Signal-poor Regions Research Articles

Oxidized Low-density Lipoproteins and Lipopolysaccharides Augment Carotid Artery Plaque Vulnerability in Hypercholesterolemic Microswine.

Atherosclerosis is a chronic inflammatory disease and hypercholesterolemia is a risk factor. This study aims to compare the potency of lipopolysaccharide (LPS) and oxidized low-density lipoproteins (oxLDL) to induce plaque formation and increase plaque vulnerability in the carotid artery of hypercholesterolemic Yucatan microswine. Atherosclerotic lesions at the common carotid artery junction and ascending pharyngeal artery were induced in hypercholesterolemic Yucatan microswine at 5-6 months of age with balloon angioplasty. LPS or oxLDL were administered intraluminally at the site of injury after occluding the arterial flow temporarily. Pre-intervention ultrasound (US), angiography, and optical coherence tomography (OCT) were done at baseline and just before euthanasia to assess post-op parameters. The images from the US, OCT, and angiography in the LPS and the oxLDL-treated group showed increased plaque formation with features suggestive of unstable plaque, including necrotic core, thin fibrous caps, and a signal poor region more with oxLDL compared to LPS. Histomorphology of the carotid artery tissue near the injury corroborated the presence of severe lesions in both LPS and oxLDL-treated pigs but more in the oxLDL group. Vascular smooth muscle and endothelial cells treated with LPS and oxLDL showed increased folds changes in mRNA transcripts of the biomarkers of inflammation and plaque vulnerability compared to untreated cells. Collectively, the results suggest that angioplasty-mediated intimal injury of the carotid arteries in atherosclerotic swine with local administration of LPS or ox-LDL induces vulnerable plaques compared to angioplasty alone and oxLDL is relatively more potent than LPS in inducing vulnerable plaque.

Optical Coherence Tomography Evaluation of Carotid Artery Stenosis and Stenting in Patients With Previous Cervical Radiotherapy.

ObjectivesCervical radiotherapy can lead to accelerated carotid artery stenosis, increased incidence of stroke, and a higher rate of in-stent restenosis in irradiated patients. Our objective was to reveal the morphological characteristics of radiation-induced carotid stenosis (RICS) and the stent–vessel interactions in patients with previous cervical radiotherapy by optical coherence tomography (OCT).Materials and MethodsBetween November 2017 and March 2019, five patients with a history of cervical radiotherapy were diagnosed with severe carotid artery stenosis and underwent carotid artery stenting (CAS). OCT was conducted before and immediately after the carotid stent implantation. Two patients received OCT evaluation of carotid stenting at 6- or 13-month follow-up.ResultsThe tumor types indicating cervical radiotherapy were nasopharyngeal carcinoma (n = 3), cervical esophageal carcinoma (n = 1), and cervical lymphoma (n = 1). The median interval from the radiotherapy to the diagnosis of RICS was 8 years (range 4–36 years). Lesion characteristics of RICS were detected with heterogeneous signal-rich tissue, dissection, and advanced atherosclerosis upon OCT evaluation. Post-interventional OCT revealed 18.2–57.1% tissue protrusion and 3.3–13.8% stent strut malapposition. Follow-up OCT detected homogeneous signal-rich neointima and signal-poor regions around stent struts. In the patient with high rates of tissue protrusion and stent strut malapposition, the 6-month neointima burden reached 48.9% and microvessels were detected.ConclusionThe morphological features of RICS were heterogeneous, including heterogeneous signal-rich tissue, dissection, and advanced atherosclerosis. Stenting was successful in all 5 patients with severe RICS. One patient, with high rates of tissue protrusion and stent strut malapposition immediately after stenting, received in-stent neointimal hyperplasia at a 6-month follow-up.

Tangential signal dropout artefact in optical frequency domain imaging.

Tangential signal dropout (TSD), which occurs when the optical frequency domain imaging (OFDI) beam strikes the vessel wall under a glancing angle and travels almost parallel to the vessel wall, is the most important imaging artefact leading to the erroneous diagnosis of lipid-rich plaques. This study aimed to evaluate the OFDI artefact of TSD, which mimics the appearance of lipid-rich plaque and macrophage (Mø) infiltration. A total of 1,019 histological cross-sections from 23 autopsy hearts were matched with the corresponding OFDI images. Of these, 232 OFDI cross-sections that contained signal-poor regions with diffuse borders were classified as lipid-rich plaques. The angle θ was calculated between the OFDI beam that strikes the edge of the luminal surface of the low-intensity region and that which strikes the surface line of the low-intensity region. On histological evaluation, 182 (78%) cross-sections were classified as histologically lipidic/Mø infiltration, while the remaining 50 (22%) cross-sections were classified as histologically non-lipidic/Mø infiltration. The angle θ was significantly smaller in the non-lipidic/Mø infiltration group than in the lipidic/Mø infiltration group (12±6° versus 37±14°, p<0.001). Receiver operating curve analysis revealed that the optimal cut-off value of the incident angle for predicting TSD was 23° with an area under the curve of 0.98. When the OFDI imaging beam strikes the tissue at an angle θ<23°, TSD artefact could occur. To eliminate image misinterpretation, our findings suggest that the OFDI catheter geometry should be considered for the accurate diagnosis of lipid-rich plaques and Mø infiltration.

