Photoacoustic Signal Research Articles

Supramolecular assembly of Polydopamine@Fe nanoparticles with near-infrared light-accelerated cascade catalysis applied for synergistic photothermal-enhanced chemodynamic therapy

Chemodynamic therapy (CDT) via Fenton-like reaction is greatly attractive owing to its capability to generate highly cytotoxic •OH radicals from tumoral hydrogen peroxide (H2O2). However, the antitumor efficacy of CDT is often challenged by the relatively low radical generation efficiency and the high levels of antioxidative glutathione (GSH) in tumor microenvironment. Herein, an innovative photothermal Fenton-like catalyst, Fe-chelated polydopamine (PDA@Fe) nanoparticle, with excellent GSH-depleting capability is constructed via one-step molecular assembly strategy for dual-modal imaging-guided synergetic photothermal-enhanced chemodynamic therapy. Fe(III) ions in PDA@Fe nanoparticles can consume the GSH overexpressed in tumor microenvironment to avoid the potential •OH consumption, while the as-produced Fe(II) ions subsequently convert tumoral H2O2 into cytotoxic •OH radicals through the Fenton reaction. Notably, PDA@Fe nanoparticles demonstrate excellent near-infrared light absorption that results in superior photothermal conversion ability, which further boosts above-mentioned cascade catalysis to yield more •OH radicals for enhanced CDT. Taken together with T1-weighted magnetic resonance imaging (MRI) contrast enhancement (r1 = 8.13 mM−1 s−1) and strong photoacoustic (PA) imaging signal of PDA@Fe nanoparticles, this design finally realizes the synergistic photothermal-chemodynamic therapy. Overall, this work offers a new promising paradigm to effectively accommodate both imaging and therapy functions in one well-defined framework for personalized precision disease treatment.

In Vivo Photoacoustic Ultrasound (PAUS) Assay for Monitoring Tendon Collagen Compositional Changes during Injury and Healing.

Tendon injury and healing involve significant changes to tissue biology and composition. Current techniques often require animal sacrifice or tissue destruction, limiting assessment of dynamic changes in tendons, including treatment response, disease development, rupture risk, and healing progression. Changes in tendon composition, such as altered collagen content, can significantly impact tendon mechanics and function. Analyses of compositional changes typically require ex vivo techniques with animal sacrifice or destruction of the tissue. In vivo evaluation of tendons is critical for longitudinal assessment. We hypothesize that photoacoustic ultrasound detects differences in collagen concentration throughout healing. We utilized photoacoustic ultrasound, a hybrid imaging modality that combines ultrasound and laser-induced photoacoustic signals to create detailed and high-resolution images of tendons, to identify its endogenous collagen composition. We correlated the photoacoustic signal to picrosirius red staining. The results show that the photoacoustic ultrasound-estimated collagen content in tendons correlates well with picrosirius red staining. This study demonstrates that photoacoustic ultrasound can assess injury-induced compositional changes within tendons and is the first study to image these targets in rat Achilles tendon in vivo.

Ultrafast measurement of photoacoustic parameters with mid-infrared frequency comb transients.

The photoacoustic (PA) effect has been widely used in various applications, including highly sensitive spectroscopy and label-free, non-invasive imaging. In this work, we demonstrate a fast and precise measurement of PA parameters for light-absorbing liquids using mid-infrared asynchronous sampling pump-probe measurements. To simulate the observed PA oscillation signals and extract various PA parameters as a function of pump power, we derived analytical solutions of the PA wave equation driven by a train of ultrashort Gaussian pump pulses. By fitting the analytical solution to the measured PA signals using a nonlinear curve fitting method, we could measure the PA parameters, including damping rate, viscosity, and natural frequency. Furthermore, the dynamic response of thermophysical properties of the chloroform solution is also investigated by measuring the variation of the Grüneisen parameter with pump power. We anticipate that this work will open new possibilities for precise in situ measurements of the thermal properties of light-absorbing liquids.

