FerriScan

FerriScan: Patient Management Guidelines

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

Requirements

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."

The Cooley's Anemia Foundation (USA) 2012 Position Statement

"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 2011 Australian Guidelines for the assessment of iron overload and iron chelation in transfusion-dependent thalassaemia major, sickle cell diseases and other congenital anaemias.

"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."

The Cooley's Anemia Foundation (USA) 2010 Position Statement

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.”

Iron Overload in Cancer Survivors

Iron overload is increasingly recognised as a possible complication in cancer survivors who received multiple blood transfusions as part of their cancer therapy. Iron overload can result from treatments for both blood and solid tumours and can persist for years after cancer treatment. Excess iron is deposited in tissues of the body, potentially causing tissue damage and organ failure. The duration of exposure to high iron burden is directly related to adverse outcomes. As such, a reliable, non-invasive, and accurate measure of body iron stores is required to manage the treatment of iron-related toxicity.

FerriScan is globally recognised as the gold standard for quantitative measurement of liver iron concentration. Liver iron concentration provides the best measurement of total body iron stores, assisting clinical decisions on initiation and adjustment of phlebotomy or chelation therapy. FerriScan can reliably and accurately screen for iron overload in cancer survivors who have a history of blood transfusions, overcoming the poor sensitivity and specificity of serum ferritin and avoiding reliance on transfusion records, which can be incomplete.

For more information on FerriScan and its clinical benefits for monitoring and managing iron overloaded patients please watch this short video:

 

Dr Angela Smith, Assistant Professor, Division of Pediatric Blood and Marrow Transplantation at the University of Minnesota, commented on the importance of monitoring and managing iron overload in cancer survivors:

“Cancer survivors with excess iron may be exposed to this iron for years ahead if untreated, so timely monitoring and reduction of iron burden is an important goal. In our recent data we found even at relatively low thresholds of serum ferritin, liver iron concentration can be elevated in these patients. Conversely, a high serum ferritin, which may be caused by inflammation or other factors, may not be reflective of high liver iron concentration.

FerriScan provides us with a standardized and reliable tool to screen cancer survivors and guide treatment where required. FerriScan is especially suitable for pediatrics as it is free-breathing and quick. It is also unaffected by the presence of fat in the liver, which can be an issue in cancer survivors as a result of their therapy. We recommend that all patients who have undergone hematopoietic stem cell transplantation (HSCT) or those who have received > 10 transfusions should be considered for assessment using FerriScan.”

For further clinical information including information in the literature and guidelines regarding the monitoring of iron overload in cancer survivors please see out Cancer Survivor Fact Sheet:

FerriScan Fact Sheet - Cancer Survivors

 

If you are interested in learning more about monitoring iron overload in cancer survivors please sign up below and we will keep you informed:

 

 

 

 

Reimbursement

Canada

FerriScan is reimbursed in all Canadian provinces as an 'Out-of-Country Medical Service'. The treating clinician must forward an application for each patient to the province's Ministry of Health (MOH) for approval. Once approved, the MOH will grant a timeframe for the patient to have their FerriScan and/or Cardiac T2*. 

To help with the application process, we've compiled a list of resources that may help you with your prior approval submissions:

Ontario

Prior Approval for Full Payment of Insured Out-of-Country (OOC) Health Services - Rescheduled FerriScan

Prior Approval for Full Payment of Insured Out-of-Country (OOC) Health Services - Annual FerriScan

Prior Approval for Full Payment of Insured Out-of-Country (OOC) Health Services - Repeat FerriScan

Prior Approval for Full Payment of Insured Out-of-Country (OOC) Health Services- Blank form

British Columbia

Out-of-Country Health Services Funding Application - Prefilled

Out-of-Country Health Services Funding Application - Blank form

Alberta

Out-of-Country Health Services Claim Form - Prefilled (If it doesn't open, try using Acrobat Reader) 

Out-of-Country Health Services Claim Form - Blank form (If it doesn't open, try using Acrobat Reader

Out-of-Country Health Services Application Process - Information

Manitoba

Pre-Approval FerriScan Information - FerriScan Info Pack (Word Doc)

Manitoba Out-of-Province Medical Referrals - Information

Saskatchewan

Pre-Approval FerriScan Information - FerriScan info Pack (Word Doc)

Coverage for Services - Unavailable in Canada - Information

Quebec

Pre-Approval FerriScan Information - FerriScan Info Pack (Word Doc)

Medical services covered outside Quebec - Information

Nova Scotia

Prior approval for out-of-country services - Information

 

Germany

Generally, in-patients receive full reimbursement for under DRG and have no out-of-pocket expenses.

For ambulatory diagnosis with FerriScan, if the patient stays less than 24 in the hospital, there is no general reimbursement. Either the patient is paying it out-of-pocket as so called IGeL or he can do an individual case by case application (Einzelfallantrag) with his health insurance.

