Non-invasive Quantification of Liver Iron With MRI

The purpose of this study is to validate magnetic resonance imaging as a biomarker of hepatic iron concentration (HIC). Excessive accumulation of iron in the body is highly toxic, specifically in the liver. Accurate, non-invasive assessment of HIC is needed for diagnosis, quantitative staging and treatment monitoring or hepatic iron overload.

Study Overview

• Status: Completed
• Conditions: Iron Overload; Hemosiderosis
• Intervention / Treatment: Device: Non-contrast MRI

Detailed Description

Excessive accumulation of iron in the body can result from abnormal intestinal absorption in hereditary hemochromatosis or repeated intravenous blood transfusions (ie: transfusional hemosiderosis). Excess body iron is highly toxic, and requires treatment aimed at reducing body iron stores. Measurement of body iron stores is critical for detection of iron overload, staging its severity and monitoring of iron-reducing therapies that are often extremely expensive (>$40,000/year) and carry their own toxicities. MRI has been shown to be very sensitive to the presence of iron. The investigators have developed an MRI-based method for rapid iron quantification (for instance, whole liver in a single breath-hold). The purpose of this work is to validate this new method using the FDA-approved Ferriscan technique (Resonance Health, Claremont, Australia) as a reference standard.

• Study Type: Observational
• Enrollment (Actual): 50

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • Wisconsin Institutes for Medical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Participants with known or suspected iron overload are identified and recruited in 3 different ways, 1) referral from the Division of Hematology/Oncology and Pediatric Hematology/Oncology, 2) via clinical reading of abdominal MRIs for evidence of iron overload, and 3) participants identified to have serum ferritin levels >500 by UW Hospital Clinical Laboratory will be invited to participant. Controls were recruited from a recruitment database.

Description

Inclusion Criteria:

• Controls: 18 years or older with no known history of iron overload or liver disease.
• Patients: 10 years or older with known or suspected iron overload

Exclusion Criteria:

• Patients with contraindications to MRI (eg. pacemaker, contraindicated metallic implants, claustrophobia, etc) and pregnant females (as determined by self-report during MRI safety screening) will be excluded.
• For control subjects, those with known liver disease will be excluded.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patient Group; Subjects with known or suspected iron overload will undergo serum iron measurements and a non-contrast MRI scan.	Device: Non-contrast MRI; Non-contrast MRI will be performed on each subject, at both 1.5T and 3.0T. Different MRI sequences (spin-echo and gradient-echo) will be used, with varying acquisition parameters (e.g., echo times, spatial resolution).
Control Group; Subjects with no known history of iron overload or liver disease will undergo a serum iron measurement and a non-contrast MRI scan.	Device: Non-contrast MRI; Non-contrast MRI will be performed on each subject, at both 1.5T and 3.0T. Different MRI sequences (spin-echo and gradient-echo) will be used, with varying acquisition parameters (e.g., echo times, spatial resolution).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Calibration Curve of Liver R2* vs. HIC Measured by FerriScan	Accuracy of non-contrast R2*-MRI for measuring hepatic iron concentration.	Up to 1 day
Correlation of Ferritin and Liver R2*	Linear correlation between serum ferritin values and MRI R2* values	up to 1 day
Correlation of Ferritin and HIC Measured by FerriScan	Linear correlation between serum ferritin values and FerriScan hepatic iron measurement.	up to 1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Variability of cardiac R2* with different imaging parameters	Robustness of Proposed Method for Cardiac R2* Estimation. Measure variability of cardiac R2* with different imaging parameters.	up to 1 day

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Investigators: Principal Investigator: Scott B Reeder, MD, PhD, University of Wisconsin, Madison

Publications and helpful links

General Publications

• Hernando D, Cook RJ, Diamond C, Reeder SB. Magnetic susceptibility as a B0 field strength independent MRI biomarker of liver iron overload. Magn Reson Med. 2013 Sep;70(3):648-56. doi: 10.1002/mrm.24848. Epub 2013 Jun 25.
• Sharma SD, Hernando D, Horng DE, Reeder SB. Quantitative susceptibility mapping in the abdomen as an imaging biomarker of hepatic iron overload. Magn Reson Med. 2015 Sep;74(3):673-83. doi: 10.1002/mrm.25448. Epub 2014 Sep 8.
• Horng DE, Hernando D, Reeder SB. Quantification of liver fat in the presence of iron overload. J Magn Reson Imaging. 2017 Feb;45(2):428-439. doi: 10.1002/jmri.25382. Epub 2016 Jul 13.

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: August 17, 2011
• First Submitted That Met QC Criteria: January 19, 2012
• First Posted (Estimate): January 25, 2012

Study Record Updates

• Last Update Posted (Actual): December 6, 2019
• Last Update Submitted That Met QC Criteria: December 4, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Iron Metabolism Disorders; Metabolism, Inborn Errors; Metal Metabolism, Inborn Errors; Iron Overload; Hemochromatosis; Hemosiderosis
• Other Study ID Numbers: 2011-0473 (Other Identifier: Institutional Review Board); A539300 (Other Identifier: UW Madison); SMPH\RADIOLOGY\RADIOLOGY (Other Identifier: UW Madison)

Drug and device information, study documents

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