Tracking macrophages with ultrasound

Abstract

Macrophages play a key role among the immune cells in host defense. They are also known to be involved in various complex processes like angiogenesis and can infiltrate disease environments like in the case of cancer and atherosclerosis. Hence, imaging macrophages and their trafficking patterns could provide important prognostic and diagnostic markers of various human diseases. Previous attempts at imaging macrophages have been limited in depth of penetration, spatial resolution, and sensitivity. We hypothesize that labelling macrophages with microbubble (MB) contrast agents could render them visible to ultrasound and potentially overcome these limitations to enable imaging of macrophage trafficking at high resolution and sensitivity deep into tissues. Here, we show that macrophages can be labeled with MB to make them echogenic. Subsequently, we demonstrate that there are ultrasound exposure settings where these macrophages can retain high echogenicity and viability without affecting their functionality. We also confirmed that these MB-labeled macrophages can be imaged invivo (7-fold increase in CNR as compared to unlabeled macrophages) following intratumoral injection into subcutaneous tumors. In summary, our research findings demonstrate a highly sensitive approach to study macrophage interactions with disease environments that may lead to novel biomarkers for disease diagnosis.