Chronic Liver Disease: Noninvasive Subharmonic Aided Pressure Estimation of Hepatic Venous Pressure Gradient

Abstract

Purpose:To compare subharmonic aided pressure estimation (SHAPE) with pressure catheter-based measurements in human patients with chronic liver disease undergoing transjugular liver biopsy. Materials and Methods:This HIPAA-compliant study had U.S. Food and Drug Administration and institutional review board approval, and written informed consent was obtained from all participants. Forty-five patients completed this study between December 2010 and December 2011. A clinical ultrasonography (US) scanner was modified to obtain SHAPE data. After transjugular liver biopsy with pressure measurements as part of the standard of care, 45 patients received an infusion of a microbubble US contrast agent and saline. During infusion, SHAPE data were collected from a portal and hepatic vein and were compared with invasive measurements. Correlations between data sets were determined by using the Pearson correlation coefficient, and statistical significance between groups was determined by using the Student t test. Results:-The 45 study patients included 27 men and 18 women (age range, 19-71 years; average age, 55.8 years). The SHAPE gradient between the portal and hepatic veins was in good overall agreement with the hepatic venous pressure gradient (HVPG) (R = 0.82). Patients at increased risk for variceal hemorrhage (HVPG > 12 mm Hg) had a significantly higher mean subharmonic gradient than patients with lower HVPGs (1.93 dB 6 0.61 [standard deviation] vs 21.47 dB 6 0.29, P , .001), with a sensitivity of 100% and a specificity of 81%, indicating that SHAPE may be a useful tool for the diagnosis of clinically important portal hypertension. Conclusion:Preliminary results show SHAPE to be an accurate noninvasive technique for estimating portal hypertension.q RSNA, 2013 Supplemental material: http://radiology.rsna.org/lookup /suppl

Origins of Portal Hypertension in Nonalcoholic Fatty Liver Disease

“…Subharmonic aided pressure estimation (SHAPE) is a novel method of dynamic contrast-enhanced (DCE) ultrasonography using encapsulated microbubble contrast material, which preferentially changes its acoustic behavior in response to ambient fluid pressure in the hepatic vessels and allows a noninvasive estimate of HVPG [77]. In a pilot study of 45 patients with variable liver diseases including 13 cases of NASH, clinically significant PHT was identified by SHAPE with a sensitivity of 89% and a specificity of 88%, while correlation with fibrosis scores was less robust [77].…”

“…In a pilot study of 45 patients with variable liver diseases including 13 cases of NASH, clinically significant PHT was identified by SHAPE with a sensitivity of 89% and a specificity of 88%, while correlation with fibrosis scores was less robust [77]. Another remarkable diagnostic approach applies the graph theory to DCE ultrasonography.…”

Non-Invasive Intra-cardiac Pressure Measurements Using Subharmonic-Aided Pressure Estimation: Proof of Concept in Humans

“…Several approaches to utilizing ultrasound contrast agents for ambient pressure estimation have been proposed, but high errors (as much as 50 mmHg or 30% relative to the reference standard) associated with these techniques have prevented pre-clinical or clinical applications (Bouakaz et al 1999, Fairbank and Scully 1977, Hök 1981, Miwa 1982, Shankar et al 1986); clinical applications would require errors on the order of 5 mmHg with the reference standard (Pickering et al 2005). One of the other approaches to utilize microbubble based ultrasound contrast agents for ambient pressure estimation is based on the subharmonic signal amplitude and this approach has been tested and used extensively by our group and others (Adam et al 2005, Andersen and Jensen 2009, 2010, Dave et al 2011, 2012a, 2012b, 2012c, Eisenbrey et al 2013, Forsberg et al 2005, Frinking et al 2012, Halldorsdottir et al 2011, 2014, Shi et al 1999). Briefly, this approach relies on eliciting ambient pressure sensitive subharmonic signals, extracting the subharmonic signal amplitude (which is at half the transmit frequency) and then, estimating ambient pressure based on a linear relationship between the subharmonic signal amplitude and the ambient pressure.…”

“…The SHAPE technique has been tested in vitro (Dave et al 2011, 2012a, Halldorsdottir et al 2011, Shi et al 1999), in pre-clinical studies (Dave et al 2012b, 2012c, Forsberg et al 2005, Halldorsdottir et al 2014) and also, in humans for portal hypertension assessment (Eisenbrey et al 2013). The cardiac applications of the SHAPE technique have been limited to pre-clinical studies to date.…”

The effects of temperature on the nonlinear oscillations of contrast enhancing microbubbles

“…The subharmonic-based pressure estimation method was implemented into a clinical scanner 14 for automated pressure estimations 15 . Since then two clinical applications, one for the estimation of hepatic venous pressure gradient 16 , and one for measuring interstitial tumor pressure 17 have been reported.…”