Photoacoustic Imaging Research Articles

Smart molecular probes with controllable photophysical property for smart medicine

AbstractPrecision medicine calls for advanced theranostics that integrate controllable diagnostic and therapeutic capabilities into one platform for disease treatment in the early stage. Phototheranostics such as fluorescence imaging (FLI), photoacoustic imaging (PAI), photodynamic therapy (PDT), and photothermal therapy (PTT) have attracted considerable attention in recent years, which mainly employ different excited‐state energy dissipation pathways of a chromophore. According to the Jablonski diagram, FLI is related to the radiative process, PAI and PTT are derived from the nonradiative thermal deactivation, and PDT originates from the triplet state energy, in which these processes are usually competitive. Therefore, it is critically important to precisely tune the photophysical energy transformation processes to realize certain diagnosis and treatment properties in optimal state for boosting biomedical applications. Currently, there are mainly two strategies including chemical structure and aggregate behavior changes that relate to the regulation of excited state energy dissipation. In this review, we will discuss the recent advances of smart molecular probes that the photophysical properties can be regulated by external triggers and their applications in biomedical fields. We will summarize the development of activatable phototheranostic molecular probes in response to stimuli such as reactive oxygen species, pH, light, hypoxia, enzyme and gas. The assembly and disassembly of molecular aggregates that greatly affect the photophysical energy transformation processes will also be highlighted. This review aims to provide valuable insights into the development of more accurate diagnostic and therapeutic systems, thereby advancing the emerging field of smart medicine.

Feasibility of Prostatitis Evaluation Based on Photoacoustic Microscopy

Abstract This study aims to investigate the feasibility of using photoacoustic microscopy for the diagnosis of prostatitis. We induced inflammation in rats to establish a model of prostatitis using Freund’s Complete Adjuvant (FCA). Prostate tissues from both the model and control groups were extracted and processed into histological sections. We explored the photoacoustic microscopy imaging results of unstained sections, consistent with the histological detection results using HE staining. Inflammation was found to enhance the photoacoustic signals. Subsequently, we conducted photoacoustic microscopy imaging on all samples, and the detection results were nearly consistent with the diagnoses made by medical professionals. Finally, we quantified the collected photoacoustic signals to classify the severity of prostatitis.

Photoacoustic Quantification of Tissue Oxygenation Using Conditional Invertible Neural Networks.

Intelligent systems in interventional healthcare depend on the reliable perception of the environment. In this context, photoacoustic tomography (PAT) has emerged as a non-invasive, functional imaging modality with great clinical potential. Current research focuses on converting the high-dimensional, not human-interpretable spectral data into the underlying functional information, specifically the blood oxygenation. One of the largely unexplored issues stalling clinical advances is the fact that the quantification problem is ambiguous, i.e. that radically different tissue parameter configurations could lead to almost identical photoacoustic spectra. In the present work, we tackle this problem with conditional Invertible Neural Networks (cINNs). Going beyond traditional point estimates, our network is used to compute an approximation of the conditional posterior density of tissue parameters given the photoacoustic spectrum. To this end, an automatic mode detection algorithm extracts the plausible solution from the sample-based posterior. According to a comprehensive validation study based on both synthetic and real images, our approach is well-suited for exploring ambiguity in quantitative PAT.

Photoacoustic tracking of photo-magnetically powered nanoparticles for cancer therapy

Abstract The in vivo propulsion and monitoring of nanoparticles (NPs) have received tremendous achievements in the past decade. Developing functional NPs that can be efficiently manipulated inside the human body with a non-invasive tracking modality is critical to clinical translation. This study synthesized a photo-magnetically powered nanoparticle (PMN) with a Fe3O4 core and gold spiky surface. The Au-nanotips ensure PMNs have a strong light absorption in the second near-infrared (NIR) window and produce outstanding photoacoustic signals. The Bio-transmission electron microscopy and simulation results prove that the assembly of PMNs under a magnetic field further enhances the photothermal conversion in cells, contributing to the reduction of ambient viscosity. Photoacoustic imaging (PAI) realized real-time monitoring of PMN movements and revealed that laser plus magnetic coupling could improve intratumoral distribution and retention. The proposed methods exhibit excellent potential for the clinical research of cancer nanotherapies.

Photoacoustic Signal Propagation Modes in Bone Tissue: a Simulation Study

Abstract Photoacoustic (PA) imaging has great potential in brain imaging. However, the strong acoustic attenuation and reverberation caused by the skull bone layers present challenges for PA brain imaging. In this work, we developed a three-dimensional (3D) photoacoustic numerical simulation platform using the finite difference time domain (FDTD) method to study PA signal generation and propagation in the human brain. This platform can simulate not only the propagation of longitudinal waves in soft tissues but also shear and longitudinal waves in hard tissues. Using this numerical simulation platform, we extensively simulated the propagation of PA waves in skull models with varying porosities, The results demonstrate that our 3D PA simulation platform accurately captures the propagation details of PA signals in the skull, including the refraction, reflection, and mode conversion of photoacoustic waves at tissue boundaries. Furthermore, an increase in skull porosity prolongs the duration of the photoacoustic signals and leads to high attenuation of PA signals for high frequency components. We expect that this study will contribute to the understanding of the impact on acoustic propagation of photoacoustic signals in cranial bone photoacoustic imaging.

