At what threshold of elevated ferritin (iron storage protein), elevated Alanine Transaminase (ALT), and elevated Aspartate Transaminase (AST) should an MRI R2* be ordered to assess for iron overload in the liver?

When to Order MRI R2* for Elevated Ferritin and Transaminases

Order MRI R2 when ferritin exceeds 1,000 μg/L in combination with elevated liver enzymes, or when there is unclear cause of hyperferritinemia with biochemical iron overload (elevated transferrin saturation and ferritin), regardless of specific ALT/AST thresholds.* 1

Primary Indications for MRI R2* Based on Laboratory Values

Ferritin-Based Thresholds

• Ferritin >1,000 μg/L with elevated liver enzymes (ALT/AST) is a strong indication for MRI R2 to assess liver fibrosis risk and quantify iron burden* 1
• The specific ALT/AST elevation level is not defined in guidelines; any elevation above normal range in context of ferritin >1,000 μg/L warrants imaging 1

When Cause of Hyperferritinemia is Unclear

• MRI R2 should be used when hyperferritinemia has an unclear etiology, particularly when both transferrin saturation and ferritin are elevated* 1
• This applies even if ferritin is below 1,000 μg/L when biochemical iron overload is present 1

When Positive Liver Iron Staining is Present

• If liver biopsy has already shown positive iron staining but quantification is needed, MRI R2 should be ordered to quantify hepatic iron concentrations* 1

Clinical Context That Modifies Thresholds

Patients WITHOUT HFE p.C282Y Homozygosity

• In patients without homozygosity for p.C282Y and/or presence of additional risk factors (metabolic syndrome, chronic alcohol excess), non-invasive MRI quantification is essential for diagnosis and management 1
• These patients require MRI R2* at lower thresholds because the diagnosis is less certain 1

Patients WITH HFE p.C282Y Homozygosity

• In homozygous p.C282Y patients with elevated transferrin saturation and hyperferritinemia without additional risk factors, MRI is not required for diagnosis but enables determination of degree of iron overload 1
• MRI R2* acts as a predictor of phlebotomies required for treatment in this population 1

Patients with Metabolic Syndrome or Chronic Liver Disease

• In patients with metabolic syndrome, increased alcohol consumption, cirrhosis, or chronic liver disease who have elevated ferritin and transaminases, MRI R2 helps distinguish true iron overload from dysmetabolic hyperferritinemia* 1
• This is critical because there is no conclusive evidence supporting phlebotomy in these patients, so accurate iron quantification guides management 1

Technical Specifications for Ordering

Preferred Method and Field Strength

• R2-based relaxometry is the first-line method with high-level evidence, recommended over other techniques* 1, 2
• Both 1.5T and 3T are acceptable, but 1.5T is preferred for suspected severe iron overload 1, 2
• 1.5T reliably quantifies up to ~40 mg/g liver iron concentration (LIC), while 3T is limited to ~26 mg/g 1, 2

Required Protocol Parameters

• Request confounder-corrected R2 with short echo times (<1 msec), short echo spacing (<1 msec), 6-12 echo times, and noise correction* 1, 2
• Fat correction must be specified to avoid significant measurement bias 1, 2

Assessment of Extrahepatic Iron

Cardiac MRI Indications

• Cardiac MRI can be performed in patients with hemochromatosis and signs of heart disease, and should be performed in juvenile forms of hemochromatosis 1
• Cardiac iron deposition is a late event occurring after liver and spleen accumulation 3

Multi-Organ Assessment

• MRI can assess iron distribution in liver, spleen, pancreas, heart, and brain when iron overload disorder is suspected 1
• Early hemochromatosis shows predominant hepatic iron with minimal spleen involvement, while ferroportin disease and transfusional overload show increased spleen iron 1

Common Pitfalls to Avoid

Relying on Ferritin Alone

• Ferritin is an acute phase reactant elevated in inflammatory and neoplastic conditions, making it insufficient alone to ascertain iron overload 1
• Transferrin saturation and ferritin are surrogates of body iron status but often inadequate without tissue quantification 1

Discordance Between Ferritin and MRI

• In 22 of 92 paired examinations, discordance between R2 and ferritin was found, particularly in patients under chelation therapy* 4
• Treatment response may be misinterpreted when only ferritin is considered, especially with unexpected ferritin changes during chelation 4

Using Different MRI Methods for Follow-up

• The same MRI method must be used for all future studies to allow accurate longitudinal comparison 5
• Different techniques and field strengths produce non-comparable results 1

Reporting Requirements

Essential Elements

• The radiology report must include the specific MRI method used, literature citation describing the calibration method, and laboratory reference values used for LIC calibration 1, 5
• Quantitative LIC values should be reported in both mg/g dry weight and μmol/g 5