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Efficient visualization of the vascular system is of key importance in biomedical research into tumor angiogenesis, cerebrovascular alterations, and other angiopathies. Optoacoustic (OA) angiography offers a promising solution combining molecular optical contrast with high resolution and deep penetration of ultrasound. However, its hybrid nature implies complex data collection and processing workflows, with significant variability in methodologies across developers and users. To streamline interoperability, we introduce SKYQUANT 3D, a Python‐based set of instructions for the Thermo Fisher Scientific Amira/Avizo 3D Visualization & Analysis Software. Our workflow simplifies the batch processing of volumetric optoacoustic angiography images, extracting meaningful quantitative information while also providing statistical analysis and graphical representation of the results. Quantification performance of SKYQUANT 3D is demonstrated using functional preclinical and clinical in vivo 3D OA angiographic tests involving ambient temperature variations and repositioning of the imaged limb. [ABSTRACT FROM AUTHOR]

Periodontitis is a public issue and imaging periodontal pocket is important to evaluate periodontitis. Regular linear transducers have limitations in imaging the posterior teeth due to their geometry restrictions. Here we characterized a transducer that can image the posterior teeth including assessment of periodontal pockets via a combination of photoacoustic and ultrasound imaging. Unlike conventional transducer design, this device has a toothbrush-shaped form factor with a side-view transducer to image molars (total size: 1 ×1.9 cm). A laser diode was integrated as the light source to reduce the cost and size and facilitates clinical transition. The in vivo imaging of a molar of a periodontal patient demonstrated that the transducer could image in the posterior area of gum in vivo; the value determined by imaging was within 7 % of the value measured clinically.

Inflammatory bowel disease (IBD) comprises a group of relapsing, chronic diseases of the gastrointestinal tract that, in addition to adults, can affect children and adolescents. To detect relapses of inflammation, these patients require close observation, frequent follow-up, and therapeutic adjustments. While reference standard diagnostics include anamnestic factors, laboratory and stool sample assessment, performing specific imaging in children and adolescents is much more challenging than in adults. Endoscopic and classic cross-sectional imaging modalities may be invasive and often require sedation for younger patients. For this reason, intestinal ultrasound (IUS) is becoming increasingly important for the non-invasive assessment of the intestine and its inflammatory affection. In this review, we would like to shed light on the current state of the art and provide an outlook on developments in this field that could potentially spare these patients more invasive follow-up procedures. [ABSTRACT FROM AUTHOR]

SIGNIFICANCE: Photoacoustic imaging has shown advantages over the periodontal probing method in measuring the periodontal probing depth, but the large size of conventional photoacoustic transducers prevents imaging of the more posterior teeth. AIM: Our aim is to develop a photoacoustic imaging system to image the more posterior periodontal pocket. APPROACH: We report a clinical hockey-stick-style transducer integrated with fibers for periodontal photoacoustic imaging. Cuttlefish ink labeled the periodontal pocket as the photoacoustic contrast agent. RESULTS: We characterized the imaging system and then measured the pocket depth of 35 swine teeth. Three raters evaluated the performance of the hockey-stick transducer. The measurements between the Williams probing (gold standard) and the photoacoustic methods were blinded but highly correlated. We showed a bias of ∼0.3  mm for the imaging-based technique versus Williams probing. The minimum inter-reliability was over 0.60 for three different raters of varying experience, suggesting that this approach to measure the periodontal pocket is reproducible. Finally, we imaged three pre-molars of a human subject. We could access more upper and posterior teeth than conventional linear transducers. CONCLUSIONS: The unique angle shape of the hockey-stick transducer allows it to image more posterior teeth than regular linear transducers. This study demonstrated the ability of a hockey-stick transducer to measure the periodontal pocket via photoacoustic imaging.

Increasing the efficiency of non-destructive control of lamellar materials with single and double-layer structure is an urgent scientific and technical task. The aim of the work was to investigate the peculiarities of excitation and reception of plate waves (PW) in single-layer and two-layer materials by pulsed laser radiation in relation to detection of cracks in them and estimation of layer thickness at one-sided sounding. A methodology has been developed and experimental studies of the influence of moving the area of laser generation of PW over the surface of dural samples relative to the crack simulator of different depth with the subsequent reception of the signal at a characteristic angle of inclination have been carried out. A significant change in the structure of the wave front at localization of the moving wave source zone in the vicinity of the crack simulator was found, accompanied by a change in the ratio of extreme values of amplitudes of the received asymmetric mode Aextr up to 14–15 dB. At receiving the symmetric s0 mode the value of Aextr does not exceed 3–4 dB. The interpretation of this effect is given. A method and scheme of thickness measurement of twolayer materials with metallized coating and non-metallic base (glass-textolite) is proposed and developed, where samples with copper coating and glass-textolite base of different thickness are used as an example. In this case, the velocity or propagation time of PW, between two small aperture (non-directional) transducers with an acoustic base of 43 mm, is used as an informative parameter. In this case, the estimated sensitivity of the measured circuit to changes in the thickness of the metal coating is of 0.5 μm, and the base – twice as much.

The work is devoted to an overview of the current state of optoacoustic fiber-optic ultrasonic transducers based on thermoelastic effect and fiber-optic interference receivers, its scope, technologies and materials used, the advantages and disadvantages of different methods and the prospects for the development of the industry.

