Objective-The purpose of this study was to develop a method for assessing tumor vascularity in a preclinical model of breast cancer using contrast-enhanced ultrasonography.Methods-Eight mice were injected with 67NR breast cancer cells on their hind limbs and imaged with ultrasonography 8 days later. Mice were injected with an ultrasound contrast agent (UCA), and a sequence of images of the resultant backscattered echoes was recorded before and after high-power "destruction" pulses for each of multiple parallel planes. From these, data maps of the maximum contrast enhancement (within each time course) were constructed for each pixel, which enabled reconstruction of high-resolution coregistered sections into a 3-dimensional (3D) volume reflecting tumor vascularity. Additional studies were performed to determine the duration and repeatability of image enhancement, and images were correlated with conventional 3D power Doppler measurements.Results-The lifetime of the UCA in vivo was found to be 4.3 ± 1.09 minutes (mean ± SD). The 3D contrast-enhanced ultrasonographic technique produced images that correlated well with power Doppler images in specific regions but also depicted additional regions of flow surrounding the power Doppler signal. The mean correlation coefficient between voxel measurements of the central slice for each animal was 0.64 ± 0.07 (P < .01). In addition, sequential studies in each animal were reproducible.Conclusions-A method producing high-resolution volumetric assessments of tumor vascularity in a preclinical model of breast cancer is shown that correlates with other ultrasonographic measures of blood flow, which may provide greater sensitivity to the microvasculature.
Keywordscontrast-enhanced ultrasonography; tumor; vascularity For a tumor to grow beyond approximately 1 to 2 mm 3 , it cannot rely on the diffusion of metabolites and therefore must recruit and develop new vessels through the well-known process of angiogenesis. 1 Secretion of multiple growth factors from the tumor causes a chemotactic response from endothelial cells, which then migrate to the site to form vessels. Typically, the neovasculature arising from this process exhibits different characteristics from Ultrasound contrast agents (UCAs) are composed of small volumes of air or gas surrounded by a stabilizing shell that remain completely intravascular, making them ideal agents for vessel imaging. 6-10 Ultrasound contrast agents reflect sound strongly because they have a very different acoustic impedance from that of blood. In the presence of a sound field, the UCA begins to expand and contract. At a low input wave pressure (<50 kPa), the microbubbles behave as simple monopole oscillators, but at a higher input pressure (50-100 kPa), they may have nonlinear behavior, producing harmonics of the incident sound. At an even higher pressure (500 kPa-1MPa), the bubbles can be destroyed by extreme expansion and contraction, which can be advantageous in some applications. 11The aim of this study was to create high-resolution 3-...