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Sci Rep. 2019 Feb 26;9(1):2840. doi: 10.1038/s41598-019-39090-9.

Cavitation dose painting for focused ultrasound-induced blood-brain barrier disruption.

Author information

1
Department of Biomedical Engineering, Washington University in St. Louis, Saint Louis, MO, 63130, USA.
2
Mallinckrodt Institute of Radiology, Washington University School of Medicine, Saint Louis, MO, 63110, USA.
3
Department of Mechanical Engineering and Materials Science, Washington University in St. Louis, Saint Louis, MO, 63130, USA.
4
Department of Radiation Oncology, Washington University School of Medicine, Saint Louis, MO, 63108, USA.
5
Department of Biomedical Engineering, Washington University in St. Louis, Saint Louis, MO, 63130, USA. hongchen@wustl.edu.
6
Department of Radiation Oncology, Washington University School of Medicine, Saint Louis, MO, 63108, USA. hongchen@wustl.edu.

Abstract

Focused ultrasound combined with microbubble for blood-brain barrier disruption (FUS-BBBD) is a promising technique for noninvasive and localized brain drug delivery. This study demonstrates that passive cavitation imaging (PCI) is capable of predicting the location and concentration of nanoclusters delivered by FUS-BBBD. During FUS-BBBD treatment of mice, the acoustic emissions from FUS-activated microbubbles were passively detected by an ultrasound imaging system and processed offline using a frequency-domain PCI algorithm. After the FUS treatment, radiolabeled gold nanoclusters, 64Cu-AuNCs, were intravenously injected into the mice and imaged by positron emission tomography/computed tomography (PET/CT). The centers of the stable cavitation dose (SCD) maps obtained by PCI and the corresponding centers of the 64Cu-AuNCs concentration maps obtained by PET coincided within 0.3 ± 0.4 mm and 1.6 ± 1.1 mm in the transverse and axial directions of the FUS beam, respectively. The SCD maps were found to be linearly correlated with the 64Cu-AuNCs concentration maps on a pixel-by-pixel level. These findings suggest that SCD maps can spatially "paint" the delivered nanocluster concentration, a technique that we named as cavitation dose painting. This PCI-based cavitation dose painting technique in combination with FUS-BBBD opens new horizons in spatially targeted and modulated brain drug delivery.

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