A Novel Approach\nto Harnessing Acoustic A‑Lines\nto Detect Circulating Tumor Cells in Flowing Blood

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