MRI QSM Imaging for Iron Overload

NCT04631718 | Completed FDA Device

• 5 other identifiers: 2020-07611R01DK117354-01A539300SMPH/RADIOLOGY/RADIOLOGYProtocol Version 9/10/2021
• Study Type: observational
• Target: 63
• Locations: 1 country
• Sites: 2

Brief Summary

The overall goal of this project is to develop and validate a novel technique for Magnetic Resonance Imaging (MRI)-based Quantitative Susceptibility Mapping (QSM) of the abdomen, for non-invasive assessment of liver iron deposition. In this work, study team will develop and optimize advanced data acquisition and image reconstruction methods to enable QSM of the abdomen. Further, investigators will determine the accuracy, repeatability, and reproducibility of abdominal QSM for iron quantification in patients with liver iron overload. Excessive accumulation of iron in various organs, including the liver, which affects both adult and pediatric populations, is toxic and requires treatment aimed at reducing body iron stores. Accurate assessment of liver iron concentration is critical for the detection and staging of iron overload as well as for longitudinal monitoring during treatment. In summary, this project will develop a novel MRI-based QSM technique designed for the abdomen and will validate it in pediatric and adult patients with liver iron overload. Upon successful validation, QSM will provide accurate, repeatable, and reproducible quantification of LIC based on a fundamental property of tissue.

Conditions

Hemochromatosis; Iron Overload

Keywords

Liver iron concentration; Magnetic Resonance Imaging (MRI)-based Quantitative Susceptibility Mapping (QSM)

Outcome Measures

Primary Outcomes (6)

• Establishing the accuracy of MRI-QSM of the liver using SQUID-BLS as a reference

  Determine the accuracy of abdominal QSM to quantify liver iron concentration at 1.5T and 3T, in pediatric and adult patients with liver iron overload, using superconducting quantum interference device (SQUID)-based biomagnetic liver susceptometry (BLS) as the reference.

  1.5 hours

• Establishing the repeatability of MRI-QSM of the liver

  Repeatability of MRI-QSM of the liver will be established in both pediatrics and adult participants. Each participant will be scanned at both 1.5T and 3T and at UW will repeat one of the field strengths to assess repeatability. Therefore, each participant at UW will undergo 3 MRI exams and each participant at Stanford 2 MRI exams. Repeatability will not be tested at Stanford in order to avoid exhaustion of the patients (many of whom will be children), and to ensure the completion of acquisitions at both field strengths for validation of accuracy versus SQUID-BLS. Scanning will take 1.5 hour at University of Wisconsin and I hour at Stanford

  up to 1.5 hours

• Establishing the reproducibility of MRI-QSM of the liver

  The reproducibility of abdominal MRI-based Quantitative Susceptibility Mapping (MRI-QSM) will be characterized across field strengths (1.5Tesla and 3Tesla), in both pediatric and adult participants with iron overload The repeated acquisitions at 1.5T and 3T will enable analysis of reproducibility of MRI-QSM across field strengths. At UW only, participants repeat either the 1.5T or 3T exam, with consideration given to the subject's schedule and magnet availability. Repeat tests will be performed after removing the participants from the magnet and repositioning with new localizer images. Repeatability will not be tested at Stanford in order to avoid exhaustion of the patients (many of whom will be children), and to ensure the completion of acquisitions at both field strengths for validation of accuracy versus SQUID-BLS. Scanning will take 1.5 hour at University of Wisconsin and I hour at Stanford

  up to 1.5 hours

• Optimizing MRI-based QSM performance by using multiple QSM reconstruction and measurement

  Multiple QSM reconstructions will be applied to each acquired dataset, to evaluate the effect of each reconstruction component on the performance of QSM. Susceptibility measurements will be made by placing a region-of-interest in each of the nine Couinaud segments of the liver. This will allow segment-by-segment analysis as well as whole-liver analysis (by averaging over the 9 segments) of the performance of QSM. The reader performing MRI analysis will be blinded to SQUID results. Scanning will take 1.5 hour at University of Wisconsin and I hour at Stanford.

  up to 1.5 hours

• MRI-QSM data acquisition with Breath held

  An optimized acquisition will obtain 3D whole liver coverage within a \~20 second breath-hold. Data will be collected at 1.5T and 3T

  1.5 hours

• MRI-QSM data acquisition with Free Breathing

  The optimized free-breathing acquisitions (using bellows, butterfly navigators, and 2D sequential acquisitions and requiring 3-5 min each) will be performed. Data will be collected at 1.5T and 3T

  1.5 hours

Secondary Outcomes (1)

• Comparison of MRI-based QSM of the liver to serum ferritin measurements

  up to 3.5 hours

Study Arms (1)

MRI based abdominal QSM

Participants with known or suspected iron overload with past serum ferritin \>500 will be recruited in this study.

Radiation: Magnetic Resonance Imaging (MRI)-based Quantitative Susceptibility Mapping (QSM)

Interventions

Magnetic Resonance Imaging (MRI)-based Quantitative Susceptibility Mapping (QSM) RADIATION

MRI-based QSM methods estimate the susceptibility of tissues based on measuring the magnetic field distortion produced by the tissues themselves. Upon successful validation, MRI-based abdominal QSM will provide accurate, repeatable, and reproducible quantification of Liver iron concentration (LIC) that is independent of the distribution of iron and does not require calibration.

MRI based abdominal QSM

Eligibility Criteria

• Age: 5 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with known or suspected iron overload will be identified and recruited from the UWHC Hematology Adult and Pediatric clinics or Stanford Hospital and Clinics. Briefly, patients will be identified and recruited in collaboration with patient providers (either by introduction during a clinical visit or by a referral from a physician), using flyers posted in relevant clinics, or from previous related studies where the patient consented to being contacted about future research opportunities.

You may qualify if:

• Ages 10 years or older at University of Wisconsin - Madison
• Age 5 years or older at Stanford
• Known or suspected iron overload

You may not qualify if:

• Patients with contraindication to MRI (e.g. pacemaker, contraindicated metallic implants, etc)
• Pregnant or trying to become pregnant (as determined by self-report during MRI safety screening)
• Patients requiring intravenous (IV) conscious sedation for imaging are not eligible; patients requiring mild, oral anxiolytics for the MRI will be allowed to participate as long as the following criteria are met:
• The subject has their own prescription for the medication.
• The informed consent process is conducted prior to the self-administration of this medication
• They come to the research visit with a driver

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• Stanford University: collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (2)

School of Medicine, Stanford University

Stanford, California, 94305, United States

Location

University of Wisconsin

Madison, Wisconsin, 53705, United States

Location

MeSH Terms

Conditions

Hemochromatosis; Iron Overload

Interventions

Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Metal Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Diego Hernando, PhD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2020
• First Posted: November 17, 2020
• Study Start: January 18, 2022
• Primary Completion: April 29, 2024
• Study Completion: April 29, 2024
• Last Updated: May 9, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)