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Senescence is an intricate physiological progression that can be instigated by a multiplicity of factors. Aberrant cellular senescence is capable of precipitating a substantial array of diseases. During chemotherapy, drugs typically tend to gradually accumulate in the liver, thereby inducing liver senescence and leading to a successive deterioration in its physiological function. β-galactosidase (β-gal), serving as a significant index in the exploration of senescence, has attracted considerable attention. In this study, a fluorescence/photoacoustic (FL/PA) biomodal probe (Gal-QCS) was developed based on a hemicyanine fluorophore for the imaging of β-gal in the process of drug-induced liver senescence. Gal-QCS demonstrates rapid responsiveness, high sensitivity, and remarkable selectivity in detecting β-gal in aqueous solutions. After incubation with β-gal, the fluorescence signal at 810 nm significantly increases, and concurrently, the photoacoustic signal at 775 nm also exhibits a substantial increment. Upon the induction of cell senescence with camptothecin, Gal-QCS can expeditiously and selectively image senescent cells. Moreover, after administering this probe to mice with liver senescence, the FL/PA signals in the livers of senescent mice were enhanced by 10.53-fold and 1.43-fold, respectively. This work robustly substantiates the potential and application prospects of Gal-QCS in detecting drug-induced liver senescence, with β-gal serving as a biomarker. [ABSTRACT FROM AUTHOR]

In vivo, molecular imaging is prevalent for biology research and therapeutic practice. Among advanced imaging technologies, photoacoustic (PA) imaging and sensing is gaining interest around the globe due its exciting features like high resolution and good (~ few cm) penetration depth. PA imaging is a recent development in ultrasonic technology that generates acoustic waves by absorbing optical energy. However, poor light penetration through tissue continues to be the key obstacle in the field. The NPs as contrast agents can assist in overcoming tissue penetration depth as NPs can produce high signal to noise (SNR) PA signal which aids reconstruction of high resolution of the PA images in deep tissue sights. Subsequently, NPs are very effective in PA based targeted and precise theranostic applications. This article detail about various NPs (organic, inorganic and hybrid) used in PA imaging and spectroscopy applications including various disease diagnosis, therapy and theranostic. It also features optical property, advantages and limitations of various NPs utilised in PA techniques which would comprehend readers about the potential of NPs in evolving PA technique from laboratory to clinical modality in future. [ABSTRACT FROM AUTHOR]

Stable neutral metal radicaloid complexes have been synthesized from a modified tetrapyrrolic pigment, bilatriene, with iridium(I) and rhodium(I) cyclooctadiene (COD) synthons. The bilatriene skeleton contains α‐linked conjugated pyrrole units, whereas an N‐confused analogue used in this work possesses β‐linked pyrrole moieties at the terminal, demonstrating a unique metal binding capability. Unprecedentedly, the metal‐COD cations are accommodated at the outer nitrogen sites, which induced the formation of open‐shell metal‐radicaloid species. The resulting compounds are highly stable under ambient conditions and demonstrated facile redox conversion to afford the corresponding cation and anion species. Furthermore, the radicaloid complexes showed a distinct second near‐infrared absorption (NIR‐II) capability extending up to 1500 nm along with high photostability. These features emphasized that the complexes can be potential NIR‐II light‐responsible photothermal and photoacoustic imaging contrast agents based on the metal‐radicaloid dye platform. [ABSTRACT FROM AUTHOR]

Aim: As non‐operative management of rectal cancer proliferates, re‐staging and surveillance methods are critical in selecting appropriate patients for organ preservation versus proctectomy. In previous work, the authors have shown that transrectal acoustic resolution photoacoustic microscopy (ARPAM) co‐registered with ultrasound can differentiate residual cancer from complete tumoural response to neoadjuvant therapy. We hypothesize that these findings are due to changes in microvascular density (MVD). Methods: Patients with rectal adenocarcinoma who underwent neoadjuvant therapy, transrectal photoacoustic imaging and resection were included. We first compared immunohistochemical staining with erythroblast transformation‐specific‐related gene (ERG) immunostain to standard CD31 to confirm adequate identification of endothelium. Tissue sections from identical blocks were stained with CD31 and ERG, and then a correlation was calculated between manually labelled CD31‐stained vessels and ERG nuclei density. Second, representative tissue blocks from responders, partial responders and non‐responders were stained with ERG. ERG nuclei density was quantified as a proxy for MVD. Results: CD31 MVD and ERG nuclei density were strongly correlated (R2 = 0.87; P < 0.01). In the tumour bed of patients after neoadjuvant therapy, MVD of complete responders (599 nuclei/mm2; 95% CI 434–764) is significantly higher (P < 0.01) than that of partial responders (185 nuclei/mm2; 95% CI 64–306) and non‐responders (117 nuclei/mm2; 95% CI 42–192). No significant difference was found between the partial responders and non‐responders (P = 0.60). Conclusion: Microvascular density appears highest in cases of complete tumour response to neoadjuvant therapy, similar to normal rectal tissue. The histological microvascular patterns seen in treated tissue may explain the imaging patterns seen in photoacoustic microscopy. [ABSTRACT FROM AUTHOR]

The complex composition of cultural heritage (CH) items presents significant challenges in assessing their condition and predicting potential risks of material degradation. Typically employed diagnostic optical methods are inevitably limited by light scattering, thus restricting in-depth investigations of objects with complex structural and optical properties. To address this issue, we introduce a novel reflection-mode optoacoustic (OA) diagnostic system for non-contact and non-invasive measurements of CH, placing emphasis on the detection of ageing-related modifications in artistic media such as paints. In this direction, the sensitivity of OA measurements was proven to be up to two orders of magnitude higher than conventional absorption spectroscopy assessments. Furthermore, we have evaluated the in-depth imaging capabilities of the developed OA system, demonstrating that it can offer superior contrast levels of sketches beneath opaque paint layers compared to standard near-infrared diagnostic techniques. The current OA imaging technology may advance state-of-the-art diagnostic capabilities in CH preservation by delivering unprecedented depth-to-resolution ratios combined with exceptional optical absorption sensitivity in a non-invasive manner. These features are crucial for the early detection of material degradation and the comprehensive analysis of CH objects, facilitating the development of optimal conservation strategies to prolong their lifespan and preserve their aesthetic value. [ABSTRACT FROM AUTHOR]

Copper sulphide nanoparticles are synthesized by laser ablation of a copper target in DMSO by a 527 nm nanosecond pulsed laser. These nanoparticles have double stoichiometry (CuS and Cu1.8S) and crystalline structures, sizes under 30 nm, and they present substantial absorbance in the second near‐infrared window and photoluminescence in the visible region. The nanoparticles are used as photothermal and photoacoustic agents at 1080 nm and 1064 nm, respectively. Utilizing as a photothermal agent, these nanoparticles rapidly exhibit local heating, photothermal stability, and a temperature change of 52.2 °C within 300 s at 1 mg mL−1 concentration and 3.23 W cm−2 laser intensity. On the other hand, while employed as a photoacoustic agent, they enhanced the contrast significantly and increased the brightness proportional to their concentrations when compared to ultrasound imaging. Additionally, the biocompatibility properties of these nanoparticles were tested with cancer cells, and they were subjected to laser ablation to assess their photothermal effects. In this article, we demonstrate that copper sulphide nanoparticles synthesized by pulsed laser ablation hold great promise for photothermal and photoacoustic applications, especially in biomedical applications. [ABSTRACT FROM AUTHOR]

