Applications of ultrasound and photoacoustics in the central nervous system

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2017-05

Authors

Hartman, Robin Kathleen

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Abstract

Ultrasound imaging has seen a new resurgence in both clinical and preclinical research as demand for affordable and accessible imaging techniques has increased. There are both therapeutic and imaging applications of ultrasound. In these studies, the feasibility of several new applications for ultrasound-based imaging techniques are explored. Specifically, a new method for measuring the flow of cerebrospinal fluid (CSF) in cerebral shunt systems of patients with hydrocephalus was investigated. A cross-correlation based speckle-tracking algorithm was used to measure displacement of flowing perfluorocarbon microbubbles in a catheter. This method was able to detect lower flow rates than other CSF flow measurement methods in the literature and could be used for both an initial evaluation of shunt function as well as a tool for studying CSF flow dynamics over time in patients with hydrocephalus. Additionally, the use of focused ultrasound (FUS) blood brain barrier (BBB) disruption for delivery of imaging contrast agents is presented. First, FUS BBB disruption was used to deliver an oxygen-sensitive two-photon contrast agent in the parenchyma of C57BL/6 mice. Both fluorescence and phosphorescence signal from the dye were detectable in the extravascular space after sonication. Then, the delivery of photoacoustic (PA) gold nanorods (AuNRs) via FUS BBB disruption was demonstrated, though further parameter optimization will be necessary. Finally, a possible PA contrast agents for Alzheimer’s Disease was tested. Antibodies for beta-amyloid were conjugated to gold nanoparticles and the conjugated nanoparticles were tested with synthetic peptides and in AD tissue samples. These studies showed that the nanoparticles could specifically bind to synthetic peptides, though electrostatic interactions with the surface the peptides were deposited on complicated interpretation of specificity of the particles. The results of the overall studies indicate that, with the increase in demand for affordable, non-invasive methods for brain imaging and, more broadly, neuroscience, there are numerous potential applications for ultrasound-based techniques.

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