Products

Phantoms

Cardiac T1 Mapping and ECV Phantom (T1MES) 


What is T1MES?

The T1 Mapping and ECV Standardization Program (“T1MES”) was developed to explore T1 mapping quality assurance on 1.5 and 3T magnets across numerous CMR centres worldwide. This program progressed with the development and regulatory approval of a T1MES phantom.

The T1MES Phantom was originally designed by a team of experts including cardiologists, physicists, engineers and national metrology institutes, led by Prof James C Moon (University College London) and Dr Peter Gatehouse (Imperial College London).

As part of this study, Resonance Health manufactured an initial batch of ~70 phantoms in 2015 for distribution to CMR centres worldwide engaged in the cardiovascular magnetic resonance program. Resonance Health is the sole manufacturer of these phantoms and due to continued requests from customers, it is expected that the next batch of phantoms will be manufactured in mid-2021.

Why use a T1MES phantom?

  1. Provides useful reassurance to centres that T1 values are unchanged for any technical reason over long periods of application;
  2. Enables some correction to be applied in case a sudden shift in technique is exposed by its regular scanning;
  3. Permits systematic inter-sequence and inter-manufacturer analyses, aiming ultimately towards corrections to a ‘standard’.

How to purchase a T1MES phantom?

If you are interested in purchasing a T1MES phantom, please register your interest now to order a phantom as part of the current or upcoming production.  To place an order, please fill out the following Order Form and return it to Resonance Health directly at .  One of the Resonance Health team members will contact you for further details of your order.

 

Spleen R2*/T2* Phantom


Resonance Health provides an analysis service to customers who require Spleen R2*/T2* analysis to quantitatively assess iron loading in the spleen.  This service is for investigational use only as regulatory clearance has not been applied for, and results are to be interpreted in the context of a clinical study.   As part of service setup, it is requested that sites initially scan a R2*/T2* Phantom using the spleen R2*/T2* imaging protocol and submit the data to Resonance Health to verify the parameter settings and image quality before subject scanning commences.

To find out more information, please contact Resonance Health directly at .

 

Cardiac T2* Phantom


Cardiac iron-loading can be assessed by MRI measurement of cardiac T2*  (cardiac T2* is globally recognised as the gold standard in the assessment of cardiac iron load via T2* measurement). As part of service setup, it is requested that sites initially scan a Cardiac T2* Phantom or a Test Patient with the Cardiac T2* imaging protocol and submit the data to Resonance Health to verify the parameter settings and image quality.

To find out more information, please contact Resonance Health directly at .

 

FerriScan Phantom Pack


The FerriScan Phantom Pack is used as part of the setup process for FerriScan to ensure standardisation and accuracy of setup of the FerriScan protocol. 

The FerriScan Phantom Pack consists of a sealed pack of vials containing a range of standardisedconcentrations of manganese chloride (MnCl2) solution. The Phantom Pack is designed to replicate the range of liver iron loading seen in clinical practice. 

The FerriScan Phantom Pack is supplied as an outer box containing the “Instructions for Use: FerriScan Phantom Pack” and a sealed inner box. The inner box is scanned as part of the MRI scanner validation procedure.   

A FerriScan Phantom Pack must be scanned by every MRI scanner during setup to ensure the correct sequence has been used and images are acquired correctly.  

Bone Marrow R2-MRI

Bone Marrow R2-MRI is an MRI-based solution for assessing iron levels in the bone marrow. Both decreased and increased bone marrow iron are of clinical significance; for example multiple blood transfusions can result in greatly increased bone marrow iron and conversely, the definitive test of iron deficiency is examination of iron from bone marrow aspirates.

Elevated Bone Marrow Iron in Bone Marrow Transplant Recipients

Elevated bone marrow iron levels prior to bone marrow transplant are associated with complications and a range of poorer health outcomes following transplant, including:

  • Lower overall survival and lower disease-free survival
  • Independent risk factor for invasive aspergillosis- a major cause of death following hematopoietic stem cell transplantation\
  • Increased risk of severe infection or bacterial infection

Quantitative assessment of bone marrow iron pre-transplant may help to predict complications and the prognosis of patients post-transplant and also inform the use of precautionary interventions (anti-bacterial, anti-fungal, iron chelation, or phlebotomy) to improve patient outcomes.

Dr Josu de la Fuente, Consultant Paediatric Haematologist and Senior Lecturer at Imperial College London and Director of the Paediatric Blood and Marrow Transplant Programme, commented:

“A non-invasive standardised method for assessing bone marrow iron may provide important additional clinical information to assist in managing patients being considered for bone marrow transplant as severe complications such as graft versus host disease can, in some cases, become more severe and costly to manage than the original disease of the patient.”

