Photoacoustic Signal Research Articles

Miniaturized preamplifier integration in ultrasound transducer design for enhanced photoacoustic imaging.

Photoacoustic imaging (PAI) utilizes the photoacoustic effect to record both vascular and functional characteristics of a biological tissue. Photoacoustic signals have typically low amplitude that cannot be read efficiently by data acquisition systems. This necessitates the use of one or more amplifiers. These amplifiers are somewhat bulky (e.g., the ZFL-500LN+, Mini-Circuits, USA, or 351A-3-50-NI, Analog Modules Inc., USA). Here, we describe the fabrication and development process of a transducer with a built-in low-noise preamplifier that is encased within the transducer housing. This new, to the best of our knowledge, design could be advantageous for applications where a compact transducer + preamplifier is required. We demonstrate the performance of this compact detection unit in a laser scanning photoacoustic microscopy system by imaging a rat ear ex vivo and a rat brain vasculature in vivo.

Photoacoustic method for measuring the elasticity of polydimethylsiloxane at various mixing ratios

Measuring elasticity without physical contact is challenging, as current methods often require deconstruction of the test sample. This study addresses this challenge by proposing and testing a photoacoustic effect-based method for measuring the elasticity of polydimethylsiloxane (PDMS) at various mixing ratios, which may be applied on the wide range of applications such as biomedical and optical fields. A dual-light laser source of the photoacoustic (PA) system is designed, employing cross-correlation signal processing techniques. The platform systems and a mathematical model for performing PDMS elasticity measurements are constructed. During elasticity detection, photoacoustic signal features, influenced by hardness and shapes, are analyzed using cross-correlation calculations and phase difference detection. Results from phantom tests demonstrate the potential of predicting Young's modulus using the cross-correlation method, aligning with the American Society for Testing and Materials (ASTM) standard samples. However, accuracy may be affected by mixed materials and short tubes. Normalization or calibration of signals is suggested for aligning with Young's coefficient.

Quantitative evaluation of the impact of variation of optical parameters on the estimation of blood hematocrit and oxygen saturation for dual-wavelength photoacoustics

Photoacoustic (PA) spectroscopy is considered to be one of the most effective ways to measure the levels of hematocrit (H) and oxygenation saturation (SO2) of blood, which are essential for diagnosing blood-related illnesses. This simulation study aims to investigate the impact of individual optical parameters, i.e., optical absorption coefficient (μ a ), scattering coefficient (μ s ), and anisotropy factor (g), on the accuracy of this technique in estimating the blood properties. We first performed the Monte Carlo simulations, using realistic optical parameters, to obtain the fluence maps for various samples. The wavelengths of the incident light were chosen to be 532, 700, 1000, and 1064 nm. Thereafter, the k-Wave simulations were executed, incorporating those fluence maps to generate the PA signals. The blood properties were obtained using the PA signals. We introduced variations in μ a , μ s , and g ranging from −10% to +10%, −10% to +10%, and −5% to +1%, respectively, at 700 and 1000 nm wavelengths. One parameter, at both wavelengths, was changed at a time, keeping others fixed. Subsequently, we examined how accurately the blood parameters could be determined at physiological hematocrit levels. A 10% variation in μ a induces a 10% change in H estimation but no change in SO2 determination. Almost no change has been seen for μ s variation. However, a 5% (−5% to 0%) variation in the g factor resulted in approximately 160% and 115% changes in the PA signal amplitudes at 700 and 1000 nm, respectively, leading to ≈125% error in hematocrit estimation and ≈14% deviation in SO2 assessment when nominal SO2=70%. It is clear from this study that the scattering anisotropy factor is a very sensitive parameter and a small change in its value can result in large errors in the PA estimation of blood properties. In the future, in vitro experiments with pathological blood (inducing variation in the g parameter) will be performed, and accordingly, the accuracy of the PA technique in quantifying blood H and SO2 will be evaluated.

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.

Tumor Microenvironment-Activatable Phototheranostic: Leveraging Nitric Oxide and Weak Acidity as Dual Biomarkers for Ratiometric Fluorescence, Photoacoustic Imaging, and Photothermal Therapy.

Tumor microenvironment-responsive phototheranostic agents are highly sought after for their ability to improve diagnostic accuracy and treatment specificity. Here, we introduce a novel single-molecule probe, POZ-NO, which is activated by nitric oxide (NO) and weak acidity, enabling dual-mode imaging and photothermal therapy (PTT) of tumors. In acidic environments with elevated NO levels, POZ-NO exhibits a distinctive ratiometric fluorescence signal shift from the red to near-infrared, accompanied by a 700 nm photoacoustic signal. Additionally, POZ-NO demonstrated potent photothermal effects upon NO and acidity activation, achieving an impressive conversion efficiency of 74.3% under 735 nm laser irradiation. In vivo studies confirm POZ-NO's ability to accurately image tumors through ratiometric fluorescence and photoacoustic modes while selectively treating tumors with PTT.

