TY - JOUR
T1 - Cavitation dose painting for focused ultrasound-induced blood-brain barrier disruption
AU - Yang, Yaoheng
AU - Zhang, Xiaohui
AU - Ye, Dezhuang
AU - Laforest, Richard
AU - Williamson, Jeffrey
AU - Liu, Yongjian
AU - Chen, Hong
N1 - Funding Information:
This work was in part supported by the Children’s Discovery Institute of Washington University and St. Louis Children’s Hospital (grant number MC-II-2017-661), American Cancer Society (grant number IRG-15-170-58), and the National Institutes of Health (NIH) grant R01MH116981 and R01EB027223. The authors wish to thank Dr. Kevin Haworth (PhD, University of Cincinnati) for insightful discussions of passive cavitation imaging.
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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, 64 Cu-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 64 Cu-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 64 Cu-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.
AB - 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, 64 Cu-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 64 Cu-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 64 Cu-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.
UR - http://www.scopus.com/inward/record.url?scp=85062144703&partnerID=8YFLogxK
U2 - 10.1038/s41598-019-39090-9
DO - 10.1038/s41598-019-39090-9
M3 - Article
C2 - 30808897
AN - SCOPUS:85062144703
SN - 2045-2322
VL - 9
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 2840
ER -