Identification of Hepatic Fibrosis Using 4D-MRI (4D-MRI Liver)

Noninvasive Stage Identification of Hepatic Fibrosis Using 4D-MRI

To date, no specific treatment options exist for liver diseases, and there is a large global effort to find drugs that will halt liver disease progression in these patients.Liver fibrosis staging is essential as a diagnostic/prognostic measure and there is an increasing demand for accurate non-invasive liver stiffness measurement tools. This research project proposes a novel MR-based quantitative Liver Deformation Biomarker (qLDB) approach for non-invasive liver fibrosis assessment by using a new technique called 4D-MRI. 4D-MRI allows to overcome the limitations of currently used techniques. Hence, 4D-MRI may help to identify a novel biomarker for non-invasive staging of liver fibrosis , and therefore improve the final diagnosis of patients suffering from liver diseases.

Study Overview

• Status: Recruiting
• Conditions: Liver Diseases
• Intervention / Treatment: Diagnostic test: 4D-MRI

Detailed Description

Chronic liver diseases represent a rising global health threat. A prolonged inflammatory state leads to progressive fibrosis that can result in liver cirrhosis associated with serious complications including loss of liver function or hepatocellular carcinoma development. A particularly strong increase in the prevalence, morbidity, and mortality occurs in fatty liver disease, such as non-alcoholic fatty liver disease (NAFLD) and alcohol-related liver disease; (ALD).To date, no specific treatment options for these conditions exist, and there is a large global effort to find drugs that will halt liver disease progression in these patients. Liver fibrosis staging is essential as a diagnostic/prognostic measure and there is an increasing demand for accurate non-invasive liver stiffness measurement tools. This research project proposes a novel MR-based quantitative Liver Deformation Biomarker (qLDB) approach for non-invasive liver fibrosis assessment by using a new technique called 4D-MRI. This technique makes it possible to overcome limitations in currently used techniques, i.e. to capture the abdominal organs with high spatial resolution in 3-dimensions at a high frame rate of 2-3 Hz and enabled an entirely new insight into the human body. The final diagnosis (i.e., stage of fibrosis) is based on quantifying changes of the liver's mechanical properties by dynamic magnetic resonance (MR) measurements and comparing the liver's elastic deformation with healthy livers. This innovative methodology allows for the first time to quantitatively measure the elastic deformation of organs during free-breathing and for an extended period, since no harmful X-rays are required. The hypothesis of the study is that the mechanical changes a liver undergoes during liver disease progression are visible in 4D-MRI data sets as a reduced elasticity. This will be assessed using our 4D-MRI approach taking into account the liver's deformation induced by natural respiration and also cardiac pulsation. The primary objective of the study is to compare liver deformation, induced at different respiratory breath-hold positions, by respiratory motion, and cardiac pulsation, between healthy subjects and patients with histologically confirmed liver cirrhosis in order to find a novel biomarker for non-invasive staging of liver fibrosis.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Magdalena Filipowicz Sinnreich, PD Dr.; Phone Number: 0613287789; Email: magdalena.filipowicz@unibas.ch
• Study Contact Backup: Name: Oliver Bieri, Prof. Dr.; Phone Number: 061 556 57 26; Email: oliver.bieri@unibas.ch

Study Locations

• Switzerland
  • Basel-Land
    • Liestal, Basel-Land, Switzerland, 4410
      • Recruiting
      • Kantonsspital Baselland (KSL)
      • Contact: Emanuel Burri, PD Dr.; Phone Number: 0619252813; Email: emanuel.burri@ksbl.ch
      • Sub-Investigator: Damien Toia, Dr. med.
  • Basel-Stadt
    • Basel, Basel-Stadt, Switzerland, 4052
      • Recruiting
      • University Hospital Basel
      • Contact: Magdalena Filipowicz Sinnreich, PD Dr.; Phone Number: 0613287789; Email: magdalena.filipowicz@unibas.ch
      • Contact: Oliver Bieri Bieri, Prof. Dr.; Phone Number: 061 556 57 26; Email: oliver.bieri@unibas.ch
      • Sub-Investigator: Philippe Cattin, Prof. Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• age ≥ 18 years
• (a) Patients with histologically confirmed chronic liver disease, including NAFLD, ALD, viral hepatitis B and C, genetic (e.g. Wilson disease, hemochromatosis) or autoimmune liver disease
• (b) Patients with acute liver inflammation or cardiac blood congestion to the liver (as assessed by laboratory values, imaging findings and clinical history)
• ability to understand and consent to participate in this study

