Two-photon microscopy for real-time monitoring of focused ultrasound-mediated drug delivery to the brain in a mouse model of Alzheimer's disease

Alison Burgess; Naomi Eterman; Isabelle Aubert; Kullervo Hynynen

doi:10.1117/12.2002124

22 February 2013 Two-photon microscopy for real-time monitoring of focused ultrasound-mediated drug delivery to the brain in a mouse model of Alzheimer's disease

Alison Burgess, Naomi Eterman, Isabelle Aubert, Kullervo Hynynen

Author Affiliations +

Proceedings Volume 8588, Multiphoton Microscopy in the Biomedical Sciences XIII; 85882L (2013) https://doi.org/10.1117/12.2002124
Event: SPIE BiOS, 2013, San Francisco, California, United States

Abstract

There is substantial evidence that focused ultrasound (FUS) in combination with microbubble contrast agent can cause disruption of the blood-brain barrier (BBB) to aid in drug delivery to the brain. We have previously demonstrated that FUS efficiently delivers antibodies against amyloid-β peptides (Aβ) through the BBB, leading to a reduction in amyloid pathology at 4 days in a mouse model of Alzheimer’s disease. In the current study, we used two-photon microscopy to characterize the effect of FUS in real time on amyloid pathology in the mouse brain. Mice were anesthetized and a cranial window was made in the skull. A custom-built ultrasound transducer was fixed to a coverslip and attached to the skull, covering the cranial window. Methoxy-X04 [2-5mg/kg] delivered intravenously 1 hr prior to the experiment clearly labelled the Aβ surrounding the vessels and the amyloid plaques in the cortex. Dextran conjugated Texas Red (70kDa) administered intravenously, confirmed BBB disruption. BBB disruption occurred in transgenic and non-transgenic animals at similar ultrasound pressures tested. However, the time required for BBB closure following FUS was longer in the Tg mice. We have conjugated Aβ antibodies to the fluorescent molecule FITC for real time monitoring of the antibody distribution in the brain. Our current experiments are aimed at optimizing the parameters to achieve maximal fluorescent intensity of the BAM10 antibody at the plaque surface. Two-photon microscopy has proven to be a valuable tool for evaluating the efficacy of FUS mediated drug delivery, including antibodies, to the Alzheimer brain.

Citation Download Citation

Alison Burgess, Naomi Eterman, Isabelle Aubert, and Kullervo Hynynen "Two-photon microscopy for real-time monitoring of focused ultrasound-mediated drug delivery to the brain in a mouse model of Alzheimer's disease", Proc. SPIE 8588, Multiphoton Microscopy in the Biomedical Sciences XIII, 85882L (22 February 2013); https://doi.org/10.1117/12.2002124

ACCESS THE FULL ARTICLE

INSTITUTIONAL
Select your institution to access the SPIE Digital Library.

SELECT YOUR INSTITUTION

PERSONAL
Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.

PERSONAL SIGN IN

No SPIE Account? Create one

PURCHASE THIS CONTENT

SUBSCRIBE TO DIGITAL LIBRARY

50 downloads per 1-year subscription

Members: $195

Non-members: $335 ADD TO CART

25 downloads per 1 - year subscription

Members: $145

Non-members: $250 ADD TO CART

PURCHASE SINGLE ARTICLE

Includes PDF, HTML & Video, when available

Members: $17.00

Non-members: $21.00 ADD TO CART

PROCEEDINGS
7 PAGES

DOWNLOAD PAPER SAVE TO MY LIBRARY

GET CITATION

RIGHTS & PERMISSIONS

Get copyright permission Get copyright permission on Copyright Marketplace

KEYWORDS

Blood brain barrier

Brain

Two photon excitation microscopy

Alzheimer's disease

Ultrasonography

Pathology

Transducers

Show All Keywords

Keywords/Phrases

Search In:

Publication Years