Wavelength-modulated photoacoustic spectroscopic instrumentation system for multiple greenhouse gas detection and in-field application in the Qinling mountainous region of China

We present a sensitive and compact quantum cascade laser-based photoacoustic greenhouse gas sensor for the detection of CO2, CH4 and CO and discuss its applicability toward on-line real-time trace greenhouse gas analysis. Differential photoacoustic resonators with different dimensions were used and optimized to balance sensitivity with signal saturation. The effects of ambient parameters, gas flow rate, pressure and humidity on the photoacoustic signal and the spectral cross-interference were investigated. Thanks to the combined operation of in-house designed laser control and lock-in amplifier, the gas detection sensitivities achieved were 5.6 ppb for CH4, 0.8 ppb for CO and 17.2 ppb for CO2, signal averaging time 1 s and an excellent dynamic range beyond 6 orders of magnitude. A continuous outdoor five-day test was performed in an observation station in China’s Qinling National Botanical Garden (E longitude 108°29’, N latitude 33°43’) which demonstrated the stability and reliability of the greenhouse gas sensor.

Understanding photoacoustic signal formation in the presence of transparent thin films

Strain-induced variation of the refractive index is the main mechanism of strain detection in photoacoustic experiments. However, weak strain-optic coupling in many materials limits the application of photoacoustics as an imaging tool. A straightforward deposition of a transparent thin film as a top layer has previously been shown to provide signal enhancement due to elastic boundary effects. In this paper, we study photoacoustic signal formation in metal covered by thin transparent films of different thicknesses and demonstrate that in addition to boundary effects, the photoacoustic response is affected by optical effects caused by the presence of the top layer. The interplay of optical effects leads to a complex temporal signal shape that strongly depends on the thickness of the thin film.

Nucleus-targeted carbon dots as peroxidase nanozyme for photoacoustic imaging and phototherapy of tumor

High-purity carbon dots (CDs) with a highly π-conjugated sp2-hybridized graphite structure were prepared by the pulse electrolysis method using the graphite plate as raw material. Photoacoustic signal together with photothermal effect was found in the CDs-dispersed suspensions under near-infrared (NIR) irradiation. For the suspension with the CDs concentration of 500 μg/mL, the photothermal conversion efficiency is high up 64.3% and the solution’s temperature can be increased to 82.2 °C under NIR irradiation. Moreover, CDs can be effectively endocytosed by human hepatoma (HepG2) cells with a few hours, act as peroxidase nanozyme to decompose H2O2 and facilitate the production of reactive oxygen species. Under NIR irradiation, CDs exhibit an outstanding apoptosis-inducing effect on HepG2 cells by the photothermal effect. In addition, in vivo experiments show that CDs can be used in photoacoustic imaging (PAI) and guiding the tumor treatment. As a result, the nucleus-targeted CDs with an unique combination of PAI and photothermal effect have potential in cancer diagnosis and treatment.

A Dual-Mode Near-Infrared Optical and Photoacoustic Imaging Agent Based on a Low Energy Absorbing Ytterbium Complex.

Near-infrared (NIR) luminescence and photoacoustic (PA) imaging have attracted increasing attention for the real-time monitoring of biological samples due to high sensitivity, resolution, and pronounced signal detection depth, respectively. For improved contrast, both techniques require imaging agents possessing high absorption in the red-NIR range. Herein, we took advantage of a ternary complex formed with the anionic ytterbium(III) tetrakis(2-thenoyltrifluoroacetonate) ([Yb(tta)4]-) and the cationic NIR-absorbing chromophore, 1,1'-diethyl-2,2'-dicarbocyanine (Cy+), to evaluate its potential to act as a dual-mode NIR luminescence and PA imaging agent. We demonstrated that, upon excitation with red-NIR light, Cy[Yb(tta)4] encapsulated into polystyrene nanoparticles is able to generate both NIR Yb3+ emission and a PA signal in an imaging experiment performed in a tissue-mimicking phantom.

Semiconducting Polymers Based on Asymmetric Thiadiazoloquinoxaline for Augmented In Vivo NIR-II Photoacoustic Imaging.

