New generation ICG-based contrast agents for ultrasound-switchable fluorescence imaging

Abstract

Recently, we developed a new technology, ultrasound-switchable fluorescence (USF), for high-resolution imaging in centimeter-deep tissues via fluorescence contrast. The success of USF imaging highly relies on excellent contrast agents. ICG-encapsulated poly(N-isopropylacrylamide) nanoparticles (ICG-NPs) are one of the families of the most successful near-infrared (NIR) USF contrast agents. However, the first-generation ICG-NPs have a short shelf life (<1 month). This work significantly increases the shelf life of the new-generation ICG-NPs (>6 months). In addition, we have conjugated hydroxyl or carboxyl function groups on the ICG-NPs for future molecular targeting. Finally, we have demonstrated the effect of temperature-switching threshold (Tth) and the background temperature (TBG) on the quality of USF images. We estimated that the Tth of the ICG-NPs should be controlled at ~38–40 °C (slightly above the body temperature of 37 °C) for future in vivo USF imaging. Addressing these challenges further reduces the application barriers of USF imaging.

A Biocompatible and Near‐Infrared Liposome for In Vivo Ultrasound‐Switchable Fluorescence Imaging

“…This scenario usually happens when the imaging target is located at a small depth (≈1–2 cm). The setting in our previous studies using the PNIPAM nanoparticles fits in this situation . However, when the imaging target is deep (>2 cm), the fluorescence generated from the (non‐100%‐off) USF contrast agents may be significantly attenuated due to tissue's scattering.…”

“…To study the fluorescence intensity changes in response to the temperature changes, an in‐house built system was implemented . Briefly, a 3 mL sample was transferred into a quartz cuvette (Hellma, Germany) and then immersed in a water bath.…”

“…This may raise safety concerns when ICG‐PNIPAM is used for in vivo USF studies. Second, compared to the ICG dye aqueous solution, the excitation peak of the ICG‐PNIPAM shifted from 788 to 660 nm and the emission peak changed from 809 to 690 nm . The aza‐BODIPY dye used in the micelle contrast agent has a similar excitation peak at 683 nm and an emission peak at 717 nm .…”

“…High‐resolution fluorescence imaging in deep tissue was achieved . Recently, the adoption of new synthesis protocols has significantly improved the stability of ICG‐PNIPAM . With the stable ICG‐PNIPAM available, researchers recently reported in vivo USF imaging in a mouse for the first time .…”

Modulation of ultrasound-switchable fluorescence for improving signal-to-noise ratio

“…[1][2][3][4][5][6] We recently developed a new imaging method for deep-tissue high-resolution imaging, which has been termed as ultrasound-switchable fluorescence (USF). [7][8][9][10][11][12][13] It has been demonstrated that USF can simultaneously achieve high SNR (or sensitivity) and high spatial resolution in tissue with a depth of centimeters. [7][8][9][10][11][12][13] In this study, we report a new method to further improve the SNR (or sensitivity) of the USF imaging without sacrificing the spatial resolution by modulating the ultrasound exposure.…”