Photoacoustic Signal Generation Research Articles

Coupling Gold Nanospheres into Nanochain Constructs for High-Contrast, Longitudinal Photoacoustic Imaging.

Structural parameters play a crucial role in determining the electromagnetic and thermal responses of gold nanoconstructs (GNCs) at near-infrared (NIR) wavelengths. Therefore, developing GNCs for reliable, high-contrast photoacoustic imaging has been focused on adjusting structural parameters to achieve robust NIR light absorption with photostability. In this study, we introduce an efficient photoacoustic imaging contrast agent: gold sphere chains (GSCs) consisting of plasmonically coupled gold nanospheres. The chain geometry results in enhanced photoacoustic signal generation originating from outstanding photothermal characteristics compared to traditional gold contrast agents, such as gold nanorods. Furthermore, the GSCs produce consistent photoacoustic signals at laser fluences within the limits set by the American National Standards Institute. The exceptional photoacoustic response of GSCs allows for high-contrast photoacoustic imaging over multiple imaging sessions. Finally, we demonstrate the utility of our GSCs for molecular photoacoustic cancer imaging, both in vitro and in vivo, through the integration of a tumor-targeting moiety.

Antibody-Conjugated Polymersomes with Encapsulated Indocyanine Green J-Aggregates and High Near-Infrared Absorption for Molecular Photoacoustic Cancer Imaging.

Imaging plays a critical role in all stages of cancer care from early detection to diagnosis, prognosis, and therapy monitoring. Recently, photoacoustic imaging (PAI) has started to emerge into the clinical realm due to its high sensitivity and ability to penetrate tissues up to several centimeters deep. Herein, we encapsulated indocyanine green J (ICGJ) aggregate, one of the only FDA-approved organic exogenous contrast agents that absorbs in the near-infrared range, at high loadings up to ∼40% w/w within biodegradable polymersomes (ICGJ-Ps) composed of poly(lactide-co-glycolide-b-polyethylene glycol) (PLGA-b-PEG). The small Ps hydrodynamic diameter of 80 nm is advantageous for in vivo applications, while directional conjugation with epidermal growth factor receptor (EGFR) targeting cetuximab antibodies renders molecular specificity. Even when exposed to serum, the ∼11 nm-thick membrane of the Ps prevents dissociation of the encapsulated ICGJ for at least 48 h with a high ratio of ICGJ to monomeric ICG absorbances (i.e., I895/I780 ratio) of approximately 5.0 that enables generation of a strong NIR photoacoustic (PA) signal. The PA signal of polymersome-labeled breast cancer cells is proportional to the level of cellular EGFR expression, indicating the feasibility of molecular PAI with antibody-conjugated ICGJ-Ps. Furthermore, the labeled cells were successfully detected with PAI in highly turbid tissue-mimicking phantoms up to a depth of 5 mm with the PA signal proportional to the amount of cells. These data show the potential of molecular PAI with ICGJ-Ps for clinical applications such as tumor margin detection, evaluation of lymph nodes for the presence of micrometastasis, and laparoscopic imaging procedures.

Influence mechanism of the temporal duration of laser irradiation on photoacoustic technique: a review.

In the photoacoustic (PA) technique, the laser irradiation in the time domain (i.e., laser pulse duration) governs the characteristics of PA imaging-it plays a crucial role in the optical-acoustic interaction, the generation of PA signals, and the PA imaging performance. We aim to provide a comprehensive analysis of the impact of laser pulse duration on various aspects of PA imaging, encompassing the signal-to-noise ratio, the spatial resolution of PA imaging, the acoustic frequency spectrum of the acoustic wave, the initiation of specific physical phenomena, and the photothermal-PA (PT-PA) interaction/conversion. By surveying and reviewing the state-of-the-art investigations, we discuss the effects of laser pulse duration on the generation of PA signals in the context of biomedical PA imaging with respect to the aforementioned aspects. First, we discuss the impact of laser pulse duration on the PA signal amplitude and its correlation with the lateral resolution of PA imaging. Subsequently, the relationship between the axial resolution of PA imaging and the laser pulse duration is analyzed with consideration of the acoustic frequency spectrum. Furthermore, we examine the manipulation of the pulse duration to trigger physical phenomena and its relevant applications. In addition, we elaborate on the tuning of the pulse duration to manipulate the conversion process and ratio from the PT to PA effect. We contribute to the understanding of the physical mechanisms governing pulse-width-dependent PA techniques. By gaining insight into the mechanism behind the influence of the laser pulse, we can trigger the pulse-with-dependent physical phenomena for specific PA applications, enhance PA imaging performance in biomedical imaging scenarios, and modulate PT-PA conversion by tuning the pulse duration precisely.

