In vivo assessment of macrophage CNS infiltration during disruption of the blood-brain barrier with focused ultrasound: a magnetic resonance imaging study.
Authors: Liu HL, Wai YY, Hsu PH, Lyu LA, Wu JS, Shen CR, Chen JC, Yen TC, Wang JJ
Focused ultrasound has been discovered to locally and reversibly increase permeability of the blood-brain barrier (BBB). However, inappropriate sonication of the BBB may cause complications, such as hemorrhage and brain tissue damage. Tissue damage may be controlled by selecting optimal sonication parameters. In this study, we sought to investigate the feasibility of labeling cells with superparamagnetic iron oxide particles to assess the inflammatory response during focused-ultrasound-induced BBB opening. We show that infiltration of phagocytes does not occur using optimal parameters of sonication. Taken together, the results of our study support the usefulness and safety of focused-ultrasound-induced BBB opening for enhancing drug delivery to the brain. These findings may have implications for the optimization of sonication parameters.
Introduction
Purpose
Drug delivery with BBB opening
Study Objective
To investigate the feasibility of labeling cells with superparamagnetic iron oxide particles to assess the inflammatory response during focused-ultrasound-induced blood–brain barrier opening.
Animal model / Human subject
Sprague–Dawley rats (sex: male, age: adult)
MRI or image guidance method
3-T scanner (Trio with Tim, Magnetom, Siemens, Erlangen, Germany)
Cargo name and characteristics
Superparamagnetic iron oxide particles (nanoparticles) used to label cells to assess inflammatory response
Outcomes and Safety
Summary of Outcomes
Focused ultrasound, when applied with optimal sonication parameters, reversibly increased BBB permeability to enhance brain drug delivery without causing phagocyte infiltration or tissue damage; the successful settings were described only as 'optimal sonication parameters' (no specific parameter values provided).
Safety-related matter
The paper notes that inappropriate sonication of the BBB can cause complications such as hemorrhage and brain tissue damage, but that tissue damage may be controlled by selecting optimal sonication parameters. The study found no phagocyte infiltration using optimal parameters and concludes that focused-ultrasound-induced BBB opening is useful and safe for enhancing drug delivery to the brain.
Brain Region
Ultrasound Parameters
Ultrasound instrument
focused ultrasound transducer (Imasonics, Besancon, France)
FUS Frequency
1.5 MHz
FUS Pressure
2.45, 1.1
FUS Mode
pulsed
Pulse duration
10 ms
Duration of a single FUS session
30 s
Focal Characteristics
diameter: 60 mm, radius of curvature: 80 mm
Treatment frequency
multiuple
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