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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]

Abstract 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. Graphical abstract

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]

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]

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.

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]

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.

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]

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]

Clotting is a physiological process that prevents blood loss after injury. An imbalance in clotting factors can lead to lethal consequences such as exsanguination or inappropriate thrombosis. Clinical methods to monitor clotting and fibrinolysis typically measure the viscoelasticity of whole blood or optical density of plasma over time. Though these methods provide insights into clotting and fibrinolysis, they require milliliters of blood which can worsen anemia or only provide partial information. To overcome these limitations, a high-frequency photoacoustic (HFPA) imaging system was developed to detect clotting and lysis in blood. Clotting was initiated in vitro in reconstituted blood using thrombin and lysed with urokinase plasminogen activator. Frequency spectra measured using HFPA signals (10–40 MHz) between non-clotted blood and clotted blood differed markedly, allowing tracking of clot initiation and lysis in volumes of blood as low as 25 µL/test. HFPA imaging shows potential as a point-of-care examination of coagulation and fibrinolysis.

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]

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]

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]

Abstract Photoacoustic (PA) imaging is a novel, rapidly expanding diagnostic technique, which has been predominately developed in the context of contemporary biomedical research studies. In this review, we demonstrate how PA technologies can break through the barriers of biomedicine to find innovative applications in cultural heritage (CH) diagnostics and laser cleaning monitoring. Having over three orders of magnitude higher transmission through strongly scattering media, compared to light in the visible and near infrared, PA signals offer substantially improved detection sensitivity, providing optical absorption contrast at high spatial resolution. This unique combination of features is employed for establishing novel diagnostic methodologies aiming to uncover well-hidden features and provide structural information in multi-layered CH objects such as paintings and documents. Finally, we demonstrate that the PA effect can be successfully utilized for the reliable monitoring of laser cleaning interventions on stonework, allowing for a safe and well-controlled cleaning procedure which will safeguard CH objects’ original surfaces. Simplicity of implementation, effectiveness and low-cost features provided by the developed diagnostic and monitoring systems, highlight the rich potential of emerging PA technologies in CH studies and offer exciting possibilities for future implementations.

Imaging systems that integrate multiple modalities can reveal complementary anatomic and functional information as they exploit different contrast mechanisms, which have shown great application potential and advantages in preclinical studies. A portable and easy-to-use imaging probe will be more conducive to transfer to clinical practice. Here, we present a tri-modal ultrasonic (US), photoacoustic (PA), and thermoacoustic (TA) imaging system with an excitation-reception collinear probe. The acoustic field, light field, and electric field of the probe were designed to be coaxial, realizing homogeneous illumination and high-sensitivity detection at the same detection position. US images can provide detailed information about structures, PA images can delineate the morphology of blood vessels in tissues, and TA images can reveal dielectric properties of the tissues. Moreover, phantoms and in vivo human finger experiments were performed by the tri-modal imaging system to demonstrate its performance. The results show that the tri-modal imaging system with the proposed probe has the ability to detect small breast tumors with a radius of only 2.5 mm and visualize the anatomical structure of the finger in three dimensions. Our work confirms that the tri-modal imaging system equipped with a collinear probe can be applied to a variety of different scenarios, which lays a solid foundation for the application of the tri-modality system in clinical trials. [ABSTRACT FROM AUTHOR]

Subsurface imaging is challenging; it is difficult to detect objects visually. In this research, a novel non-contact photoacoustic (PA) imaging system was developed to detect subsurface objects. The Rosencwaig-Gersho (RG) model was successfully employed to capture micro-object images covered by rough paint. The experiments were conducted using a copper ring with a 1-mm diameter fully coated by rough paint with an average thickness of 2.3 μm. The resulting PA images exhibited up to 72% consistency despite the rough paint; the shapes of the objects were clearly recognized before and after coating. To conduct the experiment, simulations and image acquisitions were arranged. Then, the system capability to produce tomographic images was improved by adjusting the thermal diffusion lengths, and subsurface object images were successfully acquired at depths of 2.0, 2.6, 9.8, and 52 μm. The detailed composition of image slices displayed the structure profile of subsurface objects appropriately.