Combustion synthesized La2O3: Er3+/Yb3+ phosphor for simultaneous upconversion emission and photo-thermal signal generation

The Er3+/Yb3+ doped La2O3 phosphor is prepared through combustion synthesis route and then studied using frequency upconversion (UC) and photoacoustic spectroscopic techniques. Prepared phosphor sample was annealed at high temperature ∼2100°C for short time and then structural and optical characterizations were performed. A photoacoustic cell was fabricated to record photoacoustic signal generation. Samples have shown strong upconversion emission at 409 nm, 523 nm, 548 nm, and 672 nm due to the 2H9/2 →4I15/2, 2H11/2 →4I15/2, 4S3/2 → 4I15/2 and 4F9/2→ 4I15/2 transitions, respectively. The photoacoustic measurement has revealed that heat generation in the sample increases in line with the increase in upconversion emission although both properties are opponent to each other. Studies show that prepared phosphor is efficient for generating strong upconversion emission as well as strong photoacoustic signal (also photo-thermal signal) and hence present dual functional sample seems useful for upconversion imaging as well as photo-thermal therapy.

A mathematical model for simulating photoacoustic signal generation and propagation in biological tissues

Photoacoustic (PA) medical imaging is a crossbred technique relying on light-induced ultrasonic waves due to the PA effect phenomenon recorded primarily in 1880 by A. G. Bell. Numerical simulation, also known as in-silico, studies assist scientists in minimizing incorrect PA experiments in both in-vitro and in-vivo. Numerical modeling techniques help to achieve a fast simulation process in contrast to pure mathematics alone. However, if a suitable facilitated mathematical model can be established prior to applying numerical modeling, it will be of great interest to the whole numeric model. Numerous mathematical equations, theorems, and propositions have been proposed to model the whole PA signal generation and propagation process in biological media. However, most of them are complicated and difficult to be understood by researchers, especially beginners. That’s why this paper was introduced. Our paper aims to simplify the understanding of the generation and propagation process of biomedical PA waves. We have developed a facilitated mathematical model for the entire process. The introduced developed mathematical model is based on three steps: (1) pulsed laser stimulation, (2) light diffusion, and (3) PA stress wave generation and propagation. The developed mathematical model has been implemented utilizing COMSOL Multiphysics, which relies on the finite element method (FEM) numerical modeling principle. The in-silico time-dependent study's results confirmed that the proposed mathematical model is a simple, efficient, accurate, and quick starting point for researchers to simulate biomedical PA signals' generation and propagation process utilizing any suitable software such as COMSOL multiphysics.

Tunable Interparticle Connectivity in Gold Nanosphere Assemblies for Efficient Photoacoustic Conversion.

Manipulating matter at the nanometer scale to create desired plasmonic nanostructures holds great promise in the field of biomedical photoacoustic (PA) imaging. We demonstrate a strategy for regulating PA signal generation from anisotropic nano-sized assemblies of gold nanospheres (Au NSs) by adjusting the inter-particle connectivity between neighboring Au NSs. The inter-particle connectivity is controlled by modulating the diameter and inter-particle spacing of Au NSs in the nanoassemblies. The results indicate that nanoassemblies with semi-connectivity, i.e., assemblies with a finite inter-particle spacing shorter than the theoretical limit of repulsion between nearby Au NSs, exhibit 3.4-fold and 2.4-fold higher PA signals compared to nanoassemblies with no connectivity and full connectivity, respectively. Furthermore, due to the reduced diffusion of Au atoms, the semi-connectivity Au nanoassemblies demonstrate high photodamage threshold and, therefore, excellent photostability at fluences above the current American National Standards Institute limits. The exceptional photostability of the semi-connectivity nanoassemblies highlights their potential to surpass conventional plasmonic contrast agents for continuing PA imaging. Collectively, our findings indicate that semi-connected nanostructures are a promising option for reliable, high-contrast PA imaging applications over multiple imaging sessions due to their strong PA signals and enhanced photostability.

