Photoacoustic Experiments Research Articles

The benefits of photoacoustics for the monitoring of drug stability and penetration through tissue-mimicking membranes.

The paper demonstrates the potential of photoacoustics for the identification of the mechanisms underlying drug transport through tissue-mimicking systems. Photoacoustic experiments were performed for a model transdermal delivery system, consisting of drug dithranol (in pharmaceutical form) and dodecanol-collodion (DDC) membrane. The spectroscopic data revealed a single-path photodegradation of dithranol in Vaseline (dithranol→danthrone, characterized by the 1st order decay rate of (7.85±0.31)·10-4 s-1), and a multipath degradation in the DDC system, involving danthrone and the unknown compound (characterized by the absorption band at ~400nm) as the final products. The desorption experiments performed enabled the identification of the unknown compound as the photodegradation product of dithranol molecules bound to the membrane matrix. The result led to the incorporation of the adsorption effects and heterogeneous structure of the membrane into the hydrodynamical model of mass transport. The model was tested against the photoacoustic depth-profiling data for dithranol permeation through DDC. The analysis allowed the dispersion and advection coefficients to be determined (D' = (2.05±0.03)⋅10-9 cm2 s-1 and va' = (-5.55±0.05)⋅10-7 cm s-1, respectively). Moreover, it was found, that the dithranol photodegradation rate in the non-steady state system is slower compared to the steady-state case; the effect was attributed to different permeation rates of dithranol and mobile Vaseline particles through the membrane.

Fabrication of Coaxial and Confocal Transducer Based on Sol-Gel Composite Material for Optical Resolution Photoacoustic Microscopy.

We have newly developed coaxial and confocal optical-resolution photoacoustic microscopy based on sol-gel composite materials. This transducer contains a concave-shaped piezoelectric layer with a focus depth of 5 mm and a hole with a diameter of 3 mm at the center to pass a laser beam into a phantom. Therefore, this system can directly detect an excited photoacoustic signal without prisms or acoustic lenses. We demonstrate the capability of the system through pulse-echo and photoacoustic imaging experiments. The center frequency of the fabricated transducer is approximately 7 MHz, and its relative bandwidth is 86%. An ex-vivo experiment is conducted, and photoacoustic signals are clearly obtained. As a result, 2- and 3-dimensional maximum amplitude projection images are reconstructed.

Photoacoustic imaging depth comparison at 532-, 800-, and 1064-nm wavelengths: Monte Carlo simulation and experimental validation

.Photoacoustic imaging (PAI) provides high-resolution and high-optical-contrast imaging beyond optical diffusion limit. Further improvement in imaging depth has been achieved by using near-infrared window-I (NIR-I, 700 to 900 nm) for illumination, due to lower scattering and absorption by tissues in this wavelength range. Recently, near-infrared window-II (NIR-II, 900 to 1700 nm) has been explored for PAI. We studied the imaging depths in biological tissues for different illumination wavelengths in visible, NIR-I, and NIR-II regions using Monte Carlo (MC) simulations and validated with experimental results. MC simulations were done to compute fluence in tissue, absorbance in blood vessel, and in a spherical absorber (mimicking sentinel lymph node) embedded at different depths in breast tissue. Photoacoustic tomography and acoustic resolution photoacoustic microscopy experiments were conducted to validate the MC results. We demonstrate that maximum imaging depth is achieved by wavelengths in NIR-I window () when the energy density deposited is same for all wavelengths. However, illumination using wavelengths around 1064 nm (NIR-II window) gives the maximum imaging depth when the energy density deposited is proportional to maximum permissible exposure (MPE) at corresponding wavelength. These results show that it is the higher MPE of NIR-II window that helps in increasing the PAI depth for chromophores embedded in breast tissue.

Biodegradable Biliverdin Nanoparticles for Efficient Photoacoustic Imaging.

