Clinical Characterization of Coronary Atherosclerosis With Dual-Modality OCT and Near-Infrared Autofluorescence Imaging.
ABSTRACT: The authors present the clinical imaging of human coronary arteries in vivo using a multimodality optical coherence tomography (OCT) and near-infrared autofluorescence (NIRAF) intravascular imaging system and catheter.Although intravascular OCT is capable of providing microstructural images of coronary atherosclerotic lesions, it is limited in its capability to ascertain the compositional/molecular features of plaque. A recent study in cadaver coronary plaque showed that endogenous NIRAF is elevated in necrotic core lesions. The combination of these 2 technologies in 1 device may therefore provide synergistic data to aid in the diagnosis of coronary pathology in vivo.We developed a dual-modality intravascular imaging system and 2.6-F catheter that can simultaneously acquire OCT and NIRAF data from the same location on the artery wall. This technology was used to obtain volumetric OCT-NIRAF images from 12 patients with coronary artery disease undergoing percutaneous coronary intervention. Images were acquired during a brief, nonocclusive 3- to 4-ml/s contrast purge at a speed of 100 frames/s and a pullback rate of 20 or 40 mm/s. OCT-NIRAF data were analyzed to determine the distribution of the NIRAF signal with respect to OCT-delineated plaque morphological features.High-quality intracoronary OCT and NIRAF image data (>50-mm pullback length) were successfully acquired without complication in all patients (17 coronary arteries). The maximum NIRAF signal intensity of each plaque was compared with OCT-defined type, showing a statistically significant difference between plaque types (1-way analysis of variance, p < 0.0001). Interestingly, coronary arterial NIRAF intensity was elevated only focally in plaques with a high-risk morphological phenotype (p < 0.05), including OCT fibroatheroma, plaque rupture, and fibroatheroma associated with in-stent restenosis.This OCT-NIRAF study demonstrates that dual-modality microstructural and fluorescence intracoronary imaging can be safely and effectively conducted in human patients. Our findings show that NIRAF is associated with a high-risk morphological plaque phenotype. The focal distribution of NIRAF in these lesions furthermore suggests that this endogenous imaging biomarker may provide complementary information to that obtained by structural imaging alone.
Project description:This study sought to determine whether indocyanine green (ICG)-enhanced near-infrared fluorescence (NIRF) imaging can illuminate high-risk histologic plaque features of human carotid atherosclerosis, and in coronary atheroma of living swine, using intravascular NIRF-optical coherence tomography (OCT) imaging.New translatable imaging approaches are needed to identify high-risk biological signatures of atheroma. ICG is a U.S. Food and Drug Administration-approved NIRF imaging agent that experimentally targets plaque macrophages and lipid in areas of enhanced endothelial permeability. However, it is unknown whether ICG can target atheroma in patients.Eight patients were enrolled in the BRIGHT-CEA (Indocyanine Green Fluorescence Uptake in Human Carotid Artery Plaque) trial. Five patients were injected intravenously with ICG 99 ± 25 min before clinically indicated carotid endarterectomy. Three saline-injected endarterectomy patients served as control subjects. Excised plaques underwent analysis by intravascular NIRF-OCT, reflectance imaging, microscopy, and histopathology. Next, following ICG intravenous injection, in vivo intracoronary NIRF-OCT and intravascular ultrasound imaged 3 atheroma-bearing coronary arteries of a diabetic, cholesterol-fed swine.ICG was well tolerated; no adverse clinical events occurred up to 30 days post-injection. Multimodal NIRF imaging including intravascular NIRF-OCT revealed that ICG accumulated in all endarterectomy specimens. Plaques from saline-injected control patients exhibited minimal NIRF signal. In the swine experiment, intracoronary NIRF-OCT identified ICG uptake in all intravascular ultrasound-identified plaques in vivo. On detailed microscopic evaluation, ICG localized to plaque areas exhibiting impaired endothelial integrity, including disrupted fibrous caps, and within areas of neovascularization. Within human plaque areas of endothelial abnormality, ICG was spatially related to localized zones of plaque macrophages and lipid, and, notably, intraplaque hemorrhage.This study demonstrates that ICG targets human plaques exhibiting endothelial abnormalities and provides new insights into its targeting mechanisms in clinical and experimental atheroma. Intracoronary NIRF-OCT of ICG may offer a novel, clinically translatable approach to image pathobiological aspects of coronary atherosclerosis. (Indocyanine Green Fluorescence Uptake in Human Carotid Artery Plaque [BRIGHT-CEA]; NCT01873716).