A photoacoustic (PA) imaging technique using the second near-infrared (NIR-II) window has attracted more and more attention because of its merits of deeper penetration depth and higher signal-to-noise (S/N) ratio than that using the first near-infrared (NIR-I) one. However, the design and development of high-performance PA imaging contrast agents in the NIR-II window is still a challenge. A semiconducting polymer, constructed by asymmetric units, exhibits regiorandom characteristics that effectively increase the distortion of the backbone. This increase in the degree of twist can regulate the twisted intramolecular charge transfer (TICT) effect, resulting in an enhancement of the PA signal. In this paper, an asymmetric structural acceptor strategy is developed to improve the PA signals of the resulting semiconducting polymer (PATQ-MP) in the NIR-II window with improved brightness, higher S/N ratio, and better photothermal conversion efficiency compared to polymers with the same main-chain structure containing a symmetric acceptor. DFT analysis showed that PATQ-MP containing an asymmetric acceptor monomer had a larger dihedral angle, which effectively improved the PA signal intensity by enhancing the TICT effect. The PEG-encapsulated PATQ-MP nanoparticles exhibit promising performance in the PA imaging of mouse tumors in vivo, demonstrating the clear identification of microvessels as small as 100 μm along with rapid metabolism within a span of 5 h. Therefore, this work provides a unique molecular design strategy for improving the signal intensity of PA imaging in the NIR-II window.

A dual‐resonance enhanced photoacoustic spectroscopy gas sensor based on a fiber optic cantilever beam microphone and a spherical photoacoustic cell

AbstractWe propose a novel high‐performance dual‐resonance enhanced photoacoustic spectroscopy (DRE‐PAS) gas sensor based on a highly sensitive fiber optic cantilever beam microphone and a high‐Q spherical photoacoustic cell (PAC). The first‐order resonant frequency (FORF) of the spherical PAC is analyzed by finite element analysis to match the FORF of the cantilever microphone for the double resonance enhancement of the photoacoustic signal. The photoacoustic spectroscopy (PAS) system, including the DRE‐PAS sensor, a 1532.8 nm distributed feedback laser, and a high‐speed spectrometer, has been successfully exploited for trace acetylene (C2H2) detection. The experimental results show that the limit of detection (LOD) is 106.8 parts‐per‐billion (ppb) with an integral time of 1 s, and the LOD can be further reduced to 11.03 ppb by Allan‐Werle deviation for 100 s integral time. The normalized noise equivalent absorption coefficient can be obtained as 2.44 × 10−8 cm−1 WHz−1/2. The reported DRE‐PAS gas sensor has the superior characteristics of photoacoustic signal enhancement, high sensitivity, and strong antielectromagnetic interference capability, which can provide a new solution for PAS development.

A nonlocal photoacoustic effect with variable thermal conductivity of semiconductor material subjected to laser heat source

This study explores the behavior of laser-exposed photo-excited carriers, investigating the propagation of photoacoustic waves in the thermoelastic domain. It also delves into the theoretical generation of surface acoustic waves in semiconductors through photo-thermoelastic processes. The research considers the interaction between thermomechanical and acoustic waves in a nonlocal medium with temperature-dependent thermal conductivity. Unlike relying on electron–phonon or electron-hole thermalization processes, photoacoustic waves here result from thermoelastic stress induced by the laser-induced temperature increase. The investigation accounts for the optical, mechanical, and thermoelastic properties of nanoscale semiconductor materials. Predictions of photoacoustic signals are derived by solving a combined thermal diffusion issue and a thermoelastic problem, using Laplace and Fourier transforms in the mathematical model. Numerical solutions encompass various physical fields within the time domain using the inversion technique of Laplace and Fourier transforms, such as thermal, acoustic, mechanical, and carrier density diffusion. The study evaluates and compares the influences of thermal memory and thermal conductivity presenting visual representations.

An AND-Gate Photoacoustic Probe for Cys and H2S Precise Photoacoustic Sensing in Localized Tumors.

Photoacoustic (PA) tomography has shown many promising aspects in noninvasive and precise imaging of deep-localized biomarkers. However, these traditional single-locked PA probes always face challenges in precise PA imaging with high specificity. Here, we report a novel AND-gate photoacoustic probe, BAE, to improve tumor imaging accuracy via the combination of two tumor-associated biomarkers, cysteine (Cys) and hydrogen sulfide (H2S). Only when Cys and H2S are concurrently introduced into the detection system does the absorption of BAE red-shift from the initial 680 to 810 nm, thereby showing a 5.29-fold enhancement in its PA signal at 810 nm. The good specificity of BAE is proven, since an obvious PA signal could be observed only in the solution containing both Cys and H2S and was not affected by other reactive sulfur species. After being taken up by tumors with the assistance of a nanomicelle, the AND-gate PA probe BAE was applied for dynamic real-time monitoring of Cys and H2S in vivo, achieving precise identification of tumors. This AND-gate PA probe provides a potential technical tool for precise sensing analysis of deep-seated diseases.