Design, synthesis, and characterization of pH-responsive near infrared bithiophene Aza-BODIPY

Aza-boron-dipyrromethene (Aza-BODIPY) have been favored by researchers for their excellent performance in photothermal therapy, photodynamic therapy, and bioimaging. In the field of phototherapy, Aza-BODIPY have been pushed forward because of their extensive variety and structural flexibility. Here, two bithiophene Aza-boron-dipyrromethene (Aza-BODIPY) NIR photosensitizers have been successfully synthesized (B5 and B6). Both of the bithiophene Aza-BODIPY exhibit high molar extinction coefficients and are red-shifted in wavelength. The maximum characteristic absorption peak is at 880 nm, and the maximum emission peak is at 880 nm. Bithiophene Aza-boron-dipyrromethene could simultaneously generate heat and singlet oxygen (1O2) under the irradiation of a single laser (808 nm). B5 and B6 each had photothermal conversion efficiencies of 39.84% and 58.14%. At the same time, B5 and B6 have photoacoustic signal generation under laser in the range of 680–900 nm. In addition, the ability of both to produce 1O2 at pH = 5 was significantly enhanced compared to pH = 7. as well as excellent photoacoustic properties. Most significantly, phototoxicity experiments showed that bithiophene Aza-BODIPY (B5) achieved the effect of killing 4T1 tumor cells effect. Finally, to improve the application of Aza-BODIPY, Pluronic F127 was used in self-assembly with the bithiophene Aza-BODIPY.

Photoacoustic microscopy system for biological tissue imaging

A photoacoustic microscopy system was created and examined for biological tissue. Characterization of microphone, laser, and motor stepper was done to get the most appropriate setting for the system. The object table is set in a static state in the scanning process while the radiation sources and detector move in the X-Y direction. The hardware components in this system consist of photoacoustic signal generation components, mechanical components, and photoacoustic signal detection components. The hardware components are integrated and controlled by the computer through the Raspberry-pi microcomputer software. The characterization results of the photoacoustic image system obtained the optimum system setting for detecting biological tissue, namely the frequency of the diode laser in the range of 19 kHz with a duty cycle of 30%, with a minimum motor shift of 0.2 mm. This system can image the same biological tissue as the original sample with good image contrast. The smallest sample that can be scanned is 0.75 mm. The photoacoustic penetration depth is 0.5 mm.

Biomedical Application of Photoacoustics: A Plethora of Opportunities.

The photoacoustic (PA) technique is a non-invasive, non-ionizing hybrid technique that exploits laser irradiation for sample excitation and acquires an ultrasound signal generated due to thermoelastic expansion of the sample. Being a hybrid technique, PA possesses the inherent advantages of conventional optical (high resolution) and ultrasonic (high depth of penetration in biological tissue) techniques and eliminates some of the major limitations of these conventional techniques. Hence, PA has been employed for different biomedical applications. In this review, we first discuss the basic physics of PA. Then, we discuss different aspects of PA techniques, which includes PA imaging and also PA frequency spectral analysis. The theory of PA signal generation, detection and analysis is also detailed in this work. Later, we also discuss the major biomedical application area of PA technique.

Impact of skin tone on photoacoustic oximetry and tools to minimize bias.