Utility of spectral domain OCT in differentiating optic disc drusen from papilledema in children

The purpose of this study was to test the diagnostic accuracy of optical coherence tomography (OCT) in differentiating optic disc drusen (ODD) from papilledema in children. Retrospective cross-sectional study at a tertiary-care pediatric hospital. Children with high-quality OCT imaging of ODD or papilledema. Quantitative OCT parameters and qualitative OCT features were compared for diagnostic accuracy. There were 41 eyes with ODD and 21 eyes with papilledema. Both the quantitative and qualitative OCT parameters showed highly statistically significant differences between ODD and papilledema (p ≤ 0.01 for all). For quantitative parameters (Bruch's membrane opening and retinal nerve fiber layer thicknesses), the area under the curve from the receiver operator curves ranged from 0.81 to 0.90. For qualitative parameters, the sensitivity for ODD ranged from 27% to 100% and specificity ranged from 67% to 100%. The presence of at least 1 of 3 qualitative OCT parameters (hyporeflective boot-shaped area, isolated/clustered hyperreflective bands, or signal-poor regions in the core) had a sensitivity of 90% and a specificity of 100% for ODD. Both quantitative and qualitative OCT parameters differed significantly between ODD and papilledema in this cohort of children. A combination of several qualitative OCT features had high sensitivity for ODD while effectively ruling out papilledema.

Impact of neoatherosclerosis observed at very late phase after coronary stent implantation on subsequent adverse events

Abstract Background Despite the reduction in late thrombotic events with newer generation coronary stents, late stent failure remains a concern following stent implantation. Neoatherosclerosis (NA) is a cause of in-stent restenosis and acute thrombotic occlusion originating from the stented segment by disruption of the in-stent atheroma. Although the clinical impact of NA at 1 year has been reported, clinical significance of NA observed at very later phase remains to be determined. We sought to investigate the association between optical coherence tomography (OCT) findings at very late phase after stenting and subsequent clinical outcomes. Methods A total of 195 patients with 316 stents (including 74 bare metal stents, 48 first-generation DES, and 194 second-generation DES) without stent failure who underwent OCT examination at &amp;gt;3 years (4.9 [3.9- 5.8] years) after stent implantation according to the prespecified protocol were investigated. OCT analysis included the presence of lipid-laden neointima, macrophage, malapposition, thrombus, and plaque rupture within the stents. NA was defined as having lipid-laden neointima. The criteria for the diagnosis of NA were signal-poor region in continuous flames, lipid length longer than 0.3 mm, and invisible stent strut at NA site. Quantitative OCT measurement included lipid length (LL), lipid arc, minimum lumen area (MLA) at the stented segment and minimum stent area (MSA). Major adverse cardiac events (MACE) including all-cause death, non-fatal myocardial infarction, and clinically driven revascularization were assessed. MACE-free survival rate was compared between patients with stent showing NA (NA group) and those without NA (non-NA group). Furthermore, in per-stent basis analysis, stent failure including remote revascularization and stent thrombosis of the stent after follow-up OCT examination was assessed. Results NA was identified in 50 stents (15.8%) in 38 patients (19.5%). During the median follow-up period of 2.1 [1.0- 2.8] years after OCT examination, 15 MACEs (7.7%) were captured in the total cohort, of which stent failure was observed in 5 stents (5/316, 1.6%). In patient-based analysis, patients with NA had more frequent MACE than those without (18.0% vs 5.1%, p=0.01). Kaplan-Meier analysis revealed that significantly higher MACE rate was detected in NA group than in non-NA group (χ2=5.4, Log-rank p=0.02). In stent-based analysis, NA stents had more frequent stent failure than those without (8.0% vs 0.4%, p=0.002) Conclusions NA observed by OCT at &amp;gt;3 years after implantation were associated with subsequent worse clinical outcomes in both patient and stent-based analysis. NA at the very late phase after stenting might be the therapeutic target of secondary prevention and OCT examination at very late phase after stenting may help identify high risk patients of subsequent MACE. Funding Acknowledgement Type of funding source: None

P197 Similarity and difference in in-stent neoatherosclerosis assessment between near-infrared spectroscopy and optical coherence tomography

