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High and low frequency subharmonic imaging of angiogenesis in a murine breast cancer model
Journal article   Open access   Peer reviewed

High and low frequency subharmonic imaging of angiogenesis in a murine breast cancer model

Manasi Dahibawkar, Mark A Forsberg, Aditi Gupta, Samantha Jaffe, Kelly Dulin, John R Eisenbrey, Valgerdur G Halldorsdottir, Anya I Forsberg, Jaydev K Dave, Andrew Marshall, …
Ultrasonics, v 62
Sep 2015
DOI: https://doi.org/10.1016/j.ultras.2015.04.012
PMID: 25979676
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://europepmc.org/articles/pmc4504767View
Accepted (AM)Open Access (License Unspecified),  Open

Abstract

Animals Biomarkers, Tumor - analysis Contrast Media Cyclooxygenase 2 - metabolism Disease Models, Animal Female Fluorocarbons Image Processing, Computer-Assisted Immunohistochemistry Mammary Neoplasms, Experimental - diagnostic imaging Mice Mice, Nude Neovascularization, Pathologic - diagnostic imaging Platelet Endothelial Cell Adhesion Molecule-1 - metabolism Reproducibility of Results Signal Processing, Computer-Assisted Ultrasonography Vascular Endothelial Growth Factor A - metabolism
This project compared quantifiable measures of tumor vascularity obtained from contrast-enhanced high frequency (HF) and low frequency (LF) subharmonic ultrasound imaging (SHI) to 3 immunohistochemical markers of angiogenesis in a murine breast cancer model (since angiogenesis is an important marker of malignancy and the target of many novel cancer treatments). Nineteen athymic, nude, female rats were implanted with 5×10(6) 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: 180μl/kg) and LF pulse-inversion SHI was performed with a modified Sonix RP scanner (Analogic Ultrasound, Richmond, BC, Canada) using a L9-4 linear array (transmitting/receiving at 8/4MHz in SHI mode) followed by HF imaging with a Vevo 2100 scanner (Visualsonics, Toronto, ON, Canada) using a MS250 linear array transmitting and receiving at 24MHz. The radiofrequency data was filtered using a 4th order IIR Butterworth bandpass filter (11-13MHz) to isolate the subharmonic signal. After the experiments, specimens were stained for endothelial cells (CD31), vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2). Fractional tumor vascularity was calculated as contrast-enhanced pixels over all tumor pixels for SHI, while the relative area stained over total tumor area was calculated from specimens. Results were compared using linear regression analysis. Out of 19 rats, 16 showed tumor growth (84%) and 11 of them were successfully imaged. HF SHI demonstrated better resolution, but weaker signals than LF SHI (0.06±0.017 vs. 0.39±0.059; p<0.001). The strongest overall correlation in this breast cancer model was between HF SHI and VEGF (r=-0.38; p=0.03). In conclusion, quantifiable measures of tumor neovascularity derived from contrast-enhanced HF SHI appear to be a better method than LF SHI for monitoring angiogenesis in a murine xenograft model of breast cancer (corresponding in particular to the expression of VEGF); albeit based on a limited sample size.

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Collaboration types
Domestic collaboration
Web of Science research areas
Acoustics
Radiology, Nuclear Medicine & Medical Imaging
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