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Robert Lodder: Mounting an Attack on a Furtive Form of Plaque

by Jeff Worley

Everybody knows by now that arterial plaques are bad. These fatty deposits in blood vessels that feed the heart can turn deadly when they grow large enough to obstruct blood flow to the heart, brain or other organs.

But not all plaques are created equal, and it turns out that the ones you can see aren't even the most dangerous kind. In what's no less than a major breakthrough in the field of cardiology, researchers in the past half-dozen years have found that the most nefarious plaques lurk inside the artery wall. These soft, silent killers, it turns out, are responsible for the vast majority of fatal heart attacks.

"Sadly, it's not that uncommon a story. A fit man in his 40s or 50s goes in for his annual check-up and gets a clean bill of health from his doctor. He leaves the office, his heart ticking along like a fine, Swiss watch. He goes home and within a few days—or even hours—he drops dead of a heart attack."

This scenario comes from UK's Robert Lodder in the College of Pharmacy, who has spent nearly 20 years studying plaque's role in heart attack and stroke. Recently, the Cincinnati native has been among those researchers doing pioneering work in characterizing this more silent-but-deadly form of plaque attack.

"We call these "vulnerable plaques." They're small with a soft lipid core, nearly fluid, covered by a thin, fibrous cap of protein," Lodder explains. (Lipids are the main structural components of living cells and include fats and waxes.) "As the heart beats, the arteries and plaques move, so these plaques are in constant motion, and force is exerted on the edges of the fibrous cap covering the liquid pool." Even a small tear in that cap lets a little content ooze out into blood vessels. Unfortunately, the leaked lipids quickly produce a clot, and within 60 to 90 seconds the clot occludes the whole vessel. "The result is quick: you die," Lodder says.

Once it started becoming clear to researchers and cardiologists that these sneakier plaques were causing the vast majority of fatal heart attacks—some researchers believe up to 70 percent of heart attacks are from vulnerable plaques—Lodder began to think about how best to seek and find sites where these plaques gather and bide their time. His thinking led him to bring together two unlikely partners in this seek-and-find mission—fiber optics and mathematics.

"We've known for a while that different tissues demonstrate unique spectral properties when reflected light from these tissues is measured," Lodder explains. "These properties can be used to discriminate between healthy and diseased tissue. Recent advances in the telecommunications industry have produced cost-effective, fiber-optic light sources and detection devices to send and measure light, and we can now use this technology in medicine."

Incorporating such knowledge from clinical research, Lodder developed algorithms that correlate reflected tissue signals to known patterns, producing diagnostic devices that can determine the presence and progression of diseased tissue. He patented the algorithm, used to reconstruct infrared images of this plaque, in 1995. But he didn't stop there.

"First-stage immediate treatment is important, of course, for someone having a heart attack who's brought into the emergency room," says Lodder, "and there are wonderful advances, like angioplasty and stenting, for such a patient. But now we know it's important to go further. We want to make a map of the rest of the coronary tree—all the sites that haven't just been treated—and predict where and when the next heart attack will occur so that it can be prevented."

Photo of Robert Lodder holding fiber optic catheterRobert Lodder's fiber-optic catheter, which was patented in 1996, tours the coronary arteries looking for large spectral signatures of cholesterol. If it encounters these signals, the computer marks the spot as a vulnerable plaque.

In order to make this map, Lodder needed to design a probe to do on-site inspections. So he developed a fiber-optic catheter, which was patented in 1996, to do exactly that.

The experimental procedure begins with a heart-attack patient who has just had an occluded artery opened. Lodder's catheter, which is about 3½-feet long and hooked to a computer, is inserted into the system of coronary arteries. The probe is directed to the heart and tours the entire neighborhood of vessels, sending near-infrared signals to the computer. The probe looks for large spectral signatures of cholesterol, and if it encounters these signals, the computer marks the spot as a vulnerable plaque.

"The physician sees this all on a screen," Lodder says, "so he or she can mark the identified spots on a patient's chart. Ultimately, the goal is to pinpoint the most vulnerable spots—those with the biggest lipid mass and the thinnest cap—and then predict which ones are going to lead to a heart attack and how soon."

Lodder knew this was big, and so did James Muller, then director of the Gill Heart Institute at UK. "The more we talked, the more we became convinced we needed to form a company to begin to market this technology," says Lodder. Original seed money for the company, which they called InfraReDx, came from a couple of Lexington investors, including Hilary Boone, a UK alum and well-known philanthropist. Additional funding came from the NIH.

Founded in 1998 and now headquartered in Cambridge, Massachusetts, with Muller as the company's chairman (he left for Harvard last year), InfraReDx has focused on continuing to develop the near-infrared technology to detect and treat diseased tissues, and to develop ties with manufacturers and distributors of medical devices.

Although only a stockholder in the company now, Lodder is continuing to do his part to further the company's prospects. In 2002 he published an article on the efficacy of this technique in Circulation, the top journal in the field of heart-disease research. "I hope the article continues to help the company establish the legitimacy of this technique," Lodder says. "It'd be great if more people realized it was worth investing in."

Company representatives from InfraReDx are making more and more cardiologists aware of this potentially life-saving equipment, and physicians are now using it as part of a Phase I clinical trial. In this early-stage trial, small numbers of people undergo the procedure so that its efficacy and safety can be determined. The equipment and the procedure continue to work as designed, Lodder says, but there is a downside to doing such a trial.

"It's very, very expensive. Because the computer and the laser system that powers it are not proven devices, we have to give them away to the physician," says Lodder. "Also, we have to pay all the patient's medical expenses."

InfraReDx reps are also talking with several drug companies, Lodder says, so that this technology can be coupled with targeted drug therapy. "It's one thing to tell a patient, 'Oh, I found this place in your blood vessel, and in less than a year you're going to have a fatal heart attack.' Well, this is obviously not as helpful as saying, 'Not only have I found this spot, I also have the perfect drug to keep you from having that heart attack.'" Right now, Lodder says, only a few drugs are available that can regress vulnerable plaque, but drug companies are in an all-out scramble to develop effective drugs as quickly as possible.

Developing this technology and seeing it work under the guidance of a physician is just one professional satisfaction among many for Lodder, who even as a kid knew he wanted to become a scientist. "Before I was in kindergarten I used to build labs on our dining room chairs, assembling just about any kind of gadget I could find," he says.

"I'd watch all the space launches and couldn't decide whether to be an astronaut or a scientist." His father convinced him that the odds of becoming an astronaut were daunting, so Lodder traveled the path of the scientist. He won't ever explore Outer Space firsthand, but his inner-space explorations may just lead to the saving of thousands of lives.