Abstract Backgrounds Near-infrared spectroscopy (NIRS) has been implicated to assess the composition of the atherosclerotic plaques in native coronary arteries. However, little has been reported about the assessment of neoatherosclerosis within stents by NIRS. Optical coherence tomography (OCT) is one of the current clinical standard modalities to identify neoatherosclerosis. We sought to compare NIRS and OCT assessments in the detection and evaluation of in-stent neoatherosclerosis. Methods We retrospectively analyzed 54 in-stent lesions in 52 patients who underwent both NIRS and OCT examinations before percutaneous coronary intervention (PCI). All stented segment in both PCI target and non-target lesions were investigated. NIRS analysis included lipid core burden index (LCBI)4mm. NIRS-derived lipid-rich plaque (NIRS-lipid) is defined as LCBI4mm more than 400 according to the previous studies. OCT-derived lipid-laden neointima (OCT-lipid) was defined as having a signal-poor region with diffuse border precluding visualization of stent struts of more than 90 degrees and 1mm in longitudinal length. OCT analysis included the presence or absence of lipid-laden neointima, calcification, ruptured plaque, thrombus, heterogeneous neointima and measurement of lipid length and lipid arc. Lipid volume index (LVI) was defined by OCT as the averaged lipid arc multiplied by lipid length. Max LCBI4mm were compared in lesions with co-registered OCT findings and correlations between max LCBI4mm and LVI were determined. Additionally, OCT findings predicting max LCBI4mm more than 400 were determined. Results Max LCBI4mm was 202 (7.5-460). OCT-lipid was observed in 31 (57.4%) lesions. LVI was 1283 (475-4725). Lesions with OCT-lipid has significantly higher LCBI than those without OCT-lipid (343 [106-593] vs 42 [0-260], p = 0.003). On the other hand, max LCBI were not significantly different according to the presence or absence of calcification, ruptured plaque, thrombus and heterogeneous neointima (60 [39-537] vs 227 [6-451], p = 0.913; 441 [43-547] vs 202 [6-435], p = 0.328; 245 [10-548] vs 251 [42-446], p = 0.990; 202 [40-440] vs 235 [3-471], p = 0.970, respectively). Linear regression analysis showed significant correlation between LVI and max LCBI4mm (P &amp;lt; 0.001). Receiver operating characteristic (ROC) analysis showed the best cutoff max LCBI4mm value for predicting OCT-lipid was 148 (Area under the curve [AUC] = 0.735). ROC analysis showed the best cutoff lipid length and maximum lipid arch value for predicting LCBI4mm more than 400 was 1.9 mm and 128 degrees, (AUC = 0.741, 0.732, respectively) respectively. Conclusion There is good agreement between NIRS and OCT for detection of neoatherosclerosis in stented lesions. In the in-stent lesions, the cut-off value of max LCBI for predicting OCT-lipid was smaller than the previously reported value in de novo lesions. Application of different cut-off value may be considered in in-stent lesions.

P5614The association between tissue morphology assessed with optical coherence tomography and mid and late-term results after percutaneous coronary intervention for in-stent restenosis lesions

Abstract Background It was reported that tissue morphology of in-stent restenosis (ISR) lesions assessed with optical coherence tomography (OCT) had an effect on midterm results including ISR and target lesion revascularization (TLR) rates after percutaneous coronary intervention (PCI). However, little was known about the association between tissue morphology assessed with OCT and late-term results. Methods We performed PCI treated with paclitaxel coated balloon (PCB) or drug-eluting stent (DES) for 452 ISR lesions (260 lesions with fibrous plaque and 192 lesions with lipid-laden plaque) using OCT between May 2008 and July 2016. Six- to eight-month (midterm) angiographic follow-up was performed on 422 of the 452 ISR lesions (follow-up rate: 93.4%). Furthermore, eighteen- to twenty-month (late-term) angiographic follow-up was performed on 337 of the 361 ISR lesions (follow-up rate: 93.4%) which were free from midterm TLR. We examined the association between tissue morphology, midterm-results and late-term results including ISR and TLR rates. Fibrous plaque was defined as homogeneous, signal-rich regions with low attenuation. Lipid-laden plaque was defined as diffuse border, signal poor regions with high attenuation. Results The patients were 353 men and 69 women, and the mean age was 68.8±9.6 years. PCI were performed with PCB in 285 lesions (PCB group) and DES in 137 lesions (DES group). The figure shows the angiographic midterm results of the 422 lesions and late-term results of the 337 lesions with respect to each tissue morphology and each PCI device. There was no difference in ISR and TLR rates of lesions with both fibrous and lipid-laden plaque at midterm between the two groups. ISR and TLR rates of lesions with lipid-laden plaque at late-term were significantly higher in the PCB group than in the DES group, while there was no difference in ISR and TLR rates of lesions with fibrous plaque at late-term between two groups. Figure 1 Conclusion Tissue morphology of ISR lesions might have an impact on outcomes after PCI. Morphological assessment of ISR tissue using OCT might suggest favorable types of PCI for ISR lesions.

