Multiparametric Ultrasound for the Noninvasive Diagnosis of Porto-sinusoidal Vascular Liver Disorder (CEUS-PSVD)

Explorative Study for the Application of Dynamic Contrast-enhanced Ultrasound for the Noninvasive Diagnosis of Porto-sinusoidal Vascular Liver Disorder

Porto-sinusoidal vascular disease (PSVD) is a rare clinical entity characterized by significant portal hypertension in the absence of cirrhosis on liver histology, which may or may not show specific alterations of the portal vein, sinusoids, or hepatic lobular architecture. Currently, diagnosis of this condition necessarily requires a liver biopsy and, despite some differences detected on imaging studies-and particularly on liver and spleen elastography-PSVD remains indistinguishable from cirrhosis using non-invasive tests.

Contrast-enhanced ultrasound (CEUS) is an easy-to-perform, repeatable, and cost-effective examination that enables real-time assessment of parenchymal or focal liver lesion perfusion. Moreover, the application of dynamic contrast-enhanced ultrasound (DCE-US-i.e., contrast-enhanced ultrasound followed by quantitative perfusion analysis using dedicated software, such as the VueBox Software that will be used in this study) allows integration of CEUS qualitative assessment with quantitative evaluation of tissue perfusion through analysis of time-intensity curves generated during contrast transit. From this analysis, several perfusion-related parameters can be derived (for example, peak enhancement, time to peak, or area under the curve), which have already proven useful in improving differential diagnosis of focal liver lesions and in predicting treatment response and systemic therapy outcomes.

To date, the use of DCE-US for the diagnosis of PSVD has not yet been described; however, based on the underlying histological alterations associated with this disease, it is reasonable to hypothesize that parameters obtained with this technique in the liver parenchyma of patients with PSVD may differ from those measured in patients with liver cirrhosis. The aim of the present project is to apply DCE-US in patients with PSVD and in patients with cirrhosis to evaluate potential significant differences in perfusion parameters, and to assess the feasibility of a non-invasive differential diagnosis between the two conditions using this technique in combination with elastography and bidimensional ultrasound data to develop a multiparametric diagnostic score.

Study Overview

• Status: Not yet recruiting
• Conditions: Liver Cirrhosis; Portal Hypertension, Noncirrhotic; Portal Hypertension Related to Cirrhosis; Ultrasound Elastography; Contrast-enhanced Ultrasound; Porto-sinusoidal Vascular Liver Disorder
• Intervention / Treatment: Device: Evaluation of quantitative perfusion parameters at dynamic contrast-enhanced ultrasound through Vuebox Software

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Maria Assunta Zocco; Phone Number: +39 0630155057; Email: mariaassunta.zocco@policlinicogemelli.it; raffaele.borriello@unicatt.it

Study Locations

• Italy
  • RM
    • Roma, RM, Italy, 00168
      • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
      • Contact: Maria Assunta Zocco; Phone Number: +39 0630155057; Email: mariaassunta.zocco@policlinicogemelli.it ; raffaele.borriello@unicatt.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria - PSVD group

• Histologically confirmed diagnosis of porto-sinusoidal vascular disease (PSVD);
• Presence of clinically significant portal hypertension, evidenced by at least one specific sign of portal hypertension (e.g., imaging evidence of collateral circulation or porto-systemic shunts, endoscopic evidence of esophageal or gastric varices, or history of gastrointestinal variceal bleeding);
• Age ≥ 18 years;
• Ability to understand the study information and provide written informed consent;

Inclusion criteria - Cirrhosis group

• Diagnosis of liver cirrhosis confirmed by liver histology or, alternatively, by compatible findings on imaging, laboratory tests, and physical examination together with a positive history for at least one known cause of chronic liver disease;
• Presence of clinically significant portal hypertension, evidenced by at least one specific sign of portal hypertension (e.g., imaging evidence of collateral circulation or porto-systemic shunts, endoscopic evidence of esophageal or gastric varices, or history of gastrointestinal variceal bleeding);
• Age ≥ 18 years;
• Ability to understand the study information and provide written informed consent.

Exclusion criteria - PSVD group (cases)

• Presence of other causes of portal hypertension, including but not limited to: history of bone marrow transplantation, Budd-Chiari syndrome or hepatic venous outflow obstruction, hepatic schistosomiasis, Abernethy malformation, hereditary hemorrhagic telangiectasia, sarcoidosis, congenital hepatic fibrosis, or chronic cholestatic liver diseases;
• Presence of portal, spleno-mesenteric, or hepatic vein thrombosis;
• Prior hepatic or splenic surgery;
• Presence of primary or secondary malignant liver tumors;
• Presence of a transjugular intrahepatic portosystemic shunt (TIPS) device;
• Congenital anomalies of the liver or biliary tract;
• History of heart failure;
• Contraindications to administration of SonoVue (sulfur hexafluoride microbubbles), including: prior allergic reaction to the active substance or any excipients, known right-to-left shunts, severe pulmonary hypertension (pulmonary artery pressure > 90 mmHg), uncontrolled systemic hypertension, or adult respiratory distress syndrome;
• Inadequate sonographic visualization of the right hepatic lobe;
• Pregnancy.