The Feasibility Study of Bone Fracture Assessment Based on Photoacoustic Time-of-Flight Method

Abstract Photoacoustic imaging (PAI) technology combines the advantages of acoustic resolution and optical contrast imaging within deep tissue. The commonly clinically used bone fracture detection and evaluation method is X-ray based imaging techniques. In order to study the feasibility of human radius fractures detection in non-radiation and non-invasive way, this study combined the time-of-flight (TOF) method commonly used in industrial nondestructive testing with photoacoustic technology for the detection and location of bone fractures. Firstly, the bone fracture information carried by PA signal was studied by simulating the bone models with different locations of bone fractures. The finite difference time domain (FDTD) method was used to simulate the propagation process of photoacoustic signal in bone tissue. Secondly, the PATOF diagrams formed by PA signals at different locations is obtained by using laser fixed and ultrasonic detector motion detection method. Finally, the PATOF diagrams are further analyzed and quantified. The results show that the photoacoustic bone detection method based on TOF method can effectively locate the fracture location. This study confirms the feasibility of combining PAI technique with TOF method to detect bone fractures, which indicates that PAI technique has great application prospect in bone detection field.

Reflection Artifacts Removal of Photoacoustic Imaging in Complex Medium

Abstract Photoacoustic (PA) imaging owns a great prospect in medical diagnosis because of its high contrast and capability in functional imaging. While, the detected PA signals are always a mix of direct-arrived signals (DAS) and reflected (scattered) signals (RS) in inhomogeneous and bounded samples such as human tissues. The RS can lead to many artifacts and severely affect the final image, which confuses the artifacts with the real PA sources. This paper employed a spatial singular value decomposition (SVD) filter to abstract the DAS and thus remove the reflection artifacts. We conducted experiments on an agar phantom and an in vitro tissue to verify the method. The results show that the proposed method can effectively remove RS, resulting in fewer reflection artifacts in PA images.

Research on 3D Reconstruction of Paleontological Fossils Based on Photoacoustic Microscopy

Abstract The focus on three-dimensional morphological analysis of endogenous trace fossils has emerged as a prominent aspect in the study of palaeobiological fossils. Photoacoustic imaging technology, renowned for its deep penetration, high resolution and non-destructiveness, holds considerable promise in exploring fossil morphology. In this work, a solid-coupling-based photoacoustic microscopic imaging system was developed, leveraging this technology to investigate small-scale physical fossils. The proposed system enabled layered imaging of various fossil specimens, achieving a lateral resolution exceeds 35 μm and an axial resolution superior to 8.8815 μm. The three-dimensional reconstruction results were obtained through image processing algorithms. This system was proved to be efficient to imaging the small-scale physical fossils.

The Current Status and Future Directions on Nanoparticles for Tumor Molecular Imaging.

Molecular imaging is an advanced technology that utilizes specific probes or markers in conjunction with cutting-edge imaging techniques to observe and analyze the localization, distribution, activity, and interactions of biomolecules within living organisms. Tumor molecular imaging, by enabling the visualization and quantification of molecular characteristics of tumor cells, facilitates a deeper and more comprehensive understanding of tumors, providing valuable insights for early diagnosis, treatment monitoring, and cancer biology research. However, the image quality of molecular imaging still requires improvement, and nanotechnology has significantly propelled the advancement of molecular imaging. Currently, nanoparticle-based tumor molecular imaging technologies encompass radionuclide imaging, fluorescence imaging, magnetic resonance imaging, ultrasound imaging, photoacoustic imaging, and multimodal imaging, among others. As our understanding of the tumor microenvironment deepens, the design of nanoparticle probes for tumor molecular imaging has also evolved, offering new perspectives and expanding the applications of tumor molecular imaging. Beyond diagnostics, there is a marked trend towards integrated diagnosis and therapy, with image-guided treatment playing a pivotal role. This includes image-guided surgery, photodynamic therapy, and chemodynamic therapy. Despite continuous advancements and innovative developments in molecular imaging, many of these remain in the experimental stage and require breakthroughs before they can be fully integrated into clinical practice.