Basic interpretation of intracoronary ultrasound and optical coherence tomography images: examples

Basic interpretation of intracoronary ultrasound and optical coherence tomography images: examples

Accuracy of OCT, Grayscale IVUS, and Their Combination for the Diagnosis of Coronary TCFA: An Ex Vivo Validation Study

ObjectivesThis study sought to assess the accuracy of optical coherence tomography (OCT), gray-scale intravascular ultrasound (IVUS), and their combination for detecting thin-cap fibroatheromas (TCFA). BackgroundThe extent to which the imaging characteristics of OCT and IVUS correlate with histologically defined TCFA is unknown. MethodsIVUS and OCT examinations identified focal plaques in 165 coronary arteries from 60 autopsy hearts. A total of 685 pairs of images of OCT and IVUS were compared with histology. By OCT, a TCFA was defined as a signal-poor region with diffuse borders and cap thickness <65 μm. By IVUS, a TCFA was defined by the presence of echolucent zones and/or ultrasound attenuation in areas of positive remodeling. By histology, 12 of 685 focal plaques were classified as TCFAs. ResultsWith histology as the gold standard, the sensitivity, specificity, positive predictive value, negative predictive value, and overall diagnostic accuracy for OCT-derived TCFA were 100%, 97%, 41%, 100%, and 98%, respectively. The corresponding numbers for IVUS-derived TCFA were 92%, 93%, 19%, 99%, and 93%, respectively. The histological findings underlying the false positive diagnoses of OCT for TCFA included large amounts of foam cell accumulation on the luminal surface, large amounts of microcalcifications at the surface, large amounts of hemosiderin accumulation, or organized thrombus. In contrast, histological causes of mischaracterization of TCFA by IVUS were mostly TCFA. When both OCT and IVUS criteria for TCFA were required to be met, the sensitivity, specificity, positive predictive value, negative predictive value, and overall diagnostic accuracy were 92%, 99%, 69%, 99%, and 99%, respectively. ConclusionsIn the present study, neither OCT nor IVUS were optimal to detect TCFA. The combined use of OCT and IVUS may improve TCFA detection accuracy.

Optical Coherence Tomography to Optimize Stent Deployment: Seeing is Believing

Optimal coherence tomography (OCT) is a new light-based intracoronary imaging modality with unprecedented spatial resolution. Currently, its axial resolution is only 15 mm, that is, 10 times higher than that of more classical techniques such as intravascular ultrasound (IVUS) based on ultrasounds (150 mm). Optimal coherence tomography therefore provides extremely high-quality images of the coronary wall, especially of the structures closest to the vessel lumen. Moreover, numerous studies with histological validation have confirmed its ability to adequately differentiate the distinct types of atheromatous plaque, including fibrous plaques (homogeneous, signal-rich regions), lipid plaque (progressively signal-poor regions) and calcified plaque (signal poor, sharp border lesions). For the first time, OCT allows precise measurement of the thickness of the fibrous cap covering the lipid cores and in vivo diagnosis of the presence of thin-cap fibroatheromas. Similarly, this technique can identify the characteristic signs produced by the accumulation of macrophages and cholesterol crystals in the vessel wall, as well as the presence of small ruptures of the intima and of intracoronary thrombi that could not be visualized with IVUS until now. All these properties explain the enormous attractiveness of this technique in the characterization of vulnerable plaques and in the study of the micromorphology of plaques that have already developed a complication. However, the penetration of OCT in the vessel wall is limited and consequently visualization of structures beyond the lumen (near the adventitia) is compromised when there is a substantial amount of atheromatous plaque. Equally, OCT cannot penetrate through red thrombi (fibrin-rich), which produce an intense posterior shadow. Therefore, OCT is not suitable for measuring the total volume of atheromatous plaque. To do this, IVUS remains the technique of choice when the aim is to study the progression or regression of coronary atherosclerosis. From a practical point of view, with the initial technology (time domain), image acquisition was relatively slow and, due to the need to completely eliminate blood from the interior of the

Abstract 17661: Optical Coherence Tomography Identifies Artifactual Thin-cap Fibroatheromas: A Histologic Study

