Hyeong Soo Nam

Fully Integrated High-Speed Intravascular Optical Coherence Tomography/Near-Infrared Fluorescence Structural/Molecular Imaging In Vivo Using a Clinically Available Near-Infrared Fluorescence–Emitting Indocyanine Green to Detect Inflamed Lipid-Rich Atheromata in Coronary-Sized Vessels

Background—Lipid-rich inflamed coronary plaques are prone to rupture. The purpose of this study was to assess lipid-rich inflamed plaques in vivo using fully integrated high-speed optical coherence tomography (OCT)/near-infrared fluorescence (NIRF) molecular imaging with a Food and Drug Administration–approved indocyanine green (ICG). Methods and Results—An integrated high-speed intravascular OCT/NIRF imaging catheter and a dual-modal OCT/NIRF system were constructed based on a clinical OCT platform. For imaging lipid-rich inflamed plaques, the Food and Drug Administration–approved NIRF-emitting ICG (2.25 mg/kg) or saline was injected intravenously into rabbit models with experimental atheromata induced by balloon injury and 12- to 14-week high-cholesterol diets. Twenty minutes after injection, in vivo OCT/NIRF imaging of the infrarenal aorta and iliac arteries was acquired only under contrast flushing through catheter (pullback speed up to ⩽20 mm/s). NIRF signals were strongly detected in the OCT-visualized atheromata of the ICG-injected rabbits. The in vivo NIRF target-to-background ratio was significantly larger in the ICG-injected rabbits than in the saline-injected controls (P<0.01). Ex vivo peak plaque target-to-background ratios were significantly higher in ICG-injected rabbits than in controls (P<0.01) on fluorescence reflectance imaging, which correlated well with the in vivo target-to-background ratios (P<0.01; r=0.85) without significant bias (0.41). Cellular ICG uptake, correlative fluorescence microscopy, and histopathology also corroborated the in vivo imaging findings. Conclusions—Integrated OCT/NIRF structural/molecular imaging with a Food and Drug Administration –approved ICG accurately identified lipid-rich inflamed atheromata in coronary-sized vessels. This highly translatable dual-modal imaging approach could enhance our capabilities to detect high-risk coronary plaques.

Intravascular optical imaging of high-risk plaques in vivo by targeting macrophage mannose receptors.

Macrophages mediate atheroma expansion and disruption, and denote high-risk arterial plaques. Therefore, they are substantially gaining importance as a diagnostic imaging target for the detection of rupture-prone plaques. Here, we developed an injectable near-infrared fluorescence (NIRF) probe by chemically conjugating thiolated glycol chitosan with cholesteryl chloroformate, NIRF dye (cyanine 5.5 or 7), and maleimide-polyethylene glycol-mannose as mannose receptor binding ligands to specifically target a subset of macrophages abundant in high-risk plaques. This probe showed high affinity to mannose receptors, low toxicity, and allowed the direct visualization of plaque macrophages in murine carotid atheroma. After the scale-up of the MMR-NIRF probe, the administration of the probe facilitated in vivo intravascular imaging of plaque inflammation in coronary-sized vessels of atheromatous rabbits using a custom-built dual-modal optical coherence tomography (OCT)-NIRF catheter-based imaging system. This novel imaging approach represents a potential imaging strategy enabling the identification of high-risk plaques in vivo and holds promise for future clinical implications.

Automated detection of vessel lumen and stent struts in intravascular optical coherence tomography to evaluate stent apposition and neointimal coverage

PURPOSE Intravascular optical coherence tomography (IV-OCT) is a high-resolution imaging method used to visualize the microstructure of arterial walls in vivo. IV-OCT enables the clinician to clearly observe and accurately measure stent apposition and neointimal coverage of coronary stents, which are associated with side effects such as in-stent thrombosis. In this study, the authors present an algorithm for quantifying stent apposition and neointimal coverage by automatically detecting lumen contours and stent struts in IV-OCT images. METHODS The algorithm utilizes OCT intensity images and their first and second gradient images along the axial direction to detect lumen contours and stent strut candidates. These stent strut candidates are classified into true and false stent struts based on their features, using an artificial neural network with one hidden layer and ten nodes. After segmentation, either the protrusion distance (PD) or neointimal thickness (NT) for each strut is measured automatically. In randomly selected image sets covering a large variety of clinical scenarios, the results of the algorithm were compared to those of manual segmentation by IV-OCT readers. RESULTS Stent strut detection showed a 96.5% positive predictive value and a 92.9% true positive rate. In addition, case-by-case validation also showed comparable accuracy for most cases. High correlation coefficients (R > 0.99) were observed for PD and NT between the algorithmic and the manual results, showing little bias (0.20 and 0.46 μm, respectively) and a narrow range of limits of agreement (36 and 54 μm, respectively). In addition, the algorithm worked well in various clinical scenarios and even in cases with a low level of stent malapposition and neointimal coverage. CONCLUSIONS The presented automatic algorithm enables robust and fast detection of lumen contours and stent struts and provides quantitative measurements of PD and NT. In addition, the algorithm was validated using various clinical cases to demonstrate its reliability. Therefore, this technique can be effectively utilized for clinical trials on stent-related side effects, including in-stent thrombosis and in-stent restenosis.

