Thomas Yankeelov PhD, Presenter: Nothing to Disclose

Kenneth J. Niermann MD, Abstract Co-Author: Nothing to Disclose

Edwin F. Donnelly MD, Abstract Co-Author: Nothing to Disclose

Dennis Hallahan MD, Abstract Co-Author: Nothing to Disclose

Arthur Carroll Fleischer MD, Abstract Co-Author: Nothing to Disclose

To optimize the sonographic depiction of microvessel perfusion using microbubble contrast

Ten mice were subcutaneously implanted with Lewis lung carcinoma cells. Following 10 days of growth, tumors were scanned with microbubble contrast enhanced sonography (MCES) using harmonics and pulse inversion imaging techniques. Mice received intravascular injections of microbubble contrast (Definity® Bristol-Myers/Squibb, Inc. N. Bellerica, MA). Multiple, high mechanical index (MI) pulses were administered to locally destroy the microbubbles. Analyzing the rate of signal (S) enhancement due to microbubble replenishment via a two-parameter exponential recovery model [S=A(1-exp(-Bt), (1)] returns estimates of relative blood volume (rBV) and relative perfusion (rP).

The regional contrast enhancement curves revealed significantly different levels of perfusion and peak amplitude. Representative intratumoral regions pooled from four mice exhibited higher rP, 1.04±0.46 (mL/s), and higher rBV, 17.71±8.93, as compared to those in normal muscle tissue adjacent to the apparent tumor border, with values of rP 0.20±0.09 (mL/s) and rBV of 5.74±4.72. Notably, there was an appreciable paucity of contrast uptake in the most central regions of tumors.

Microbubble contrast, used in conjunction with the sonographic techniques of harmonics and pulse inversion, can effectively depict microvessel perfusion and discriminate between normal tissue and neovascularized tumor tissue. These data are consistent with the premise that active peripheral regions of tumors have a more extensively developed blood supply than normal tissue, while the necrotic intratumoral regions exhibit diminished blood flow. We are developing these techniques to assess tumor growth and treatment response in murine models of human cancer. With further development, MCES may be used to reliably ascertain varying degrees of neovascularization and, thus, be used clinically for early detection of ovarian malignancies and in other soft tissue tumors in the evaluation of response to antiangiogenic chemotherapy.Reference1. Wei K, et al. Circulation 1998;97:473-483.

Yankeelov, T, Niermann, K, Donnelly, E, Hallahan, D, Fleischer, A, Sonographic Depiction of Microvessel Perfusion in an in Vivo Animal Tumor Model.  Radiological Society of North America 2004 Scientific Assembly and Annual Meeting, November 28 - December 3, 2004 ,Chicago IL. http://archive.rsna.org/2004/4410052.html