Diseases of the liver don’t tend to generate the same kinds of urgent public discussion as other deadly, progressive conditions like breast cancer, AIDS or diabetes.
But liver cancer and liver cirrhosis together kill more people worldwide each year (2 million plus) than those conditions. And the incidence is growing — especially the condition known as nonalcoholic fatty liver disease, which tends to crop up in people with obesity or diabetes and can lead to cirrhosis and cancer.
Diagnosing early signs of liver problems is challenging, but several tools exist. A company in Rochester called Resoundant Inc., backed by the Mayo Clinic, has developed one such tool called MR elastography (MRE) that is billed as cheaper and far less invasive than a liver biopsy. The company recently had its 1,000th MRE system installed in a hospital.
The technology behind the device was invented by experts at Mayo, including radiologist and inventor Dr. Richard Ehman, who led a team in the 1990s that discovered how to detect extremely subtle vibrational waves in tissue using a standard magnetic-resonance imaging (MRI) machine.
“We actually published in Science, so it was a big discovery. A picture of the waves that we were able to image were on the cover,” Ehman noted.
Indeed, the Sept. 29, 1995 cover of Science shows an image of red and purple waves propagating from two sources, looking like stones thrown into a psychedelic pond. The caption described how a new MRI technique could “quantitatively depict mechanical waves with amplitudes on the order of hundreds of nanometers and could lead to the development of a medical imaging modality.”
That’s exactly what has happened.
Ehman said physicians have long used their sense of touch as a powerful diagnostic tool — “many cancers are first diagnosed through touch,” he noted — because touch can reveal whether a tissue is unusually stiff and possibly diseased. It took 10 years to figure out how to apply the breakthrough of MRI-visible waves in tissue to analysis of liver stiffness.
Over time a diseased liver becomes tough and fibrotic, and eventually cirrhotic, but it’s not practical to touch it to test its stiffness. So other methods have been developed to detect problems. Taking a small snip of a person’s liver tissue and then doing a biopsy has long been used to assess potential fibrosis, but it’s an invasive test and carries a small risk of creating serious problems for the patient.
Commercial lab companies offer tests that can look for biomarkers, or telltale chemical traces of liver damage, in a patient’s blood serum. Other methods include using MRI to detect the motion of water molecules in cellular tissue (“diffusion-weighted imaging”) or using a specialized ultrasound system to measure mechanical waves in the tissue (“transient elastography”).
Resoundant’s magnetic resonance elastography device is essentially an add-on to a standard MRI machine made by GE, Philips or Siemens. The system includes a device that looks like a small drum that is placed on the patient’s abdomen to generate small, precise vibrations, plus software that analyzes the resulting MRI images to find regions of the liver where stiffness indicates fibrosis or cirrhosis.
Early versions of the MRE system were tested at Mayo starting in 2007 and eventually found wide acceptance among Ehman’s colleagues.
“We had it used on hundreds and hundreds of patients. And eventually our clinicians said they didn’t want to have to use this as an experimental practice — they wanted to use this in regular practice now. And they wanted to use it instead of biopsy,” he said.
But the big companies that made MRI scanners weren’t initially interested in investing in MRE as a sellable product. So the Mayo Clinic established Resoundant, which developed the system and then partnered with the MRI makers to integrate the MRE components.
Today all of the components for the Resoundant system are made in Rochester and can be installed in new or pre-existing MRI scanners. (Tax forms show that Resoundant is a private company that remains majority-controlled by Mayo Clinic. Mayo also owns the patents.)
“MRE was invented at the Mayo Clinic,” Chief Operating Officer Troy Ziegler said via e-mail. “Resoundant licenses the intellectual property and pays royalties to the Mayo Clinic.”
Ziegler said Resoundant isn’t involved in selling MRI systems to end users. Including the MRE capability typically adds 5 to 10 percent to the cost of a standard MRI system.
Journal articles show that MRE is beginning to be used more widely as questions about liver health become more common.
“MRE has been established as an accurate method in the evaluation of chronic liver disease, and the liver stiffness is considered an accurate marker for staging of liver fibrosis in chronic viral hepatitis,” an article in the peer-reviewed journal Gut and Liver reported last year.
Chronic liver disease, which can lead to cirrhosis, can be caused by a variety of problems including infections of hepatitis B or C, long-term alcohol abuse and metabolic syndrome. Nonalcoholic fatty liver disease has become the most common chronic liver disease, including notably high rates in South America and Asia and a fast-growing incidence in the U.S., according to an article in Nature Reviews Gastroenterology & Hepatology.
Patient advocate Cathy Mumford of California has a relatively uncommon condition that caused her liver fibrosis, but she credits the diagnostic power of MRE with opening her eyes to medical facts that may have saved her life.
Mumford has primary biliary cholangitis, or PBC, a chronic disease that destroys bile ducts in the liver and causes inflammation and scarring that can lead to full cirrhosis. She said the condition is understood well enough by clinicians so that liver biopsies aren’t typically used to diagnose it anymore, as it progresses from liver inflammation in stage 1 to full cirrhosis in stage 4.
Believing she had stage 1 symptoms, Mumford had been planning a monthslong trip in the Pacific Ocean. Then she got an MRE scan.
“When I got the scan, people were scurrying around the room and talking and bringing more people in the room. And I’m like, what’s going on?” Mumford said. Her doctor “called that night and said, I am scared, Cathy. I don’t know what’s going on. This is showing you have cirrhosis, and we all thought it was stage 1. ... I was immediately sent for further testing, and within a month, we knew.”
The MRE scan had correctly found that she was in stage 4 and she needed to make some changes, including not traveling thousands of miles from medical care for months at a time, she said.
“I reached out to Resoundant and said, I think you saved my life,” she said. “I had cirrhosis, and I thought I was at stage 1. And I would not have known that without MRE.”