Peripheral arterial disease (PAD) leads to chronic vascular occlusion and results in end organ damage in critically perfused limbs. There are currently no clinical methods available to determine the muscular damage induced by chronic mal-perfusion. This monocentric prospective cross-sectional study investigated n = 193 adults, healthy to severe PAD, in order to quantify the degree of calf muscle degeneration caused by PAD using a non-invasive hybrid ultrasound and single wavelength optoacoustic imaging (US/SWL-OAI) approach. While US provides morphologic information, SWL-OAI visualizes the absorption of pulsed laser light and the resulting sound waves from molecules undergoing thermoelastic expansion. US/SWL-OAI was compared to multispectral data, clinical disease severity, angiographic findings, phantom experiments, and histological examinations from calf muscle biopsies. We were able to show that synergistic use of US/SWL-OAI is most likely to map clinical degeneration of the muscle and progressive PAD.

Abstract Background Cationic dyes are widely used as biomarkers for optical imaging. However, most of these are hydrophobic and cannot be employed in vivo without chemical conjugation or modification. Herein, we report for the first time the use of bacterial outer membrane vesicles (OMVs) as nanocarriers of cationic dyes for cancer theranostics. Results We demonstrate that cationic dyes (IR780, Cy7, and Cy7.5) form stable complexes with negatively charged bacterial-OMVs, improving the dyes’ in vivo circulation and optoacoustic properties. Such OMV-Dye complexes are biodegradable and safe for in vivo applications. Importantly, this method of cationic dye loading is faster and easier than synthetic chemistry approaches, and the efficient tumor accumulation of OMV-Dyes enables sensitive tumor detection using optoacoustic technology. As a proof-of-concept, we generated OMV-IR780 for optoacoustics-guided in vivo tumor phototherapy in a mouse model. Conclusions Our results demonstrate cationic dye-bound OMVs as promising novel nanoagents for tumor theranostics.

Real‐time imaging and functional assessment of the intestinal tract and its transit pose a significant challenge to conventional clinical diagnostic methods. Multispectral optoacoustic tomography (MSOT), a molecular‐sensitive imaging technology, offers the potential to visualize endogenous and exogenous chromophores in deep tissue. Herein, a novel approach using the orally administered clinical‐approved fluorescent dye indocyanine green (ICG) for bedside, non‐ionizing evaluation of gastrointestinal passage is presented. The authors are able to show the detectability and stability of ICG in phantom experiments. Furthermore, ten healthy subjects underwent MSOT imaging at multiple time points over eight hours after ingestion of a standardized meal with and without ICG. ICG signals can be visualized and quantified in different intestinal segments, while its excretion is confirmed by fluorescent imaging of stool samples. These findings indicate that contrast‐enhanced MSOT (CE‐MSOT) provides a translatable real‐time imaging approach for functional assessment of the gastrointestinal tract. [ABSTRACT FROM AUTHOR]

Parkinson's disease is a devastating neurodegenerative disorder characterized by loss of neuromelanin‐containing dopaminergic neurons. Novel 3D culture systems like human midbrain‐like organoids (hMOs) enable new research avenues for patient‐specific therapies, but cannot reach their full potential unless rapid optical imaging of entire organoids is enabled. Currently, hMOs have to undergo tissue clearing processes before imaging to overcome light scattering. Since tissue clearing is a lengthy chemical procedure, large ensemble studies and pharmacological longitudinal studies, which require live cultures, are impossible. To address this obstacle, raster scanning optoacoustic mesoscopy (RSOM) is considered for imaging intact hMOs. RSOM is an optical imaging technique that leverages the optoacoustic effect to overcome the need of tissue clearing. Moreover, by using tomographic principles, large specimens can be imaged within minutes. The results confirm that RSOM can image the neuromelanin distribution in complete hMOs at a single‐cell resolution. Whole hMO volumes of standard size can be imaged in 4 min. Comparison with bright‐field microscopy and histology confirms the ground truth of the RSOM images. This work opens several research opportunities regarding neuromelanin in hMOs with potential to boost research in Parkinson disease. [ABSTRACT FROM AUTHOR]

Background and Purpose: Novel light‐ and sound‐based technologies like multispectral optoacoustic tomography (MSOT) with co‐registered reflected‐ultrasound computed tomography (RUCT) could add additional value to conventional ultrasound (US) for disease phenotyping in pediatric spinal muscular atrophy (SMA). The aim of this study was to investigate the quality of RUCT compared to US for qualitative and quantitative assessment of imaging neuromuscular disorders. Methods: Subanalyzing the MSOT SMA study, 288 RUCT and 276 US images from 10 SMA patients (mean age 9.0 ± 3.7) and 10 gender‐ and age‐matched healthy volunteers (HV; mean age 8.7 ± 4.3) were analyzed for quantitative (grayscale levels [GSLs]) and qualitative (echogenicity, distribution pattern, Heckmatt scale, and muscle texture) muscle changes. RUCT and US measures were further correlated with clinical standard motor outcomes. Results: Quantitative agreement using GSLs revealed significantly higher GSLs in muscles of SMA patients compared to healthy muscles in both techniques (US mean GSL [SD] SMA vs. HV: 110.70 [27.8] vs. 68.85 [19.2], p <.0001; RUCT mean GSL [SD] SMA vs. HV: 91.81 [21.8] vs. 59.86 [8.2], p <.0001) with good correlation with motor outcome tests, respectively. Qualitative agreement between methods for muscle composition was excellent for differentiation of pathological versus healthy muscles, echogenicity, and distribution pattern, moderate for Heckmatt scale, and poor for muscle texture. Conclusions: The data suggest that RUCT may allow the assessment of basic qualitative and quantitative measures for muscular diseases with comparable results to conventional US. [ABSTRACT FROM AUTHOR]