The accuracy and efficacy of laser ablation procedures depend on the accurate placement of the laser applicator within the diseased tissue, monitoring the real-time temperature during the ablation procedure, and mapping the extent of the ablated region. Ultrasound (US) imaging has been widely used to guide ablation procedures. While US imaging offers significant advantages for guiding ablation procedures, its limitations include low imaging contrast, angular dependency, and limited ability to monitor the temperature. Photoacoustic (PA) imaging is a relatively new imaging modality that inherits the advantages of US imaging and offers enhanced capabilities for laser-guided ablations, such as accurate, angle-independent tracking of ablation catheters, the potential for quantitative thermometry, and monitoring thermal lesion formation. This work provides an overview of ultrasound-guided procedures and how different US-related artifacts limit their utility, followed by introducing PA as complementary to US as a solution to address the existing limitations and improve ablation outcomes. Furthermore, we highlight the integration of PA-driven features into existing US-guided laser ablation systems, along with their limitations and future outlooks. Integrated US/PA-guided laser ablation procedures can lead to safer and more precise treatment outcomes. [ABSTRACT FROM AUTHOR]

Significance: A Fabry-Perot (FP) polymer film sensor can be used to detect acoustic waves in a photoacoustic endoscope (PAE) if the dimensions can be adequately scaled down in size. Current FP sensors have limitations in size, sensitivity, and array configurability. Aim: We aim to characterize and demonstrate the imaging performance of a miniature FP sensor to evaluate the effects of reduced size and finite dimensions. Approach: A transfer matrix model was developed to characterize the frequency response of a multilayer miniature FP sensor. An analytical model was derived to describe the effects of a substrate with finite thickness. Finite-element analysis was performed to characterize the temporal response of a sensor with finite dimensions. Miniature 2 × 2 mm2 FP sensors were designed and fabricated using gold films as reflective mirrors on either side of a parylene C film deposited on a glass wafer. A single-wavelength laser was used to interrogate the sensor using illumination delivered by fiber subprobes. Imaging phantoms were used to verify FP sensor performance, and in vivo images of blood vessels were collected from a live mouse. Results: The finite thickness substrate of the FP sensor resulted in echoes in the time domain signal that could be removed by back filtering. The substrate acted as a filter in the frequency domain. The finite lateral sensor dimensions produced side waves that could be eliminated by surface averaging using an interrogation beam with adequate diameter. The fabricated FP sensor produced a noise-equivalent pressure = 0.76 kPa, bandwidth of 16.6 MHz, a spectral full-width at-half-maximum = 0.2886 nm, and quality factor Q = 2694. Photoacoustic images were collected from phantoms and blood vessels in a live mouse. Conclusions: A miniature wafer-based FP sensor design has been demonstrated with scaled down form factor for future use in PAE. [ABSTRACT FROM AUTHOR]

Photoacoustic imaging is commonly utilized in biomedical research due to its capability to provide the functional and structural details of imaging targets, featuring optical contrast and ultrasound resolution. This imaging technique has also found applications in industry, particularly in non-destructive testing, such as in surface crack detection. However, the cost of photoacoustic systems and the time required for scanning and image reconstruction limit their use in non-destructive testing. In this study, low-cost photoacoustic equipment was combined with machine learning techniques and applied in surface crack detection. This scanning technique achieved a 97% offline prediction accuracy. Additionally, it demonstrated a reduction in system complexity compared to traditional photoacoustic imaging techniques. This reduction in complexity results from using a single scanning line as input to the machine learning model, unlike the imaging technique, which requires multiple scanning lines to reconstruct the photoacoustic image. [ABSTRACT FROM AUTHOR]

As a novel imaging modality based on photoacoustic effects, photoacoustic imaging (PAI) has shown great potential in biomedical applications, especially in the field of cancer. The purpose of our research was to identify collaborations between different institutions, authors, and countries, and to explore the hotspots and prospects of PAI research in the field of cancer. We downloaded publications on PAI research from the Science Citation Index-Expanded (SCI-E) of the Web of Science Core Collection database. Bibliometric analysis was performed using VOSviewer and CiteSpace software. A total of 2561 papers related to PAI research in the field of cancer were identified. A total of 10,105 authors participated in the PAI study, of which the majority (69.33%) authors participated in only 1 article. China (1638, 63.96%) was the country with the most articles in this field, and the Chinese Academy of Sciences (329, 12.85%) was the most productive institution. ACS Applied Materials & Interfaces (146, 5.70%) was the most productive journal and ACS Nano (7262 co-citations) was the most co-cited journal. Current hot topics of PAI research in the cancer field were the construction and development of multifunctional photoacoustic nanoprobes to achieve the integration of tumor detection and treatment. The application of photoacoustic imaging in the field of cancer is in the vigorous development stage and has a bright prospect. There was a wealth of cooperation between authors, countries, and institutions. Our findings can provide information about the future direction of funding agencies and research groups. [ABSTRACT FROM AUTHOR]

Background: Characterizations based on anatomically realistic phantoms are highly effective to perform accurate technical validation of imaging systems. Specifically for photoacoustic imaging (PAI), although a variety of phantom models with simplified geometries are reported, an unmet need still exists to establish morphologically realistic heterogeneous pre‐clinical phantoms. So the development of a mouse‐mimicking phantom can reduce the use of animals for the validation and standardization studies of pre‐clinical PAI systems and thus eventually translate the PAI technology to clinical research. Purpose: Here we designed, developed, and fabricated a stable phantom that mimics the detailed morphology of a mouse, to be used as a realistic tool for PAI. Methods: The mouse phantom, has been designed by using a combination of image modeling and 3D‐printing techniques. As a tissue‐mimicking material, we have used copolymer‐in‐oil‐based material that was recently proposed by the International Photoacoustic Standardization Consortium (IPASC). In particular, the anatomically realistic phantom has been modeled by using the real atlas of a mouse as a reference. The mouse phantom includes a 3D‐printed skeleton and the main abdominal organs such as the liver, spleen, and kidneys obtained by using doped copolymer‐in‐oil material with 3D‐printed molds. In addition, the acoustic and optical properties of the tissue‐mimicking material and the long‐term stability have been broadly characterized. Results: Furthermore, our studies showed that the phantom is durable and stable for more than 200 days, under normal storage and repeated use. Fabrication protocol is easy to reproduce. As a result, the proposed morphologically realistic mouse phantom offers durability, material compatibility, and an unprecedented realistic resemblance to the actual rodents' anatomy in PAI. Conclusion: This durable morphologically realistic mouse phantom would minimize the animal experiments in compliance with the 3R principle of Replacement, Reduction, and Refinement. To our knowledge, this is the first time an anatomically realistic heterogeneous mouse phantom has been proposed for PAI in pre‐clinical animal imaging and tested its durability over 200 days. [ABSTRACT FROM AUTHOR]

Fluorescence and photoacoustic imaging techniques offer valuable insights into cell- and tissue-level processes. However, these optical imaging modalities are limited by scattering and absorption in tissue, resulting in the low-depth penetration of imaging. Contrast-enhanced imaging in the near-infrared window improves imaging penetration by taking advantage of reduced autofluorescence and scattering effects. Current contrast agents for fluorescence and photoacoustic imaging face several limitations from photostability and targeting specificity, highlighting the need for a novel imaging probe development. This review covers a broad range of near-infrared fluorescent and photoacoustic contrast agents, including organic dyes, polymers, and metallic nanostructures, focusing on their optical properties and applications in cellular and animal imaging. Similarly, we explore encapsulation and functionalization technologies toward building targeted, nanoscale imaging probes. Bioimaging applications such as angiography, tumor imaging, and the tracking of specific cell types are discussed. This review sheds light on recent advancements in fluorescent and photoacoustic nanoprobes in the near-infrared window. It serves as a valuable resource for researchers working in fields of biomedical imaging and nanotechnology, facilitating the development of innovative nanoprobes for improved diagnostic approaches in preclinical healthcare. [ABSTRACT FROM AUTHOR]