High-sensitivity trace gas detection based on differential Helmholtz photoacoustic cell with dense spot pattern

A high-sensitivity photoacoustic spectroscopy (PAS) sensor based on differential Helmholtz photoacoustic cell (DHPAC) with dense spot pattern is reported in this paper for the first time. A multi-pass cell based on two concave mirrors was designed to achieve a dense spot pattern, which realized 212 times excitation of incident laser. A finite element analysis was utilized to simulate the sound field distribution and frequency response of the designed DHPAC. An erbium-doped fiber amplifier (EDFA) was employed to amplify the output optical power of the laser to achieve strong excitation. In order to assess the designed sensor's performance, an acetylene (C2H2) detection system was established using a near infrared diode laser with a central wavelength 1530.3 nm. According to experimental results, the differential characteristics of DHPAC was verified. Compared to the sensor without dense spot pattern, the photoacoustic signal with dense spot pattern had a 44.73 times improvement. The minimum detection limit (MDL) of the designed C2H2-PAS sensor can be improved to 5 ppb when the average time of the sensor system is 200 s.

Photoacoustic Imaging Using Polysaccharide-Porphyrin Complexes by Photoirradiation at Long Wavelengths.

Photoacoustic (PA) imaging is a novel biological imaging technique with superior depth resolution compared to fluorescence imaging. The efficacy of PA imaging depends on contrast agents that possess considerable absorbance at longer wavelengths, coupled with high permeability in biological tissue and minimal fluorescence, achieved through mitigating aggregation-caused quenching (ACQ) that attenuates PA intensity. Despite the successful transfer of porphyrin 2 featuring amino moieties from polysaccharides to liposomes, most of 2 incorporated within λ-carrageenan (CGN-2 complex) remained in CGN under acidic lysosomal conditions (pH 5.0). Consequently, the CGN-2 complex exhibited a strong PA signal under 680 nm photoirradiation in Colon26 cells owing to the ACQ of 2. Moreover, the PA intensity of the CGN-2 complex was further enhanced under 780 nm photoirradiation owing to the increased absorbance at 780 nm facilitated by the redshift of the Q-band at pH 5.0.

Influence of Local Thermodynamic Non-Equilibrium to Photothermally Induced Acoustic Response of Complex Systems

In this paper, the time-resolved model of the photoacoustic signal for samples with a complex inner structure is derived including local non-equilibrium of structural elements with multiple degrees of freedom, i.e., structural entropy of the system. The local non-equilibrium is taken into account through the fractional operator. By analyzing the model for two types of time-dependent excitation, a very short pulse and a very long pulse, it is shown that the rates of non-equilibrium relaxations in complex samples can be measured by applying the derived model and time-domain measurements. Limitations of the model and further directions of its development are discussed.

Adaptively multi-scale microstructure characterization of cancellous bone via photoacoustic signal decomposition

Osteoporosis is a systemic disease with a high incidence in the elderly and seriously affects the quality of life of patients. Photoacoustic (PA) technology, which combines the advantages of light and ultrasound, can provide information about the physiological structure and chemical information of biological tissues in a non-invasive and non-radiative way. Due to the complex structural characteristics of bone tissue, PA signals generated by bone tissue are non-stationary and nonlinear. However, conventional PA signal processing methods are not effective for non-stationary signal processing. In this study, an empirical mode decomposition (EMD)-based Hilbert-Huang transform (HHT) PA signal analysis method, called HHT PA signal analysis (HPSA), was developed to assess the microstructure information of bone tissue, which is closely related to bone health. The feasibility of the HPSA method in bone health assessment was proven by numerical simulation and experimental studies on animal samples with different bone volume/total volume (BV/TV) and bone mineral densities. First, based on adaptive EMD, the different modes correlated with multi-scale information were mined from the PA signal, the correlations between different intrinsic mode function (IMF) modes and BV/TVs were analyzed, and the optimal mode for more efficient PA time–frequency analysis was selected. Second, multi-wavelength HPSA was used to assess the changes in the chemical components of the bone tissue. The results demonstrate that the HPSA method can distinguish bones with different BV/TVs and microstructure conditions adaptively with high efficiency. They further emphasize the potential of PA techniques in characterizing biological tissues in bones for early and rapid detection of bone diseases.

