Localized Blood–Brain Barrier Opening in Ovine Model Using Image-Guided Transcranial Focused Ultrasound

Kyungho Yoon; Wonhye Lee; E. Chen; Ji Eun Lee; Phillip Croce; Amanda Cammalleri; Lori Foley; Allison L. Tsao; Seung Schik Yoo

doi:10.1016/j.ultrasmedbio.2019.05.023

Localized Blood–Brain Barrier Opening in Ovine Model Using Image-Guided Transcranial Focused Ultrasound

Kyungho Yoon, Wonhye Lee, E. Chen, Ji Eun Lee, Phillip Croce, Amanda Cammalleri, Lori Foley, Allison L. Tsao, Seung Schik Yoo

School of Mathematics and Computing

Research output: Contribution to journal › Article › peer-review

15 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	2391-2404
Number of pages	14
Journal	Ultrasound in Medicine and Biology
Volume	45
Issue number	9
DOIs	https://doi.org/10.1016/j.ultrasmedbio.2019.05.023
Publication status	Published - 2019 Sept

Bibliographical note

Funding Information:
This study was supported by the National Institutes of Health ( R01 MH111763 to S.S.Y.). We acknowledge Dr. Yongzhi Zhang for supporting tissue extraction, Ms. Linda B. Xu for editorial support and Dr. Christine G. Lian for her contribution to histologic analysis. We thank the Dana–Farber/Harvard Cancer Center in Boston, Massachusetts, for use of the Specialized Histopathology Core, which provided histology and immunohistochemistry service. The Dana–Farber/Harvard Cancer Center is supported in part by National Cancer Institute Cancer Center Support Grant P30 CA06516 .

Publisher Copyright:
© 2019 World Federation for Ultrasound in Medicine & Biology

All Science Journal Classification (ASJC) codes

Radiological and Ultrasound Technology
Biophysics
Acoustics and Ultrasonics

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10.1016/j.ultrasmedbio.2019.05.023

Cite this

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title = "Localized Blood–Brain Barrier Opening in Ovine Model Using Image-Guided Transcranial Focused Ultrasound",

abstract = "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.",

author = "Kyungho Yoon and Wonhye Lee and E. Chen and Lee, {Ji Eun} and Phillip Croce and Amanda Cammalleri and Lori Foley and Tsao, {Allison L.} and Yoo, {Seung Schik}",

note = "Funding Information: This study was supported by the National Institutes of Health ( R01 MH111763 to S.S.Y.). We acknowledge Dr. Yongzhi Zhang for supporting tissue extraction, Ms. Linda B. Xu for editorial support and Dr. Christine G. Lian for her contribution to histologic analysis. We thank the Dana–Farber/Harvard Cancer Center in Boston, Massachusetts, for use of the Specialized Histopathology Core, which provided histology and immunohistochemistry service. The Dana–Farber/Harvard Cancer Center is supported in part by National Cancer Institute Cancer Center Support Grant P30 CA06516 . Publisher Copyright: {\textcopyright} 2019 World Federation for Ultrasound in Medicine & Biology",

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AU - Croce, Phillip

AU - Cammalleri, Amanda

AU - Foley, Lori

AU - Tsao, Allison L.

AU - Yoo, Seung Schik

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N2 - 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.

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Localized Blood–Brain Barrier Opening in Ovine Model Using Image-Guided Transcranial Focused Ultrasound

Abstract

Bibliographical note

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