transparent fluid with a pulsed laser can result in the generation of extremely large thermal gradients. For example, when a laser with a pulse width of 10 ns and a fluence of 1 J/cm2 irradiates a region with an absorption of 1 cm1 having the thermal properties of liquid water, a thermal gradient on the order of 105 K/m at the interface is produced. Here, it is shown that the effect of such thermal gradients on photoacoustic waves from an infinite half space and from a uniformly irradiated sphere is the production of fast transients on the leading edges of the waves. The character of the transients is determined from an additional source term in the wave equation for pressure that obtains when heat conduction is taken into account. Experiments are reported showing the predicted transients on photoacoustic waves from absorbing layers in contact with transparent fluids irradiated with 10 ns laser pulses.

Efficient Intracellular Delivery of Molecules with High Cell Viability Using Nanosecond-Pulsed Laser-Activated Carbon Nanoparticles

Conventional physical and chemical methods that efficiently deliver molecules into cells are often associated with low cell viability. In this study, we evaluated the cellular effects of carbon nanoparticles believed to emit photoacoustic waves due to nanosecond-pulse laser activation to test the hypothesis that this method could achieve efficient intracellular delivery while maintaining high cell viability. Suspensions of DU145 human prostate carcinoma cells, carbon black (CB) nanoparticles, and calcein were exposed to 5–9 ns long laser pulses of near-infrared (1064 nm wavelength) light and then analyzed by flow cytometry for intracellular uptake of calcein and cell viability by propidium iodide staining. We found that intracellular uptake increased and in some cases saturated at high levels with only small losses in cell viability as a result of increasing laser fluence, laser exposure time, and as a unifying parameter, the total laser energy. Changing interpulse spacing between 0.1 and 10 s intervals showed no significant change in bioeffects, suggesting that the effects of each pulse were independent when spaced by at least 0.1 s intervals. Pretreatment of CB nanoparticles to intense laser exposure followed by mixing with cells also had no significant effect on uptake or viability. Similar uptake and viability were seen when CB nanoparticles were substituted with India ink, when DU145 cells were substituted with H9c2 rat cardiomyoblast cells, and when calcein was substituted with FITC-dextran. The best laser exposure conditions tested led to 88% of cells with intracellular uptake and close to 100% viability, indicating that nanosecond-pulse laser-activated carbon nanoparticles can achieve efficient intracellular delivery while maintaining high cell viability.

Thermally Induced Photoacoustic Transients Produced by Laser-Irradiated Fluid Spheres

Pulsed laser irradiation of a weakly absorbing fluid sphere in a transparent medium results in the production of a large thermal gradient at the surface of the sphere. The rapid transfer of heat from the sphere to the surrounding fluid as a result of the thermal gradient generates high frequency photoacoustic transients which affect the leading edge of a photoacoustic wave. Here, the character of the photoacoustic wave is determined by solving a modified wave equation for the photoacoustic effect. A solution to the heat diffusion equation is determined, which, together with the heating function for the optical source, provides the source term for the wave equation for pressure. The wave equation is then solved with appropriate boundary conditions using Laplace transform techniques to give the photoacoustic waveform. The relative magnitude of the transient to the N-shaped wave is shown to be determined, in part, by the laser pulse length.

Characterizing Phantom Arteries with Multi-channel Laser Ultrasonics and Photo-acoustics

Multi-channel photo-acoustic and laser ultrasonic waves are used to sense the characteristics of proxies for healthy and diseased vessels. The acquisition system is non-contacting and non-invasive with a pulsed laser source and a laser vibrometer detector. As the wave signatures of our targets are typically low in amplitude, we exploit multi-channel acquisition and processing techniques. These are commonly used in seismology to improve the signal-to-noise ratio of data. We identify vessel proxies with a diameter on the order of 1 mm, at a depth of 18 mm. Variations in scattered and photo-acoustic signatures are related to differences in vessel wall properties and content. The methods described have the potential to improve imaging and better inform interventions for atherosclerotic vessels, such as the carotid artery.

Nonlinear photoacoustic microscopy via a loss modulation technique: from detection to imaging

In order to achieve high-resolution deep-tissue imaging, multi-photon fluorescence microscopy and photoacoustic tomography had been proposed in the past two decades. However, combining the advantages of these two imaging systems to achieve optical-spatial resolution with an ultrasonic-penetration depth is still a field with challenges. In this paper, we investigate the detection of the two-photon photoacoustic ultrasound, and first demonstrate background-free two-photon photoacoustic imaging in a phantom sample. To generate the background-free two-photon photoacoustic signals, we used a high-repetition rate femtosecond laser to induce narrowband excitation. Combining a loss modulation technique, we successfully created a beating on the light intensity, which not only provides pure sinusoidal modulation, but also ensures the spectrum sensitivity and frequency selectivity. By using the lock-in detection, the power dependency experiment validates our methodology to frequency-select the source of the nonlinearity. This ensures our capability of measuring the background-free two-photon photoacoustic waves by detecting the 2nd order beating signal directly. Furthermore, by mixing the nanoparticles and fluorescence dyes as contrast agents, the two-photon photoacoustic signal was found to be enhanced and detected. In the end, we demonstrate subsurface two-photon photoacoustic bio-imaging based on the optical scanning mechanism inside phantom samples.

