title: Safety Validation of Repeated Blood-Brain Barrier Disruption Using Focused Ultrasound.
abstract: The purpose of this study was to investigate the effects on the brain of multiple sessions of blood-brain barrier (BBB) disruption using focused ultrasound (FUS) in combination with micro-bubbles over a range of acoustic exposure levels. Six weekly sessions of FUS, using acoustical pressures between 0.66 and 0.80 MPa, were performed under magnetic resonance guidance. The success and degree of BBB disruption was estimated by signal enhancement of post-contrast T1-weighted imaging of the treated area. Histopathological analysis was performed after the last treatment. The consequences of repeated BBB disruption varied from no indications of vascular damage to signs of micro-hemorrhages, macrophage infiltration, micro-scar formations and cystic cavities. The signal enhancement on the contrast-enhanced T1-weighted imaging had limited value for predicting small-vessel damage. T2-weighted imaging corresponded well with the effects on histopathology and could be used to study treatment effects over time. This study demonstrates that repeated BBB disruption by FUS can be performed with no or limited damage to the brain tissue.
authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: thiele.kobus@radboudumc.nl.
authors.forename: Thiele
authors.initials: T
authors.lastname: Kobus
authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Natalia
authors.initials: N
authors.lastname: Vykhodtseva
authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Magdalini
authors.initials: M
authors.lastname: Pilatou
authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Yongzhi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Nathan
authors.initials: N
authors.lastname: McDannold
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000473:pathology* / Q000502:physiology / Q000528:radiation effects*; D019220:High-Energy Shock Waves; D011829:Radiation Dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D013010:Sonication / Q000379:methods*
keywords: Blood–brain barrier disruption; Focused ultrasound; Histologic evaluation; Magnetic resonance guidance; Multiple sessions; Safety study