Quantitative Assessment of Tumor Enhancement by Ultrastable Lipid-Coated Microbubbles as a Sonographic Contrast Agent

Abstract

We have previously reported that ultrastable lipid-coated microbubbles make a suitable ultrasonic contrast agent in the brain, causing increased intensity of echoes that persists for many hours. We showed that intravenously administered lipid-coated microbubbles accumulate selectively in rat brain gliomas with echogenicity enhancement for up to 1 hour, allowing visualization of the growing lesions 40% (2 days) earlier than can be seen without contrast. This work is a detailed evaluation of the accumulation of the lipid-coated microbubbles in tumor and the effect of the bubbles on the echogenicity of insonified tumors. Using a lipid-specific stain, we measured and characterized the distribution of the bubbles in the brain and tumor. We showed that on the scan, the enhancement of the tumor is accompanied by a change in the signal-to-noise ratio of the echoes from the tumor. We identified characteristic textural changes associated with contrast-enhanced tumor using spectral analysis.