Hassaan Ahmed BSc, Presenter: Nothing to Disclose

Ting-Yim Lee MSc, PhD, Abstract Co-Author: Grant, General Electric Company Royalties, 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

To quantitatively evaluate acute tumor response following focused ultrasound (FUS) and microbubble (MB) treatment using dynamic contrast-enhanced computed tomography (DCE-CT) in a rat glioma model.

A stereotactic frame was used to surgically implant 1 x 106 C6 glioma cells in the right cerebral hemisphere of three rats. When the tumor occupied about 50% of the implanted hemisphere, it was trans-cranially sonicated with a 10ms burst length and a 1 Hz repetition frequencyfor 120s, at an acoustic power of 0.5W using a 0.563-MHz FUS system (FUS Instruments Inc., Canada). The sonications were guided by baseline axial CT images and the corresponding blood-brain-barrier (BBB) permeability surface area product (PS) and cerebral blood flow (CBF) maps calculated by CT Perfusion (GE Healthcare). A region in the contralateral hemisphere was also sonicated 5 minutes following the tumor sonication to confirm the targeted axial slice. Definity (Lantheus Medical Imaging, USA) microbubbles at a dose of 20 µl/kg were administered simultaneously with both sonications. Serial DCE-CT scans were performed out to 4 hours post sonication to monitor the acute response in BBB PS and CBF. 

The tumor BBB PS at 150 minutes post sonication (2.7 +/- 1.3 ml/min/100g) was significantly lower (p < 0.05) than at baseline (5.7 +/- 1.7 ml/min/100g), but that at 15 minute post (6.0 +/- 1.8 ml/min/100g) was similar to baseline. The tumor CBF indicated a decreasing trend immediately following sonication, and returned to baseline levels at around 150 minutes post sonication. 

A decreasing BBB PS following FUS and MB treatment over the tumor region, as opposed to the transient 3-4 times increase that is observed over healthy tissue, was a surprising result. The trend of an acute drop in CBF following sonication suggests that the tumor may undergo vasoconstriction following treatment. Although FUS and MB treatment in a tumor may not be beneficial for increased drug delivery, our preliminary results suggest that perhaps it could be used to disrupt or destroy tumor vasculature as a form of treatment. 

FUS and MB treatment have been shown to increase drug delivery over healthy and brain tumor regions, but our results suggest it may also be used to disrupt or potentially destroy tumor vasculature. 

Ahmed, H, Lee, T, Hynynen, K, Chopra, R, Quantitative Evaluation of Acute Tumor Response Following Focused Ultrasound and Microbubble Treatment Using Dynamic Contrast Enhanced-computed Tomography.  Radiological Society of North America 2013 Scientific Assembly and Annual Meeting, December 1 - December 6, 2013 ,Chicago IL. http://archive.rsna.org/2013/13019253.html