Endoscopic micro-optical coherence tomography with extended depth of focus using a binary phase spatial filter

Micro-optical coherence tomography (μOCT) is an advanced imaging technique that acquires a three-dimensional microstructure of biological samples with a high spatial resolution, up to 1 μm, by using a broadband light source and a high numerical aperture (NA) lens. As high NA produces a short depth of focus (DOF), extending the DOF is necessary to obtain a reasonable imaging depth. However, due to the complexity of optics and the limited space, it has been challenging to fabricate endoscopic μOCT, which is essential for clinical translation. Here, we report an endoscopic μOCT probe with an extended DOF by using a binary phase spatial filter. The imaging results from latex beads demonstrated that the μOCT probe achieved an axial resolution of 2.49 μm and a lateral resolution of 2.59 μm with a DOF extended by a factor of 2. The feasibility of clinical use was demonstrated by ex vivo imaging of the rabbit iliac artery.

A bi-directional assessment of spontaneous coronary artery dissection by three-dimensional flythrough rendering of optical coherence tomography images

A 71-year-old woman was admitted to our hospital due to unstable chest pain. Coronary angiography demonstrated a complex eccentric lesion with 80% narrowing of the right coronary arterial lumen ( Panel A ). Intravascular optical coherence tomography (IV-OCT) revealed typical characteristics of spontaneous coronary artery …

Characterization of lipid-rich plaques using spectroscopic optical coherence tomography

Abstract. Intravascular optical coherence tomography (IV-OCT) is a high-resolution imaging method used to visualize the internal structures of walls of coronary arteries in vivo. However, accurate characterization of atherosclerotic plaques with gray-scale IV-OCT images is often limited by various intrinsic artifacts. In this study, we present an algorithm for characterizing lipid-rich plaques with a spectroscopic OCT technique based on a Gaussian center of mass (GCOM) metric. The GCOM metric, which reflects the absorbance properties of lipids, was validated using a lipid phantom. In addition, the proposed characterization method was successfully demonstrated in vivo using an atherosclerotic rabbit model and was found to have a sensitivity and specificity of 94.3% and 76.7% for lipid classification, respectively.

Comprehensive intravascular imaging of atherosclerotic plaque in vivo using optical coherence tomography and fluorescence lifetime imaging

Comprehensive imaging of both the structural and biochemical characteristics of atherosclerotic plaque is essential for the diagnosis and study of coronary artery disease because both a plaque’s morphology and its biochemical composition affect the level of risk it poses. Optical coherence tomography (OCT) and fluorescence lifetime imaging (FLIm) are promising optical imaging methods for characterizing coronary artery plaques morphologically and biochemically, respectively. In this study, we present a hybrid intravascular imaging device, including a custom-built OCT/FLIm system, a hybrid optical rotary joint, and an imaging catheter, to visualize the structure and biochemical composition of the plaque in an atherosclerotic rabbit artery in vivo. Especially, the autofluorescence lifetime of the endogenous tissue molecules can be used to characterize the biochemical composition; thus no exogenous contrast agent is required. Also, the physical properties of the imaging catheter and the imaging procedures are similar to those already used clinically, facilitating rapid translation into clinical use. This new intravascular imaging catheter can open up new opportunities for clinicians and researchers to investigate and diagnose coronary artery disease by simultaneously providing tissue microstructure and biochemical composition data in vivo without the use of exogenous contrast agent.

Intravascular Optical Molecular Imaging of a Macrophage Subset Within Intraplaque Hemorrhages

Intraplaque hemorrhages (IPH) accelerate plaque destabilization via oxidative stress, free cholesterol secretion, macrophage accumulation, and necrotic core expansion. Macrophages in these hemoglobin-exposed segments differentiate into a distinct phenotype characterized by the expression of CD163

Spectroscopic optical coherence tomography: A review of concepts and biomedical applications

ABSTRACT Optical coherence tomography (OCT) is a 3-dimensional high-resolution imaging modality based on an interferometry and is widely used in a large variety of medical fields. Spectroscopic OCT (S-OCT) is a signal-processing method that uses the raw interferograms generated by OCT to investigate depth-resolved spectroscopic profiles of a sample. The spectroscopic information provided by S-OCT can be used to enhance the contrast of OCT images and overcome the limitations of gray-scale OCT images that describe only morphology. In this review, we present the concepts behind S-OCT as well as acquisition methods and description of obtainable spectroscopic properties. Furthermore, this review covers the biomedical applications of the spectroscopic information that can be obtained with S-OCT, including measurements of hemoglobin concentrations, blood oxygen saturation levels, atherosclerotic plaque detection, evaluation of burn injuries, contrast enhancement using exogenous contrast agents, and detection of precancerous lesions.