Photoacoustic imaging has emerged as a promising imaging platform with a high tissue penetration depth. However, biodegradable nanoparticles, especially those for photoacoustic imaging, are rare and limited to a few polymeric agents. The development of such nanoparticles holds great promise for clinically translatable diagnostic imaging with high biocompatibility. Metabolically digestible and inherently photoacoustic imaging probes can be developed from nanoprecipitation of biliverdin, a naturally occurring heme-based pigment. The synthesis of nanoparticles composed of a biliverdin network, cross-linked with a bifunctional amine linker, is achieved where spectral tuning relies on the choice of reaction media. Nanoparticles synthesized in water or water containing sodium chloride exhibit higher absorbance and lower fluorescence compared to nanoparticles synthesized in 2-(N-morpholino)ethanesulfonic acid buffer. All nanoparticles display high absorbance at 365 and 680 nm. Excitation at near-infrared wavelengths leads to a strong photoacoustic signal, while excitation with ultraviolet wavelengths results in fluorescence emission. In vivo photoacoustic imaging experiments in mice demonstrated that the nanoparticles accumulate in lymph nodes, highlighting their potential utility as photoacoustic agents for sentinel lymph node detection. The biotransformation of these agents was studied using mass spectroscopy, and they were found to be completely biodegraded in the presence of biliverdin reductase, a ubiquitous enzyme found in the body. Degradation of these particles was also confirmed in vivo. Thus, the nanoparticles developed here are a promising platform for biocompatible biological imaging due to their inherent photoacoustic and fluorescent properties as well as their complete metabolic digestion.

Improved adsorption and photocatalytic removal of methylene blue by MoO3 thin films: Role of the sputtering power, film thickness, and sputtering working pressure

The role of the sputtering power, film thickness, and sputtering working pressure on the adsorption capacity and photocatalytic activity of MoO3 thin films was studied. The MoO3 thin films were deposited at room temperature by radio frequency reactive magnetron sputtering and subsequently post-annealed in air at 500 °C. X-ray diffractograms revealed the presence of the α- and β-MoO3 crystalline phases. The thin film adsorption was assessed by the removal of methylene blue (MB) from aqueous solutions under dark conditions. In addition, the photocatalytic activity for the most adsorbent films was evaluated by the degradation of MB aqueous solutions under UV-irradiation. Raman spectroscopy measurements showed a strong MB adsorption on the film surface. Photoacoustic spectroscopy experiments confirmed the adsorption of MB on the catalyst surface; specifically, a strong hypsochromic shift of the absorption bands indicated that MB forms aggregates on the MoO3 surface. The maximum adsorption and photocatalytic performances were observed for the samples deposited at 60 W and 12.0 mTorr, with a thickness of 400 nm. The results are explained in terms of the stoichiometry, as well as the structural, optical, and morphological properties of the films.

3D Photoacoustic Tomography System Based on Full-View Illumination and Ultrasound Detection

A 3D photoacoustic computed tomography (3D-PACT) system based on full-view illumination and ultrasound detection was developed and applied to 3D photoacoustic imaging of several phantoms. The system utilized an optics cage design to achieve full-view uniform laser illumination and completed 3D scanning with the rotation of a dual-element transducer (5 MHz) and the vertical motion of imaging target, which obtains the best solution in the mutual restriction relation between cost and performance. The 3D-PACT system exhibits a spatial resolution on the order of 300 μm, and the imaging area can be up to 52 mm in diameter. The transducers used in the system provides tomography imaging with large fields of view. In addition, the coplanar uniform illumination and acoustic detection configuration based on a quartz bowl greatly enhances the efficiency of laser illumination and signal detection, making it available for use on samples with irregular surfaces. Performance testing and 3D photoacoustic experiments on various phantoms verify that the system can perform 3D photoacoustic imaging on targets with complex surfaces or large sizes. In future, efforts will be made to achieve full-body 3D tomography of small animals and a multimodal 3D imaging system.

