Photoacoustic Imaging Technique Research Articles

Advances in Photoacoustic Endoscopic Imaging Technology for Prostate Cancer Detection

The rapid progress in biomedical imaging technology has generated considerable interest in new non-invasive photoacoustic endoscopy imaging techniques. This emerging technology offers significant benefits, including high spectral specificity, strong tissue penetration, and real-time multidimensional high-resolution imaging capabilities, which enhance clinical diagnosis and treatment of prostate cancer. This paper delivers a thorough review of current prostate cancer screening techniques, the core principles of photoacoustic endoscopy imaging, and the latest research on its use in detecting prostate cancer. Additionally, the limitations of this technology in prostate cancer detection are discussed, and future development trends are anticipated.

NIR-II femtosecond laser-induced nonlinear absorption facilitates foreground-extraction photoacoustic imaging by monolayer WS2-PVP nanosheets

Exogenous contrast agents have been extensively applied in photoacoustic (PA) molecular imaging for disease diagnosis, benefiting from their advantageous optical, thermal, and internal delivery properties. However, their in vivo performance was inevitably interfered by background tissue optical absorption, resulting in low imaging contrast and sensitivity. Here, we report a NIR-II femtosecond laser-induced nonlinearly enhanced PA imaging technique based on two-photon absorption of monolayer WS2-PVP nanosheets (NSs), which facilitates foreground extraction of the targeting region with the background signal being significantly suppressed. The optical nonlinearity of the monolayer WS2-PVP NSs was first demonstrated by a Z-scan system under the irradiation of a femtosecond laser to be 0.38, with an antithesis of virtually zero for the tissue-mimicking sample. Experiments on tissue-mimicking phantoms and in vitro chicken breast showed that the nonlinear PA enhancement of monolayer WS2-PVP NSs can facilitate foreground-extraction imaging at deep-seated position up to 4 mm. In addition, the in vivo foreground-extraction imaging ability by using monolayer WS2-PVP NSs was further demonstrated by mouse tumor models, where the tumor regions were specifically extracted with high imaging contrast. This work proposed a nonlinearly enhanced contrast mechanism of PA nanoprobes, prefiguring great potential for high-contrast and high-specificity PA molecular imaging.

Glutathione-activated biotin-targeted dual-modal imaging probe with improved PDT/PTT synergistic therapy

BackgroundGlutathione (GSH), a highly abundant thiol compound within cells, plays a critical role in physiological processes and exhibits close correlation with cancer. Among molecular imaging technologies, most probes have relatively short emission wavelengths and lack photoacoustic imaging (PA) capability, resulting in the inability to obtain tissue images with high penetration depth. The presence of GSH in the tumor microenvironment neutralizes ROS, diminishing the therapeutic effect of PDT, thus resulting in often unsatisfactory therapeutic efficacy. Therefore, it is imperative to develop a dual-modal probe for the detection of GSH and the diagnosis and treatment of cancer. ResultsIn this study, we synthesized a novel dual-modal probe, Cy-Bio-GSH, utilizing near-infrared fluorescence (NIRF) and photoacoustic (PA) imaging techniques for GSH detection. The probe integrates cyanine dye as the fluorophore, nitroazobenzene as the recognition moiety, and biotin as the tumor-targeting moiety. Upon reacting with GSH, the probe emits NIR fluorescence at 820 nm and generates a PA signal. Significantly, this reaction activates the photodynamic and photothermal properties of the probe. By depleting GSH and employing a synergistic photothermal therapy (PTT) treatment, the therapeutic efficacy of photodynamic therapy (PDT) is remarkably enhanced. In-vivo experiments confirm the capability of the probe to detect GSH via NIRF and PA imaging. Notably, the combined tumor-targeting ability and PDT/PTT synergistic therapy enhance therapeutic outcomes for tumors and facilitate their ablation. SignificanceA novel tumor-targeting and dual-modal imaging probe (Cy-Bio-GSH) is synthesized, exhibiting remarkable sensitivity and selectivity to GSH, enabling the visualization of GSH in cells and the differentiation between normal and cancer cells. Cy-Bio-GSH enhances PDT/PTT with effective killing of cancer cells and makes the ablation of tumors in mice. This work represents the first tumor-targeting probe for GSH detection, and provides crucial tool for cancer diagnosis and treatment by dual-modal imaging with improved PDT/PTT synergistic therapy.

