Ultrasound Imaging of Portal Hypertension Using Microbubbles

Increased pressure in the blood vessels of the liver, especially the portal vein, can lead to significant complications including internal bleeding. Each bleeding episode carries up to a 20% risk of death. Currently, clinicians evaluate portal hypertension through the hepatic venous pressure gradient (HVPG) determined by the gradient in pressure readings between wedged and free hepatic vein catheter positions via a transjugular approach. An accurate marker for portal hypertension would impact literally millions of Americans with liver disease.

Our collaboration has developed and implemented an innovative ultrasound technique called subharmonic-aided pressure estimation (SHAPE) for noninvasive pressure measurements.  The technique relies on the nonlinear ultrasound physics of microbubble resonance and the sensitivity of this behavior on the instantaneous local blood pressure. In 2014, we conducted a first-in-humans, pilot study of this technique's ability to estimate portal pressures in 45 patients undergoing transjugular liver biopsy. 

This work was supported by an NIDDK Challenge Grant (RC1 DK087365). The SHAPE gradient between the portal and hepatic veins was in good agreement with the corresponding HVPG (R = 0.82). More importantly, subjects with portal hypertension (HVPG > 10 mmHg) showed significantly higher subharmonic gradients than those with lower HVPGs (p < 0.001). Based on those encouraging results, beginning in 2016 with NIH support (R01 DK098526) we began a large scale clinical trial of the novel implementation of SHAPE in 300 patients undergoing a transjugular liver biopsy at Thomas Jefferson University (TJU) and the Hospital of the University of Pennsylvania (HUP).