Influence of water vapor concentration on photoacoustic spectroscopy‐based characteristic gas analysis of transformer faults

AbstractThe water vapor in the ambient air affects the accuracy of the photoacoustic (PA) dissolved gas analysis system for transformer health monitoring. A laser PA system was evaluated by dry and humidified standard gases to study the influence of water vapor concentration on PA gas detection. Theoretical analysis was conducted on the effect of gas molecule relaxation on PA signal detection. A high‐frequency resonant PA cell and a low‐frequency nonresonant PA cell were used to detect acetylene (C2H2) and carbon monoxide (CO), respectively. The experimental results show that the PA signal of humidified CO is about 12 times higher than PA signal of dry gas for the resonant PA detection system, respectively. In addition, as the frequency is increased from 30 to 980 Hz, the PA signals of humidified and dry CO attenuate by 1.5 and 6.9 times, respectively.

Probe fusion all-optic OCT-PAM dual-mode imaging system for biomedical imaging

We proposed a non-contact photoacoustic (PA) detection method using spectral domain optical coherence tomography (SDOCT). Two interference spectrums (A-lines) were acquired before and after the PA excitation with SDOCT. PA signal propagated within the sample causing the vibration. The vibration inner the sample introduced phase change between the acquired two A-lines. Thus, the PA signal can be detected by evaluating the difference in phase between the two A-lines. Based on the method, an OCT-PAM dual-mode imaging system was constructed. In the system, SDOCT served as the detection unit for PAM. Thus, the combination of the two imaging modalities was simplified. Another advantage of the system is that it realizes non-contact all-optic detection, which is attractive for biomedical imaging. Using the system, we imaged phantoms of carbon fibers, asparagus leaves and human hairs. Furthermore, the cortical vasculature of rat was imaged in vivo and the flow status was evaluated quantitatively.

Enhanced photoacoustic signal processing using empirical mode decomposition and machine learning

ABSTRACT In this study, we propose a robust photoacoustic (PA) signal processing framework for a material independent defect detection using empirical mode decomposition (EMD) and machine learning algorithms. First, a database of the PA signals with 960 samples has been obtained from aluminium, iron, plastic and wood materials using a laser, microphone and data acquisition board-based PA apparatus. Second, the EMD based time and time-frequency domain techniques are proposed to extract robust cross-material feature space focusing on laser induced acoustic signal, and the decomposed intrinsic mode (IMF) with 14 extracted features are performed on totally 960 samples PA signals to evaluate k-nearest neighbour (k-NN), decision tree (DT) and support vector machine (SVM) classifiers. Inter- material and cross-material evaluations are performed, and the accuracy rates up to 100% for SVM and 97.77% for k-NN are yielded.

Pressure-Compensated Fiber-Optic Photoacoustic Sensors for Trace SO2 Analysis in Gas Insulation Equipment.

A high-sensitivity fiber-optic photoacoustic sensor with pressure compensation is proposed to analyze the decomposition component SO2 in high-pressure gas insulation equipment. The multiple influence mechanism of pressure on photoacoustic excitation and cantilever detection has been theoretically analyzed and verified. In the high-pressure environment, the excited photoacoustic signal is enhanced, which compensates for the loss of sensitivity of the cantilever. A fiber-optic F-P cantilever is utilized to simultaneously measure static pressure and dynamic photoacoustic wave, and a spectral demodulation method based on white light interference is applied to calculate the optical path difference of the F-P interferometer (FPI). The real-time pressure is judged through the linear relationship between the average optical path difference of FPI and the pressure, which gives the proposed fiber-optic photoacoustic sensor the inherent advantages of being uncharged and resistant to electromagnetic interference. The average optical path difference of FPI is positively related to pressure, with a responsivity of 0.6 μm/atm, which is based on changes in the refractive index of gas. In the range of 1-4 atm, the SO2 sensor has a higher detection sensitivity at high-pressure, which benefits from the pressure compensation effect. With the pressure environment of gas insulation equipment at 4 atm as the application background, the SO2 gas is tested. The detection limit is 20 ppb with an averaging time of 400 s.

Tuning Tumor Targeting and Ratiometric Photoacoustic Imaging by Fine-Tuning Torsion Angle for Colorectal Liver Metastasis Diagnosis.

