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  Tapping the potential synergy of
  radiology, pathology

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September 2006
Feature Story

Karen Lusky

Pathologist Richard Friedberg, MD, PhD, has been making the same argument about radiology and pathology since 1997, which is the year he helped the VA Atlanta Healthcare Network (VISN 7) create a single Diagnostic Medicine Service Line that combined radiology, nuclear medicine, and pathology across three states.

His argument, in a nutshell, is this: “Pathology and imaging deal with the same stuff… Whether you put an electron through the patient to image a mass or put photons through a biopsy to make an interpretable image—it’s just two ways of getting the diagnostic answer,” says Dr. Friedberg, chairman of pathology at Baystate Health, Springfield, Mass., and a professor at Tufts School of Medicine. In both cases, he adds, “something comes in the door, you do something to it scientifically, interpret the results clinically, and report your findings.”

Today, Dr. Friedberg sees that core commonality between pathology and imaging as the basis for their potential alignment in the service delivery and diagnostic arenas. For example, “one-stop diagnostic shopping to me is a ‘no brainer,’” he says. And “just as there’s been a convergence of anatomical pathology, clinical and molecular, I foresee a higher-order convergence” between radiology and pathology on the diagnostic side.

As for the prospect of one-stop diagnostics, Dr. Friedberg notes that Quest and LabCorp are “run by bright people continually looking for ways to expand their markets.

“They already have patients coming in their front doors, many of whom are in need of multiple diagnostic modalities. So why not look for additional services to provide to the same population? The end result—getting diagnostic information back to the right individual—is the same.”

To Shane Foreman, president of 3d Health in Chicago, an outpatient strategy consulting firm, “the marrying of imaging and lab services makes perfect sense.” From a profit perspective, “the bigger bounce is in adding diagnostic imaging to labs” rather than vice versa, he says, noting that “people tend to grossly underestimate the operational prowess required to run a profitable lab.” But “in non-certificate-of-need states, the barriers to labs going into diagnostic imaging aren’t there.”

The melding of in vivo imaging and in vitro diagnostics arrived in the vendor marketplace this past summer when imaging and information technology giant Siemens Medical Solutions announced it had acquired Diagnostic Products Corp. and Bayer Diagnostics. The DPC deal is closed, and the Bayer deal is set to close later this year or in early 2007, says Mohammad Naraghi, MD, PhD, senior vice president of global business development for Siemens Medical.

Siemens’ acquisitions allow it to pursue what the company is calling “molecular medicine,” which is where “in vivo imaging meets in vitro diagnostics,” says Bruce Friedman, MD, active emeritus professor, Department of Pathology, University of Michigan Medical School, Ann Arbor.

On the in vivo side, Siemens last year acquired CTI Molecular Imaging, which “significantly enhanced” its “footprint and presence in in vivo molecular medicine,” Dr. Naraghi says. “By combining that with the acquisition of DPC and Bayer Diagnostics…we have significantly enhanced our position in lab diagnostics with a focus on immunodiagnostics and DNA testing.”

While Siemens’ acquisitions stunned some with their size and suddenness, the company has been tracking the development of molecular medicine for some time. “The management team came to the strong conviction that we need to lead and drive this change toward incorporating molecular diagnostics in an integrated diagnostics portfolio that is heavily based on a strong IT backbone,” Dr. Naraghi says.

Take lung cancer, for example, he says. “As the resolution and technology of imaging improves,” so does the capability to see ever smaller nodules in the lung which could be “indolent or harmless” rather than malignant, Dr. Naraghi says. But that “distinction can only be made by molecular fingerprinting of the nodules.” And that’s where in vitro capability and associated technology comes into play, he adds, using “antibodies targeted against specific cell antigens.”

In combining molecular diagnostics with imaging, one also “needs intelligent IT to identify and classify nodules based on their potential for being malignant—and then present that information to physicians in a format that is easy for them to handle,” Dr. Naraghi says. “That’s really the power of a company that has the potential to integrate in vivo and in vitro diagnostics, with strong health care IT solutions,” he says.

Diagnosing and managing prostate cancer is also well suited to a combination of in vivo and in vitro capability, in Dr. Naraghi’s view. He says Siemens can envision more specific in vitro tests than prostate-specific antigen.

“The testing would stratify whether a person should have imaging” performed with a “molecular contrast agent—an antibody, for example—targeted against the cancer receptors or molecules,” he says. The approach would allow specific tagging of prostate cancer to localize it and decide whether to intervene and how.

Siemens’ strategy to some extent is banking on future developments, but will they come through? Louis Fink, MD, director of the core laboratory for the Nevada Cancer Institute in Las Vegas, predicts that “antibody imaging, using a lot of information from pathology, is going to take a major leap forward.” That’s true not only in diagnostic imaging but also in targeted therapeutics. (In antibody imaging, he explains, antibodies directed against target tumor tissues are labeled with radioactive or nonradioactive detectors and injected into the patient, allowing tumor visualization and location.)

“The tools of pathology involved in this endeavor include elucidating the antigenic composition of tumors in order to find and eradicate tumors,” Dr. Fink says. “There’s been talk about doing this for a long time, but it’s now coming to fruition—for example, using the anti-CD20 antibody [Rituximab] to treat B-cell lymphomas.”

Another potential area of interaction between imaging and pathology is in assessing apoptosis and cell death after cancer therapy, Dr. Fink says. “We need to find a way to know whether therapy is efficacious shortly after its initiation,” to avoid administering toxic therapies that have no effect on the tumor, he says. “A combination of both blood assays and imaging may be used to assess tumoricidal effects.”