 

UK

FerriScan is reimbursed at public hospitals through the local NHS Trust system.

 

USA

FerriScan has been used in the United States since 2005, when FDA clearance for FerriScan was obtained. Since that time, approximately 10,000 FerriScans have been performed for US patients at a number of US hospitals and radiology facilities.

The cost of the MRI scan (or part of the cost) is usually covered by insurance companies (payers). Pre-authorisation is recommended, as is common for MRI testing. However, the cost associated with the FerriScan image analysis may not be covered, resulting in the hospital or patient having to cover this cost, together with any co-pay associated with the imaging.

FerriScan has now been deemed eligible for reimbursement by some US Insurance Companies:

  • Health Net. Prior authorization is required to confirm the medical necessity of a FerriScan
  • Kaiser Permanente SE Atlanta. Prior authorization is required to confirm the medical necessity of a FerriScan
  • Medical Mutual of Ohio. No prior authorization is required

Resonance Health is currently working on gaining a suitable CPT code for the MRI post processing work. 

 

Rest of World

Resonance Health is continuing to work with the clinical community and patient organisations towards appropriate funding pathways for patients who need to access to FerriScan and Cardiac T2* services.

Please email for further information.

 

Updated: 22nd-December-2017

FerriScan® Information for Patients

FerriScan - the Non-invasive Liver Iron Test

FerriScan is a magnetic resonance imaging (MRI)-based technology for the non-invasive measurement of liver iron concentration. The test is designed to assist in the diagnosis and treatment planning for patients with iron loading disorders (commonly referred to as "iron overload" conditions).

Perth patient, John Falconer, who was diagnosed with haemochromatosis when he was 75, says that FerriScan was a great alternative to an invasive liver biopsy.

"I have had three MRI's now and would recommend FerriScan to anyone. The results are quick and give a very informative report and accurate reading of your iron liver concentration. The scans have helped monitor and plan my treatment. I certainly wouldn't have wanted to have a liver biopsy."
- John Falconer.

What Does FerriScan Offer You?

  • A non-invasive - safe and painless alternative to biopsy.
  • An accurate result, allowing for early disease detection which can prevent long term damage.
  • Large image area which decreases sampling error and provides a more reliable and meaningful result than liver biopsy.
  • A faster alternative, resulting in reduced anxiety for patients by providing a reduction in testing and result waiting times.
  • A test which can be used repeatedly, allowing for increased quality of life through more efficient testing and treatment programs.

"I was a nurse and yet I'd never heard of haemochromatosis or iron overload. I thought if I hadn't heard of it, then there were probably many in the medical community who hadn't either and people were most likely walking around with iron overload like me and remaining undetected for years. The FerriScan was quick and painless and is an excellent alternative to liver biopsy for patients who want to find out their exact level of iron loading. The Haemochromatosis Society is working with the providers of FerriScan, Resonance Health, to promote awareness of iron overload and improve health outcomes for people affected by this disease."
- Margaret Rankin; Patron and Past President of Haemochromatosis Australia.

FerriScan Fact Sheets

 

 

FerriScan® Information for Clinicians

FerriScan is being used by clinicians in over 30 countries worldwide to aid their diagnosis, management and monitoring of iron overload.

FerriScan is a solution with proven value in improving the health outcomes of patients suffering from diseases such as thalassaemia, sickle cell disease, haemochromatosis and myelodysplastic syndrome.

Frequently Asked Questions

Case Studies

A number of case studies referencing FerriScan have been published by centres of excellence:

Use of FerriScan in Disease Management

FerriScan provides the clinician with:

  • A baseline measurement of the precise concentration and distribution of iron in the liver
  • Assistance in providing a definitive iron overload diagnosis
  • The ability to optimise treatment based on the level of iron loading; thereby enabling positive treatment outcomes

Use of FerriScan in Iron Overload Management Protocols

Iron Overload Information and Evidence of FerriScan Use (Presentations)

Scientific Evidence in Iron Overload Measurement

Resonance Health has developed a reputation for the highest standards of scientific rigour, which is underpinned by our company-wide commitment to quality and continuous improvement.

FerriScan has been validated by international regulatory authorities and is widely used by major pharmaceutical companies in clinical trial settings.

A number of scientific publications have provided evidence for the use of FerriScan in clinical management of iron overload conditions.

FerriScan: Patient Management Guidelines

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.

For a compiled list of treatment guidelines involving R2 MRI (FerriScan), please click here.

