In-stent restenosis in the drug eluting stent assayed by optical coherence tomography

Hospital of Holy Pope Giovanni XXIII, Bergamo, Italy, Department of Interventional Cardiology, Institute of Cardiology, Chisinau, the Republic of MoldovaBackground: In order to study the mechanisms and morphological aspects of the in-stent restenosis (ISR) have been evaluated restenosis lesions referred to drug eluting stent (DES) of the first generation using optical coherence tomography technique (OCT). Material and methods: The study underwent 39 patients with ISR induced recurrent angina or acute coronary syndrome including 66 stents from which were: 44 stents (28 patients) of the first generation of DES (19 – Cypher TM and 23 – Taxus®), and 22 stents (11 patients) of the second DES generation (9 Xience TM 2 Promus TM), 10 ZES (Resolute TM), and one stent Nobori TM. Has been made quantitative and morphological analysis of tissue pattern of ISR using the following OCT criteria: 1) morphologically homogenous neointima; 2)morphologically heterogeneous neointima; and 3) neoatherosclerosis. Results: It has been established that in the first generation of DES morphological homogenous pattern was present in both ISR developed after 1 year and later. However, the optical aspect with heterogeneous presentation had a prevalence decline in dynamics. The heterogeneous model had a higher prevalence in actual generation of DES in both incipient (< 1 year) and late presentation. Conclusions: The phenomenon of neoatherosclerosis has presented a significantly less frequency in the late restenosis of actual generation of DES. Our results suggest that restenosis phenomenon in actual generation of DES has a different morphological and evolution pattern in time in comparison with ISR of the first generation of DES

Intracoronary optical coherence tomography

The cardiovascular departments of the hospital of Holy Pope Giovanni XXIII in Bergamo, Italy and of the Institute of Cardiology in Chisinau, the Republic of Moldova have a fruitful history of collaboration in the field of interventional cardiology and intracoronary imaging in particular. We have recently expanded our collaboration by adding the method of Optical Coherence Tomography (OCT) into the armamentarium of imaging in the catheterization laboratory. OCT is an innovative, real time, tomographic imaging modality able to visualize tissues at microstructure level. It delivers the rays of near-infrared light through the wall of the coronary artery using small diameter optical fibres. The light that illuminates the vessel is absorbed and backscattered or reflected by the structures of the tissues with different degrees of density, thus creating an image with an axial resolution of 10-20 µm. This technology allows acquiring high definition images of long segments of coronaries for a few seconds. For the time being, OCT is mainly used in the researches, providing insights into the pathophysiology of the atherosclerotic plaque and the vascular response to stenting. It also has a potential for clinical application, such as pre-interventional evaluation of coronary arteries, procedures guidance and follow-up assessment of vascular healing after the stent implantation. A joined database has been created by the two institutions in an effort to study in vivo the morphology of the coronary arteries in different pathologies. This review is focused on the potential fields of application of OCT in different clinical and scientific institutions

Automated analysis of fibrous cap in intravascular optical coherence tomography images of coronary arteries

Thin-cap fibroatheroma (TCFA) and plaque rupture have been recognized as the most frequent risk factor for thrombosis and acute coronary syndrome. Intravascular optical coherence tomography (IVOCT) can identify TCFA and assess cap thickness, which provides an opportunity to assess plaque vulnerability. We developed an automated method that can detect lipidous plaque and assess fibrous cap thickness in IVOCT images. This study analyzed a total of 4,360 IVOCT image frames of 77 lesions among 41 patients. To improve segmentation performance, preprocessing included lumen segmentation, pixel-shifting, and noise filtering on the raw polar (r, theta) IVOCT images. We used the DeepLab-v3 plus deep learning model to classify lipidous plaque pixels. After lipid detection, we automatically detected the outer border of the fibrous cap using a special dynamic programming algorithm and assessed the cap thickness. Our method provided excellent discriminability of lipid plaque with a sensitivity of 85.8% and A-line Dice coefficient of 0.837. By comparing lipid angle measurements between two analysts following editing of our automated software, we found good agreement by Bland-Altman analysis (difference 6.7+/-17 degree; mean 196 degree). Our method accurately detected the fibrous cap from the detected lipid plaque. Automated analysis required a significant modification for only 5.5% frames. Furthermore, our method showed a good agreement of fibrous cap thickness between two analysts with Bland-Altman analysis (4.2+/-14.6 micron; mean 175 micron), indicating little bias between users and good reproducibility of the measurement. We developed a fully automated method for fibrous cap quantification in IVOCT images, resulting in good agreement with determinations by analysts. The method has great potential to enable highly automated, repeatable, and comprehensive evaluations of TCFAs.Comment: 18 pages, 9 figure