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]

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]

Using near-infrared femtosecond pulses, we move single gold nanoparticles (AuNPs) along biological fibers, such as collagen and actin filaments. While the AuNP is sliding on the fiber, its trajectory is measured in three dimensions (3D) with nanometer resolution providing a high-resolution image of the fiber. Here, we systematically moved a single AuNP along nanometer-size collagen fibers and actin filament inside chinese hamster ovary K1 living cells, mapping their 3D topography with high fidelity.

Early stage cancer detection technologies can provide functional information and potentially decrease the mortality rate caused by cervical cancer. In our previous work, a miniaturized ultrasound and photoacoustic endoscopic system has been developed to image the cervical tissue through the cervical canal to fulfills the need for a safe, low-cost, and high-resolution functional diagnostic system. However, the miniaturized size of endoscope and American National Standards Institute safety limits cause constraints of using high-intensity illumination during imaging. In addition, the strong light scattering of tissues limits the light penetration depth. Fortunately, the cervix anatomy allows for the delivery of additional light from the ectocervix by using an external illumination system. Here we propose a dual, co-planar illumination system, which can provide adequate illumination to the cervical tissue via combined internal and external light delivery strategies. Therefore, an increase in the area of light-tissue interaction allows us to raise the laser light energy while keeping fluence under safety limits. Thus, a reliable PA imaging can be obtained for the whole cervical tissue thickness. The system performance was tested using a Monte Carlo simulation, and laser-light fluence was calculated and compared at different depths within a simulated cervical-tissue model. The results indicated a higher and more uniform fluence in the Monte Carlo simulations. In addition, the photoacoustic imaging of the proposed system was evaluated by two cervical tissue-mimicking phantoms with human blood and graphite rods as inclusions inside it. In accordance with the simulations, the phantom study revealed a more reliable photoacoustic signal for the entire depth of the phantoms with an improved contrast to noise ratio and signal to noise ratio, and a higher coverage ratio of the imaging field of view. In summary, the dual-mode illumination system can provide more realistic information of inclusions within the tissue while considering safety limits, which can lead to more accuracy in biomarker detection for cervical cancer diagnostics. [ABSTRACT FROM AUTHOR]

Breast conserving surgery (BCS) offering similar surgical outcomes as mastectomy while retaining breast cosmesis is becoming increasingly popular for the management of early stage breast cancers. However, its association with reoperation rates of 20% to 40% following incomplete tumor removal warrants the need for a fast and accurate intraoperative surgical margin assessment tool that offers cellular, structural and molecular information of the whole specimen surface to a clinically relevant depth. Biophotonic technologies are evolving to qualify as such an intraoperative tool for clinical assessment of breast cancer surgical margins at the microscopic and macroscopic scale. Herein, we review the current research in the application of biophotonic technologies such as photoacoustic imaging, Raman spectroscopy, multimodal multiphoton imaging, diffuse optical imaging and fluorescence imaging using medically approved dyes for breast cancer detection and/or tumor subtype differentiation toward intraoperative assessment of surgical margins in BCS specimens, and possible challenges in their route to clinical translation. [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]

Rheological properties, such as elasticity and viscosity, are fundamental biomechanical parameters that are related to the function and pathological status of cells and tissues. In this paper, an innovative photoacoustic microrheology (PAMR), which utilized the time and phase characteristics of photoacoustic (PA) response, was proposed to extract elastic modulus and viscosity. The feasibility and accuracy of the method were validated by tissue-mimicking agar-gelatin phantoms with various viscoelasticity values. PAMR realized single cell elasticity and viscosity mappings on the adipocyte and myocyte with micrometer scale. In clinical samples, normal blood cells and iron deficiency anemia cells were successfully distinguished due to their various rheological properties. This method expands the scope of conventional PA imaging and opens new possibilities for developing microrheological technology, prefiguring great clinical potential for interrogating mechanocellular properties. [ABSTRACT FROM AUTHOR]

We use a modified Mach-Zehnder interferometer to measure surface displacement resulting from the thermoelastic response of a target to the absorption of a short laser pulse with axial and temporal resolutions of 0.1 nm and 3 ns, respectively. These measurements are used in conjunction with a solution to the thermoelastic wave equation and a nonlinear optimization algorithm to extract optical attenuation depth. We demonstrate the ability to determine the effective optical attenuation depth of homogeneous targets with either diffuse or specular reflecting surfaces with a precision of

We introduce a minimally invasive technique for optoacoustic imaging of turbid media using optical interferometric detection of surface displacement produced by thermoelastic stress transients. The technique exploits endogenous or exogenous optical contrast of heterogeneous tissues and the low attenuation of stress wave propagation to localize and image subsurface absorbers in optically turbid media. We present a system that utilizes a time-resolved high-resolution interferometer capable of angstrom-level displacement resolution and nanosecond temporal resolution to detect subsurface blood vessels within model tissue phantoms and a human forearm in vivo.

