Background-Intravascular ultrasound-derived virtual histology (VH IVUS) is used increasingly in clinical research to assess composition and vulnerability of coronary atherosclerotic lesions. However, the ability of VH IVUS to quantify individual plaque components, in particular the size of the destabilizing necrotic core, has never been validated. We tested for correlation between VH IVUS necrotic core size and necrotic core size by histology in porcine coronary arteries with human-like coronary disease. Methods and Results-In adult atherosclerosis-prone minipigs, 18 advanced coronary lesions were assessed by VH IVUS in vivo followed by postmortem microscopic examination (histology). We found no correlation between the size of the necrotic core determined by VH IVUS and histology. VH IVUS displayed necrotic cores in lesions lacking cores by histology. Conclusions-We found no correlation between necrotic core size determined by VH IVUS and real histology, questioning the ability of VH IVUS to detect rupture-prone plaques, so-called thin-cap fibroatheromas. (Circ Cardiovasc Imaging. 2010;3:384-391.)

Subtle differences in neointimal formation induced by current DES can be reproducibly analyzed in vivo by OCT. However, OCT measurement of stent area seems to have less correlation with histology.

Stenting of ULMCA is feasible and offers good long-term outcome. Implantation of DES for ULMCA decreased the risk of long-term MACCE, and particularly improved survival in patients with distal ULMCA disease.

Background-We aimed to demonstrate that, by separating endothelial progenitor cell capture from sirolimus delivery through the application of drug to the abluminal surface of the stent, the degree of endothelialization can be enhanced. Methods and Results-Stainless steel R Stents, with biodegradable SynBiosys polymer coating with sirolimus abluminally applied and surface modified with anti-CD34 antibody were prepared at 2 dosages (low-dose sirolimus [LD-Combo, 2.5 g sirolimus/mm] and full-dose sirolimus [Combo, 5 g sirolimus/mm). These Combo stents and the Cypher stent (10 g sirolimus/mm) were deployed in 98 normal porcine arteries and harvested for pharmacokinetic analysis at 0.25, 1, 3, 7, 14, 28, and 35 days. The LD-Combo stents showed faster early release (50% total dose in 72 hours) than the Combo and Cypher. At 30 days, drug release was near complete with both Combo stents, whereas 20% of drug remained on the Cypher stents. To assess efficacy, a total of 50 stents (Xience Vϭ8, Cypherϭ8, Genous bioengineered R stentϭ6, LD-Comboϭ14, and Comboϭ14) were implanted in 18 pigs for 14 and 28 days. Optical coherence tomography was performed, and stents were harvested for histology. At 28 days, there was less neointimal thickness with Combo (0.173Ϯ0.088 mm) compared with Cypher (0.358Ϯ0.225 mm), LD-Combo (0.316Ϯ0.228 mm), and Xience V (0.305Ϯ0.252 mm; PϽ0.00001). Immunohistochemical analysis of endothelialization showed that Genous bioengineered R stent had the highest degree of platelet endothelial cell adhesion molecule expression (87%) followed by the Combo (75%), LD-Combo (65%), and Cypher (58%). Conclusions-Both optical coherence tomography and histology demonstrate that anti-CD34 sirolimus-eluting stents promote endothelialization while reducing neointimal formation and inflammation. (Circ Cardiovasc Interv. 2010;3:257-266.)

Objective-To determine the accuracy of detection of different tissue types of intravascular ultrasound-virtual histology (IVUS-VH) in a porcine model of complex coronary lesions. Methods and Results-Coronary lesions were induced by injecting liposomes containing human oxidized low-density lipoprotein into the adventitia of the arteries. IVUS-VH imaging was performed in vivo at 8.2Ϯ1.6 weeks after injection. A total of 60 vascular lesions were analyzed and compared with their correspondent IVUS-VH images. Correlation analysis was performed using linear regression models. Key Words: animal model Ⅲ intravascular ultrasound Ⅲ vulnerable plaque C omplex atherosclerotic plaques containing specific morphological features appear to be responsible for the majority of major coronary events. 1-4 Therefore, the accurate identification and characterization of these lesions has become one of the major challenges of interventional cardiology. 5 Several catheter-based imaging devices designed and built to characterize such features are currently undergoing development. 6 -10 Mainly because of the lack of a large animal model of atherosclerotic vascular disease, the initial development of these technologies is based on the construction of mathematical algorithms based on data acquired from ex vivo evaluation of postmortem human arterial specimens. Therefore, the translation of these algorithms of detection into an in vivo setting may not be universally accurate.Virtual histology is an intravenous ultrasound (IVUS)-based technology that studies the spectral analysis of the radio frequency signals backscattered from the plaque during IVUS imaging and reconstructs the morphology of the plaque through color-coded maps. 11 Although this technique has been validated in vitro and ex vivo in human coronary arteries [11][12][13][14] and preliminary clinical experience has been published, 15,16 little data have been published on histological correlates of images acquired in vivo. 17 In the present study, we describe the histological characteristics of complex coronary lesions analyzed in vivo using intravascular ultrasoundvirtual histology (IVUS-VH) in a porcine model of disease.