CONTRAST-ENHANCED PHOTOACOUSTIC IMAGING USING INDOCYANINE GREEN-CONTAINING NANOPARTICLES

Contrast agents are attracting a great deal of attention in photoacoustic imaging. Here we introduce an exogenous contrast agent that provides high photoacoustic signal amplitude at the near-infrared wavelength. Our agents consist of Indocyanine green (ICG) and phospholipid–polyethylene glycol (PL–PEG), entitled ICG–PL–PEG nanoparticles. These nanoparticles have overcome numerous limitations of ICG, such as poor aqueous stability, concentration-dependent aggregation and lack of target specificity. ICG–PL–PEG nanoparticles are biocompatible and relatively nontoxic. All the components of ICG–PL–PEG nanoparticles have been approved for human use. Upon pulsed laser irradiation, the nanoparticles are more efficient in producing photoacoustic waves than ICG alone. The results showed that ICG–PL–PEG nanoparticles act as good contrast agents for photoacoustic imaging. These unique ICG–PL–PEG nanoparticles have great potential in clinical applications.

Photoacoustic pulse wave forming along the rotation axis of an ellipsoid droplet: a geometric calculation study

A geometric calculation method is developed to study the pulsed photoacoustic wave forming of an arbitrarily shaped droplet. It is found that for an ellipsoid droplet, either a prolate ellipsoid or an oblate ellipsoid, strict analytical formulas for describing the wave profile developed along the rotation axis can be derived. The results show intriguing differences compared to those of a sphere droplet in terms of the multiple geometric parameters being in effect, the pulse wave profile variant, and the existing of unlimited points of infinite tensile pressure.

Analytical one-dimensional model for laser-induced ultrasound in planar optically absorbing layer

Ultrasound generated by means of laser-based photoacoustic principles are in common use today and applications can be found both in biomedical diagnostics, non-destructive testing and materials characterisation. For certain measurement applications it could be beneficial to shape the generated ultrasound regarding spectral properties and temporal profile. To address this, we studied the generation and propagation of laser-induced ultrasound in a planar, layered structure. We derived an analytical expression for the induced pressure wave, including different physical and optical properties of each layer. A Laplace transform approach was employed in analytically solving the resulting set of photoacoustic wave equations. The results correspond to simulations and were compared to experimental results. To enable the comparison between recorded voltage from the experiments and the calculated pressure we employed a system identification procedure based on physical properties of the ultrasonic transducer to convert the calculated acoustic pressure to voltages. We found reasonable agreement between experimentally obtained voltages and the voltages determined from the calculated acoustic pressure, for the samples studied. The system identification procedure was found to be unstable, however, possibly from violations of material isotropy assumptions by film adhesives and coatings in the experiment. The presented analytical model can serve as a basis when addressing the inverse problem of shaping an acoustic pulse from absorption of a laser pulse in a planar layered structure of elastic materials.

Ultrasound-guided photoacoustic image reconstruction: image completion and boundary suppression

Photoacoustic (PA) image reconstruction of data acquired with conventional linear arrays suffers from incompleteness due to limited bandwidth and limited view. This problem is compounded by the dominance of boundary signals suppressing other weaker PA sources. In this study, we propose a method that uses a naturally coregistered ultrasound image to enhance the PA image reconstruction, with the dual aim to reconstruct the sources that suffer from incompleteness and reveal weak sources near a strong boundary. In this method, an ultrasound image provides the input for a PA wave field simulation. The simulated PA field can be combined with the measured fields to complete the partial reconstruction or to suppress the dominant boundary signals. Experimental validation of the method was performed with two different phantoms and in vivo data from the lower arm of a healthy volunteer.

Photoacoustic transients produced by laser generated, ultrahigh thermal gradients

Irradiation of an absorbing surface in contact with a transparent fluid by a pulsed laser can result in generation of enormous thermal gradients. Here it is shown that the effect of such thermal gradients on photoacoustic waves is the production of fast transients that accompany the leading edge of the wave. Calculations show that the transients can be accounted for by an additional source term in the wave equation for pressure. Experiments are reported showing the predicted transients on waves from absorbing layers submerged in transparent fluids irradiated with 10 ns laser pulses.