Sentinel lymph node (SLN) biopsy is an integral part of treatment planning for a variety of cancers as it evaluates whether a tumor has metastasized, an event that significantly reduces survival probability. However, this invasive procedure is associated with patient morbidity, and misses small metastatic deposits, resulting in the removal of additional nodes for tumors with high metastatic probability despite a negative SLN biopsy. To prevent this over-treatment and its associated morbidities for patients that were truly negative, we propose a tissue oxygen imaging method called Photoacoustic Lifetime Imaging (PALI) as an alternative or supplementary tool for SLN biopsy. As the hyper-metabolic state of cancer cells significantly depresses tissue oxygenation compared to normal tissue even for small metastatic deposits, we hypothesize that PALI can sensitively and specifically detect metastases. Before this hypothesis is tested, however, PALI’s maximum imaging depth must be evaluated to determine the cancer types for which it is best suited. To evaluate imaging depth, we developed and simulated a phantom composed of tubing in a tissue-mimicking, optically scattering liquid. Our simulation and experimental results both show that PALI’s maximum imaging depth is 16 mm. As most lymph nodes are deeper than 16 mm, ways to improve imaging depth, such as directly delivering light to the node using penetrating optical fibers, must be explored.

Detection and visualization of β-galactosidase (β-gal) is essential to reflect its physiological and pathological effects on human health and disease, but it is still challenging to precisely track β-gal in vivo owing to the limitation of current analytical methods. In our work, we reported a photoacoustic (PA) nanoprobe for selective imaging of the endogenous β-gal in vivo. Our nanoprobe Cy7-β-gal-LP was constructed by encapsulation of a near-infra red (NIR) dye Cy7-β-gal within a liposome (LP, DSPE-PEG2000-COOH). The dye Cy7-β-gal was synthesized based on a dye Cy-OH where the hydroxyl group was replaced by a β-D-galactopyranoside residue, which can be recognized by β-gal as an enzyme hydrolytic site. With the addition of β-gal, the absorbance of Cy7-β-gal exhibited a significant red shift with the absorption peak moved from 600nm to 680nm, which should generate a switch-on PA signal at 680nm in the presence of β-gal. In addition, as the fluorescence of the dye was totally quenched due to aggregation within the liposome, Cy7-β-gal-LP exhibited high PA conversion efficiency. With the nanoprobe, we achieved the selective PA detection and imaging of β-gal in the tumor-bearing mice.

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.

Subsurface imaging is challenging; it is difficult to detect objects visually. In this research, a novel non-contact photoacoustic (PA) imaging system was developed to detect subsurface objects. The Rosencwaig-Gersho (RG) model was successfully employed to capture microobject images covered by rough paint. The experiments were conducted using a copper ring with a 1-mm diameter fully coated by rough paint with an average thickness of 2.3 μm. The resulting PA images exhibited up to 72% consistency despite the rough paint; the shapes of the objects were clearly recognized before and after coating. To conduct the experiment, simulations and image acquisitions were arranged. Then, the system capability to produce tomographic images was improved by adjusting the thermal diffusion lengths, and subsurface object images were successfully acquired at depths of 2.0, 2.6, 9.8, and 52 μm. The detailed composition of image slices displayed the structure profile of subsurface objects appropriately. [ABSTRACT FROM AUTHOR]