Mechanical Assessment in Atherosclerosis Based on Photoacoustic Viscoelasticity Imaging

Early identification of vulnerable plaques is a major challenge in diagnosis and assessment of atherosclerosis. In atherosclerotic plaque development, the proportion change in components caused plaque mechanical property change and induced plaque rupture. In this paper, a photoacoustic viscoelasticity imaging (PAVEI) technique was proposed to measure the viscosity–elasticity ratio of atherosclerotic plaque and evaluated for the potential in characterizing vulnerable plaques. Apolipoprotein E-knockout mice fed with a high-fat/high-cholesterol diet were chosen as the atherosclerotic model. Plaque component phantoms were examined to demonstrate the high efficiency of PAVEI in detecting the proportion change in components compared to single elasticity or viscosity detection. Finally, atherosclerotic plaques from mice aortas at different stages were imaged by PAVEI, which provided an insight into the compositional and functional characterization of vulnerability plaques and suggested its potential applications in the identification of high-risk plaques.

Semiconducting Polymers Based on Asymmetric Thiadiazoloquinoxaline for Augmented In Vivo NIR-II Photoacoustic Imaging.

A photoacoustic (PA) imaging technique using the second near-infrared (NIR-II) window has attracted more and more attention because of its merits of deeper penetration depth and higher signal-to-noise (S/N) ratio than that using the first near-infrared (NIR-I) one. However, the design and development of high-performance PA imaging contrast agents in the NIR-II window is still a challenge. A semiconducting polymer, constructed by asymmetric units, exhibits regiorandom characteristics that effectively increase the distortion of the backbone. This increase in the degree of twist can regulate the twisted intramolecular charge transfer (TICT) effect, resulting in an enhancement of the PA signal. In this paper, an asymmetric structural acceptor strategy is developed to improve the PA signals of the resulting semiconducting polymer (PATQ-MP) in the NIR-II window with improved brightness, higher S/N ratio, and better photothermal conversion efficiency compared to polymers with the same main-chain structure containing a symmetric acceptor. DFT analysis showed that PATQ-MP containing an asymmetric acceptor monomer had a larger dihedral angle, which effectively improved the PA signal intensity by enhancing the TICT effect. The PEG-encapsulated PATQ-MP nanoparticles exhibit promising performance in the PA imaging of mouse tumors in vivo, demonstrating the clear identification of microvessels as small as 100 μm along with rapid metabolism within a span of 5 h. Therefore, this work provides a unique molecular design strategy for improving the signal intensity of PA imaging in the NIR-II window.

Advancing microplastic surveillance through photoacoustic imaging and deep learning techniques

Microplastic contamination presents a significant global environmental threat, yet scientific understanding of its morphological distribution within ecosystems remains limited. This study introduces a pioneering method for comprehensive microplastic assessment and environmental monitoring, integrating photoacoustic imaging and advanced deep learning techniques. Rigorous curation of diverse microplastic datasets enhances model training, yielding a high-resolution imaging dataset focused on shape-based discrimination. The introduction of the Vector-Quantized Variational Auto Encoder (VQVAE2) deep learning model signifies a substantial advancement, demonstrating exceptional proficiency in image dimensionality reduction and clustering. Furthermore, the utilization of Vector Quantization Microplastic Photoacoustic imaging (VQMPA) with a proxy task before decoding enhances feature extraction, enabling simultaneous microplastic analysis and discrimination. Despite inherent limitations, this study lays a robust foundation for future research, suggesting avenues for enhancing microplastic identification precision through expanded sample sizes and complementary methodologies like spectroscopy. In conclusion, this innovative approach not only advances microplastic monitoring but also provides valuable insights for future environmental investigations, highlighting the potential of photoacoustic imaging and deep learning in bolstering sustainable environmental monitoring efforts.

Dual-modal Photoacoustic and Ultrasound Imaging: from preclinical to clinical applications.

Photoacoustic imaging is a novel biomedical imaging modality that has emerged over the recent decades. Due to the conversion of optical energy into the acoustic wave, photoacoustic imaging offers high-resolution imaging in depth beyond the optical diffusion limit. Photoacoustic imaging is frequently used in conjunction with ultrasound as a hybrid modality. The combination enables the acquisition of both optical and acoustic contrasts of tissue, providing functional, structural, molecular, and vascular information within the same field of view. In this review, we first described the principles of various photoacoustic and ultrasound imaging techniques and then classified the dual-modal imaging systems based on their preclinical and clinical imaging applications. The advantages of dual-modal imaging were thoroughly analyzed. Finally, the review ends with a critical discussion of existing developments and a look toward the future.