Photoacoustic imaging is low‐risk, and noninvasive tool for imaging biological tissues that acoustically respond to absorbed irradiating nonionized short laser pulse by tissue, then the image of light energy absorption distribution in the tissue has been reconstructed by image reconstruction algorithms. Indeed, photoacoustic tomography is a hybrid imaging modality that combines pure optical and acoustic imaging methods to take advantage of them, therefore, it contains high optical contrast with good ultrasonic resolution. However, improving its main parts is challenging. One of the most important parts of photoacoustic imaging is image reconstruction using appropriate algorithms. There are various image reconstruction methods. Image reconstruction based on an algebraic algorithm can reconstruct a clear image without artifact, but the algorithm is typically time‐consuming. This paper deals with this drawback of the algorithm. Simulations demonstrate significant improvement in the processing time of reconstructed images achieved by our proposed algorithm as compared to the phase‐controlled algorithm. Based on the image reconstruction algorithm in circular scanning geometry presented in this article, the processing time required to create a 2D tomographic image is reduced from 60 to 3.89 s compared to our previous work, which was based on a phase‐controlled algorithm. This improvement was based on inspiration from the experiences of our past works in dealing with various image reconstruction algorithms, which ultimately led to improvement in the calculation time. [ABSTRACT FROM AUTHOR]

We used photoacoustic imaging (PAI) to visualize and compare acoustic intensity levels in pneumonia-affected and healthy chicken lungs. After histological confirmation of pneumonia, the samples were scanned and subjected to a 532- nm diode laser in a photoacoustic imaging system. The acoustic intensity level of pneumonia-affected tissue was examined and compared with that of healthy lung samples. The optimum laser frequency and duty cycle for imaging the samples were 17 kHz and 30%, respectively. The acoustic intensity levels of pneumonia-affected tissue and healthy lungs were -82.5 ± 1.8 dB and -79.9 ± 1.3 dB, respectively. We found that a simple PAI device consisting of a diode laser and condenser microphone could distinguish between pneumonia-affected and healthy lungs. Pneumonia-affected lungs produced less acoustic intensity than that healthy lungs, as supported by histological studies. [ABSTRACT FROM AUTHOR]

Accurate and early detection of atherosclerosis (AS) is imperative for their effective treatment. However, fluorescence probes for efficient diagnosis of AS often encounter insufficient deep tissue penetration, which hinders the reliable assessment of plaque vulnerability. In this work, a reactive oxygen species (ROS) activated near-infrared (NIR) fluorescence and photoacoustic (FL/PA) dual model probe TPA-QO-B is developed by conjugating two chromophores (TPA-QI and O–OH) and ROS-specific group phenylboronic acid ester. The incorporation of ROS-specific group not only induces blue shift in absorbance, but also inhibits the ICT process of TPA-QO-OH, resulting an ignorable initial FL/PA signal. ROS triggers the convertion of TPA-QO-B to TPA-QO-OH, resulting in the concurrent amplification of FL/PA signal. The exceptional selectivity of TPA-QO-B towards ROS makes it effectively distinguish AS mice from the healthy. The NIR emission can achieve a tissue penetration imaging depth of 0.3 cm. Moreover, its PA 775 signal possesses the capability to penetrate tissues up to a thickness of 0.8 cm, ensuring deep in vivo imaging of AS model mice in early stage. The ROS-triggered FL/PA dual signal amplification strategy improves the accuracy and addresses the deep tissue penetration problem simultaneously, providing a promising tool for in vivo tracking biomarkers in life science and preclinical applications. [ABSTRACT FROM AUTHOR]

Recent advances in medical imaging include integrating photoacoustic and optoacoustic techniques with conventional imaging modalities. The developments in the latter have led to the use of optics combined with the conventional ultrasound technique for imaging intravascular tissues and applied to different areas of the human body. Conventional ultrasound is a skin contact-based method used for imaging. It does not expose patients to harmful radiation compared to other techniques such as Computerised Tomography (CT) and Magnetic Resonance Imaging (MRI) scans. On the other hand, optical Ultrasound (OpUS) provides a new way of viewing internal organs of the human body by using skin and an eye-safe laser range. OpUS is mostly used for binary measurements since they do not require to be resolved at a much higher resolution but can be used to check for intravascular imaging. Various signal processing techniques and reconstruction methodologies exist for Photo-Acoustic Imaging, and their applicability in bioimaging is explored in this paper. [ABSTRACT FROM AUTHOR]

Three-dimensional (3D) handheld photoacoustic (PA) and ultrasound (US) imaging performed using mechanical scanning are more useful than conventional 2D PA/US imaging for obtaining local volumetric information and reducing operator dependence. In particular, 3D multispectral PA imaging can capture vital functional information, such as hemoglobin concentrations and hemoglobin oxygen saturation (sO2), of epidermal, hemorrhagic, ischemic, and cancerous diseases. However, the accuracy of PA morphology and physiological parameters is hampered by motion artifacts during image acquisition. The aim of this paper is to apply appropriate correction to remove the effect of such motion artifacts. We propose a new motion compensation method that corrects PA images in both axial and lateral directions based on structural US information. 3D PA/US imaging experiments are performed on a tissue-mimicking phantom and a human wrist to verify the effects of the proposed motion compensation mechanism and the consequent spectral unmixing results. The structural motions and sO2 values are confirmed to be successfully corrected by comparing the motion-compensated images with the original images. The proposed method is expected to be useful in various clinical PA imaging applications (e.g., breast cancer, thyroid cancer, and carotid artery disease) that are susceptible to motion contamination during multispectral PA image analysis. [ABSTRACT FROM AUTHOR]

A 50-year-old woman with no past medical history presented with a left anterior chest wall mass that was clinically soft, mobile, and non-tender. A targeted ultrasound (US) showed findings suggestive of a lipoma. However, focal "mass-like" nodules seen within the inferior portion suggested malignant transformation of a lipomatous lesion called for cross sectional imaging, such as MRI or invasive biopsy or excision for histological confirmation. A T1-weighted image demonstrated a large lipoma that has a central fat-containing region surrounded by an irregular hypointense rim in the inferior portion, confirming the benignity of the lipoma. An ultrasound-guided photoacoustic imaging (PA) of the excised specimen to derive the biochemical distribution demonstrated the "mass-like" hypoechoic regions on US as fat-containing, suggestive of benignity of lesion, rather than fat-replacing suggestive of malignancy. The case showed the potential of PA as an adjunct to US in improving the diagnostic confidence in lesion characterization. [ABSTRACT FROM AUTHOR]

The quality of ultrasound and photoacoustic imaging primarily depends on the performance of piezoelectric transducer elements, which is closely related to the acoustic and electrical properties of piezoelectric materials. With the increasing demand for high-performance, low-cost piezoelectric materials, a high-temperature-resistant <001>-textured ferroelectric ceramic Pb(In 1/2 Nb 1/2)O 3 -Pb(Sc 1/2 Nb 1/2)O 3 -PbTiO 3 (PIN-PSN-PT) has been developed. In recent years, low-cost textured ceramic materials have exhibited high piezoelectric constants (d 33) and large electromechanical coupling coefficients (k t). In this study, an ultrasonic transducer based on PIN-PSN-PT textured ceramic was successfully manufactured for the first time. The transducer has a center frequency of 4.7 MHz, −6 dB bandwidth of 60 %, effective k t of 0.76, and two-way insertion loss (IL) of −34 dB. Photoacoustic imaging experiments on carbon fiber-reinforced polymer (CFRP) were conducted to evaluate the sensitivity and imaging quality of the transducer. The results indicate that the use of PIN-PSN-PT textured ceramics holds great potential in developing acoustic sensors for photoacoustic non-destructive testing applications. [Display omitted] • This study introduces a novel textured ceramic, PIN-PSN-PT, for fabricating 1–3 composite-based transducers, enabling high reception sensitivity. • The transducer features a central frequency of 4.7 MHz, a −6 dB bandwidth of 60 %, an electromechanical coupling coefficient of 0.76, and a bidirectional insertion loss of −34 dB. • PIN-PSN-PT offers lower time and production costs compared to PZT while delivering equivalent or superior electromechanical performance. [ABSTRACT FROM AUTHOR]

