There is significant histopathological and clinical evidence that near-infrared auto-fluorescence (NIRAF) complements optical coherence tomography (OCT) for detecting high-risk coronary plaque. Here, we determined the accuracy of an OCT-NIRAF imaging system and catheter for detecting NIRAF in human coronary lesions. OCT-NIRAF pullback imaging was performed on human cadaver coronary arteries (n=33 from 14 patients) during PBS perfusion via a fully integrated OCT-NIRAF imaging system and catheter (NIRAF ex. 633 nm, 1 mW power; em. 660-740nm). Confocal NIRAF images were acquired from corresponding unstained formalin-fixed paraffin-embedded sections (Olympus FLUOVIEW FV1000; ex. 635 nm; em. 655-755nm). OCT-NIRAF and confocal NIRAF images were registered using known pullback speed, anatomical landmarks, and fiducial features (e.g., calcification), and spatially overlapped by affine transformation of the confocal NIRAF images. Each image was split into 8, 45º-sectors, emanating from the catheter location. Each 45°-sector was determined to be positive if <5% of the intima contained confocal NIRAF, and if <5% of 45°-arc (2.25°) of the catheter-based NIRAF signal was above the system’s detection limit. A total of 1896 45°-sectors from 291 distinct coronary locations were analyzed using confocal NIRAF as the gold standard. Considering superficial confocal NIRAF foci within 0.5 mm from the luminal surface, sensitivity and specificity were 90.0% (95%CI: 69.8- 100.0%) and 90.2% (95%CI: 88.8-91.7%), respectively. Within 0.5 mm to 1.0 mm depth from the luminal surface, the sensitivity was 36.4% (95%CI: 15.0-57.8%) and specificity was 90.1% (95%CI: 88.6-91.5%). These results indicate that the OCT-NIRAF system/catheter’s ability to detect NIRAF is depth dependent and accurate in plaque regions (within 0.5 mm from the luminal surface) that are most responsible for precipitating coronary events.
Coronary arteries are covered by a thin layer of endothelial cells (ECs). Impairment of ECs is at the origin of coronary atherosclerosis and its clinical manifestations. However, the study of ECs in humans remains elusive because of a lack of an imaging tool with sufficient resolution. We have developed a light-based 1-µm-resolution microscopic imaging technology termed micro-optical coherence tomography (µOCT) that can be implemented in a coronary catheter. In this study, we investigated the capability of µOCT to visualize EC morphology. We stripped the endothelium from 36 fresh swine coronary segments with cyanoacrylate glue. Histology showed that the stripping procedure successfully removed ECs from the swine coronary arteries. Coronary segments were then imaged in 3D with µOCT, and were processed for histology and scanning electron microscopy (SEM). µOCT images of stripped vs. intact sites were volume rendered in 3D and visually compared. 3D-µOCT allowed visualization of EC pavementing on intact artery surfaces that was strongly correlated to that seen by SEM. EC pavementing disappeared, and surface roughness calculated by computed root mean squared error diminished significantly at the sites with stripped EC compared with intact sites. µOCT was also utilized in human cadaver coronary arteries, showing its capability of identifying EC morphology of human coronary plaque harboring leukocyte adhesion, EC stent strut tissue coverage, and lack of ECs at lesions with necrotic core or superficial nodular calcifications. In conclusion, µOCT enables EC visualization in coronary arteries, suggesting that it could be useful in patients with coronary artery disease to better understand the role of ECs in the pathogenesis of coronary artery disease.
Optical coherence tomography (OCT) has been a useful clinical tool for diagnosing coronary artery disease through a flexible catheter, but its full promise relies on resolving cellular and sub-cellular structures in vivo. Previously, visualizing cellular structures through an imaging catheter is not possible due to limited depth of focus (DOF) of a tightly focused Gaussian beam: typically, a Gaussian beam with 2-3 μm resolution has a DOF within 100 μm, which is not sufficient for in vivo catheter imaging. Therefore, we developed a self-imaging wavefront division optical system that generates a coaxially-focused multimode (CAFM) beam with a DOF that is approximately one order of magnitude longer than that of a Gaussian beam. In this study, we present a high-resolution, extended DOF catheter based on self-imaging wavefront division optics. The catheter generates a CAFM beam with a lateral resolution of 3 μm and a DOF close to 2 mm. To correct the aberration introduced by catheter sheath, we incorporated a cylindrical prism to compensate the sheath astigmatism. When the catheter is incorporated into a micro-resolution OCT (μOCT) system with rotational scanning mechanics, cellular-resolution cross-sectional images of the coronary artery wall can be obtained. The device serves as an important step toward characterizing cellular and sub-cellular structures in vivo for coronary artery disease diagnosis.
Background: Birefringent crystals such as cholesterol and monosodium urate have recently been identified as possible pharmacologic targets for the treatment of coronary artery disease. The size of these crystals can be very small (on the order of 1 µm), making them difficult to identify. To image these microscopic crystals and enhance contrast, we modified existing micro optical coherence tomography system so that it was capable of obtaining polarization-sensitive images (PS-µOCT).
A spectrometer-based PS-µOCT system was developed using a 270 nm wide broadband light source centered at 765 nm. Light was polarized using a polarizer and coupled to a SMF. The polarized light after SMF was divided into reference and sample arms using a beam splitter. Images of orthogonal polarization states were acquired sequentially by inserting and removing a quarter wave plate in the reference arm. The orthogonal PS- µOCT image components were used to generate birefringent images of the tissue.
The axial resolution of the PS-µOCT system was 1.9 mm and the lateral resolution was 2 microns and the SNR was 92 dB. PS-µOCT was able to clearly identify isolated cholesterol and uric acid crystals. When used to image cadaver coronary arteries, the PS-µOCT images of crystals had up to 11 dB improved contrast compared to images obtained with a standard µOCT system.
Results show that the use of PS-µOCT improves image contrast for isolated crystals and crystals within coronary atherosclerotic plaque and suggest that it could be useful for understanding their roles in the development and progression of coronary artery disease.
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