The major optical absorbers in tissue are melanin and oxy/deoxy-hemoglobin, but the impact of skin tone and pigmentation on biomedical optics is still not completely understood or adequately addressed. Melanin largely governs skin tone with higher melanin concentration in subjects with darker skin tones. Recently, there has been extensive debate on the bias of pulse oximeters when used with darker subjects. Photoacoustic (PA) imaging can measure oxygen saturation similarly as pulse oximeters and could have value in studying this bias. More importantly, it can deconvolute the signal from the skin and underlying tissue. Here, we studied the impact of skin tone on PA signal generation, depth penetration, and oximetry. Our results show that subjects with darker skin tones exhibit significantly higher PA signal at the skin surface, reduced penetration depth, and lower oxygen saturation compared to subjects with lighter skin tones. We then suggest a simple way to compensate for these signal differences.

On the theory of nonlinear photoacoustic signal generation during gas-microphone detection

A theory is proposed for of the generation of the first two harmonics of a nonlinear photoacoustic signal of a solids sample with an arbitrary value of thermal conductivity. For limiting cases (thermally thin and thick samples) has been obtained simple expressions for the dependence of the amplitude of the excited photoacoustic signal from the emissivity of the sample and the thermophysical parameters of the sample, gas and substrates, including their thermal coefficients. Keywords: photoacoustics, thermal nonlinearity, second harmonic.

Theoretical aspects of Photoacoustic Signal Generation with Solid Crystals

Today, non-destructive analysis techniques play an important role in industrial applications and scientific, as well as technological research. Photoacoustic method is one of such non-destructive methods in which generation of acoustic waves takes place due to the absorption of the modulated incident radiation. Photoacoustic signal is a base for photoacoustic research. The generation of the photoacoustic signal is related to the nature of the cell used for investigation. Though a variety of explainations about signal generation in photoacoustic interaction are reported by many researchers, many aspects are yet to be studied in detail. While investigating a solid crystal in photoacoustics, factors as mode of operation, scheme of excitation, the shape of the cell, and pressure fluctuations in the cell are considered for analysing photoacoustic signal generation. Also, design and performance optimization of the photoacoustic cell play paramount role in determining efficiency of related signal generation. In this paper, theoretical aspects of photoacoustic signal generation for solid crystals are presented. While obtaining the expression for pressure fluctuations with solid crystal, cylindrical configuration of photoacoustic cell is preferred to get a better signal–to–noise ratio. Along with the analysis of other factors, pressure fluctuations generated by the enclosed gas in photoacoustic cell is mathematically determined.

Morphology-dependent resonance enhanced nonlinear photoacoustic effect in nanoparticle suspension: a temporal-spatial model.

The morphology-dependent resonances (MDRs) hotspot, ubiquity formed between the pairs of nanoparticles in close vicinity, has garnered considerable recent attention. By extending this phenomenon to pulse-laser irradiated nanoparticle suspension, we demonstrate that such collective optical/thermal enhancement can give rise to the nonlinear photoacoustic (PA) generation. In this study, a temporal-spatial analytical expression is derived to quantitatively describe the nonlinear PA signal generation from nanoparticles, incorporating the Grüneisen increase at the microscopic individual particle level and MRDs enhancement at the macroscopic suspension level. The dependence of PA nonlinearity on the critical contributors, including the laser pulse width, the particle size, and the statistical interparticle spacing, is quantitatively discussed. The theory is well validated with the finite element method (FEM) and experimentally proved with semiconducting polymer nanoparticles (SPN) suspension. This work may pave a new direction towards effective MDR based nonlinear PA contract agent design.

Theoretical Investigation of Photoacoustics From Cancer Cells: Modified Models

Photoacoustic (PA) technology has wide applications in cell study. However, photoacoustics from cancer cells lacks adequate understanding. Here, we establish two modified models for theoretical investigation of photoacoustics from cancer cells. The first model is based on endogenous absorbers of cancer cells, which can be measured by label-free PA microscopy. Different from previous studies about PA for cancer cells that are limited to melanoma cells, our model considers general cancer cells. Further, the feasibility of cancer cell cycle analysis via PA spectrum analysis is demonstrated. The second model is based on exogenous absorbers, e.g., nanoparticles (NPs), in cancer cells. The interactions between NPs and cells in PA signal generation are considered. The nucleus-to-cytoplasm ratio, refractive index, cellular uptake of NPs, NPs size heterogeneity and cell size are modeled to evaluate the contribution of each factor to the change of PA signal amplitudes, which is valuable to guide experiments for cancer cell identification by utilizing different PA signal amplitudes between normal cells and cancer cells. In conclusion, our study comprehensively investigates photoacoustics from cancer cells, which lays theoretical groundwork for future research on PA techniques for cancer cells and is expected to be useful for cancer diagnosis, treatment, and prognosis.