Introduction: Current methods to identify thin-cap fibroatheroma (TCFA) with optical coherence tomography (OCT) are qualitative. While two mechanisms for the appearance of false TCFA have been identified and include macrophages that cause superficial shadowing and tangential light dropout, we report three new mechanisms for the appearance of false TCFAs in OCT images. Methods: 13 coronary arteries from 8 human cadaver hearts (6 male, 2 female, aged 63 ± 12 years) were imaged with OCT. OCT TCFAs were identified independently by three expert OCT readers and defined by a bright homogenous fibrous cap overlying a diffusely shadowed signal-poor region. Analysis was performed to confirm the identification of TCFA or to identify the histologic origin of the OCT TCFA appearance. Arc length of the signal-poor region of each OCT TCFA was also measured. Results: 38 OCT TCFA were identified, of which only 5 were verified with histology. Measurements of arc length and thickness of the cap are summarized in the table. Of the 33 false TCFA, three morphologic plaque types were identified: thick-cap fibroatheroma (TkFA; N=18), pathologic intimal thickening (PIT; N=10), and fibrocalcific (FC; N=5). New mechanisms for the signal-poor regions that appeared as lipid cores included loose connective tissue (N=7), neovasculature (N=3), and proteoglycans (N=4). Superficial shadowing of macrophages caused the appearance of TCFA in 5 cases. In the 18 TkFA cases, OCT underestimated the thickness of the fibrous cap (45.2 ± 4.0 μm by OCT compared to 197.5 ± 18.8 μm by histology). Conclusion: Using an arc length of greater than 90 degrees will aid in differentiating true from false TCFA. Additionally, due to incomplete light penetration, TkFA can be mistaken for TCFA. These results demonstrate that caution should be used when diagnosing vulnerable plaque with OCT.

Assessment of coronary atherosclerosis using optical coherence tomography.

Optical coherence tomography (OCT) is a catheter-based imaging system that uses near-infrared light to produce cross-sectional images of the coronary arteries. With its extraordinarily high resolution (10-20 μm), OCT allows clinicians to observe various morphological features of coronary atherosclerosis in vivo. For example, intimal thickening presents as homogeneous, signal-rich regions on OCT, while fibroatheroma with a lipid-rich necrotic core is characterized by the presence of signal-poor regions with a diffuse border. Furthermore, plaque rupture is detected in 50〜70% of culprit lesions of acute coronary syndrome (ACS), and plaque erosion develops over areas of intimal thickening and/or thick-cap fibroatheroma. Meanwhile, calcified nodules are common in older patients with hypertension and chronic renal disease. Platelet-rich thrombi are visualized as low backscattering structures and often detected in patients with unstable angina, whereas red blood cell-rich thrombi exhibit a high backscattering structure with signal-free shadowing and are frequently noted in patients with acute myocardial infarction. Moreover, OCT-derived thin cap fibroatheroma has been shown to be a predictor of subsequent plaque progression and acute coronary events, while vasa vasorum and the macrophage density are associated with a thin fibrous cap and large necrotic core as well as increased serum levels of inflammatory biomarkers. One current challenge of OCT examinations is to detect morphologic characteristics capable of discriminating vulnerable from stable plaques. The ability to detect vulnerable plaques in vivo would allow physicians to identify patients at high risk for adverse coronary events, thus significantly helping to prevent ACS.

Comparison of diagnostic accuracy between multidetector computed tomography and virtual histology intravascular ultrasound for detecting optical coherence tomography-derived fibroatheroma

Histopathological studies have reported that optical coherence tomography (OCT) can accurately detect fibroatheroma that is involved in not only culprit lesion of acute coronary syndrome but also no-reflow phenomenon after percutaneous coronary intervention. Studies have demonstrated superiority of OCT in plaque characterization and interruption of arterial wall component. At current, multidetector computed tomography (MDCT) and virtual histology intravascular ultrasound (VH-IVUS) are considered as alternative imaging devices for coronary plaque characterization. This study aimed to compare the diagnostic accuracy for detecting fibroatheroma between MDCT and VH-IVUS using OCT as the reference standard. Forty-three lesions from 27 patients assessed by MDCT, VH-IVUS, and OCT were included in this study. Fibroatheroma was defined by OCT as a signal-poor region with a fast signal drop-off and little or no signal backscattering within the lesion. From 43 lesions, OCT revealed 21 fibroatheromas. Ring-like sign assessed by MDCT and positive remodeling assessed by IVUS were more frequently observed in OCT-fibroatheroma than non-OCT-fibroatheroma. The remodeling index of OCT-fibroatheroma assessed by MDCT and IVUS were higher than those of non-OCT-fibroatheroma. The sensitivity, specificity, positive predict values, negative predict values and accuracy of ring-like sign by MDCT and VH-IVUS for detecting OCT-fibroatheroma were 43, 95, 90, 64, 70 % and 71, 45, 56, 63, 58 %, respectively. Our results suggest that both accuracies of MDCT and VH-IVUS to detect OCT-fibroatheroma are insufficient. We need to apply appropriate device for searching vulnerable plaque.