Deep learning segmentation of fibrous cap in intravascular optical coherence tomography images

Thin-cap fibroatheroma (TCFA) is a prominent risk factor for plaque rupture. Intravascular optical coherence tomography (IVOCT) enables identification of fibrous cap (FC), measurement of FC thicknesses, and assessment of plaque vulnerability. We developed a fully-automated deep learning method for FC segmentation. This study included 32,531 images across 227 pullbacks from two registries. Images were semi-automatically labeled using our OCTOPUS with expert editing using established guidelines. We employed preprocessing including guidewire shadow detection, lumen segmentation, pixel-shifting, and Gaussian filtering on raw IVOCT (r,theta) images. Data were augmented in a natural way by changing theta in spiral acquisitions and by changing intensity and noise values. We used a modified SegResNet and comparison networks to segment FCs. We employed transfer learning from our existing much larger, fully-labeled calcification IVOCT dataset to reduce deep-learning training. Overall, our method consistently delivered better FC segmentation results (Dice: 0.837+/-0.012) than other deep-learning methods. Transfer learning reduced training time by 84% and reduced the need for more training samples. Our method showed a high level of generalizability, evidenced by highly-consistent segmentations across five-fold cross-validation (sensitivity: 85.0+/-0.3%, Dice: 0.846+/-0.011) and the held-out test (sensitivity: 84.9%, Dice: 0.816) sets. In addition, we found excellent agreement of FC thickness with ground truth (2.95+/-20.73 um), giving clinically insignificant bias. There was excellent reproducibility in pre- and post-stenting pullbacks (average FC angle: 200.9+/-128.0 deg / 202.0+/-121.1 deg). Our method will be useful for multiple research purposes and potentially for planning stent deployments that avoid placing a stent edge over an FC.Comment: 24 pages, 9 figures, 2 tables, 2 supplementary figures, 3 supplementary table

A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization

BACKGROUND: The need for repeated treatment of restenosis of a treated vessel remains the main limitation of percutaneous coronary revascularization. Because sirolimus (rapamycin) inhibits the proliferation of lymphocytes and smooth-muscle cells, we compared a sirolimus-eluting stent with a standard uncoated stent in patients with angina pectoris. METHODS: We performed a randomized, double-blind trial to compare the two types of stents for revascularization of single, primary lesions in native coronary arteries. The trial included 238 patients at 19 medical centers. The primary end point was in-stent late luminal loss (the difference between the minimal luminal diameter immediately after the procedure and the diameter at six months). Secondary end points included the percentage of in-stent stenosis of the luminal diameter and the rate of restenosis (luminal narrowing of 50 percent or more). We also analyzed a composite clinical end point consisting of death, myocardial infarction, and percutaneous or surgical revascularization at 1, 6, and 12 months. RESULTS: At six months, the degree of neointimal proliferation, manifested as the mean (+/-SD) late luminal loss, was significantly lower in the sirolimus-stent group (-0.01+/-0.33 mm) than in the standard-stent group (0.80+/-0.53 mm, P<0.001). None of the patients in the sirolimus-stent group, as compared with 26.6 percent of those in the standard-stent group, had restenosis of 50 percent or more of the luminal diameter (P<0.001). There were no episodes of stent thrombosis. During a follow-up period of up to one year, the overall rate of major cardiac events was 5.8 percent in the sirolimus-stent group and 28.8 percent in the standard-stent group (P<0.001). The difference was due entirely to a higher rate of revascularization of the target vessel in the standard-stent group. CONCLUSIONS: As compared with a standard coronary stent, a sirolimus-eluting stent shows considerable promise for the prevention of neointimal proliferation, restenosis, and associated clinical events

