An increasing number of patient treatment guidelines for thalassaemia, sickle cell disease, myelodysplastic syndrome and haemochromatosis recommend using MRI to quantitatively measure liver iron concentration. Please note that a reference to R2 MRI is referring to FerriScan.
The following are excerpts from treatment guidelines – click on the title to view the full document.
UK Forum on Haemoglobin Disorders, Standards for the Clinical Care of Children and Adults with Thalassaemia in the UK, 2016
(Extracts from) Monitoring and Management of Iron Overload
Liver Iron Concentration LIC should be assessed using a validated and standardised MR technique. R2 (FerriScan) is preferable to R2* because the methodology is more robustly standardised and has been licensed for use in routine clinical practice. MRI LIC methods should not be used interchangeably. In particular, sequential MRI estimations in an individual patient should be done with the same methodology.
A new, lower age limit for the commencement of MRI monitoring is suggested:
LIC and Myocardial iron should be monitored regularly in patients from age 7 or younger if able to tolerate MRI scanning without sedation.
Whilst the R2* techniques have been improved by various groups… the calibrations differ. At present a consensus has not been reached on the standardisation of R2* methodology for clinical use.
In addition to the stated Requirements please click here to read further Recommendations
Association of the Scientific Medical Societies in Germany, Guideline for diagnosis and treatment of secondary iron overload in patients with congenital anemias, 2015
FerriScan is recommended to clinicians in Germany for the management of congenital anemias such as Sickle Cell Disease.
US Department of Health and Human Services, Evidence-based Management of Sickle Cell Disease, Expert Panel Review, 2014
"In patients who receive chronic transfusion therapy, perform serial assessment of iron overload to include validated liver iron quantification methods such as liver biopsy, or MRI R2 or MRI T2* and R2* techniques. The optimal frequency of assessment has not been established and will be based in part on the individual patient’s characteristics. (Strong Recommendation, Moderate-Quality Evidence)"
Thalassaemia International Federation, Guidelines for the Management of Transfusion Dependent Thalassaemia, 3rd Edition, 2014
"A note of caution is that the different MRI techniques may not be equivalent – at least in the manner they are currently calibrated and practiced. The first widely used technique was the T2* technique (Anderson 2001), where liver biopsy was used to calibrate the method. Although this demonstrated the principle of T2* to measure liver iron, unfortunately due to factors such as long echo times (TE 2.2-20.1 ms), and multi breath-hold acquisition, the calibration differs from later techniques, and can underestimate LIC by two-fold. Therefore studies using this calibration may underestimate LIC (Garbowski 2009). The R2 based Ferriscan technique appears to have acceptable linearity and reproducibility up to LIC values of about 30 mg/g dry wt (St Pierre 2005), with an average sensitivity of >85% and specificity of >92% up to an LIC of 15 mg/g dry wt, and has been registered in the EU and US. For calibration of Ferriscan, the MRI machine must use a Phantom supplied by the company, while the data acquired is sent via internet for analysis by dedicated Ferriscan software (payment per scan analyzed). A particular advantage of this technique is that it can be applied with little training, at any centre with a reasonably up-to-date MRI machine"
The Fred Hutchinson Cancer Research Center / Seattle Cancer Care Alliance – Long-term follow-up after hematopoietic stem cell transplant general guidelines for referring physicians (July 2014)
"While measurement of liver iron concentration is the gold standard, an iron-specific magnetic resonance imaging test (FerriScan) is highly accurate in measuring liver iron and is an alternative to liver biopsy for the measurement of hepatic iron content."
The Northern California Comprehensive Thalassemia Network and Children's Hospital, Oakland – 2012 Thalassemia Standards of Care Guideline
"The Use of Imaging to Monitor iron Overload and Chelation Therapy.
LIC is one way to determine total body iron content. While liver biopsy determination of LIC has been recommended for years, recent progress with MRI imaging provides an expedient and non- invasive way to directly measure LIC…”. “A FerriScan is a commercially available and validated system for quantitative MRI measurements of iron."
"May 31, 2012 – The Cooley’s Anemia Foundation strongly supports the consensus recommendations of the Thalassemia Clinical Research Network (TCRN) to obtain at least annual MRI for hepatic iron and cardiac iron T2* MRI beginning at age 10 years (with more frequent measurements considered for patients with cardiac T2* <10-20 ms) and an annual liver iron measurement, without a specified starting age, for transfusion-dependent patients and to adjust chelation in response to these measurements. We recommend that hepatic MRI methods be available to patients with thalassemia and other iron overload disorders."
"FerriScan® R2 is an FDA approved, MRI-based proprietary data analysis method capable of accurately measuring liver iron concentrations in patients regardless of the amount of iron in their liver, a feature particularly important for thalassemia patients with heavy iron loading. MRI image data are acquired on a local scanner and electronically transmitted to a central data analysis center that is ISO 13485 certified."
University Health Network, Toronto General Hospital, Canada – 2012 Guidelines for the Care of Patients in the UHN Red Blood Cells Disorders Program.
Toronto General Hospital provides FerriScan for measurement of LIC in patients with thalassemia, sickle cell disease and other transfusion-dependent anaemias under this program. The Guidelines state:
"R2-MRI (FerriScan) appears to be the most accurate non-invasive measure of hepatic iron loading."
