The use of focused ultrasound (FUS) with microbubbles has been proven to induce transient blood–brain barrier opening (BBB-opening). However, FUS-induced inertial cavitation of microbubbles can also result in erythrocyte extravasations. Here we investigated whether induction of submicron bubbles to oscillate at their resonant frequency would reduce inertial cavitation during BBB-opening and thereby eliminate erythrocyte extravasations in a rat brain model. FUS was delivered with acoustic pressures of 0.1–4.5 MPa using either in-house manufactured submicron bubbles or standard SonoVue microbubbles. Wideband and subharmonic emissions from bubbles were used to quantify inertial and stable cavitation, respectively. Erythrocyte extravasations were evaluated by in vivo post-treatment magnetic resonance susceptibility-weighted imaging, and finally by histological confirmation. We found that excitation of submicron bubbles with resonant frequency-matched FUS (10 MHz) can greatly limit inertial cavitation while enhancing stable cavitation. The BBB-opening was mainly caused by stable cavitation, whereas the erythrocyte extravasation was closely correlated with inertial cavitation. Our technique allows extensive reduction of inertial cavitation to induce safe BBB-opening. Furthermore, the safety issue of BBB-opening was not compromised by prolonging FUS exposure time, and the local drug concentrations in the brain tissues were significantly improved to 60 times (BCNU; 18.6 µg versus 0.3 µg) by using chemotherapeutic agent-loaded submicron bubbles with FUS. This study provides important information towards the goal of successfully translating FUS brain drug delivery into clinical use.
Line drawing is a style of image abstraction where the perceptual content of the image is conveyed using distinct straight or curved lines. However, extracting semantically salient lines is not trivial and mastered only by skilled artists. While many parametric filters have successfully extracted accurate and coherent lines, their results are sensitive to parameter choice and easily lead to either an excessive or insufficient number of lines. In this work, we present an interactive system to generate concise line abstractions of arbitrary images via a few user specified strokes. Specifically, the user simply has to provide a few intuitive strokes on the input images, including tracing roughly along edges and scribbling on the region of interest, through a sketching interface. The system then automatically extracts lines that are long, coherent and share similar textural structures to form a corresponding highly detailed line drawing. We have tested our system with a wide variety of images. Our experimental results show that our system outperforms state-of-the-art techniques in terms of quality and efficiency.
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