Date of Award
Master of Science (MS)
Most common diagnosis and therapeutic methods have low effectiveness when used on brain diseases. The key obstacle is that the blood-brain barrier (BBB) prevents most drugs from entering the brain. Some strategies have been developed to improve the efficiency of drug delivery crossing BBB. Among all these strategies, focused ultrasound-mediated BBB opening (FUS-BBB Opening) stands out since it is noninvasive and can be located to the target area. Detailed studies are required on the distribution of drugs delivered by FUS-BBB opening and the effects of FUS parameters on the distribution. This thesis proposes a pipeline involving tissue clearing and lightsheet microscopy to study the distribution of BSA relative to vessels in mouse brains treated with FUS and the effect of ultrasound pressure on the delivery pattern.
As mentioned before, slices (1 mm thick) from mouse brains treated with FUS were cleared until their transparency meets the requirement of large-volume three-dimensional (3D) imaging. Blood vessels and BSA clusters inthe 3D images obtained from lightsheet microscopy were segmented and the distance of every cluster from the nearest vessel was collected in the distance map.
Comparing the distance maps of different pressures, it is indicated that FUS with the pressure of 0.4 MPa significantly increases the amount of BSAclusters in brains, especially those distributed closer to the outer surface of vessels. BSA delivered by 0.2 MPa FUS and 0.4 MPa FUS has different distribution patterns relative to vessels. At the same time, this thesis discussed the feasibility of this pipeline to study FUS-BBB opening-induced drug delivery.
Song Hu, Chao Zhou, Hong Chen