Abstract
Micron-sized liquid perfluorocarbon (PFC) droplets are currently being investigated as activatable agents for medical imaging and cancer therapy. After injection into the bloodstream, superheated PFC droplets can be vaporized to a gas phase for ultrasound imaging, or for cancer therapy via targeted drug delivery and vessel occlusion. Droplet vaporization has been previously demonstrated using acoustic methods. We propose using laser irradiation as a means to induce PFC droplet vaporization using a method we term optical droplet vaporization (ODV). In order to facilitate ODV of PFC droplets which have negligible absorption in the infrared spectrum, optical absorbing nanoparticles were incorporated into the droplet. In this study, micron-sized PFC droplets loaded with silica-coated lead sulfide (PbS) nanoparticles were evaluated using a 1064 nm laser and ultra-high frequency photoacoustic ultrasound (at 200 and 375 MHz). The photoacoustic response was proportional to nanoparticle loading and successful optical droplet vaporization of individual PFC droplets was confirmed using photoacoustic, acoustic, and optical measurements. A minimum laser fluence of 1.4 J/cm2 was required to vaporize the droplets. The vaporization of PFC droplets via laser irradiation can lead to the activation of PFC agents in tissues previously not accessible using standard ultrasound-based techniques.
Highlights
Perfluorocarbons (PFCs) are non-toxic, chemically and biologically inert compounds [1] with unique physical properties that enable their use in a wide range of medical applications
In this paper we demonstrate that a photoacoustic signal can be measured from micron-sized PFC droplets containing PbS nanoparticles before vaporization
We demonstrate that laser light may be used to vaporize nanoparticle-loaded PFC droplets when irradiated above a threshold laser fluence, and confirm that the resulting bubbles can be detected via ultrasound methods
Summary
Perfluorocarbons (PFCs) are non-toxic, chemically and biologically inert compounds [1] with unique physical properties that enable their use in a wide range of medical applications. PFP droplets have poor ultrasound contrast due to their acoustic impedance which is similar to that of the surrounding tissue, droplets must be converted to gas bubbles to enable their use as an effective ultrasound contrast agent. The conversion from droplets to bubbles is induced via ultrasound irradiation once a threshold pressure is achieved [10] In this approach large peak negative ultrasonic pressures that may be harmful to normal surrounding tissue (e.g., 10 to 13 MPa at approximately 3.0 MHz in canine kidney [11]) have been reported during transcutaneous acoustic droplet conversion (ADV). Ultrasound beams cannot effectively penetrate gaseous enclosures in the human body, such as the lungs Another method is required to induce the therapeutic function of the droplets in these locations
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