Imaging of macrophage trafficking with ultrasound

Project Summary Imaging of macrophage trafficking can reveal important molecular, cellular, and functional characteristics of the host tissue and support the discovery of new biomarkers for improved diagnosis, prognosis, and treatment monitoring. Over the past years, macrophage imaging using different modalities has undergone significant

development, however existing modalities offer suboptimal tradeoffs between depth of penetration, specificity, sensitivity, and resolution. Although ultrasound (US) could potentially address this challenge, while also providing portable assessment (e.g., in an outpatient setting) at potentially lower costs, there is a paucity of investigations

using ultrasound for macrophage imaging. The central hypothesis of this proposal is that labelling macrophages with microbubble (MB) ultrasound contrast agents to augment their contrast can enable imaging of macrophage trafficking with high sensitivity deep into tissues without compromising resolution. To test the above hypothesis,

first the detection limit of MB-labeled macrophages under different US imaging pulse sequencies will be determined (in vitro). After identifying the minimum number of MB-labeled macrophages that can be detected in vitro, the sensitivity of imaging MB labeled macrophages with US in healthy mice (in vivo) will be assessed next.

Finally, as a proof of concept, the ability to monitor macrophage trafficking to diseased organ and to facilitate diagnosis will be assessed in the context of solid tumors (in tumors). If successful, the proposed research will provide a novel framework for macrophage imaging and tracking using ultrasound to support the discovery and

clinical translation of new US methods and technology for macrophage-based diagnostics and therapy monitoring.