Dual-modality optical coherence tomography and frequency-domain fluorescence lifetime imaging microscope system for intravascular imaging

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 40-μm lateral resolution for OCT and <100 μm 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.

Mechanically Rotating Intravascular Ultrasound (IVUS) Transducer: A Review

“…Thus, more than one imaging modality has been integrated into the IVUS images. For example, IVUS/intravascular optical coherence tomography (IV-OCT) [ 184 , 185 , 186 , 187 , 188 , 189 ] and IVUS/near-infrared spectroscopy (NIRS) [ 190 , 191 , 192 , 193 , 194 ] are currently available for practical use, and IVUS images with near-infrared fluorescence (NIRF) [ 195 , 196 , 197 , 198 , 199 ], fluorescence lifetime imaging (FLIm) [ 200 , 201 , 202 , 203 , 204 ], and intravascular photoacoustic (IVPA) [ 123 , 205 , 206 , 207 , 208 ] have been investigated at the laboratory level. These combinations can complement the drawbacks of each imaging modality while providing more clinical information.…”

Double-Clad Fiber-Based Multifunctional Biosensors and Multimodal Bioimaging Systems: Technology and Applications

“…Monolithic ball lensbased probe with proximal rotary joint [41] Ex vivo structural imaging and compositional contrast in unlabeled biological samples.…”

“… DCF-based probes and catheters. ( A ) Monolithic all-fiber needle probe [ 25 ]; ( B ) monolithic ball lens-based probe [ 41 ]; ( C ) micro-motor-based probe [ 36 ]; ( D ) capsule catheter [ 42 ]. Images reprinted with permissions from refs.…”

A Transparent Ultrasound Array for Real-time Optical, Ultrasound and Photoacoustic Imaging

“…Pure optical imaging methods such as fluorescence imaging enables biochemical information of targeted cells and tissue (e.g. autofluorescence from metabolic co-factors NAD/NADH: nicotinamide adenine dinucleotide) and therefore allows high diagnostic sensitivity and specificity [7][8][9][10]. Deep tissue US and PA imaging modalities provide higher imaging depth and better spatial resolution (scalable with ultrasound parameters, typically 1/100 th of an imaging depth, that is 0.5 mm spatial resolution at 5 cm depth) compared to deep tissue optical imaging with a spatial resolution of about 1/5 th of an imaging depth.…”