"MRI is the primary tool used to monitor and make decisions regarding change in chelator dose or strategy."
"The expert panel considers it to be a very useful method of monitoring liver iron load and in directing iron chelation therapy. An appropriate monitoring strategy would comprise annual R2 MRI for the majority, while this can be extended to every 2 years for patients with normal LIC or at the lower end of the ideal range (e.g. 3 – 5 mg/g dry weight) when there has been no change to chelator regimen, and perhaps increased to every 6 months in at-risk patients, such as those with LIC above 15 mg/g dry weight. LIC results should also be correlated with standard liver function tests."
FerriScan and other MRI iron assessment methods provide a non-invasive and cost-effective means to monitor liver iron concentration in transfused patients with thalassemia, sickle cell disease and other blood disorders as well as patients with haemochromatosis."
"FerriScan is an MRI-based technology capable of accurately measuring liver iron concentrations in all patients regardless of the amount of iron in their liver, a feature particularly important for patients with heavy iron loading often found with thalassemia. Some of the other MRI-based methods are less accurate at higher iron concentrations."
"The Cooley’s Anemia Foundation believes that MRI iron assessments, including FerriScan, should be available to all patients who rely on iron overload measuring to identify excess iron which accumulates in the liver and which leads to serious complications such as liver fibrosis and organ failure. Regular monitoring of liver iron can improve the management of iron overload leading to prolonged and improved quality of life. There is significant clinical and scientific evidence available to support this technique as a means to monitor liver iron concentrations in patients with thalassemia."
The 2008 “Guidelines for the clinical management of Thalassaemia” (updated 2nd edition), written by the Thalassemia International Federation (TIF):
“LIC can also now be measured using MRI techniques, previously limited to a relatively narrow linear range. One recently described approach, is the R2 or FerriScan technique which appears to have acceptable linearity and reproducibility over the range of clinical interest (St Pierre TG, et al, 2005). The technique demonstrates an average sensitivity of >85% and specificity of >92% up to an LIC of 15 mg/g dry wt, and has been registered in the EU and US. For calibration, the MRI machine must use a Phantom supplied by the company, while the data acquired is sent via internet for analysis by dedicated FerriScan software (payment per scan analysed). A particular advantage of this technique is that it can be applied with little training, at any centre with a reasonably up-to-date MRI machine.”
The Italian Society of Hematology Practice Guidelines published in 2008:
“Nine studies of at least 10 thalassemic patients that evaluated the accuracy of measurement of LIC by MRI, and included a quantitative measurement of MRI signal and a detailed description of the patient population were selected. Strong linear correlations (R2=approximately 1.0) were demonstrated in four studies. The best result was obtained with the R2 methodology which resulted in a curvilinear relationship between R2 and LIC by biopsy over the entire clinically relevant range of LICs” and “evidence of the accuracy of non-invasive methods for assessment of liver iron concentration is sufficient to recommend MRI technology as a feasible alternative to liver biopsy. R2 sequences and individual local calibration are recommended”.
The “Standards for the clinical care of children and adults with Thalassaemia in the UK” published by the UK Thalassaemia Society in 2008 (2nd edition):
“All patients should have access to MRI modalities (Cardiac T2* MRI and either R2 or T2* of liver) for monitoring myocardial and liver iron. MRI is an attractive alternative for liver iron estimation since magnetic relaxation times are sensitive to tissue iron levels. The R2 (1/T2) technique (Ferriscan®) has been registered in the European Union, and can be done on a standard MRI scanner, with data sent electronically to a commercial organization for analysis (St. Pierre et al 2005). The T2* technique has the advantage that it can be done at the same time as the T2* cardiac scan (Anderson et al 2001) but is probably less accurate in measuring liver iron levels.”
The “Standards for the clinical care of adults with sickle cell disease in the UK” published by the UK Sickle Cell Society in 2008 (1st edition):
“All patients who have been previously transfused or are currently undergoing regular transfusions, whether top-up or exchange, should have regular quantitative monitoring of liver iron concentration using MRI”. "The quantitation of liver iron by MRI is one of the most significant recent advances in iron monitoring. The most widely adopted method is based on the measurement of tissue proton transverse relaxation rates (R2), showing excellent correlation with liver iron concentration (LIC) measured by biopsy. Algorithms predicting risk of complications from liver biopsy LICs have been applied to LICs obtained by MRI, and hepatic iron remains the best measure of total body iron loading."
The Nursing Practice Guideline: Care of the patients with sickle cell disease and iron overload, published by the International Association of Sickle Cell Nurses and Physician Assistants in 2008:
“Effective management of iron overload begins with frequent assessment of iron burden. Ideally this should be a quantitative method of iron measurement which is safe, effective and provides a high level of accuracy.” It lists FerriScan as achieving these criteria and thus is a suitable method for measuring LIC."
Wells and colleagues state in their publication from 2008 “Iron overload in myelodysplastic syndromes: a Canadian consensus guideline”:
“The most accurate and precise MRI technique for measurement of LIC was developed by St. Pierre et al., who found mean liver proton relaxation rates (R2) correlated strongly with LIC, as determined by biopsy across a broad range of LIC values.”