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Assessment of temporary cerebral effects induced by focused ultrasound with optical coherence tomography angiography.

Authors: Tsai MT, Zhang JW, Wei KC, Yeh CK, Liu HL

Focused ultrasound (FUS) in combination with microbubbles temporally and locally increases the permeability of the blood-brain barrier (BBB) for facilitating drug delivery. However, the temporary effects of FUS on the brain microstructure and microcirculation need to be addressed. We used label-free optical coherence tomography (OCT) and OCT angiography (OCTA) to investigate the morphological and microcirculation changes in mouse brains due to FUS exposure at different power levels. Additionally, the recovery progress of the induced effects was studied. The results show that FUS exposure causes cerebral vessel dilation and can be identified and quantitatively analyzed via OCT/OCTA. Micro-hemorrhages can be detected when an excessive FUS exposure power is applied, causing the degradation of OCTA signal owing to strong scattering by leaked red blood cells (RBCs) and weaker backscattered intensity from RBCs in vessels. The vessel dilation effect due to FUS exposure was found to abate in several hours. This study demonstrates that the FUS-induced cerebral transiently dilated effects can be <i>in-vivo</i> differentiated and monitored with OCTA, and shows the feasibility of using OCT/OCTA as a novel tool for long-time monitoring of cerebral vascular dynamics during FUS-BBB opening process.

Introduction

Purpose Drug delivery with BBB opening
Study Objective To evaluate and monitor, using label-free OCT/OCTA, the morphological and microcirculation changes and recovery in mouse brains after focused ultrasound-induced blood-brain barrier opening at varying power levels.
Animal model / Human subject Mouse (Mus musculus), strain not specified, age not specified, sex not specified

Outcomes and Safety

Summary of Outcomes Focused ultrasound with microbubbles caused transient cerebral vessel dilation (resolving in several hours) detectable by OCT/OCTA at moderate/low (non-excessive) power levels, while excessive/high FUS power produced micro-hemorrhages and OCTA signal degradation.
Duration of biological effect several hours
Safety-related matter FUS exposure caused transient cerebral vessel dilation that abated within several hours, and excessive FUS exposure power produced micro-hemorrhages (observed as OCTA signal degradation from leaked red blood cells), indicating potential adverse effects requiring monitoring.

Brain Region

Visualization unavailable

Ultrasound Parameters

Focal Characteristics Focal depth: None; Focal length: None; Aperture size: None
Treatment frequency single session

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