Abstract
Almost every variety of medical imaging technique relies heavily on exogenous contrast agents to generate high-resolution images of biological structures. Organic small molecule contrast agents, in particular, are well suited for biomedical imaging applications due to their favorable biocompatibility and amenability to structural modification. PET/SPECT, MRI, and fluorescence imaging all have a large host of small molecule contrast agents developed for them, and there exists an academic understanding of how these compounds can be developed. Optoacoustic imaging is a relatively newer imaging technique and, as such, lacks well-established small molecule contrast agents; many of the contrast agents used are the same ones which have found use in fluorescence imaging applications. Many commonly-used fluorescent dyes have found successful application in optoacoustic imaging, but others generate no detectable signal. Moreover, the structural features that either enable a molecule to generate a detectable optoacoustic signal or prevent it from doing so are poorly understood, so design of new contrast agents lacks direction. This review aims to compile the small molecule optoacoustic contrast agents that have been successfully employed in the literature to bridge the information gap between molecular design and optoacoustic signal generation. The information contained within will help to provide direction for the future synthesis of optoacoustic contrast agents.
Highlights
While there are some endogenous contrast agents used in optoacoustic imaging, the use of exogenous contrast agents such as small molecule dyes is necessary for a wider range of biological activities including acidosis [8,9]
This review focuses on widely-used, commercially-available NIR dyes that are commonly used in fluorescence imaging, and their potential for optoacoustic imaging
While there are a variety of commercially-available small molecule dyes that have shown promise as optoacoustic contrast agents, the need for more improved optoacoustic contrast agents is still great
Summary
While the development of near-infrared dyes has increased the depth of fluorescent detection, the visualization of these dyes remains limited to a few millimeters Emerging technologies, such as fluorescence molecular tomography, have improved this to depths of up to 10 cm, the instrumentation for this has not yet reached a clinically-relevant size, and cannot be used to provide real-time guidance [2,3,4]. Because most tissues are relatively transparent to light in the range of 650 to 900 nm, MSOT uses NIR light to excite molecules which generate soundwaves These ultrasonic waves are considerably less scattered in tissue than photons, which allows for deeper tissue penetration (>3 cm) with higher accuracy and resolution than purely optical imaging [6,7]. While there are some endogenous contrast agents used in optoacoustic imaging, the use of exogenous contrast agents such as small molecule dyes is necessary for a wider range of biological activities including acidosis [8,9]
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