Project description:AbstractBackground?Pathological studies have reported that patients with acute coronary syndrome (ACS) may have different plaque morphologies at culprit lesions, and one of the underlying mechanisms for ACS is plaque erosion. However, the morphological features of plaque erosion obtained by multiple intracoronary imaging modalities have not been fully elucidated.Case summary?We experienced two cases with ACS of culprit lesions exhibiting optical coherence tomography (OCT)-defined plaque erosion. Additional examinations using near-infrared spectroscopy (NIRS)–intravascular ultrasound and coronary angioscopy suggested the presence of two distinct phenotypes of plaque erosion. These two types of erosion differ in the extent of NIRS-derived lipid core burden and coronary angioscopy-derived luminal surface colour.Discussion?OCT-defined plaque erosion may not be the unique entity but have at least two distinct plaque morphologies, and NIRS and/or coronary angioscopy may provide incremental ability of discriminating these plaque phenotypes classified as plaque erosion by OCT.
Project description:Intravascular optical coherence tomography (IV-OCT) is an imaging modality that can be used for the assessment of intracoronary stents. Recent publications pointed to the fact that 3D visualizations have potential advantages compared to conventional 2D representations. However, 3D imaging still requires a time consuming manual procedure not suitable for on-line application during coronary interventions. We propose an algorithm for a rapid and fully automatic 3D visualization of IV-OCT pullbacks. IV-OCT images are first processed for the segmentation of the different structures. This also allows for automatic pullback calibration. Then, according to the segmentation results, different structures are depicted with different colors to visualize the vessel wall, the stent and the guide-wire in details. Final 3D rendering results are obtained through the use of a commercial 3D DICOM viewer. Manual analysis was used as ground-truth for the validation of the segmentation algorithms. A correlation value of 0.99 and good limits of agreement (Bland Altman statistics) were found over 250 images randomly extracted from 25 in vivo pullbacks. Moreover, 3D rendering was compared to angiography, pictures of deployed stents made available by the manufacturers and to conventional 2D imaging corroborating visualization results. Computational time for the visualization of an entire data sets resulted to be ~74 sec. The proposed method allows for the on-line use of 3D IV-OCT during percutaneous coronary interventions, potentially allowing treatments optimization.
Project description:AIMS:Identification of invasive and radionuclide imaging markers of coronary plaque vulnerability by a single, widely available non-invasive technique may provide the opportunity to identify vulnerable plaques and vulnerable patients in broad populations. Our aim was to assess whether radiomic analysis outperforms conventional assessment of coronary computed tomography angiography (CTA) images to identify invasive and radionuclide imaging markers of plaque vulnerability. METHODS AND RESULTS:We prospectively included patients who underwent coronary CTA, sodium-fluoride positron emission tomography (NaF18-PET), intravascular ultrasound (IVUS), and optical coherence tomography (OCT). We assessed seven conventional plaque features and calculated 935 radiomic parameters from CTA images. In total, 44 plaques of 25 patients were analysed. The best radiomic parameters significantly outperformed the best conventional CT parameters to identify attenuated plaque by IVUS [fractal box counting dimension of high attenuation voxels vs. non-calcified plaque volume, area under the curve (AUC): 0.72, confidence interval (CI): 0.65-0.78 vs. 0.59, CI: 0.57-0.62; P?<?0.001], thin-cap fibroatheroma by OCT (fractal box counting dimension of high attenuation voxels vs. presence of low attenuation voxels, AUC: 0.80, CI: 0.72-0.88 vs. 0.66, CI: 0.58-0.73; P?<?0.001), and NaF18-positivity (surface of high attenuation voxels vs. presence of two high-risk features, AUC: 0.87, CI: 0.82-0.91 vs. 0.65, CI: 0.64-0.66; P?<?0.001). CONCLUSION:Coronary CTA radiomics identified invasive and radionuclide imaging markers of plaque vulnerability with good to excellent diagnostic accuracy, significantly outperforming conventional quantitative and qualitative high-risk plaque features. Coronary CTA radiomics may provide a more accurate tool to identify vulnerable plaques compared with conventional methods. Further larger population studies are warranted.