Novel hyaluronic acid-modified temperature-sensitive nanoparticles for synergistic chemo-photothermal therapy

This study has developed a versatile nano-system with the combined advantages of photothermal effect, active tumor-targeting, temperature-sensitive drug release, and photoacoustic imaging. The nano-system consists of the core of the phase change material (PCM), the outer polypyrrole (PPY) shell and the hyaluronic acid (HA) modified in the PPY shell. The obtained composite nanoparticles (denoted as DTX/PPN@PPY@HA) were spherical with a mean diameter of about 232.7 nm. In vivo and in vitro photoacoustic imaging experiments show that DTX/PPN@PPY@HA is an effective photoacoustic contrast agent, which can be used for accurate localization of tumor region and real-time guidance of photothermal chemotherapy. DTX/PPN@PPY@HA shows good photothermal effects and temperature-sensitive drug release. In addition, cellular experiments showed that DTX/PPN@PPY@HA could be efficiently internalized into tumor cells and produce significant cytotoxicity with the help of near-infrared (NIR) laser. Furthermore, the remarkable inhibition of DTX/PPN@PPY@HA against tumor growth was achieved in 4T1 tumor-bearing mice model.

Transmission and photoacoustic spectroscopy of organosulphur and aromatic hydrocarbons using coherent synchrotron radiation

This article describes transmission and photoacoustic spectroscopy experiments performed using coherent synchrotron radiation (CSR) at the Canadian Light Source. The storage ring was operated at energies of 1.0 and 1.5 GeV, with currents between 0.8 and 8.6 mA and synchrotron frequencies from 4.0 to 7.7 kHz. Relationships among these parameters and the associated energy curves were characterized in detail. Spectra of organosulphur and aromatic hydrocarbon compounds acquired using CSR exhibited absorption bands near 20 cm−1, likely due to translational and rotational motion in dimers. The location and extent of usable CSR can be modified through adjustment of the ring energy, synchrotron frequency, and ring current, making this radiation suitable for acquisition of spectra at very low wavenumbers.

A preliminary study of photoacoustic/ultrasound dual-mode imaging in melanoma using MAGE-targeted gold nanoparticles

Nanoprobes are small enough to circulate within the vasculature and can reach tumour tissues through the endothelial gap, providing a new strategy for accurate tumour monitoring and imaging-guided antitumour therapy at the molecular level. Both photoacoustic and ultrasonic imaging are noninvasive tools for cancer detection via the application of nanoprobes. In this study, a polymeric multifunctional nanoparticle probe loaded with gold nanorods (Au-NRs) and liquid perfluorocarbon (perfluorinated hexane/PFH) and conjugated to a monoclonal antibody (MAGE-1 antibody) to melanoma-associated antigens (MAGE) targeting melanoma was successfully prepared by the double emulsion and carbodiimide methods as a targeted photoacoustic/ultrasound dual-mode imaging contrast agent (MAGE-Au-PFH-NPs). Cell-targeting experiments in vitro showed large amounts of MAGE-Au-PFH-NPs surrounding B16 melanoma cells in the targeted group. The photoacoustic signal in the targeted group was significantly increased, and the duration was longer than that in the untargeted group in vivo. The photoacoustic signal of the nanoprobes was enhanced with increased Au-NR concentration in the photoacoustic experiment in vitro. The enhanced signal was observed by ultrasound after 808-nm laser irradiation. A cytotoxicity and biocompatibility test showed that MAGE-Au-PFH-NPs exhibited good biological safety. The MAGE-Au-PFH-NPs can be used as a photoacoustic/ultrasound dual-mode contrast agent to lay the foundation for a promising new approach for the noninvasive targeting, monitoring and treatment of tumours.

Molecular imaging of tumor photoimmunotherapy: Evidence of photosensitized tumor necrosis and hemodynamic changes.