Intravascular ultrasound findings in the multicenter, randomized, double-blind RAVEL (RAndomized study with the sirolimus-eluting VElocity balloon- expandable stent in the treatment of patients with de novo native coronary artery Lesions) trial

BACKGROUND: The goal of this intravascular ultrasound investigation was to provide a more detailed morphological analysis of the local biological effects of the implantation of a sirolimus-eluting stent compared with an uncoated stent. METHODS AND RESULTS: In the RAVEL trial, 238 patients with single de novo lesions were randomized to receive either an 18-mm sirolimus-eluting stent (Bx VELOCITY stent, Cordis) or an uncoated stent (Bx VELOCITY stent). In a subset of 95 patients (sirolimus-eluting stent=48, uncoated stent=47), motorized intravascular ultrasound pullback (0.5 mm/s) was performed at a 6-month follow-up. Stent volumes, total vessel volumes, and plaque-behind-stent volumes were comparable. However, the difference in neointimal hyperplasia (2+/-5 versus 37+/-28 mm3) and percent of volume obstruction (1+/-3% versus 29+/-20%) at 6 months between the 2 groups was highly significant (P<0.001), emphasizing the nearly complete abolition of the proliferative process inside the drug-eluting stent. Analysis of the proximal and distal edge volumes showed no significant difference between the 2 groups in external elastic membrane or lumen and plaque volume at the proximal and distal edges. There was also no evidence of intrastent thrombosis or persisting dissection at the stent edges. Although there was a higher incidence of incomplete stent apposition

Interstudy reproducibility of the second generation, Fourier domain optical coherence tomography in patients with coronary artery disease and comparison with intravascular ultrasound: a study applying automated contour detection

Recently, Fourier domain OCT (FD-OCT) has been introduced for clinical use. This approach allows in vivo, high resolution (15 micron) imaging with very fast data acquisition, however, it requires brief flushing of the lumen during imaging. The reproducibility of such fast data acquisition under intracoronary flush application is poorly understood. To assess the inter-study variability of FD-OCT and to compare lumen morphometry to the established invasive imaging method, IVUS. 18 consecutive patients with coronary artery disease scheduled for PCI were included. In each target vessel a FD-OCT pullback (MGH system, light source 1,310 nm, 105 fps, pullback speed 20 mm/s) was acquired during brief (3 s) injection of X-ray contrast (flow 3 ml/s) through the guiding catheter. A second pullback was repeated under the same conditions after re-introduction of the FD OCT catheter into the coronary artery. IVUS and OCT imaging was performed in random order. FD-OCT and IVUS pullback data were analyzed using a recently developed software employing semi automated lumen contour and stent strut detection algorithms. Corresponding ROI were matched based on anatomical landmarks such as side branches and/or stent edges. Inter-study variability is presented as the absolute difference between the two pullbacks. FD-OCT showed remarkably good reproducibility. Inter-study variability in native vessels (cohort A) was very low for mean and minimal luminal area (0.10 ± 0.38, 0.19 ± 0.57 mm[superscript 2], respectively). Likewise inter-study variability was very low in stented coronary segments (cohort B) for mean lumen, mean stent, minimal luminal and minimal stent area (0.06 ± 0.08, 0.07 ± 0.10, 0.04 ± 0.09, 0.04 ± 0.10 mm[superscript 2], respectively). Comparison to IVUS morphometry revealed no significant differences. The differences between both imaging methods, OCT and IVUS, were very low for mean lumen, mean stent, minimal luminal and minimal stent area (0.10 ± 0.45, 0.10 ± 0.36, 0.26 ± 0.54, 0.05 ± 0.47 mm[superscript 2], respectively). FD-OCT shows excellent reproducibility and very low inter-study variability in both, native and stented coronary segments. No significant differences in quantitative lumen morphometry were observed between FD-OCT and IVUS. Evaluating these results suggest that FD-OCT is a reliable imaging tool to apply in longitudinal coronary artery disease studie