Thienoisoindigo (TIIG) has been extensively employed as promising building block of near-infrared (NIR) dyes and organic semiconductor materials. Herein, heavy-atom-free TIIG-based NIR dye TIIGTPA is reported as photosensitizer for combinational photodynamic and photothermal therapy and photoacoustic imaging (PAI). By introducing two methoxy-substituted triphenylamines as the rotors and electron donors at the periphery sites of the electron-deficient TIIG core, dye TIIGTPA featuring Donor-Acceptor-Donor (D-A D) structure is constructed with intensive NIR absorption. Through co-assembly with amphipathic F-127, water-soluble TIIGTPA NPs were prepared with good superoxide anion radical (O 2 -•) production and high photothermal conversion efficiency (PCE) of 59.0 % under 730 nm photoirradiation. Additionally, the excellent photothermal effect enabled a superior photoacoustic response for tumor blood vessel visualization through PAI. All results indicated the favorable potential of TIIGTPA NPs for PAI-mediated combinational phototherapy. • Heavy-atom-free TIIG-based NIR dye TIIGTPA was synthesized. • TIIGTPA NPs showed good superoxide anion radical (O 2 -•) production. • TIIGTPA NPs exhibited high PCE of 59.0 % under 730 nm photoirradiation. • A superior photoacoustic response for tumor blood vessel visualization through PAI. [ABSTRACT FROM AUTHOR]

Recent investigations have revealed the tight connections between carboxylesterase (CE) and the lipid metabolism-associated disorders. In this work, based on the previous reports, a photoacoustic (PA) probe Hcy-CE was developed for the in vivo imaging of CE in two lipid metabolism disorders. The reaction with CE led to the departure of the carbamate quencher together with the linkage, thus to release of the reporter Hcy to exhibit the turn-on signals of PA reporting accompanied with the absorbance and fluorescence modes. The responses in all three modes showed high consistency. In the PA mode, the linear correlation range was CE level 0–10 U/L, while the limit of detection value was 0.52 U/mL. The optical performance of the probe Hcy-CE in the solution system was practical with high steadiness and selectivity. Moreover, Hcy-CE exhibited potential capability of monitoring the CE level in the induced foam cells. In particular, Hcy-CE realized the in vivo imaging of the CE level from multiple views and continuous cross-sections in the model mice of different groups. The combination of the PA imaging with the blood biochemical tests and immunohistochemically staining methods might help distinguish the three statuses of different mice from each other. This work provided meaningful information for the accurate diagnosis and regulation of the lipid metabolism-related disorders. [Display omitted] • Imaging carboxylesterase in atherosclerosis and obesity with photoacoustic response. • A photoacoustic probe developed with practical stability and selectivity. • Achieving to distinguish the atherosclerosis and obesity groups from the healthy status. • In vivo photoacoustic imaging of atherosclerosis and obesity consistent with histological staining. Recent investigations have revealed the tight connections between carboxylesterase (CE) and the lipid metabolism-associated disorders. In this work, based on the previous reports, a photoacoustic (PA) probe Hcy-CE was developed for the in vivo imaging of CE in two lipid metabolism disorders. The reaction with CE led to the departure of the carbamate quencher together with the linkage, thus to release of the reporter Hcy to exhibit the turn-on signals of PA reporting accompanied with the absorbance and fluorescence modes. The responses in all three modes showed high consistency. In the PA mode, the linear correlation range was CE level 0–10 U/L, while the limit of detection value was 0.52 U/mL. The optical performance of the probe Hcy-CE in the solution system was practical with high steadiness and selectivity. Moreover, Hcy-CE exhibited potential capability of monitoring the CE level in the induced foam cells. In particular, Hcy-CE realized the in vivo imaging of the CE level from multiple views and continuous cross-sections in the model mice of different groups. The combination of the PA imaging with the blood biochemical tests and immunohistochemically staining methods might help distinguish the three statuses of different mice from each other. This work provided meaningful information for the accurate diagnosis and regulation of the lipid metabolism-related disorders. [ABSTRACT FROM AUTHOR]

Objective: Two-dimensional (2D) photoacoustic (PA) imaging based on array transducers provide high spatial resolution in the lateral direction by adopting receive dynamic focusing. However, the quality of PA image is often deteriorated by poor elevational resolution which is achieved by an acoustic lens. To overcome this limitation, we present a three-dimensional (3D) image reconstruction method using a commercial one-dimensional (1D) array transducer. Methods: In the method, the elevational resolution is improved by applying synthetic aperture focusing (SAF) technique along the elevational direction. For this, a commercially available 1D array transducer with an acoustic lens is modeled and appropriate synthetic focusing delay that can minimize the effect of the acoustic lens is derived by mathematical analysis. Results: From the simulation and experiment results, it was demonstrated that the proposed method can enhance the image quality of PA imaging, i.e., elevational resolution and signal-to-noise ratio (SNR). Conclusion: 3D PA images with improved elevational resolution were achieved using a clinical 1D array transducer. Significance: The presented method may be useful for clinical application such as detecting microcalcification, imaging of tumor vasculature and guidance of biopsy in real time. [ABSTRACT FROM AUTHOR]

Photoacoustic imaging (PAI) is a rapidly emerging modality in biomedical research with the advantages of noncontact operation, high optical resolution, and deep penetration. Great efforts and progress in the development of PAI agents with improved imaging resolution and sensitivity have been made over the past 2 decades. Among them, organic agents are the most promising candidates for preclinical/clinical applications due to their outstanding in vivo properties and facile biofunctionalities. Motivated by the unique properties of aggregation-induced emission (AIE) luminogens (AIEgens), various optical probes have been developed for bioanalyte detection, multimodal bioimaging, photodynamic/photothermal therapy, and imaging-guided therapeutics. In particular, AIE-active contrast agents have been demonstrated in PAI applications with excellent performance in imaging resolution and tissue permeability in vivo. This paper presents a brief overview of recent progress in AIE-based agents in the field of photoacoustic imaging. In particular, we focus on the basic concepts, data sorting and comparison, developing trends, and perspectives of photoacoustic imaging. Through numerous typical examples, the way each system realizes the desired photoacoustic performance in various biomedical applications is clearly illustrated. We believe that AIE-based PAI agents would be promising multifunctional theranostic platforms in clinical fields and will facilitate significant advancements in this research topic. [ABSTRACT FROM AUTHOR]

Intracellular bioactive molecules are essential for the maintenance of homeostasis in living organisms. Abnormal levels of them are closely related to the occurrence and development of some diseases. Hence, the direct and accurate visualization of these bioactive molecules is of vital importance for exploring their pathological roles. However, the low‐content, short‐lived, and widely distributed properties of bioactive molecules impede the comprehensive analysis of them dramatically. Fluorescence and photoacoustic dual‐mode imaging technology provides a new solution to the above issue. Specifically, the combination of fluorescence and photoacoustic, which possesses the advantages of high resolution and in‐depth tissue analysis, enables a more in‐depth and systematic exploration of the pathogenic mechanisms of bioactive molecules. Moreover, due to the structural tailorability of small molecule probes, numerous small molecule dual‐mode probes have been developed to meet the demand for real‐time tracking and visualization of bioactive molecules in living cells or in vivo. Hence, in this review, we briefly summarize the key advances in small molecule fluorescence and photoacoustic dual‐modal probes within recent years (2015–2021). A particular focus is placed on the design strategies and biological applications of probes for the detection of various bioactive molecules in vivo. Furthermore, the challenges and further prospects in this hot field are highlighted. [ABSTRACT FROM AUTHOR]

