Macrophage imaging in solid tumors using non-linear ultrasound

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Premdas, Pranav
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Abstract
In cancer research, visualizing and tracking macrophage trafficking in solid tumors has major implications for cancer diagnosis, prognosis, and therapy as well as advancing our understanding of immune‐cell biology. Despite advances in imaging technologies to monitor macrophages, the lack of real-time imaging methods with high sensitivity and resolution in deep tissue to characterize the motion dynamics and macrophage interaction with the TME in vivo remains a challenge. In this study we show that microbubble labelled macrophages along with non-linear imaging can overcome the traditional limitations of US imaging to track and study the behavioural and functional information of macrophages in solid tumors with excellent sensitivity (one macrophage) and resolution (~100µm). Crucially, microbubble labeling and sonication at mechanical indexes below 0.35 does not affect macrophage viability and migration capabilities supporting the notion that ultrasound imaging can be used for nondestructive longitudinal macrophage detection and tracking. Importantly, the labelled macrophages display highly nonlinear behavior upon sonication allowing to visualize them with high specificity using nonlinear US imaging. Consistent with these findings, we observed that nonlinear ultrasound imaging alongside robust motion correction and image registration techniques developed in this study can selectively monitor intratumoral macrophage injection and intravenous macrophage accumulation in solid tumors in rodents for at least 4 to 8 hours after administration. In summary, our investigations demonstrated that ultrasound can provide a noninvasive and scalable imaging technology to study the complex problem of immune cell trafficking in solid tumors while providing a potential tool for cancer diagnosis and therapy.
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2024-04-29
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