An Analytical Expression Of The Photoacoustic Signal For A Pulsed Laser With A Sinusoidal Radial Profile

Photoacoustic signal depends on several laser factors, particularly the pulse duration, energy, wavelength, beam-width and repetition rate of the pulsed laser. Although these dependencies are well tested through experiments, they can also be investigated via theoretical approaches for the research into photoacoustic signal generation in parallel to advances in laser technologies. In this study, the photoacustic signal is presented analytically by solving the photoacoustic wave equation for an optical absorber heated up by a pulsed laser. The spatial and temporal parts of the pulsed laser are modeled by a sampling (sinc) function and a Gaussian function, respectively. The radial profile obtained experimentally by using a spatial light modulator can be modeled accurately with a sampling function. Pulsed lasers can lead to nonlinear effects. This nonlinear mechanism has various advantageous for the photoacoustic imaging. These short pulsed lasers have a close-to-sinusoidal variation in the central pulse region so that the spatial part of the laser is modeled by a sampling function in this work. For the photoacoustic wave, a detailed expression is obtained analytically in terms of the pulse duration and beam-width. The photoacoustic signal is observed in terms of time for various detector positions. Moreover, a detailed analysis is conducted to obtain a correlation between the photoacoustic signal and the laser factors. Therefore, the resulting quantification of the physical laser factors can offer a useful theoretical guide for the applications of photoacoustics. The sampling modeling presented by this study can also be helpful for the understanding of the nonlinear mechanism in photoacoustics.

Selection of laser pulse width for efficient generation of photoacoustic signals in liquid-filled thin capillary embedded in soft material

To design an instrumentation system for evaluating contrast agents of photoacoustic imaging, the optimal pulse width of the excitation laser is discussed in this paper. A pulsed semiconductor laser with a moderate pulse width (15–129 ns) and low peak power (1 W) is adopted in the proposed system. Black ink is selected as the reference sample, which is filled in a glass capillary embedded in a soft phantom. Our aim is that the pulse width matches the acoustic resonance of the target and the center frequency of the receiving transducer (5 MHz) to obtain sufficient strength of the ultrasonic signal with minimal laser power. A series of experiments reveal a clear relationship between the laser pulse width and the maximal amplitude of the resonance mode. Acoustic resonance occurs inside the capillary whose frequencies can be precisely predicted as the radial eigen mode. The laser pulse width and concentration of the sample showed little influence on these resonance frequencies as expected. To efficiently utilize the signal enhancement effect due to the resonance, several resonance mode candidates are investigated and discussed. It then becomes clear that the second angular and zeroth radial order mode is useful for capillaries with sub-millimeter inner diameters. It was demonstrated that the concentration of samples had very limited influence on the frequencies. Finally, consideration based on two delayed attenuating vibrations is successfully conducted to explain the experimental results.

