Regulating interparticle proximity in plasmonic nanosphere aggregates to enhance photoacoustic response and photothermal stability.

Designing plasmonic nanoparticles for biomedical photoacoustic (PA) imaging involves tailoring material properties at the nanometer scale. A key in developing plasmonic PA contrast nanoagents is to engineer their enhanced optical responses in the near-infrared wavelength range, as well as heat transfer properties and photostability. This study introduces anisotropic plasmonic nanosphere aggregates with close interparticle proximity as photostable and efficient contrast agent for PA imaging. Silver (Ag), among plasmonic metals, is particularly attractive due to its strongest optical response and highest heat conductivity. Our results demonstrate that close interparticle proximity in silver nanoaggregates (AgNAs), spatially confined within a polymer shell layer, leads to blackbody-like optical absorption, resulting in robust PA signals through efficient pulsed heat generation and transfer. Additionally, our AgNAs exhibit a high photodamage threshold highlighting their potential to outperform conventional plasmonic contrast agents for high-contrast PA imaging over multiple imaging sessions. Furthermore, we demonstrate the capability of the AgNAs for molecular PA cancer imaging in vivo by incorporating a tumor-targeting peptide moiety.

Hyper-Branched Gold Nanoconstructs for Photoacoustic Imaging in the Near-Infrared Optical Window.

In plasmonic nanoconstructs (NCs), fine-tuning interparticle interactions at the subnanoscale offer enhanced electromagnetic and thermal responses in the near-infrared (NIR) wavelength range. Due to tunable electromagnetic and thermal characteristics, NCs can be excellent photoacoustic (PA) imaging contrast agents. However, engineering plasmonic NCs that maximize light absorption efficiency across multiple polarization directions, i.e., exhibiting blackbody absorption behavior, remains challenging. Herein, we present the synthesis, computational simulation, and characterization of hyper-branched gold nanoconstructs (HBGNCs) as a highly efficient PA contrast agent. HBGNCs exhibit remarkable optical properties, including strong NIR absorption, high absorption efficiency across various polarization angles, and superior photostability compared to conventional standard plasmonic NC-based contrast agents such as gold nanorods and gold nanostars. In vitro and in vivo experiments confirm the suitability of HBGNCs for cancer imaging, showcasing their potential as reliable PA contrast agents and addressing the need for enhanced imaging contrast and stability in bioimaging applications.

A Review of Endogenous and Exogenous Contrast Agents Used in Photoacoustic Tomography with Different Sensing Configurations.

Optical-based sensing approaches have long been an indispensable way to detect molecules in biological tissues for various biomedical research and applications. The advancement in optical microscopy is one of the main drivers for discoveries and innovations in both life science and biomedical imaging. However, the shallow imaging depth due to the use of ballistic photons fundamentally limits optical imaging approaches' translational potential to a clinical setting. Photoacoustic (PA) tomography (PAT) is a rapidly growing hybrid imaging modality that is capable of acoustically detecting optical contrast. PAT uniquely enjoys high-resolution deep-tissue imaging owing to the utilization of diffused photons. The exploration of endogenous contrast agents and the development of exogenous contrast agents further improve the molecular specificity for PAT. PAT's versatile design and non-invasive nature have proven its great potential as a biomedical imaging tool for a multitude of biomedical applications. In this review, representative endogenous and exogenous PA contrast agents will be introduced alongside common PAT system configurations, including the latest advances of all-optical acoustic sensing techniques.

Advances in imaging techniques of the blood-brain barrier and clinical application.

The blood-brain barrier (BBB) is an important structure that maintains the normal function of the central nervous system (CNS). The functional structure of BBB is closely related to diseases of CNS, including degenerative diseases, brain tumours, traumatic brain injury, stroke, etc. Imaging methods were commonly used to monitor the integrity of BBB, such as DCE-MRI, DSC-MRI, and PET, this contributes to understand the process of related diseases and develop appropriate treatment options. In recent years, many studies had shown that the MRI methods (ASL, IVIM, CEST, etc.) could evaluate blood-brain barrier function, which use endogenous contrast agents and become an increasingly great concern. Another image methods (FUS, uWB-eMPs) can open up the normal BBB, allowing macromolecular drugs across the locally opening BBB, which could be beneficial to the treatment of some brain diseases. In this review, we briefly introduce the theory of BBB imaging modalities and its clinical application.

Exogenous Contrast Agents in Photoacoustic Imaging: An In Vivo Review for Tumor Imaging.

The field of cancer theranostics has grown rapidly in the past decade and innovative 'biosmart' theranostic materials are being synthesized and studied to combat the fast growth of cancer metastases. While current state-of-the-art oncology imaging techniques have decreased mortality rates, patients still face a diminished quality of life due to treatment. Therefore, improved diagnostics are needed to define in vivo tumor growths on a molecular level to achieve image-guided therapies and tailored dosage needs. This review summarizes in vivo studies that utilize contrast agents within the field of photoacoustic imaging-a relatively new imaging modality-for tumor detection, with a special focus on imaging and transducer parameters. This paper also details the different types of contrast agents used in this novel diagnostic field, i.e., organic-based, metal/inorganic-based, and dye-based contrast agents. We conclude this review by discussing the challenges and future direction of photoacoustic imaging.

Photoacoustic microscopy: principles and biomedical applications.

Photoacoustic microscopy (PAM) has become an increasingly popular technology for biomedical applications, providing anatomical, functional, and molecular information. In this concise review, we first introduce the basic principles and typical system designs of PAM, including optical-resolution PAM and acoustic-resolution PAM. The major imaging characteristics of PAM, i.e. spatial resolutions, penetration depth, and scanning approach are discussed in detail. Then, we introduce the major biomedical applications of PAM, including anatomical imaging across scales from cellular level to organismal level, label-free functional imaging using endogenous biomolecules, and molecular imaging using exogenous contrast agents. Lastly, we discuss the technical and engineering challenges of PAM in the translation to potential clinical impacts.

Photoacoustic Imaging for Cancer Detection and Staging.

Cancer is one of the leading causes of death in the world. Diagnosing a cancer at its early stages of development can decrease the mortality rate significantly and reduce healthcare costs. Over the past two decades, photoacoustic imaging has seen steady growth and has demonstrated notable capabilities to detect cancerous cells and stage cancer. Furthermore, photoacoustic imaging combined with ultrasound imaging and augmented with molecular targeted contrast agents is capable of imaging cancer at the cellular and molecular level, thus opening diverse opportunities to improve diagnosis of tumors, detect circulating tumor cells and identify metastatic lymph nodes. In this paper we introduce the principles of photoacoustic imaging, and review recent developments in photoacoustic imagingas an emerging imaging modality for cancer diagnosis and staging.