Time Series Forecasting for Sparse Ring-shaped Array Photoacoustic Imaging Reconstruction

Abstract Photoacoustic computed tomography (PACT), which provides high optical absorption contrast and deep acoustic penetration, plays an important role in non-invasive biomedical imaging area. As the decrease of array elements, the reconstructed image suffers from severe artifacts. Recent studies utilize deep learning methods to improve the imaging quality of PACT based on image network design, but few were reported with raw data. To address this issue, this paper proposes a Wave to Wave Convolution Gate Recurrent-Net (WWCG-Net) to reconstruct photoacoustic image based on time series acoustic signal prediction. Simulation and experiment results show the superiority of our method compared with linear interpolation (LI) and eXtreme Gradient Boosting (XGBoost) in term of suppress artifact and improve resolution.

Circular phase shift migration based photoacoustic computational tomography

Abstract In the recent several decades, photoacoustic technique has proved to be capable of noninvasive biomedical imaging with scalable spatial resolution and high penetration depth. To achieve faithful image reconstruction, various method has been proposed, such as back projection, phase shift migration, model-based method, etc. These methods have simple implementations in homogeneous media, whereas in the cases of heterogeneous media (e.g., layered media), complicated modifications with respect to wave propagation at layer interface are always necessary. Here, we propose a frequency domain algorithm extension of phase shift migration in polar coordinates, which is obtained by making second order approximation to the optoacoustic point spread function in cylindrical coordinates and thereafter step by step wavenumber-frequency domain wave field extrapolation along the axial direction. Theoretical simulation and phantom experimental results demonstrate that the proposed circular phase shift migration method can well solve the layered heterogeneous reconstructive problem without modifying the wave propagation model. The acoustic diffraction limited acoustic resolution (up to 225 μm) and high imaging SNR (at least 16 dB) are obtained.

The deterioration of microstructure and biochemical components in cancellous bone characterizing by the photoacoustic microscopy imaging

Abstract Background/Objective: Osteoporosis is mainly characterized by a deterioration of microstructure and a loss of biochemical components in bone tissues. Developing an imaging technique for measuring bone tissue microstructure and the biochemical components is of great significance for the early diagnosis of osteoporosis. Photoacoustic microscopy (PAM) has the advantage of high optical resolution and the potential to diagnose osteoporosis. In this study, we investigated the feasibility of the photoacoustic microscopy (PAM) technique for bone tissue imaging, and the deterioration of microstructure and biochemical components in cancellous bone was characterized by the PAM. Statement of Contribution/Methods: We performed the optical-resolution photoacoustic microscopy (OR-PAM) for bone tissue imaging and the trabecular microstructure and hydroxyapatite (HAP) were degraded by immersion in JYBL-I solution. The PAM imaging method was developed for the measurement of the surface and subsurface of cancellous bone with a high resolution. Specifically, a 532 nm pulse laser was used to excite the PA signal from the bone. The PA signal sampling frequency was 80 MHz. A motor rotated a 15 MHz central frequency transducer to receive 1000 × 1000 × 250 points data. The envelope of the signal was obtained using the Hilbert transform for reconstruction. Then, the JYBL-I solution was used to reduce the HAP component in the bone. The PAM imaging was performed after different immersion times, (i.e., at 0, 5, and 10 mins). In the PAM measurement of the cancellous bone, the imaging area was a cylinder with an 8 mm diameter and an 8 μm/pixel resolution. Results/Discussion: The results showed that the trabecular microstructure could be imaged with a relatively high quality using the PAM technique. With the different extent of HAP degradation by immersion in JYBL-I solution, some trabecular bone disappeared corresponding with PA signals decreased significantly in amplitude. Conclusion: These results indicate that the PA technique has potential application in the characterization of bone microstructure and biochemical components with a high resolution.

Dual-mode photoacoustic and ultrasonic quantitative evaluation of cancellous bone

Abstract Bone diseases, especially osteoporosis, is highly prevalent, and the chronic consequences often have debilitating effects on patients. Early diagnosis and intervention are desired, but existing bone assessment methods do not allow for regular screening as required for such early detection. We were inspired to explore the potential of photoacoustic (PA) imaging for bone assessment due to its molecular imaging capabilities and its shared advantages with ultrasonics (US). In this study, an experimental system was constructed for PA/US dual-mode imaging of cancellous bone, and the resulting images were analysed based on a new quantitative framework. The results from the quantitative analysis clearly differentiated cancellous bones with varying apparent densities, demonstrating the potential of such a method for efficient bone assessment.