Raster-scan optoacoustic mesoscopy (RSOM) offers high-resolution non-invasive insights into skin pathophysiology, which holds promise for disease diagnosis and monitoring in dermatology and other fields. However, RSOM is quite vulnerable to vertical motion of the skin, which can depend on the part of the body being imaged. Motion correction algorithms have already been proposed, but they are not fully automated, they depend on anatomical segmentation pre-processing steps that might not be performed successfully, and they are not site- specific. Here, we determined for the first time the magnitude of the micrometric vertical skin displacements at different sites on the body that affect RSOM. The quantifi- cation of motion allowed us to develop a site-specific correction algorithm. The algorithm is fully automated and does not need prior anatomical information. We found that the magnitude of the vertical motion depends strongly on the site of imaging and is caused by breathing, heart beating, and arterial pulsation. The developed algorithm resulted in more than 2-fold improvement in the signal-to-noise ratio of the reconstructed images at every site tested. Proposing an effective automated motion correction algorithm paves the way for realizing the full clinical potential of RSOM. [ABSTRACT FROM AUTHOR]

Detection and visualization of β -galactosidase (β -gal) is essential to reflect its physiological and pathological effects on human health and disease, but it is still challenging to precisely track β -gal in vivo owing to the limitation of current analytical methods. In our work, we reported a photoacoustic (PA) nanoprobe for selective imaging of the endogenous β -gal in vivo. Our nanoprobe Cy7- β -gal-LP was constructed by encapsulation of a near-infra red (NIR) dye Cy7- β -gal within a liposome (LP, DSPE-PEG2000-COOH). The dye Cy7- β -gal was synthesized based on a dye Cy-OH where the hydroxyl group was replaced by a β -D-galactopyranoside residue, which can be recognized by β -gal as an enzyme hydrolytic site. With the addition of β -gal, the absorbance of Cy7- β -gal exhibited a significant red shift with the absorption peak moved from 600 nm to 680 nm, which should generate a switch-on PA signal at 680 nm in the presence of β -gal. In addition, as the fluorescence of the dye was totally quenched due to aggregation within the liposome, Cy7- β -gal-LP exhibited high PA conversion efficiency. With the nanoprobe, we achieved the selective PA detection and imaging of β -gal in the tumor-bearing mice. [ABSTRACT FROM AUTHOR]

EGFR is a promising cell surface target for in vivo imaging that is highly overexpressed in hepatocellular carcinoma (HCC), a common cancer worldwide. Peptides penetrate easily into tumors for deep imaging, and clear rapidly from the circulation to minimize background. We aim to demonstrate use of an EGFR specific peptide to detect HCC xenograft tumors in mice with photoacoustic imaging. Nude mice implanted with human HCC cells that overexpress EGFR were injected intravenously with Cy5.5-labeled EGFR and scrambled control peptides respectively. Photoacoustic images collected from 0 to 24 h. Photoacoustic signal peaked in tumors at 3 h post-injection. Images from 0 to 1.8 cm beneath the skin revealed increased target-to-background (T/B) ratio from tumors. The T/B ratio was significantly greater for the EGFR versus control peptide. Clearance of signal was observed by ∼24 h. EGFR overexpression was validated with immunofluorescence and immunohistochemistry. A peptide specific for EGFR delivered systemically can detect HCC xenograft tumors in vivo with photoacoustic imaging.

Endoscopic integrated photoacoustic and ultrasound imaging has the potential for early detection of cancer in the gastrointestinal tract. Currently, a slow imaging speed is one of the limitations for clinical translation. Here, we developed a high-speed integrated endoscopic PA and US imaging system, which is able to perform PA and US imaging simultaneously up to 50 frames per second. Using this system, the architectural morphology and vasculature of the rectum wall were visualized from a Sprague Dawley rat in vivo. [ABSTRACT FROM AUTHOR]