Photoacoustic imaging is an emerging biomedical imaging technique that combines optical contrast and ultrasound resolution to create unprecedented light absorption contrast in deep tissue. Thanks to its fusional imaging advantages, photoacoustic imaging can provide multiple structural and functional insights into biological tissues such as blood vasculatures and tumors and monitor the kinetic movements of hemoglobin and lipids. To better visualize and analyze the regions of interest, segmentation and quantitative analyses were used to extract several biological factors, such as the intensity level changes, diameter, and tortuosity of the tissues. Over the past 10 years, classical segmentation methods and advances in deep learning approaches have been utilized in research investigations. In this review, we provide a comprehensive review of segmentation and quantitative methods that have been developed to process photoacoustic imaging in preclinical and clinical experiments. We focus on the parametric reliability of quantitative analysis for semantic and instance-level segmentation. We also introduce the similarities and alternatives of deep learning models in qualitative measurements using classical segmentation methods for photoacoustic imaging. [ABSTRACT FROM AUTHOR]

Here, we report the facile synthesis of Cu(II) tetraaryl-tetranaphtoporphyrin CuTNP showing an extremely sharp, intense Q band above 700 nm via retro-Diels-Alder approach. The highly saddled structure of CuTNP was confirmed using X-ray single-crystal diffraction. The optical and magnetic properties of CuTNP, as well as its excellent reversible redox behaviours, were thoroughly examined both experimentally and theoretically. The water-soluble nanocomposites encapsulating CuTNP by bent amphiphilic molecules were successfully developed, which kept the intense Q band of CuTNP in water. The strong photoacoustic response of CuTNP was detected, suggesting its potential as a photoacoustic imaging agent. This work provides metal-coordinated linearly π-extended porphyrins as potential functional materials for future biomedical applications. [ABSTRACT FROM AUTHOR]

For combining optical and ultrasonic imaging methodologies, photoacoustic imaging (PAI) is the most important and successful hybrid technique, which has greatly contributed to biomedical research and applications. Its theoretical background is based on the photoacoustic effect, whereby a modulated or pulsed light is emitted into tissue, which selectively absorbs the optical energy of the light at optical wavelengths. This energy produces a fast thermal expansion in the illuminated tissue, generating pressure waves (or photoacoustic waves) that can be detected by ultrasonic transducers. Research has shown that optical absorption spectroscopy offers high optical sensitivity and contrast for ingredient determination, for example, while ultrasound has demonstrated good spatial resolution in biomedical imaging. Photoacoustic imaging combines these advantages, i.e., high contrast through optical absorption and high spatial resolution due to the low scattering of ultrasound in tissue. In this review, we focus on advances made in PAI in the last five years and present categories and key devices used in PAI techniques. In particular, we highlight the continuously increasing imaging depth achieved by PAI, particularly when using exogenous reagents. Finally, we discuss the potential of combining PAI with other imaging techniques. [ABSTRACT FROM AUTHOR]

With the advent of stem cell therapy for spinal cord injuries, stroke, burns, macular degeneration, heart diseases, diabetes, rheumatoid arthritis and osteoarthritis; the need to track the survival, migration pathways, spatial destination and differentiation of transplanted stem cells in a clinical setting has gained increased relevance. Indeed, getting regulatory approval to use these therapies in the clinic depends on biodistribution studies. Although optoacoustic imaging (OAI) or photoacoustic imaging can detect functional information of cell activities in real-time, the selection and application of suitable contrast agents is essential to achieve optimal sensitivity and contrast for sensing at clinically relevant depths and can even provide information about molecular activity. This review explores OAI methodologies in conjunction with the specific application of exogenous contrast agents in comparison to other imaging modalities and describes the properties of exogenous contrast agents for quantitative and qualitative monitoring of stem cells. Specific characteristics such as biocompatibility, the absorption coefficient, and surface functionalization are compared and how the labelling efficiency translates to both short and long-term visualization of mesenchymal stem cells is explored. An overview of novel properties of recently developed optoacoustic contrast agents and their capability to detect disease and recovery progression in clinical settings is provided which includes newly developed exogenous contrast agents to monitor stem cells in real-time for multimodal sensing. [ABSTRACT FROM AUTHOR]

Photoacoustic imaging is a novel, rapidly expanding technique, which has recently found several applications in artwork diagnostics, including the uncovering of hidden layers in paintings and multilayered documents, as well as the thickness measurement of optically turbid paint layers with high accuracy. However, thus far, all the presented photoacoustic-based imaging technologies dedicated to such measurements have been strictly limited to thin objects due to the detection of signals in transmission geometry. Unavoidably, this issue restricts seriously the applicability of the imaging method, hindering investigations over a wide range of cultural heritage objects with diverse geometrical and structural features. Here, we present an epi-illumination photoacoustic apparatus for diagnosis in heritage science, which integrates laser excitation and respective signal detection on one side, aiming to provide universal information in objects of arbitrary thickness and shape. To evaluate the capabilities of the developed system, we imaged thickly painted mock-ups, in an attempt to reveal hidden graphite layers covered by various optically turbid paints, and compared the measurements with standard near-infrared (NIR) imaging. The obtained results prove that photoacoustic signals reveal underlying sketches with up to 8 times improved contrast, thus paving the way for more relevant applications in the field. [ABSTRACT FROM AUTHOR]

Implementation of piezoelectric multilayer ceramic (MLC) is an effective way to reduce impedance and improve the performance of linear-array transducer for ultrasonic system applications. However, the ultrasonic image derived from a planar linear-array transducer generally suffers from degradation of lateral resolution and contrast. In this article, we designed and fabricated a focused 5-MHz 128-element linear-array ultrasonic transducer with concave structure using five-layered 0.1Pb (Ni1/3Nb2/3)O3 -0.35Pb(Zn1/3Nb2/3)O3 -0.15Pb(Mg1/3Nb2/3)O3-0.1PbZrO3-0.3PbTiO3 (PNN-PZN-PMN-PZ-PT) piezo- electric ceramic. The transducer showed a bandwidth of 63% at −6 dB and the lateral resolution up to 0.33 mm. An improved transmission signal of 90% higher than a commercial single-layer ceramic transducer was also achieved. We further demonstrated high-resolution photoacoustic imaging with the obtained concave linear-array transducer. [ABSTRACT FROM AUTHOR]

Wide-scale adoption of optoacoustic imaging in biology and medicine critically depends on availability of affordable scanners combining ease of operation with optimal imaging performance. Here we introduce LightSpeed: a low-cost real-time volumetric handheld optoacoustic imager based on a new compact software-defined ultrasound digital acquisition platform and a pulsed laser diode. It supports the simultaneous signal acquisition from up to 192 ultrasound channels and provides a hig-bandwidth direct optical link (2x 100G Ethernet) to the host-PC for ultra-high frame rate image acquisitions. We demonstrate use of the system for ultrafast (500Hz) 3D human angiography with a rapidly moving handheld probe. LightSpeed attained image quality comparable with a conventional optoacoustic imaging systems employing bulky acquisition electronics and a Q-switched pulsed laser. Our results thus pave the way towards a new generation of compact, affordable and high-performance optoacoustic scanners. [ABSTRACT FROM AUTHOR]

