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

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.

Photoacoustic tomography has emerged as a prominent medical imaging technique that leverages its hybrid nature to provide deep penetration, high resolution, and exceptional optical contrast with notable applications in early cancer detection, functional brain imaging, drug delivery monitoring, and guiding interventional procedures. Test phantoms are pivotal in accelerating technology development and commercialization, specifically in photoacoustic (PA) imaging, and can be optimized to achieve significant advancements in PA imaging capabilities.
The analysis of material properties, structural characteristics, and manufacturing methodologies of test phantoms from existing imaging technologies provides valuable insights into their applicability to PA imaging. This investigation enables a deeper understanding of how phantoms can be effectively employed in the context of PA imaging.
Three primary categories of test phantoms (simple, intermediate, and advanced) have been developed to differentiate complexity and manufacturing requirements. In addition, four sub-categories (tube/channel, block, test target, and naturally occurring phantoms) have been identified to encompass the structural variations within these categories, resulting in a comprehensive classification system for test phantoms.
Based on a thorough examination of literature and studies on phantoms in various imaging modalities, proposals have been put forth for the development of multiple PA-capable phantoms, encompassing considerations related to the material composition, structural design, and specific applications within each sub-category.
The advancement of novel and sophisticated test phantoms within each sub-category is poised to foster substantial progress in both the commercialization and development of PA imaging. Moreover, the continued refinement of test phantoms will enable the exploration of new applications and use cases for PA imaging.

Photo-mediated ultrasound therapy (PUT) is a novel therapeutic technique based on the combination of ultrasound and laser. The underlying mechanism of PUT is the enhanced cavitation effect inside blood vessels. The enhanced cavitation activity can result in bio-effects such as reduced perfusion in microvessels. The reduced perfusion effect in microvessels in the eye has the potential to control the progression of eye diseases such as diabetic retinopathy and age-related macular degeneration. Several in vivo studies have demonstrated the feasibility of PUT in removing microvasculature in the eye using rabbit eye model and vasculature in the skin using rabbit ear model. Numerical studies using a bubble dynamics model found that cavitation is enhanced during PUT due to the dramatic increase in size of air/vapor nuclei in blood. In addition, the study conducted to model cavitation dynamics inside a blood vessel during PUT found stresses induced on the vessel wall during PUT are higher than that at normal physiological levels, which may be responsible for bio-effects. The concentration of vasodilators such as nitric oxide and prostacyclin were also found to be affected during PUT in an in vitro study, which may limit blood perfusion in vessels. The main advantage of PUT over conventional techniques is non-invasive, precise, and selective removal of microvessels with high efficiency at relatively low energy levels of ultrasound and laser, without affecting the nearby structures. However, the main limitation of vessel rupture/hemorrhage needs to be overcome through the development of real-time monitoring of treatment effects during PUT. In addition to the application in removing microvessels, PUT-based techniques were also explored in treating other diseases. Studies have found a combination of ultrasound and laser to be effective in removing blood clots inside veins, which has the potential to treat deep-vein thrombosis. The disruption of atherosclerotic plaque using combined ultrasound and laser was also tested, and the feasibility was demonstrated.

The prevalence of diabetes is increasing globally. More than 690 million cases of diabetes are expected worldwide by 2045. Continuous blood glucose monitoring is essential to control the disease and avoid long-term complications. Diabetics suffer on a daily basis with the traditional glucose monitors currently in use, which are invasive, painful, and cost-intensive. Therefore, the demand for non-invasive, painless, economical, and reliable approaches to monitor glucose levels is increasing. Since the last decades, many glucose sensing technologies have been developed. Researchers and scientists have been working on the enhancement of these technologies to achieve better results. This paper provides an updated review of some of the pioneering non-invasive optical techniques for monitoring blood glucose levels that have been proposed in the last six years, including a summary of state-of-the-art error analysis and validation techniques.

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

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.

Photoacoustic imaging, with the capability to provide simultaneous structural, functional, and molecular information, is one of the fastest growing biomedical imaging modalities of recent times. As a hybrid modality, it not only provides greater penetration depth than the purely optical imaging techniques, but also provides optical contrast of molecular components in the living tissue. Conventionally, photoacoustic imaging systems utilize bulky and expensive class IV lasers, which is one of the key factors hindering the clinical translation of this promising modality. Use of LEDs which are portable and affordable offers a unique opportunity to accelerate the clinical translation of photoacoustics. In this paper, we first review the development history of LED as an illumination source in biomedical photoacoustic imaging. Key developments in this area, from point-source measurements to development of high-power LED arrays, are briefly discussed. Finally, we thoroughly review multiple phantom, ex-vivo, animal in-vivo, human in-vivo, and clinical pilot studies and demonstrate the unprecedented preclinical and clinical potential of LED-based photoacoustic imaging.

The retinal pigment epithelium (RPE) is essential to the health of the retina and the proper functioning of the photoreceptors. The RPE is rich in melanosomes, which contain the pigment melanin. Changes in RPE pigmentation are seen with normal aging and in diseases such as albinism and age-related macular degeneration. However, most techniques used to this day to detect and quantify ocular melanin are performed ex vivo and are destructive to the tissue. There is a need for in vivo imaging of melanin both at the clinical and pre-clinical level to study how pigmentation changes can inform disease progression. In this manuscript, we review in vivo imaging techniques such as fundus photography, fundus reflectometry, near-infrared autofluorescence imaging, photoacoustic imaging, and functional optical coherence tomography that specifically detect melanin in the retina. These methods use different contrast mechanisms to detect melanin and provide images with different resolutions and field-of-views, making them complementary to each other.

The visualization capabilities of various ocular imaging instruments can generally be categorized into photographic (e.g. gonioscopy, Pentacam, RetCam) and optical tomographic (e.g. optical coherence tomography (OCT), photoacoustic (PA) imaging, ultrasound biomicriscopy (UBM)) methods. These imaging instruments allow vision researchers and clinicians to visualize the iridocorneal angle, and are essential in the diagnosis and management of glaucoma. Each of these imaging modalities has particular benefits and associated drawbacks in obtaining repeatable and reliable measurement in the evaluation of the angle. This review article in this context summarized recent progresses in anterior chamber imaging techniques in glaucoma diagnosis and follow-up procedures.