Protocol - Determination of Liver Iron Concentration by Ferriscan
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 Ferriscan (MRI R2).
The choice of quantifying liver iron by magnetic resonance imaging (MRI) R2* or by Ferriscan (MRI R2) depends on the expertise and equipment available to investigators.
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 Ferriscan (MRI R2)
A description of MR studies for the determination of liver iron by R2 can be found in St Pierre et al., 2004. Briefly, MR scans are performed on a 1.5 Tesla scanner. Axial image slices through the liver are acquired in breathing subjects with a single-spin-echo pulse sequence with a pulse repetition time of 2500 milliseconds and spin-echo times ranging from 6 to 18 milliseconds. Images are then sent to a commercial laboratory for processing using proprietary Ferriscan software.
Personnel and Training Required
A trained magnetic resonance imaging (MRI) technician is required to administer the MRI, and MRIs must be processed by proprietary Ferriscan software at a licensed laboratory.
A magnetic resonance imaging (MRI) machine with a field strength of 1.5 Tesla and spin-echo sequence with a minimum echo time of 6 milliseconds.
|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
Adolescent, Adult, Senior
Ages 9 and older
MRI is a non-invasive, valid, and reliable method that has been used to quantify liver iron content in National Institutes of Health–funded clinical trials.
|caDSR Common Data Elements (CDE)||Magnetic Resonance Imaging R2* Liver Iron Concentration Unit of Measure||7765250||CDE Browser|
Process and Review
Protocol Name from Source
St. Pierre, T. G., et al. Single spin-echo proton transverse relaxometry of iron-loaded liver. NMR Biomedicine, 2004
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
St. Pierre, T. G., Clark, P. R., & Chua-anusorn, W. (2004). Single spin-echo proton transverse relaxometry of iron-loaded liver. NMR in Biomedicine, 17(7), 446–458.
American College of Radiology. (2019). ACR-AAPM technical standard for diagnostic medical physics performance monitoring of magnetic resonance imaging (MRI) equipment. 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
Gandon, Y., Olivie, D., Guyader, D., Aube, C., Oberti, F., Sebille, V., & Deugnier, Y. (2004). Non-invasive assessment of hepatic iron stores by MRI. The Lancet, 363, 357–362.
St. Pierre, T. G., Clark, P. R., Chua-anusom, W., Fleming, A. J., Jeffrey, G. P., Olynyk, J. K., Pootrakul, P., Robins, E., & Lindeman, R. (2005). Noninvasive measurement and imaging of liver iron concentration using proton magnetic resonance. Blood, 105(2), 855–861.
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):806-10.
|Variable Name||Variable ID||Variable Description||dbGaP Mapping|
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|
There are no publications listed for this protocol.