Journal
ULTRASOUND IN MEDICINE AND BIOLOGY
Volume 45, Issue 9, Pages 2391-2404Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ultrasmedbio.2019.05.023
Keywords
Focused ultrasound; Blood-brain barrier; Drug delivery; Dynamic contrast-enhanced magnetic resonance imaging; Pharmacokinetics; Independent component analysis
Funding
- National Institutes of Health [R01 MH11176 3]
- National Cancer Institute Cancer Center Support Grant [P30 CA06516]
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Transcranial application of focused ultrasound (FUS) combined with vascular introduction of microbubble contrast agents (MBs) has emerged as a non-invasive technique that can temporarily create a localized opening in the blood-brain barrier (BBB). Under image-guidance, we administered FUS to sheep brain after intravenous injection of microbubbles. BBB opening was confirmed by performing dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to detect the extravasated gadolinium-based magnetic resonance contrast agents. Through pharmacokinetic analysis as well as independent component analysis of the DCE-MRI data, we observed localized enhancement in BBB permeability at the area that subjected to acoustic pressure of 0.48 MPa (mechanical index = 0.96). On the other hand, application of a higher pressure at 0.58 MPa resulted in localized, minor cerebral hemorrhage. No animals exhibited abnormal behavior during the post-FUS survival periods up to 2 mo. Our data suggest that monitoring for excessive BBB disruption is important for safe translation of the method to humans. (C) 2019 World Federation for Ultrasound in Medicine & Biology. All rights reserved.
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