BackgroundBecause driver mutations provide selective advantage to the mutant clone, they tend to occur at a higher frequency in tumor samples compared to selectively neutral (passenger) mutations. However, mutation frequency alone is insufficient to identify cancer genes because mutability is influenced by many gene characteristics, such as size, nucleotide composition, etc. The goal of this study was to identify gene characteristics associated with the frequency of somatic mutations in the gene in tumor samples.ResultsWe used data on somatic mutations detected by genome wide screens from the Catalog of Somatic Mutations in Cancer (COSMIC). Gene size, nucleotide composition, expression level of the gene, relative replication time in the cell cycle, level of evolutionary conservation and other gene characteristics (totaling 11) were used as predictors of the number of somatic mutations. We applied stepwise multiple linear regression to predict the number of mutations per gene. Because missense, nonsense, and frameshift mutations are associated with different sets of gene characteristics, they were modeled separately. Gene characteristics explain 88% of the variation in the number of missense, 40% of nonsense, and 23% of frameshift mutations. Comparisons of the observed and expected numbers of mutations identified genes with a higher than expected number of mutations– positive outliers. Many of these are known driver genes. A number of novel candidate driver genes was also identified.ConclusionsBy comparing the observed and predicted number of mutations in a gene, we have identified known cancer-associated genes as well as 111 novel cancer associated genes. We also showed that adding the number of silent mutations per gene reported by genome/exome wide screens across all cancer type (COSMIC data) as a predictor substantially exceeds predicting accuracy of the most popular cancer gene predicting tool - MutsigCV.Electronic supplementary materialThe online version of this article (10.1186/s12859-018-2455-0) contains supplementary material, which is available to authorized users.

The administration of bone marrow-derived stem cells may provide a new treatment option for patients with heart failure. Transcatheter cell injection may require multi-imaging modalities to optimize delivery. This study sought to evaluate whether endomyocardial injection of mesenchymal precursor cells (MPCs) could be guided by real-time 3D echocardiography (RT3DE) in treating chronic, postinfarction (MI) left ventricular (LV) dysfunction in sheep. Four weeks after induction of an anterior wall myocardial infarction in 39 sheep, allogeneic MPCs in doses of either 25 ´ 10 6 (n = 10), 75 ´ 10 6 (n = 9), or 225 ´ 10 6 (n = 10) cells or nonconditioned control media (n = 10) were administered intramyocardially into infarct and border zone areas using a catheter designed for combined fluoroscopic and RT3DE-guided injections. LV function was assessed before and after injection. Infarct dimension and vascular density were evaluated histologically. RT3DE-guided injection procedures were safe. Compared to controls, the highest dose MPC treatment led to increments in ejection fraction (3 ± 3% in 225M MPCs vs. -5 ± 4% in the control group, p < 0.01) and wall thickening in both infarct (4 ± 4% in 225M MPCs vs. −3 ± 6% in the control group, p = 0.02) and border zones (4 ± 6% in 225M MPCs vs. −8 ± 9% in the control group, p = 0.01). Histology analysis demonstrated significantly higher arteriole density in the infarct and border zones in the highest dose MPC-treated animals compared to the lower dose or control groups. Endomyocardial implantation of MPCs under RT3DE guidance was safe and without observed logistical obstacles. Significant increases in LV performance (ejection fraction and wall thickening) and neovascularization resulted from this technique, and so this technique has important implications for treating patients with postischemic LV dysfunction.

The interaction of platelets with the polymeric surface of drug eluting stents has not been fully described in the literature. Our aim was to analyze the patterns of activation and deposition of platelets exposed to two different stent platforms; (a) the polymeric surface of the paclitaxel eluting stent (Taxus((R)) stent, PES,) and (b) the metallic surface of a stent with identical structural design (Express((R)) stent, BMS). Platelet activation was tested by deploying stents in an in vitro flow chamber model. Anticoagulated blood of 25 healthy volunteers was circulated (flow rate 10 ml/min for 60 min) into the flow chamber system. P-selectin expression, glycoprotein IIb/IIIa activation (PAC-1 binding) and platelet-monocyte complexes (PMC) formation were evaluated at 0, 10, 30 and 60 min. Surface platelet deposition was assessed by surface electron microscopy in stents implanted in the in vitro system for 60 min and in stents implanted in normal porcine coronary arteries for 24 h. Platelet activation evaluation showed a higher P-Selectin expression (92.9% of baseline in PES versus 68.3 % in BMS, P = 0.01) and higher PMC formation (125.7 % of baseline in PES versus 75.6% in BMS, P < 0.01) in the PES compared to the BMS control group. PAC-1 binding levels did not differ among groups. In the in vitro study, SEM analysis of the stent surface showed no statistical differences on platelet deposition between the groups. In addition, presence of proteinaceous material was more frequently seen on the BMS group (moderate to complete coverage = 80% in BMS versus 26% in PES, P < 0.01). In the in vivo study, complete platelet coverage was similar between groups (PES = 7% versus BMS = 8%, P = NS). However, there was an overall trend towards less platelet deposition on the BMS surface (mild and moderate coverage = 83%, 9% in BMS versus 49%, 44% in PES, P < 0.001 for both) but thrombus formation was not observed in either group. The polymeric surface of the PES appears to induce a higher degree of platelet activation and deposition compared to the BMS surface. The biological implications of these findings on the patterns of vascular healing need to be further studied in vivo. Condensed Abstract The interaction of human platelets with the surface of drug eluting stents has not been fully characterized. Patterns of platelet activation and adhesion were evaluated in vitro and in vivo after exposing platelets to the surface of the paclitaxel-eluting stent and identical bare metal stent. The degree of PMC formation and P-selectin expression was increased in PES compared to BMS. In the in vivo study, complete platelet coverage was similar between groups. There was an overall trend towards less platelet deposition on the BMS surface, however, thrombus formation was not observed on either surface. The polymeric surface of the PES appears to induce a higher degree of platelet activation and deposition compared to the BMS surface.