Background: Cationic dyes are widely used as biomarkers for optical imaging. However, most of these are hydrophobic and cannot be employed in vivo without chemical conjugation or modification. Herein, we report for the first time the use of bacterial outer membrane vesicles (OMVs) as nanocarriers of cationic dyes for cancer theranostics. Results: We demonstrate that cationic dyes (IR780, Cy7, and Cy7.5) form stable complexes with negatively charged bacterial-OMVs, improving the dyes' in vivo circulation and optoacoustic properties. Such OMV-Dye complexes are biodegradable and safe for in vivo applications. Importantly, this method of cationic dye loading is faster and easier than synthetic chemistry approaches, and the efficient tumor accumulation of OMV-Dyes enables sensitive tumor detection using optoacoustic technology. As a proof-of-concept, we generated OMV-IR780 for optoacoustics-guided in vivo tumor phototherapy in a mouse model. Conclusions: Our results demonstrate cationic dye-bound OMVs as promising novel nanoagents for tumor theranostics. [ABSTRACT FROM AUTHOR]

Abstract Real‐time imaging and functional assessment of the intestinal tract and its transit pose a significant challenge to conventional clinical diagnostic methods. Multispectral optoacoustic tomography (MSOT), a molecular‐sensitive imaging technology, offers the potential to visualize endogenous and exogenous chromophores in deep tissue. Herein, a novel approach using the orally administered clinical‐approved fluorescent dye indocyanine green (ICG) for bedside, non‐ionizing evaluation of gastrointestinal passage is presented. The authors are able to show the detectability and stability of ICG in phantom experiments. Furthermore, ten healthy subjects underwent MSOT imaging at multiple time points over eight hours after ingestion of a standardized meal with and without ICG. ICG signals can be visualized and quantified in different intestinal segments, while its excretion is confirmed by fluorescent imaging of stool samples. These findings indicate that contrast‐enhanced MSOT (CE‐MSOT) provides a translatable real‐time imaging approach for functional assessment of the gastrointestinal tract.

Inflammatory bowel disease (IBD) comprises a group of relapsing, chronic diseases of the gastrointestinal tract that, in addition to adults, can affect children and adolescents. To detect relapses of inflammation, these patients require close observation, frequent follow-up, and therapeutic adjustments. While reference standard diagnostics include anamnestic factors, laboratory and stool sample assessment, performing specific imaging in children and adolescents is much more challenging than in adults. Endoscopic and classic cross-sectional imaging modalities may be invasive and often require sedation for younger patients. For this reason, intestinal ultrasound (IUS) is becoming increasingly important for the non-invasive assessment of the intestine and its inflammatory affection. In this review, we would like to shed light on the current state of the art and provide an outlook on developments in this field that could potentially spare these patients more invasive follow-up procedures.

The proper design of near-infrared light-absorbing agents enables efficient optoacoustic imaging-guided phototherapy. In particular, several croconaine-based organic agents with excellent optical properties have been recently reported for this purpose. However, most of them absorb light below 800 nm, limiting deep-tissue imaging applications. To this end, we utilized a recently described novel croconaine derivative (CR880) to develop CR880-based nanoparticles (CR880-NPs) for effective in vivo delivery, deep tissue optoacoustic imaging and photothermal therapy applications. Radicals and strong π–π stacking in CR880 result in an 880 nm absorption peak with no blue-shift upon condensing to the solid phase. DSPE-PEG2000-formulated CR880-NPs exhibited high optoacoustic generation efficiency and photostability, and could be visualized in the tumors of three different mouse tumor models (breast, brain, and colon tumor) with high image contrast. The high photothermal conversion efficiency of CR880-NPs (∼58%) subsequently enabled efficient in vivo tumor elimination using a low energy laser, while remaining biocompatible and well-tolerated. This work introduces a promising novel agent for cancer theranostics of challenging deep-seated tumors.

A number of optoacoustic (or photoacoustic) microscopy and mesoscopy techniques have successfully been employed for non-invasive tumor angiography. However, accurate rendering of tortuous and multidirectional neoplastic vessels is commonly hindered by the limited aperture size, narrow bandwidth and insufficient angular coverage of commercially available ultrasound transducers. We exploited the excellent flexibility and elasticity of a piezo polymer (PVDF) material to devise a fisheye-shape ultrasound detector with a high numerical aperture of 0.9, wide 1–30 MHz detection bandwidth and 27 mm diameter aperture suitable for imaging tumors of various size. We show theoretically and experimentally that the wide detector’s view-angle and bandwidth are paramount for achieving a detailed visualization of the intricate arbitrarily-oriented neovasculature in experimental tumors. The developed approach is shown to be well adapted to the tasks of experimental oncology thus allows to better exploit the angiographic potential of optoacoustics.

