Photoacoustic Waves Research Articles

Nonlinear optical and photoacoustic properties of aqueous crystalline hemoglobin. Towards facile detection of hemoglobin concentration in blood

In this work, nonlinear optical properties of hemoglobin are studied under the irradiation of a blue LED laser beam. The z-scan setup is applied in order to determine nonlinear optical responses. Photoacoustic waves are created in a hearable sound region. Sounds are recorded by a microphone and analyzed by using Fourier transform to evaluate the sonic frequencies. The suspensions of hemoglobin in water are prepared in the range of 120–160 mg/mL that is in the range of hemoglobin concentration in blood. It is found that the amplitude of photoacoustic (PA) signals and nonlinear absorption coefficients depend directly to the hemoglobin concentration. On the other hand, blood of rabbit is studied using this method and results are compared with the crystalline hemoglobin findings. It is concluded that the frequency domain of photoacoustic waves created by hemoglobin is similar to that observed for the blood sample. It means that the main portion of photoacoustic response in blood is due to its hemoglobin content and amplitude of the sonic signals is directly related to the concentration of hemoglobin. FT-IR studies confirmed that the vibrational levels of hemoglobin had no a significant effect on the recorded PA signals and the main PA effect has been originated from explosion of the micro- and nano-bubbles. Moreover, from the UV–Vis spectrum of hemoglobin, it can be conferred that absorption of the blue photons by the porphyrin ring leads to the evaporation of water molecules and generation of the mentioned bubbles responsible for the created sonic waves after explosion. This study would be considered as a fast and simple method to determine hemoglobin concentration in the real blood samples using nonlinear optical and photoacoustic characterizations.

Neural Stimulation In Vitro and In Vivo by Photoacoustic Nanotransducers

Summary Neuromodulation is an invaluable approach for the study of neural circuits and clinical treatment of neurological diseases. Here, we report semiconducting polymer nanoparticles based photoacoustic nanotransducers (PANs) for neural stimulation in vitro and in vivo. Our PANs strongly absorb the nanosecond pulsed laser in the near-infrared second window (NIR-II) and generate localized acoustic waves. PANs are shown to be surface modified and selectively bind onto neurons. PAN-mediated activation of primary neurons in vitro is achieved with ten 3-ns laser pulses at 1,030 nm over a 3-ms duration. In vivo neural modulation of mouse brain activities and motor activities is demonstrated by PANs directly injected into brain cortex. With submillimeter spatial resolution and negligible heat deposition, PAN stimulation is a new non-genetic method for precise control of neuronal activities, opening up potentials in non-invasive brain modulation.

The Effect of Laser and Ultrasound Synchronization in Photo-Mediated Ultrasound Therapy.

Photo-mediated ultrasound therapy (PUT) is a novel, non-invasive, agent-free, highly selective, and precise anti-vascular technique. PUT removes microvessels through promoting cavitation activity precisely in targeted microvessels by applying synchronized nanosecond laser pulses and ultrasound bursts. The synchronization between laser and ultrasound is critical to the outcome of PUT. Through theoretical simulation and experimental study, the effect of synchronization between laser pulses and ultrasound bursts on cavitation activity during PUT is evaluated. By using a theoretical model, we found that cavitation activity was enhanced when laser pulses and ultrasound bursts were synchronized such that the produced photoacoustic wave overlaid the rarefactional phase of the ultrasound wave. This finding was then verified through in vitro studies where cavitation was monitored by using a passive cavitation detector. Furthermore, we demonstrated that the in vivo treatment outcome of PUT in rabbits was directly related to the synchronization between laser and ultrasound. The anti-vascular effect could only be observed when laser and ultrasound were properly synchronized in vivo. PUT is more efficient when the laser-induced photoacoustic wave overlays the rarefactional phase of the ultrasonic wave. This is a systematic study to investigate the synchronization effect of PUT, which would be significant for further understanding the mechanism and further improving the treatment efficiency of PUT.

Numerical solution to the time-independent inhomogeneous photoacoustic wave equation using the Born series methods.

