ABSTRACT FINAL ID: 2101
TITLE: Pulse Shaping for Improved Diagnosis of Portal Hypertension Using Subharmonic Aided Pressure Estimation
SPONSORSHIP - THIS STUDY WAS SPONSORED BY: (IF THIS ABSTRACT WAS NOT SPONSORED PLEASE INDICATE):
Thomas Jefferson University
University of Pennsylvania
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov identifier: NCT02489045
Background & Hypothesis
Subharmonic aided pressure estimation (SHAPE) is based on the inverse relationship between the subharmonic amplitude of contrast microbubbles (obtained by transmitting at the fundamental frequency fo and receiving at fo/2) and the ambient pressure. A noninvasive ultrasound based pressure estimation procedure would be a major development in the diagnosis of portal hypertension and less invasive than the current hepatic venous pressure gradient (HVPG) measurement. The hypothesis of this study was that portal vein pressures can be monitored and quantified noninvasively in humans using SHAPE, after optimizing waveforms in canines, and correlate to measured HVPG in patients undergoing a transjugular liver biopsy (TJLB) with HVPG measurement.
A Logiq 9 ultrasound scanner with a 4C curvi-linear probe (GE, Milwaukee, WI) was used to acquire radio frequency data. The SHAPE mode was set to transmit 4 cycle pulses at 2.5 MHz and receive subharmonic signals at 1.25 MHz. The contrast agent Sonazoid (GE, Oslo, Norway) was infused at a rate of 0.024 μL/kg/min. 8 different pulse waveforms (3 narrowband and 5 broadband) were implemented and tested in vitro and in vivo in 3 canines. Selection of the best waveform for SHAPE was based on the decrease in the subharmonic signal amplitude with increasing ambient pressure and correlation coefficients. Next, TJLB subjects were enrolled. Post TJLB, patients received an infusion of Sonazoid in recovery area, with sonographer blinded to HVPG results. An ROI within the portal vein was selected and an automated power control algorithm was initiated to determine the optimal acoustic output power for maximum SHAPE sensitivity. Cine loops were collected in triplicate, averaged and compared to the HVPG.
A linear decrease in subharmonic amplitude with increased pressure was observed for all waveforms (r from -0.77 to -0.93; p<0.001) in vitro. Data from 1 of the 3 canines was eliminated for technical reasons, while the other 2 produced similar results to those obtained in vitro (r from -0.72 to -0.98; p<0.01). Overall, the broadband pulses performed better (p<0.05). Within the broadband group, the Gaussian windowed binomial filtered square wave was the most sensitive. 53 TJLB subjects were studied (median age 60 ± 9, 60.4% male). The linear relationship between the SHAPE gradient and HVPG over the patient dataset showed a good correlation (r2 = 0.82).
The Gaussian windowed binomial filtered square wave makes the SHAPE technique more sensitive to pressure estimation. Current results in this clinical trial indicate that SHAPE may be useful for non-invasive estimation of portal pressures.