Monday, June 8, 2009
A heartfelt collaboration:
K-STATE RESEARCHER AND SONS SHED LIGHT ON PLAQUE, HEART DISEASE
MANHATTAN -- Kansas State University's David L. Wetzel, a professor of grain science and industry, is known around the world for using microspectroscopy to do chemical analysis of single cells and parts of cells. That is, he uses the spectrum of light to get information about biological samples.
Though typically Wetzel conducts grain science-related research, such as determining the distinct chemical signatures of hard and soft wheat, his recent focus is heart disease, the No. 1 killer in the Western world. Wetzel's interest has a personal connection. He is a three-time heart attack survivor.
For Wetzel and other heart disease patients and their doctors, plaque is the enemy, the target of cholesterol-lowering medications, exercise programs and improving the diet. In particular, the lipid form of plaque, or soft plaque, is more unstable and poses a greater imminent health risk than a plaque formation that is mineralized or fibrous. Lipid plaque can rupture suddenly, and the ensuing events within the body can lead to sudden cardiac death.
When Wetzel showed images from his spectroscopy research on heart disease -- chemical analytical images of aorta tissue from a pathology sample that showed lipid deposition on the aorta wall -- to his two sons, who are both medical doctors, they all realized they were seeing the chemical microstructure of plaque as it existed inside the wall of the vessel.
Son Mark Wetzel, who earned a bachelor's in biochemistry from K-State, is a physician with Manhattan Medical Associates, while son Louis Wetzel, who earned a bachelor's degree in chemistry from K-State, is vice chair and medical director of radiology at the University of Kansas Medical Center.
The physicians brought their clinical experiences to the research. They said that if a cardiologist had an intravascular ultrasound image of a patient that showed an area of unknown deposition as dark spots, then knowing whether the spots are lipid or fibrous could make a difference in how aggressively the patient is treated.
In a presentation at an international conference in late 2008 and a publication in April 2009, "Team Wetzel" and their collaborator at the University of Kentucky described the background for and potential value of a new, catheter-based system to provide a biochemical analysis of plaque within the coronary arteries of living patients.
Preliminary spectroscopic data came from David Wetzel's summer research at a national laboratory. He directs K-State's Microbeam Molecular Spectroscopy Lab, one of a few labs in the world with research-grade instrumentation for doing chemical microspectroscopic imaging in mid-infrared and near-infrared spectral ranges.
For many years David Wetzel had "beam time" for spectroscopic analysis of various biological samples at the National Synchrotron Light Source of Brookhaven National Laboratory, a U.S. Department of Energy-funded facility. The synchrotron is considered the brightest light on earth.
Some University of Kentucky experiments involving heart tissue were being done by colleague Robert A. Lodder, and David Wetzel offered to do a series of tissue analyses using the synchrotron. They were addressing basic research questions: could spectroscopic analysis reveal plaque forming in the vessels, and could the chemical composition of plaque be detected?
David Wetzel used the mid-infrared portion of the light spectrum to analyze aortic tissue samples from a male mouse that had suffered the equivalent of a stroke. Next, he looked at mouse heart tissue designed to mimic aneurysm formation, and lastly, he studied the heart tissue from a human cadaver.
"The microspectroscopic data did reveal the chemical composition of the aorta walls," David Wetzel said. "We were able to show the chemical nature of the plaque sample as fibrous or lipid. Our analysis of those post-mortem tissues provided the basis for understanding the biochemical analysis of heart vessels of a living patient by using an optical near-infrared catheter."
Wetzel and Lodder prepared several articles about the Brookhaven experimental work.
The University of Kentucky research group patented an optical catheter the Food and Drug Administration approved for clinical use in April 2008, the InfraReDx LipiScan NIR Catheter Imaging System. The intravascular near-infrared catheter and spectrometer is in use at six U.S. clinical facilities so far.
David Wetzel also presented a talk about the project in October 2008 at a medical spectroscopy meeting in Brazil, "Shedding light on disease: Optical diagnosis for the new millennium." In addition, the paper "Imminent cardiac risk assessment via optical intravascular biochemical analysis," by Wetzel, Wetzel, Wetzel and Lodder appeared April 9 in The Analyst, a publication of the British Royal Society of Chemistry.
"We are an unusual team with a unique perspective on heart disease," David Wetzel said. “By presenting at that particular conference, I think we're helping bridge a communication gap, so to speak, between biomedical spectral analysts and clinicians."
As medical practitioners, Mark Wetzel and Louis Wetzel contributed case studies of their heart patients. Mark Wetzel specializes in preventive cardiology and performs echocardiography. In the Kansas City area and the Midwest, Louis Wetzel pioneered the use of Cardiac CTA or Computed Tomography Angiogram, a noninvasive method to see disease in the heart arteries.
"Our contribution from the synchrotron work at Brookhaven National Lab was evaluating mouse heart tissue and human heart tissue samples using mid-infrared and near-infrared in order to prove the concept -- that spectral analysis can characterize and distinguish between stable and unstable kinds of plaque," David Wetzel said.
The collaborators said that chemical analysis of plaque is now a reality. They also said that in theory, having this add-on device offers great promise to improve the treatment of coronary atherosclerosis. But when and how it is best used, and whether its use has long-term benefit are yet to be determined.