DAVIS, Calif.--Given that heart disease remains the leading cause of death both in the United States and worldwide, new methods of monitoring heart health are constantly needed. At present, methods such as ultrasound, fluorescents or angiograms are standard approaches for investigating blood vessels for possible constrictions, but they are far from foolproof.
Laura Marcu's biomedical engineering lab at the University of California, Davis (UC Davis), however, has combined two technologies to produce a more advanced technique that can retrieve both better and more information. Their work was detailed in a Scientific Reports paper titled “In vivo label-free structural and biochemical imaging of coronary arteries using an integrated ultrasound and multispectral fluorescence lifetime catheter system.”
Marcu's lab, as noted on the UC Davis website, focuses on “promoting better diagnosis, treatment and prevention of human diseases through advancements in biophotonics technology – a field at the interface of physical sciences, engineering, biology and medicine. Our research projects target research for development of optical spectroscopy and imaging techniques for medical diagnostics and integration of these techniques in multimodal tissue diagnostic platforms, including high-frequency ultrasound technologies.”
The approach in question certainly fits those characteristics, as it unites intravascular ultrasound (IVUS) with fluorescence lifetime imaging (FLIm). FLIm is an imaging technique in which an image is produced based on the differences in the decay rate of a given fluorescent sample. In addition to imaging arteries, this new catheter is also capable of collecting structural and biochemical information about the arterial plaque found, which could potentially help to better predict a patient's risk of heart attack. IVUS, for its part, is a familiar technique for detecting plaque, as it can penetrate any accumulated plaque to determine its depth, though it's unable to offer specifics in terms of plaque rupture risk.
The new catheter, which combines a fiber optic and an ultrasound probe in an intravascular catheter, was tested in living pig hearts and ex-vivo samples of human coronary arteries. It proved flexible enough to navigate coronary arteries in living patients with standard procedures, and this approach does not require either injected fluorescent tracers or further modification of catheterization procedures. In addition, the researchers were able to overcome the issue of heart motion interfering with the ability to quickly collect data, using a transparent solution to displace blood enabled them to get a clear view of artery walls.
This imaging approach works by sending short laser pulses through the fiber optic to excite molecules in tissue, consequently releasing a small amount of light. The intensity and duration of that light is based on the biochemical composition of the tissue, such as the proportions of collagen, elastin or lipids.
“Current results show that FLIm parameters linked to the amount of structural proteins (e.g. collagen, elastin) and lipids (e.g. foam cells, extracellular lipids) in the first 200 μm of the intima provide important biochemical information that can supplement IVUS data for a comprehensive assessment of plaques pathophysiology. The unique FLIm-IVUS system evaluated here has the potential to provide a comprehensive insight into atherosclerotic lesion formation, diagnostics and response to therapy,” the authors wrote in the abstract.
The team had explored this approach before, noting in the paper that they had developed a catheter in previous work that had a “small cross-section profile (3.2 Fr) relying on sequential scanning of the field of view by independent FLIm and IVUS imaging cores integrated into a single sheath and imaging section.” While it wasn't flexible enough for use in vivo, upon applying it to ex-vivo human coronary arteries, the researchers were able to “differentiate between eight different plaque subtypes, identifying for example thin cap fibroatheroma (TCFA) with 90-percent sensitivity and 100-percent specificity using pathological features such as the presence of macrophages in the fibrous cap.”
The authors suggest that there is utility for their imaging technique beyond evaluating patients for heart attack risking, explaining that “the effect of therapeutic agents on biochemical and structural composition of plaque could be evaluated, leading to a non-invasive method to monitor efforts aimed at acute coronary syndromes prevention.”
As for the next step for this work, Marcu’s group is seeking U.S. Food and Drug Administration approval to test the new imaging technology on human patients.