The Mayo Clinic has developed an imaging technology that may replace painful liver biopsies for some patients and provide an early warning of liver disease to others.
Chronic liver disease is painful enough without having to endure the discomfort of periodic needle biopsies to test for cirrhosis. For some patients, that pain may no longer be necessary with the introduction of Resoundant, a new imaging device and MR technique that was developed by Mayo Clinic Medical Devices (MCMD), a division of the Mayo Clinic in Rochester, Minn.
When installed on MRI scanners, Resoundant will be able to noninvasively measure liver fibrosis using its proprietary imaging technique known as Magnetic Resonance Elastography (MRE). The resulting “elastogram” is a color-coded diagnostic image that reveals both the location and level of liver fibrosis with 99% specificity and 100% sensitivity.
The Mayo Clinic is already using Resoundant on patients and is in the process of licensing the technology to several original equipment manufacturers (OEMs). Jim Potter, director of MCMD, said that Resoundant has the potential not only to replace needle biopsies for some patients, but also to accurately measure stages of liver disease and help decrease common errors related to liver disease staging.
“If the gold standard is needle biopsy, what this device may do is minimize a number of those biopsies,” Potter said. “So, if I go in for an MRE and the test is showing no growths at all—no fibrosis or tumors—then odds are pretty good that my physician is not going to recommend a biopsy.”
In its final form, Resoundant is used in conjunction with a typical contrast-enhanced MR abdominal exam. The technology can be adapted to both high- and low-field magnets.
The Resoundant system consists of a ping-pong-paddle-shaped “passive driver” that is placed on top of the patient’s abdomen.
Next, an external “active driver” sends a mechanical energy called “shear waves” through a tube that leads to the passive driver and subsequently into the patient’s liver. The patient feels a slight vibration on the abdomen for approximately 45 seconds.
A proprietary software application translates the received data into a color-coded elastogram, which accurately identifies areas of liver fibrosis and their staging. (See diagram “Acoustic Driver System for MRE” below.)
Developing Resoundant and MRE
The idea for Resoundant was first developed by a team of Mayo researchers led by Richard Ehman, MD, professor of radiology and chair of radiology at Mayo. In the 1990s, Ehman and his group researched how shear waves could be detected as they moved through certain materials. By using a special MRI sequence, Ehman’s team was able to follow the shear waves and calculate the stiffness of the material.
Product name: Resoundant, developed by the Mayo Clinic in Rochester, Minn.
What it is: A new imaging device integrated with an MRI that accurately measures liver fibrosis and may also provide an early warning for liver disease. For some patients with known liver disease, Resoundant may be a noninvasive alternative to needle biopsies. The imaging technique that uses the Resoundant device is called Magnetic Resonance Elastography (MRE).
How it works: During an MR abdominal exam, a powerful acoustic device generates “shear waves” that travel through a tube and into a passive driver that is placed over the abdomen. The reflected shear waves are processed into an “elastogram,” a color-coded image of the liver that shows varying degrees of liver elasticity.
When it will be available: Various MRI manufacturers are licensing the technology from Mayo. Resoundant should be available as an optional feature in new MRs in early 2009. There also may be the possibility of upgrading an existing MR.
Next, the team went to work on refining the way that the shear waves were generated and transmitted through various substances: gel phantoms, animal models, and eventually, human liver tissue.
Meng Yin, PhD, a research fellow at Mayo Clinic College of Medicine under Ehman, was instrumental in inventing the unique acoustic driver system that generates the shear waves.
The third challenge was the processing of the shear wave data. Armando Manduca, PhD, professor of bioengineering and associate professor of biophysics at Mayo, created a unique algorithm that processed the shear wave data into the color-coded elastogram image, which shows the variations of stiffness in the liver tissue.
Finally, after several small clinical trials, Ehman and his researchers published a 2007 study in Clinical Gastroenterology and Hepatology in which 50 patients with varying types of liver disease and varying types of fibrosis were imaged using MRE. They also imaged 35 patients known to be without liver disease. The results showed that MRE was near perfect in accurately detecting different stages of liver disease while correctly identifying all patients who were without disease.1
Jayant A. Talwalkar, MD, MPH, associate professor of medicine, division of gastroenterology and hepatology at Mayo, is one of the co-authors of that 2007 study. He said, “We found that MRE is very successful in identifying who has advanced fibrosis. So on a scale of 0 to 4, with 4 being cirrhosis from a biopsy, people with stage 3 and stage 4 are detected very accurately, and a normal result on that scan is almost universally consistent with normal liver or no fibrosis.”
With this study and other past data in hand, Mayo began the process to license its new technology to MRI companies.
Talwalkar said that the initial goal of the technology was to find a way to systematically discover whether someone needed a liver biopsy or not.