Photoacoustic (PA) tomography is an emerging biomedical imaging technology for precision cancer medicine. Conventional small-molecule PA probes usually exhibit a single PA signal and poor tumor targeting that lack the imaging reliability. Here, we introduce a series of cyanine/hemicyanine interconversion dyes (denoted Cy-HCy) for PA/fluorescent dual-mode probe development that features optimized ratiometric PA imaging and tunable tumor-targeting ability for precise diagnosis and resection of colorectal cancer (CRC). Importantly, Cy-HCy can be presented in cyanine (inherent tumor targeting and long NIR PA wavelength) and hemicyanine (poor tumor targeting and short NIR PA wavelength) by fine-tuning torsion angle and the ingenious transformation between cyanine and hemicyanine through regulation optically tunable group endows the NIR ratiometric PA and tunable tumor-targeting properties. To demonstrate the applicability of Cy-HCy dyes, we designed the first small-molecule tumor-targeting and NIR ratiometric PA probe Cy-HCy-H2S for precise CRC liver metastasis diagnosis, activated by H2S (a CRC biomarker). Using this probe, we not only visualized the subcutaneous tumor and liver metastatic cancers in CRC mouse models but also realized PA and fluorescence image-guided tumor excision. We expect that Cy-HCy will be generalized for creating a wide variety of inherently tumor-targeting NIR ratiometric PA probes in oncological research and practice.

Quartz Enhanced Photoacoustic Spectroscopy on Solid Samples.

Quartz-Enhanced Photoacoustic Spectroscopy (QEPAS) is a technique in which the sound wave is detected by a quartz tuning fork (QTF). It enables particularly high specificity with respect to the excitation frequency and is well known for an extraordinarily sensitive analysis of gaseous samples. We have developed the first photoacoustic (PA) cell for QEPAS on solid samples. Periodic heating of the sample is excited by modulated light from an interband cascade laser (ICL) in the infrared region. The cell represents a half-open cylinder that exhibits an acoustical resonance frequency equal to that of the QTF and, therefore, additionally amplifies the PA signal. The antinode of the sound pressure of the first longitudinal overtone can be accessed by the sound detector. A 3D finite element (FE) simulation confirms the optimal dimensions of the new cylindrical cell with the given QTF resonance frequency. An experimental verification is performed with an ultrasound micro-electromechanical system (MEMS) microphone. The presented frequency-dependent QEPAS measurement exhibits a low noise signal with a high-quality factor. The QEPAS-based investigation of three different solid synthetics resulted in a linearly dependent signal with respect to the absorption.

Photoacoustic imaging-based in situ biofouling monitoring in underwater optical windows—A novel approach

The accuracy of optical instruments is inevitably affected by marine biofouling as their optical windows become obscured in seawater. The continuous removal of biofouling imposes a substantial energy burden on the offshore instruments. Therefore, monitoring biofouling and selecting an appropriate time for biofouling removal is essential. However, an efficient in situ monitoring strategy for biofouling in underwater optical windows is currently lacking. To address these challenges, we conducted exploratory research on a new technology based on photoacoustic imaging for the in situ monitoring of marine biofouling in optical windows. First, poly methyl methacrylate coupons were hung and immersed in the coastal waters of Qingdao for varying durations during the sea trials. Evident photoacoustic signals from the biofouling attached to the surfaces of the coupons were collected by means of photoacoustic experimental platform. Two-dimensional photoacoustic images were reconstructed using photoacoustic microscopy. On comparing the optical and photoacoustic images of biofouling, photoacoustic images can more effectively reflect the degree of biological fouling. Finally, the optical and photoacoustic images of coupons subjected to ultrasonic treatment were compared and analyzed to further review the feasibility of fouling monitoring based on photoacoustic technology. These findings provide new insights into in situ detection of marine biofouling.

A firm-push-to-open and light-push-to-lock strategy for a general chemical platform to develop activatable dual-modality NIR-II probes.