The Worldwide Network for Blood and Marrow Transplantation estimates that more than 50,000 patients are transplanted annually for certain cancers, such as leukaemia, lymphoma, myelodysplasia, or for diseases that affect the production of bone marrow cells, such as aplastic anaemia, severe immune system illnesses, sickle cell disease, and thalassaemia. Patients also require bone marrow transplantation as a result of chemotherapy for other diseases.

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Bone Marrow R2-MRI as an Alternative to Biopsy for Assessing Bone Marrow Iron Levels

The current gold-standard for assessing bone marrow iron is histopathological grading, which is semi-quantitative, non-standardised, and subject to large inter-observer error. Bone Marrow R2-MRI is non-invasive, quantitative, and correlates significantly with iron in bone marrow biopsy

(Figure 5: example in paroxysmal nocturnal hemoglobinuria).

 

 

Bone Marrow R2-MRI Process

Image data acquisition is performed at partner radiology centres across the globe with verified MRI scanners; ensuring quality control and standardisation of data acquisition. Data are then transferred electronically to Resonance Health’s ISO-certified central Service Centre via a secure online system.

Every MRI dataset undergoes stringent quality control checks, standardised patented analysis, a second read of analysis results, and quality assurance release. The report is then transmitted electronically back to the radiology centre with a mean R2 value reported in the range 10 to 200s-1. Normal range is 13.6 to 40.0 s-1.

Key Bone Marrow R2-MRI Features

  • Non-invasive, no contrast agents, and a scan time of approximately 10 minutes
  • Quantitative results correlate significantly with iron in bone marrow biopsy
  • Acquired with the FerriScan MRI scanning protocol – a single MRI scan can provide a picture of total body iron stores plus specific bone marrow iron levels
  • Image analysis and reporting is performed at a central ISO 13485 certified Service Centre
  • Now available for clinical application in Europe, Australia, and New Zealand for clinical studies and pharmaceutical trials globally.
  • Requires no breath-hold and may therefore be used for paediatric patients
  • Suitable for 1.5 T MRI scanners
  • There is no requirement for customers to purchase new software or hardware
  • Charge per scan only – no licence or subscription fees
  • Results available within a target time of two business days

Bone Marrow R2-MRI Availability

With the standard high level of scientific rigour and ISO-certified quality of all of Resonance Health’s services, Bone Marrow R2-MRI is now available for clinical application in Europe, Australia, and New Zealand. It is also available globally for clinical studies and pharmaceutical trials.

Comprehensive Iron Health Assessment

Bone Marrow R2-MRI data is acquired with the same MRI scanning protocol as FerriScan® - the regulatory cleared and globally recognised gold standard for measurement of liver iron concentration (LIC) - the most effective measure of total body iron stores. Bone Marrow R2-MRI can be performed as a standalone assessment or combined with FerriScan to provide more complete picture of a patient’s iron status. Resonance Health also provides a regulatory authority cleared Cardiac T2* measurement for heart iron assessment to enable better-informed decisions for the management of patients at risk of iron-induced organ damage.

FerriScan is currently used to assess body iron stores prior to transplant at leading institutions. The new bone marrow specific test has the potential to further assist clinical decision making pathways for patients being considered for bone marrow transplantation. Improved monitoring and management of iron prior to transplantation may assist in decreasing complications and improving health outcomes.

Please contact  to discuss partnering on your clinical, study, or trial needs. You can also download the Bone Marrow R2-MRI fact sheet here.

 
 
 
 
 
 
 
 

Products

Resonance Health currently has two products on the market; FerriScan® (with or without a Cardiac T2* component) and HepaFat-Scan®.

These products are magnetic resonance imaging based solutions that provide quantitative liver measurements, with the distinctive advantage over liver biopsy of being non-invasive. The products are provided via a unique Quality Assured Service Delivery model. All data is analysed in a central Service Centre with a patient report being returned to our customers. 

FerriScan and HepaFat-Scan have regulatory clearance in the USA, Europe and Australia and have been clinically validated against liver biopsy; demonstrating accurate, reliable and reproducible results.

FerriScan®

FerriScan is globally recognised as the gold standard for the quantitative measurement of liver iron concentration. It is extensively used in clinical settings for the management of patients with potentially life-threatening iron overload disorders and by pharmaceutical companies for the assessment of their investigational products in clinical trials.

FerriScan is also offered as a dual service in combination with a Cardiac T2* measurement to allow a more comprehensive assessment of iron overload.

