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RESEARCH PROFILES Heart-smart spectroscopy We thought we knew the culprit behind heart attacks—hardened blockages, known to doctors as “stable” or “calcified” plaques, which are composed largely of cholesterol and stony calcium hydroxy apatite. These plaques gradually grow outward, pinching off the blood flow in our arteries. But there may be something much more dangerous lurking, the presence of which isn’t betrayed by physical symptoms, stress tests, or angiograms. It’s called a “vulnerable” or “unstable” plaque, and cardiologists now think that these plaques cause up to two-thirds of all heart attacks. “There is a growing belief among cardiologists,” says Gerwin Puppels of Erasmus University Rotterdam (The Netherlands), “that the plaques that actually cause clinical symptoms, such as chest pains during physical activity, are not the [plaques] most likely to cause heart attacks and lead to sudden death.” Unlike the more familiar stable plaques, vulnerable plaques are not hardened and do not normally block blood vessels, Puppels says. They lie more-or-less flat along the wall of an artery—a small pool of lipids covered by a thin fibrous cap and surrounded by inflammatory cells. In this stealthy state, the plaques do no known harm. But at any moment, one could rupture, releasing the sticky lipid pool, around which a life-threatening blood clot could rapidly form. Detecting these symptomless plaques before they rupture is the challenge. And in the August 15 issue of Analytical Chemistry (pp 3771–3775), Hendrik P. Buschman, Arnoud van der Laarse, Gerwin J. Puppels, Michael L. Wach, and colleagues at Leiden University, Erasmus University Rotterdam (both in The Netherlands), Cirrex, Inc. (formerly Visionex), and Renishaw p.l.c. (U.K.) describe a new fiber-optic probe for locating and ana-
lyzing vulnerable plaques in vivo. success of these probes is optical filterSeveral techniques for detecting ing, which prevents the tiny Raman vulnerable plaques have already been signal from being swamped. The redeveloped: intravascular ultrasound to searchers embed filters to remove the image arterial walls; IR detection of unwanted Raman scattering from the “hot spots”, because some data have laser-delivery fiber, and they embed shown that vulnerable plaques are up more filters to block laser light from to 5 degrees warmer than their surentering the fibers dedicated to carryroundings; and noninvasive magnetic ing the Raman signal. resonance imaging, which can reveal “The engineering associated with the locations and types of plaques. integrating such high-performance filBut for sheer specificity, it’s hard to tering into an optical fiber is very diffibeat Raman spectroscopy. Because evcult,” says Wach. Normally, these comery chemical compound has its own ponents occupy a space the size of a Raman signature, the components of cigar box. “Then we couple that filtereven complex mixtures can be identiing with ‘beam steering’ to optimize fied. The value of Raman spectroscopy the signal collection and control how for studying human tissues has long deeply you probe the tissue,” he adds. been known, and the technique has been widely used Forward viewing fiber probe in vitro. But until now, reFilters searchers have not been able to make a Raman probe Zone from which that is small enough for delRaman signal is collected icate areas, such as arteries, and is still sensitive. Signal collection fibers (seven 300-mm fibers around a central “The Raman effect is exLaser delivery fiber 400-mm fiber) tremely weak,” explains Wach. “For every billion Side viewing fiber probe photons you send out, only Side viewing tip Laser delivery fiber a very, very few are Raman(fused silica) scattered.” Detecting this minuscule signal is troublesome enough. UnfortunateGold-plated mirror ly, living tissue isn’t the only Signal collection fibers (seven Filters thing that generates Raman 300-mm fibers around a central 400-mm fiber) scattering; the silica in the optical fiber that carries laser Two versions of the in vivo Raman probe. light to the tissue does as well. Thus, a meter or so of optical fiber yields a much stronger signal than the millimeters of tissue being studied. Given the usefulness of such a probe, To make a suitable probe, Wach it may come as a surprise that medical and his Cirrex co-workers began with applications are not driving this techa set of optical fibers: one fiber to denology; telecommunications are. The liver laser light to the tissues and other filtering associated with Raman specindividual fibers to carry the returning troscopy in optical fibers is of great inRaman-scattered light. The key to the terest to the telecommunications indus-
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try, which is trying to move away from monochromatic optical fibers to colormultiplexed optical fibers, Wach explains. Nevertheless, the new probe may be useful for both clinical diagnostics and pharmaceutical studies. In the current paper, the researchers report that they were able to collect spectra from arterial walls and plaques in vivo and in vitro and distinguish vulnerable plaques from calcified plaques. The high-risk vulnerable plaques have an obvious signature, Puppels says. “For example, [they] lack the very distinctive signal contributions from hydroxy apatite—the calcification—that is present in [stable] plaques,” he explains. “They also show a strong signal contribution [from] cholesterol.” Best of all, the data can be collected quickly. Once the probe is in place, samples can be measured in