Histogram Analysis of Lipid-Core Plaques in Coronary Computed Tomographic Angiography

In coronary computed tomographic angiography (CTA), low attenuation of coronary atherosclerotic plaque is associated with lipid-rich plaques. However, an overlap in Hounsfield units (HU) between fibrous and lipid-rich plaque as well as an influence of luminal enhancement on plaque attenuation was observed and may limit accurate detection of lipid-rich plaques by CTA. We sought to determine whether the quantitative histogram analysis improves accuracy of the detection of lipid-core plaque (LCP) in ex vivo hearts by validation against histological analysis. Human donor hearts were imaged with a 64-slice computed tomographic scanner using a standard coronary CTA protocol, optical coherence tomography (OCT), a histological analysis. Lipid-core plaque was defined in the histological analysis as any fibroatheroma with a lipid/necrotic core diameter of greater than 200 μm and a circumference greater than 60 degrees as well as a cap thickness of less than 450 μm. In OCT, lipid-rich plaque was determined as a signal-poor region with diffuse borders in 2 quadrants or more. In CTA, the boundaries of the noncalcified plaque were manually traced. The absolute and relative areas of low attenuation plaque based on pixels with less than 30, less than 60, and less than 90 HU were calculated using quantitative histogram analysis. From 5 hearts, a total of 446 cross sections were coregistered between CTA and the histological analysis. Overall, 55 LCPs (12%) were identified by the histological analysis. In CTA, the absolute and relative areas of low attenuation plaque less than 30, less than 60, and less than 90 HU were 0.14 (0.31) mm2 (4.22% [9.02%]), 0.69 (0.95) mm2 (18.28% [21.22%]), and 1.35 (1.54) mm2 (35.65% [32.07%]), respectively. The low attenuation plaque area correlated significantly with histological lipid content (lipid/necrotic core size [in square millimeter] and a portion of lipid/necrotic core on the entire plaque) at all thresholds but was the strongest at less than 60 HU (r = 0.53 and r = 0.48 for the absolute and relative areas, respectively). Using a threshold of 1.0 mm2 or greater, the absolute plaque area of less than 60 HU in CTA yielded 69% sensitivity and 80% specificity to detect LCP, whereas sensitivity and specificity were 73% and 71% for using 25.0% or higher relative area less than 60 HU. The discriminatory ability of CTA for LCP was similar between the absolute and relative areas (the area under the curve, 0.744 versus 0.722; P = 0.37). Notably, the association of the low attenuation plaque area in CTA with LCP was not altered by the luminal enhancement for the relative (P = 0.48) but for the absolute measurement (P = 0.03). Similar results were achieved when validated against lipid-rich plaque by OCT in a subset of 285 cross sections. In ex vivo conditions, the relative area of coronary atherosclerotic plaque less than 60 HU in CTA as derived from quantitative histogram analysis has good accuracy to detect LCP as compared with a histological analysis independent of differences in luminal contrast enhancement.

The true character of lipid rich plaque by intravascular imaging: message from pathologist to cardiologist

Purpose: Vascular imaging, such as intravascular ultrasound (IVUS), optical coherence tomography (OCT) and coronary angioscopy (CAS), becomes widespread to characterize the coronary artery plaques. Most of the cardiologists believe that these imaging devices could detect atherosclerotic plaque component; therefore it is possible to diagnose the vulnerable plaque. However, lack of histopathological validation study may lead misinterpretation of these imaging. We have compared intravascular imaging with histopathology of coronary plaques by our autopsy cases and evaluated the histological character of imaging-basis lipid rich plaque (LRP) and thin cap fibroatheroma (TCFA). Methods: Freshly harvested 55 coronary arteries from 20 hearts with non-cardiac death were examined ex-vivo vascular imaging including IVUS, OCT and CAS within 6 hours after death. These arteries were imaged with IVUS and >70 mm length of intimal lesions were identified as focal plaque. OCT-basis LRP were defined by signal-poor regions with fibrous cap thickness <300μm. TCFA was defined as LRP with fibrous cap thickness <65μm. CAS examinations were performed for each focal plaque to evaluate plaque color and all focal plaques were graded as either white or yellow. The border characteristic of yellow plaque was also assessed as sharp or diffuse. Results: Forty plaques (19%) were matched with the OCT-basis LRP and 17 plaques (8%) with TCFA in 211 OCT-observed focal plaques. OCT-basis LRP were highly associated with lipid deposition within plaques (85%). However, 41% of those plaques demonstrated extracellular lipid accumulation without necrotic debris, cholesterin crystals, and massive inflammation, which are known as fibro-fatty plaque. Furthermore, false-positive diagnoses of OCT-basis LRP included micro-calcification, hemosiderin deposition, or organized thrombus by their histology. The sensitivity for detecting LRP by OCT was 58%. Of CAS-observed 180 plaques, 64 plaques (35%) were categorized as yellow plaques. Only 24 plaques out of 64 yellow plaques (37.5%) contained necrotic debris by histology. Most yellow plaques with sharp border contained superficial calcium deposition without lipid accumulation. Other yellow plaques demonstrated superficial extracelluler lipid deposition or foam cells infiltration over fibrous plaque, which are known as pathological intimal thickening or intimal xanthoma. Conclusion: Atherosclerotic plaques of coronary artery are heterogeneous. We need to keep in mild that vascular imaging modalities have a limitation in detecting vulnerable plaque.

