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.

Grant Number: 1R21EB035375-01
NIH Institute/Center: NIH
Principal Investigator: Konstantinos-Costas Arvanitis