MR Elastography

MR elastography (MRE) is a phase contrast MRI technique that measures tissue stiffness non-invasively and maps it across a whole organ. Increased stiffness is a marker of fibrosis, inflammation, congestion and tumour.

A passive driver placed on the body surface produces low frequency mechanical waves (50 to 60 Hz for the liver, 20 to 90 Hz for other organs) that travel through the tissue.

A motion sensitive gradient echo or spin echo sequence images the wave propagation, and an inversion algorithm converts the wave pattern into a colour map of stiffness in kilopascals (kPa).

The most common application is the liver. The study adds 5 to 10 minutes to a liver MRI.

The patient lies supine with the driver (a flat disc) strapped over the right lower chest, over the liver, and holds the breath at end expiration for 15 to 20 seconds for each slice. Three or four slices are acquired.

MRE is also used in the spleen, pancreas, kidney, breast, brain, heart, muscle and lung in specialist centres. Brain MRE uses a head cradle and a pillow driver.

Chronic liver disease affects over 800 million people worldwide (fatty liver in about 25%, viral hepatitis, alcohol, autoimmune and genetic causes). Fibrosis stage determines prognosis and management, and liver biopsy, the reference test, is invasive, sampling a very small part of the liver, and carries a small risk.

MRE has an area under the curve of about 0.95 to 0.98 for advanced fibrosis and cirrhosis, better than ultrasound transient elastography or shear wave ultrasound in obesity and ascites. It examines the whole liver, and has a technical failure rate of 3 to 5%.

Indications.

• Staging of liver fibrosis in chronic liver disease: metabolic dysfunction associated steatotic liver disease, viral hepatitis, alcohol related and autoimmune liver disease.
• Detection of cirrhosis and assessment of portal hypertension risk.
• Monitoring of fibrosis after treatment (antiviral therapy, weight loss, drugs).
• Patients where ultrasound elastography fails or is unreliable (obesity, ascites, narrow rib spaces).
• Characterisation of focal liver lesions as an adjunct (malignant tumours are stiffer than most benign lesions).
• Pancreas: chronic pancreatitis, autoimmune pancreatitis and tumours (research and specialist).
• Spleen stiffness for portal hypertension.
• Brain: normal pressure hydrocephalus, dementia, tumour consistency before surgery (research and specialist).
• Muscle disease, breast lesions and cardiac and lung applications (research).

Not for patients who cannot hold a breath, and not as a first test for acute liver injury.

Contraindications and precautions.

• The usual MRI safety screen. Hepatic iron overload makes the images unusable with the usual gradient echo method, so spin echo or other sequences are used.
• Claustrophobia, large body size exceeding the bore, and inability to lie still or hold the breath.
• Fasting for 4 to 6 hours before the scan, because food raises portal flow and liver stiffness for up to 3 hours.
• Acute hepatitis, cholestasis and heart failure with liver congestion raise stiffness without fibrosis, and measurements are not interpreted as fibrosis then.
• Contrast is not needed for MRE. The study is often combined with proton density fat fraction and T2* or iron quantification.
• Pregnancy: acceptable if clinically needed, without contrast.

Preparation and technique.

The patient fasts for 4 to 6 hours. The driver is placed against the chest wall over the liver in the mid-clavicular line at the xiphisternum level, and fixed with a strap. A pneumatic tube connects it to the active driver outside the scan room.

Coronal scout images set the slices. A 2D gradient echo sequence with motion encoding is acquired at four slice levels in four breath holds, with 4 phase offsets, giving wave images, magnitude images and the stiffness map. A 3D version with whole liver coverage is available.

The operator draws regions of interest on the stiffness maps, avoiding large vessels, the edges of the liver, areas of poor wave amplitude (confidence mask), the gallbladder fossa and focal lesions. The mean stiffness is reported in kilopascals.

Normal appearances.

The normal liver has a stiffness of under 2.5 kPa (about 2.0 to 2.5) at 60 Hz. The wave images show regular, well propagated waves of good amplitude through the whole liver, and the confidence maps cover most of the liver.

The spleen is stiffer than the liver (about 3.5 to 4.0 kPa). The pancreas is about 1.2 kPa, the normal kidney about 4 to 5 kPa in the cortex, and the normal brain about 2 to 3 kPa. Reference values differ by method and organ.

Interpretation.