HepaFat-Scan®

HepaFat-Scan provides a quantitative measurement of hepatic steatosis as a volume percentage of fat in liver tissue. It is available for the screening, diagnosis, treatment planning, and monitoring of patients at risk from fatty liver disease in a variety of clinical settings. Potential clinical applications include gastroenterology, hepatology, and surgical applications, as well as use by primary care physicians.

HepaFat-Scan® - MRI Measurement of Liver Fat

HepaFat-Scan is a non-invasive MRI-based solution for measuring the volume fraction of fat in liver tissue. HepaFat-Scan is provided as an image analysis service; with analysis and reporting provided from the Resonance Health ISO 13485 certified Service Centre via our Quality Assured Service Delivery model.

The HepaFat-Scan software is the first and only method with regulatory clearances (USA - FDA, Europe - CE Mark, Australia - TGA) for quantitative measurement of liver fat that has been clinically validated against independent measurements of the volume fraction of fat in liver biopsy specimens in a clinical study.

HepaFat-Scan reports volumetric fraction of fat in the liver, a measure that can be directly compared to a volumetric biopsy fat fraction measurement.

HepaFat-Scan is now available for routine clinical use and for use in pharmaceutical company clinical trials.

HepaFat-Scan Key Features: 

  • HepaFat-Scan is clinically validated against biopsy measurements of liver fat (59 cases)
  • Clinically insignificant bias compared with biopsy (1.4%)
  • Image analysis and reporting is performed at a central ISO 13485 certified Service Centre
  • HepaFat-Scan has international regulatory clearance and approvals (USA, Europe, Australia)
  • Results are available with a targeted turnaround time of two business days
  • HepaFat-Scan is non-invasive, requires no contrast agents and has a scan time of approximately two minutes
  • Single breath hold scan
  • Large liver region >300 times larger than biopsy, reducing sampling error
  • Results are accurate, reliable and reproducible over time and between MRI centres and models of scanner - making it suitable for clinical trials
  • There is no requirement for customers to purchase new software or hardware, resulting in minimal training requirements
  • High sensitivity and specificity when compared against histopathological assessment of steatosis
  • Suitable for 1.5 and 3 Tesla MRI scanners 

To see more information, view the HepaFat-Scan Fact Sheet.

Why Use HepaFat-Scan to Measure Liver Fat

HepaFat-Scan is quick, easy and painless, with an MRI scan time of only two minutes. HepaFat-Scan does not require any contrast agents and being MRI based there is no risk from radiation.

Histopathological assessment of a patient’s liver fat levels from a liver biopsy is commonly considered the gold standard for clinical assessment of liver fat. However, it is subjective, has a poor reproducibility and significant sampling error and suffers from the risks associated with an invasive procedure.

Ultrasound, while widely available, only has a sensitivity of approximately 70% and this is further reduced in obese patients. It is additionally hampered by factors such as fibrosis, edema and extrahepatic adipose tissue.

CT is also a widely available imaging modality that evaluates hepatic steatosis indirectly based on hepatic x-ray attenuation. Several factors other than fat (e.g. iron, copper, glycogen, fibrosis, edema, ingestion of drugs such as amiodarone and gold) affect CT attenuation values, resulting in unavoidable errors in fat quantification and low sensitivity for mild-moderate steatosis. Moreover, as CT relies on ionizing radiation, it is not suitable for use in children and for longitudinal monitoring of adults with liver fat. MR has also been used for quantitative assessment of fat and is widely accepted as superior compared to ultrasound and CT.

HepaFat-Scan is used in conjunction with a specific MRI data acquisition protocol that is a variation of the Dixon Method. Many MR fat quantification methods such as Magnetic Resonance Spectroscopy (MRS) and other Dixon based imaging methods report the fat:water proton ratio. This ratio is not directly comparable to a fat measurement from a liver biopsy specimen as it neither represents the percentage of parenchyma involved with fat nor the volume fraction of fat in the biopsy. Resonance Health has addressed this issue with HepaFat-Scan.

HepaFat-Scan measures the volumetric fat fraction of the liver tissue. This is a measure that is directly comparable to what can be seen and measured in a biopsy specimen; that is the fraction of the tissue that is observed to be fat. Hence, HepaFat-Scan can be used as a surrogate for liver biopsy measurement of hepatic steatosis.

/Hepafat-scan-Service-Model

Potential Clinical Applications

Gastroenterology and Hepatology Applications

  • Initial workup for NAFLD diagnosis and for patient education and counselling.
  • Liver fat analysis on patients already being screened or monitored for fibrosis or cirrhosis. Recent research indicates that patients with NAFLD and NASH can develop liver cancer without progressing through cirrhosis.