Photoacoustic flow cytometry is a method to detect rare analytes in fluids. We developed photoacoustic flow cytometry to detect pathological cells in body fluids, such as circulating tumor cells or bacteria in blood. In order to induce specific optical absorption in bacteria, we use modified bacteriophage that precisely target bacterial species or subspecies for rapid identification. In order to reduce detection variability and to halt the lytic lifescycle that results in lysis of the bacteria, we attached dyed latex microspheres to the tail fibers of bacteriophage that retained the bacterial recognition binding sites. We tested these microsphere complexes using Salmonella enterica (Salmonella) and Escherichia coli (E. coli) bacteria and found robust and specific detection of targeted bacteria. In our work we used LT2, a strain of Salmonella, against K12, a strain of E. coli. Using Det7, a bacteriophage that binds to LT2 and not to K12, we detected an average of 109.3 ± 9.0 of LT2 versus 2.0 ± 1.7 of K12 using red microspheres and 86.7 ± 13.2 of LT2 versus 0.3 ± 0.6 of K12 using blue microspheres. These results confirmed our ability to selectively detect bacterial species using photoacoustic flow cytometry. [ABSTRACT FROM AUTHOR]

One of the important tasks in optoacoustics today is the development of methods and tools for generating high-frequency ultrasound (above 1 MHz) in liquids and other media. To expand the frequency range of ultrasound, it was proposed to use coatings consisting of focusing spheres on a fiber tip. The methodology of calculating the ultrasound spectra depending on the sphere size, index of refraction, and parameters of laser radiation was developed. Two cases of small and large spheres in strongly and weakly absorbing media were simulated. The experimental results were analyzed in the approximations allowing a fairly accurate estimation of the spectrum and indicatrix of the generated ultrasound upon laser excitation through a converter based on a coating of transparent spheres. A good agreement between the model and experimental result was obtained. [ABSTRACT FROM AUTHOR]

IntroductionAntibiotic resistance in bacterial species constitutes a growing problem in the clinical management of infections. Not only does it limit therapeutic options, but application of ineffective antibiotics allows resistant species to progress prior to prescribing more effective treatment to patients. Methicillin resistance in Staphylococcus aureus is a major problem in clinical infections as it is the most common hospital acquired infection.MethodsWe developed a photoacoustic flow cytometer using engineered bacteriophage as probes for rapid determination of methicillin resistance in Staphylococcus aureus with thirteen clinical samples obtained from keratitis patients. This method irradiates cells under flow with 532 nm laser light and selectively generates acoustic waves in labeled bacterial cells, thus enabling detection and enumeration of them. Staphylococcus aureus isolates were classified from culture isolation as either methicillin resistant or susceptible using cefoxitin disk diffusion testing. The photoacoustic method enumerates bacterial cells before and after treatment with antibiotics. Decreasing counts of bacteria after treatment indicate susceptible strains. We quantified the bacterial cells in the treated and untreated samples.ResultsUsing k-means clustering on the data, we achieved 100% concordance with the classification of Staphylococcus aureus resistance using culture.DiscussionPhotoacoustics can be used to differentiate methicillin resistant and susceptible strains of bacteria from ocular infections. This method may be generalized to other bacterial species using appropriate bacteriophages and testing for resistance using other antibiotics.

Thermally induced optical reflection of sound (THORS) provides a means to manipulate sound waves without the need for traditional acoustically engineered structures. By photothermally exciting a medium, with infrared light, a barrier can be formed due to abrupt changes in compressibility of the excited medium. Discovery and initial characterization of the THORS phenomenon utilized air saturated with ethanol vapor as the absorbing medium and a CO2 laser, operating at 9.6 µm, as the excitation source to achieve acoustic reflection efficiencies of 25–30% of the incident wave. In this work, we demonstrate for the first time, the ability to generate THORS barriers in ambient air (i.e., without the need for ethanol vapor). Employing atmospheric water vapor as the absorbing medium and a modulated, multiline carbon monoxide laser, operating at 5.5 ± 0.25 µm, THORS barriers capable of acoustic and ultrasonic reflection–suppression efficiencies greater than 70% are readily generated. To achieve these significant reflection–suppression efficiencies, the temporal dynamics of THORS barriers in ambient air were characterized using 300 kHz ultrasonic pulses incident on the barriers, revealing three different operational regimes. In the first regime, a single laser pulse generates a transient THORS barrier that lasts tens of milliseconds and exhibits minimal acoustic reflectivity. In the second regime, multiple laser pulses interact with the water vapor prior to complete relaxation of the THORS barrier from the previous excitation pulse, resulting in an additive response and reflectivity/suppression efficiencies as great as 72%. Finally, in the third regime, non-modulated continuous wave (CW) excitation of the water vapor occurs resulting in no measurable acoustic reflectivity/suppression from the THORS barrier. This work characterizes these different regimes and the optimal modulation timing to generate efficient continuous acoustic barriers using THORS. Graphical Abstract [ABSTRACT FROM AUTHOR]