Low-Cost Scalable PCB-Based 2-D Transducer Arrays for Volumetric Photoacoustic Imaging.

Photoacoustic (PA) imaging provides deep tissue molecular imaging of chromophores with optical absorption contrast and ultrasonic resolution. Present PA imaging techniques are predominantly limited to one 2D plane per acquisition. 2D ultrasound transducers, required for real-time 3D PA imaging, are high-cost, complex to fabricate and have limited scalability in design. We present novel PCB-based 2D matrix ultrasound transducer arrays that are capable of being bulk manufactured at low-cost without using laborious ultrasound fabrication tools. The 2D ultrasound array specifications are easily scalable with respect to widely available PCB design and fabrication tools at low cost. To demonstrate scalability, we fabricated low (11 MHz) frequency 8x8 matrix array and high (40 MHz) frequency 4x4 matrix array by directly bonding an undiced polyvinylidene fluoride (PVDF) piezoelectric material of desired thickness to the custom designed PCB substrate. Characterization results demonstrate wideband PA receive sensitivity for both low (87%) and high (188%) frequency arrays. Volumetric PA imaging results of light absorbing targets inside optical scattering medium demonstrate improved spatial resolution and field of view with increase in aperture size.

Phasor field based photoacoustics: A virtual orthogonal wavefield model for nonnegative photoacoustic computational tomography

The phasor field technique has substantially aided the advancement of the time of flight imaging field and sparked intense scientific research interest during the past several years. Recently, phasor field approach was brought to the field of photoacoustic imaging and results in greatly enhanced image SNR and less artifact interference. This paper aims to establish the foundation for a comprehensive physical framework for phasor field based photoacoustics. To demonstrate the rigorousness of the phasor field based photoacoustics, this work gives a derivation of its virtual forward propagation and backward phasor field reconstruction. Phasor field based photoacoustic system works by creating chunks of initial orthogonal photoacoustic vibration, propagating the virtual orthogonal phasor waves, and performing backward phasor field reconstruction. We present here a formal study of phasor field framework utilizing spherical harmonic function decomposition based point spread function (PSF) analysis and provide a rigorous theoretical explanation for its nonnegative imaging capability of phasor field photoacoustic imaging. Simulation and experimental results reported in the paper support the effectiveness of the phasor field photoacoustic method for nonnegative imaging reconstruction. Moreover, the virtual nature of phasor field method enables flexibility and compatibility with different reconstructive mechanism for optimized imaging performance. Phasor field method the potential to advance the photoacoustic imaging techniques across multiple fields, benefiting various applications and enabling new avenues of research and development.

Resonance frequency measurement to identify stiffness variations based on photoacoustic imaging.

Linear assumption on the level of stiffness in a tissue shows a significant correlation with disease. Photoacoustic imaging techniques that are non-contact by design have been developed in this study to detect differences in phantom (soft tissue mimicking materials) stiffness. This study aims to detect differences in phantom stiffness based on the results of image reconstruction at the resonance frequency. Four phantom agars with differing concentrations were made to achieve different stiffnesses. The position of each phantom agar's highest photoacoustic signal amplitude is identified by a frequency modulation sweep. The characterization results show an increase in resonance frequency along with an increase in phantom stiffness. The image difference can be detected because the intensity of the photoacoustic image in samples that have a resonance frequency with laser modulation is comparatively higher than in other samples.

Heavy water coupling gel for short-wave infrared photoacoustic imaging.

Changes in lipid, water, and collagen (LWC) content in tissue are associated with numerous medical abnormalities (cancer, atherosclerosis, and Alzheimer's disease). Standard imaging modalities are limited in resolution, specificity, and/or penetration for quantifying these changes. Short-wave infrared (SWIR) photoacoustic imaging (PAI) has the potential to overcome these challenges by exploiting the unique optical absorption properties of . This study's aim is to harness SWIR PAI for mapping LWC changes in tissue. The focus lies in devising a reflection-mode PAI technique that surmounts current limitations related to SWIR light delivery. To enhance light delivery for reflection-mode SWIR PAI, we designed a deuterium oxide (, "heavy water") gelatin (HWG) interface for opto-acoustic coupling, intended to significantly improve light transmission above 1200nm. HWG permits light delivery up to 1850nm, which was not possible with water-based coupling ( light delivery up to 1350nm). PAI using the HWG interface and the Visualsonics Vevo LAZR-X reveals a signal increase up to 24dB at 1720nm in lipid-rich regions. By overcoming barriers related to light penetration, the HWG coupling interface enables accurate quantification/monitoring of biomarkers like LWC using reflection-mode PAI. This technological stride offers potential for tracking changes in chronic diseases (in vivo) and evaluating their responses to therapeutic interventions.