Near-infrared photoimmunotherapy (NIR PIT) employs the photoabsorbing dye IR700 conjugated to antibodies specific for cell surface epidermal growth factor receptor (EGFR). NIR PIT has shown highly selective cytotoxicity in vitro and in vivo. Cell necrosis is thought to be the main mode of cytotoxicity based mainly on in vitro studies. To better understand the acute effects of NIR PIT, molecular imaging studies were performed to assess its cellular and vascular effects. In addition to in vitro studies for cytotoxicity of NIR PIT, the in vivo tumoricidal effects and hemodynamic changes induced by NIR PIT were evaluated by 13C MRI using hyperpolarized [1,4-13C2] fumarate, R2* mapping from T2*-weighted MRI, and photoacoustic imaging. In vitro studies confirmed that NIR PIT resulted in rapid cell death via membrane damage, with evidence for rapid cell expansion followed by membrane rupture. Following NIR PIT, metabolic MRI using hyperpolarized fumarate showed the production of malate in EGFR-expressing A431 tumor xenografts, providing direct evidence for photosensitized tumor necrosis induced by NIR PIT. R2* mapping studies showed temporal changes in oxygenation, with an accompanying increase of deoxyhemoglobin at the start of light exposure followed by a sustained decrease after cessation of light exposure. This result suggests a rapid decrease of blood flow in EGFR-expressing A431 tumor xenografts, which is supported by the results of the photoacoustic imaging experiments. Our findings suggest NIR PIT mediates necrosis and hemodynamic changes in tumors by photosensitized oxidation pathways and that these imaging modalities, once translated, may be useful in monitoring clinical treatment response.

TDDFT calculations and photoacoustic spectroscopy experiments used to identify phenolic acid functional biomolecules in Brazilian tropical fruits in natura

Time-dependent density functional theory (TDDFT) calculations of electronic transitions have been widely used to determine molecular structures. The excitation wavelengths and oscillator strengths obtained with the hybrid exchange-correlation functional B3LYP in conjunction with the ADZP basis set are employed to simulate the UV–Vis spectra of eight phenolic acids. Experimental and theoretical UV–Vis spectra reported previously in the literature are compared with our results. The fast, sensitive and non-destructive technique of photoacoustic spectroscopy (PAS) is used to determine the UV–Vis spectra of four Brazilian tropical fresh fruits in natura. Then, the PAS along with the TDDFT results are for the first time used to investigate and identify the presence of phenolic acids in the fruits studied in this work. This theoretical method with this experimental technique show to be a powerful and cheap tool to detect the existence of phenolic acids in fruits, vegetables, cereals, and grains. Comparison with high performance liquid chromatography results, when available, is also carried out.

Photoacoustic imaging in scattering media by combining a correlation matrix filter with a time reversal operator

Acoustic scattering medium is a fundamental challenge for photoacoustic imaging. In this study, we reveal the different coherent properties of the scattering photoacoustic waves and the direct photoacoustic waves in a matrix form. Direct waves show a particular coherence on the antidiagonals of the matrix, whereas scattering waves do not. Based on this property, a correlation matrix filter combining with a time reversal operator is proposed to preserve the direct waves and recover the image behind a scattering layer. Both numerical simulations and photoacoustic imaging experiments demonstrate that the proposed approach effectively increases the image contrast and decreases the background speckles in a scattering medium. This study might improve the quality of photoacoustic imaging in an acoustic scattering environment and extend its applications.

A Marchenko equation for acoustic inverse source problems.

From acoustics to medical imaging and seismology, one strives to make inferences about the structure of complex media from acoustic wave observations. This study proposes a solution that is derived from the multidimensional Marchenko equation, to learn about the acoustic source distribution inside a volume, given a set of observations outside the volume. Traditionally, this problem has been solved by backpropagation of the recorded signals. However, to achieve accurate results through backpropagation, a detailed model of the medium should be known and observations should be collected along a boundary that completely encloses the volume of excitation. In practice, these requirements are often not fulfilled and artifacts can emerge, especially in the presence of strong contrasts in the medium. On the contrary, the proposed methodology can be applied with a single observation boundary only, without the need of a detailed model. In order to achieve this, additional multi-offset ultrasound reflection data must be acquired at the observation boundary. The methodology is illustrated with one-dimensional synthetics of a photoacoustic imaging experiment. A distribution of simultaneously acting sources is recovered in the presence of sharp density perturbations both below and above the embedded sources, which result in significant scattering that complicates the use of conventional methods.