Although transrectal ultrasound (TRUS) imaging is widely used for screening and diagnosing prostate cancer, it is often not found on TRUS images, depending on its stage, size, and location. In addition, due to the weak echo signal and the low contrast of TRUS images, it is difficult to diagnose early-stage prostate cancers and distinguish malignant tumors from benign prostatic hyperplasia. For this reason, TRUS image-guided biopsy is mandatory to confirm the malignancy of the suspicious tumor, but the diagnostic accuracy of initial biopsy is only 20%–30%, so that the patients inevitably undergo repeated biopsies. TRUS-photoacoustic (TRUS-PA) imaging is one way to resolve those problems. However, the development of a TRUS-PA probe, in which an ultrasound array transducer and optical fibers are integrated, is demanding because the overall size of the probe should be as small as possible for the convenience of the patients, while providing the desired performances. Here, we report a recently developed TRUS-PA probe. The core element of the TRUS-PA is a miniaturized 128-element, 7-MHz convex array transducer of which size in the lateral and elevational directions is 11.4 and 5 mm, respectively. A new concept of a flexible printed circuit board was also developed to limit the size of the TRUS-PA probe to less than 15 mm. From the performance evaluation, it was found that the developed array with a field-of-view of 134° has a center frequency of 6.75 MHz, a −6-dB fractional bandwidth of 66%, and a crosstalk of less than −45 dB. In the tissue-mimicking phantom test andex vivoexperiments, the miniaturized convex array proved to be capable of providing combined US and PA images with acceptable imaging quality in spite of its small size. [ABSTRACT FROM AUTHOR]

Optoacoustic (photoacoustic) technique is a novel diagnostic platform that can be used for noninvasive measurements of physiologic variables, functional imaging, and hemodynamic monitoring. This technique is based on generation and time-resolved detection of optoacoustic (thermoelastic) waves generated in tissue by short optical pulses. This provides probing of tissues and individual blood vessels with high optical contrast and ultrasound spatial resolution. Because the optoacoustic waves carry information on tissue optical and thermophysical properties, detection, and analysis of the optoacoustic waves allow for measurements of physiologic variables with high accuracy and specificity. We proposed to use the optoacoustic technique for monitoring of a number of important physiologic variables including temperature, thermal coagulation, freezing, concentration of molecular dyes, nanoparticles, oxygenation, and hemoglobin concentration. In this review we present origin of contrast and high spatial resolution in these measurements performed with optoacoustic systems developed and built by our group. We summarize data obtained in vitro, in experimental animals, and in humans on monitoring of these physiologic variables. Our data indicate that the optoacoustic technology may be used for monitoring of cerebral blood oxygenation in patients with traumatic brain injury and in neonatal patients, central venous oxygenation monitoring, total hemoglobin concentration monitoring, hematoma detection and characterization, monitoring of temperature, and coagulation and freezing boundaries during thermotherapy.

The synthesis and characterization of a series of donor-π-acceptor-π-donor (D-A-D) curcuminoid molecules is presented herein that incorporates π-extended aryl and electron-donating amino terminal functionalization. Computational evaluation shows these molecules possess quadrupolar character with the lowest energy transitions displaying high molar extinction coefficients with broad tunability through manipulation of terminal donating groups. Consistent with their quadrupolar nature, these molecules show varying degrees of solvatochromic behavior in both their absorption and emission spectra, which has been analyzed by Lippert-Mataga and Kamlet-Taft analysis. Photophysical and photoacoustic (PA) properties of these molecules have been investigated by the optical photoacoustic z-scan (OPAZ) method. Selected curcuminoid molecules display nonlinear behavior at a high laser fluence through excited state absorption that translates to the production of an enhanced photoacoustic emission. A relative comparison of "molar PA emission" is also presented with the crystal violet linear optical absorbing/linear PA emitting system being utilized as a standard reference material for OPAZ experiments. Furthermore, PA tomography experiments are presented to illustrate the enhanced PA contrast obtainable via an excited state absorption. [ABSTRACT FROM AUTHOR]

Optoacoustic (photoacoustic) technique is a novel diagnostic platform that can be used for noninvasive measurements of physiologic variables, functional imaging, and hemodynamic monitoring. This technique is based on generation and time-resolved detection of optoacoustic (thermoelastic) waves generated in tissue by short optical pulses. This provides probing of tissues and individual blood vessels with high optical contrast and ultrasound spatial resolution. Because the optoacoustic waves carry information on tissue optical and thermophysical properties, detection, and analysis of the optoacoustic waves allow for measurements of physiologic variables with high accuracy and specificity. We proposed to use the optoacoustic technique for monitoring of a number of important physiologic variables including temperature, thermal coagulation, freezing, concentration of molecular dyes, nanoparticles, oxygenation, and hemoglobin concentration. In this review we present origin of contrast and high spatial resolution in these measurements performed with optoacoustic systems developed and built by our group. We summarize data obtained in vitro, in experimental animals, and in humans on monitoring of these physiologic variables. Our data indicate that the optoacoustic technology may be used for monitoring of cerebral blood oxygenation in patients with traumatic brain injury and in neonatal patients, central venous oxygenation monitoring, total hemoglobin concentration monitoring, hematoma detection and characterization, monitoring of temperature, and coagulation and freezing boundaries during thermotherapy. [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]