NIR-II Nanoprobes: A Review of Components-Based Approaches to Next-Generation Bioimaging Probes.

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.

Non-invasive evaluation of transdermal drug delivery using 3-D transient triplet differential (TTD) photoacoustic imaging

Transdermal drug delivery (TDD) is less invasive and avoids first-pass metabolism, making it an attractive method for treating various diseases such as diabetes and hypertension. However, current methods for evaluating TDD systems lack in vivo descriptions of drug distribution in the skin. In this study, we demonstrate the capability of the Transient Triplet Differential (TTD) method, a non-invasive and background-free photoacoustic imaging technique, for accurately mapping drug distribution and evaluating different TDD systems. Our findings show that the TTD method can provide high sensitivity and specificity for targeted drug extraction and visualize 3D drug distribution in the skin. Furthermore, in vivo experiments confirmed the potential of the TTD method in evaluating the clinical performance of TDD. It’s predictable that the TTD method can be a reliable and non-invasive approach for evaluating TDD systems and offer valuable insights into TDD research and development.

Single-shot photoacoustic imaging with single-element transducer through a spatiotemporal encoder.

Current photoacoustic (PA) imaging modalities typically require either serial detection with a single-element transducer or parallel detections with an ultrasonic array, indicating a dilemma between system cost and imaging throughput. PA topography through ergodic relay (PATER) was recently developed to address this bottleneck. However, PATER requires object-specific calibration due to varied boundary condition and must be recalibrated through pointwise scanning for each object before measurements, which is time-consuming and severely limits practical application. We aim to develop a new single-shot PA imaging technique that only requires a one-time calibration for imaging different objects using a single-element transducer. We develop an imaging method, PA imaging through a spatiotemporal encoder (PAISE), to address the above issue. The spatial information is effectively coded into unique temporal features by the spatiotemporal encoder, which allows for compressive image reconstruction. An ultrasonic waveguide is proposed as a critical element to guide the PA waves from the object into the prism, which effectively accounts for the varied boundary condition of different objects. We further add irregular-shaped edges on the prism to introduce randomized internal reflections and further facilitate the scrambling of acoustic waves. The proposed technique is validated through comprehensive numerical simulations and experiments, and it is demonstrated that PAISE can successfully overcome the changed boundary condition and can image different samples given a single calibration. The proposed PAISE technique is capable of single-shot widefield PA imaging with a single-element transducer and does not require sample-specific calibration, which successfully overcomes the major limitation of previous PATER technology.

Recent Advances in Ultrasound and Photoacoustic Analysis for Thyroid Cancer Diagnosis

AbstractThyroid cancer is one of the most commonly diagnosed cancers worldwide, with a continuously increasing incidence rate in recent decades. Although ultrasonography, which is the current screening method in clinical workflows, has successfully triaged cancerous nodules for biopsy, overdiagnosis has also grown due to the relatively low specificity of the method. Studies are conducted to overcome this overdiagnosis issue by complementing ultrasonography with additional image‐based analysis techniques. This review presents an overview of the current advances in clinical trials using advanced ultrasound (US) and photoacoustic (PA) imaging techniques for thyroid nodules in humans. A summary of initial trials by Doppler US and US elastography to improve the classification accuracy of thyroid nodules is presented. Furthermore, recent PA techniques with multispectral analyses utilizing clinically available machines are explored. By amending the existing ultrasonography, the advanced US and PA techniques can enhance the triaging accuracy by analyzing both structural and functional information of thyroid nodules in vivo.