The traditional Born series (TBS) and convergent Born series (CBS) methods to numerically solve the time-independent inhomogeneous photoacoustic (PA) wave equation are discussed. The performance of these algorithms is examined for a circular PA source (a disk of radius, a=5µm) in two dimensions. The speed of sound within the source region was gradually decreased from vs=1950 to 1200 m/s, but the same quantity for the ambient medium was fixed to vf=1500m/s. The PA fields were calculated over a large frequency band from f=7.3 to 2000 MHz. Accordingly, the wave number (kf=2πf/vf) varied from kf=0.03 to 8.38µm-1. The TBS method does not offer converging solutions when kfa≥25 for vs=1950m/s and kfa≥9 for vs=1200m/s. These have been observed in both the near and far fields. However, the solutions for the CBS technique converge in all cases. Both methods facilitate accurate solutions if the computational domain contains a collection of monodisperse/polydisperse disks considered in this study. Our numerical results suggest that the CBS protocol can provide accurate solutions under various test conditions.

Improved Photoacoustic Imaging of Numerical Bone Model Based on Attention Block U-Net Deep Learning Network

Photoacoustic (PA) imaging can provide both chemical and micro-architectural information for biological tissues. However, photoacoustic imaging for bone tissue remains a challenging topic due to complicated ultrasonic propagations in the porous bone. In this paper, we proposed a post-processing method based on the convolution neural network (CNN) to improve the image quality of PA bone imaging in a numerical model. To be more adaptive for imaging bone samples with complex structure, an attention block U-net (AB-U-Net) network was designed from the standard U-net by integrating the attention blocks in the feature extraction part. The k-wave toolbox was used for the simulation of photoacoustic wave fields, and then the direct reconstruction algorithm—time reversal was adopted for generating a dataset of deep learning. The performance of the proposed AB-U-Net network on the reconstruction of photoacoustic bone imaging was analyzed. The results show that the AB-U-Net based deep learning method can obtain the image presented as a clear bone micro-structure. Compared with the traditional photoacoustic reconstruction method, the AB-U-Net-based reconstruction algorithm can achieve better performance, which greatly improves image quality on test set with peak signal to noise ratio (PSNR) and structural similarity increased (SSIM) by 3.83 dB and 0.17, respectively. The deep learning method holds great potential in enhancing PA imaging technology for bone disease detection.

Systematic analysis of frequency dependent differential photoacoustic cross-section data for source size estimation.

A frequency dependent differential photoacoustic cross-section (DPACS) over a large frequency band (100-1000 MHz) was computed, and subsequently, morphological parameters of a photoacoustic (PA) source were quantified. The Green's function approach was utilized for calculating the DPACS for spheroidal droplets with varying aspect ratios, Chebyshev particles with different waviness and deformation parameters, and normal red blood cells and cells affected by hereditary disorders (e.g., spherocytosis, elliptocytosis, and stomatocytosis). The theoretical framework considers that PA waves propagate through an acoustically dispersive and absorbing medium and are detected by a planar detector of finite size. The frequency dependent DPACS profile was fitted with tri-axial ellipsoid, finite cylinder, and toroid form factor models to obtain size and shape information of the PA source. The tri-axial ellipsoid form factor model was found to provide better estimates of the shape parameters compared to other models for a variety of sources. The inverse problem framework may motivate developing PA-based technology to assess single-cell morphology.

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AbstractVascular disrupting agents (VDAs) can be used to damage the tumour vasculature, suppressing oxygen and nutrition supply to the tumour tissue. Photoacoustic imaging was used to assess the structural and functional changes of the tumour vasculature and evaluate the efficacy of the VDAs. Tissues are irradiated with short laser pulses and the photoacoustic waves are analyzed to extract vessel size and hemoglobin composition to evaluate the VDA, hours after administration.Further details can be found in the article by Muhannad N Fadhel, Sila Appak Baskoy, Yanjie Wang, Eno Hysi, and Michael C. Kolios (e202000209). image

Plane photoacoustic wave generation in liquid water using irradiation of terahertz pulses

We demonstrate photoacoustic wave propagation with a plane wavefront in liquid water using a terahertz (THz) laser pulse. The THz light can effectively generate the photoacoustic wave in water because of strong absorption via a stretching vibration mode of the hydrogen bonding network. The excitation of a large-area water surface irradiated by loosely focused THz light produces a plane photoacoustic wave. This is in contrast with conventional methods using absorbers or plasma generation using near-infrared laser light. The photoacoustic wave generation and plane wave propagation are observed using a system with a THz free-electron laser and shadowgraph imaging. The plane photoacoustic wave is generated by incident THz light with a small radiant exposure of < 1 mJ/cm2 and delivered 600 times deeper than the penetration depth of THz light for water. The THz-light-induced plane photoacoustic wave offers great advantages to non-invasive operations for industrial and biological applications as demonstrated in our previous report (Yamazaki et al. in Sci Rep 10:9008, 2020).

Effect of laser pulse shaping on photoacoustic dosimetry in retinal models.