Exclusion Criteria:

• Medical implant like cardiac pacemaker, pump, hip prosthesis
• Metallic objects in the body (e.g. splinters after an accident)
• Persons who have undergone brain or cardiac surgery
• Claustrophobia
• Body Weight >140kg or as provided by the MR manufacturer
• Pregnant and lactating women
• (a) Active hepatocellular carcinoma (HCC) (remark: patients with a history of HCC and curative treatment can be included)
• (a) CHILD C cirrhosis
• (a) and (b) Patients with overt ascites (except if they respond to diuretic treatment and the ascites resolves)
• (c) Metabolic syndrome, BMI >30 kg/m2
• (c) Acute or chronic liver disease
• Patients not willing or able to give a written informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 4D-MRI assessment for patients with liver diseases; patients with chronic liver diseases, acute liver inflammation or cardiac blood congestion to the liver will be assessed by MRI	Diagnostic test: 4D-MRI; Novel MR-imaging (MRI) and postprocessing techniques, making it possible to capture breathing-induced abdominal motion, including liver motion, under free-breathing. For the first time, these techniques - called 4D-MRI - were able to capture the abdominal organs with high spatial resolution in 3-dimensions at a high frame rate of 2-3 Hz and enabled an entirely new insight into the human body.
Experimental: 4D-MRI assessment for healthy volunteers (control group); healthy control subjects will be assessed by MRI	Diagnostic test: 4D-MRI; Novel MR-imaging (MRI) and postprocessing techniques, making it possible to capture breathing-induced abdominal motion, including liver motion, under free-breathing. For the first time, these techniques - called 4D-MRI - were able to capture the abdominal organs with high spatial resolution in 3-dimensions at a high frame rate of 2-3 Hz and enabled an entirely new insight into the human body.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the spatial-temporal deformation fields	To find out whether the spatial-temporal deformation fields, as induced by natural respiration and cardiac pulsation, and as assessed by dynamic MR measurements, are changed in liver cirrhosis if compared to healthy livers.	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of mechanical changes with 4D-MRI	To assess whether the mechanical changes a liver undergoes during liver disease progression are visible in 4D-MRI data sets as a progressively reduced elasticity, and can be correlated to histological data of the study participants	90 days
Differential Diagnosis	To assess whether the liver's mechanical properties/elastic deformation can differentiate between liver fibrosis (due to chronic liver disease) and acute inflammatory processes/venous blood congestion	90 days
Superiority Assessment of 4D-MRI vs.US elastography	To assess whether 4D-MRI shows improved sensitivity and specificity if compared to US-elastography in staging hepatic fibrosis	90 days
Superiority Assessment of 4D-MRI vs, standard MRI	To assess whether 4D-MRI shows improved sensitivity and specificity if compared to standard clinical liver MRI in staging hepatic fibrosis	90 days

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Investigators: Principal Investigator: Magdalena Filipowicz Sinnreich, PD Dr., University Hospital of Basel

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2021
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: May 17, 2022
• First Submitted That Met QC Criteria: May 17, 2022
• First Posted (Actual): May 23, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 17, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: liver fibrosis; Magnetic resonance imaging (MRI); liver stiffness; elastography; non-alcoholic fatty liver (NAFLD); alcohol-related liver disease (ALD); liver deformation
• Additional Relevant MeSH Terms: Pathologic Processes; Digestive System Diseases; Fibrosis; Liver Diseases
• Other Study ID Numbers: 2020-02669; th22Bieri

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No