In this section
@article{Morse:2019:10.1148/radiol.2019181625,
author = {Morse, SV and Pouliopoulos, AN and Chan, TG and Copping, MJ and Lin, J and Long, NJ and Choi, JJ},
doi = {10.1148/radiol.2019181625},
journal = {Radiology},
pages = {459--466},
title = {Rapid short-pulse ultrasound delivers drugs uniformly across the murine blood-brain barrier with negligible disruption},
url = {http://dx.doi.org/10.1148/radiol.2019181625},
volume = {291},
year = {2019}
}
TY - JOUR
AB - Background Previous work has demonstrated that drugs can be delivered across the blood-brain barrier by exposing circulating microbubbles to a sequence of long ultrasound pulses. Although this sequence has successfully delivered drugs to the brain, concerns remain regarding potentially harmful effects from disrupting the brain vasculature. Purpose To determine whether a low-energy, rapid, short-pulse ultrasound sequence can efficiently and safely deliver drugs to the murine brain. Materials and Methods Twenty-eight female wild-type mice underwent focused ultrasound treatment after injections of microbubbles and a labeled model drug, while three control mice were not treated (May-November 2017). The left hippocampus of 14 mice was exposed to low-energy short pulses (1 MHz; five cycles; peak negative pressure, 0.35 MPa) of ultrasound emitted at a rapid rate (1.25 kHz) in bursts (0.5 Hz), and another 14 mice were exposed to standard long pulses (10 msec, 0.5 Hz) containing 150 times more acoustic energy. Mice were humanely killed at 0 (n = 5), 10 (n = 3), or 20 minutes (n = 3) after ultrasound treatment. Hematoxylin-eosin (H-E) staining was performed on three mice. The delivered drug dose and distribution were quantified with the normalized optical density and coefficient of variation. Safety was assessed by H-E staining, the amount of albumin released, and the duration of permeability change in the blood-brain barrier. Statistical analysis was performed by using the Student t test. Results The rapid short-pulse sequence delivered drugs uniformly throughout the parenchyma. The acoustic energy emitted from the microbubbles also predicted the delivered dose (r = 0.97). Disruption in the blood-brain barrier lasted less than 10 minutes and 3.4-fold less albumin was released into the brain than with long pulses. No vascular or tissue damage from rapid short-pulse exposure was observable using H-E staining. Conclusion The rapid short-pulse ultrasound sequence is a minimally
AU - Morse,SV
AU - Pouliopoulos,AN
AU - Chan,TG
AU - Copping,MJ
AU - Lin,J
AU - Long,NJ
AU - Choi,JJ
DO - 10.1148/radiol.2019181625
EP - 466
PY - 2019///
SN - 0033-8419
SP - 459
TI - Rapid short-pulse ultrasound delivers drugs uniformly across the murine blood-brain barrier with negligible disruption
T2 - Radiology
UR - http://dx.doi.org/10.1148/radiol.2019181625
UR - https://www.ncbi.nlm.nih.gov/pubmed/30912718
UR - http://hdl.handle.net/10044/1/69485
VL - 291
ER -
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Kate Hobson
Email: k.hobson@imperial.ac.uk
