Hassaan Ahmed BSc, Presenter: Nothing to Disclose

Ting-Yim Lee MSc, PhD, Abstract Co-Author: Research Grant, General Electric Company Consultant, General Electric Company License agreement, General Electric Company

Kullervo H. Hynynen PhD, Abstract Co-Author: Nothing to Disclose

Rajiv Chopra PhD, Abstract Co-Author: Shareholder, Profound Medical Inc Shareholder, FUS Instruments Inc Shareholder, Harmonic Medical Inc Consultant, Thornhill Research Inc

Adam Waspe, Abstract Co-Author: Nothing to Disclose

To evaluate focused ultrasound (FUS) induced blood-brain-barrier (BBB) disruption using Dynamic Contrast-Enhanced Computed Tomography (DCE-CT) in a rabbit model. 

Three rabbits were trans-cranially sonicated for 180s at an acoustic power of 0.5-0.6 W using a 0.563-MHz FUS system (FUS Instruments Inc., Canada). The sonications were guided by axial CT images to the right striatum, and were delivered as pulses with a 10ms burst length and a 1 Hz repetition frequency. Definity (Lantheus Medical Imaging, USA) microbubbles at a dose of 20 µl/kg were administered simultaneously with the sonication. For each rabbit, DCE-CT scans were performed to measure the BBB permeability surface area product (PS). For the quantitative analysis of BBB PS maps calculated by CT Perfusion (GE Healthcare), circular regions of interest were drawn on the sonicated and contralateral regions. Evans Blue dye (7-10 ml) was also injected immediately after sonication. The animals were sacrificed at 3-5 hours post sonication, and the brain excised, sectioned and examined for damage and extravasation of Evans Blue dye.  

The BBB PS at 15 minute post sonication was significantly greater (p < 0.05) in the sonicated hemisphere (1.5 +/- 0.8 ml/min/100g) than in the contralateral hemisphere (0.17 +/- 0.06 ml/min/100g). The average BBB PS for the three rabbits plotted over time and the BBB PS maps for a representative rabbit sonicated at 0.6 W are provided in the figure. There were no signs of macroscopic tissue damage including hemorrhage from the gross histology findings.  

This study demonstrates that it is possible to reversibly induce BBB disruption without causing any visible damage to the tissue, and that DCE-CT derived BBB PS measurements can be used to evaluate the disruption. BBB PS peaked at 5 - 15 minute post sonication and thereafter began to decrease – suggesting a distinct window for increased drug delivery.  

FUS-induced BBB disruption provides a promising method of selectively increasing drug delivery to the brain and DCE-CT is a quantitative method for evaluating the disruption. 

Ahmed, H, Lee, T, Hynynen, K, Chopra, R, Waspe, A, Focused Ultrasound Induced Blood-Brain-Barrier Disruption: Quantitative Evaluation Using Dynamic Contrast Enhanced-Computed Tomography.  Radiological Society of North America 2012 Scientific Assembly and Annual Meeting, November 25 - November 30, 2012 ,Chicago IL. http://archive.rsna.org/2012/12026468.html