Quantification of Microvascular Tortuosity during Tumor Evolution Using Acoustic Angiography

Abstract

The recent design of ultra-broadband, multifrequency ultrasound transducers has enabled high-sensitivity, high-resolution contrast imaging, with very efficient suppression of tissue background using a technique called acoustic angiography. Here we perform the first application of acoustic angiography to evolving tumors in mice predisposed to develop mammary carcinoma, with the intent of visualizing and quantifying angiogenesis progression associated with tumor growth. Metrics compared include vascular density and two measures of vessel tortuosity quantified from segmentations of vessels traversing and surrounding 24 tumors and abdominal vessels from control mice. Quantitative morphologic analysis of tumor vessels revealed significantly increased vascular tortuosity abnormalities associated with tumor growth, with the distance metric elevated approximately 14% and the sum of angles metric increased 60% in tumor vessels versus controls. Future applications of this imaging approach may provide clinicians with a new tool in tumor detection, differentiation or evaluation, though with limited depth of penetration using the current configuration.

Keywords: Acoustic angiography; Angiogenesis; Contrast agent; Microbubble; Microvasculature; Superharmonic imaging; Tortuosity; Ultrasound.