Characterizing Focused Ultrasound-Induced Changes using 2-Photon Microscopy and MRI in a Mouse Model of Alzheimer’s Disease.

Motivation: Focused ultrasound (FUS) with microbubbles is a promising technology for opening the blood-brain barrier (BBB) to deliver therapeutics to the brain. Answering fundamental questions about the process of BBB opening will aid in the translation of this method to the clinic. Goal(s): Use FUS, 2-photon microscopy, MRI and immunohistochemistry to investigate FUS-induced changes in wild type and 5X-FAD AD mice. Approach: A cross-sectional study involving MRI, 2PM, and IHC to examine BBB opening at multiple timepoints in a disease model. Results: Results suggest BBB opening occurs in capillaries and that the BBB opening is similar between WT and 5X-FAD mice. Impact: DCE imaging and sub-micron imaging of the microvasculature after BBB opening provide insight into which vessels are opened after FUS and improve pharmacokinetic understanding of the paravascular space in an Alzheimer's Disease model.