Imaging of macrophage accumulation in solid tumors with ultrasound

Ashley Alva, Chulyong Kim, Pranav Premdas, Yann Ferry, Hohyun Lee, Nidhi Lal, Bowen Jing, Edward Botchwey, Brooks D. Lindsey and Costas Arvanitis ()
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Ashley Alva: Georgia Institute of Technology
Chulyong Kim: Georgia Institute of Technology
Pranav Premdas: Georgia Institute of Technology
Yann Ferry: Georgia Institute of Technology and Emory University
Hohyun Lee: Georgia Institute of Technology
Nidhi Lal: Georgia Institute of Technology and Emory University
Bowen Jing: Georgia Institute of Technology and Emory University
Edward Botchwey: Georgia Institute of Technology and Emory University
Brooks D. Lindsey: Georgia Institute of Technology and Emory University
Costas Arvanitis: Georgia Institute of Technology

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: Abstract Imaging macrophage trafficking in solid tumors has major implications for cancer diagnosis, prognosis, and therapy. Here, we show that macrophage labeling with lipid-shelled microbubbles enables ultrasound imaging at single-cell level. Crucially, microbubble labeling and sonication at low mechanical indexes do not affect macrophage viability, migration, phenotype, and cytokine secretion profile, supporting the notion that ultrasound imaging can be used for nondestructive macrophage imaging. Despite the damping exerted on the microbubble oscillations by the cellular compartments, the microbubbles exhibit highly nonlinear behavior upon sonication, allowing for high specificity nonlinear US imaging under in vitro and in vivo conditions. Subsequently, we demonstrate that nonlinear ultrasound imaging can selectively monitor macrophage accumulation and extravasation in solid tumors in rodents for at least 8 h after intravenous administration. These findings establish ultrasound as a noninvasive platform for immune cell trafficking in solid tumors and highlight its potential to advance cancer diagnosis, monitoring, and therapy.

Date: 2025
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DOI: 10.1038/s41467-025-61624-1

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