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01 Mar 2017
Universities of Michigan and Washington combine laser-induced reflectance and fluorescence in multimodal probe.
Cardiovascular disease caused by atherosclerosis, a build-up of plaque on the inner walls of arteries which affects normal blood flow, is a major health problem worldwide.But atherosclerosis is not a simple process, and scientists continue to investigate the factors controlling both plaque formation and the vulnerability of inflamed atherosclerotic plaque to rupture, which can be a precipitating factor in thrombosis and ischemia. High quality intraluminal imaging of arteries and atherosclerosis is an important part of this research.
A project under way at the University of Michigan and the University of Washington has developed an imaging technique that may prove highly valuable, based around a scanning fiber endoscope (SFE) 1.2 mm in diameter. It could lead to a standalone platform for real-time structural, chemical and biological images of large vascular surfaces, allowing clinicians to classify the extent of atherosclerosis and learn more about the condition. The proof-of-concept research into the new scanning fiber angioscopy (SFA) technique was published in Nature Biomedical Engineering.
The instrument collects laser-induced reflectance and fluorescence simultaneously, by scanning blue, green and red laser light at wavelengths of 424, 488 and 642 nm respectively in a spiral pattern on the tissue surface. Reflectance and fluorescence, from both extrinsic or intrinsic fluorophores, is collected through a ring of optical fibres within the periphery of the same ultrathin flexible catheter, so that co-registered images of the area being analyzed can be built up.
The SFE technology is based on work by Eric Seibel at the University of Washington, who originally designed it for early detection of cancer and the imaging of cancer cells that are invisible with existing clinical endoscopes, but has continued to develop the design for other biomedical applications too.
"This new SFE has the added feature of wide-field fluorescence endoscopy with either grayscale or full-color reflectance," commented Seibel. "Hence this instrument offers multimodal concurrent imaging operation in fluorescence and reflectance."
Development of an SFE offering both modalities involved addressing the different criteria for adequate signal levels in each of these channels, accommodating scenarios where the fluorescence signal was low and close to the instrument's own noise level, compared to the higher signal levels received from reflectance. The project tackled this by taking cues from the field of laser scanning microscopy, and its use of fluorescence contrast in imaging.
"We also needed to develop methods that could compensate for distance, specular reflectance and spectral overlap, in order to make the SFE fluorescence video quantitative," noted Seibel. "That gives the image greater diagnostic potential, especially with biomarkers."
Thin and flexible
Researchers tested the new SFA technique on ex vivo samples of human arteries, and in vivo examination of the aorta in rabbits, proving that the design offers several practical benefits for the imaging of atherosclerosis, not least its small diameter and high degree of flexibility.
"The front-viewing optics of the SFA system provide sharp remote imaging of vascular surfaces without the need for approaching or crossing potentially unstable atherosclerotic lesions," said Savastano. "This provides a safety edge for invasive imaging of vulnerable and complicated atherosclerosis compared to side-viewing technology, such as OCT. In addition, by generating wide field-of-view images with large depth of focus, it only requires a clear field of view for a very short time - even a single video frame - compared with lateral view devices that require rotational pullback to reconstruct images."
An approach combining reflectance with laser-induced fluorescence emission from intrinsic arterial fluorophores allows the platform to generate high-resolution endoscopic videos of healthy and diseased arteries without altering their biochemical makeup with added labels, improving the ability to detect and classify different stages of atherosclerotic lesions.
It also yields images with a spatial resolution of approximately 12 microns at typical imaging distances, said to be more than twenty-times higher than commercially available fiber-bundle angioscopes can provide, allowing visualization of smaller targets and improved recognition of the hallmarks of complicated and vulnerable atherosclerotic lesions.
"Non-invasive techniques such as positron emission tomography and MRI have emerged for molecular imaging of atherosclerosis, but the intricate complexity of the condition often demands higher resolution diagnostic approaches able to detect the key markers of plaque vulnerability with high specificity and spatial resolution," commented Savastano.
"We have proved that multimodal SFA can be used for biological imaging of atherosclerotic plaque vulnerability with a resolution far above non-invasive technology. In addition to improving primary prevention of cerebrovascular and cardiovascular disease, the ability to image biological endpoints of plaque vulnerability could also provide valuable information to clinicians monitoring responses to lifestyle changes and drugs."
Translation of the SFE into the interventional neurovascular clinic is now on the agenda, with work under way to develop and optimize the endovascular techniques that will be required for an upcoming move into clinical settings. VerAvanti, a developer of medical devices spun out from the University of Washington, is bringing the SFA technology to market and is in the final stages of product development. The current intention is that CE-marked and FDA-cleared product will appear by the last quarter of 2017.
About the Author
Tim Hayes is a contributor to Optics.org.
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