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Picturing Liver Disease with Shear Waves: August 28, 2008

Although quick and nearly painless, liver biopsies cause anxiety for many patients. Insertion of a needle to remove a small sample of liver tissue is minor surgery, and has the potential for rare, but serious complications. But for the 170 million individuals worldwide who live with chronic hepatitis C, a major cause of liver disease, biopsies may be necessary to detect the development of fibrosis or scarring of liver tissue, which can impair liver function.

Magnetic resonance elastography can detect liver fibrosis. Top row: Conventional MR images of two different patients fail to show the presence of liver fibrosis. Center row: Acoustic waves are generated in the abdomen with a driver device and imaged with a special MRI technique that is able to image the waves. Bottom row: The wave images are processed to generate quantitative images showing the stiffness of tissue (elastograms). The patient on the right has a markedly elevated liver stiffness, averaging 7 kiloPascals, indicating the presence of moderately advanced liver fibrosis. The patient on the left has a normal liver stiffness of approximately 2 kiloPascals. Image courtesy of Richard Ehman.

Many other diseases also cause fibrosis of the liver, often without any symptoms. If the ongoing damage to the liver is not diagnosed and stopped through treatment, it may progress to cirrhosis, an irreversible condition in which the liver fails to function.

However, biopsies only provide information about one area of the liver. If fibrosis is not evenly distributed throughout the organ, the sample may under- or over-estimate the true extent of disease. Imaging is also used to diagnose diseases in the liver, but standard medical imaging technologies are not sensitive enough to diagnose fibrosis.

To overcome these limitations, Dr. Richard Ehman, professor of radiology at the Mayo Clinic in Rochester, Minnesota, and colleagues have developed a new imaging technique that gives precise data on the liver’s stiffness or elasticity. Their noninvasive approach, called magnetic resonance elastography (MRE), uses a special magnetic resonance imaging (MRI) technique to capture snapshots of shear waves, a special type of sound wave, as they move through the tissue. The technology creates “elastograms” or images that show tissue stiffness.

“For centuries, physicians have used simple touch as a powerful diagnostic technique to detect tumors and other abnormalities in accessible regions of the body,” says Dr. Ehman. “That technique, which is called palpation, can sometimes be used to detect the presence of advanced liver disease because a cirrhotic liver becomes very hard. MRE allows sensitive measurement of changes in liver tissue stiffness that indicates the presence of early fibrosis, so the condition can be diagnosed reliably and treatment given before the disease progresses to irreversible cirrhosis.”

Enhancing MRI

To generate shear waves within the liver, Ehman’s team developed a flat drum-like vibration source that is placed against the abdominal wall. A novel MRI technique developed at Mayo Clinic captures images of the waves, which are analyzed with an algorithm or set of mathematical equations developed especially for the MRE process. The algorithm translates the wave images into a quantitative map of tissue stiffness. Because it takes just 15 seconds to acquire images for the elastogram, an MRE study folds seamlessly into a conventional MRI exam of the abdomen.

Several groups are studying other approaches for imaging tissue stiffness. Investigators in Europe have developed a method that measures the movement of shear waves in tissue using ultrasound imaging. Researchers at Duke University are investigating a noninvasive liver imaging technique called acoustic radiation force impulse imaging.

“I think that MRI-based and ultrasound-based technologies for quantitative elastography both have great potential to contribute to patient care,” says Ehman. “They will each likely find specific clinical applications that exploit their unique features.

Tracking Liver Disease and Tumors

The Mayo Clinic has been using MRE for patient care since early 2007, with over 600 patient examinations performed at facilities in Minnesota, Arizona, and Florida. The technique is also being used in research at the University of Texas M.D. Anderson Cancer Center in Houston, the University of Wisconsin, Madison, the University of California, San Diego, and Johns Hopkins University in Baltimore, Maryland.

In addition to monitoring fibrosis development, Ehman and his team have used MRE to characterize liver tumors, which typically are much stiffer than normal tissue. Their results showed that malignant tumors were stiffer than benign tumors and normal liver tissue. Based on their findings, the team is pursuing three-dimensional MRE to refine the technique so that the data are more accurately depicted in the elastogram.

New Possibilities

Although Ehman and his team tested MRE on the liver initially, additional studies are underway in the brain, breast, kidney, and prostate. “The goal was to create an imaging technology with very broad applications,” he says. In the case of the brain, the researchers theorize that diseases such as Alzheimer’s may affect the mechanical properties of the brain. Imaging studies with MRE may help characterize the brain lesions associated with Alzheimer’s. MRE studies could also be useful in understanding the mechanisms of brain trauma.

Ehman notes that measuring a tissue’s mechanical properties such as stiffness can also help increase our understanding of what causes disease. “Researchers are beginning to understand the profound ways in which the mechanical environment affects the behavior of cells,” he says. Abnormal stiffness in tissue has been shown to contribute to the development of a number of diseases, from liver fibrosis to cancer.

“MRE opens a new window into our understanding of tumor biology,” says Dr. Vivian Lee, professor of radiology, physiology, and neuroscience and senior vice president and chief scientific officer at New York University’s Langone Medical Center. “We now have a tool to start to understand at a molecular level how and why fibrosis and increased stiffness develops as a property of tumors.”

Adds Ehman, “We’ve just scratched the surface of what can be done. MRE will allow us to begin to explore some of these new areas and access a whole new range of unexplored imaging biomarkers.”

This work is supported in part by the National Institute of Biomedical Imaging and Bioengineering.

References

Venkatesh SK, Yin M, Glockner JF, Takahashi N, Araoz PA, Talwalkar JA, Ehman RL. MR elastography of liver tumors: preliminary results. American Journal of Roentgenology. 2008;190:1534–40.

Yin M, Woollard J, Wang X, Torres VE, Harris PC, Ward CJ, Glaser KJ, Manduca A, Ehman RL. Quantitative assessment of hepatic fibrosis in an animal model with magnetic resonance elastography. Magnetic Resonance in Medicine. 2007;58:346–53.

Yin M, Talwalkar JA, Glaser KJ, Manduca A, Grimm RC, Rossman PJ, Fidler JL, Ehman RL. Assessment of hepatic fibrosis with magnetic resonance elastography. Clinical Gastroenterology and Hepatology. 2007;5:1207–13.

Kruse SA, Rose GH, Glaser KJ, Manduca A, Felmlee JP, Jack CR Jr, Ehman RL. Magnetic resonance elastography of the brain. NeuroImage. 2008;39:231–7.

Richard Ehman