The aim of this work is to generate defined tones that cover the human hearing range in aqueous media for a later application in middle or inner ear implants. In our experiments, we investigated the characteristics of single laser pulses and pulse trains with different laser repetition rates of nanosecond laser pulses that were focused into aqueous media in a small volume. The frequency of the generated tones was limited by the spectral properties of the single acoustic pulses, which depended on the medium. Tones with fundamental frequencies above 8 kHz were generated using laser pulses focused into water. By replacing water with gel, tones between 500 Hz and 20 kHz could be produced. The generation of tones in the low‐frequency range was only possible when laser pulse trains with pulse density modulated pulse patterns were applied in gel. This enabled the generation of tones between 20 Hz and 2 kHz. Consequently, the combination of different pulse patterns for the different frequency ranges allows generating optoacoustic tones between 20 Hz and 20 kHz in gel. Thus, we can cover the complete range of human hearing through optoacoustically generated tones. [ABSTRACT FROM AUTHOR]

Phthalocyanines (Pcs) are widely developed in cancer phototherapy due to their definite chemical structure and tunable photosensitivity. However, their in vivo application is hampered by low water solubility and non-specific biodistribution. Here,a strategy of sialylation-modulation is developed for the first time to highly improve the bioavailability of Pcs. The sialylated Pcs (ZnPc-4SA) not only has good hydrophilicity, but also can self-assemble into nanoparticles (ZnPc-4SA NPs). These nanoformulations retain the excellent photophysical properties of Pcs, which in turn reflects excellent optoacoustic and phototherapeutic properties. Importantly, ZnPc-4SA NPs exhibit boosted tumor accumulation due to the passive targeting and sialic acid-mediated E-selectin targeting. Besides, the phototoxicity of ZnPc-4SA NPs can effectively trigger cell apoptosis and tumor elimination upon laser irradiation. Therefore, sialylation engineering strategy provides a new option for hydrophobic drugs modification with enhanced tumor theranostics., (© 2024 Wiley‐VCH GmbH.)

Periodontitis is a public issue and imaging periodontal pocket is important to evaluate periodontitis. Regular linear transducers have limitations in imaging the posterior teeth due to their geometry restrictions. Here we characterized a transducer that can image the posterior teeth including assessment of periodontal pockets via a combination of photoacoustic and ultrasound imaging. Unlike conventional transducer design, this device has a toothbrush-shaped form factor with a side-view transducer to image molars (total size: 1 ×1.9 cm). A laser diode was integrated as the light source to reduce the cost and size and facilitates clinical transition. The in vivo imaging of a molar of a periodontal patient demonstrated that the transducer could image in the posterior area of gum in vivo; the value determined by imaging was within 7 % of the value measured clinically.

Microvascular changes in diabetes affect the function of several critical organs, such as the kidneys, heart, brain, eye, and skin, among others. The possibility of detecting such changes early enough in order to take appropriate actions renders the development of appropriate tools and techniques an imperative need. To this end, several sensing and imaging techniques have been developed or employed in the assessment of microangiopathy in patients with diabetes. Herein, we present such techniques; we provide insights into their principles of operation while discussing the characteristics that make them appropriate for such use. Finally, apart from already established techniques, we present novel ones with great translational potential, such as optoacoustic technologies, which are expected to enter clinical practice in the foreseeable future.

In optoacoustic (photoacoustic) tomography, several parameters related to tissue and detector features are needed for image formation, but they may not be known a priori. An autofocus (AF) algorithm is generally used to estimate these parameters. However, the algorithm works iteratively and is therefore impractical for clinical imaging with planar geometry systems due to the long reconstruction times. We have developed a fast autofocus (FAF) algorithm for 3D optoacoustic systems with planar geometry. Such an algorithm exploits the symmetries of the planar geometry and a virtual source concept to reduce the dimensionality of the parameter estimation problem. The dimensionality reduction makes FAF much simpler computationally than the conventional AF algorithm. We show that the FAF algorithm required about 5 s to provide accurate estimates of the speed of sound in simulated data and experimental data obtained using an imaging system that is poised to enter the clinic. The applicability of FAF for estimating other image formation parameters is discussed. We expect the FAF algorithm to contribute decisively to the clinical use of optoacoustic tomography systems with planar geometry. [ABSTRACT FROM AUTHOR]

An iterative algorithm to enhance the quality of optoacoustic images is proposed based on the Banach fixed point theorem. Numerical simulation of the propagation of ultrasound waves and image reconstruction for media with characteristics close to soft biological tissues has been performed. The problem of eliminating distortions and artifacts in optoacoustic images has been modeled for four iterative schemes. The efficiency of the approach has been demonstrated even for a few iterations. [ABSTRACT FROM AUTHOR]

• Piezopolymer detectors overcome the bandwidth limitation of piezoceramic detectors. • Damped piezopolymer detectors preserve broadband pulse shape in optoacoustic measurements. • PVDF-TrFE detectors achieve high sensitivity of 6.4 µV/Pa over a wide 1–30 MHz bandwidth. Piezoelectric detectors are integral part of modern ultrasound imaging systems. Their utility has also been extended beyond the established methodologies into the emerging realm of hybrid optoacoustic imaging. Conventional piezoceramic detectors, however, struggle to combine high detection sensitivity with ultrawide bandwidth, both considered critical for attaining optimal optoacoustic imaging performance. Our research, both theoretical and empirical, unveils that damped piezopolymer detectors fabricated from PVDF-TrFE are markedly capable of achieving a synergistic blend between broad bandwidth and superb sensitivity. Experimental evaluations reflected an average sensitivity of 15.5 µV/Pa within a 1–10 MHz band for a 120 µm thick detector and 6.4 µV/Pa within a 1–30 MHz band for a 20 µm thick detector, thus outperforming conventional piezoelectric analogues. The resultant noise equivalent pressure (NEPs) values were 0.3 Pa and 1.2 Pa for the 20 µm and 120 µm detectors, respectively. Our findings herald a significant stride towards enhancing the efficacy of ultrawideband ultrasound and optoacoustic imaging systems. [ABSTRACT FROM AUTHOR]