Surgical Applications

  • Scanning of patients with liver disease or liver cancer to provide guidance with treatment planning. The liver percent fat may help to determine how much liver can be safely resected or to determine whether to use a surgical or non-surgical treatment. A high level of liver fat may have a detrimental outcome on liver surgery.
  • Screening for suitability of living donors for liver transplants by assisting in determining the viability of the liver
  • Pre and post operative analysis of bariatric patients to track clinical outcomes.

Applications by Primary Care Physicians

  • HepaFat-Scan may be useful to screen patients prior to prescribing known hepatotoxic medications.
  • Monitoring of patients undergoing an intervention (e.g. limiting alcohol consumption or weight loss)
  • Monitoring of patients prescribed medications known to induce steatosis

HepaFat-Scan Clinical Validation

Resonance Health has completed a clinical study comparing 59 patient measurements of liver fat fraction using HepaFat-Scan and stereological analysis of liver biopsy sections. Stereology is a computer assisted analysis of each biopsy specimen to quantify the volume fraction of the biopsy that is fat. The HepaFat-Scan results can be directly compared against the biopsy measurements as both report a volume percentage of fat. The results of the comparison are illustrated in the figure below. A linear relationship between the two sets of measurements was found with a clinically insignificant bias (1.4% by Bland Altman analysis) between the two types of measurement.

clinical validation graph- HepaFat-Scan

The figure displays a comparison of HepaFat-Scan measurements of liver fat fraction with those measured from biopsy sections using stereology (n=59). The solid line is the line of equivalence. Symbols are colour/shape-coded to indicate the NAS CRN steatosis grade assessed by a histopathologist according to the below table using the Nonalcoholic Steatohepatitis Clinical Research Network grading scheme [Design and Validation of a Histological Scoring System for Nonalcoholic Fatty Liver Disease, Hepatology, June 2005, Kleiner et al]:

  • Grade 0: < 5% parenchymal involvement by steatosis
  • Grade 1: 5% - 33% parenchymal involvement by steatosis
  • Grade 2: >33%-66% parenchymal involvement by steatosis
  • Grade 3: >66% parenchymal involvement by steatosis

All grades of steatosis were represented in the study [Grade 0 (47%); Grade 1 (13%); Grade 2 (9%); Grade 3 (30%)]. The patients in the study had a range of aeitiologies including autoimmune hepatitis (n=3), alcoholic liver disease (n=2), chronic viral hepatitis B/C (n=16), non-alcoholic fatty liver disease (n=10), nonalcoholic steatohepatitis (n=17), primary sclerosing cholangitis (n=4).

Sensitivity and Specificity of HepaFat-Scan
Steatosis Grades

Grade 0 vs 1-3

(≥5%)

Grades 0-1 vs 2-3

(≥33%)

Grades 0-2 vs 3

(≥66%)

Sensitivity (%)

(95% conf interval)

96.77 (83-100) 100.00 (83-100) 100.00 (78-100)

Specificity (%)

(95% conf interval)

96.00 (80-100) 94.44 (81-99) 87.80 (74-96)
AUROC (standard error) 0.963 (0.032) 0.996 (0.005) 0.971 (0.019)
 

If you wish to use the HepaFat-Scan service or would like to know more about HepaFat-Scan, please send an email to

 
 

Cardiac T2* with FerriScan® – Dual Analysis Service

Cardiac T2* for Iron Assessment is a service that is offered seperately or as part of a dual analysis package with FerriScan to provide more comprehensive information regarding body iron stores.

The Liver and Heart in Iron Overload

Changes in liver iron concentration generally precede changes in heart iron loading, acting as an early warning of possible future cardiac complications. An immediate risk of iron-induced arrhythmia and cardiac failure can be assessed by MRI measurement of Cardiac T2*. Iron-induced damage to heart tissue can be halted and reversed if appropriate and timely chelation therapy is commenced.

Regular assessment of iron overload through Resonance Health’s quality assured FerriScan and Cardiac T2* Dual Analysis Service enables better informed decisions on the management of patients at risk of iron-induced organ damage.

Key Cardiac T2* Features

  • Provides important information for assessing the risk of cardiac failure or arrhythmia
  • Cardiac T2* is the most widely accepted MRI-based method for assessing heart iron loading
  • Cardiac T2* is charged per scan only and can be established on most 1.5T MRI scanners
  • Cardiac T2* is regulatory cleared by the FDA, TGA, and CE Mark

For further information, please refer to the FerriScan and Cardiac T2*Fact Sheet.