Compressed Sensing for Biomedical Photoacoustic Imaging: A Review.

Photoacoustic imaging (PAI) is a rapidly developing emerging non-invasive biomedical imaging technique that combines the strong contrast from optical absorption imaging and the high resolution from acoustic imaging. Abnormal biological tissues (such as tumors and inflammation) generate different levels of thermal expansion after absorbing optical energy, producing distinct acoustic signals from normal tissues. This technique can detect small tissue lesions in biological tissues and has demonstrated significant potential for applications in tumor research, melanoma detection, and cardiovascular disease diagnosis. During the process of collecting photoacoustic signals in a PAI system, various factors can influence the signals, such as absorption, scattering, and attenuation in biological tissues. A single ultrasound transducer cannot provide sufficient information to reconstruct high-precision photoacoustic images. To obtain more accurate and clear image reconstruction results, PAI systems typically use a large number of ultrasound transducers to collect multi-channel signals from different angles and positions, thereby acquiring more information about the photoacoustic signals. Therefore, to reconstruct high-quality photoacoustic images, PAI systems require a significant number of measurement signals, which can result in substantial hardware and time costs. Compressed sensing is an algorithm that breaks through the Nyquist sampling theorem and can reconstruct the original signal with a small number of measurement signals. PAI based on compressed sensing has made breakthroughs over the past decade, enabling the reconstruction of low artifacts and high-quality images with a small number of photoacoustic measurement signals, improving time efficiency, and reducing hardware costs. This article provides a detailed introduction to PAI based on compressed sensing, such as the physical transmission model-based compressed sensing method, two-stage reconstruction-based compressed sensing method, and single-pixel camera-based compressed sensing method. Challenges and future perspectives of compressed sensing-based PAI are also discussed.

Speckle Variance Photoacoustic Microscopy for Microhemodynamic Imaging.

Relying on the strong optical absorption of hemoglobin to pulsed laser energy, photoacoustic microscopy provides morphological and functional information on microvasculature label-freely. Here, we propose speckle variance photoacoustic microscopy (SV-PAM), which harnesses intrinsic imaging contrast from temporal-varied photoacoustic signals of moving red blood cells in blood vessels, for recovering three-dimension hemodynamic images down to capillary-level resolution within the microcirculatory tissue beds in vivo. Calculating the speckle variance of consecutive photoacoustic B-scan frames acquired at the same lateral position enables accurate identification of blood perfusion and occlusion, which provides interpretations of dynamic blood flow in the microvasculature, in addition to the microvascular anatomic structures. We demonstrate high-resolution hemodynamic imaging of vascular occlusion and reperfusion in the microvasculature of mice ears in vivo. The results suggest that our SV-PAM is potentially invaluable for biomedical hemodynamic investigations, for example, imaging ischemic stroke and hemorrhagic stroke.

Fiber optic photoacoustic gas sensor enhanced by multi-pass cell with overlapping phantom spots

A neotype fiber optic photoacoustic gas sensor with overlapping phantom spots based multi-pass is proposed, which greatly improves the reflection times and the length of gas absorption path. Moreover, the detection accuracy of photoacoustic spectroscopy (PAS) system is independent of the optical interference effect caused by overlapping spots, which is different from tunable diode laser absorption spectroscopy (TDLAS) technology. A mathematical model including light beam motion space, spot size and overlap discrimination of multi-pass structure based on overlapping phantom spots is established. The incident light is reflected up to dozens of times in the resonator with a diameter of only 8 mm. The emergent light does not need to converge on a photodetector, which reduces the difficulty of adjusting the optical path and promotes the realization of overlapping phantom spots. The experimental results show that the amplitude of photoacoustic signal is improved by about 40 times compared with the single spot structure. Appling high-sensitivity optical fiber cantilever to detect the sound pressure signal. The detection limit of C2H2 gas reaches 8.2 ppt. The normalized noise equivalent absorption (NNEA) coefficient of the gas sensor is achieved to be 9.3×10−11 cm−1WHz−1/2.

TT-type resonator-based differential photoacoustic spectroscopy for trace gas detection.

