Investigation of Focused Ultrasound with a Contrast Agent on Local Blood-Brain Barrier Disruption
Date Issued
2007
Date
2007
Author(s)
Yang, Feng-Yi
Abstract
It has been shown that focused ultrasound (FUS) can disrupt the blood–brain barrier (BBB) noninvasively and reversibly at target locations when applied in the presence of ultrasound contrast agent (UCA). In this study, the dose-dependent effects of UCA on BBB disruption were investigated in the brains of male Wistar rats sonicated by 1.0-MHz pulsed FUS, with the UCA present at different doses. The BBB disruption was evaluated quantitatively based on the extravasation of Evans Blue (EB). The amount of EB extravasation in the brain increased with the quantity of UCA injected into the femoral vein prior to sonication. The use of a suitable dose of UCA resulted in the BBB disruption being concentrated in the focal region instead of the entire brain. From the histological examination, there was no neuronal damage when UCA was used at a low dose, but the higher doses result in the appearance of apoptotic cells and the number of apoptotic cells decreased symmetrically with distance from the focus. Moreover, comparing the effects of UCA at the various doses reveals no obvious differences in the temperature rise at the inner and outer skull surfaces. Our results indicate that a local BBB disruption combined with an acceptable impact on the brain tissue can be produced by using an appropriate UCA dose with transcranial FUS sonication.inally, this study was to examine the steering and focusing ability of a contact hemispherical ultrasound transducer (80 mm radius of curvature, 160 mm diameter) for transskull brain diseases therapy without skull-specific aberration correction. A simulation program was used to investigate the effect of ultrasound transducer parameters on the steering and focusing ability for transskull therapy. The acoustic pressure distribution and the grating lobes in tissues were used to determine the steering and focusing ability of this transducer for a set of given conditions. Simulation results demonstrated that this hemispherical phased array transducer with low frequencies can steer a high-pressure focal zone for a large range in the brain. The peak and size of the high-pressure focal zone mainly depend on ultrasound frequency and the steering distance of the focal zone. By comparing the peak pressures between the focal zone and the grating lobe, 0.1 MHz transducer performed the desired results for large ranges (140 mm x-y direction and 138 mm z direction) of beam steering.The results reveal the feasibility of using a hemispherical phased array transducer with beam steering method at low frequency for brain diseases therapy within almost full range of the brain without performing a craniectomy.
Subjects
Focused ultrasound
Ultrasound contrast agent
Transcranial
Blood–brain-barrier disruption
Beam steering
Ultrasound transducer
Type
thesis
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