Siemens’ bold move integrating in vivo and in vitro represents the rubber hitting the road in the vendor arena. But in the clinical realm, one new company, Amigenics in Las Vegas, believes it can improve patient care by tapping the synergy between sophisticated genetic testing and imaging. Amigenics opened a clinic in Las Vegas in June to test, evaluate, and manage patients with diseases influenced by genes. The clinic, which accepts patients only on a consultant basis, also provides pre- and post-genetic testing counseling.

Robb Rowley, MD, chief of medical services for Amigenics, says “imaging and genetics are powerful tools that can diagnose [a patient] before disease burden becomes a significant issue…”

Three of the four company founders came from the development side of genetics, says Peter Cartwright, president and CEO of Amigenics. In fact, the four realized “almost simultaneously” that there’s a gap between developing technologies and using them in clinical practice, he says. As a result, Amigenics isn’t about developing technology. “We have been there and done that,” Cartwright says. “Instead, we are taking advantage of what already exists.”

Amigenics’ management of a patient who turned out to have hemochromatosis illustrates how they combine genetic testing and imaging to help avoid invasive procedures and improve outcomes.

When Amigenics first evaluated the patient, his chief complaints were cough and fatigue. An MRI showed he had infiltrative cardiomyopathy, says Eric Hanson, MD, MPH, chief of scientific research and education for the company. The patient’s “heart was enlarged in a certain area that partially obstructed the blood flow into the aorta, which was causing some of his symptoms.”

Genetic testing revealed the man had “one of the HFE gene mutations [homozygous H63D],” Dr. Hanson says. He notes that hemochromatosis used to be viewed as a single-gene disorder but now it’s known that multiple genes are involved.

The Amigenics workup identified that the patient’s hypertrophic obstruction was influenced by a high level of iron deposits that could be quantified by a 3.0T MRI system using an imaging protocol developed by Tom Perkins, senior clinical scientist for Philips Medical Systems, Dr. Hanson says. “And we were able to give a quantitative measurement of iron in the heart itself, the liver, and the brain in a noninvasive way,” he adds. “Previously, the only quantitative iron measurement from tissue other than blood required a core liver biopsy.”

The patient had been scheduled to have a myomectomy of the heart to clear the obstruction. But fortunately, no surgery was needed and the patient is doing well with once-a-week phlebotomy to remove blood, Dr. Hanson says.

Amigenics also combines knowledge about BRCA testing and imaging modalities to help patients with a positive BRCA result weigh the risks and benefits of MRI versus mammography. Dr. Hanson says some research indicates that people with a damaged or mutated BRCA gene may have increased susceptibility to the carcinogenic effects of radiation exposure. Thus, a patient who tests positive for BRCA might consider integrating MRI into a mammography screening protocol, he says, to reduce the number of mammograms.

Dr. Hanson notes that a University of Bonn study indicated that MRI is more sensitive than mammography in detecting breast cancer in high-risk women. But it costs more and produces more false-positives. “One MRI study for detecting breast cancer in women with BRCA mutations was 100 percent sensitive, but it also had 17 percent false-positives. Therefore, each patient must have the risks and benefits of genetic testing and imaging personalized to their current situation and to ensure proper longitudinal surveillance for early onset of disease.”

Erica Ramos, MS, CGC, senior genetic consultant for Amigenics, says insurance coverage for the genetic testing and imaging is good overall, “although gaps exist.” It’s her sense that insurers are starting to see the “big picture” in realizing it pays to use the technologies to prevent illness or to detect it early. How might the merging of imaging and pathology play out for pathologists? Dr. Friedberg predicts diagnostic medicine will “become a field whether the pathologist is the first or second part. But if you believe Star Trek,” he says, “we’re headed toward technology” of the kind “where Scotty would wave the wand over Jim Kirk and know what was going on with him.” He notes the widespread preference to have diagnoses made noninvasively.

Andrew Quon, MD, clinical assistant professor of radiology/nuclear medicine at Stanford University, says, “There is always going to be a role for pathology because we have learned time and time again that to get the true answer of what is going on at the cellular level, you have to look at the tissue.” Or “that’s going to be true over the intermediate future, at least,” he adds.

But imaging’s advantage over pathology is that it can look at cellular function in the context of real time, Dr. Quon says. “The pathological specimen can tell you it’s a type of cancer” that will respond to “a certain type of therapy. But those cellular functions may change or may be turned off in the body. We are finding a number of receptors that can be turned on and off in vivo, such as angiogenesis receptors on tumors,” he says.

The University of Michigan’s Dr. Friedman says that as imaging and, more specifically, molecular imaging capability evolves, surgical pathology based primarily on morphologic observations rather than cell biology and function will “decline in influence.” But surgical pathology won’t disappear. Instead, he foresees a combination of molecular imaging and sophisticated investigation of tissue using various special stains in order to better understand tumor biology. “That’s how the hematopathologists operate, through morphologic and sophisticated molecular observations,” he says.

Dr. Friedman also predicts strong economic force for more collaboration between diagnostic/molecular imaging and pathology/molecular diagnostics—“so powerful, that what analysts are saying about the potential synergy of a combination of radiology and pathology is accurate.

“Analysts say that if this combination or synergy provides greater diagnostic competence on the part of commercial labs,” Dr. Friedman says, “the nonprofit hospital will have to compete with that. Right now, however, the large reference labs themselves are not integrated with imaging centers,” but that “goal could be pursued.”

In other words, economics and competition may drive the integration. “That’s Siemens’ vision of it, and they’re putting a multi-billion dollar bet on it,” Dr. Friedman says.


Karen Lusky is a writer in Brentwood, Tenn.