Photoacoustic (PA) imaging has the potential to revolutionize functional medical imaging in healthcare due to the valuable information on tissue physiology contained in multispectral photoacoustic measurements. Clinical translation of the technology requires conversion of the high-dimensional acquired data into clinically relevant and interpretable information. In this work, we present a deep learning-based approach to semantic segmentation of multispectral photoacoustic images to facilitate image interpretability. Manually annotated photoacoustic and ultrasound imaging data are used as reference and enable the training of a deep learning-based segmentation algorithm in a supervised manner. Based on a validation study with experimentally acquired data from 16 healthy human volunteers, we show that automatic tissue segmentation can be used to create powerful analyses and visualizations of multispectral photoacoustic images. Due to the intuitive representation of high-dimensional information, such a preprocessing algorithm could be a valuable means to facilitate the clinical translation of photoacoustic imaging.

In recent years, there has been a progressive trend towards less invasive technologies for detecting metastatic cancer and guiding therapy with the goal of lower morbidity, better outcomes, and superior cosmetic appearance than traditional methods. This mini-review examines three emerging noninvasive hybrid technologies for detecting primary cancer, metastasis and guiding thermal therapy. Real-time thermoacoustic imaging and thermometry potentially provides valuable and critical feedback for guiding focused microwave ablation therapy. Label-free photoacoustic monitoring of cancer cells is a promising clinical diagnostic and theranostic tool for detecting metastatic disease and monitoring the response to therapy. Finally, immunologically targeted gold nanoparticles combined with photoacoustic imaging is able to detect lymph node micrometastasis in mouse models of breast cancer. These emerging techniques have the potential to improve the decision to biopsy, provide more accurate prognosis, and enhance the efficacy of therapy for early and late stage cancers. [ABSTRACT FROM AUTHOR]

Photoacoustic computed tomography (PACT) has become a promising imaging modality from laboratory to clinical research. Of many components of PACT system, the ultrasound (US) array transducer is an essential device to simultaneously receive photoacoustic (PA) signals from several directions in a parallel manner. Many research groups and companies have developed various types of US array transducers while accounting the properties of the PA waves to achieve better image quality, deeper imaging depth, faster imaging speed, and a wider field of view. In this review, we present the implementation and application of the state-of-the-art PACT systems using several types of curved US arrays: arc-shaped, ring-shaped, and hemispherical array transducers. Furthermore, we discuss the current limitations of PACT and also potential future directions for enhancing them. [ABSTRACT FROM AUTHOR]

Optoacoustic (OA) spectral properties of various sources mimicking normal and pathological red blood cells (RBCs) have been studied. The shapes of normal RBC and cells suffering from stomatocytosis (denoted by ST) were generated using mathematical models. However, the shape corresponding to the cells affected by echinocytosis (referred to as ET) was constructed by uniformly distributing half prolate spheroids on a central spherical object. The OA field emitted by an acoustically inhomogeneous source was calculated for a wide acoustic frequency bandwidth (1–1500 MHz with an increment 5 MHz) by solving the time-independent wave equation employing a modified Green's function approach. The OA spectra averaged over 200 orientations for normal RBC and STs demonstrate similar features (one minimum occurring nearly at 906 MHz). The same graphs for ETs are remarkably different from that of normal RBC and exhibit better match with that of a spherical RBC (first minimum appearing at around 425 MHz). The spectral features of ETs above 425 MHz may enable us to differentiate diseased cells (echinocytosis) from normal RBCs. [ABSTRACT FROM AUTHOR]

Proximal spinal muscular atrophy (SMA) is a rare progressive, life limiting genetic motor neuron disease. While promising causal therapies are available, meaningful prognostic biomarkers for therapeutic monitoring are missing. We demonstrate handheld Multispectral Optoacoustic Tomography (MSOT) as a novel non-invasive imaging approach to visualize and quantify muscle wasting in pediatric SMA. While MSOT signals were distributed homogeneously in muscles of healthy volunteers (HVs), SMA patients showed moth-eaten optoacoustic signal patterns. Further signal quantification revealed greatest differences between groups at the isosbestic point for hemoglobin (SWL 800 nm). The SWL 800 nm signal intensities further correlated with clinical phenotype tested by standard motor outcome measures. Therefore, handheld MSOT could enable non-invasive assessment of disease burden in SMA patients.