Exclusion criteria - Cirrhosis group

• Decompensated cirrhosis or Child-Pugh class C;
• Cryptogenic cirrhosis;
• Presence of other causes of portal hypertension (same list as for PSVD exclusions: history of bone marrow transplantation, Budd-Chiari syndrome or hepatic venous outflow obstruction, hepatic schistosomiasis, Abernethy malformation, hereditary hemorrhagic telangiectasia, sarcoidosis, congenital hepatic fibrosis, chronic cholestatic diseases);
• Presence of portal, spleno-mesenteric, or hepatic vein thrombosis;
• Prior hepatic or splenic surgery;
• Presence of primary or secondary malignant liver tumors;
• Presence of a transjugular intrahepatic portosystemic shunt (TIPS) device;
• Congenital anomalies of the liver or biliary tract;
• History of heart failure;
• Contraindications to administration of SonoVue (sulfur hexafluoride microbubbles), including: prior allergic reaction to the active substance or any excipients, known right-to-left shunts, severe pulmonary hypertension (pulmonary artery pressure > 90 mmHg), uncontrolled systemic hypertension, or adult respiratory distress syndrome;
• Inadequate sonographic visualization of the right hepatic lobe;
• Pregnancy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PSVD (Porto-Sinusoidal Vascular Disorder); Participants with confirmed porto-sinusoidal vascular disease undergoing DCE-US with quantitative perfusion analysis using the VueBox software device	Device: Evaluation of quantitative perfusion parameters at dynamic contrast-enhanced ultrasound through Vuebox Software; Patients from the two arms will undergoing dynamic contrast-enhanced ultrasound, and CEUS videoclips will be analyzed through the software VueBox to evaluate perfusion parameters. These parameters will be compared among the two arms and integrated with other ultrasound-derived data to analyze differences and to elaborate a multiparametric diagnostic score
Experimental: Cirrhosis; Participants with confirmed liver cirrhosis undergoing DCE-US with quantitative perfusion analysis using the VueBox software device	Device: Evaluation of quantitative perfusion parameters at dynamic contrast-enhanced ultrasound through Vuebox Software; Patients from the two arms will undergoing dynamic contrast-enhanced ultrasound, and CEUS videoclips will be analyzed through the software VueBox to evaluate perfusion parameters. These parameters will be compared among the two arms and integrated with other ultrasound-derived data to analyze differences and to elaborate a multiparametric diagnostic score

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak enhancement (PE) measured on DCE-US (VueBox)	Maximum intensity of the signal in the time-intensity curve at dynamic contrast-enhanced ultrasound	Baseline
Time to peak (TTP) measured on DCE-US (VueBox)	The time required from the beginning of the exam to reach the peak enhancement	Baseline
Area under the time-intensity curve (AUC) measured on DCE-US (VueBox)	The total area under the time-intensity curve reflecting the quantity of contrast media passed through the region of interest	Baseline
Wash-in rate (slope) measured on DCE-US (VueBox)	Tangent at the ascending part of the time-intensity curve	Baseline
Mean Transit Time measured on DCE-US (VueBox)	Mean time taken by contrast to pass through the ROI	Baseline
Rise Time measured on DCE-US (VueBox)	Time from peak enhancement to point where tangent of ascending curve across x-axis	Baseline
Wash-out rate measured on DCE-US (VueBox)	The tangent at the descending part of the time-intensity curve	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic sensitivity and specificity of predefined perfusion parameter cut-offs for identifying PSVD (ROC analysis)	Differences among PSVD and cirrhosis in perfusion parameters will be analyzed in order to identify the cut-offs with the best sensitivity and specificity to identify PSVD from DCE-US.	Baseline
Performance of a multiparametric diagnostic score combining DCE-US parameters, liver stiffness, spleen stiffness, and B-mode ultrasound features	The mentioned cut-offs in DCE-US parameters will be combined with the bidimensional ultrasound data, Doppler data and elastography data to elaborate a noninvasive diagnostic score to predict the presence of PSVD	Baseline
Correlation between quantitative DCE-US parameters and risk of portal vein thrombosis at 12 months.	DCE-US parameters will be correlated with the incidence of portal vein thrombosis in order to detect if these parameters may be predictive of developing this condition, potentially allowing to identify the cohort of patients who would benefit more from prophylactic anticoagulation	from enrollement to 12 months
Incidence of portal vein thrombosis at 12 months	The proportion of patients developing porta vein thrombosis at 12 months	From baseline to 12 months
Incidence of disease-related complications (ascites decompensation, hepatic encephalopathy, variceal bleeding) at 12 months in both arms	Nunmber of portal hypertension-related complications per patient in both arms from the enrollement to 12 months	From enrollement to 12 months

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Investigators: Principal Investigator: Maria Assunta Zocco, Fondazione Policlinico Universitario A. Gemelli, IRCCS

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: November 25, 2025
• First Submitted That Met QC Criteria: March 20, 2026
• First Posted (Actual): March 25, 2026

Study Record Updates

• Last Update Posted (Actual): March 25, 2026
• Last Update Submitted That Met QC Criteria: March 20, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: liver cirrhosis; chronic liver disease; ultrasound elastography; porto-sinusoidal vascular liver disorder; liver ultrasound; dynamic contrast-enhanced ultrasound
• Additional Relevant MeSH Terms: Pathologic Processes; Digestive System Diseases; Liver Diseases; Fibrosis; Pathological Conditions, Signs and Symptoms; Liver Cirrhosis; Hypertension, Portal
• Other Study ID Numbers: 8071

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No