A novel TT-type resonator was proposed for the first time, to our knowledge, to realize differential photoacoustic (PA) detection for trace gas measurement. The special design of the TT-type resonator allows us to install the microphone at the resonant center of the acoustic field to maximize the use of the absorption-induced PA signal. To meet the requirement of low gas consumption and easy integration, the TT-type resonator-based PA cell was fabricated as a fiber-coupled module with an inner volume of only 1.1 ml. For validation, the TT-type PA cell was integrated to a photoacoustic spectroscopy (PAS) system for acetylene detection. As a result, a linearity of 0.99999 was achieved in a concentration range from 0 to 5000 ppm with a noise equivalent sensitivity of 101 ppb. The proposed TT-type resonator contributes a new style of PA cell structure to the field of PAS gas detection, combining the advantages of easy integration, low gas consumption, differential detection, and photoacoustic enhancement together.

Hyaluronic acid functionalized iron–platinum nanoparticles for photothermal therapy and photoacoustic imaging

This study represents an innovative approach to construct multi-functional nanoplatforms for cancer diagnosis and therapy by combining hyaluronic acid (HA) with iron-platinum nanoparticles (FePt NPs). These HA-coated FePt NPs, referred to as FePt@HA NPs, demonstrated remarkable biocompatibility, high absorption, and excellent light-to-heat conversion properties in the near-infrared (NIR) region, making them ideal candidates for photothermal therapy (PTT). In vitro studies revealed their effective cancer cell eradication under NIR laser irradiation, while in vivo experiments on mice showcased their superior heating capabilities. Moreover, FePt@HA NPs exhibited a distinct and strong photoacoustic (PA) signal, facilitating enhanced and precise intra-tumoral PA imaging. Our results highlight the potential of FePt@HA NPs as promising photothermal agents for future PTT applications. They offer high selectivity, precision, and minimal side effects in cancer treatment, along with their valuable PA imaging application for tumor localization and characterization.

Augmenting authenticity for non-invasive in vivo detection of random blood glucose with photoacoustic spectroscopy using Kernel-based ridge regression

Photoacoustic Spectroscopy (PAS) is a potential method for the noninvasive detection of blood glucose. However random blood glucose testing can help to diagnose diabetes at an early stage and is crucial for managing and preventing complications with diabetes. In order to improve the diagnosis, control, and treatment of Diabetes Mellitus, an appropriate approach of noninvasive random blood glucose is required for glucose monitoring. A polynomial kernel-based ridge regression is proposed in this paper to detect random blood glucose accurately using PAS. Additionally, we explored the impact of the biological parameter BMI on the regulation of blood glucose, as it serves as the primary source of energy for the body’s cells. The kernel function plays a pivotal role in kernel ridge regression as it enables the algorithm to capture intricate non-linear associations between input and output variables. Using a Pulsed Laser source with a wavelength of 905 nm, a noninvasive portable device has been developed to collect the Photoacoustic (PA) signal from a finger. A collection of 105 individual random blood glucose samples was obtained and their accuracy was assessed using three metrics: Root Mean Square Error (RMSE), Mean Absolute Difference (MAD), and Mean Absolute Relative Difference (MARD). The respective values for these metrics were found to be 10.94 (mg/dl), 10.15 (mg/dl), and 8.86%. The performance of the readings was evaluated through Clarke Error Grid Analysis and Bland Altman Plot, demonstrating that the obtained readings outperformed the previously reported state-of-the-art approaches. To conclude the proposed IoT-based PAS random blood glucose monitoring system using kernel-based ridge regression is reported for the first time with more accuracy.

Single Side-Chain-Modulatory of Hemicyanine for Optimized Fluorescence and Photoacoustic Dual-Modality Imaging of H2S In Vivo.

Near-infrared fluorescence (NIRF)/photoacoustic (PA) dual-modality imaging integrated high-sensitivity fluorescence imaging with deep-penetration PA imaging has been recognized as a reliable tool for disease detection and diagnosis. However, it remains an immense challenge for a molecule probe to achieve the optimal NIRF and PA imaging by adjusting the energy allocation between radiative transition and nonradiative transition. Herein, a simple but effective strategy is reported to engineer a NIRF/PA dual-modality probe (Cl-HDN3) based on the near-infrared hemicyanine scaffold to optimize the energy allocation between radiative and nonradiative transition. Upon activation by H2S, the Cl-HDN3 shows a 3.6-fold enhancement in the PA signal and a 4.3-fold enhancement in the fluorescence signal. To achieve the sensitive and selective detection of H2S in vivo, the Cl-HDN3 is encapsulated within an amphiphilic lipid (DSPE-PEG2000) to form the Cl-HDN3-LP, which can successfully map the changes of H2S in a tumor-bearing mouse model with the NIRF/PA dual-modality imaging. This work presents a promising strategy for optimizing fluorescence and PA effects in a molecule probe, which may be extended to the NIRF/PA dual-modality imaging of other disease-relevant biomarkers.