Assessing the microarchitecture and microenvironment of cancer in vivo by photoacoustic imaging techniques

Majority of current studies on photoacoustic (PA) imaging are focused on the total signal magnitudes as the reflection of the macroscopic optical absorption by specific chemical contents at single or multiple optical wavelengths. Our recent research has demonstrated that the frequency domain power distribution of radio-frequency PA signals contains the microscopic information of the optically absorbing materials in biological samples. In this research, I will present our recent development of quantitative PA methods for in vivo evaluation of histological microarchitectures of biological tissues as well as potential clinical applications of these methods such as the assessment of prostate cancer aggressiveness. In addition, powered by our recently developed polyacrylamide hydrogel nanoparticles containing a variety of functional contrast agents, multi-wavelength PA imaging plus spectral unmixing technique can enable quantitative mapping of the chemical and metabolic properties in cancer microenvironments, such as tissue oxygenation, pH level, and ion concentrations. Imaging of these chemical makeups of an entire tumor in vivo, non-invasively, with high sensitivity and high spatial resolution can shed new light to the understanding of cancer onset, progress, and responses to therapies.

Agar Gel as a Non-Invasive Coupling Medium for Reflectance Photoacoustic (PA) Imaging: Experimental Results on Wall-Painting Mock-Ups.

The new reflectance set-up configuration extended the applicability of the photoacoustic (PA) imaging technique to art objects of any thickness and form. Until now, ultrasound gel or distilled water have been necessary as coupling mediums between the immersion-type transducer and the object’s surface. These media can compromise the integrity of real artwork; therefore, known applications of reflectance PA imaging have been limited to only experimental mock-ups. In this paper, we evaluate an alternative non-invasive PA coupling medium, agar gel, applied in two layers of different consistency: first, rigid—for the protection of the object’s surface, and second, fluid—for the transducer’s immersion and movement. Agar gel is widely used in various conservation treatments on cultural heritage objects, and it has been proven to be safely applicable on delicate surfaces. Here, we quantify and compare the contrast and signal-to-noise ratio (SNR) of PA images, obtained in water and in agar gel on the same areas, at equal experimental conditions. The results demonstrate that the technique’s performance in agar is comparable to that in water. The study uncovers the advanced potential of the PA approach for revealing hidden features, and is safely applicable for future real-case studies.

Fast Fourier Transform-weighted Photoacoustic Imaging by In Vivo Magnetic Alignment of Hybrid Nanorods.

Photoacoustic (PA) imaging uses photon-phonon conversion for high-resolution tomography of biological tissues and functions. Exogenous contrast agents are often added to improve the image quality, but the interference from endogenous molecules diminishes the imaging sensitivity and specificity. We report a background-free PA imaging technique based on the active modulation of PA signals via magnetic alignment of Fe3O4@Au hybrid nanorods. Switching the field direction creates enhanced and deactivated PA imaging modalities, enabling a simple pixel subtraction to effectively minimize background noises. Under an alternating magnetic field, the nanorods exhibit PA signals of coherently periodic changes that can be converted into a sharp peak in a frequency domain via the fast Fourier transform. Automatic pixel-wise screening of nanorod signals performed using a computational algorithm across a time-sequence set of PA images regenerates a background-free PA image with significantly improved contrast, specificity, and fidelity.

In-vivo functional and structural retinal imaging using multiwavelength photoacoustic remote sensing microscopy

Many important eye diseases as well as systemic disorders manifest themselves in the retina. Retinal imaging technologies are rapidly growing and can provide ever-increasing amounts of information about the structure, function, and molecular composition of retinal tissue in-vivo. Photoacoustic remote sensing (PARS) is a novel imaging modality based on all-optical detection of photoacoustic signals, which makes it suitable for a wide range of medical applications. In this study, PARS is applied for in-vivo imaging of the retina and estimating oxygen saturation in the retinal vasculature. To our knowledge, this is the first time that a non-contact photoacoustic imaging technique is applied for in-vivo imaging of the retina. Here, optical coherence tomography is also used as a well-established retinal imaging technique to navigate the PARS imaging beams and demonstrate the capabilities of the optical imaging setup. The system is applied for in-vivo imaging of both microanatomy and the microvasculature of the retina. The developed system has the potential to advance the understanding of the ocular environment and to help in monitoring of ophthalmic diseases.

Targeting Endogenous Hydrogen Peroxide at Bone Defects Promotes Bone Repair (Adv. Funct. Mater. 10/2022)

Bone Repair In article 2111208, Fengxuan Han, Zhuang Liu, Bin Li, and co-workers visualize, for the first time, reactive oxygen species (ROS) in the bone injury microenvironment using a photoacoustic imaging technique. Following that, gelatin methacryloyl (GelMA)-based composite hydrogels containing hollow manganese dioxide nanoparticles, which decompose ROS to generate oxygen and release encapsulated bone morphogenetic protein-2-associated peptide in an “on-demand” fashion, are applied in bone defects and collectively enhance bone repair.