Photoacoustic sensing can be a powerful technique to obtain real-time feedback of laser energy dose in treatments of biological tissue. However, when laser therapy uses pulses with microsecond duration, they are not optimal for photoacoustic pressure wave generation. This study examines a programmable fiber laser technique using pulse modulation in order to optimize the photoacoustic feedback signal to noise ratio (SNR) in a context where longer laser pulses are employed, such as in selective retinal therapy. We have demonstrated with a homogeneous tissue phantom that this method can yield a greater than seven-fold improvement in SNR over non-modulated square pulses of the same duration and pulse energy. This technique was further investigated for assessment of treatment outcomes in leporine retinal explants by photoacoustic mapping around the cavitation-induced frequency band.

Quantitative Study of the Nonlinearly Enhanced Photoacoustic/Photothermal Effect by Strong LSPR-Coupled Nanoassemblies.

The extensive exploration of the collective optical and thermal effects for localized surface plasmon resonance (LSPR)-coupled nanoassemblies has propelled much recent research and development in fields of photoacoustic (PA) imaging and photothermal (PT) therapy, while the rational design and proper engineering of these assemblies under quantitative guidance is still a highly challenging task. In this work, by utilizing the finite element analysis (FEA) method and taking gold nanochains as example, the authors quantitatively studied the coupling optical/thermal response of the nanoassemblies and the associated nonlinearly enhanced PA/PT effect. Results show that compared with their individuals, the strong electromagnetic/thermal coupling between the individuals of the nanoassemblies results in a several-time enhancement of the per-particle-weighted optical absorption, consequential thermal field enhancement, and initial PA pressure, resulting in nonlinearly amplified energy conversion from incident light to heat and PA waves. The dependence of the nonlinear PA/PT enhancement on the assembly chain length, the size of the individuals, the interparticle distance, and the size uniformity of the building blocks is quantitatively discussed. PA experiments on gold nanochains and gold nanospheres are performed to validate the proposition, and the experiments well silhouetted the theoretical discussion. This work paves the way for the rational construction and optimization of plasmonic nanoassemblies with improved PA/PT conversion efficiency.

H2 Detection Using Plasmonically Generated Surface Photoacoustic Waves in Pd Nanoparticle-Deposited GaN Microcantilevers.

Detection of H2 using plasmonic amplification of surface photoacoustic (SPA) waves generated in Pd nanoparticle-deposited GaN piezotransistive microcantilevers has been investigated using a pulsed 520 nm laser. Using 1.5 nm thickness of the Pd functionalization layer, H2 detection down to 1.5 ppm was demonstrated with a high signal-to-noise ratio, underscoring the feasibility of sub-ppm level detection using this novel sensing method. Adsorption of H2 in Pd nanoparticles (NPs) changes their plasmonic absorption spectra because of Pd lattice expansion, in addition to changing their work function. The high sensitivity exhibited by the SPA-based H2 detection method is attributed to a combination of changes in the plasmonic spectrum and work function of Pd NPs and was observed to be a strong function of Pd thickness, biasing conditions, and probe laser power. A comparison of the SPA-based detection technique with traditional chemidiode and chemiresistor sensors, integrated in the functionalized piezotransistor, indicated a superior detection performance of the former.

Simulation of Photoacoustic waves based Eigen-value and Eigen- function in Different Geometrical Resonance Cells

We reported the simulation of photo acoustic signal which can be generated due to interaction between laser and molecules inside suitable designed cavities. We started with simulation of the eigenvalues and eigenfunctions acoustic waves generated in resonance cylindrical shape. The second step is done with rectangular box where we show that the eigenvalues and eigenvectors of acoustic wave have less efficiency than that from cylindrical. In addition, the effect of losses due to edges in the structure shape of rectangular has an extra reason to damping acoustic wave&#x0D; قمنا بعمل محاكاة للإشارة الضوء-صوتية الناتجة بسبب التفاعل بين الليزر والجزيئات داخل تجاويف مصممة بشكل مناسب. بدأنا بمحاكاة الموجات الصوتية ذات القيم الذاتية والدوال الذاتية المتولدة في الشكل الأسطواني الرنيني في الخطوة الثانية تمت الحسابات باستخدام صندوق مستطيل حيث لاحظنا أن كفاءة القيم الذاتية والمتجهات الذاتية للموجة الصوتية أقل من تلك الموجودة في الأشكال الأسطوانية. بالإضافة إلى ذلك ، فإن تأثير الخسائر بسبب الحواف في شكل هيكل المستطيل له سبب إضافي لتثبيط الموجة الصوتية