Activatable near-infrared (NIR) imaging in the NIR-II range is crucial for deep tissue bioanalyte tracking. However, designing such probes remains challenging due to the limited availability of general chemical strategies. Here, we introduced a foundational platform for activatable probes, using analyte-triggered smart modulation of the π-conjugation system of a NIR-II-emitting rhodamine hybrid. By tuning the nucleophilicity of the ortho-carboxy moiety, we achieved an electronic effect termed "firm-push-to-open and light-push-to-lock," which enables complete spirocyclization of the probe before sensing and allows for efficient zwitterion formation when the light-pushing aniline carbamate trigger is transformed into a firm-pushing aniline. This platform produces dual-modality NIR-II imaging probes with ~50-fold fluorogenic and activatable photoacoustic signals in live mice, surpassing reported probes with generally below 10-fold activatable signals. Demonstrating generality, we successfully designed probes for hydrogen peroxide (H2O2) and hydrogen sulfide (H2S). We envision a widespread adoption of the chemical platform for designing activatable NIR-II probes across diverse applications.

Tumor-specific enhanced NIR-II photoacoustic imaging via photothermal and low-pH coactivated AuNR@PNIPAM-VAA nanogel

BackgroundProperly designed second near-infrared (NIR-II) nanoplatform that is responsive tumor microenvironment can intelligently distinguish between normal and cancerous tissues to achieve better targeting efficiency. Conventional photoacoustic nanoprobes are always “on”, and tumor microenvironment-responsive nanoprobe can minimize the influence of endogenous chromophore background signals. Therefore, the development of nanoprobe that can respond to internal tumor microenvironment and external stimulus shows great application potential for the photoacoustic diagnosis of tumor.ResultsIn this work, a low-pH-triggered thermal-responsive volume phase transition nanogel gold nanorod@poly(n-isopropylacrylamide)-vinyl acetic acid (AuNR@PNIPAM-VAA) was constructed for photoacoustic detection of tumor. Via an external near-infrared photothermal switch, the absorption of AuNR@PNIPAM-VAA nanogel in the tumor microenvironment can be dynamically regulated, so that AuNR@PNIPAM-VAA nanogel produces switchable photoacoustic signals in the NIR-II window for tumor-specific enhanced photoacoustic imaging. In vitro results show that at pH 5.8, the absorption and photoacoustic signal amplitude of AuNR@PNIPAM-VAA nanogel in NIR-II increases up obviously after photothermal modulating, while they remain slightly change at pH 7.4. Quantitative calculation presents that photoacoustic signal amplitude of AuNR@PNIPAM-VAA nanogel at 1064 nm has ~ 1.6 folds enhancement as temperature increases from 37.5 °C to 45 °C in simulative tumor microenvironment. In vivo results show that the prepared AuNR@PNIPAM-VAA nanogel can achieve enhanced NIR-II photoacoustic imaging for selective tumor detection through dynamically responding to thermal field, which can be precisely controlled by external light.ConclusionsThis work will offer a viable strategy for the tumor-specific photoacoustic imaging using NIR light to regulate the thermal field and target the low pH tumor microenvironment, which is expected to realize accurate and dynamic monitoring of tumor diagnosis and treatment.

Wintersweet-like Nanohybrids of Titanium-doped Cerium Vanadate Loaded with Polypyrrole for Tumor Theranostic.

Compromises between enhanced on-targeting reactivity and precise real-time monitoring in the tumor microenvironment (TME) are the main roadblocks for catalytic cancer therapy. The hallmark of a high level of hydrogen peroxide (H2O2) and acidic extracellular environment of the hypoxia solid tumor can underpin therapeutic and tracking performance. Herein, this work provides an activatable wintersweet-like nanohybrid consisting of titanium (Ti) doped cerium vanadate nanorods with the modification of polypyrrole (PPy)nanoparticles (CeVO4-Ti@PPy) for combinatorial therapies of breast carcinoma. The Ti dopants in the size-controllable CeVO4 nanorods lower the energy barrier (0.5eV) of the rate-determining steps and elaborate peroxidase-like (POD-like)activities to improve the generation of toxic hydroxyl radical (·OH) according to the density functional theory (DFT) calculation. The multiple enzyme-like activities, including the intrinsic glutathione peroxidase (GPx) and catalase (CAT), achieve a record-high therapeutic efficiency. Coupling this oxidative stress with the photothermal effects of PPy enables enhanced catalytic tumor necrosis. The exterior PPy heterogeneous structure can be further doped with protons in the local acidic environment to intensify photoacoustic signals, allowing the non-invasive accurate tracking of tumors. The theranostic performance displayed negligible attenuated signals in near-infrared (NIR) windows. This organic-inorganic nanohybrid with a heterogeneous structure provides the potential to improve the overall outcomes of catalytic therapy.