Analysis of the Measurement System and Optimization of the Measurement Procedure for Detection of Thermal Memory Effects by Photoacoustic Experiments

Experimental verification of thermal memory effects represents a challenge that is important from both fundamental and practical points of view. Recent theoretical studies suggest that the thermal memory effect should lead to thermal resonances in the modulation frequency characteristics of photoacoustic response. Therefore, studies of thermal resonances in photoacoustic response represent an alternative for detection of the thermal memory effect and measurement of thermal memory properties. Since the resonances were not observed, this paper analyzes standard measurement setups and shows that the experimental technique should be optimized to provide a better chance of detection of thermal memory effects by photoacoustic measurements. The results show that a proper selection of modulation frequencies and the knowledge of the approximate transfer function of the electronic part of the photoacoustic measurement system are prerequisites for detection of thermal resonances in the modulation frequency characteristics of photoacoustic response.

Targeted multifunctional nanoparticles probe mediated photoacoustic imaging and treatment study of breast carcinoma in vitro

Objective To investigate the ability of targeting in vitro breast carcinoma and photoacoustic-mediate apoptosis of breast carcinoma of the nanoparticle probe loaded with Fe3O4 and observe its consequence of photoacoustic imaging in vitro. Methods The polymeric multifunctional nanoparticles probe that was loaded with Fe3O4 and connected with Herceptin targeting breast carcinoma was prepared in the use of double emulsion method and carbodiimide method. General physical property, the condition of Herceptin connected with nanoparticles and the ability of targeting of the probe were tested. The different concentration of nanoparticles was imaged by photoacoustic. The inhibiting effect of targeting nanoparticles on breast carcinoma cells was evaluated in vitro. Results The targeting polymeric multifunctional nanoparticles probes loaded with Fe3O4 were prepared successfully with average particle diameter of (235.4±53.75)nm and Zeta potential (-13.4±4.7)mV. Fe3O4 particles dispersed on the shell of the probes. Antibody Herceptin was successfully connected with the surface of the nanoprobes. There were massive targeting nanoprobes surround the breast carcinoma cell strains SKBR3 in the targeting group in vitro. The photoascoustic signal of the nanoprobes enhanced with the increase of Fe3O4 concentration in photoacoustic experiment in vitro. The apoptotic rate of breast carcinoma increased after the laser irradiation in the cell inhibition experiment in vitro. That proved the obvious inhibition of breast carcinoma cells was caused by photothermal effect of the prepared nanoprobes. Conclusions The prepared polymeric multifunctional nanoparticles probe that was loaded with Fe3O4 and connected with Herceptin targeting breast carcinoma can be used as a photoacoustic contrast agent, which can inhibit the proliferation of breast carcinoma by targeting photoacoustic therapy. Key words: Photoacoustic techniques; Targeted nanoparticle probe; Breast neoplasms; Magnetite nanoparticles

Photoacoustic sensor for trace detection of post-blast explosive and hazardous molecules

The development of a sensor based on laser photoacoustic spectroscopic technique for detection of nanogram quantity of hazardous molecules, drugs and post-blast explosive is discussed. Traces of explosive and hazardous molecules on nanogram scales collected by swiping small pieces of paper on the contaminated surfaces have been detected. The Photoacoustic cell used in the sensor is of T type. The cell is designed using COMSOL software and developed with a compatible sensitive microphone. The photoacoustic signal is detected via indirect method. Sample kept in the cell was not in direct contact of the microphone. Indirect photoacoustic experiments have been done in closed cell. Tunable quantum cascade laser having tunability in the wavelength range of 7–9μm (wavenumber 1400–1100cm−1) was used in the experiments. A phase sensitive data acquisition system has also been developed. The developed sensor is capable to identify traces of explosives up to the order of ppb level in post blast materials.

Helmholtz Resonances in Photoacoustic Experiment with Laser-Sintered Polyamide Including Thermal Memory of Samples

A minimum volume photoacoustic (PA) cell, employed as an acoustic resonator, is presented. A model of the PA cell transfer function, as a combination of two Helmholtz resonators, is derived. Frequency PA response is described as the product of theoretically derived pressure variation and the transfer function of the PA cell. The derived model is applied to the frequency PA measurements, performed on laser-sintered polyamide. It is shown that the derived model explains the occurrence of resonant peaks in the high-frequency domain (\({>}\)10 kHz), in both amplitude and phase measurements, obtained by a gas-microphone minimal volume PA cell. The implementation of the model in the growing possibilities of sample characterization using gas-microphone PA cell is discussed.

