Journal
ULTRASOUND IN MEDICINE AND BIOLOGY
Volume 42, Issue 2, Pages 481-492Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ultrasmedbio.2015.10.009
Keywords
Focused ultrasound; Blood-brain barrier disruption; Multiple sessions; Safety study; Magnetic resonance guidance; Histologic evaluation
Funding
- NIH [P01 CA174645]
- ERC [PIOF-GA-2012-331813]
- Dutch Cancer Society [KWF 2013-5861]
- CIMIT
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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. (C) 2016 World Federation for Ultrasound in Medicine & Biology.
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