Abstract

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.

Highlights

  • Probing the molecular contrast is one of the key advantages of optical-based sensing approaches.By adding the spatial dimension, the development of optical microscopy—from classical bright-field microscopy to other advanced optical imaging modalities, has been one of the main drivers for discoveries and researches in both life science and biomedical imaging

  • There is a huge demand for biomedical imaging modalities that can provide non-invasive deep-tissue imaging with high spatial resolution

  • For Photoacoustic tomography (PAT) with exogenous contrast agents, Li et al developed a reflection-mode photoacoustic microscopy (PAM) system with an optical-acoustic combiner to track micro-rocket robots which were coated with 100-nm-thick gold layer, achieving single micro-robot in vivo imaging in the bloodstream of a mouse ear with a resolution of 3.2 μm under 532-nm pulsed laser excitation (Figure 11) [132]

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Summary

Introduction

Probing the molecular contrast is one of the key advantages of optical-based sensing approaches. By adding the spatial dimension, the development of optical microscopy—from classical bright-field microscopy to other advanced optical imaging modalities (e.g., multiphoton and light-sheet microscopy), has been one of the main drivers for discoveries and researches in both life science and biomedical imaging These optical imaging modalities can provide rich molecular contrast and generate high-resolution images for visualizing subcellular features such as organelles. There is a huge demand for biomedical imaging modalities that can provide non-invasive deep-tissue imaging with high spatial resolution. As the attenuation of PA waves in biological tissues is ~3 orders of magnitude weaker than that of photons, the ultrasonic detection nature of PAT allows deeper imaging depth at high resolution when compared with optical microscopy. With the understanding of the information available for PAT with or without exogenous contrasts, common configurations of reflection-mode PAT systems and the latest advances in different all-optical acoustic sensing techniques used in PAT will be highlighted

Endogenous Contrast Agents
Absorption
Hemoglobin
Melanin
Photoacoustic Tomography with Multiple Endogenous Contrasts
Exogenous Contrast Agents
Principle of Exogenous Contrast Agent Design
Targeting Mechanisms and Ligands
Photoacoustic Compounds for Exogenous Contrast Agents
Nanoparticles
Metallic Nanoparticles
Calculated
Carbon Nanotubes
Molecular Photoacoustic Contrast Agents
Cyanine Dyes
Tetrapyrrole
Molecular
Reflection-Mode Photoacoustic Microscopy
Parabolic Mirror
All-Optical
Optical
Photoacoustic Remote Sensing
Fabry–Perot Interferometer
Findings
Conclusions
Full Text
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