MRI QSM Imaging for Iron Overload

MRI-based Quantitative Susceptibility Mapping of Hepatic Iron Overload

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.

Study Overview

• Status: Recruiting
• Conditions: Iron Overload; Hemochromatosis
• Intervention / Treatment: Radiation: Magnetic Resonance Imaging (MRI)-based Quantitative Susceptibility Mapping (QSM)

• Study Type: Observational
• Enrollment (Estimated): 80

Contacts and Locations

• Study Contact: Name: Study Coordinator; Phone Number: (608) 807-9594; Email: Radstudy@uwhealth.org

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Not yet recruiting
      • School of Medicine, Stanford University
      • Contact: Shreyas Vasanawala, MD, PhD; Phone Number: 650-723-8087; Email: vasanawala@stanford.edu
      • Principal Investigator: Shreyas Vasanawala
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • Recruiting
      • University of Wisconsin
      • Contact: Study Coordinator; Phone Number: 608-807-9594; Email: Radstudy@uwhealth.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• 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.

Description

Inclusion Criteria:

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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

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); 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of MRI-based QSM of the liver to serum ferritin measurements	MRI-based QSM of the liver will be compared to serum ferritin measurements to validate MRI-QSM method. MRI-QSM visit will be scheduled within +/-2 days of serum ferritin measurement visit	up to 3.5 hours

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Stanford University
• Investigators: Principal Investigator: Diego Hernando, PhD, University of Wisconsin, Madison

Study record dates

Study Major Dates

• Study Start (Actual): January 18, 2022
• Primary Completion (Estimated): March 1, 2024
• Study Completion (Estimated): March 1, 2025

Study Registration Dates

• First Submitted: November 10, 2020
• First Submitted That Met QC Criteria: November 10, 2020
• First Posted (Actual): November 17, 2020

Study Record Updates

• Last Update Posted (Actual): January 18, 2024
• Last Update Submitted That Met QC Criteria: January 17, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Liver iron concentration; Magnetic Resonance Imaging (MRI)-based Quantitative Susceptibility Mapping (QSM)
• 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: 2020-0761; A539300 (Other Identifier: UW Madison); SMPH/RADIOLOGY/RADIOLOGY (Other Identifier: UW Madison); 1R01DK117354-01 (U.S. NIH Grant/Contract); Protocol Version 9/10/2021 (Other Identifier: UW Madison)

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.: No