Biomedical photoacoustics beyond thermal expansion using triggered nanodroplet vaporization for contrast-enhanced imaging

Abstract

since being discovered by Alexander Bell, photoacoustics may again be seeing major resurgence in biomedical imaging. Photoacoustics is a non-ionizing, functional imaging modality capable of high contrast images of optical absorption at depths significantly greater than traditional optical imaging techniques. optical contrast agents have been used to extend photoacoustics to molecular imaging. Here we introduce an exogenous contrast agent that utilizes vaporization for photoacoustic signal generation, providing significantly higher signal amplitude than that from the traditionally used mechanism, thermal expansion. our agent consists of liquid perfluorocarbon nanodroplets with encapsulated plasmonic nanoparticles, entitled photoacoustic nanodroplets. upon pulsed laser irradiation, liquid perfluorocarbon undergoes a liquid-to-gas phase transition generating giant photoacoustic transients from these dwarf nanoparticles. once triggered, the gaseous phase provides ultrasound contrast enhancement. We demonstrate in phantom and animal studies that photoacoustic nanodroplets act as dualcontrast agents for both photoacoustic and ultrasound imaging through optically triggered vaporization.

Engineering optically triggered droplets for photoacoustic imaging and therapy

“…There has been progress towards modifying the optical absorbing structure within the droplet core in order to maximize the temperature rise and thus lower the optical fluence required to produce ODV [8,11]. In addition, ODV in the near-infrared (NIR) region of the spectrum, where the optical penetration within tissue is large, has been demonstrated by incorporating NIR absorbing gold nanorods into the droplet core or clustered gold nanospheres on the droplet surface [8][9][10].…”

“…Under sufficiently high laser fluence, a phase transition is induced; a process termed optical droplet vaporization (ODV). ODV based contrast agents have several advantages over photoacoustic contrast agents that rely solely on photothermal heating to produce acoustic waves in that a) the vaporization event produces an exceptionally strong photoacoustic response, exceeding that from the thermoelastic expansion and allowing for improved photoacoustic imaging contrast, b) the microbubbles created through ODV can provide ultrasound contrast in dual mode imaging scenarios and c) the light absorbing species incorporated into the droplets remain after vaporization and can be used to provide lasting enhanced photoacoustic contrast [7][8][9]. There has been progress towards modifying the optical absorbing structure within the droplet core in order to maximize the temperature rise and thus lower the optical fluence required to produce ODV [8,11].…”

“…More recently, phase change agents have been proposed as promising photoacoustic contrast agents [7][8][9][10][11][12][13]. In this case, PFC droplets are designed to absorb light at the wavelength of interest by incorporating a light absorbing species within the droplet or on the periphery.…”

Plasmonic Nanoparticles with Quantitatively Controlled Bioconjugation for Photoacoustic Imaging of Live Cancer Cells

“…From this standpoint, microscopic imaging of single or small numbers of cancer cells is highly desirable and of special significance 19, 20. This, however, imposes demanding requirements on the resolution and sensitivity of PAI because most cancer cells are very small in size (≈10 μm) and exhibit little endogenous absorption contrast (except melanoma cells) 21, 22, 23, 24, 25, 26. To achieve high‐sensitivity PAI at the cellular level, exogenous contrast agent is preferably used to enhance optical absorption and amplify photoacoustic signal generation efficiency 27, 28, 29…”

Biomedical photoacoustics: fundamentals, instrumentation and perspectives on nanomedicine

“…60 Perfluorocarbon (PFC) nanodroplets as promising probes for optical molecular imaging were integrated with plasmonic nanoparticles for US/PAI and therapy. 61,62 With the growing translation to clinics, PFC nanodroplets have been refined with biocompatibility and nontoxicity. 63 It is noted that PFC nanodroplets display a unique profile of phase transition under ambient conditions, so it is possible to utilize them for Figure 5 Images acquired before and after injecting sWNt-rGD as well as control plain sWNts obtained by Us (gray) and PA (green) imaging.…”