Fluorescein sodium as a marker for focused ultrasound-induced blood-brain barrier disruption: a case report in a porcine model.
Authors: Xu Y, On TJ, Preul MC
Transcranial low-intensity focused ultrasound (FUS) enables noninvasive, targeted, and reversible blood-brain barrier (BBB) disruption, facilitating drug delivery and liquid biopsy of the brain. Using fluorescein sodium (FNa) with macroscopic widefield fluorescence and microscopic confocal laser endomicroscopy (CLE) imaging, we assessed BBB permeability after applying a frameless, electromagnetic-guided FUS system in a porcine model and confirmed with established MRI protocol and conventional histology. Both macroscopic and microscopic FNa fluorescence imaging findings correlated with contrast-enhanced MRI, providing direct evidence of BBB disruption. This approach demonstrates the utility of FNa for evaluating BBB permeability in preclinical studies.
Introduction
Purpose
Drug delivery with BBB opening
Study Objective
To evaluate whether fluorescein sodium widefield and confocal laser endomicroscopy imaging can detect and characterize focused ultrasound–induced blood–brain barrier disruption in a porcine model and correlate findings with contrast-enhanced MRI and histology.
Animal model / Human subject
swine, Yorkshire, not specified, not specified
Disease model
healthy
MRI or image guidance method
Frameless electromagnetic neuronavigation with permanent-magnet sensor tracking; CT and MRI datasets fused for 3D reconstruction and image-guided transducer positioning
Targeted brain region(s)
Cortex
Outcomes and Safety
Summary of Outcomes
Frameless, neuronavigation-guided FUS successfully opened the BBB in a porcine model, verified by real-time MRI and confocal laser endomicroscopy
Duration of biological effect
not reported
Safety-related matter
Histology showed localized microbleeding and red blood cell extravasation, but no significant vascular or cellular injury was observed acutely.
Brain Region
Ultrasound Parameters
Ultrasound instrument
Cordance Medical FUS system
FUS Frequency
250 kHz
FUS Intensity
not reported
FUS Pressure
0.3 MPa
FUS Mode
pulsed
Pulse duration
10 ms
Duration of a single FUS session
120 s
Treatment frequency
Single session
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