Diagnosing Portal Hypertension with Noninvasive Subharmonic Pressure Estimates from a US Contrast Agent

Abstract

Background The current standard for assessing the severity of portal hypertension is the invasive acquisition of hepatic venous pressure gradient (HVPG). A noninvasive US-based technique called subharmonic-aided pressure estimation (SHAPE) could reduce risk and enable routine acquisition of these pressure estimates. Purpose To compare quantitative SHAPE to HVPG measurements to diagnose portal hypertension in participants undergoing a transjugular liver biopsy. Materials and Methods This was a prospective cross-sectional trial conducted at two hospitals between April 2015 and March 2019 (ClinicalTrials.gov identifier, NCT02489045). This trial enrolled participants who were scheduled for transjugular liver biopsy. After standard-of-care transjugular liver biopsy and HVPG pressure measurements, participants received an infusion of a US contrast agent and saline. During infusion, SHAPE data were collected from a portal vein and a hepatic vein, and the difference was compared with HVPG 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. Receiver operating characteristic analysis was performed to determine the sensitivity and specificity of SHAPE. Results A total of 125 participants (mean age ± standard deviation, 59 years ± 12; 80 men) with complete data were included. Participants at increased risk for variceal hemorrhage (HVPG ≥12 mm Hg) had a higher mean SHAPE gradient compared with participants with lower HVPGs (0.79 dB ± 2.53 vs -4.95 dB ± 3.44; P < .001), which is equivalent to a sensitivity of 90% (13 of 14; 95% CI: 88, 94) and a specificity of 80% (79 of 99; 95% CI: 76, 84). The SHAPE gradient between the portal and hepatic veins was in good overall agreement with the HVPG measurements (r = 0.68). Conclusion Subharmonic-aided pressure estimation is an accurate noninvasive technique for detecting clinically significant portal hypertension. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Kiessling in this issue.

Figures

Graphical abstract

Figure 1:

Flow diagram shows participant enrollment and subharmonic-aided pressure estimation (SHAPE) scanning. HVPG = hepatic venous pressure gradient.

Figure 2:

Images show automated power optimization algorithm. A, Maximum intensity projection of subharmonic imaging; blue square represents region of interest selected within portal vein. B, Three stages of subharmonic signal generation, namely occurrence, growth, and saturation, with changing incident pressures from 0% to 100% of maximum acoustic pressures. C, The y axis represents change in subharmonic amplitude mapped from top figure; point represented by highest peak is selected as it produces highest subharmonic-aided pressure estimation sensitivity. First peak, albeit the highest, is outside “growth” phase and is therefore not selected as optimal point.

Figure 3:

Frequency distribution for hepatic venous pressure gradient (HVPG) values for all participants.

Figure 4:

Dual imaging with B-mode (black and white) and subharmonic imaging (gold) on left and right, respectively, of each image. A, A 54-year-old man diagnosed with hepatitis who had normal hepatic venous pressure gradient (HVPG) value (2 mm Hg) with bright subharmonic signal from portal vein (PV) and inadequate signal from hepatic vein (HV). B, A 58-year-old woman diagnosed with drug-induced liver injury who had a HVPG of 12 mm Hg with considerable subharmonic signal in both PV and HV.

Figure 5:

Scatterplot shows correlation between noninvasively determined subharmonic gradient—average subharmonic amplitude in hepatic vein minus that in portal vein and corresponding hepatic venous pressure gradient, measured by using balloon occlusion catheter. HVPG = hepatic venous pressure gradient, SHAPE = subharmonic-aided pressure estimation.

Figure 6:

Box plots show subharmonic gradient (calculated as average subharmonic amplitude in hepatic vein minus that in portal vein) in participants with, A, clinically significant portal hypertension (HVPG >10 mm Hg) and in those at lower risk (HVPG <10 mm Hg), B, in participants at risk for variceal bleeding (HVPG >12 mm Hg) and in those at lower risk (HVPG <12 mm Hg). C, Receiver operating characteristic curves demonstrate ability to use subharmonic-aided pressure estimation (SHAPE) to identify participants with portal hypertension (HVPG >10 mm Hg) and, D, participants at risk for variceal bleeding (HVPG >12 mm Hg); accuracy of 95%. AUC = area under receiver operating characteristic curve, HVPG = hepatic venous pressure gradient.