Project description:Although directional coronary atherectomy (DCA) is designed to effectively reduce plaque volume by debulking in patients with ischemic heart disease, excision of fibroatheroma has potential to cause distal embolization and periprocedural myocardial infarction. The patients had intravascular ultrasound-derived attenuated plaques in the culprit lesions. A DCA catheter was inserted over a filter-based embolic protection device. After DCA, filter no-reflow phenomenon occurred, and embolized debris was retrieved by the filter device. We describe the novel use of a filter-based embolic protection device during intravascular imaging-guided DCA, particularly in patients at high risk of distal embolization. <<b>Learning objective:</b> The presence of intravascular ultrasound-derived attenuated plaques is at increased risk of distal embolization of debris and periprocedural myocardial infarction during directional atherectomy. A filter-based embolic protection device is available during intracoronary imaging-guided directional coronary atherectomy, particularly in patients at high risk of distal embolization.>.
Project description:<h4>Aims</h4>Coronary high-intensity plaques (HIPs) with a high plaque-to-myocardial signal intensity ratio (PMR) on non-contrast T1-weighted imaging in patients with stable coronary artery disease (CAD) are associated with future coronary events. To characterize the morphological substrate of HIP, we performed a correlative optical coherence tomography (OCT) study.<h4>Methods and results</h4>We examined 137 lesions in 105 patients with stable angina pectoris or silent myocardial ischaemia scheduled for percutaneous coronary intervention (PCI) using a 3?T magnetic resonance scanner. Pre-interventional OCT was performed for PCI target lesions. HIP was defined as PMR???1.4. Of the 137 lesions, 34% were HIP and 66% were non-HIP. The prevalence of lipid-rich plaque (96% vs. 70%, P?<?0.001), macrophage accumulation (65% vs. 46%, P?=?0.046), cholesterol crystals (46% vs. 22%, P?=?0.006), and healed plaque rupture (multiple layers of different optical densities overlaying a large lipid accumulation, 72% vs. 18%, P?<?0.001) was significantly higher in the HIP group than the non-HIP group; no significant differences were observed for the presence of thin cap fibroatheroma, intracoronary thrombus, and plaque rupture between the two groups. Multivariable stepwise logistic regression analysis showed that HIP was significantly associated with the presence of healed plaque rupture [odds ratio (OR) 9.32; 95% confidence interval (95% CI) 4.05-22.71; P?<?0.001] and lipid-rich plaque (OR 4.38; 95% CI 1.08-29.77; P?=?0.038).<h4>Conclusions</h4>The significant association between HIP- and OCT-derived healed plaque rupture and large lipid core provides new insights into the characteristics of high-risk plaques, even in clinically stable CAD.
Project description:Optical coherence tomography (OCT) is a high-resolution imaging technique that is increasingly used for intracoronary imaging to characterize coronary atherosclerotic plaques and vascular responses after coronary stent implantation. Introduction of optical frequency-domain imaging (OFDI; second generation OCT) has simplified practical use of this novel imaging modality resulting in a more widespread availability in interventional cardiology. Here we highlight recent insights into the acute and chronic vascular response after coronary stent implantation by OCT imaging. OCT provides cross-sectional images with approximately 10-fold higher resolution as compared to intravascular-ultrasound (IVUS), allowing for precise evaluation of tissue coverage and malapposition of coronary stent struts. More than 30 studies using OCT to compare vascular responses to different stents have now been reported. Recent studies have examined the relation between OCT-image characteristics and tissue composition around stent struts. OCT is used for evaluation of novel stent concepts, such as bioengineered stents and bioabsorbable stents, where it provides more accurate information than IVUS. While intracoronary OCT imaging is further developed, including faster 3D-OCT-image-reconstruction, larger OCT studies/registries with standardized analysis will provide more insights into clinical implications of observations from OCT-imaging after coronary stent implantation.
