Assessment of Contrast-Enhanced Ultrasound Detection Limit for Abdominal Hemorrhage

Hemorrhage is the leading cause of preventable death from trauma, with most fatalities occurring in prehospital settings. The current standard for point-of-care hemorrhage detection is the focused assessment with sonography in trauma (FAST) exam, or computed tomography (CT) angiography after hospital arrival. Contrast-enhanced ultrasound (CEUS) has been proposed as a next-generation FAST exam, due to potential for: 1) differentiating active versus inactive bleeding; 2) localizing bleeding sources; and 3) guiding percutaneous and/or endovascular treatments to temporize bleeding for prolonged transport. While these advantages have been reported in human trauma case studies, characterization of the minimum hemorrhage rate detectable by CEUS remains a translational research need. Prior work using conventional B-mode imaging and microvascular CEUS algorithms showed the detection of 5 mL/min flow in a generic hemorrhage phantom. Here, we apply nonlinear imaging waveforms [pulse inversion (PI) and amplitude modulation (AM)] with an iterative spatiotemporal filter that further enhances contrast signals [fast iterative shrinkage-thresholding algorithm (FISTA)] to detect significantly lower flow rates in an anatomically realistic abdominal hemorrhage phantom. We demonstrate detection of bleeding at a minimum flow rate of 0.5 mL/min, comparable to multidetector CT. We achieve this detection limit even with 10% of the standard contrast dose (area under the receiver operating characteristic (ROC) curve of 0.90 and 0.84 for PI + FISTA and AM + FISTA, respectively, compared to 0.38 for conventional B-mode), suggesting that CEUS examination is feasible throughout contrast wash-in/wash-out. Finally, to bridge toward in vivo characterization, we present a novel porcine liver hemorrhage model tailored to evaluating CEUS capabilities.