Endothelial dysfunction versus early atherosclerosis: a study with high resolution imaging

Purpose: Endothelial dysfunction has been shown to be of prognostic significance in predicting major coronary events. Characterization of microstructural changes of the vessel wall in coronary segment with endothelial dysfunction may have potential prognostic importance for detection of ischemic heart disease (IHD). Methods: We studied 5 patients with IHD, found to have normal or near normal angiograms. These patients received graded doses of intracoronary acetylcholine (10-6, 10-5 and 10-4 mol/L over 3 minutes at 10 minutes intervals) to assess endothelial dysfunction. Epicardial endothelial dysfunction was defined as >30% epicardial vessel diameter reduction during testing. An intracoronary bolus dose of 1000 μg of nitroglycerin was administered to relieve vasoconstriction; IVUS was performed 10 minutes after relief of vasoconstriction and OCT 20 minutes later. The OCT imaging wire was positioned at the site, and 1 cm proximal and distal to of the observed coronary vasomotor abnormality. Each OCT image was analyzed by two independent observers who were blinded to the results. Using OCT imaging, the intima is identified by a signal-rich layer near to the lumen, the media by a signal-poor middle layer, and the adventitia by a signal-rich outer layer. Loss of layered architecture reflects early sign of atherosclerosis. Results: A total of 7 coronary segments showed vasoconstriction. Wall morphology was evaluated by IVUS. Subjects with normal smooth coronaries exhibited a thickness of the coronary wall<1mm. We obtained a total of 83 OCT images. There were 49 images of dysfunctional sites and 34 of the control segments. Of the 49 images of dysfunctional sites, 9 (19.4%) showed the usual layer structure of a normal artery (three-layer structure: intima, media and adventitia), and the remaining 40 (81.6%) showed early structural changes (single intimal thickened layer up to 380 micron). 16 of these 40 images revealed small signal-poor regions compatible with lipid deposits. Imaging of the control segments showed the usual three-layer structure in 5 (14.7%) images, small signal-poor regions in 14 (41.2%) images, and early structural changes in the remaining 15 (44.1%) images. Conclusions: Our findings indicate that endothelial dysfunction and early atherosclerosis, although related in many coronary segments, may exist separately. Functional alterations can be identified safely at a stage when atherosclerotic lesions are not detectable by any imaging technique. Acetylcholine testing may be useful in designing early effective interventions that restore endothelial function.

Enhanced Depth Imaging Optical Coherence Tomography of Optic Nerve Head Drusen

To assess the value of enhanced depth imaging optical coherence tomography (EDI OCT) in diagnosing and evaluating optic nerve head drusen (ONHD) compared with conventional diagnostic methods. Prospective, comparative, cross-sectional study. Thirty-four patients with clinically visible or suspected ONHD in either eye based on dilated optic disc examination or optic disc stereophotography and without ocular comorbidity. Spectral-domain OCT of the optic nerve head in both conventional (non-EDI) and EDI modes, ultrasound B-scan, and standard automated perimetry were performed on both eyes of all participants. Detection and findings of ONHD between EDI OCT and conventional diagnostic methods. Sixty-eight eyes were clinically classified into 3 groups: 32 eyes with definite ONHD, 25 eyes with suspected ONHD, and 11 normal-appearing fellow eyes. In the definite ONHD group, EDI OCT, non-EDI OCT, and ultrasound B-scan were positive for ONHD in all eyes and visual field (VF) was abnormal in 24 eyes. In the suspected ONHD group, EDI OCT, non-EDI OCT, ultrasound B-scan, and VF were positive in 17, 14, 7, and 3 eyes, respectively; 8 eyes had no evidence of ONHD in any of the tests. In normal-appearing fellow eyes, EDI OCT, non-EDI OCT, ultrasound B-scan, and VF were positive in 3, 1, 1, and 0 eyes, respectively; 4 eyes had no evidence of ONHD in any of the tests. Enhanced depth imaging OCT had a significantly higher ONHD detection rate than ultrasound B-scan in all eyes (52/68 eyes vs. 40/68 eyes; P<0.001), in eyes with clinically suspected ONHD or normal-appearing fellow eyes (20/36 eyes vs. 8/36 eyes; P<0.001), and in eyes with clinically suspected ONHD (17/25 eyes vs. 7/25 eyes; P = 0.002). Enhanced depth imaging OCT-detected ONHD appeared as signal-poor regions surrounded by short, hyper-reflective bands or isolated/clustered hyper-reflective bands without a signal-poor core. In non-EDI OCT, posterior surfaces of the ONHD and deep-seated hyper-reflective bands were invisible or less clear than in EDI OCT. Enhanced depth imaging OCT detects lesions likely representing ONHD more often and better assesses their shape and structure than conventional tests.