Key Resonance Health Dual Analysis Service Features

  • Provides a more complete picture of body iron loading than FerriScan or Cardiac T2* alone
  • Image analysis and reporting is performed at a central ISO 13485 certified Service Centre

 

If you wish to use the Cardiac T2* service or would like to know more about Cardiac T2*, please email  for more information.

 
 

FerriScan® – MRI Measurement of Liver Iron Concentration

FerriScan® provides an accurate measurement of liver iron concentration (LIC) through a non-invasive, MRI-based technology. The measurement is performed in a central Service Centre and provided via our unique Quality Assured Service Delivery model.

FerriScan® was regulatory cleared by the FDA for the measurement of LIC in 2005. In January 2013 FerriScan gained an additional clearance from the FDA as a companion diagnostic to aid in the identification and monitoring of non-transfusion-dependent thalassemia patients receiving therapy with deferasirox. FerriScan is internationally recongized as the gold standard in liver iron concentration (LIC) measurement.

The FerriScan process uses patented R2-MRI imaging technology. Acquired magnetic resonance images are securely transmitted to the Resonance Health Service Centre. The patented FerriScan analysis procedure produces a mean LIC measurement and a colour coded map reflecting the iron distribution across the liver.

FerriScan analysis provides proven accuracy in the determination of liver iron concentration and has the highest sensitivity and specificity over the range of liver iron concentrations of any MRI-based method of LIC measurement. Results that are reliable and reproducible over time and across different models of MRI scanner.

FerriScan was originally calibrated against liver biopsy in 105 patients with various iron overload conditions. A further multi-centre validation study on five different scanners with 233 patients concluded:

  • The FerriScan technique is robust
  • There is no shift in accuracy or precision across different MRI scanners
  • FerriScan is unaffected by fibrosis or chelation therapy
  • FerriScan can be used with patients of all ages

FerriScan is recommended in multiple clinical patient management guidelines. 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.

Key FerriScan Features

  • FerriScan provides an accurate, validated MRI-based measurement of liver iron concentration
  • FerriScan is regulatory cleared by the FDA, TGA, and CE Mark
  • FerriScan is non-invasive, requires no contrast agents and has a scan time of approximately 10 minutes
  • FerriScan has high sensitivity and specificity for measuring LIC
  • Image analysis and LIC reporting is performed at a central ISO 13485 certified Service Centre
  • FerriScan has international regulatory clearance and approvals (USA, Europe, Australia)
  • Results are available within a target time of two business days
  • FerriScan can measure LIC over the entire range encountered in clinical practice
  • FerriScan results are clinically validated to be unaffected by inflammation, fibrosis or cirrhosis
  • FerriScan requires no breath-hold and may therefore be used for paediatric patients
  • Results are accurate, reliable and reproducible over time and between MRI centres and models of scanner
  • There is no requirement for customers to purchase new software or hardware, resulting in minimal training requirements
  • FerriScan is suitable for 1.5 Tesla MRI scanners
  • FerriScan is charged per scan only

To see more information, view the FerriScan Fact Sheet.

Why Use FerriScan R2-MRI to Measure Liver Iron Concentration? 

FerriScan is quick, easy and painless, with an MRI scan time of only ten minutes. FerriScan does not require any contrast agents and being MRI based there is no risk from radiation.

The accurate Liver iron Concentration (LIC) measurement can be used by clinicians to monitor iron loading and adjust treatment regimes accordingly.

FerriScan provides a more accurate and reliable measure of LIC at any point in time than that provided by serum ferritin and patients need no longer undergo the painful, time consuming process of liver biopsy.

Unlike liver biopsy, which provides an analysis of LIC in only one small area, FerriScan analyses a cross-section of the liver. This area is typically thousands of times larger than biopsy, hence significantly reducing the biopsy sampling error.

The analysis of data by trained experts within a quality-controlled environment eliminates issues of inter-observer variability.

FerriScan is being used by clinicians in over 45 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.

From a Clinician’s Perspective

Dr Josu de la Fuente, Consultant Paediatric Haematologist and Senior Lecturer at Imperial College London and Director of the Paediatric Blood and Marrow Transplant Programme, speaks about the clinical benefits of FerriScan:

FerriScan is included in the routine treatment protocols for Thalassaemia at the Imperial College Healthcare. For example, information about Thalassemia and evidence for the use of FerriScan in paediatric management is included in the following protocol:

Additional FerriScan Information for Clinicians 

Service Delivery

Ferriscan-Service-Model

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.

If you wish to use the FerriScan service or would like to know more about FerriScan, please email .

 

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