Search Results (26)

Elevated extracellular potassium (K⁺) in the tumor microenvironment (TME) of breast and other cancers is increasingly recognized as a critical factor influencing tumor progression and immune suppression. Current methods for noninvasive mapping of the potassium distribution in tumors are limited. Here, we employed photoacoustic chemical imaging (PACI) with a solvatochromic dye-based, potassium-sensitive nanoprobe (SDKNP) to quantitatively visualize extracellular potassium levels in an orthotopic metaplastic breast cancer mouse model, Ccn6-KO. Tumors of three distinct sizes (5 mm, 10 mm, and 20 mm) were imaged using multi-wavelength photoacoustic imaging at five laser wavelengths (560, 576, 584, 605, and 625 nm). Potassium concentration maps derived from spectral unmixing of the photoacoustic images at the five laser wavelengths revealed significantly increased potassium levels in larger tumors, confirmed independently by inductively coupled plasma mass spectrometry (ICP-MS). The PACI results matched ICP-MS measurements, validating PACI as a robust, noninvasive imaging modality for potassium mapping in tumors in vivo. This work establishes PACI as a promising tool for studying the chemical properties of the TME and provides a foundation for future studies evaluating the immunotherapy response through ionic biomarker imaging. Full article

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

Photoacoustic imaging (PAI) is an emerging biomedical imaging modality, offering numerous advantages, including high resolution and high contrast. In its application to brain imaging, however, the photoacoustic (PA) signals from brain tissue weaken considerably due to the distortion effects of the skull. This attenuation reduces the resolution and contrast significantly. To address this issue, here we describe a Log-MSR algorithm that combines the logarithmic depth logarithmic enhancement (Log) algorithm and the multi-scale Retinex (MSR) algorithm. In this method, the Log algorithm performs local weighted compensation based on signal attenuation for different depths, while the MSR algorithm improves the contrast of the image. The proposed Log-MSR algorithm was tested and validated using several phantom and in vivo experiments. The enhanced images constructed by the Log-MSR algorithm were qualitatively and quantitatively analyzed in terms of brain structure and function. Our results show that the Log-MSR algorithm may provide a significant enhancement to photoacoustic imaging of deep brain tissue. Full article

Photoacoustic tomography is a fast-growing biomedical imaging modality that combines rich optical contrast with a high acoustic resolution, at depths in tissues. Building upon the foundation of this technique, novel quantitative photoacoustic tomography fully leverages its advantages while further delivering improved quantification capabilities to produce high-accuracy concentration estimates, which has attracted substantial research interest in recent years. The kernel challenge associated with quantitative photoacoustic tomography is an optical inverse problem aiming to recover the absorption coefficient distribution from the conventional photoacoustic image. Although the crucial importance of the optical inversion has been widely acknowledged, achieving it has remained a persistent challenge due to the inherent non-linearity and non-uniqueness. In the past decade, numerous methods were proposed and have made noticeable progress in addressing this concern. Nevertheless, a review has been conspicuously absent for a long time. Aiming to bridge this gap, the present study comprehensively investigates the recent research in this field, and methods identified with significant value are introduced in this paper. Moreover, all included methods are systematically classified based on their underlying principles. Finally, we summarize each category and highlight its remaining challenges and potential future research directions. Full article

Based on the observations made in rheumatology clinics, autoimmune disease (AD) patients on immunosuppressive (IS) medications have variable vaccine site inflammation responses, whose study may help predict the long-term efficacy of the vaccine in this at-risk population. However, the quantitative assessment of the inflammation of the vaccine site is technically challenging. In this study analyzing AD patients on IS medications and normal control subjects, we imaged the inflammation of the vaccine site 24 h after mRNA COVID-19 vaccinations were administered using both the emerging photoacoustic imaging (PAI) method and the established Doppler ultrasound (US) method. A total of 15 subjects were involved, including 6 AD patients on IS and 9 normal control subjects, and the results from the two groups were compared. Compared to the results obtained from the control subjects, the AD patients on IS medications showed statistically significant reductions in vaccine site inflammation, indicating that immunosuppressed AD patients also experience local inflammation after mRNA vaccination but not in as clinically apparent of a manner when compared to non-immunosuppressed non-AD individuals. Both PAI and Doppler US were able to detect mRNA COVID-19 vaccine-induced local inflammation. PAI, based on the optical absorption contrast, shows better sensitivity in assessing and quantifying the spatially distributed inflammation in soft tissues at the vaccine site. Full article