A novel, highly biocompatible, well soluble melanin-based probe obtained from the conjugation of melanin macromolecule to bovine serum albumin (BSA) was tested as a contrast agent for photoacoustic tumor imaging. Five soluble conjugates (PheoBSA A-E) were synthesized by oxidation of dopamine (DA) in the presence of variable amounts of BSA. All systems showed the similar size and absorbance spectra, being PheoBSA D (DA:BSA ratio 1:2) the one showing the highest photoacoustic efficiency. This system was then selected for the investigations as it showed a marked enhancement of the photoacoustic (PA) contrast in the tumor region upon iv injection. Biodistribution studies confirmed the accumulation of PheoBSA D within the tumor region and showed fast renal elimination, lack of cell toxicity, and good hemocompatibility. A higher PA contrast enhancement was observed in the case of PC3 prostate tumor xenograft when compared to the TS/A breast one, likely reflecting different vascularization/extravasation properties between the two tumor murine models. The improved PA properties shown by PheoBSA D allowed to set up a 3D dynamic contrast-enhanced (DCE) approach that demonstrated a persistent increase of the PA signal in the tumor region for a long period. Overall, the herein reported results demonstrate that PheoBSA D is a promising blood pool contrast agent for in vivo PA imaging, particularly useful for the set-up of 3D DCE-PA approaches to monitor tumor vascular properties. [ABSTRACT FROM AUTHOR]

• Photoacoustic computed tomography allowed longitudinal monitoring of gold nanorods labeled hydrogel in a small animal model over a period of 8 weeks. • Gold nanorods in hydrogels generated sufficient and consistent contrast for longitudinal monitoring. • Quantitative volume analysis with photoacoustic computed tomography allowed the evaluation of hydrogel degradation in vivo. • Multispectral photoacoustic computed tomography allowed simultaneous evaluation of vascularization based on the intrinsic contrast generated by hemoglobin Longitudinal in vivo monitoring is essential for the design and evaluation of biomaterials. An ideal method would provide three-dimensional quantitative information, high spatial resolution, deep tissue penetration, and contrast between tissue and material structures. Photoacoustic (PA) or optoacoustic imaging is a hybrid technique that allows three-dimensional imaging with high spatial resolution. In addition, photoacoustic imaging allows for imaging of vascularization based on the intrinsic contrast of hemoglobin. In this study, we investigated photoacoustic computed tomography (PACT) as a tool for longitudinal monitoring of an implanted hydrogel in a small animal model. Hydrogels were loaded with gold nanorods to enhance contrast and imaged weekly for 8 weeks. PACT allowed non-invasive three-dimensional, quantitative imaging of the hydrogels over the entire 8 weeks. Quantitative volume analysis was used to evaluate the in vivo degradation kinetics of the implants which deviated slightly from in vitro predictions. Multispectral imaging allowed for the simultaneous analysis of hydrogel degradation and local vascularization. These results provide support for the substantial potential of PACT as a tool for insight into biomaterial performance in vivo. Image, graphical abstract [ABSTRACT FROM AUTHOR]

Thermometry is the key factor for achieving successful thermal therapy. Although invasive thermometry with a probe has been used for more than four decades, this method can only detect the local temperature within the probing volume. Noninvasive temperature imaging using a tomographic technique is ideal for monitoring hot-spot formation in the human body. Among various techniques, such as X-ray computed tomography, microwave tomography, echo sonography, and magnetic resonance (MR) imaging, the proton resonance frequency shift method of MR thermometry is the only method currently available for clinical practice because its temperature sensitivity is consistent in most aqueous tissues and can be easily observed using common clinical scanners. New techniques are being proposed to improve the robustness of this method against tissue motion. MR techniques for fat thermometry were also developed based on relaxation times. One of the latest non-MR techniques to attract attention is photoacoustic imaging. Unlabelled Image [ABSTRACT FROM AUTHOR]

Introduction: Imaging technologies have been developed to assist physicians and dentists in detecting various diseases. Photoacoustic imaging (PAI) is a new technique that shows great applicability to soft tissues. This study aimed to investigate the effect of diode laser intensity modulation on photoacoustic (PA) image quality. Methods: The prototype of the PAI system in this study utilized a non-ionizing 532 nm continuouswave (CW) diode laser illumination. Samples in this study were oral soft tissues of Sprague-Dawley rats fixed in 10% formalin solution. PA images were taken ex vivo by using the PAI system. The laser exposure for oral soft tissue imaging was set in various duty cycles (16%, 24%, 31%, 39%, and 47%). The samples were embedded in paraffin, and PA images were taken from the paraffinembedded tissue blocks in a similar method by using duty cycles of 40%, 45%, 50%, 55%, 60% respectively to reveal the influence of the laser duty cycle on PA image quality. Results: The oral soft tissue is clearly shown as a yellow to red area in PA images, whereas the nonbiological material appears as a blue background. The color of the PA image is determined by the PA intensity. Hence, the PA intensity of oral soft tissue was generally higher than that of the nonbiological material around it. The Kruskal-Wallis test followed by Mann-Whitney post-hoc analysis revealed significant differences (P < 0.05) in the quality of PA images produced by using a 16%-47% duty cycle of laser intensity modulation for direct imaging of oral soft tissue fixed in 10% formalin solution. The PA image quality of paraffin-embedded tissue was higher than that of direct oral soft tissue images, but no significant differences in PA image quality were found between the groups. Conclusion: The PAI system built in this study can image oral soft tissue. The sample preparation and the diode laser intensity modulation may influence the PA image quality for oral soft tissue imaging. Nonetheless, the influence of diode laser intensity modulation is not significant for the PA image quality of paraffin-embedded tissue. [ABSTRACT FROM AUTHOR]

Purpose: Blood-brain barrier disruption (BBBD) is of interest for treating neurodegenerative diseases and tumors by enhancing drug delivery. Focused ultrasound (FUS) is a powerful method to alleviate BBB challenges; however, the detection of BBB opening by non-invasive methods remains limited. The purpose of this work is to demonstrate that 3D transcranial color Doppler (3DCD) and photoacoustic imaging (PAI) combined with custom-made nanoparticle (NP)-mediated FUS delivery can detect BBBD in mice.Procedures: We use MRI and stereotactic ultrasound-mediated BBBD to create and confirm four openings in the left hemisphere and inject intravenously indocyanine green (ICG) and three sizes (40 nm, 100 nm, and 240 nm in diameter) of fluorophore-labeled NPs. We use PAI and fluorescent imaging (FI) to assess the spatial distribution of ICG/NPs in tissues.Results: A reversible 41 ± 12 % (n = 8) decrease in diameter of the left posterior cerebral artery (PCA) relative to the right after FUS treatment is found using CD images. The spectral unmixing of photoacoustic images of the in vivo (2 h post FUS), perfused, and ex vivo brain reveals a consistent distribution pattern of ICG and NPs at *FUS locations. Ex vivo spectrally unmixed photoacoustic images show that the opening width is, on average, 1.18 ± 0.12 mm and spread laterally 0.49 ± 0.05 mm which correlated well with the BBB opening locations on MR images. In vivo PAI confirms a deposit of NPs in tissues for hours and potentially days, is less sensitive to NPs of lower absorbance at a depth greater than 3 mm and too noisy with NPs above an absorbance of 85.4. FI correlates well with ex vivo PAI to a depth of 3 mm in tissues for small NPs and 4.74 mm for large NPs.Conclusions: 3DCD can monitor BBBD over time by detecting reversible anatomical changes in the PCA. In vivo 3DPAI at 15 MHz combined with circulating ICG and/or NPs with suitable properties can assess BBB opening 2 h post FUS. [ABSTRACT FROM AUTHOR]