Development of a MEMS hotplate-based photoacoustic CO2 sensor

Instead of the conventional use of micro-electro-mechanical system (MEMS) hotplate for metal oxide semiconductor (MOS) or nondispersive infrared (NDIR) gas sensing, it was used for photoacoustic (PA) gas sensing. A low-cost MEMS microphone was used for the development of this MEMS hotplate PA carbon dioxide (CO2) sensor. To the knowledge of the authors, this is the first time that a MEMS hotplate and a MEMS microphone are combined for use in gas sensing with high modulation frequency. NDIR sensors use much more expensive photodetectors compared to the MEMS microphone used in this work. The MEMS hotplate and MEMS microphone have the desired characteristics of low power consumption, small size and low cost. The hotplate as a blackbody is a good infrared emitter which is suitable for CO2 detection around the 4.26 µm absorption band. Despite the significant radiation power loss due to high modulation frequency, the remaining/reduced power radiation power was still sufficient to excite CO2 molecules for PA signal generation. Temperature analysis on the sensor showed that PA signal decreases with an increase in temperature, which implies that compensation must be provided for such temperature effects. This work provides alternative optical gas sensing that is comparatively inexpensive compared to the conventional NDIR sensors and by using components that can be easily mass-produced, thereby making a valuable contribution to the fight against air pollution and global warming.

Extending Imaging Depth in PLD-Based Photoacoustic Imaging: Moving Beyond Averaging.

Pulsed laser diodes (PLDs) promise to be an attractive alternative to solid-state laser sources in photoacoustic tomography (PAT) due to their portability, high-pulse repetition frequency (PRF), and cost effectiveness. However, due to their lower energy per pulse, which, in turn, results in lower fluence required per photoacoustic signal generation, PLD-based photoacoustic systems generally have maximum imaging depth that is lower in comparison to solid-state lasers. Averaging of multiple frames is usually employed as a common practice in high PRF PLD systems to improve the signal-to-noise ratio of the PAT images. In this work, we demonstrate that by combining the recently described approach of subpitch translation on the receive-side ultrasound transducer alongside averaging of multiple frames, it is feasible to increase the depth sensitivity in a PLD-based PAT imaging system. Here, experiments on phantom containing diluted India ink targets were performed at two different laser energy level settings, that is, 21 and [Formula: see text]. Results obtained showed that the imaging depth improves by ~38.5% from 9.1 to 12.6 mm for 21- [Formula: see text] energy level setting and by ~33.3% from 10.8 to 14.4 mm for 27- [Formula: see text] energy level setting by using λ /4-pitch translation and average of 128 frames in comparison to λ -pitch data acquired with the average of 128 frames. However, the achievable frame rate is reduced by a factor of 2 and 4 for λ /2 and λ /4 subpitch translation, respectively.

Improved laser-ultrasonic excitation for imaging of seismic physical modeling

In this study, a laser ultrasonic technology (LUT) was employed for seismic physical model (SPM) imaging. To promote an efficient light-to-ultrasonic-wave conversion, a functionalised Au film was used as a medium because of its stronger photoacoustic (PA) effect. Numerical analysis and experiments were performed to characterise the entire SPM imaging process, including the generation of PA signals, transmission of PA inside the SPM, and collection of echo data for the reconstruction of SPM images using the time-of-flight algorithm. The results show that the Au film coating on the SPM produces a strong PA effect, which significantly improves the imaging depth and resolution of the SPM based on the strong high-frequency ultrasonic wave excitation. The proposed method opens new avenues for SPM imaging using optical technology.

Theoretical and Experimental Investigation of a Laser-Induced Photoacoustic Effect near a Hole in Internally Stressed Metal Plates

This paper is an experimental and theoretical study of changes in a laser-induced photoacoustic signal near a hole in metal plates of D16 aluminum alloy. The process of photoacoustic signal generation from metals is analyzed within the classical thermoelasticity framework, with account for only the thermal effect of laser irradiation on metal lattice deformation. A comparison is made of photoacoustic experimental and theoretical results obtained for a mechanically stressed aluminum alloy plate with a hole. The effect of external mechanical stresses on the behavior of laser photoacoustic signals near the hole is studied experimentally and theoretically. It is found that the classical theory of thermoelasticity is not enough to correctly describe the stress dependence of the photoacoustic signal near a hole in aluminum alloy plates. In order for the obtained experimental and theoretical results to agree, along with the thermal effect of laser irradiation on the lattice, it is necessary to account for the additional effect of the electron gas. A calibration procedure of the laser photoacoustic signal with respect to stress is described. It is shown that internal stresses in metals can be estimated by the photoacoustic method in combination with the hole drilling method.