Andrew Marshall, Abstract Co-Author: Nothing to Disclose

Jaydev Kardam Dave PhD, MS, Abstract Co-Author: Nothing to Disclose

Flemming Forsberg PhD, Presenter: Equipment support, Toshiba Corporation Equipment support, Siemens AG Research collaboration, General Electric Company Research collaboration, Ultrasonix Medical Corporation Research collaboration, Toshiba Corporation Advisory Board, Siemens AG Advisory Board, Toshiba Corporation

Valgerdur Halldorsdottir MSc, Abstract Co-Author: Nothing to Disclose

Anya Isabelle Forsberg, Abstract Co-Author: Nothing to Disclose

Manasi Dahibawkar BSc, Abstract Co-Author: Nothing to Disclose

Traci B. Fox MS, RT, Abstract Co-Author: Nothing to Disclose

Ji-Bin Liu MD, Abstract Co-Author: Research Grant, GluMetrics, Inc

To compare contrast-enhanced subharmonic ultrasound imaging (SHI) of breast tumor neovascularity to three immunohistochemical markers of angiogenesis in nude rats.

Seventy athymic, nude, female rats were implanted with 5 x 106 breast cancer cells (MDA-MB-231) in the mammary fat pad. The contrast agent Definity (Lantheus Medical Imaging, N Billerica, MA) was injected in a tail vein (dose: 36 μl) and fundamental ultrasound imaging as well as pulse-inversion SHI was performed in triplicate with a modified Sonix RP scanner (Ultrasonix Imaging, Richmond, BC, Canada) using a L9-4 linear array (transmitting at 8 MHz and receiving at 4 MHz in SHI mode). Studies were performed 21, 24 and 28 days post implantation (based on our prior experience). After the experiments, specimens were stained for endothelial cells (CD31), vascular endothelial growth factor (VEGF), and cyclooxygenase-2 (COX-2). Fractional tumor vascularity (FV) was calculated from digital images as contrast enhanced pixels over tumor area (for SHI; averaged over the 3 injections) and staining over tumor area (for specimens). Results were compared using a linear regression analysis.

Of the 70 rats implanted 45 (64 %) exhibited tumor growth and 32 were successfully imaged. SHI depicted the tortuous morphology of tumor neovessels and delineated areas of necrosis better than fundamental ultrasound imaging, due to the marked suppression of tissue signals. VEGF varied significantly over time (p<0.031), while the strongest correlation determined by linear regression in this breast cancer model was between SHI and percent area stained with VEGF (r = 0.53).

Quantitative contrast-enhanced SHI measures of tumor neovascularity in a breast cancer xenograft models appear to provide a noninvasive marker for angiogenesis corresponding to the expression of VEGF; albeit based on a limited sample size.

In the future SHI may be used to monitor response for patients treated with anti-VEGF drug therapies.

Marshall, A, Dave, J, Forsberg, F, Halldorsdottir, V, Forsberg, A, Dahibawkar, M, Fox, T, Liu, J, Comparing Immunohistochemical Markers of Angiogenesis to Subharmonic Imaging of Vascularity in a Murine Breast Cancer Model.  Radiological Society of North America 2013 Scientific Assembly and Annual Meeting, December 1 - December 6, 2013 ,Chicago IL. http://archive.rsna.org/2013/13026100.html