Photoacoustic flow cytometry is a method to detect rare analytes in fluids. We developed photoacoustic flow cytometry to detect pathological cells in body fluids, such as circulating tumor cells or bacteria in blood. In order to induce specific optical absorption in bacteria, we use modified bacteriophage that precisely target bacterial species or subspecies for rapid identification. In order to reduce detection variability and to halt the lytic lifescycle that results in lysis of the bacteria, we attached dyed latex microspheres to the tail fibers of bacteriophage that retained the bacterial recognition binding sites. We tested these microsphere complexes using Salmonella enterica (Salmonella) and Escherichia coli (E. coli) bacteria and found robust and specific detection of targeted bacteria. In our work we used LT2, a strain of Salmonella, against K12, a strain of E. coli. Using Det7, a bacteriophage that binds to LT2 and not to K12, we detected an average of 109.3±9.0 of LT2 versus 2.0±1.7 of K12 using red microspheres and 86.7±13.2 of LT2 versus 0.3±0.6 of K12 using blue microspheres. These results confirmed our ability to selectively detect bacterial species using photoacoustic flow cytometry.

Optoacoustic signals are typically reconstructed into images using inversion algorithms applied in the time-domain. However, time-domain reconstructions can be computationally intensive and therefore slow when large amounts of raw data are collected from an optoacoustic scan. Here we considered a fast weighted ${\omega }-{k}$ (FWOK) algorithm operating in the frequency domain to accelerate the inversion in raster-scan optoacoustic mesoscopy (RSOM), while seamlessly incorporating impulse response correction with minimum computational burden. We investigated the FWOK performance with RSOM measurements from phantoms and mice in vivo and obtained 360-fold speed improvement over inversions based on the back-projection algorithm in the time-domain. This previously unexplored inversion of in vivo optoacoustic data with impulse response correction in frequency domain reconstructions points to a promising strategy of accelerating optoacoustic imaging computations, toward video-rate tomography. [ABSTRACT FROM AUTHOR]

Inflammation is the phenotypic form of various diseases. Recent development in molecular imaging provides new insights into the diagnostic and therapeutic evaluation of different inflammatory diseases as well as diseases involving inflammation such as cancer. While conventional imaging techniques used in the clinical setting provide only indirect measures of inflammation such as increased perfusion and altered endothelial permeability, optical imaging is able to report molecular information on diseased tissue and cells. Optical imaging is a quick, noninvasive, nonionizing, and easy-to-use diagnostic technology which has been successfully applied for preclinical research. Further development of optical imaging technology such as optoacoustic imaging overcomes the limitations of mere fluorescence imaging, thereby enabling pilot clinical applications in humans. By means of endogenous and exogenous contrast agents, sites of inflammation can be accurately visualized in vivo. This allows for early disease detection and specific disease characterization, enabling more rapid and targeted therapeutic interventions. In this review, we summarize currently available optical imaging techniques used to detect inflammation, including optical coherence tomography (OCT), bioluminescence, fluorescence, optoacoustics, and Raman spectroscopy. We discuss advantages and disadvantages of the different in vivo imaging applications with a special focus on targeting inflammation including immune cell tracking. [ABSTRACT FROM AUTHOR]

Optoacoustic (OA) field computation by utilizing k-Wave simulation toolbox for six commonly used nanoparticles (NPs) has been performed. The characterization of NPs is often accomplished by the numerical simulation approach. Although, these simulation techniques are complicated, very costly, time-taking and arduous. Accordingly, there is a prerequisite for a fast, economical, and a simple simulation approach to comprehend the OA signal produced from different shapes of NPs. The technique has been employed to calculate the OA spectrum produced by nano size shapes [i.e. sphere, oblate, prolate, pentagon, hexagon, and star] over a large frequency band (10–200 GHz). The shapes of NPs were generated by utilizing simple mathematical equations. The first frequency minimum of OA spectrum approximately occurs at 48, 47, 80, 37, 58, and 57 GHz for nano sphere, oblate, prolate, pentagon, hexagon, and star, respectively when calculated in the direction of the symmetry axis. The same spectral feature appears nearly at 48, 22, 21, 32, 30, and 31 GHz, respectively, for those NPs when computed from the perpendicular direction. The NPs structure can be characterized by investigating single NP OA spectrum. The time taken by simulation for each NP is as short as the 12 min (simulated in the desktop having Intel(R) Core(TM) i7-6700U CPU working at 3.4 GHz and having 16 GB RAM) which is a remarkable increment over formerly communicated simulation time of a few hours employing analytical techniques.

The article describes a determination method of the laser radiation with specific parameters effect on the eye tissues based on optoacoustic probing. Low-power probing laser with 7-10 ns pulses generates acoustic waves at the aiming point. The waves propagate through the medium (saline in a cuvette) to acoustic receiver. The characteristics of the acoustic wave give basis for estimation of optical absorption coefficient - a parameter that determines temperature in the affected area after applying therapeutic laser. Calculation of the temperature pattern was performed using a three-dimensional thermal conductivity model that enabled determination of temperature distribution at any local point during coagulation and immediately after. To compare the results with pre-calculated temperature field values, direct temperature measurement was taken from the surface of the absorbing layer. The experiment was performed on six human chorioretinal tissue samples in vitro; the obtained optical absorption coefficient values did not exceed 120-300 cm-1 with maximum error margin of 20 %. The computational model was seen to be in good agreement with experimental thermocouple measurements.