Difference in neointimal appearance between early and late restenosis after sirolimus-eluting stent implantation assessed by optical coherence tomography

Late in-stent restenosis (ISR) is an important clinical issue in the drug-eluting stent era. Autopsy studies have reported different underlying mechanisms between early ISR and late ISR. The aim of the present study was to compare the neointimal tissue appearance between early ISR (<1 year) and late ISR (>1 year) after sirolimus-eluting stent (SES) implantation using optical coherence tomography (OCT). We examined the neointimal tissue appearance in 48 ISR lesions after SES implantation [30 early ISR lesions (8±1 months after stenting) and 18 late ISR lesions (34±14 months after stenting)] by OCT. ISR was defined as percent diameter stenosis more than 50% within the stented segment in angiography. Lipid-rich neointima was characterized by signal-poor regions with diffuse borders. Thin-cap fibroatheroma (TCFA)-like neointima was defined by lipid-rich neointima with cap thickness 65 μm or less. In the OCT findings, heterogeneous neointima was more often observed in the late ISR group compared with the early ISR group (89 vs. 43%, P=0.002). Although the frequency of intraluminal thrombus was not different between the two groups (P=0.085), the frequency of lipid-rich neointima (83 vs. 27%, P<0.001), TCFA-like neointima (39 vs. 10%, P=0.028), microchannels within neointima (67 vs. 27%, P=0.007), and neointimal disruption (33 vs. 3%, P=0.008) was significantly higher in the late ISR group. In the present OCT study, it was found that atherosclerotic progression of neointima, such as lipid-rich neointima, TCFA-like neointima, microchannels, and neointimal disruption, was more often observed in late ISR lesions after SES implantation compared with early ISR ones.

Volumetric Characterization of Human Coronary Calcification by Frequency-Domain Optical Coherence Tomography

Coronary artery calcification (CAC) presents unique challenges for percutaneous coronary intervention. Calcium appears as a signal-poor region with well-defined borders by frequency-domain optical coherence tomography (FD-OCT). The objective of this study was to demonstrate the accuracy of intravascular FD-OCT to determine the distribution of CAC. Cadaveric coronary arteries were imaged using FD-OCT at 100-μm frame interval. Arteries were subsequently frozen, sectioned and imaged at 20-μm intervals using the Case Cryo-Imaging automated system(TM). Full volumetric co-registration between FD-OCT and cryo-imaging was performed. Calcium area, calcium-lumen distance (depth) and calcium angle were traced on every cross-section; volumetric quantification was performed offline. In total, 30 left anterior descending arteries were imaged: 13 vessels had a total of 55 plaques with calcification by cryo-imaging; FD-OCT identified 47 (85%) of these plaques. A total of 1,285 cryo-images were analyzed and compared with corresponding co-registered 257 FD-OCT images. Calcium distribution, represented by the mean depth and the mean calcium angle, was similar, with excellent correlation between FD-OCT and cryo-imaging respectively (mean depth: 0.25±0.09 vs. 0.26±0.12mm, P=0.742; R=0.90), (mean angle: 35.33±21.86° vs. 39.68±26.61°, P=0.207; R=0.90). Calcium volume was underestimated in large calcifications (3.11±2.14 vs. 4.58±3.39mm(3), P=0.001) in OCT vs. cryo respectively. Intravascular FD-OCT can accurately characterize CAC distribution. OCT can quantify absolute calcium volume, but may underestimate calcium burden in large plaques with poorly defined abluminal borders.

IN-STENT LIPID-RICH PLAQUE IN HIGH CHOLESTEROL DIET RABBIT VALIDATED BY INTRAVASCULAR OPTICAL COHERENCE TOMOGRAPHY AND HISTOLOGY

ObjectivesIn-stent lipid-rich plaque had been found frequently in patients underwent stent implantation by optical coherence tomography (OCT) and intravascular ultrasound (IVUS). The paucity of a reliable animal model limits the...