“Up to this point, it’s been a bit of guesswork. If we think someone has advanced fibrosis or cirrhosis because they have other labs that are changing, or the liver’s starting to look a little nodular on an image, it helps to verify that. But what we’re looking for these days is the earlier stages [of liver disease] so that we can initiate treatment sooner.”
The Resoundant technology’s high sensitivity for liver disease has allowed Mayo physicians to spare many patients from having a painful, unnecessary—and more expensive—liver biopsy.
In addition, Talwalkar said that the technology is ideal for patients with confirmed liver disease that have no treatment, such as hepatitis C.
“If someone has early disease or is not a candidate for treatment, the recommendations have been to just biopsy them every 3 to 5 years. Some of those people would benefit from that [protocol], but others won’t, especially a patient that you’d never treat. By using MRE, we can follow these patients, and when it looks like there has been more disease, then we’ll biopsy those people if that’s needed.”
Talwalkar went on to say that there have only been a few Mayo physicians who have recommended a biopsy after the MRE indicated a disease progression. In each of those cases, the biopsy correlated with the new stage of fibrosis seen on the MRE scan. Typically, a physician may order a biopsy after an MRE to learn more about the pathology of the liver tissue.
Potter also highlighted how MRE exams in lieu of a biopsy can help reduce pain and discomfort, as well as biopsy complications and errors. He said, “The gold standard is to do a needle biopsy [to test for fibrosis], but if you don’t have that needle in the exact right spot, you’re either going to get a false negative or a misstaging in addition to any complications from sticking a needle into somebody’s liver.” In addition, a misstaging could lead to prescribing more or less medication than needed.
Potential for Future Uses
Although Resoundant and MRE are currently being used for liver disease diagnosis, there are ongoing studies for other applications beyond the liver. In addition, as the technology becomes more available, other physicians will find more uses.
“We’re looking at imaging the brain, prostate, the female organs,” Potter said. “Anything that has an elastic property to it, we can image.”
Talwalkar added, “Certainly, cancers are harder and stiffer. ? You could potentially envision [MRE] detecting areas that might be cancerous in various tissues such as breast, for example, which would be too deep to actually appreciate with the fingertip touch, when you palpate. So that’s one possibility.”
Similarly, investigators are looking into prostate imaging applications, where the shear waves would enter the prostate and allow for the examination of the surface, as well as the interior, to see if there are nodules that might be suspicious for cancer.
For these other types of studies, the passive driver and the MRE algorithms will have to be modified. Right now, only the abdomen passive driver is in clinical use and clinically tested for liver applications. However, like MRI coil sets, MCMD may eventually develop different-shaped passive drivers that will be optimized for different parts of the anatomy.
|During an MRI exam, an acoustic device generates “shear waves” that go through a tube and into a passive driver that is placed over the abdomen. The reflected shear waves are processed into an “elastogram,” a color-coded image of the liver that shows varying degrees of liver elasticity.|
Costs, Reimbursement, and Coverage
Another benefit to MRE compared to a biopsy is its lower cost to the patient and insurers. While a liver biopsy can cost thousands of dollars, an MRE with Resoundant will cost the same as an abdominal scan—about one-third of the cost of a biopsy.
For now, MRE has no CPT code, so insurers will not reimburse specifically for the procedure. Instead, MRE will be performed and reimbursed as part of an abdominal MRI scan.
As to the actual cost to the health care provider, Mayo Clinic will sell Resoundant to MR OEMs for distribution to health care providers. Consequently, MRI manufacturers licensing the technology will set the price.
However, Potter said that Mayo is licensing Resoundant so that it is an affordable option and will therefore reach the most number of patients. He also confirmed that Resoundant’s technology would not be exclusive to a single MRI manufacturer.
“This is a product that’s changing patient care, so we would never exclusively license it. Our main objective here is to improve patient outcome, and if we license it to just one player, that’s only going to affect 40% of the market, and there’d be a fairness issue.”
Considering that an MRE takes only another 45 seconds beyond a normal abdominal scan, an imaging center’s workflow should not be affected. The technologist needs only a minute to place the passive driver onto the patient’s abdomen.
In fact, a full abdominal exam may not even be necessary. “If all you want to know is what the stiffness of the liver is, you don’t necessarily need a full contrast-enhanced exam,” Talwalkar said. “We have the ability to take a noncontrast image of the liver, where you get some information about the size and shape.”
Very little training will be needed to use the Resoundant technology and interpret the MRE results. Any training that is needed will be handled by the MRI manufacturers.
In terms of availability, the first production run of the Resoundant system will begin on June 9, 2008. OEMs will incorporate it into their scanning equipment over the next 6 to 12 months and will be able to offer the technology sometime in 2009.
Tor Valenza is a staff writer for Medical Imaging. For more information, contact .
- Yin M, Talwalkar JA, Glaser KJ, et al. Assessment of hepatic fibrosis with magnetic resonance elastography. Clin Gastroenterol Hepatol. 2007;5(10):1207-1213.e2.