Atherosclerosis occurs when fat, cholesterol, and other substances build up on the walls of arteries, making these blood vessels thick and hard. A heart attack or stroke can occur when an atherosclerotic plaque in a blood vessel ruptures or breaks off.

“Atherosclerosis, which causes heart attacks and strokes, is the leading cause of death in Western societies, exceeding all cancer types combined, and is therefore a major public health problem. ” said research team member leader Laura Malk of the University of Wisconsin. Davis, California. “Better clinical management enabled by advanced intravascular imaging tools will improve patient outcomes by providing more accurate information to help cardiologists tailor treatment and supporting the development of new treatments.” will benefit.”

Published in the journal of Optica Publishing Group Biomedical Optics Express, researchers describe a new flexible device that combines fluorescence lifetime imaging (FLIM) and polarization-sensitive optical coherence tomography (PSOCT) to capture rich information about the composition, morphology, and microstructure of atherosclerotic plaques. I’m explaining. The study was a collaborative project with his OCT experts Brett Bouma and Martin Billiger of the Wellman Center for Optical Medicine at Massachusetts General Hospital.

“With further testing and development, our device could be used for longitudinal studies that obtain intravascular images from the same patient at different time points, providing images of plaque evolution and response to therapeutic interventions.” said Julian Beck, lead author of the paper. . “This will be extremely valuable for better understanding disease progression, assessing the effectiveness of new drugs and treatments, and guiding stenting procedures used to restore normal blood flow. ”

Get views like never before

Most of what scientists know about how atherosclerosis forms and progresses over time comes from histopathological studies of postmortem coronary artery specimens. The development of imaging systems such as intravascular ultrasound and intravascular OCT has made it possible to study plaques in living patients, but improved methods and tools are needed to investigate and characterize atherosclerosis. is still needed.

To address this need, researchers embarked on a multi-year research project to develop and validate multispectral FLIM as an intravascular imaging modality. FLIM provides insight into features such as the composition of the extracellular matrix (the protein scaffold between cells), the presence of inflammation, and the degree of calcification inside the artery. Previous studies combined FLIM with intravascular ultrasound, while this new study combined it with PSOCT. PSOCT provides high-resolution morphological information along with birefringence and depolarization measurements. FLIM and PSOCT together provide an unprecedented amount of information about plaque morphology, ultrastructure, and biochemical composition.

“Birefringence provides information about plaque collagen, an important structural protein that helps stabilize lesions, and depolarization is related to lipid content, which contributes to plaque destabilization,” said Bec. Ta. “Overall, this hybrid approach can provide the most detailed image of plaque characteristics of all intravascular imaging modalities reported to date.”

Two imaging modalities in one device

The development of multimodal intravascular imaging systems compatible with coronary catheterization is technically challenging. It requires very thin (less than 1 mm) flexible catheters that can be maneuvered into blood vessels with sharp twists and turns. High imaging speeds of approximately 100 frames/s are also required to limit cardiac motion artifacts and ensure adequate imaging of the artery interior.

To integrate FLIM and PSOCT into a single device without compromising the performance of either imaging modality, the researchers used optical components previously developed by Marcu’s lab and other research groups. did. The key to achieving high PSOCT performance is a newly designed rotating collimator with high optical throughput and high return loss (the ratio of the power reflected towards the light source compared to the power incident on the device). did. The catheter system they developed has dimensions and flexibility similar to intravascular imaging devices currently in clinical use.

After testing the new system using engineered tissue and demonstrating basic functionality in well-characterized samples, researchers believe the system can be used to measure the properties of healthy coronary arteries isolated from pigs. showed that it can also be used. Finally, in vivo testing in pig hearts demonstrated that the performance of the hybrid catheter system was sufficient to support work toward clinical validation. All these tests showed that the FLIM-PSOCT catheter system was able to simultaneously acquire co-registered FLIM data across four different spectral bands and PSOCT backscatter intensity, birefringence, and depolarization information.

Next, the researchers plan to use an intravascular imaging system to image plaques in human coronary arteries ex vivo. By comparing the optical signals acquired using this system with plaque features identified by expert pathologists, we can better understand the features that can be identified by FLIM-PSOCT and use them to develop predictive models. Masu. They also plan to proceed with trials to support clinical validation of the system in patients.