Optoacoustic (photoacoustic) diagnostic modality is a technique that combines high optical contrast and ultrasound spatial resolution. We proposed using the optoacoustic technique for a number of applications, including cancer detection, monitoring of thermotherapy (hyperthermia, coagulation, and freezing), monitoring of cerebral blood oxygenation in patients with traumatic brain injury, neonatal patients, fetuses during late-stage labor, central venous oxygenation monitoring, and total hemoglobin concentration monitoring as well as hematoma detection and characterization. We developed and built optical parametric oscillator-based systems and multiwavelength, fiber-coupled highly compact, laser diode-based systems for optoacoustic imaging, monitoring, and sensing. To provide sufficient output pulse energy, a specially designed fiber-optic system was built and incorporated in ultrasensitive, wideband optoacoustic probes. We performed preclinical and clinical tests of the systems and the optoacoustic probes in backward mode for most of the applications and in forward mode for the breast cancer and cerebral applications. The high pulse energy and repetition rate allowed for rapid data acquisition with high signal-to-noise ratio from cerebral blood vessels, such as the superior sagittal sinus, central veins, and peripheral veins and arteries, as well as from intracranial hematomas. The optoacoustic systems were capable of automatic, real-time, continuous measurements of blood oxygenation in these blood vessels. [ABSTRACT FROM AUTHOR]

Optical imaging is a rapidly progressing medical technique that can benefit from the development of new and improved optical imaging agents suitable for use in vivo. However, the molecular rules detailing what optical agents can be processed and encapsulated into in vivo presentable forms are not known. We here present the screening of series of highly hydrophobic porphyrin, phthalocyanine, and naphthalocyanine dye macrocycles through a self-assembling Flash NanoPrecipitation process to form a series of water dispersible dye nanoparticles (NPs). Ten out of 19 tested dyes could be formed into poly(ethylene glycol) coated nanoparticles 60-150 nm in size, and these results shed insight on dye structural criteria that are required to permit dye assembly into NPs. Dye NPs display a diverse range of absorbance profiles with absorbance maxima within the NIR region, and have absorbance that can be tuned by varying dye choice or by doping bulking materials in the NP core. Particle properties such as dye core load and the compositions of co-core dopants were varied, and subsequent effects on photoacoustic and fluorescence signal intensities were measured. These results provide guidelines for designing NPs optimized for photoacoustic imaging and NPs optimized for fluorescence imaging. This work provides important details for dye NP engineering, and expands the optical imaging tools available for use. [ABSTRACT FROM AUTHOR]

We demonstrate the application of an extended field of view hybrid microscope, integrating distinct optical and photoacoustic (PA) contrast modes, for the precise three-dimensional anatomy delineation of the ciliary body/iris structures in healthy rabbit eyes ex vivo. The glutaraldehyde- induced autofluorescence and the intrinsic PA signals provided by each of the employed imaging modalities were characterized by a high spatial complementarity, offering thus rich morphological information regarding the pars plana and pars plicata ciliary body portions, the iris as well as, the attached zonule fiber strands. The bimodal microscopy approach presented could find application on studies involving the ocular accommodation mechanism or pathological ciliary body conditions, as a powerful diagnostic technique contributing to the understanding of ocular physiology and function. [ABSTRACT FROM AUTHOR]

Pigments in vegetative tissues have been a subject of intense research during the previous decades, since they play an active role in several molecular mechanisms regarding plants' physiology and function. Towards this direction, the imaging modality that has been extensively employed and represents the state of the art for mapping pigments' distribution is confocal microscopy. Despite the advantage of a high spatial resolution however, confocal microscopy provides a rather limited imaging depth and requires necessarily strong fluorescence properties from the specimen under observation. To overcome such limitations, we propose a hybrid, photoacoustic and optical imaging methodology for the delineation of various vegetative pigments, such as chlorophylls, anthocyanins and betalains in different plant species. The superior sensitivity and the high contrast complementarity of the hybrid technique, render it a powerful alternative to the conventional fluorescence imaging modalities, significantly expanding the current state of the art. [ABSTRACT FROM AUTHOR]