The combination of positron emission tomography (PET)/photoacoustic imaging (PAI)/fluorescence imaging (FLI) for diagnosis allows to exploit the strengths and overcome the weaknesses of each modality. In this context, dyes displaying photophysical properties for both fluorescence and photoacoustic imaging in the near infra-red (NIR) window are ideal to maximize their signal-to-noise ratio. Herein, were synthetized a series of new meso - O -alkyl cyanine-7 derivatives, and the derivative bearing an azide was coupled to a highly functionalized C -glycosyl platform resulting in an imaging probe which exhibited both high molar absorptivity and fluorescence quantum yield (>15 %), excellent characteristics for FLI and for PAI. Successfully radiolabeled with fluorine-18 via a [18F]F–C bond, this probe additionally allowed PET imaging. Altogether, these results revealed the multimodal PET/PAI/FLI imaging potential of this probe based on meso - O -alkyl heptamethine cyanine. Moreover, a late-stage CuAAC coupling with two model peptides c (RGDfK) was successfully performed to demonstrate the feasibility and the versatility of the vector conjugation step, foreshadowing of the expected targeting possibilities of this original platform for efficient disease diagnosis by multimodal imaging. • Synthesis of a probe based on meso - O -alkyl cyanine-7 for PET/PAI/FLI imaging. • Excellent well-balanced photophysical properties for concomitant FLI and PAI. • [18F]F-radiolabelling via a [18F]F–C bond. • Late-stage CuAAC coupling with model peptides. [ABSTRACT FROM AUTHOR]

• Photoacoustic imaging merges optical and ultrasound benefits. • Biomedical applications of dual-modality imaging. • Importance of diverse imaging techniques. • Future directions in bimodal imaging technology. Photoacoustic imaging (PAI) is an emerging biomedical imaging technique that combines the advantages of optical and ultrasound imaging, enabling the generation of images with both optical resolution and acoustic penetration depth. By leveraging similar signal acquisition and processing methods, the integration of photoacoustic and ultrasound imaging has introduced a novel hybrid imaging modality suitable for clinical applications. Photoacoustic-ultrasound imaging allows for non-invasive, high-resolution, and deep-penetrating imaging, providing a wealth of image information. In recent years, with the deepening research and the expanding biomedical application scenarios of photoacoustic-ultrasound bimodal systems, the immense potential of photoacoustic-ultrasound bimodal imaging in basic research and clinical applications has been demonstrated, with some research achievements already commercialized. In this review, we introduce the principles, technical advantages, and biomedical applications of photoacoustic-ultrasound bimodal imaging techniques, specifically focusing on tomographic, microscopic, and endoscopic imaging modalities. Furthermore, we discuss the future directions of photoacoustic-ultrasound bimodal imaging technology. [ABSTRACT FROM AUTHOR]

A handheld approach to 3D photoacoustic imaging is essential in clinical applications. To this end, we develop a 3D handheld photoacoustic imager for dynamic (temporally and spatially) volumetric visualization. In this 3D imager, the optically transmitting part and the acoustically receiving part are integrated into a single handheld probe with a compact size about 160 mm $\times64$ mm $\times40$ mm. Besides, a dedicated imaging reconstruction algorithm for the heterogeneous medium is developed based on the phase-shift migration method in the frequency domain, which deals well with the stratified condition in the designed system. Dynamic 3D imaging supporting flexible handheld operation is demonstrated with needle biopsy and in vitro temperature measurement for photothermal therapy. The development of such a 3D handheld photoacoustic system paves the way for compact and handheld-operating implementations, and its further clinical exploration is promising. [ABSTRACT FROM AUTHOR]

Minimally-invasive monitoring of electrophysiological neural activities in real-time—that enables quantification of neural functions without a need for invasive craniotomy and the longer time constants of fMRI and PET—presents a very challenging yet significant task for neuroimaging. In this paper, we present in vivo functional PA (fPA) imaging of chemoconvulsant rat seizure model with intact scalp using a fluorescence quenching-based cyanine voltage-sensitive dye (VSD) characterized by a lipid vesicle model mimicking different levels of membrane potential variation. The framework also involves use of a near-infrared VSD delivered through the blood-brain barrier (BBB), opened by pharmacological modulation of adenosine receptor signaling. Our normalized time-frequency analysis presented in vivo VSD response in the seizure group significantly distinguishable from those of the control groups at sub-mm spatial resolution. Electroencephalogram (EEG) recording confirmed the changes of severity and frequency of brain activities, induced by chemoconvulsant seizures of the rat brain. The findings demonstrate that the near-infrared fPA VSD imaging is a promising tool for in vivo recording of brain activities through intact scalp, which would pave a way to its future translation in real time human brain imaging. [ABSTRACT FROM AUTHOR]

Metal nanoparticles especially of noble metals are used as an exogenous contrast agent for biomedical photoacoustic (PA) imaging in the tissue transmission window extending from visible to near infrared 700-1100 nm band. Different geometrical configurations of gold and silver nanoparticles like spherical core-shell, nanorod, and nanocages are promising candidates for thermoplasmonics, photothermal therapy, photothermal imaging, and photoacoustic imaging. In the current study, we simulated the photoacoustic response of gold and silica core-shell nanoparticle in water medium. Finite element simulations were carried out to study the spectral absorption response and effect of nanosecond laser pulse excitation on the spatial/temporal temperature as well as photoacoustic pressure variations of different core-shell geometry of nanoparticle. We have optimized the dimensions of gold nanosphere, gold-silica, and silica-gold core-shell geometries for optimum photoacoustic conversion efficiency. Further, the effect of shell thickness on the pulse photoacoustic signals for core-shell gold-silica and silica-gold nanoparticle has been studied. We concluded that silica-gold core-shell nanoparticles possess better photoacoustic conversion efficiency in comparison to gold nanosphere and gold-silica core-shell geometries. The prime aim of this study is to design efficient nano-probes for photoacoustic imaging, photoacoustic tomography, photothermal therapy, and drug delivery. [ABSTRACT FROM AUTHOR]

Photoacoustic (PA) imaging offers great promise for deep molecular imaging of optical reporters but has difficulties in imaging multiple molecular probes simultaneously in a strong blood background. Photoswitchable chromoproteins like BphP1 have recently allowed for sensitive PA detection by reducing high-blood background signals but lack multiplexing capabilities. We propose a method known as difference- spectra demixing for multiplexing multiple photoswitchable chromoproteins and introduce a second photoswitchable chromoprotein, sGPC2. sGPC2 has a far-red and orange state with peaks at 700 and 630 nm, respectively. It is roughly one-tenth the size of BphP1 and photoswitches four times as fast (2.4% per mJ/cm2). We simultaneously image Escherichia coli expressing sGPC2 and BphP1 injected in mice in vivo. Difference-spectra demixing obtained successful multiplexed images of photoswitchable molecular probes, resulting in a 21.6-fold increase in contrast-to-noise ratio in vivo over traditional PA imaging and an 8% to 40% reduction in erroneously demixed signals in comparison with traditional spectral demixing. PA imaging and characterization were conducted using a custom-built photoswitching PA imaging system. [ABSTRACT FROM AUTHOR]

Ultrasound (US) imaging is a well-established diagnostic technique to image soft tissues in real time, while photoacoustic (PA) is an emerging imaging technique employed to collect molecular information. Integration of PA and US imaging provides complementary information enhancing diagnostic accuracy without employing ionizing radiations. The development of contrast agents able to combine PA and US features is pivotal to improve the significance of PAUS imaging and for PAUS-guided treatment of neoplasms. Here, we demonstrate in relevant ex-vivo models that disassembling passion fruit-like nano-architectures ( pf NAs) can be employed in PAUS imaging. pf NAs are composed by silica nanocapsules comprising aggregates of commercial NIR-dyes-modified polymers and ultrasmall gold nanoparticles. The intrinsic US and PA features of pf NAs have been fully characterized and validated in tissue-mimicking materials and in ex vivo preparations. Moreover, the application of a multi-parametric approach has allowed the increase of information extrapolated from collected images for a fine texture analysis. [ABSTRACT FROM AUTHOR]

