Ultrasound Imaging and Therapeutics Research Laboratory

Laser Activated PFCnDs as a Tool in Neurological Applications

Summary

Laser-activated perfluorocarbon nanodroplets (PFCnDs) are a versatile tool capable of changing phase from liquid to gas when excited with laser energy.1 This phase-change behavior allows droplets to play a role in diagnostic and therapeutic applications.2 For example, PFCnD activation can be harnessed to mechanically open biological barriers, by stretching tight junctions, increasing the uptake in mechanotransduction pathways, and creating pores in cell membranes. Furthermore, laser-activated PFCnDs produce both ultrasound (US) and photoacoustic (PA) contrast and therefore are utilized in a variety of imaging techniques, from super-resolution imaging to molecular and functional imaging (Fig. 1).3,4,5,6 Laser-activated PFCnDs can be synthesized with additional cargo or targeting moieties, also allowing for localized delivery of therapeutics or contrast agents.2

This project focuses on these droplet characteristics and their utility in neurological applications, where noninvasive, local, and repeatable monitoring and therapy has the potential to improve current diagnosis and treatment outcomes. Specifically, laser-activated PFCnDs are synthesized to open neurological barriers, such as the blood brain barrier and blood-spinal cord barrier. PFCnDs are also being investigated as delivery vehicles and contrast agents for the CNS, enabling exploration of PFCnDs as a versatile agent for monitoring and treatment of neurological diseases.

Figure 1
Figure 1 A) Depiction of in vivo experimental setup for BBB opening B) Cartoon of PFCnDs interacting with the endothelial lining, allowing for barrier opening C) Photograph of Evans Blue staining of right side of brain opened using laser irradiation and PFCnDs D) Ex Vivovivo USPA imaging of brain tissue containing PA dye particles that have extravasated after BBB opening E) Immunohistochemistry staining of extravasated immunoglobulin G ^

Further Reading

  • K. Hallam, S.Y. Emelianov, “Towards optimization of blood brain barrier opening induced by laser-activated perfluorocarbon nanodroplets,” Biomed. Opt. Express 10(7), 3139-3151 (2019)
  • K. Hallam, E. Donnelly, A. Karpiouk, R. Hartman, and S. Emelianov, “Laser-activated perfluorocarbon nanodroplets: a new tool for blood brain barrier opening,” Biomed. Opt. Express 9, 4527-4538 (2018)

References

  1. Wilson, K., Homan, K. & Emelianov, S. Biomedical photoacoustics beyond thermal expansion using triggered nanodroplet vaporization for contrast-enhanced imaging. Nat Commun 3, 618, doi:10.1038/ncomms1627 (2012).^
  2. Rapoport, N. Drug-Loaded Perfluorocarbon Nanodroplets for Ultrasound-Mediated Drug Delivery. Adv Exp Med Biol 880, 221-241, doi:10.1007/978-3-319-22536-4_13 (2016).^
  3. Luke, G. P., Hannah, A. S. & Emelianov, S. Y. Super-Resolution Ultrasound Imaging in Vivo with Transient Laser-Activated Nanodroplets. Nano Lett 16, 2556-2559, doi:10.1021/acs.nanolett.6b00108 (2016).^
  4. Yoon, H. et al. Contrast-enhanced ultrasound imaging in vivo with laser-activated nanodroplets. Med Phys 44, 3444-3449, doi:10.1002/mp.12269 (2017).^
  5. Hannah, A. S., Luke, G. P. & Emelianov, S. Y. Blinking Phase-Change Nanocapsules Enable Background-Free Ultrasound Imaging. Theranostics 6, 1866-1876, doi:10.7150/thno.14961 (2016).^
  6. Yoon, H., Hallam, K.A., Yoon, C.  and Emelianov, S.Y. Super-resolution imaging with ultrafast ultrasound imaging of optically triggered perfluorohexane nanodroplets. IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control., doi:10.1109/TUFFC.2018.2829740 (2018).^