The photoacoustic response of polypyrrole particles was studied in relation to the type and amount of oxidant used for their synthesis by photoacoustic spectroscopy. At the same time, a detailed study of the molecular structure of these particles was performed using infrared and Raman spectroscopy. It was found that the particles prepared using superstoichiometric amounts of the oxidizer, n Py: n Oxi = 1:3, in the case of FeCl 3 and stochiometric n Py: n Oxi = 1:1, in the case of (NH 4) 2 S 2 O 8 - showed the best photoacoustic output. At ratios n Py: n Oxi oxidants equal to or less than 1:2 in the case of FeCl 3 , oligomers and polypyrrole with a longer kinetic chain length might be formed, whereas the higher oxidant content no longer affects the quality of the product. In the case of oxidation by (NH 4) 2 S 2 O 8 , amounts of oxidant higher than 1:2 led to the formation of over-oxidized products. Although nanoparticles prepared at the stoichiometric ratios of both oxidizing agents were equivalent in terms of the molecular structure determined by the IR and Raman spectra, the particles prepared by (NH 4) 2 S 2 O 8 show a slightly stronger PA signal. [Display omitted] • The photoacoustic response of polypyrrole depends more on the stoichiometry than on the type of oxidant used for oxidation. • The primary polymer structure and the stoichiometry of the oxidants affects the structure and morphology of the polypyrrole nanoparticles. • The oxidation by APS around the stoichiometric optimum leads to the material with stronger photoacoustic signal. • The reaction is more prone to overoxidation at above APS stochiometric optimum in comparison with ferric chloride. [ABSTRACT FROM AUTHOR]

In this paper, a novel photoacoustic viscoelasticity imaging (PAVEI) technique that provides viscoelastic information of biological tissues is presented. We deduced the process of photoacoustic (PA) effect on the basis of thermal viscoelasticity theory and established the relationship between the PA phase delay and the viscoelasticity for soft solids. By detecting the phase delay of PA signal, the viscoelasticity distribution of absorbers can be mapped. Gelatin phantoms with different densities and different absorption coefficients were used to verify the dependence of PAVEI measurements. Moreover, tissue mimicking phantoms mixed with fat and collagen at different concentrations were used to testify the feasibility of this technique with reliable contrast. Finally, the PAVEI was successfully applied to discrimination between biological tissue constituents. Our experimental results demonstrate that this novel technique has the potential for visualizing the anatomical and biomechanical properties of biological tissues.

Real-Time Optoacoustic Monitoring of RF Ablation Introduction Due to lack of reliable imaging contrast from catheter radiofrequency ablation (RFA) lesions, the vast majority of current procedures rely on indirect indicators of ablation activity, resulting in a significant number of arrhythmia reoccurrences after RFA procedures and the need for repeat surgeries. The objective of this work is to develop an accurate method for on-the-fly assessment of the durability and size of lesions formed during RFA procedures. Method and Results Radiofrequency catheter ablation on freshly excised porcine ventricular myocardial tissue was optoacoustically monitored by means of pulsed-laser illumination in the near-infrared spectrum. Lesion formation during ablation was captured at a rate of 10 Hz with a 256-detector optoacoustic imaging probe. Postablated samples were imaged using multispectral excitation in the wavelength range 740-860 nm to determine the lesion contrast spectrum. Tomographic reconstruction was performed to generate 3-dimensional images of the lesions, which were compared to photographs depicting the final ablated tissue samples. Video-rate 3-dimensional tomographic reconstructions depict formation of the lesion with high contrast and spatial resolution. The size and geometry of the lesion was shown to be in excellent agreement with the histological examinations. The wavelength dependence of the lesion contrast shows a contrast peak near 780 nm. Conclusion Deep-tissue 3-dimensional monitoring of RFA lesion generation in real time was demonstrated for the first time in this work. The results suggest the potential of optoacoustic monitoring for providing critical feedback on lesion position and size during radiofrequency catheter ablation, improving safety and efficacy of these treatments. [ABSTRACT FROM AUTHOR]