Abstract
.Significance: Detailed biochemical and morphological imaging of the plaque burdened coronary arteries holds the promise of improved understanding of atherosclerosis plaque development, ultimately leading to better diagnostics and therapies.Aim: Development of a dual-modality intravascular catheter supporting swept-source optical coherence tomography (OCT) and frequency-domain fluorescence lifetime imaging (FD-FLIM) of endogenous fluorophores with UV excitation.Approach: We instituted a refined approach to endoscope development that combines simulation in a commercial ray tracing program, fabrication, and a measurement method for optimizing ball-lens performance. With this approach, we designed and developed a dual-modality catheter endoscope based on a double-clad fiber supporting OCT through the core and fluorescence collection through the first cladding. We varied the relative percent of UV excitation launched into the core and first cladding to explore the potential resolution improvement for FD-FLIM. The developed catheter endoscope was optically characterized, including measurement of spatial resolution and fluorescent lifetimes of standard fluorophores. Finally, the system was demonstrated on fresh ex vivo human coronary arteries.Results: The developed endoscope was shown to have optical performance similar to predictions derived from the simulation approach. The FLIM resolution can be improved by over a factor of 4 by primarily illuminating through the core rather than the first cladding. However, time-dependent solarization losses need to be considered when choosing the relative percentage. We ultimately chose to illuminate with 7% of the power transmitting through the core. The resulting catheter endoscope had lateral resolution for OCT and lateral resolution for FD-FLIM. Images of ex vivo coronary arteries are consistent with expectations based on histopathology.Conclusions: The results demonstrate that our approach for endoscope simulation produces reliable predictions of endoscope performance. Simulation results guided our development of a multimodal OCT/FD-FLIM catheter imaging system for investigating atherosclerosis in coronary arteries.
Highlights
Atherosclerosis is the leading cause of morbidity and mortality in the United States.[1,2] It is characterized as a systemic, progressive disease process in which the arterial wall thickens through a process of inflammation, oxidative stress, and dyslipidemia.[3,4] These arterial plaques may rupture leading to thrombosis and occlusion of the vessel and in myocardial infarction, stroke, or limb injury.[5]
The predominant optical intravascular imaging approach, optical coherence tomography (OCT) has been shown to be capable of providing high-resolution structural images revealing the morphological components of plaque in humans.[3]
We describe a dual-modality intravascular OCT/fluorescence lifetime imaging microscopy (FLIM) system based on swept-source OCT and frequencydomain FD-FLIM
Summary
Atherosclerosis is the leading cause of morbidity and mortality in the United States.[1,2] It is characterized as a systemic, progressive disease process in which the arterial wall thickens through a process of inflammation, oxidative stress, and dyslipidemia.[3,4] These arterial plaques may rupture leading to thrombosis and occlusion of the vessel and in myocardial infarction, stroke, or limb injury.[5]. Fluorescence lifetime imaging microscopy (FLIM) is robust to fluorescence intensity fluctuations and able to measure the relative concentration of lipids and collagen.[12,13,14] The measure and identification of lipoproteins is important for finding so-called “vulnerable” plaques that are prone to rupture causing a sudden coronary event
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