Bias-flow liners (BFL) are used as part of the cooling mechanism in airplane turbines and they also enable the reduction of noise emission. The attenuating principle is based on the interaction between sound waves and air flow. This turbulent aeroacoustic interaction occurs on a microscopic level and under harsh conditions. Therefore, in order to investigate local aeroacoustic phenomena, the distribution of the local sound field impedance, defined as sound pressure over acoustic particle velocity, is measured non-invasively. This work focuses on the non-invasive measurement of the local sound pressure. A fast camera-based holographic measurement system for the two dimensional tomographic measurement of the local sound pressure with high spatial resolution is presented. It features a spatial resolution of 52 μm with a simultaneous acquisition of up to 1600 measuring points. This enables the observation of sub-mm aeroacoustic effects, which are expected in the near field over the BFL's surface, while reducing the measurement duration by three orders of magnitude compared to single point measurement systems. An experimental validation of the camera-based tomographic system is carried out by reference measurements. The system was applied at an acoustical model and an aeroacoustic model. The measured local sound pressure variations are discussed for both models. This work seeks to enable the non-invasive investigation of sound pressure, in order to further understand aeroacoustic effects, their sound attenuating properties and increase the attenuation capability of a BFL without degrading the overall performance of turbines.

Erythrocytes were mathematically modeled taking into account their oxygen saturation. We present the results of an experimental study of optoacoustic signal formation in a liquid containing erythrocyte models in the form of polystyrene spheres with nanoparticles. Carbon nanotubes immobilized to the erythrocyte models were used as contrast agents. The obtained acoustic signal profiles for a series of laser pulses allow the conclusion that one can to assess the qualitative and quantitative composition of erythrocytes in a laser-irradiated liquid. The article was prepared based on materials in a report at the Third All-Russian Acoustic Conference (September 21–25, 2020, St. Petersburg). [ABSTRACT FROM AUTHOR]

Purpose: Photoacoustics (optoacoustics) is a hybrid technology utilizing light excitation of acoustic responses in targets of interest. It has found numerous applications in biomedicine, including eye research, because of its ability to report both morphological and functional data about the interrogated tissue. This presentation will give an overview of current applications. Methods: Wavelength-dependent absorption of light in a tissue chromophore causes local heating, leading to a thermoelastic expansion-contraction cycle. If nanosecond pulses of light are used to excite this process, the resulting pressure wave is an ultrasound signal propagating through the tissue and detectable at the tissue surface. This is highly advantageous because of the known properties of ultrasound propagation in tissue and the ability to use standard, medical ultrasound equipment for detection. The time of arrival and amplitude of ultrasound signals provide information about the location and nature of the absorber. Results: Due to the wavelength dependence of the photoacoustic response, functional and physiological applications are possible. For example, retinal oximetry can be determined from the different optical absorption properties of oxy- and deoxyhemoglobin. Multispectral imaging of the posterior segment can identify pigments such as melanin or lipofuscin or the nature of foreign bodies. The technique can be combined with other imaging modalities such as ultrasound and optical coherence tomography to produce high-resolution images of retinal structures along with functional information. Conclusion: Photoacoustic technology is a powerful noninvasive tool for ocular research and to study ocular morphology, fundamental physiological parameters, cellular responses, and molecular expression. [ABSTRACT FROM AUTHOR]

Photo-or optoacoustic imaging (OAI) allows quantitative imaging of target tissues. Using multi-wavelength illumination with subsequent ultrasound detection, it may visualize a variety of different chromophores at centimeter depth. Despite its non-invasive, label-free advantages, the precision of repeated measurements for clinical applications is still elusive. We present a multilayer analysis of n = 1920 imaging datasets obtained from a prospective clinical trial (NCT03979157) in n = 10 healthy adult volunteers. All datasets were analyzed for 13 single wavelengths (SWL) between 660 nm–1210 nm and five MSOT-parameters (deoxygenated/oxygenated/total hemoglobin, collagen and lipid) by a semi-automated batch mode software. Intraclass correlation coefficients (ICC) were good to excellent for intrarater (SWL: 0.82–0.92; MSOT-parameter: 0.72−0.92) and interrater reproducibility (SWL: 0.79−0.87; MSOT-parameter: 0.78−0.86), with the exception for MSOT-parameter lipid (interrater ICC: 0.56). Results were stable over time, but exercise-related effects as well as inter-and intramuscular variability were observed. The findings of this study provide a framework for further clinical OAI implementation.

This work describes the design, development and added value of breast-supporting cups to immobilize and position the pendant breast in photoacoustic tomographic imaging. We explain the considerations behind the choice of the material, the shape and sizes of a cup-shaped construct for supporting the breast in water in an imaging tank during full-breast imaging. We provide details of the fabrication, and other processing and testing procedures used. Various experiments were conducted to demonstrate the added value of using these cups. We show that breast movement during a measurement time of four minutes is reduced from maximum 2 mm to 0.1 mm by the use of cups. Further, the presence of the cup, centered in the aperture leading to the imaging tank, ensures that the breast can be reproducibly positioned at the center of the field-of-view of the detection aperture in the tank. Finally, since an accurate delineation of the water-tissue boundary can now be made, the use of the cup enables accurate application of a two-speed of sound model for reconstruction. All in all, we demonstrate that the use of cups to support the breast provides clear enhancement in contrast and resolution of breast images in photoacoustic imaging.