Effect of the absorption coefficient of aluminium plates on their thermoelastic bending in photoacoustic experiments

The open-cell photoacoustic signal measured in the transmission configuration for aluminum thin plates with thicknesses of 280 μm, 197 μm, and 112 μm is experimentally and theoretically analyzed, in the 20 Hz–7 kHz modulation frequency range. It is shown that the observed differences between the predictions of the standard thermoelastic model and the experiment data of both the amplitude and phase of the photoacoustic signal can be overcome by considering the aluminum samples coated with a thin layer of black paint as volume-absorber materials. This new approach provides a quite good agreement with the obtained experimental data, in the whole frequency range, and yields an effective absorption coefficient of (16 ± 2) mm−1, for a 280 μm-thick sample. The introduction of the finite absorption coefficient led to the correct ratio between the thermal diffusion and thermoelastic components of the photoacoustic signal. Furthermore, it is found that the “volume-absorber” approach accurately describes the behavior of the amplitude, but not that of the phase recorded for a 112 μm-thick sample, due to its relatively strong thermoelastic bending, which is not considered by this theory. Within the approximation of the small bending, the proposed “volume-absorber” model provides a reliable description of the photoacoustic signal for Al samples thicker than 112 μm, and extends the applicability of the classical “opaque” approach.

Near-Infrared Squaraine Dye Encapsulated Micelles for in Vivo Fluorescence and Photoacoustic Bimodal Imaging.

Combined near-infrared (NIR) fluorescence and photoacoustic imaging techniques present promising capabilities for noninvasive visualization of biological structures. Development of bimodal noninvasive optical imaging approaches by combining NIR fluorescence and photoacoustic tomography demands suitable NIR-active exogenous contrast agents. If the aggregation and photobleaching are prevented, squaraine dyes are ideal candidates for fluorescence and photoacoustic imaging. Herein, we report rational selection, preparation, and micelle encapsulation of an NIR-absorbing squaraine dye (D1) for in vivo fluorescence and photoacoustic bimodal imaging. D1 was encapsulated inside micelles constructed from a biocompatible nonionic surfactant (Pluoronic F-127) to obtain D1-encapsulated micelles (D1(micelle)) in aqueous conditions. The micelle encapsulation retains both the photophysical features and chemical stability of D1. D1(micelle) exhibits high photostability and low cytotoxicity in biological conditions. Unique properties of D1(micelle) in the NIR window of 800-900 nm enable the development of a squaraine-based exogenous contrast agent for fluorescence and photoacoustic bimodal imaging above 820 nm. In vivo imaging using D1(micelle), as demonstrated by fluorescence and photoacoustic tomography experiments in live mice, shows contrast-enhanced deep tissue imaging capability. The usage of D1(micelle) proven by preclinical experiments in rodents reveals its excellent applicability for NIR fluorescence and photoacoustic bimodal imaging.

Organosilicon phantom for photoacoustic imaging.

Photoacoustic imaging is an emerging technique. Although commercially available photoacoustic imaging systems currently exist, the technology is still in its infancy. Therefore, the design of stable phantoms is essential to achieve semiquantitative evaluation of the performance of a photoacoustic system and can help optimize the properties of contrast agents. We designed and developed a polydimethylsiloxane (PDMS) phantom with exceptionally fine geometry; the phantom was tested using photoacoustic experiments loaded with the standard indocyanine green dye and compared to an agar phantom pattern through polyethylene glycol-gold nanorods. The linearity of the photoacoustic signal with the nanoparticle number was assessed. The signal-tonoiseratio and contrast were employed as image quality parameters, and enhancements of up to 50 and up to 300%, respectively, were measured with the PDMS phantom with respect to the agar one. A tissue-mimicking (TM)-PDMS was prepared by adding TiO2 and India ink; photoacoustic tests were performed in order to compare the signal generated by the TM-PDMS and the biological tissue. The PDMS phantom can become a particularly promising tool in the field of photoacoustics for the evaluation of the performance of a PA system and as a model of the structure of vascularized soft tissues.