• Liver stiffness thresholds (60 Hz, 2D method) approximate to: under 2.5 kPa normal; 2.5 to 3.0 normal or inflammation; 3.0 to 3.5 stage 1 to 2 fibrosis; 3.5 to 4.0 stage 2 to 3; 4.0 to 5.0 stage 3 to 4; over 5.0 probable cirrhosis. A value over 3.0 to 3.6 kPa is the usual cut off for significant fibrosis, and over 4.1 to 5.0 kPa for advanced fibrosis or cirrhosis.
• A normal value (under 2.5 kPa) has a high negative predictive value (about 95%) for significant fibrosis.
• Grey zone values (2.5 to 3.5 kPa) cannot separate stages reliably. Clinical context, other tests or biopsy are used.
• Fibrosis pattern: diffuse stiffness raised over the whole liver. Focal stiffening occurs around tumours and abscesses.
• Inflammation: acute hepatitis, drug injury and flares raise stiffness without fibrosis (by up to 1 to 2 kPa). Repeat after resolution.
• Congestion: right heart failure, constrictive pericarditis and hepatic venous outflow obstruction raise stiffness and reverse after treatment.
• Cholestasis: biliary obstruction raises stiffness, and measurement after relief gives a better fibrosis estimate.
• Steatosis alone does not increase stiffness significantly. The proton density fat fraction is measured in the same study.
• Focal lesions: hepatocellular carcinoma and metastases are stiffer than benign cysts, haemangioma and focal nodular hyperplasia, with overlap. The result adds to, and does not replace, the contrast study.
• Spleen stiffness: raised in portal hypertension (over about 8 to 10 kPa suggests varices at risk), but values depend on the method.
• Wave quality: reports note wave amplitude, the area of valid measurement and any technical failure.
• Other organs: higher kidney stiffness in fibrosis and chronic kidney disease, higher pancreas stiffness in chronic pancreatitis and cancer, brain stiffness changes in dementia and hydrocephalus.

Critical values and findings needing immediate action.

• Stiffness in the cirrhotic range: hepatology review, endoscopic screening for varices, and surveillance for hepatocellular carcinoma every 6 months.
• Signs of portal hypertension (splenomegaly, collaterals, high spleen stiffness): assessment for varices and decompensation.
• Unexpected focal lesion in a stiff liver: contrast MRI and multidisciplinary review for hepatocellular carcinoma.
• Rapid increase in stiffness: look for acute inflammation, obstruction, congestion or vascular occlusion.
• Iron overload on the same study: iron studies and treatment planning.

Limitations and artefacts.

• Liver stiffness is raised by inflammation, congestion, cholestasis, infiltration (amyloid), recent meal and high venous pressure. A value must be read with transaminases, bilirubin, cardiac status and fasting state.
• Iron overload (low T2* signal) degrades the wave images with gradient echo MRE. Spin echo echo planar MRE overcomes this to some extent.
• Obesity and ascites reduce wave penetration, though MRE is better than ultrasound elastography for these. Massive ascites can still cause failure.
• Poor breath holding, wave attenuation and a driver in the wrong position give invalid results. Confidence maps identify unreliable areas.
• Thresholds depend on the manufacturer, frequency and sequence (2D or 3D). Values from different scanners and from ultrasound elastography are not interchangeable.
• The grey zone between fibrosis stages makes the intermediate stages unreliable. A normal MRE does not exclude early fibrosis.
• Measurements near large vessels, the diaphragm, ribs and the gallbladder are unreliable.
• Spleen and pancreas MRE are less validated, and thresholds are not agreed.
• Access, cost and the need for the extra hardware and software limit use.

Special groups.

• Patients with fatty liver and diabetes: those with advanced fibrosis need liver and cardiovascular risk management, and MRE with proton density fat fraction gives both fat and stiffness in one study.
• Patients after treatment for hepatitis B or C: stiffness may fall as inflammation settles, though cirrhosis does not fully reverse.
• Patients with heart failure or single ventricle circulation after palliative surgery: congested liver stiffness raises, and fibrosis assessment is affected.
• Children: validated for liver disease, with sedation or breath hold coaching. Biliary atresia, cystic fibrosis liver disease and metabolic liver disease are common indications.
• Pregnant patients: avoid unless essential.
• Regions: chronic hepatitis B and C, alcohol and schistosomal periportal fibrosis are common, and MRE is scarce. Transient elastography, ultrasound, blood based fibrosis scores and biopsy are used.

Follow up tests.

• Ultrasound based transient elastography or shear wave elastography for repeat monitoring.
• Serum fibrosis markers and indexes calculated from age, platelet count, aspartate and alanine aminotransferase, and albumin.
• Liver biopsy for unclear cases or mixed disease.
• Upper endoscopy for oesophageal varices when cirrhosis is likely.
• Ultrasound with alpha fetoprotein, or multiphase MRI or CT, for hepatocellular carcinoma surveillance.
• Viral serology, autoimmune markers, ferritin and transferrin saturation, and metabolic workup for the cause.
• Referral to hepatology, gastroenterology, endocrinology or transplant services.