Easy Setup for Radiology Centres

Following an easy setup process, Resonance Health provides a range of clinical image analysis services of MRI scans via a unique quality assured service delivery model:

  • FerriScan® – the global gold standard for the measurement of liver iron concentration (LIC)
  • Cardiac T2* - assessment of cardiac iron (FerriScan add-on)
  • HepaFat-Scan® - measurement of volumetric liver fat fraction (VLFF)
  • Bone Marrow R2-MRI – assessment of bone marrow iron

Image data is securely transferred to Resonance Health’s central ISO certified Service Centre, where it is analysed by our team of experts. Result reports are then made available for download by authorised Radiology staff.

  • Services are charged per analysis only – there are no subscription or licence fees
  • Radiology Centres are not required to purchase any additional hardware or software
  • The imaging protocols require no contrast agents and can be established on most 1.5 Tesla scanners from Siemens, GE, and Phillips.

4 Step Easy Setup Process

To learn more about our services and how they can benefit your Radiology Centre, download our information sheets below.

Technical Requirements for Acquiring FerriScan and Bone Marrow Images

FerriScan requires an approximately 10 minute scan using a single spin echo sequence.

Minimum Radiology Centre requirements for the acquisition of suitable data for FerriScan and Bone Marrow R2-MRI:

  • MRI scanner with a field strength of 1.5 Tesla
  • Single spin echo sequence with a minimum TE of 6.0 ms
  • A torso / chest / abdomen receiver coil
  • The ability to transfer images to a networked computer with an internet connection

Technical Requirements for Acquiring Cardiac T2* Images

Cardiac T2* requires a single breath hold scan using a multi gradient echo sequence.

Minimum Radiology Centre requirements for the acquisition of suitable data for Cardiac T2*:

  • Radiology Centre personnel with experience in acquiring cardiac images.
  • MRI scanner with a field strength of 1.5 Tesla and a cardiac MRI package that includes:
    • Radio Frequency coil suitable for acquiring cardiac images
    • ECG facility
    • Single breath-hold, multi-echo T2* sequence with:
      • Total of 8 echo times
      • Minimum TE between 2 and 3 ms
      • Maximum TE between 16 and 23 ms
  • The ability to transfer images to a networked computer with an internet connection

Technical Requirements for Acquiring HepaFat-Scan Images

HepaFat-Scan requires one to three single breath hold scans using a gradient echo sequence (the number of breath holds being dependent on the scanner model).

Minimum Radiology Centre requirements for the acquisition of suitable data for HepaFat-Scan:

  • MRI scanner with a field strength of 1.5 Tesla
  • Gradient echo sequence
  • A torso / chest / abdomen receiver coil
  • The ability to transfer images to a networked computer with an internet connection

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Iron Overload

What is iron overload?

Iron overload is the accumulation of excess iron in the body. People who receive multiple blood transfusions in the course of treatment for certain diseases are at particular risk of iron overload as the body has no natural mechanism for excreting iron. One unit of transfused red cells delivers approximately 250mg of iron to the body. People with thalassaemia, sickle cell anaemia, Diamond Blackfan anaemia and myelodysplastic syndrome may receive regular blood transfusions, resulting in a need to monitor total body iron, and where appropriate, to remove it through chelation therapy. More recently, iron overload is becoming increasing recognised as a complication in cancer survivors who received multiple blood transfusions as part of their cancer therapy. To read more about the application of FerriScan in this setting please refer here: Iron Overload in Cancer Survivors.

Iron overload can also be caused by excessive absorption of iron from the diet, as occurs in the hereditary disease haemochromatosis.

 

Clinicians managing these conditions require a complete picture of a patient’s body iron stores to inform their decisions on treatment options.

Accurate monitoring of liver iron concentration (LIC) provides essential information in the prevention of iron-related complications and premature death in iron overloaded patients.

Organ iron load graph
Modell B. Br Med Bull. 1976;32:270

This graph shows the organs in which iron deposition occurs when there is excess iron in the bloodstream.

The liver is the primary site of iron storage in the body.

Why Monitor Liver Iron?

Deposits of iron in tissues cause organ damage, and accumulation occurs primarily in the liver. Once the iron-binding capacity of the liver has been exceeded, deposition occurs in other organs, such as the heart. This causes a greater risk of cardiac complications and premature death.

Therefore, monitoring of liver iron concentration provides an early warning of potential cardiac iron loading and its attendant health implications.

Update on Imaging: Detection of Iron in Liver in Heart - Webcast and Powerpoint presentation by Professor Tim St Pierre – from European Society of Haematology website: 'The Curriculum in Iron Metabolism and Related Disorders'

Why Monitor Cardiac Iron?

The deposition of cardiac iron has profound implications for patient health and indicates that urgent measures must be taken to reduce body iron loading.

An analysis of both liver and cardiac iron therefore enables clinicians to get a more complete picture of body iron loading, to appraise the immediate health risks to the patient and inform their decisions on treatment options.

FerriScan® and Cardiac T2*Fact Sheet