Functional NIRS study of blood brain barrier disruption when induced by focused ultrasound and intra-arterial mannitol infusion

Enhancing brain fluid movement across blood brain barrier (BBB) has been recognized as a potential treatment of neurodegenerative diseases. Moreover, BBB opening is of high interest also in brain drug delivery in the treatment of brain tumors/cancers. However, efficient therapies which are based on BBB opening are still limited because of insufficient understanding of mechanisms and safety issues. Currently, there are few promising methodologically diverse BBB opening approaches. In this paper, we use functional near-infrared spectroscopy (fNIRS) for the first time for monitoring cerebral hemoglobin and water concentration changes during BBB opening in mouse brain by using two different techniques: intra-arterial mannitol infusion (IAM) and focused ultrasound (FUS). Both of these BBB opening techniques are already in clinical use but their hemo- and hydrodynamic implications have not been investigated from comparative aspect. Two fibre detectors were attached on both sides of the mouse brain and the source fibre was attached on middle of forehead. Further, by using a combination of three wavelengths 690nm, 830nm and 980nm, that have sufficient light penetration in the mouse brain, we can show average dynamics of hemoglobin and water in the whole brain, synchronized with BBB opening. To validate the level of BBB opening we used Evans blue dye and show its accumulation in the brain parenchyma tissue with the corresponding fNIRS responses.