Project description:We have developed a novel miniature integrated optical coherence tomography (OCT)-intravascular ultrasound (IVUS) probe, with a 1.5-mm-long rigid part and 0.9-mm outer diameter, for real-time intracoronary imaging of atherosclerotic plaques and guiding of interventional procedures. By placing the OCT ball lens and IVUS transducer back-to-back at the same axial position, this probe can provide automatically coregistered, coaxial OCT-IVUS imaging. To demonstrate its real-time capability, three-dimensional OCT-IVUS imaging of a pig's coronary artery displaying in polar coordinates, as well as images of three major types of atherosclerotic plaques in human cadaver coronary segments, were obtained using this probe and our upgraded system. Histology validation is also presented.
Project description:Acute coronary syndromes (ACS) secondary to coronary vessel plaques represent a major cause of cardiovascular morbidity and mortality worldwide. Advancements in imaging technology over the last 3 decades have continuously enabled the study of coronary plaques via invasive imaging methods like intravascular ultrasound (IVUS) and optical coherence tomography (OCT). The introduction of near-infrared spectroscopy (NIRS) as a modality that could detect the lipid (cholesterol) content of atherosclerotic plaques in the early nineties, opened the potential of studying "vulnerable" or rupture-prone, lipid-rich coronary plaques in ACS patients. Most recently, the ability of NIRS-IVUS to identify patients at risk of future adverse events was shown in a prospective multicenter trial, the Lipid-Rich-plaque Study. Intracoronary NIRS-IVUS imaging offers a unique method of coronary lipid-plaque characterization and could become a valuable clinical diagnostic and treatment monitoring tool.
Project description:A combination optical coherence tomography and near-infrared spectroscopy (OCT-NIRS) coronary imaging system is being developed to improve the care of coronary patients. While stenting has improved, complications continue to occur at the stented site and new events are caused by unrecognized vulnerable plaques. An OCT-NIRS device has potential to improve secondary prevention by optimizing stenting and by identifying vulnerable patients and vulnerable plaques. OCT is already in widespread use world-wide to optimize coronary artery stenting. It provides automated lumen detection and can identify features of coronary plaques not accurately identified by angiography or intravascular ultrasound. The ILUMIEN IV study, to be completed in 2022, will determine if OCT-guided stenting will yield better clinical outcomes than angiographic guidance alone. While the superb spatial resolution of OCT enables the identification of many plaque structural features, the detection by OCT of lipids, an important component of vulnerable plaques, is limited by suboptimal specificity and interobserver agreement. In contrast, NIRS has been extensively validated for lipid-rich plaque detection against the gold-standard of histology and is the only FDA-approved method to identify coronary lipids. Studies in patients have demonstrated that NIRS detects lipid in culprit lesions causing coronary events. In 2019, the positive results of the prospective Lipid-Rich Plaque Study led to FDA approval of NIRS for detection of high-risk plaques and patients. The complementarity of OCT for plaque structure and NIRS for plaque composition led to the sequential performance of NIRS and OCT imaging in patients. NIRS identified lipid while OCT determined the thickness of the cap over the lipid pool. The positive results obtained with OCT and NIRS imaging led to development of a prototype combined OCT-NIRS catheter that can provide co-registered OCT and NIRS data in a single pullback. The data will provide structural and chemical information likely to improve stenting and deliver more accurate identification of vulnerable plaques and vulnerable patients. More precise diagnosis will then lead to OCT-NIRS guided treatment trials to improve secondary prevention. Success in secondary prevention will then facilitate development of improved primary prevention with invasive imaging and effective treatment of patients identified by non-invasive methods.