A Novel Approach to Harnessing Acoustic A-Lines to Detect Circulating Tumor Cells in Flowing Blood

Circulating tumor cells (CTCs) are associated with tumor burden and treatment response and, as hallmarks of the initiation of tumor dissemination, can predict the likelihood of metastatic progression before widespread tumors can be detected by standard anatomic imaging. However, early diagnosis of recurrence through the detection of CTCs is limited by their low prevalence in blood and the limited sensitivity of existing technologies. To address these challenges, we investigated the use of ultrasound and targeted microbubbles (MBs) for early CTC detection. While MBs have been used in cardiovascular/molecular tumor imaging, there is limited research on their acoustic properties when bound to CTCs. We developed a hydrophone system for detecting characteristic A-lines from CTCs encapsulating MBs. Our study is the first to identify distinctive characteristics in the acoustic frequency response of MBs bound to different cancer CTCs using in vitro suspensions and in vivo mice that will benefit metastatic cancer detection and management.