Protocol - Determination of Liver Iron Concentration by R2*
This protocol includes a brief background describing how magnetic resonance imaging (MRI) is used to determine the concentration of iron in the liver and provides references for quantifying liver iron by MRI R2*.
The choice of quantifying iron in the liver by magnetic resonance imaging (MRI) R2* or by Ferriscan (MRI R2) depends on investigators’ expertise and available equipment.
The Sickle Cell Disease Curative Therapies Working Group recommends that participants with a liver iron concentration greater than 10 milligrams per gram by MRI should be assessed for liver fibrosis by liver biopsy, magnetic resonance elastography, or transient elastography.
Description of Quantification of Liver Iron by Magnetic Resonance Imaging (MRI)
MRI indirectly visualizes iron by imaging water protons as they diffuse near iron deposits. In tissues with significant iron concentrations, the magnetic iron deposits destroy the homogeneity of the magnetic field. Water protons moving through these significantly different magnetic profiles become desynchronized from one another causing the MRI image to darken at a rate proportional to the iron concentration.
MRI images for determination of iron content are generated by refocusing the desynchronized water protons either by a radio-frequency (rf) pulse, termed a spin echo, or by an additional magnetic field known as a gradient, termed a gradient echo. The longer the echo times (TE), the darker the images. The decline in image intensity is characterized by a half-life time constant, known as T2 if a spin echo is used, or T2* if a gradient echo is used. The reciprocal of the time constant, or the rate of image darkening, is known as R2 (reciprocal of T2) or R2* (reciprocal of T2*).
Quantifying Liver Iron by MRI R2*
A description of MR studies for the determination of liver iron by R2* can be found in the Methods section of Garbowski et al., 2014. Briefly, MR scans are performed on a 1.5 Tesla scanner. A transverse slice is imaged through the center of the liver using a multi-echo single breath-hold gradient echo T2* sequence. The regions of interest should be homogenous liver tissue from separate anterior, lateral, and posterior areas. All measurements should be performed in triplicate by independent imagers across three different regions of interest.
A description of imaging parameters can be found in Wood et al., 2016
Personnel and Training Required
A trained magnetic resonance imaging (MRI) technician is required to administer the MRI, and MRIs must be interpreted (“read”) by a trained radiologist, cardiologist, or other medical doctor.
A magnetic resonance imaging (MRI) machine at 1.5 Tesla with multiple-echo, gradient echo sequence for R2*/T2* evaluation
|Specialized requirements for biospecimen collection||No|
|Average time of greater than 15 minutes in an unaffected individual||Yes|
Mode of Administration
Complex instrumentation-based assessment
Child, Adolescent, Adult, Senior
Ages 9 and older
MRI is a non-invasive, valid, and reliable method that has been used to quantify iron in the liver in National Institutes of Health–funded clinical trials.
|caDSR Common Data Elements (CDE)||First Acute Graft Versus Host Disease Maximum Overall Grade Date||7544370||CDE Browser|
Process and Review
Protocol Name from Source
Garbowski, M. W., Carpenter, J.-P., Smith, G., Roughton, M., Alam, M. H., He, T., Pennell, D. J., & Porter, J. B. (2014). Biopsy-based calibration of T2* magnetic resonance for estimation of liver iron concentration and comparison with R2 Ferriscan. Journal of Cardiovascular Magnetic Resonance, 16, 40.
Principles of Iron Estimation by MRI and Discussion of the Technical Considerations Necessary for Accurate Measurements
Wood, J. C., & Ghugre, N. (2008). Magnetic resonance imaging assessment of excess iron in thalassemia, sickle cell disease, and other iron overload diseases. Hemoglobin, 32(1–2), 85–96.
Quantifying Liver Iron by MRI R2*
Garbowski, M. W., Carpenter, J. P., Smith, G., Roughton, M., Alam, M. H., He, T., Pennell, D. J., & Porter, J. B. (2014). Biopsy-based calibration of T2* magnetic resonance for estimation of liver iron concentration and comparison with R2 Ferriscan. Journal of Cardiovascular Magnetic Resonance, 16, 40.
American College of Radiology. (2019). ACR-AAPM technical standard for diagnostic medical physics performance monitoring of magnetic resonance imaging (MRI) equipment. https://www.acr.org/-/media/ACR/Files/Practice-Parameters/MR-Equip.pdf
American College of Radiology. (2020). ACR-SAR-SPR practice parameter for the performance of magnetic resonance imaging (MRI) of the liver (Res. 27). https://www.acr.org/-/media/ACR/Files/Practice-Parameters/MR-Liver.pdf
Ghugre, N. R., Gonzalez-Gomez, I., Butensky, E., Noetzli, L., Fischer, R., Williams, R., Harmatz, P., Coates, T. D., & Wood, J. C. (2009). Patterns of hepatic iron distribution in patients with chronically transfused thalassemia and sickle cell disease. American Journal of Hematology, 84(8), 480–483.
Wood, J. C. (2017). The use of MRI to monitor iron overload in SCD. Blood Cells, Molecules, and Diseases, 67, 120–125.
Wood, J. C., Cohen, A. R., Pressel, S. L., Aygun, B., Imran, H., Luchtman-Jones, L., Thompson, A. A., Fuh, B., Schultz, W. H., Davis, B. R., Ware, R. E., & TWiTCH Investigators. (2016). Organ iron accumulation in chronically transfused children with sickle cell anaemia: Baseline results from the TWiTCH trial. British Journal of Haematology, 172(1), 122–130.
Wood, J. C., Pressel, S., Rogers, Z. R., Odame, I., Kwiatkowski, J. L., Lee, M. T., Owen, W. C., Cohen, A. R., St. Pierre, T., Heeney, M. M., Schultz, W. H., Davis, B. R., & Ware, R. E. (2015). Liver iron concentration measurements by MRI in chronically transfused children with sickle cell anemia: Baseline results from the TWiTCH trial. American Journal of Hematology, 90(9), 806–810.
|Variable Name||Variable ID||Variable Description||dbGaP Mapping|
|PX851201040000||Were all measurements performed in more||N/A|
|PX851201030000||Were the regions of interest imaged from more||N/A|
|PX851201010000||Were magnetic resonance imaging (MRI) scans more||N/A|
|PX851201020000||Was a transverse slice of the liver iamged more||N/A|
Noninvasive Determination of Liver Iron Concentration
August 16, 2021
Noninvasive quantification of iron in the liver using magnetic resonance imaging (MRI)
Chronic red blood cell transfusions can lead to accumulation of toxic iron levels in the liver, heart, and endocrine organs. The concentration of iron in the liver reflects total iron in the body, and elevated liver iron is a risk factor for liver fibrosis and cardiac disease.
Liver, heart, endocrine, iron overload, iron
|Protocol ID||Protocol Name|
|851201||Determination of Liver Iron Concentration by R2*|
|851202||Determination of Liver Iron Concentration by Ferriscan|
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