Probing the Spatial Impulse Response of Ultrahigh-Frequency Ultrasonic Transducers with Photoacoustic Waves

Characterizing the radiated or received acoustic field of ultrasonic transducers using the spatial impulse response (SIR) represents an important step in testing, design, and optimization of ultrasonic transducers. However, for the ultrahigh-frequency acoustic field, conventional methods, such as the hydrophone method and the small-ball reflection method, are limited by narrow bandwidth and poor spatial resolution. Here, we propose a method to obtain the transducer's SIR through its response to photoacoustic waves, which allows high-precision acoustic field measurements, with spatial resolution as fine as 1.7 \textmu{}m. We subsequently measure the SIRs of two focused ultrasonic transducers, with 20 and 93 MHz center frequencies, and confirm that the three-dimensional acoustic fields can be accurately reconstructed using the angular spectrum approach. More importantly, this method is unique to receive-only ultrasonic detectors, the SIR of which could not be measured previously with conventional methods, and it could facilitate ultrasonic transducer design, as well as other related fields, such as nondestructive evaluation, biomedical imaging, and particle manipulation.

Cross-sectional photoacoustic tomography image reconstruction with a multi-curve integration model

Background and objectiveIn acoustic inversion of photoacoustic tomography (PAT), an imaging model that precisely describes both the ultrasonic wave propagation and the detector properties is of crucial importance. Inspired by the multi-stripe integration model in clinical X-ray computed tomography systems, in this work, we introduce the Multi-Curve-Integration-based acoustic inversion for cross-sectional Photoacoustic Tomography (MCI-PAT). MethodsWe assumed that in cross-sectional PAT system, the three-dimensional (3-D) wave propagation problem could be reduced to a two-dimensional (2-D) problem in a limited, yet sufficient field of view. Under such condition, the MCI-PAT imaging model is generated by integrating several circular acoustic curves, the centers of which are points evenly distributed on the finite-size ultrasonic transducer surface. In this way, the spatial detector response is taken into account, while its computational burden does not largely increase because the integration process is performed only on a 2-D plane. ResultsAs proven by simulation, phantom and in vivo small animal experiments, the MCI-PAT method leads to promising improvement in PAT image quality. Comparing to traditional imaging models that considered only a single acoustic curve, our proposed method successfully improved the visibility of small structures and achieved evident enhancement on signal-to-noise ratio. ConclusionsThe performance of the MCI-PAT method demonstrates that for cross-sectional PAT, a 2-D simplification of the propagation of multiple photoacoustic waves is feasible. Due to its simplicity, our method can be used as an add-on to current system models considering only a single acoustic curve.

Photoacoustic method for real-time assessment of salt content in aqueous solutions

In 2004, the Food and Drug Administration established the foundations for the application of process analytical technologies (PAT) in real-time control of the drug manufacturing process, where progress has been essentially directed to solid formulations. In order to enlarge the application of PAT principles to injectable drug products, the development of appropriate manufacturing process control tools is mandatory. Photoacoustics is a non-invasive technique with the potential for application in real-time control of the manufacturing process of injectable drug products. Herein, we applied a photoacoustic method for the determination of the concentration of salts (sodium chloride) in mono-salt formulations by measuring the changes induced in the speed of sound by density changes. This method was explored using two modes of generating the photoacoustic wave and two detectors with central frequencies of 10 MHz and 100 MHz. The results were analyzed using a 2k full-factorial design, considering the generation mode and detection as independent variables. The optimized method was subsequently validated according to the International Council for Harmonisation (ICH) standards. The method showed good linearity, precision, and accuracy, with a lower limit of quantification of 0.05% (w/v) of NaCl and a limit of detection of 0.02% (w/v) of NaCl. Due to its simplicity and high throughput, this method has potential applicability as PAT in the manufacturing of injectable drug products.

Photoacoustic laser effects in live mouse blastocysts: pilot safety studies of DNA damage from photoacoustic imaging doses

To investigate the laser safety of photoacoustic imaging. In photoacoustic imaging, a pulsed laser of several nanoseconds is used to illuminate biological tissue, and photoacoustic waves generated by optical absorption are used to form images of the tissue. Photoacoustic imaging is emerging in clinical applications; however, its potential use in reproductive medicine has yet to be reported. Assessment of photoacoustic laser safety before its adoption by clinical reproductive medicine. Academic medical center. Blastocyst-stage mouse embryos. Potential DNA damage of photoacoustic laser exposure on preimplantation mouse blastocyst stage embryos was examined. Different embryos groups were exposed to either 5- or 10-minute 15-Hz laser doses (typical clinical doses) and 1-minute 1-kHz laser dose (significantly higher dose), respectively. A terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was used to identify the rate of DNA damage in the laser-exposed blastocysts. The negative control blastocyst group (no laser exposure) had a mean of 10.7 TUNEL-positive nuclei. The 5- and 10-minute 15-Hz laser-exposed groups had a mean of 11.25 and 12.89 TUNEL-positive nuclei, respectively. The embryos exposed to the 1-kHz laser for 1 minute had an average mean of 12.0 TUNEL-positive nuclei. We demonstrated that typical lasers and exposure times used for photoacoustic imaging do not induce increased cell death in mouse blastocysts.

One-step fluorescence photoacoustic tomography with the optical radiative transfer model

We present adjoint-based Jacobian as well as gradient evaluations and corresponding reconstruction schemes to solve the fully nonlinear, optical radiative transfer modeled one-step fluorescence photoacoustic tomographic (FPAT) problem, which aims to reconstruct the map of absorption coefficient of the exogenous fluorophore from boundary photoacoustic data. The radiative transport equation (RTE) and frequency-domain photoacoustic equation have been employed to model light and photoacoustic wave propagation, respectively. Levenberg-Marquardt and Broyden-Fletcher-Goldfarb-Shanno reconstruction schemes have been used corresponding to the evaluated Jacobians and gradients, respectively. Numerical reconstructions obtained from the two schemes have been validated for scattering-dominant as well as nonscattering-dominant media in 2D. To the best of our knowledge, these are the first one-step FPAT reconstruction results in literature based on the optical RTE model.

Limited-View and Sparse Photoacoustic Tomography for Neuroimaging with Deep Learning

Photoacoustic tomography (PAT) is a non-ionizing imaging modality capable of acquiring high contrast and resolution images of optical absorption at depths greater than traditional optical imaging techniques. Practical considerations with instrumentation and geometry limit the number of available acoustic sensors and their “view” of the imaging target, which result in image reconstruction artifacts degrading image quality. Iterative reconstruction methods can be used to reduce artifacts but are computationally expensive. In this work, we propose a novel deep learning approach termed pixel-wise deep learning (Pixel-DL) that first employs pixel-wise interpolation governed by the physics of photoacoustic wave propagation and then uses a convolution neural network to reconstruct an image. Simulated photoacoustic data from synthetic, mouse-brain, lung, and fundus vasculature phantoms were used for training and testing. Results demonstrated that Pixel-DL achieved comparable or better performance to iterative methods and consistently outperformed other CNN-based approaches for correcting artifacts. Pixel-DL is a computationally efficient approach that enables for real-time PAT rendering and improved image reconstruction quality for limited-view and sparse PAT.

Broadband and Ultrasensitive Graphene-Based Mechanical Wave Detector with Nanosecond Response Used for Biological Photoacoustic Imaging.

Achieving broadband and sensitive mechanical wave detection with fast time response remains a great challenge. Here, we exploited the polarization-sensitive absorption characteristics and ultrafast photoelectric response of graphene to construct a broadband and ultrasensitive detector with a nanosecond response for mechanical wave detection. The unprecedented performance of the graphene-based detector allowed us to detect high-frequency mechanical waves over 100 MHz with a detection limit of 0.18 kPa. Moreover, we applied the detector in high-contrast photoacoustic imaging of human hairs and a mouse hindlimb to demonstrate its capability in detection of photoacoustic waves. This device could also find application in other areas such as THz detection and modulation.

Ultra-compact QEPAS acoustic detection module with acoustic wave confinement

An ultra-compact acoustic detection module (ADM) was developed for trace gas detection by use of quartz-enhanced photoacoustic spectroscopy (QEPAS). Different from the conventional QEPAS ADM, a gas enclosure was employed to confine the photoacoustic waves and excite the acoustic azimuthal and radial modes. Finite element modelling (FEM) method was used to analyze the acoustic modes and pressure distribution. The geometrical parameters of the ADM were optimized to enhance the sensor performance. The developed QEPAS ADM was only ~0.05 mL and ~0.15 g, significantly reducing the QEPAS sensor volume and weight, and improving the QEPAS system gas flush time by orders of magnitude. As a proof of concept, H2O was detected by the ultra-compact spectrophone employing a telecommunication diode laser. A detection limit of 2 ppm was achieved.