Confounder-Corrected Quantitative MRI Biomarker of Hepatic Iron Content

Study Overview
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Brief Summary
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The purpose of this multi-site research is to validate a rapid magnetic resonance based confounder-corrected R-2 mapping method as a quantitative imaging biomarker of liver iron concentrations.

Detailed Description
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This multi-center, multi-vendor study will validate a rapid magnetic resonance-based confounder-corrected R2* mapping method as a quantitative imaging biomarker of liver iron concentration (LIC). 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. Measurement of LIC is critical for detection and staging of iron overload, and for monitoring iron-reducing chelator therapies that are expensive and have side effects. Magnetic Resonance Imaging (MRI) is a widely available, accessible, and safe technology, and it is very sensitive to the presence of iron in tissue. Translation of an MRI biomarker of liver iron concentration into broad clinical use requires that it is clinically feasible, precise, robust to changes in scan parameters, calibrated to a validated reference standard of LIC, and is reproducible across sites and manufacturers. There are currently no available MRI methods that meet these requirements. R2*-MRI holds the greatest promise to meet these requirements. R2* mapping can be performed very rapidly with whole-liver 3D coverage in a single 20s breath-hold. Protocol Modification approved to include additional liver susceptibility measurements for approximately 10 participants (already enrolled at the UW) via recently acquired Superconducting Quantum Interference Device (SQUID). The completion of this additional imaging will depend upon the successful set up and installation of this device. Per a protocol amendment approved on 10/11/21, the investigators are re-opening the study and increasing enrollment for control subjects. Up to 20 control subjects (changed from 5) will be enrolled.

Official Title
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Confounder-Corrected Quantitative Magnetic Resonance Imaging (MRI) Biomarker of Hepatic Iron Content

Conditions
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Iron Overload, Hemochromatosis, Hemosiderosis

Intervention / Treatment
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* Device: MRI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: know or suspected iron overload minimum age: Stanford- 8years , University of Wisconsin - 10 years, John Hopkins follow- 10 years, University of Texas-Southwestern - 18 years Exclusion Criteria: contraindication to magnetic resonance imaging

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 89 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patient Group<br>Subjects with known or suspected iron overload will undergo serum ferritin measurement and an MRI scan. | Device: MRI<br>* R2 MRI scan<br>* Other names: Magnetic Resonance Imaging;|
| Control Group<br>Subjects with no known history of iron overload or liver disease will undergo an MRI scan. | Device: MRI<br>* R2 MRI scan<br>* Other names: Magnetic Resonance Imaging;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Calibration curve of liver R2* vs LIC measured by Ferriscan at each of the sites | The hypothesis is that equivalence between R2 measured with different protocols with higher repeatability than standard MRI iron imaging measurement and with linear calibration to liver iron concentration will be demonstrated. This project will be considered a success if the reproducibility of confounder-corrected R2 MRI is established: the hypothesis is that calibrations at all sites will be equivalent. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Precision: Difference in UW-measured R2* vs Average | Repeat scans will be used at each site to determine precision of R2 liver iron concentration. Repeat scans on n=25 subjects per site will be used to determine Bland-Altman 95% limits of agreement (LOA) by plotting the difference in UW-measured R2* vs average. | 2 years | 
| Diagnostic Accuracy | In addition to correlation with liver iron concentration (technical accuracy), the diagnostic accuracy through receiver operator characteristic curve analysis will also be determined. | 2 years | 
| Robustness Assessed via Linear Mixed Effects Regression | At each site and field strength, R2* measurements from the eight different protocols will be compared to assess robustness. Robustness will be assessed via linear mixed effects regression. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MRI, Iron overload