Simulation tools for photoacoustic wave propagation have played a key role in advancing photoacoustic imaging by providing quantitative and qualitative insights into parameters affecting image quality. Classical methods for numerically solving the photoacoustic wave equation rely on a fine discretization of space and can become computationally expensive for large computational grids. In this work, we applied Fourier Neural Operator (FNO) networks as a fast data-driven deep learning method for solving the 2D photoacoustic wave equation in a homogeneous medium. Comparisons between the FNO network and pseudo-spectral time domain approach were made for the forward and adjoint simulations. Results demonstrate that the FNO network generated comparable simulations with small errors and was orders of magnitude faster than the pseudo-spectral time domain methods (~26× faster on a 64 × 64 computational grid and ~15× faster on a 128 × 128 computational grid). Moreover, the FNO network was generalizable to the unseen out-of-domain test set with a root-mean-square error of 9.5 × 10⁻³ in Shepp–Logan, 1.5 × 10⁻² in synthetic vasculature, 1.1 × 10⁻² in tumor and 1.9 × 10⁻² in Mason-M phantoms on a 64 × 64 computational grid and a root mean squared of 6.9 ± 5.5 × 10⁻³ in the AWA2 dataset on a 128 × 128 computational grid. Full article

Intravenous injection is a rapid, low-cost, and direct method that is commonly used to deliver multifarious biotherapeutics and vaccines. However, intravenous injection often causes trauma or tissue injury that requires professional operation. Transdermal drug delivery overcomes the aforementioned defects, and the microneedles (MNs) array is one of the most promising transdermal drug delivery platforms. Timely, precise, and non-invasive monitoring and evaluation of the effects of MNs in transdermal administration is significant to the research of drug efficiency response to specific diseases. In this sense, photoacoustic computed tomography (PACT), which provides wavelength-selective and deep-penetrating optical contrast, could be a promising imaging tool for in situ evaluation of the treatment effects. In this work, we propose the use of PACT to non-invasively assess the effects of real-time drug delivery in glioma tumors through transdermal administration with degradable indocyanine green-loaded hyaluronic acid MNs (ICG-HA-MNs). The outcome is systematically and quantitatively compared with that via intravenous injection. It is found that the photoacoustic signals of ICG in the tumor site express a faster elevation and shorter duration time in the intravenous injection group; by contrast, the photoacoustic signals demonstrate a lower intensity but prolonged duration time in the MNs group. The observed phenomenon indicates faster response but shorter drug duration for intravenous injection, which is in contrast with the lower loading but prolonged performance for transdermal drug delivery with MNs. These results exhibit good consistency with the earlier, common-sense findings reported from other aspects, confirming that PACT can serve as a potential imaging tool to precisely, non-invasively, and quickly evaluate in situ drug delivery effects and provide constructive guidance for the design and fabrication of microneedles. Full article

Photoacoustic (PA) imaging systems are spreading in the biomedical community, and the development of new PA contrast agents is an active area of research. However, PA contrast agents are usually characterized with spectrophotometry or uncalibrated PA imaging systems, leading to partial assessment of their PA efficiency. To enable quantitative PA spectroscopy of contrast agents in vitro with conventional PA imaging systems, we have developed an adapted calibration method. Contrast agents in solution are injected in a dedicated non-scattering tube phantom imaged at different optical wavelengths. The calibration method uses a reference solution of cupric sulfate to simultaneously correct for the spectral energy distribution of excitation light at the tube location and perform a conversion of the tube amplitude in the image from arbitrary to spectroscopic units. The method does not require any precise alignment and provides quantitative PA spectra, even with non-uniform illumination and ultrasound sensitivity. It was implemented on a conventional imaging setup based on a tunable laser operating between 680 nm and 980 nm and a 5 MHz clinical ultrasound array. We demonstrated robust calibrated PA spectroscopy with sample volumes as low as 15 μL of known chromophores and commonly used contrast agents. The validated method will be an essential and accessible tool for the development of new and efficient PA contrast agents by improving their quantitative characterization. Full article

Photoacoustic imaging (PAI) is an invaluable tool in biomedical imaging, as it provides anatomical and functional information in real time. Its ability to image at clinically relevant depths with high spatial resolution using endogenous tissues as contrast agents constitutes its major advantage. One of the most important applications of PAI is to quantify tissue oxygen saturation by measuring the differential absorption characteristics of oxy and deoxy Hb. Consequently, PAI can be utilized to monitor tumor-related hypoxia, which is a crucial factor in tumor microenvironments that has a strong influence on tumor invasiveness. Reactive oxygen species (ROS)-based therapies, such as photodynamic therapy, radiotherapy, and sonodynamic therapy, are oxygen-consuming, and tumor hypoxia is detrimental to their efficacy. Therefore, a persistent demand exists for agents that can supply oxygen to tumors for better ROS-based therapeutic outcomes. Among the various strategies, NP-mediated supplemental tumor oxygenation is especially encouraging due to its physio-chemical, tumor targeting, and theranostic properties. Here, we focus on NP-based tumor oxygenation, which includes NP as oxygen carriers and oxygen-generating strategies to alleviate hypoxia monitored by PAI. The information obtained from quantitative tumor oxygenation by PAI not only supports optimal therapeutic design but also serves as a highly effective tool to predict therapeutic outcomes. Full article

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

Presently, breast cancer diagnostic methods are dominated by mammography. Although drawbacks of mammography are present including ionizing radiation and patient discomfort, not many alternatives are available. Ultrasound (US) is another method used in the diagnosis of breast cancer, commonly performed on women with dense breasts or in differentiating cysts from solid tumors. Handheld ultrasound (HHUS) and automated breast ultrasound (ABUS) are presently used to generate reflection images which do not contain quantitative information about the tissue. This limitation leads to a subjective interpretation from the sonographer. To rectify the subjective nature of ultrasound, ultrasound tomography (UST) systems have been developed to acquire both reflection and transmission UST (TUST) images. This allows for quantitative assessment of tissue sound speed (SS) and acoustic attenuation which can be used to evaluate the stiffness of the lesions. Another imaging modality being used to detect breast cancer is photoacoustic tomography (PAT). Utilizing much of the same hardware as ultrasound tomography, PAT receives acoustic waves generated from tissue chromophores that are optically excited by a high energy pulsed laser. This allows the user to ideally produce chromophore concentration maps or extract other tissue parameters through spectroscopic PAT. Here, several systems in the area of TUST and PAT are discussed along with their advantages and disadvantages in breast cancer diagnosis. This overview of available systems can provide a landscape of possible intersections and future refinements in cancer diagnosis. Full article

The intervertebral discs (IVD) are among the essential organs of the human body, ensuring the mobility of the spine. These organs possess a high proportion of water. However, as the discs age, this content decreases, which can potentially lead to various diseases called degenerative disc diseases. This water content is therefore an important indicator of the well-being of the disc. In this paper, we propose photoacoustic imaging as a means of probing a disc and quantitatively recovering its molecular composition, which should allow concluding on its state. An adjoint-assisted gradient descent scheme is implemented to recover the optical absorption coefficient in the disc, from which, if spectroscopic measurements are performed, the molecular composition can be deduced. The algorithm was tested on synthetic measurements. A realistic numerical phantom was built from magnetic resonance imaging of an actual IVD of a pig. A simplified experiment, with a single laser source, was performed. Results show the feasibility of using photoacoustics imaging to probe IVDs. The influences of exact and approximate formulations of the gradient are studied. The impact of noise on the reconstructions is also evaluated. Full article

In photoacoustic imaging, the use of arrayed laser sources brings several advantages. Acoustic waves can be generated with flexible control of wavefronts, bringing functionality such as ultrasonic beam steering and focusing. The use of arrays reduces the optical intensity while increasing the strength of the ultrasonic wave, bringing the advantages of improved signal-to-noise ratio (SNR) while avoiding laser-induced damage. In this paper, we report a numerical model for studying the generation and shaping of acoustic wavefronts with laser arrays. The propagation of mechanical waves, photoacoustically generated by thermal expansion, is simulated and discussed in detail. In addition, a partially delayed distributed array is studied both theoretically and quantitatively. The developed model for wavefront control through time-delayed laser pulses is shown to be highly suited for the optimization of laser array generation schemes. Full article

Optical-resolution photoacoustic microscopy (OR-PAM) is a promising noninvasive biomedical imaging technology with label-free optical absorption contrasts. Performance of OR-PAM is usually closely related to the optical-acoustic combiner. In this study, we propose an optical-acoustic combiner based on a flat acoustic reflector and an off-axis parabolic acoustic mirror with a conical bore. Quantitative simulation and experiments demonstrated that this combiner can provide better acoustic focusing performance and detection sensitivity. Moreover, OR-PAM is based on the combiner suffer low optical disorders, which guarantees the good resolution. In vivo experiments of the mouse brain and the iris were also conducted to show the practicability of the combiner in biomedicine. This proposed optical-acoustic combiner realizes a high-quality optical-acoustic confocal alignment with minimal optical disorders and acoustic insertion loss, strong acoustic focusing, and easy implementation. These characteristics might be useful for improving the performance of OR-PAM. Full article

Vascular damage is one of the therapeutic mechanisms of photodynamic therapy (PDT). In particular, short-term PDT treatments can effectively destroy malignant lesions while minimizing damage to nonmalignant tissue. In this study, we investigate the feasibility of label-free quantitative photoacoustic microscopy (PAM) for monitoring the vasculature changes under the effect of PDT in mouse ear melanoma tumors. In particular, quantitative vasculature evaluation was conducted based on Hessian filter segmentation. Three-dimensional morphological PAM and depth-resolved images before and after PDT treatment were acquired. In addition, five quantitative vasculature parameters, including the PA signal, vessel diameter, vessel density, perfused vessel density, and vessel complexity, were analyzed to evaluate the influence of PDT on four different areas: Two melanoma tumors, and control and normal vessel areas. The quantitative and qualitative results successfully demonstrated the potential of the proposed PAM-based quantitative approach to evaluate the effectiveness of the PDT method. Full article