First-in-Human Study of Acoustic Angiography in the Breast and Peripheral Vasculature

Abstract

Screening with mammography has been demonstrated to increase breast cancer survival rates by about 20%. However, the current system in which mammography is used to direct patients toward biopsy or surgical excision also results in relatively high rates of unnecessary biopsy, as 66.8% of biopsies are benign. A non-ionizing radiation imaging approach with increased specificity might reduce the rate of unnecessary biopsies. Quantifying the vascular characteristics within and surrounding lesions represents one potential target for assessing likelihood of malignancy via imaging. In this clinical report, we describe the translation of a contrast-enhanced ultrasound technique, acoustic angiography, to human imaging. We demonstrate the feasibility of this technique with initial studies in imaging the hand, wrist, and breast using Definity® microbubble contrast agent and a mechanically-steered prototype dual-frequency transducer in healthy volunteers. Finally, this approach was used to image pre-biopsy BI-RADS 4–5 lesions <2 cm in depth in 11 patients. Results indicate that sensitivity and spatial resolution are sufficient to image vessels as small as 0.2 mm in diameter at depths of ~15 mm in the human breast. Challenges observed include motion artifacts, as well as limited depth of field and sensitivity, which could be improved by correction algorithms and improved transducer technologies.

Advances in translational imaging of the microcirculation

“…As ultrasound technologies continue to improve, these methods will become more widespread and accessible. For example, acoustic angiography that uses dual‐frequency ultrasound transducer technology to enhance spatial resolution and contrast‐to‐tissue ratio was recently used to visualize the microcirculation in the human breast 181 …”

Microvascular Ultrasonic Imaging of Angiogenesis Identifies Tumors in a Murine Spontaneous Breast Cancer Model

“…Using this technique, researchers have observed microvascular patterns which exhibit significant differences in both morphology and density of microvasculature, in both rat and mouse tumor models [14][15][16][17][18][19][20][21]. It was also recently demonstrated to be feasible for imaging microvasculature in humans, depicting breast vasculature as small as 200 μm to a depth of approximately 15 mm [22].…”

Use of 3-D Contrast-Enhanced Ultrasound to Evaluate Tumor Microvasculature After Nanoparticle-Mediated Modulation

“…Instead of receiving at several times the transmit frequency (as in the case of AA), subharmonic imaging receives at 1/2 the transmit frequency, and since microbubbles are most responsive near their resonance, around 1-6 MHz depending on the size and shell composition, sub-harmonic imaging suffers from very poor spatial resolution limiting its utility in preclinical applications. Due to the reliance of AA receiving high frequencies, good spatial resolution is achieved at the expense of poor depth of penetration into tissue, and thus the AA technique is likely limited to imaging preclinical animal models, or superficial clinical targets of a few cm (Shelton et al 2017). This is not the first study to implement AA to evaluate tumor response to therapy, as previous studies have shown both mouse and rat models responding to anti-angiogenic therapy (Rojas et al 2018), and broad beam radiation (Kasoji et al 2018).…”