Development of Novel MRI Methods for Detecting, Discriminating, and Measuring Liver Fibrosis and Congestion in Fontan Patients

In this research study, the investigators will conduct a prospective cross-sectional study of pediatric and adult Fontan patients that will correlate a variety of quantitative MRI biomarkers with histopathologic data.

Study Overview

• Status: Terminated
• Conditions: Liver Fibrosis
• Intervention / Treatment: Device: Non-Contrast Magnetic Resonance Imaging

Detailed Description

The purpose of this study is to develop noninvasive MRI methods for detecting, discriminating, and measuring liver fibrosis and congestion in the adolescent and adult Fontan population by correlating quantitative imaging measurements with histopathologic data, using a cross-sectional approach.

Over 5 years, approximately 40 pediatric and adult subjects (approximately 8 subjects per year) undergoing clinically-indicated liver biopsy for the evaluation of either 1) focal liver lesions/masses, or 2) suspected liver fibrosis/parenchymal disease will be recruited to participate in this study. Subjects will undergo research MR imaging within ±2 weeks of the liver biopsy procedure. A variety of MRI biomarkers will be correlated with histopathologic data obtained from the clinically indicated liver biopsy.

• Study Type: Observational
• Enrollment (Actual): 6

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 99 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Eligible subjects will be identified through Cincinnati Children's Hospital Medical Center's (CCHMC) cardiology or hepatology clinics, or through CCHMCs Fontan Management Program

Description

Inclusion Criteria:

• Single ventricle physiology congenital heart disease status post Fontan palliation
• Undergoing clinically-indicated liver biopsy
• Ability to tolerate 60 minutes in an MRI scanner without sedation

Exclusion Criteria:

• Known contraindication to MR imaging (e.g., implanted non-MRI compatible device)
• Known or suspected pregnancy. Female subjects of child bearing potential will undergo urine pregnancy testing prior to imaging

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Fontan patients; Pediatric and adult Fontan patients will undergo MRI (Magnetic Resonance Imaging) of the liver using novel, non-contrast MRI methods. These MR methods will be used to detect, discriminate and measure liver fibrosis and congestion. The resulting quantitative imaging measurements will be correlated with histopathologic data obtained from a clinically-indicated liver biopsy.	Device: Non-Contrast Magnetic Resonance Imaging; The investigators plan to prospectively assess the correlation of liver fibrosis and congestion measurements obtained from novel, non-contrast MR imaging methods to histopathologic data obtained from a clinically-indicated liver biopsy in Fontan patients.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MR elastography data correlation to histologic data	MR elastography of the liver data will be correlated with histopathologic data obtained from non-lesional liver tissue. Histologic fibrosis and congestion will be scored by a pathologist using semi-quantitative grading systems (e.g., METAVIR scoring system for fibrosis	60 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MR T1 mapping data (corrected and uncorrected) correlation to histologic data	MR T1 mapping liver data (corrected and uncorrected) will be correlated with histopathologic data obtained from non-lesional liver tissue. Histologic fibrosis and congestion will be scored by a pathologist using semi-quantitative grading systems (e.g., METAVIR scoring system for fibrosis)	60 minutes
MR T1rho data correlation to histologic data	MR T1rho liver data will be correlated with histopathologic data obtained from non-lesional liver tissue. Histologic fibrosis and congestion will be scored by a pathologist using semi-quantitative grading systems (e.g., METAVIR scoring system for fibrosis)	60 minutes
MR T2 mapping data correlation to histologic data	MR T2 mapping liver data will be correlated with histopathologic data obtained from non-lesional liver tissue. Histologic fibrosis and congestion will be scored by a pathologist using semi-quantitative grading systems (e.g., METAVIR scoring system for fibrosis)	60 minutes
MR Diffusion weighted data correlation to histologic data	MR Diffusion weighted liver data will be correlated with histopathologic data obtained from non-lesional liver tissue. Histologic fibrosis and congestion will be scored by a pathologist using semi-quantitative grading systems (e.g., METAVIR scoring system for fibrosis)	60 minutes

Collaborators and Investigators

• Sponsor: Children's Hospital Medical Center, Cincinnati
• Investigators: Principal Investigator: Jonathan Dillman, MD,MSc, Children's Hospital Medical Center, Cincinnati

Study record dates

Study Major Dates

• Study Start (Actual): May 9, 2018
• Primary Completion (Actual): March 30, 2022
• Study Completion (Actual): March 30, 2022

Study Registration Dates

• First Submitted: May 16, 2018
• First Submitted That Met QC Criteria: May 16, 2018
• First Posted (Actual): May 29, 2018

Study Record Updates

• Last Update Posted (Actual): March 7, 2024
• Last Update Submitted That Met QC Criteria: March 5, 2024
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: MRI; Liver fibrosis; Fontan surgery; Novel Methods
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis
• Other Study ID Numbers: CIN_FALD MRI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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