All-optical photoacoustic imaging system using fiber ultrasound probe and hollow optical fiber bundle

An all-optical 3D photoacoustic imaging probe that consists of an optical fiber probe for ultrasound detection and a bundle of hollow optical fibers for excitation of photoacoustic waves was developed. The fiber probe for ultrasound is based on a single-mode optical fiber with a thin polymer film attached to the output end surface that works as a Fabry Perot etalon. The input end of the hollow fiber bundle is aligned so that each fiber in the bundle is sequentially excited. A thin and flexible probe can be obtained because the probe system does not have a scanning mechanism at the distal end.

A One-Dimensional Solution of the Photoacoustic Wave Equation and its Relationship with Optical Absorption

A study based on the general solution of the one-dimensional photoacoustic (PA) wave equation for an acoustic plane source is presented. This study relies on obtaining the impulse response of the PA system considering a heating function proportional to the Lambert–Beer law and spatially bounded by a rectangle function. The PA pressure is obtained by convoluting the impulse response with the temporal profile of the exciting pulse of light. With the obtained solution, it is possible to comprise, on a single expression, the PA pressure profile for optically thin samples (whose dimensions are smaller than the optical absorption length) and optically opaque samples (whose dimensions are larger than the optical absorption length). In the limit of weak absorption, the solution is in good agreement with the one for a uniform distribution of energy. Also, a study of the dependence of the acoustic pressure with the duration of the laser pulse is included.

Numerical evaluation of linearized image reconstruction based on finite element method for biomedical photoacoustic imaging

An image reconstruction algorithm for biomedical photoacoustic imaging is discussed. The algorithm solves the inverse problem of the photoacoustic phenomenon in biological media and images the distribution of large optical absorption coefficients, which can indicate diseased tissues such as cancers with angiogenesis and the tissues labeled by exogenous photon absorbers. The linearized forward problem, which relates the absorption coefficients to the detected photoacoustic signals, is formulated by using photon diffusion and photoacoustic wave equations. Both partial differential equations are solved by a finite element method. The inverse problem is solved by truncated singular value decomposition, which reduces the effects of the measurement noise and the errors between forward modeling and actual measurement systems. The spatial resolution and the robustness to various factors affecting the image reconstruction are evaluated by numerical experiments with 2D geometry.

Simultaneous three-dimensional photoacoustic and laser-ultrasound tomography.

A tomographic setup that provides the co-registration of photoacoustic (PA) and ultrasound (US) images is presented. For pulse-echo US-tomography laser-induced broadband plane ultrasonic waves are produced by illuminating an optically absorbing target with a short near-infrared laser pulse. Part of the same pulse is frequency doubled and used for the generation of PA waves within the object of interest. The laser-generated plane waves are scattered at the imaging object and measured with the same interferometric detector that also acquires the photoacoustic signals. After collection and separation of the data image reconstruction is done using back-projection resulting in three-dimensional, co-registered PA and US images. The setup is characterized and the resolution in PA and US mode is estimated to be about 85 µm and 40 µm, respectively. Besides measurements on phantoms the performance is also tested on a biological sample.

All-Optical Photoacoustic Detection of Absorbers in Tissue Phantoms

Visualizing and characterizing vascular structures is important for many areas of health care, from accessing difficult veins and arteries for laboratory testing, to diagnosis and treatment of cardiovascular disease. Photoacoustic (PA) imaging, one of the fastest growing fields of biomedical imaging, is well suited for this task. PA imaging is based on the photoacoustic effect, which starts with a pulsed laser source incident on biological tissue. If the wavelength of the source matches an absorption wavelength of a chromophore within the tissue, a portion of the pulse energy is absorbed by the chromophore and converted into heat. A subsequent increase in temperature, followed by an increase in pressure occurs. Acoustic waves are emitted when this pressure relaxes, which can be detected at the surface of the tissue. PA imaging is considered absorption based, therefore spectroscopic information can be extracted. Yet, unlike purely optical imaging techniques, multiple centimeters of depth can be imaged. Vascular structures, in particular, can be viewed with high contrast using PA imaging, because the absorption coefficient of blood is up to six orders of magnitude higher than surrounding tissues [1]. Additional chromophores, such as lipids in atherosclerotic plaque, are beginning to be imaged using PA techniques in vitro [2]. Contacting piezoelectric transducers are often used for detecting acoustic waves in PA imaging. In many clinical situations, however, these transducers are unfavorable due to environmental constraints, or frequency response and spatial resolution needs [3]. The ability to image without contacting the patient, and without the need for personnel to manually control a transducer, creates the opportunity for this technique to be useful in both clinical and surgical procedures. A non-contact system has the potential to be used by practitioners who require access to the vascular system such as surgeons, nurses, and phlebotomists. An additional application of this device is as an aid for surgical procedures, such as catheter interventions. Interferometry is beginning to be explored as a method of non-contact PA imaging [4]. In this study, an experiment toward non-contact photoacoustic imaging was accomplished. A broadband interferometer was used, which measured particle velocity remotely. Absorbing structures in tissue mimicking phantoms were detected at various depths with the use of an all-optical, computer-controlled photoacoustic system.