Gold nanoparticles (AuNPs) are used as a contrast agent of the photoacoustic (PA) imaging. The efficiency of AuNPs has been discussed with the absorption cross section. However, the effects of the scattering of the light by AuNPs and surrounding medium on the PA signal from AuNPs have not been discussed. The PA signals from the aqueous solution of AuNPs were examined in the numerical simulation and the experiment. In the numerical simulation, the absorption and scattering cross sections of spherical and polyhedral AuNPs were calculated by Mie theory and discrete dipole approximation. Monte Carlo simulation calculated the absorbed light energy in the aqueous solution of AuNPs. Based on the PA wave equation, the PA signals were simulated. In the experiment, the PA signal from the aqueous solution of AuNP was measured by use of a piezoelectric film and a Q-switched Nd:YAG laser operated at 532 nm. The results of the numerical simulation and the experiment agreed well. In the numerical simulation and the experiment, a single Au nanocube with 50-nm edge generated the peak value of the PA signal significantly. It was approximately 350 times and twice as large as the peak values of the spherical AuNPs with 10- and 50-nm diameters, respectively. The peak value of the PA signal depended on both the absorption and scattering coefficients of the AuNPs and the surrounding medium. The peak value increased with the scattering coefficient in a quadratic manner. The character of the temporal profile of the PA signal such as full width at half maximum depended on the scattering coefficient of the AuNPs. [ABSTRACT FROM AUTHOR]

We previously launched a high-resolution photoacoustic (PA) imaging scanner based on a unique lensless design for in vivo skin imaging. The design, imaging algorithm and characteristics of the system are described in this paper. Neither an optical lens nor an acoustic lens is used in the system. In the imaging head, four sensor elements are arranged quadrilaterally, and by checking the phase differences for PA waves detected with these four sensors, a set of PA signals only originating from a chromophore located on the sensor center axis is extracted for constructing an image. A phantom study using a carbon fiber showed a depth-independent horizontal resolution of 84.0 ± 3.5 µm, and the scan direction-dependent variation of PA signals was about ± 20%. We then performed imaging of vasculature phantoms: patterns of red ink lines with widths of 100 or 200 μm formed in an acrylic block co-polymer. The patterns were visualized with high contrast, showing the capability for imaging arterioles and venues in the skin. Vasculatures in rat burn models and healthy human skin were also clearly visualized in vivo. [ABSTRACT FROM AUTHOR]

We have developed laser-activated perfluorocarbon nanodroplets containing copper sulfide nanoparticles (CuS NPs) for contrast-enhanced ultrasound and photoacoustic imaging. As potential clinical contrast agents, CuS NPs have favorable properties including biocompatibility, biodegradability, and enhance contrast in photoacoustic images at clinically relevant depths. However, CuS NPs are not efficient optical absorbers when compared to plasmonic nanoparticles and therefore, contrast enhancement with CuS NPs is limited, requiring high concentrations to generate images with sufficient signal-to-noise ratio. We have combined CuS NPs with laser-activated perfluorocarbon nanodroplets (PFCnDs) to achieve enhanced photoacoustic contrast and, more importantly, ultrasound contrast while retaining the favorable clinical characteristics of CuS NPs. The imaging characteristics of synthesized CuS-PFCnD constructs were first tested in tissue-mimicking phantoms and then in in vivo murine models. The results demonstrate that CuS-PFCnDs enhance contrast in photoacoustic (PA) and ultrasound (US) imaging. Upon systemic administration in vivo, CuS-PFCnDs remain stable and their unique vaporization provides sufficient PA/US contrast that can be further exploited for contrast-enhanced background-free imaging. The conducted studies provide a solid foundation for further development of CuS-PFCnDs as PA/US diagnostic and eventually therapeutic agents for clinical applications. [ABSTRACT FROM AUTHOR]

Coronary heart disease (the presence of coronary atherosclerotic plaques) is a significant health problem in the industrialized world. A clinical method to accurately visualize and characterize atherosclerotic plaques is needed. Intravascular photoacoustic (IVPA) imaging is being developed to fill this role, but questions remain regarding optimal imaging wavelengths. We utilized a Monte Carlo optical model to simulate IVPA excitation in coronary tissues, identifying optimal wavelengths for plaque characterization. Near-infrared wavelengths (≤1800 nm) were simulated, and single- and dual-wavelength data were analyzed for accuracy of plaque characterization. Results indicate light penetration is best in the range of 1050 to 1370 nm, where 5% residual fluence can be achieved at clinically relevant depths of ≥2 mm in arteries. Across the arterial wall, fluence may vary by over 10-fold, confounding plaque characterization. For single-wavelength results, plaque segmentation accuracy peaked at 1210 and 1720 nm, though correlation was poor (<0.13). Dual-wavelength analysis proved promising, with 1210 nm as the most successful primary wavelength (≈1.0). Results suggest that, without flushing the luminal blood, a primary and secondary wavelength near 1210 and 1350 nm, respectively, may offer the best implementation of dual-wavelength IVPA imaging. These findings could guide the development of a costeffective clinical system by highlighting optimal wavelengths and improving plaque characterization. [ABSTRACT FROM AUTHOR]

The lymphatic system is responsible for fluid homeostasis and immune cell trafficking and has been implicated in several diseases, including obesity, diabetes, and cancer metastasis. Despite its importance, the lack of suitable in vivo imaging techniques has hampered our understanding of the lymphatic system. This is, in part, due to the limited contrast of lymphatic fluids and structures. Photoacoustic imaging, in combination with optically absorbing dyes or nanoparticles, has great potential for noninvasively visualizing the lymphatic vessels deep in tissues. Multispectral photoacoustic imaging is capable of separating the components; however, the slow wavelength switching speed of most laser systems is inadequate for imaging lymphatic pumping without motion artifacts being introduced into the processed images. We investigate two approaches for visualizing lymphatic processes in vivo. First, single-wavelength differential photoacoustic imaging is used to visualize lymphatic pumping in the hindlimb of a mouse in real time. Second, a fast-switching multiwavelength photoacoustic imaging system was used to assess the propulsion profile of dyes through the lymphatics in real time. These approaches may have profound impacts in noninvasively characterizing and investigating the lymphatic system. [ABSTRACT FROM AUTHOR]

We propose a compact and easy to use photoacoustic imaging (PAI) probe structure using a single strand of optical fiber and a beam combiner doubly reflecting acoustic waves for convenient detection of lymph nodes and cancers. Conventional PAI probes have difficulty detecting lymph nodes just beneath the skin or simultaneously investigating lymph nodes located in shallow as well as deep regions from skin without any supplementary material because the light and acoustic beams are intersecting obliquely in the probe. To overcome the limitations and improve their convenience, we propose a probe structure in which the illuminated light beam axis coincides with the axis of the ultrasound. The developed PAI probe was able to simultaneously achieve a wide range of images positioned from shallow to deep regions without the use of any supplementary material. Moreover, the proposed probe had low transmission losses for the light and acoustic beams. Therefore, the proposed PAI probe will be useful to easily detect lymph nodes and cancers in real clinical fields. [ABSTRACT FROM AUTHOR]

All-optically integrated photoacoustic (PA) and optical coherence tomography (OCT) dual-mode imaging technology that could offer comprehensive pathological information for accurate diagnosis in clinic has gradually become a promising imaging technology in the aspect of biomedical imaging during the recent years. This review refers to the technology aspects of all-optical PA detection and system evolution of optically integrated PA and OCT, including Michelson interferometer dual-mode imaging system, Fabry-Perot (FP) interferometer dual-mode imaging system and Mach-Zehnder interferometer dual-mode imaging system. It is believed that the optically integrated PA and OCT has great potential applications in biomedical imaging. [ABSTRACT FROM AUTHOR]