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Focused ultrasound-mediated noninvasive blood-brain barrier modulation: preclinical examination of efficacy and safety in various sonication parameters

 Jaewoo Shin  ;  Chanho Kong  ;  Jae Sung Cho  ;  Jihyeon Lee  ;  Chin Su Koh  ;  Min-Sik Yoon  ;  Young Cheol Na  ;  Won Seok Chang  ;  Jin Woo Chang 
 NEUROSURGICAL FOCUS, Vol.44(2) : E15, 2018 
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BBB = blood-brain barrier ; BBB opening ; EB = Evans blue ; FUS = focused ultrasound ; MB = microbubble ; PRF = pulse repetition frequency ; UCA = ultrasound contrast agent ; blood-brain barrier ; drug delivery ; focused ultrasound ; noninvasive ; sonication factor
OBJECTIVE The application of pharmacological therapeutics in neurological disorders is limited by the ability of these agents to penetrate the blood-brain barrier (BBB). Focused ultrasound (FUS) has recently gained attention for its potential application as a method for locally opening the BBB and thereby facilitating drug delivery into the brain parenchyma. However, this method still requires optimization to maximize its safety and efficacy for clinical use. In the present study, the authors examined several sonication parameters of FUS influencing BBB opening in small animals. METHODS Changes in BBB permeability were observed during transcranial sonication using low-intensity FUS in 20 adult male Sprague-Dawley rats. The authors examined the effects of FUS sonication with different sonication parameters, varying acoustic pressure, center frequency, burst duration, microbubble (MB) type, MB dose, pulse repetition frequency (PRF), and total exposure time. The focal region of BBB opening was identified by Evans blue dye. Additionally, H & E staining was used to identify blood vessel damage. RESULTS Acoustic pressure amplitude and burst duration were closely associated with enhancement of BBB opening efficiency, but these parameters were also highly correlated with tissue damage in the sonicated region. In contrast, MB types, MB dose, total exposure time, and PRF had an influence on BBB opening without conspicuous tissue damage after FUS sonication. CONCLUSIONS The study aimed to identify these influential conditions and provide safety and efficacy values for further studies. Future work based on the current results is anticipated to facilitate the implementation of FUS sonication for drug delivery in various CNS disease states in the near future.
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1. College of Medicine (의과대학) > Dept. of Neurosurgery (신경외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Shin, Jaewoo(신재우) ORCID logo https://orcid.org/0000-0002-6335-1292
Chang, Won Seok(장원석) ORCID logo https://orcid.org/0000-0003-3145-4016
Chang, Jin Woo(장진우) ORCID logo https://orcid.org/0000-0002-2717-0101
Cho, Jae Sung(조재성)
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