Evaluation of laser speckle contrast imaging as an intrinsic method to monitor blood brain barrier integrity

Suzie Dufour,Ofer Levi,Dene Ringuette,Yaaseen Atchia,Raanan Gad,Iliya Sigal

doi:10.1364/boe.4.001856

Abstract

The integrity of the blood brain barrier (BBB) can contribute to the development of many brain disorders. We evaluate laser speckle contrast imaging (LSCI) as an intrinsic modality for monitoring BBB disruptions through simultaneous fluorescence and LSCI with vertical cavity surface emitting lasers (VCSELs). We demonstrated that drug-induced BBB opening was associated with a relative change of the arterial and venous blood velocities. Cross-sectional flow velocity ratio (veins/arteries) decreased significantly in rats treated with BBB-opening drugs, ≤0.81 of initial values.

Highlights

Exchanges between the blood and the central nervous system (CNS) are highly controlled by the blood brain barrier (BBB), essentially composed of endothelial tight junctions and astrocytic glial cell endfeet wrapped around small brain vessels [1]
As BBB opening is known to have an effect on cerebral blood flow [18], we studied the effect of BBB opening on blood flow velocity maps acquired with Laser Speckle Contrast Imaging (LSCI)
We expected to observe a decrease in venous velocity following BBB disruption due to capillary leakage, but this predicted reduction of the venous flow was observed in only 45% of the veins in the Region of Interest (ROI) and, interestingly, an increase in arterial flow velocities was observed in 64% of the arteries in the ROI, across all animals in our study

Summary

Introduction

Exchanges between the blood and the central nervous system (CNS) are highly controlled by the blood brain barrier (BBB), essentially composed of endothelial tight junctions and astrocytic glial cell endfeet wrapped around small brain vessels [1]. Lack of BBB permeability represents a challenge for drug delivery into the CNS [6, 7]. Many techniques are being developed to locally alter the barrier integrity and allow optimized local drug release into brain tissue [8,9,10]. MRI or CT scanners are used to monitor BBB integrity [11,12,13,14], as various MRI and CT parameters were proven to vary with BBB opening [11]. MRI and CT scanners are expensive to operate, are not optimized for prolonged measurement periods, and limit access to the subject during the recording period

Methods

Results

Discussion

Conclusion