Highly sensitive photoacoustic gas sensor based on near-concentric cavity.

The precise detection of trace gases in the atmosphere is vital for both environmental preservation and human health. Addressing the inherent challenges in enhancing the sensitivity of photoacoustic spectroscopy, a highly sensitive photoacoustic gas detection method utilizing a near-concentric cavity was proposed. By constructing a near-concentric optical cavity, laser reflections within the photoacoustic cell were substantially amplified, resulting in enhanced sensitivity of photoacoustic signal detection. Additionally, to align with the optical path characteristics of the near-concentric cavity, a miniaturized dumbbell-like photoacoustic cell was designed. Characterized by its high-frequency resonance, this design effectively mitigated background noise while maintaining a high sound pressure level. Experimental results demonstrated a remarkable enhancement in both signal intensity and signal-to-noise ratio by factors of 22.06 and 21.26, respectively, compared to traditional excitation methods. According to the 1σ standard, with a laser power of 21 mW, the setup achieved a detection limit of 10.15 ppb for NO2. The corresponding normalized noise equivalent absorption was calculated to be 2.84 × 10-9 cm-1WHz-1/2, with a gas consumption rate of merely 15.19 mL.

Off-plane quartz-enhanced photoacoustic spectroscopy.

In this work, we developed off-plane quartz-enhanced photoacoustic spectroscopy (OP-QEPAS). In the OP-QEPAS the light beam went neither through the prong spacing of the quartz tuning fork (QTF) nor in the QTF plane. The light beam is in parallel with the QTF with an optimal distance, resulting in low background noise. A radial-cavity (RC) resonator was coupled with the QTF to enhance the photoacoustic signal by the radial resonance mode. By offsetting both the QTF and the laser position from the central axis, we enhance the effect of the acoustic radial resonance and prevent the noise generated by direct laser irradiation of the QTF. Compared to IP-QEPAS based on a bare QTF, the developed OP-QEPAS with a RC resonator showed a >10× signal-to-noise ratio (SNR) enhancement. The OP-QEPAS system has great advantages in the use of light emitting devices (LEDs), long-wavelength laser sources such as mid-infrared quantum cascade lasers, and terahertz sources. When employing a LED as the excitation source, the noise level was suppressed by ∼2 orders of magnitude. Furthermore, the radial and longitudinal resonance modes can be combined to further improve the sensor performance.

Fiber-Optic Photoacoustic Gas Microsensor Dual Enhanced by Helmholtz Resonator and Interferometric Cantilever.

A high-sensitivity fiber-optic photoacoustic (PA) gas microsensor is demonstrated with dual enhancement based on acoustics and detection. Due to the characteristic of small size, a Helmholtz resonator is integrated into a miniature PA sensor. The acoustically amplified PA signal is detected by a high-sensitivity fiber Fabry-Perot (F-P) interferometric cantilever. The first-order resonant frequencies of the interferometric cantilever and Helmholtz resonator are matched by subtle adjustments. The weak PA signal is significantly enhanced in a volume of only 0.35 mL, which breaks the volume limitation of the resonance modes in traditional PA sensing systems. To improve the resolution of the microsensor, a white light interferometry (WLI)-based spectral demodulation algorithm is utilized. The experimental results indicate that the minimum detection limit of acetylene (C2H2) drops to about 15 ppb with an averaging time of 100 s, corresponding to the normalized noise equivalent absorption (NNEA) coefficient of 2.7 × 10-9 W·cm-1·Hz-1/2. The dual resonance enhanced fiber-optic PA gas microsensor has the merits of high sensitivity, intrinsic safety, and compact structure.