Physics-driven deep learning photoacoustic tomography

Physics-driven deep learning photoacoustic tomography

3D computational modeling of multispectral photoacoustic microscopy: Simulations aiding systematic optimization and data acquisition

Abstract Photoacoustic microscopy (PAM), a fruitful application modality for photoacoustic imaging, is capable of directly measuring optical absorption properties in skin tissue, providing high-contrast, high-resolution medical images as well as functional and pathologic information. However, optical attenuation and unknown optical and acoustic nonuniformities limit its imaging performance in deep tissue regions. New instrumentation, image reconstruction, and artificial intelligence methods are being investigated to overcome these limitations, and a reliable PAM simulation tool is required for the effective implementation of these methods. In this paper, we propose and validate a 3D quantitative computational multispectral PAM imaging model. It provides a theoretical basis for the application of quantitative PAM in skin diagnosis and aids in the development and optimization of PAM devices, as well as the acquisition of deep learning datasets.

Photoacoustic/ultrasound dual-modality imaging of Sentinel lymph node with carbon nanoparticles

Abstract Sentinel lymph node (SLN) biopsy is a widely used method for identifying axillary lymph node metastasis in breast cancer patients, offering an avoidance of unnecessary axillarydissections and a lower incidence of lymphedema and other complications. However, the nuclide localization has added complexity to the procedure due to its accessibility. Methylene blue and other small molecule dyes have been widely used due to their convenience, but they have been found to have lower specificity and sensitivity. Carbon nanoparticles (CNPs), as a new type of tracer, are safe and show improved specificity. However, the significant optical absorption in human tissues still renders the detection of deep lymph nodes challenging. To overcome these challenges, we developed a high-sensitivity ultrasound probe optimized for photoacoustic imaging. Based on the new probe, we constructed a high-sensitivity photoacoustic/ultrasound dual-modality imaging system. A pilot clinical study has been conducted on two patients, preliminarily verifying the system’s ability to locate SLN when combined with the CNPs.

A Comprehensive Review: Versatile Imaging Probe Based on Chemical Materials for Biomedical Applications.

Imaging probe and contrast agents play significant role in combating cancer. Based on special chemical materials, imaging probe can convert cancer symptoms into information-rich images with high sensitivity and signal amplification, accompanying with detection, diagnosis, drug delivery and treatment. In the paper, some inorganic and organic chemical materials as imaging probe, including Ultrasound imaging (US), Optical imaging (OP), Photoacoustic imaging (PA), X-ray Computed Tomography (CT), Magnetic Resonance imaging (MRI), Radionuclide imaging (RNI) probe, as well as multi-modality imaging probe for diagnosis and therapy of tumour were introduced. The sophisticated and comprehensive chemical materials as imaging probe were highlighted in detail. Meanwhile, the advantages and disadvantages of the imaging probe were compared. In order to provide some reference and help researchers for construction imaging probe for tumour diagnosis and treatment, it attempts to exhaustively cover the whole field. Finally, the prospect and challenge for imaging probe were discussed.

Reversibly photoswitchable protein assemblies with collagen affinity for in vivo photoacoustic imaging of tumors.

Recent advancements in photoacoustic (PA) imaging have leveraged reversibly photoswitchable chromophores, known for their dual absorbance states, to enhance imaging sensitivity through differential techniques. Yet, their deployment in tumor imaging has faced obstacles in achieving targeted delivery with high efficiency and specificity. Addressing this challenge, we introduce innovative protein assemblies, DrBphP-CBD, by genetically fusing a photosensory module from Deinococcus radiodurans bacterial phytochrome (DrBphP) with a collagen-binding domain (CBD). These protein assemblies form sub-100-nanometer structures composed of 24 DrBphP dimers and 12 CBD trimers, presenting 24 protein subunits. Their affinity for collagens, combined with impressive photoswitching contrast, markedly improves PA imaging precision. In various tumor models, intravenous administration of DrBphP-CBD has demonstrated enhanced tumor targeting and retention, augmenting contrast in PA imaging by minimizing background noise. This strategy underscores the clinical potential of DrBphP-CBD as PA contrast agents, propelling photoswitchable chromoproteins to the forefront of precise cancer diagnosis.

Novel two-dimensional FeB nanosheets for photoacoustic imaging-guided NIR-photothermal therapy

The development of biosafe near infrared (NIR)-photothermal nanomaterials is meaningful for tumor-targeted photothermal therapy and photoacoustic imaging for high-performance theranostics, but still challenging. Herein, we propose a new ultrasound-assisted chemical etching method based on the Fenton reaction to synthesize a novel kind of two-dimensional iron boride nanosheets (FBN) as NIR-photothermal nanomaterials. The developed FBN theranostic agent exhibits high NIR adsorption and NIR-photothermal conversion efficiencies, realizing biosafe and high efficacy of photoacoustic imaging-guided tumor-targeted NIR-photothermal therapy of tumor mice.

π-Bridge Regulates Donor–Acceptor Interactions for Long-Wavelength Photoacoustic Imaging and Enhanced Photothermal Therapy

π-Bridge Regulates Donor–Acceptor Interactions for Long-Wavelength Photoacoustic Imaging and Enhanced Photothermal Therapy