MRI QSM Imaging for Iron Overload

• ClinicalTrials.gov Identifier: NCT04631718
• Recruitment Status: Recruiting
• First Posted: November 17, 2020
• Last Update Posted: March 23, 2023
• Sponsor: University of Wisconsin, Madison
• Collaborators: Stanford University; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Information provided by (Responsible Party): University of Wisconsin, Madison

Study Description

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.

Condition or disease	Intervention/treatment
Hemochromatosis; Iron Overload	Radiation: Magnetic Resonance Imaging (MRI)-based Quantitative Susceptibility Mapping (QSM)

Study Design

• Study Type: Observational
• Estimated Enrollment: 80 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: MRI-based Quantitative Susceptibility Mapping of Hepatic Iron Overload
• Actual Study Start Date: January 18, 2022
• Estimated Primary Completion Date: March 2024
• Estimated Study Completion Date: March 2025

Groups and Cohorts

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.

Outcome Measures

Primary Outcome Measures :

1. Establishing the accuracy of MRI-QSM of the liver using SQUID-BLS as a reference [ Time Frame: 1.5 hours ]
   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.
2. Establishing the repeatability of MRI-QSM of the liver [ Time Frame: up to 1.5 hours ]

   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

3. Establishing the reproducibility of MRI-QSM of the liver [ Time Frame: up to 1.5 hours ]

   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

4. Optimizing MRI-based QSM performance by using multiple QSM reconstruction and measurement [ Time Frame: up to 1.5 hours ]

   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.

5. MRI-QSM data acquisition with Breath held [ Time Frame: 1.5 hours ]
   An optimized acquisition will obtain 3D whole liver coverage within a ~20 second breath-hold. Data will be collected at 1.5T and 3T
6. MRI-QSM data acquisition with Free Breathing [ Time Frame: 1.5 hours ]
   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

Secondary Outcome Measures :

1. Comparison of MRI-based QSM of the liver to serum ferritin measurements [ Time Frame: up to 3.5 hours ]
   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

Eligibility Criteria

• Ages Eligible for Study: 5 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• 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.

Criteria

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, claustrophobia, etc)
• Pregnant or trying to become pregnant (as determined by self-report during MRI safety screening)

Contacts and Locations

Contacts

Contact: Study Coordinator; (608) 807-9594; Radstudy@uwhealth.org

Locations

United States, California

School of Medicine, Stanford University; Not yet recruiting

Stanford, California, United States, 94305

Contact: Shreyas Vasanawala, MD, PhD 650-723-8087 vasanawala@stanford.edu

Principal Investigator: Shreyas Vasanawala

United States, Wisconsin

University of Wisconsin; Recruiting

Madison, Wisconsin, United States, 53705

Contact: Study Coordinator 608-807-9594 Radstudy@uwhealth.org

Sponsors and Collaborators

University of Wisconsin, Madison

Stanford University

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

• Principal Investigator: Diego Hernando, PhD; University of Wisconsin, Madison

More Information

• Responsible Party: University of Wisconsin, Madison
• ClinicalTrials.gov Identifier: NCT04631718
• Other Study ID Numbers: 2020-0761; 1R01DK117354-01 ( U.S. NIH Grant/Contract ); A539300 ( Other Identifier: UW Madison ); SMPH/RADIOLOGY/RADIOLOGY ( Other Identifier: UW Madison ); Protocol Version 9/10/2021 ( Other Identifier: UW Madison )
• First Posted: November 17, 2020
• Last Update Posted: March 23, 2023
• Last Verified: March 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by University of Wisconsin, Madison:

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

Additional relevant MeSH terms:

Hemochromatosis; Iron Overload; Hemosiderosis; Iron Metabolism Disorders; Metabolic Diseases; Metal Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn