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BackgroundThe micro-architectonics of the subarachnoid space (SAS) remain partially understood and largely ignored, likely the result of the inability to image these structures in vivo. We explored transvascular imaging with high-frequency optical coherence tomography (HF-OCT) to interrogate the SAS.MethodsIn vivo HF-OCT was performed in 10 dogs in both the posterior and anterior cerebral circulations. The conduit vessels used were the basilar, anterior spinal, and middle and anterior cerebral arteries through which the perivascular SAS was imaged. The HF-OCT imaging probe was introduced via a microcatheter and images were acquired using a contrast injection (3.5 mL/s) for blood clearance. Segmentation and three-dimensional rendering of HF-OCT images were performed to study the different configurations and porosity of the subarachnoid trabeculae (SAT) as a function of location.ResultsOf 13 acquisitions, three were excluded due to suboptimal image quality. Analysis of 15 locations from seven animals was performed showing six distinct configurations of arachnoid structures in the posterior circulation and middle cerebral artery, ranging from minimal presence of SAT to dense networks and membranes. Different locations showed predilection for specific arachnoid morphologies. At the basilar bifurcation, a thick, fenestrated membrane had a unique morphology. SAT average thickness was 100 µm and did not vary significantly based on location. Similarly, the porosity of the SAT averaged 91% and showed low variability.ConclusionWe have demonstrated the feasibility to image the structures of the SAS with transvascular HF-OCT. Future studies are planned to further map the SAT to increase our understanding of their function and possible impact on neurovascular pathologies.

Optical coherence tomography (OCT) technology is a well-established diagnostic tool in multiple fields of medicine. Intravascular OCT has been used for more than a decade for the clinical imaging of coronary arteries, however, its use for the imaging of the human cerebrovasculature has been delayed by the challenges posed by the elevated vascular tortuosity. A novel high-frequency OCT (HF-OCT) probe designed for neurovascular use was evaluated in tortuous, ex vivo, human intracranial anatomy and, using an in vivo canine model, for the dynamic imaging of intracranial arteries and the subarachnoid trabecula (SAT). Using four cadavers, we investigated HF-OCT probe navigation and imaging performances in human anterior arterial circulation (from the M4 segment to internal carotid artery), in the posterior arterial circulation (from the P4 segment to vertebrobasilar junction) and in a broad range of venous sinuses. HF-OCT was able to gain distal access through elevated tortuosity and generate high-quality imaging data depicting vessel morphology, the vessel wall pathology (e.g., atherosclerotic disease and dissecting lesions), and the subarachnoid trabecula (SAT). Using an in vivo canine model, the HF-OCT probe was used to record stationary dynamic data in multiple intracranial vascular locations. Data showed the motion of the arteries and the SAT, including collisions between vessels, membranes, and the interaction between the SAT and the blood vessels. HF-OCT data allowed for the quantification of the dynamics of the vessels and the SAT, including vessel lateral motion with respect to the parenchyma, and collisions between large and small arteries. Results showed that the HF-OCT probe can overcome delivery obstacles in tortuous cerebrovascular anatomy and provide high-quality and high-resolution imaging at multiple distal locations, including M4 and P4 segments of the anterior and posterior circulations. HF-OCT has the potential to facilitate a better understanding of fine anatomical details of the cerebrovascular and perivascular environment, neurovascular disease, and collect real time information about the dynamics of the subarachnoid space and arteries and become a valuable diagnostic tool.

BackgroundHigh-frequency optical coherence tomography (HF-OCT) is an intra-vascular imaging technique capable of assessing device-vessel interactions at spatial resolution approaching 10 µm. We tested the hypothesis that adequately deployed Woven EndoBridge (WEB) devices as visualized by HF-OCT lead to higher aneurysm occlusion rates.MethodsIn a leporine model, elastase-induced aneurysms (n=24) were treated with the WEB device. HF-OCT and digital subtraction angiography (DSA) were performed following WEB deployment and repeated at 4, 8, and 12 weeks. Protrusion (0-present, 1-absent) and malapposition (0-malapposed, 1-neck apposition >50%) were binary coded. A device was considered ‘adequately deployed’ by HF-OCT and DSA if apposed and non-protruding. Aneurysm healing on DSA was reported using the 4-point WEB occlusion score: A or B grades were considered positive outcome. Neointimal coverage was quantified on HF-OCT images at 12 weeks and compared with scanning electron microscopy (SEM).ResultsAdequate deployment on HF-OCT correlated with positive outcome (P=0.007), but no statistically significant relationship was found between good outcome and adequate deployment on DSA (P=0.289). Absence of protrusion on HF-OCT correlated with a positive outcome (P=0.006); however, malapposition alone had no significant relationship (P=0.19). HF-OCT showed a strong correlation with SEM for the assessment of areas of neointimal tissue (R²=0.96; PConclusionHF-OCT visualizes features that can determine adequate device deployment to prognosticate early aneurysm occlusion following WEB implantation and can be used to longitudinally monitor aneurysm healing progression.

Intravascular imaging has emerged as a valuable tool for the treatment of coronary and peripheral artery disease; however, no solution is available for safe and reliable use in the tortuous vascular anatomy of the brain. Endovascular treatment of stroke is delivered under image guidance with insufficient resolution to adequately assess underlying arterial pathology and therapeutic devices. High-resolution imaging, enabling surgeons to visualize cerebral arteries' microstructure and micron-level features of neurovascular devices, would have a profound impact in the research, diagnosis, and treatment of cerebrovascular diseases. Here, we present a neurovascular high-frequency optical coherence tomography (HF-OCT) system, including an imaging console and an endoscopic probe designed to rapidly acquire volumetric microscopy data at a resolution approaching 10 microns in tortuous cerebrovascular anatomies. Using a combination of in vitro, ex vivo, and in vivo models, the feasibility of HF-OCT for cerebrovascular imaging was demonstrated., High resolution intravascular imaging in the brain is limited by the high tortuosity of the vasculature. Here the authors present a fiber optic imaging technology using high-frequency optical coherence tomography (HF-OCT) to provide volumetric high resolution images in the highly tortuous cerebral vasculature.

Background Tissue growth over covered branches is a leading cause of delayed thrombotic complications after flow-diverter stenting (FDS). Due to insufficient resolution, no imaging modality is clinically available to monitor this phenomenon. Objective To evaluate high-frequency optical coherence tomography (HF-OCT), a novel intravascular imaging modality designed for the cerebrovascular anatomy with a resolution approaching 10 microns, to monitor tissue growth over FDS in an arterial bifurcation model. Methods FDS were deployed in a rabbit model (n = 6), covering the aortic bifurcation. The animals were divided in different groups, receiving dual antiplatelet therapy (DAPT) (n = 4), aspirin only (n = 1), and no treatment (n = 1). HF-OCT data were obtained in vivo at 3 different time points in each animal. For each cross-sectional image, metal and tissue coverage of the jailed ostium was quantified. Scanning electron microscopy images of harvested arteries were subsequently obtained. Results Good quality HF-OCT data sets were successfully acquired at implant and follow-up. A median value of 41 (range 21-55) cross-sectional images were analyzed per ostium for each time point. Between 0 and 30 d after implant, HF-OCT analysis showed a significantly higher ostium coverage when DAPT was not given. After 30 d, similar growth rates were found in the DAPT and in the aspirin group. At 60 d, a coverage of 90% was reached in all groups. Conclusion HF-OCT enables an accurate visualization of tissue growth over time on FDS struts. The use of FDS in bifurcation locations may induce a drastic reduction of the jailed-branch ostium area.

The implantation of flow diverters requires administration of dual anti-platelet therapy, posing the potential for complications. The p48MW HPC (phenox, Bochum, Germany) hydrophilic-coated flow diverting stent is designed to be anti-thrombotic, thus opening the potential for single anti-platelet therapy. We deploy a novel intravascular high-resolution imaging technique, high-frequency optical coherence tomography (HF-OCT), to study in an animal model the acute thrombus formation on coated p48MW devices versus uncoated control devices. Three pigs were implanted with 4 flow diverters each, two test hydrophilic-coated devices, and two control uncoated devices (p48MW). Each pig was treated with a different anti-platelet regime: no anti-platelet therapy, aspirin only, aspirin and clopidogrel. Twenty minutes after the flow diverter was implanted, an HF-OCT data set was acquired. Acute clot formed on the flow diverter at each covered side branch was measured from the HF-OCT slices. Factors considered to be important were the device type (pHPC versus bare metal), aspirin, clopidogrel, and vessel location. A linear model was constructed from the significant factors. Both coating (p

BackgroundHigh-frequency optical coherence tomography (HF-OCT) is an intravascular imaging method that allows for volumetric imaging of flow diverters in vivo.ObjectiveTo examine the hypothesis that a threshold for both volume and area of communicating malapposition can be predictive of early aneurysm occlusion.MethodsFifty-two rabbits underwent elastase aneurysm formation, followed by treatment with a flow diverter. At the time of implant, HF-OCT was acquired to study the rate and degree of communicating malapposition. Treated aneurysms were allowed to heal for either 90 or 180 days and euthanized following catheter angiography. Healing was dichotomized into aneurysm remnant or neck remnant/complete occlusion. Communicating malapposition was measured by HF-OCT using a semi-automatic algorithm able to detect any points where the flow diverter was more than 50 µm from the vessel wall. This was then summed across image slices to either a volume or area. Finally, a subsampled population was used to train a statistical classifier for the larger dataset.ResultsNo difference in occlusion rate was found between device type or follow-up time (p=0.28 and p=0.67, respectively). Both volume and area of malapposition were significantly lower in aneurysms with a good outcome (p3 or a normalized area less than 0.69 as quantified by HF-OCT was predictive of occlusion (pConclusionsHF-OCT allows for measurements of both volume and area of malapposition and, from these measurements, an accurate prediction for early aneurysm occlusion can be made.

Journal of the American Heart Association 10(20), 1-29 (2021). doi:10.1161/JAHA.121.020834, Published by American Heart Association, New York, NY

Diagnosis of cerebrovascular disease includes vascular neuroimaging techniques such as computed tomography (CT) angiography, magnetic resonance (MR) angiography (with or without use of contrast agents) and catheter digital subtraction angiography (DSA). These techniques provide mostly information about the vessel lumen. Vessel wall imaging with MR seeks to characterize cerebrovascular pathology, but with resolution that is often insufficient for small lesions. Intravascular imaging techniques such as ultrasound and optical coherence tomography (OCT), used for over a decade in the peripheral circulation, is not amendable to routine deployment in the intracranial circulation due to vessel caliber and tortuosity. However, advances in OCT technology including the probe profile, stiffness and unique distal rotation solution, holds the promise for eventual translation of OCT into the clinical arena. As such, it is apropos to review this technology and present the rationale for utilization of OCT in the cerebrovasculature.

Introduction High Frequency Optical Coherence Tomography (HF-OCT)1 is an intra-vascular imaging technique to assess device-vessel interactions and neointimal tissue growth at unprecedented spatial resolution (~10µm). In this study, we tested the hypothesis that an adequately deployed (as visualized by HF-OCT) Woven EndoBridge (WEB, Microvention, Aliso Viejo, CA) will lead to a higher aneurysm occlusion rate at 12-week follow-up in an animal model of aneurysms. Methods Elastase-induced rabbit aneurysms (n=24) were treated with the WEB device. HF-OCT (Vis-M; Gentuity LLC, Sudbury MA) and DSA were performed after WEB deployment and repeated at 4, 8, and 12 weeks. Protrusion and malapposition were binary coded (0- present, 1- absent; 0- malapposed, 1- neck apposition >50%), respectively, on HF-OCT and DSA. A device was considered adequately deployed if it was scored as 1 on both metrics. Aneurysm healing on DSA was interpreted using the 4-point WEB occlusion score (WOS)2; with A-B considered a positive outcome. HF-OCT images acquired at 12 weeks were analyzed and neointimal coverage quantified. Scanning electron microscopy (SEM) was performed of the explanted specimens. Results Discrepancy between HF-OCT and DSA was found: HF-OCT classified as adequately deployed a total of 5 cases, whereas 8 cases were classified as adequately deployed by DSA images. Acceptable WOS grade at 12 weeks was seen in 21% of cases (n=5): 80% of those cases (n=4) were classified as adequately deployed based by HF-OCT; whereas only 60% of those cases (n=3) classified adequate by DSA. A significant interaction between adequate deployment on HF-OCT and positive outcome was confirmed (p=0.007). However, there was no statistically significant relationship between good outcome and adequate deployment based on DSA images (p=0.289). Based on HF-OCT images, the absence of the protrusion was related with a positive outcome (p=0.006); however, malapposition had no significant interaction with positive outcome (p=0.19). The area of neointimal tissue quantified by HF-OCT showed a strong correlation with SEM assessment (R²=0.96; p Conclusion HF-OCT may be valuable prognosticate adequate aneurysm occlusion with the WEB and can be used to monitor aneurysm healing longitudinally. Absence of protrusion was associated with subsequent aneurysm occlusion; however, malapposition alone did not show an effect on the rate of aneurysm healing. Reference Stroke. 2018:Nov29:STROKEAHA118022315 2. AJNR 2014;35:432–8. Disclosures Z. Vardar: None. R. King: None. A. Kraitem: None. E. Langan: None. L. Peterson: None. B. Duncan: None. C. Raskett: None. V. Anagnostakou: None. M. Gounis: None. A. Puri: None. G. Ughi: None.

Introduction A new method of intravascular imaging is introduced, high-frequency optical coherence tomography (HF-OCT), with resolution unprecedented for in vivo imaging (~10µm). Here we describe the first preclinical observations of cerebrovascular imaging with this new technology. Methods Two dogs were imaged using HF-OCT. A 6F straight guiding catheter was initially positioned into the right vertebral artery up to the origin of the right lateral spinal ramus anastomoticus and the basilar artery was accessed with an SL-10 microcatheter. In the first dog access was achieved through the main lumen of the vertebral artery coursing along the vertebral column around the C1 vertebral body and finally the vertebrobasilar junction and the basilar artery. In the second dog access was achieved through the right lateral spinal ramus and the anterior spinal artery, the diamond shaped confluence of anastomotic channels between vertebral arteries and spinal rami into the basilar artery. In both animals the microcatheter was advanced up to the P1-P2 segment of the left PCA in order to facilitate positioning of the HF-OCT wire which was unsheathed from the microcatheter. Using contrast at a flow rate of 4 ml/sec to wash out the blood in the vessels imaging of the basilar artery from distal to proximal was performed. Results Detailed images of the basilar artery, lower cerebellar arteries, basilar perforators, vertebrobasilar junction, spinal perforators were obtained (figure 1). Due to the high resolution of the method, the layers of the vessel wall were imaged. What was even more interesting was the ability to image beyond the artery into the structural components of the subarachnoid space with the arachnoid membranes and what we believe to be the arachnoid trabeculae. Venous structures and nerve root origins were also recognized. Conclusion HF-OCT imaging can offer detailed visualization not only of the vessel wall, the branching pattern of basilar and spinal perforators but also of structures of the subarachnoid space impossible to study with other imaging modalities due to inadequate resolution. The clinical implication of such an analysis is yet to be discovered. Disclosures V. Anagnostakou: None. Z. Vardar: None. A. Puri: None. G. Ughi: None. M. Gounis: None.

Introduction: Optical coherence tomography (OCT) has played an important role in the diagnosis and treatment guidance in coronary artery disease. However, existing OCT systems are not suitable for routine neurovascular applications due to the size and tortuosity of the arteries. Hypothesis: We seek to demonstrate a prototype high-frequency OCT (HF-OCT) capable of high-resolution imaging in simulated cerebrovascular anatomy. Methods: A low-profile HF-OCT system was constructed with an image resolution approaching 10μm. Using an in vitro, patient-specific model of the circle of Willis with circulating porcine blood, we characterized the delivery of the device and ability to image in a tortuous path. Also, human cadaver intracranial atherosclerosis plaques were imaged with HF-OCT and assessed by an expert imager. Finally, neurovascular devices were implanted in 8 pigs (Fig 1) and HF-OCT imaging was compared with gold-standard DSA and CT. Results: In the phantom, optimal blood clearance was achieved through an intermediate catheter (5 Fr Navien) with infusion of contrast at 5 ml/s in the internal carotid and basilar artery, and 3 ml/sec in the MCA. The in vivo study demonstrated that both malapposition of devices or thrombus formation along the device surface could be reliably diagnosed among 3 reviewers (Fleiss’s kappa of 0.87 and 0.9, respectively). This agreement was superior to DSA and CT. Imaging in tortuous swine brachial showed in all cases imaging free of artifacts, uniform illumination and ability to visualize vessel wall layers. Plaque types including ‘lipid pools’, fibrotic, and calcific tissue from cadaver specimens of ICAD could be adequately depicted by HF-OCT. Conclusion: In vitro, in vivo and ex vivo characterization of a novel HF-OCT device has shown it is capable of imaging in the tortuous intracranial vascular anatomy. This technology has to potential to aid in the diagnosis of cerebrovascular disease and guide optimal endovascular treatment.

The implantation of flow diverters requires administration of dual anti-platelet therapy, posing the potential for complications. The p48MW HPC (phenox, Bochüm, Germany) hydrophilic-coated flow diverting stent is designed to be anti-thrombotic, thus opening the potential for single anti-platelet therapy. We deploy a novel intravascular high-resolution imaging technique, high-frequency optical coherence tomography (HF-OCT), to study in an animal model the acute thrombus formation on coated p48MW devices versus uncoated control devices.Three pigs were implanted with 4 flow diverters each, two test hydrophilic-coated devices, and two control uncoated devices (p48MW). Each pig was treated with a different anti-platelet regime: no anti-platelet therapy, aspirin only, aspirin and clopidogrel. Twenty minutes after the flow diverter was implanted, an HF-OCT data set was acquired. Acute clot formed on the flow diverter at each covered side branch was measured from the HF-OCT slices. Factors considered to be important were the device type (pHPC versus bare metal), aspirin, clopidogrel, and vessel location. A linear model was constructed from the significant factors.Both coating (p 0.001) and aspirin (p = 0.003) were significantly related to reduction in clot burden, leading to an approximate 100-fold and 50-fold reduction in clot, respectively.This study shows the power of HF-OCT not only in the detection of clot but also the quantification of clot burden. In an animal model, the pHPC-coated p48MW significantly reduced acute thrombus formation over jailed side branches as compared to the bare metal p48MW that was nearly eliminated when combined with aspirin administration.

A single imaging modality for the assessment of coronary artery disease has fundamental limitations that may impair a complete and detailed evaluation of coronary pathology. In an attempt to overcome these drawbacks, novel hybrid, multimodality catheters that integrate complementary imaging technologies have been developed to provide a more comprehensive profile of the underlying vascular disease state. Recent studies have introduced dual-probe devices combining IVUS imaging with optical coherence tomography (OCT) for an improved evaluation of coronary lumen morphology and vessel wall pathology. Furthermore, IVUS and OCT probes have been individually combined with chemical near-infrared spectroscopy (NIRS) and molecular near-infrared fluorescence (NIRF) imaging in an effort to increase the specificity and sensitivity of intravascular imaging to detect coronary disease pathobiology. Additional hybrid catheter imaging technologies such as photoacoustics and fluorescence lifetime imaging are promising new alternative technologies. The aim of this chapter is to review the emerging multimodal imaging approaches for the coronary arteries and describe their ability to overcome the inherent limitations of stand-alone imaging. Advances of multimodality intravascular imaging in the context of clinical applications will be discussed, together with the technical challenges for their successful translation.

Introduction High frequency optical coherence tomography (HF-OCT) is an intra-vascular imaging modality designed for cerebrovascular anatomy. With a spatial resolution approaching 10 µm, HF-OCT can visualize the interaction between the vessel wall and neurovascular devices in great detail.1, 2 In this study, we sought to evaluate its use to monitor tissue growth over flow diverter stents (FDS) in an arterial bifurcation rabbit model. Materials and methods Six FDS (Pipeline Embolization devices) were deployed in 6 animals, covering the iliac bifurcation. Four animals were treated with double antiplatelet therapy (10 mg/kg aspirin and clopidogrel), 1 with aspirin (10 mg/kg) and 1 was not given any treatment. HF-OCT data were obtained at three different time points per each animal (at implant for all animals then 14 and 60 or 7 and 30 days). For each ostium section, manual segmentation was performed to quantify the percentage of the ostium surface covered by metal and tissue (figure 1A). Results Good quality HF-OCT data sets were successfully acquired in all cases. An average of 35 sections (with a spacing between sections of approximately 70 µm) were analyzed per ostium for each time point. Between 0 and 30 days after implant, HF-OCT analysis showed a significantly higher ostium coverage when DAPT was not given. After 30 days, similar growth rates were found in the DAPT and in the aspirin group (Figure 1B). At 60 days a high 90% coverage rate was reached in both groups. Conclusions HF-OCT enables an accurate visualization of tissue growth over time on FDS struts. HF-OCT imaging can contribute in the pre-clinical evaluation of novel neurovascular devices and, in the near-future, it could potentially contribute to a personalized care, helping the physicians in determining and modulating the ideal antiplatelet regimen for each patient. References Chen C-J, Kumar JS, Chen SH, et al. Optical coherence tomography: future applications in cerebrovascular imaging. Stroke 2018. Gounis MJ, Ughi GJ, Marősfoi M, et al. Intravascular optical coherence tomography for neurointerventional surgery. Stroke 2018. Disclosures J. Caroff: None. G. J. Ughi: 4; C; Gentuity LLC. 5; C; Employee of Gentuity LLC. R. King: None. M. Marosfoi: None. E. Langan: None. M. Gounis: None.

Introduction The use of flow diverters has emerged as an effective treatment of aneurysm. One of the major limitations of flow diverters is the need to put patients on dual anti-platelet therapy (DAPT). The exposure of bare metal struts leads to platelet activation. A method to assess the degree of neointimal tissue ingrowth over the surface of the device could permit patient-specific tailoring of DAPT. Currently, the standard of follow-up for flow diverter patients is digital subtraction angiography (DSA); however, it has been previously reported DSA appearance of complete aneurysm occlusion is not always reliable with continued aneurysm growth.1 There have been reported cases of very delayed complications after DAPT has been stopped,2 although rare, such complications can be catastrophic. High Frequency Optical Coherence Tomography (HF-OCT) is a novel intravascular imaging technique designed for use in cerebrovascular anatomy with a spatial resolution approaching 10 microns. In this study, we sought to compare HF-OCT with state-of-the-art DSA for the in vivo evaluation of complete aneurysm occlusion. Methods Flow diverters were implanted in 15 rabbits, at least 21 days after a standard elastase aneurysm creation. Six of the rabbits were imaged at 15 days post implant, including both DSA and HF-OCT to assess healing of the aneurysm. The remaining 9 rabbits were allowed to heal for 60 days, at which point they also received HF-OCT. Finally, the rabbits were euthanized, perfused with formalin, and the aneurysms were explanted for histological analysis. Results Fifteen days following implant, one aneurysm was seen to be fully occluded on DSA, but HF-OCT demonstrated an aneurysm remnant, and the struts remained uncovered (figure 1D-E). At 60 days post-implant, another aneurysm appeared fully healed on DSA, yet HF-OCT demonstrated that the aneurysm remained in communication with the parent artery (figure 1A-B). This observation was later confirmed on SEM (figure C). Conclusions Preliminary evidence is presented showing that DSA alone is insufficient to confirm complete aneurysm occlusion. HF-OCT may reliably show parent artery remodeling and inform patient-specific decisions regarding duration of DAPT. References AJNR June 2012;33(6):1150–1155. J Neurosurg 2016;125:929–935. Disclosures R. King: None. M. Marsofoi: None. E. Langan: None. M. Shazeeb: None. G. Ughi: 4; C; Gentuity LLC. 5; C; Gentuity LLC. C. Raskett: None. A. Puri: None. M. Gounis: None.

Introduction The development of High Frequency OCT1 (HF-OCT) allows for higher resolution intra-arterial imaging, such that vascular remodeling in response to stents and next generation intrasaccular devices (NGID) can be interrogated. We hypothesize that imperfections or gaps in the neck coverage of an aneurysm after treatment with a NGID will be predictive of failed aneurysm occlusion. Materials and methods Two aneurysms were made in each of six dogs, one sidewall aneurysm on the distal right common carotid artery (CCA), and a bifurcation aneurysm proximally at the apex of an anastomosis between the left and right CCAs. One aneurysm was excluded due to thrombosis at the time of treatment. Each aneurysm was treated with either detachable coils, or NGID, with a 7:4 randomization NGID:COIL. At implant, HF-OCT was obtained after each aneurysm was successfully packed. At 180 days, animals were assessed for final aneurysm occlusion by DSA. Separately, the HF-OCT data sets were automatically segmented such that gaps in the coverage of the aneurysm neck could be identified and used to predict if the aneurysm occlusion at 180 days. Results The overall rate of occlusion was not seen to be different between the NGID and COIL group (p=0.45) on the Raymond-Roy scale.2 All of the NGID constructs were successfully segmented, and the associated larges gap in the neck coverage for each was determined. A gap in the NGID construct at the level of the neck greater than 1 mm2 predicted failed aneurysm occlusion at 180-days (p = 0.047). This threshold correctly classified all aneurysms. Conclusions HF-OCT allows not only for the imaging and segmentation of intra-arterial devices in vivo, but showed great potential as a robust diagnostic tool. Preliminary evidence collected in this study showed that HF-OCT can prognosticate aneurysm treatment success at the time of treatment. References Stroke. 2018:Nov29:STROKEAHA118022315 Stroke. 2003;34(6):1398–1403. Disclosures R. King: None. M. Marosfoi: None. J. Caroff: None. G. Ughi: 4; C; Gentuity LLC. 5; C; Gentuity LLC. D. Groth: None. M. Gounis: None. A. Puri: None.

Introduction The use of stents in the treatment of wide neck aneurysms, and more recently the adoption of flow diverters, are important tools for the treatment of aneurysms.1 One major complication of such implants is thromboembolism, requiring the use of dual anti-platelet therapy (DAPT). However, due to variable response and inherent risks of DAPT, new stents are being developed with anti-thrombogenic coatings with the goal to reduce or eliminate the need for DAPT. Methods A novel hydrophilic polymer coating (HPC) applied to a nitinol substrate has been shown to resist platelet aggregation in vitro.2 We sought to demonstrate preliminary evidence to confirm this observation in vivo. Three pigs were used with different regimens: no antiplatelet medication (NAPT), 81 mg aspirin (SAPT), and 81 mg aspirin with 75 mg Clopidogrel (DAPT). Two control and two coated devices were implanted in each animal. High Frequency Optical Coherence Tomography (HF-OCT), with a spatial resolution approaching 10 microns, was used to study acute thrombus formation along the surface of the device. HF-OCT acquisitions were acquired 20 minutes following device implant. Specifically, the total clot volume on each side branch opening (SBO) was segmented with manual input by a blinded user. Statistical analyses were performed to determine the relative benefit of the HPC coating and the antiplatelet regiment for prevention of platelet aggregation, a linear model was constructed to interrogate the relative importance. Results The figure 1 shows one section from each device type. It was found that device type and aspirin where significantly correlated with thrombus volume over SBOs. Mean thrombus volume per mm2 of SBO for coated versus control devices was 0.00033 mm versus 0.087 mm, respectively (p = 0.005). Mean clot per SBO was 0.004 mm versus 0.15 mm in animals receiving aspirin versus NAPT (p Conclusions This preliminary evidence shows the dramatic effect that the coating can have on the acute thrombus formation. Further, this novel HF-OCT technology allows for quantitative measurements of the amount of thrombus formed on the surface of a flow diverter, not just the presence. Finally, this study shows the possibility that the combined effect of aspirin and this new coating may be sufficient antiplatelet therapy. References Neurosurgery 2017;80:40–48. CardioVasc Intervent Radiol 2018;41:1779–1785. Disclosures R. King: None. E. Langan: None. M. Marosfoi: None. G. Ughi: 4; C; Gentuity LLC. 5; C; Gentuity LLC. C. Raskett: None. M. Gounis: 2; C; Phenox

Introduction Intravascular optical coherence tomography (OCT) has an established role in the diagnosis and image guided treatment of coronary artery disease. However, due to the profile and design of the catheter, these devices are not suitable for routine application in neurointerventional surgery. We aim to demonstrate that new generation high frequency OCT (HF-OCT) can image stents and flow diverters used to treat intracranial aneurysms with acceptable workflow deployed in neurointerventional surgery. Materials and methods An HF-OCT prototype was built (Gentuity, Sudbury MA) that is compatible with standard microcatheters (0.017’). An in vitro flow loop consisting of a patient-specific vascular replica and using porcine blood as a working fluid was deployed to test contrast infusion protocols necessary to remove blood from the target vascular section. Subsequently, eight pigs were implanted bilaterally with flow diverters and stents. The presence of acute platelet aggregation on the surface of the devices and malapposition of the device to the vessel wall was assessed by 3 raters reviewing digital subtraction angiography (DSA), high resolution cone beam CT (CBCT), and HF-OCT. Finally, using the tortuous porcine brachial artery, HF-OCT was performed, and image quality assessed. Results In the in vitro experiment, the optimized contrast infusion protocol was delivery of contrast through the intermediate catheter (0.058’ Navien, Medtronic Neurovascular, Irvine CA) delivering the HF-OCT device at a rate of 5 ml/s for 20–25 ml of contrast. This protocol resulted in complete clearing of highly attenuating erythrocytes for an optically clear field. In the pig study, the agreement by the reviewers (Fleiss kappa) regarding clot formation at 3 distinct locations along the flow diverter was 0.49, 0.67 and 0.90 for DSA, CBCT and HF-OCT, respectively. The agreement for diagnosing malapposition at these locations was 0.18, 0.67 and 0.87 for DSA, CBCT, and HF-OCT, respectively. In the porcine tortuosity model, in all cases, navigation and imaging was performed with uniform illumination and free from artifact. Conclusion An HF-OCT device has been built that is compatible with neurointerventional surgery workflow and cerebrovascular anatomy. Preclinical data demonstrate consistent improvement to diagnose acute platelet aggregation and malapposition of flow diverters as compared to existing imaging modalities (figure 1). Disclosures A. Puri: 1; C; NIH. M. Marosfoi: None. G. Ughi: 4; C; Gentuity. 5; C; Gentuity. R. King: None. E. Langan: None. J. Chueh: None. M. Gounis: 1; C; NIH.

Aims: The PRISON IV trial investigated the next-generation sirolimus-eluting stent (SES) with ultra-thin struts and biodegradable polymer against the second-generation everolimus-eluting stent (EES) with thin struts and durable polymer in patients with successfully recanalised chronic total occlusions (CTO). In this study, we examined the secondary optical coherence tomography endpoints. Methods and results: The main PRISON IV trial randomised 330 patients to either SES or EES. At nine months, 281 (85%) patients underwent repeat angiography. Of these, 60 consecutive patients received optical coherence tomography divided over both stent groups. The mean number of struts analysed was 750±337 and 633±358 in SES and EES patients, respectively (p=0.07). The minimal lumen area, minimal stent area, maximal neointima area and neointimal thickness were comparable between the groups (4.8±2.1 and 4.4±1.5 mm2; 5.3±1.8 and 5.3±1.4 mm2; 2.5±2.0 and 2.2±1.5 mm2; 0.7±1.7 and 0.4±0.2 mm). The percentage of uncovered struts was higher with EES (6.2±7.5% and 11.9±13.4%, p=0.04), whereas the percentage of malapposed struts and mean number of coronary evaginations were significantly higher with SES (2.9±4.0% and 1.2±2.4%, p=0.02; 18.5±17.7 and 5.3±3.1, p=0.004). Conclusions: The optical coherence tomography findings of this substudy demonstrated improved strut coverage with ultra-thin strut SES with bioresorbable polymer compared to thin-strut EES with durable polymer in CTO. On the other hand, SES showed a higher rate of stent strut malappositon and coronary evaginations. The clinical relevance of these findings remains to be demonstrated.

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.

Objectives 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. Background 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. Methods 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. Results 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. Conclusions 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)

Aims: We aimed to compare healing responses with optical coherence tomography, and clinical and angiographic outcome after treatment of coronary bifurcation lesions with a dedicated stent versus a conventional culotte technique. Methods and results: Forty patients with true and complex coronary bifurcation lesions were randomly assigned to treatment with the Axxess™ bifurcation stent in the proximal main vessel (MV) and additional BioMatrix™ stents in the branches (Biosensors Europe SA, Morges, Switzerland), versus a culotte technique using XIENCE™ stents (Abbott Vascular, Santa Clara, CA, USA). The primary endpoint of percentage of uncovered struts at nine months was similar with the dedicated strategy vs. culotte in the proximal MV (median 17.8 [IQR 3.3-24.7] vs. 6.8 [2.0-20.5]; p=0.19), bifurcation core (9.5 [5.7-19.5] vs. 4.0 [0.7-17.6]; p=0.17), distal MV (2.6 [2.3-18] vs. 2.2 [0.5-6.0]; p=0.09) and side branch (5.7 [1.5-11.5] vs. 1.9 [0-5.8]; p=0.14). As compared with culotte, a strategy using Axxess resulted in a significantly larger lumen in the proximal MV both acutely (minimum lumen diameter 3.03±0.51 vs. 2.71±0.44 mm, p=0.04) and at follow-up (mean lumen area 10.0±2.1 vs. 7.1±1.8 mm 2 , p

BackgroundHigh frequency optical coherence tomography (HF-OCT) is a novel intravascular imaging technology developed for use in the cerebral vasculature. We hypothesize that HF-OCT characterization of intrasaccular device neck coverage can prognosticate exclusion of the aneurysm from the circulation.MethodsBifurcation and sidewall aneurysms were made in six dogs. Seven aneurysms were treated with next generation intrasaccular devices (NGID) and four with traditional platinum coils. HF-OCT was performed to interrogate gaps in the neck coverage, coil herniation, or acute thrombus formation. Animals were re-imaged at 7, 30, 90, and 180 days following aneurysm embolization. An automated image processing method segmented the devices at the neck of the aneurysm and quantified neck coverage. The largest coverage gap was used to predict aneurysm occlusion at 180 days.ResultsNo difference was found in occlusion rates between the coil and NGID groups (P=0.45). Successful segmentation of the NGID construct was achieved in all cases. A coverage gap >1 mm2 was found to predict failed aneurysm occlusion (P=0.047). This threshold was able to predict all cases of failed occlusion. The average number of devices needed to treat the aneurysm was lower in the NGID group (1.9 vs 6.75, P=0.009). HF-OCT showed strong agreement with scanning electron microscopy (bias 0.0024 mm2 (95% CI −0.0279, 0.0327)).ConclusionsHF-OCT enables precise and accurate measurement of coverage gaps at the neck of aneurysms treated with intrasaccular devices in vivo. We provide in vivo evidence that uniform aneurysm neck coverage by intrasaccular devices is critical for aneurysm occlusion.

Intravascular optical coherence tomography (OCT) is capable of acquiring 3-dimensional (3D) data of coronary arteries allowing for the assessment of plaques, stents, thrombus, side branches, and other relevant structures in a 3D fashion. Given that state-of-the-art OCT systems acquire images at a very high frame rate (up to 200 frames per second), typically a very large number of images per pullback (ie, 500 or more) need to be analyzed. The manual assessment of stents, plaques, and other structures is time-consuming, cumbersome, and inefficient and thus not suitable for on-line analysis during percutaneous coronary intervention procedures.

We sought to assess in-stent variations in fractional flow reserve (FFR) in patients with previous percutaneous coronary intervention (PCI) and to associate any drop in FFR with findings by optical coherence tomography (OCT) imaging. Suboptimal post-PCI FFR values were previously associated with poor outcomes. It is not known to which extent in-stent pressure loss contributes to reduced FFR. In this single-arm observational study, 26 patients who previously underwent PCI with drug-eluting stent or scaffold implantation were enrolled. Motorized FFR pullback during continuous intravenous adenosine infusion and OCT assessments was performed. Post-PCI FFR 0.03 was associated with suboptimal FFR. In patients with suboptimal FFR, the OCT analyses revealed higher mean neointimal area (respectively: 1.06 ± 0.80 vs. 0.51 ± 0.23 mm2; p = 0.018) and higher neointimal thickness of covered struts (respectively 0.11 ± 0.07 vs. 0.06 ± 0.01 mm; p = 0.021). Suboptimal FFR values following stent-implantation are mainly caused by significant in-stent pressure loss during hyperemia. This finding is associated to a larger neointimal proliferation.

A 74-year-old man presented with an acute anterior ST-elevation myocardial infarction. Urgent coronary angiography showed a suboccluded proximal left anterior descendens (LAD) artery due to segment...

The scope of this text is to critically review the most important recent advances in the field of optical coherence tomography, both from a clinical, scientific, and technical point of view. In recent years, important steps forward have been put in the field of optimization of PCI (with a focus on optimal sizing of stents and optimization of stent expansion after implantation) and the differentiation and its possible applications of various underlying morphologic characteristics of acute coronary syndrome lesions. Several efforts have been made to elucidate underlying mechanical causes of stent thrombosis, based on optical coherence tomography (OCT) imaging. This had led to the recognition of neoatherosclerosis as an important cause for very late stent thrombosis, fueling new research into this area and to the development of intracoronary devices which could be even more safe for patients on the very long term. With an ever increasing use for clinical and scientific applications in coronary artery disease, OCT has come to a mature and solid tool in the armamentarium of the coronary artery disease specialist. With new areas deserving more intensified focus and several innovations ahead, it seems that OCT is there to defend its position as the standard intracoronary imaging modality for the next decennium.

Background Vessel wall injury after drug-eluting stent (DES) implantation can be characterized in detail by optical coherence tomography (OCT). Little is known about the healing course of these phenomena. Methods and results In 62 lesions (62 patients), the incidence of acute vessel trauma was assessed in the stented region and the edge segments immediately after DES implantation. The healing course of these injuries was assessed at 9-month OCT follow-up using a software algorithm allowing for reliable spatial comparison of baseline and follow-up cross-sectional images. Tissue prolapse (TP) and tissue protrusions were detected in 81 and 35% of lesions, respectively. A total of 342 intra-stent dissection flaps (ISD) and 114 intra-stent dissection cavities (ISC) were visualized in 98 and 81% of lesions, respectively. Thirty-five lesions (56%) showed edge dissections (EDs). No residual TP or protrusion was observed at follow-up. Incomplete healing was seen in 8% of ISD and in 20% of ISC. For ED, a residual flap was observed in one-third of the initially dissected stent edges. Incomplete healing of acute vessel injury was associated with the presence of underlying atherosclerotic disease at baseline. Uncovered and malapposed stent struts were observed more often with incomplete healing of vessel injury at follow-up. Conclusions Acute vessel wall trauma is highly prevalent immediately after DES implantation. Most of these injuries are minor and resolve at mid-term follow-up. Incomplete healing of ISDs seems to be associated with other OCT findings suggesting delayed arterial healing.

Intravascular optical coherence tomography (IVOCT) is rapidly becoming the method of choice for the in vivo investigation of coronary artery disease. While IVOCT visualizes atherosclerotic plaques with a resolution

Aims: Fibrin deposition and absent endothelium characterize unhealed stents that are at heightened risk of stent thrombosis. Optical coherence tomography (OCT) is increasingly used for assessing stent tissue coverage as a measure of healed stents, but cannot precisely identify whether overlying tissue represents physiological neointima. Here we assessed and compared fibrin deposition and persistence on bare metal stent (BMS) and drug-eluting stent (DES) using near-infrared fluorescence (NIRF) molecular imaging in vivo, in combination with simultaneous OCT stent coverage. Methods and results: Rabbits underwent implantation of one BMS and one DES without overlap in the infrarenal aorta (N = 20 3.5 × 12 mm). At Days 7 and/or 28, intravascular NIRF-OCT was performed following the injection of fibrin-targeted NIRF molecular imaging agent FTP11-CyAm7. Intravascular NIRF-OCT enabled high-resolution imaging of fibrin overlying stent struts in vivo, as validated by histopathology. Compared with BMS, DES showed greater fibrin deposition and fibrin persistence at Days 7 and 28 (P < 0.01 vs. BMS). Notably, for edge stent struts identified as covered by OCT on Day 7, 92.8 ± 9.5% of DES and 55.8 ± 23.6% of BMS struts were NIRF fibrin positive (P < 0.001). At Day 28, 18.6 ± 10.6% (DES) and 5.1 ± 8.7% (BMS) of OCT-covered struts remained fibrin positive (P < 0.001). Conclusion: Intravascular NIRF fibrin molecular imaging improves the detection of unhealed stents, using clinically translatable technology that complements OCT. A sizeable percentage of struts deemed covered by OCT are actually covered by fibrin, particularly in DES, and therefore such stents might remain prothrombotic. These findings have implications for the specificity of standalone clinical OCT assessments of stent healing., National Institutes of Health (U.S.) (NIH grant R01HL108229), National Institutes of Health (U.S.) (NIH grant R01HL122388), American Heart Association (#13POST14640021), American Heart Association (#13GRNT17060040), Massachusetts General Hospital (MGH ECOR Support Fund), National Institutes of Health (U.S.) (NIH R01GM49039), National Institutes of Health (U.S.) (NIH R01HL093717), Kanae Foundation for Research Abroad

Objective— To validate optical coherence tomography (OCT) imaging for assessment of vascular healing in a preclinical animal model and human autopsy cases and to translate the findings to the assessment of vascular healing after drug-eluting stent implantation in clinical practice. Approach and Results— Drug-eluting and bare metal stents were imaged 28 and 42 days after implantation in atherosclerotic rabbits using OCT and simultaneously evaluated by histology. After coregistration with histology, gray-scale signal intensity (GSI) was measured for identified mature or immature neointimal tissue. Autopsy specimens were imaged with OCT and GSI values correlated with histology. Finally, prospective OCT imaging and GSI measurements were acquired in 10 patients undergoing follow-up 6 months after stenting with drug-eluting stents. Histopathologic and OCT morphometric analysis of implanted stents showed excellent correlation. Neointimal growth and vessel healing at 28 days in the animal model best correlated with human stented arteries at 6 months. In animal and human autopsy specimens, mature neointimal tissue consistently showed higher GSI values. Receiver operating characteristic curve analysis displayed high sensitivity and specificity for detection of mature neointima in animal (96% and 79%, respectively) and human autopsy (89% and 71%, respectively) data. In patients undergoing OCT follow-up 6 months after drug-eluting stent implantation, prospective GSI analysis revealed that a minimum of 27.7% of areas above stent struts represented mature neointima. Conclusions— Novel GSI analysis of OCT imaging data allows distinction between mature and immature neointimal tissue in animal models, autopsy specimens, and patients undergoing invasive surveillance in simple atherosclerotic lesions.

Aims: Qualitative criteria for plaque tissue characterisation by OCT are well established, but quantitative methods lack systematic validation in vivo. High optical attenuation coefficient μt has been associated with unstable plaque features, such as lipid core. The purpose of this study was to validate optical coherence tomography (OCT) attenuation imaging for tissue characterisation in vivo, specifically to detect lipid core in coronary atherosclerotic plaques, and to evaluate quantitatively the ability of OCT attenuation imaging to differentiate thin-cap (TCFA) and thick-cap fibroatheroma (FA). Methods and results: We prospectively enrolled 85 patients undergoing imaging of a native coronary segment by both OCT and near-infrared spectroscopy and intravascular ultrasound (NIRS-IVUS). Ninetyeight NIRS-positive 4 mm plaque segments were selected and matched to the OCT data. Two experienced OCT readers classified the plaque type using OCT criteria. A cap thickness of 65 μm was used to differentiate TCFA and FA. We computed an index of plaque attenuation (IPA) in the 4 mm blocks, and assessed the association of this index with plaque type. IPA differentiated between TCFA and FA (AUC=0.82 in ROC analysis; p

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).

Background: Atheroma inflammation impairs plaque stability and promotes plaque progression and complications. However, it is unknown how measures of plaque biology relate to changes in plaque burden, and whether plaque biology can independently predict plaque progression in coronary-sized arteries. This study evaluated the ability of intravascular near-infrared fluorescence (NIRF) biological imaging to inform experimental atheroma progression in vivo. Methods: Atherosclerosis was induced by balloon-injury in the aorta of 14 cholesterol-fed rabbits. Serial intravascular ultrasound (IVUS) and dual-modality intravascular NIRF - optical coherence tomography (OCT) imaging was performed following injection of a NIRF molecular imaging agent of plaque inflammatory protease activity (ProSense VM110; n=7), or impaired plaque endothelial permeability (indocyanine green (ICG); n=7). Plaque progression was further assessed by IVUS change in plaque burden. Regression analysis was used to evaluate the association of NIRF with plaque progression. In vivo imaging results were corroborated by ex vivo fluorescence reflectance imaging, fluorescence microscopy, and histopathology. Results: Quantitative analysis of 1,811 axial images spanning individual plaques, the change in NIRF plaque biological signals from 8 to 12 weeks strongly correlated with IVUS plaque burden from 8 to 12 weeks (ProSense VM110: r=0.774; ICG: r=0.572; p Conclusion: Plaque pathobiology and plaque burden progress in concert as assessed by translatable intravascular NIRF imaging technology. The baseline NIRF inflammation and impaired plaque permeability signals independently predict plaque progression. Integrated biological-microstructural imaging may enhance the ability to detect high-risk plaques at risk of progression.

Intravascular optical coherence tomography (OCT) is a high-resolution catheter-based imaging method that provides three-dimensional microscopic images of coronary artery in vivo, facilitating coronary artery disease treatment decisions based on detailed morphology. Near-infrared spectroscopy (NIRS) has proven to be a powerful tool for identification of lipid-rich plaques inside the coronary walls. We have recently demonstrated a dual-modality intravascular imaging technology that integrates OCT and NIRS into one imaging catheter using a two-fiber arrangement and a custom-made dual-channel fiber rotary junction. It therefore enables simultaneous acquisition of microstructural and composition information at 100 frames/second for improved diagnosis of coronary lesions. The dual-modality OCT-NIRS system employs a single wavelength-swept light source for both OCT and NIRS modalities. It subsequently uses a high-speed photoreceiver to detect the NIRS spectrum in the time domain. Although use of one light source greatly simplifies the system configuration, such light source exhibits pulse-to-pulse wavelength and intensity variation due to mechanical scanning of the wavelength. This can be in particular problematic for NIRS modality and sacrifices the reliability of the acquired spectra. In order to address this challenge, here we developed a robust data acquisition and processing method that compensates for the spectral variations of the wavelength-swept light source. The proposed method extracts the properties of the light source, i.e., variation period and amplitude from a reference spectrum and subsequently calibrates the NIRS datasets. We have applied this method on datasets obtained from cadaver human coronary arteries using a polygon-scanning (1230-1350nm) OCT system, operating at 100,000 sweeps per second. The results suggest that our algorithm accurately and robustly compensates the spectral variations and visualizes the dual-modality OCT-NIRS images. These findings are therefore crucial for the practical application and clinical translation of dual-modality intravascular OCT-NIRS imaging when the same swept sources are used for both OCT and spectroscopy.

Objectives We evaluated healing responses with optical coherence tomography (OCT), and clinical and angiographic outcome after bifurcation stenting with the TRYTON Side-Branch Stent™. Background Dedicated bifurcation stents have been proposed as a potential alternative for treatment of true coronary bifurcation lesions. Methods We treated 20 consecutive patients with coronary bifurcation lesions and significant involvement of the side-branch (SB) with the TRYTON Stent and an additional XIENCE-V™ everolimus-eluting stent. At 9 months, we assessed the ratio of uncovered to total stent struts (RUTSS) with OCT, angiographic late luminal loss (LLL), and in-stent and in-segment restenosis. Clinical endpoints at 1 year included major adverse cardiac events (MACE) and their components [target lesion revascularization (TLR), myocardial infarction (MI), and cardiac death]. Results LLL (N = 16) was 0.34 (0.17–0.46), 0.29 (0.24–0.48) and 0.57 (0.29–0.73) mm in the proximal main vessel (MV), distal MV and SB, respectively. In-bifurcation binary in-stent restenosis occurred in four patients (25%), in-segment restenosis in five (31.25%). The RUTSS (N = 13) was 4.0 ± 5.8, 0.7 ± 1.3, 0, and 2.5 ± 3.6% in the proximal MV, distal MV, SB, and polygon of confluence, respectively. At 1 year, MACE occurred in 5 (25%) [4 TLR (20%), 3 MI (15%)]. Conclusion The homogeneous stent strut coverage and the low LLL in the MV reflect proper healing characteristics of the TRYTON Stent in combination with the XIENCE-V™ stent. However, proximal MV edge and ostial SB restenoses together with overall clinical outcomes do not fulfill expectations of a dedicated bifurcation stent. © 2012 Wiley Periodicals, Inc.

Objectives: The purpose of this document is to make the output of the International Working Group for Intravascular Optical Coherence Tomography (IWG-IVOCT) Standardization and Validation available to medical and scientific communities, through a peer-reviewed publication, in the interest of improving the diagnosis and treatment of patients with atherosclerosis, including coronary artery disease. Background: Intravascular optical coherence tomography (IVOCT) is a catheter-based modality that acquires images at a resolution of ∼10 μm, enabling visualization of blood vessel wall microstructure in vivo at an unprecedented level of detail. IVOCT devices are now commercially available worldwide, there is an active user base, and the interest in using this technology is growing. Incorporation of IVOCT in research and daily clinical practice can be facilitated by the development of uniform terminology and consensus-based standards on use of the technology, interpretation of the images, and reporting of IVOCT results. Methods: The IWG-IVOCT, comprising more than 260 academic and industry members from Asia, Europe, and the United States, formed in 2008 and convened on the topic of IVOCT standardization through a series of 9 national and international meetings. Results: Knowledge and recommendations from this group on key areas within the IVOCT field were assembled to generate this consensus document, authored by the Writing Committee, composed of academicians who have participated in meetings and/or writing of the text. Conclusions: This document may be broadly used as a standard reference regarding the current state of the IVOCT imaging modality, intended for researchers and clinicians who use IVOCT and analyze IVOCT data.

Background The optimal treatment of bare metal stent restenosis is still not defined. The most employed contemporary option is the implantation of a drug-eluting stent (DES). However, this procedure implies the addition of a second metal layer in the vessel wall, which is linked to delayed healing. Furthermore, there may be a increased risk of malapposition of both struts of the bare metal and the newly implanted drug-eluting stent. These phenomena may give rise to an increased risk of stent thrombosis in this patient population. Recently, drug-eluting balloons (DEB) have been proposed as a new treatment strategy for bare metal stent restenosis. The initial results of this technique look promising. Objectives To compare healing processes after treatment of bare metal stent (BMS) in-stent restenosis (ISR) with balloon dilatation using DEB versus implantation of DES. Study design This is a prospective, multicentre (University Hospitals Leuven and ZOL Hospital Genk, Belgium) randomised clinical trial with clinical, angiographic and OCT follow-up at nine months. Patients with bare metal stent restenosis and an indication for repeat PCI are randomised to treatment with a paclitaxel-eluting balloon (SeQuent Please, B-Braun, Melsungen, Germany) versus a Xience V/ Xience Prime everolimus-eluting stent (Abbott Vascular, Santa Clara, CA, USA). The primary objective of this study is to evaluate the vascular healing response of the vessel wall after balloon angioplasty with a paclitaxel-eluting balloon versus implantation of a drug-eluting stent in patients with in-stent restenosis in a coronary artery. The primary endpoint of the study is stent strut coverage and stent strut apposition at nine months, as assessed with OCT. Conclusions Currently no prospectively collected data on vessel wall healing after treatment of in-stent restenosis, whether with DES or with DEB, are available. Therefore, the SEDUCE trial will yield pivotal insights on this important topic and guide further optimisation of the interventional treatment for this condition.

The implantation of intracoronary stents is currently the standard approach for the treatment of coronary atherosclerotic disease. The widespread adoption of this technology has boosted an intensive research activity in this domain, with continuous improvements in the design of these devices, aiming at reducing problems of restenosis (re-narrowing of the stented segment) and thrombosis (sudden occlusion due to thrombus formation). Recently, a new, light-based intracoronary imaging modality, optical coherence tomography (OCT), was developed and introduced into clinical practice. Due to its very high axial resolution (10-15 μm), it allows for in vivo evaluation of both stent strut apposition and neointima coverage (a marker of healing of the treated segment). As such, it provides valuable information on proper stent deployment, on the behaviour of different stent types in-vivo and on the effect of new types of stents (e.g. drug-eluting stents) on vessel wall healing. However, the major drawback of the current OCT methodology is that analysis of these images requires a tremendous amount of-currently manual-post-processing. In this manuscript, an algorithm is presented that allows for fully automated analysis of stent strut apposition and coverage in coronary arteries. The vessel lumen and stent struts are automatically detected and segmented through analysis of the intensity profiles of the A-lines. From these data, apposition and coverage can then be measured automatically. The algorithm was validated using manual assessments by two experienced operators as a reference. High Pearson's correlation coefficients were found (R = 0.96-0.97) between the automated and manual measurements while Bland-Altman analysis showed no significant bias with good limits of agreement. As such, it was shown that the presented algorithm provides a robust and fast tool to automatically estimate apposition and coverage of stent struts in in-vivo OCT pullbacks. This will be important for the integration of this technology in clinical routine and for the analysis of datasets of larger clinical trials.

Objectives To assess the anatomical and functional impact of final kissing balloon inflation (FKBI) after implantation of a dedicated bifurcation stent system. Background Current evidence suggests clinical benefit of FKBI in patients undergoing bifurcation dilatation using the Tryton side branch stent (Tryton-SBS). We hypothesized that FKBI improves anatomical reconstruction and functional results of bifurcation treated by Tryton-SBS. Methods An unselected group of patients with complex bifurcation coronary lesions undergoing percutaneous coronary intervention (PCI) with Tryton-SBS underwent paired anatomical assessment with two- and three-dimensional quantitative coronary analysis (2D- and 3D-QCA), and optical coherence tomography (OCT), including 3D reconstruction before and after FKBI. Functional assessment by fractional flow reserve (FFR) was performed in the main branch (MB) and side branch (SB) before and after FKBI. Results Paired pre- and post-FKBI data were obtained in 10 patients. By OCT imaging, FKBI increased both the SB ostial area (4.93 ± 2.81 vs. 7.43 ± 2.87 mm2, P

International audience; Optical coherence tomography (OCT) is an optical diagnostic modality that can acquire cross-sectional images of the microscopic structure of the esophagus, including Barrett's esophagus (BE) and associated dysplasia. We developed a swallowable tethered capsule OCT endomicroscopy (TCE) device that acquires high-resolution images of entire gastrointestinal (GI) tract luminal organs. This device has a potential to become a screening method that identifies patients with an abnormal esophagus that should be further referred for upper endoscopy. Currently, the characterization of the OCT-TCE esophageal wall data set is performed manually, which is time-consuming and inefficient. Additionally, since the capsule optics optimally focus light approximately 500 µm outside the capsule wall and the best quality images are obtained when the tissue is in full contact with the capsule, it is crucial to provide feedback for the operator about tissue contact during the imaging procedure. In this study, we developed a fully automated algorithm for the segmentation of in vivo OCT-TCE data sets and characterization of the esophageal wall. The algorithm provides a two-dimensional representation of both the contact map from the data collected in human clinical studies as well as a tissue map depicting areas of BE with or without dysplasia. Results suggest that these techniques can potentially improve the current TCE data acquisition procedure and provide an efficient characterization of the diseased esophageal wall.

Background: Restenosis of coronary stents causes substantial morbidity. Inflammation drives restenosis by activating smooth muscle cells to form obstructive neointima. Recent data suggests that colchicine, an anti-proliferative and anti-inflammatory agent, may reduce clinical stent restenosis. Here we assessed the effects of colchicine on in vivo stent-induced inflammatory protease activity and subsequent restenosis using serial intravascular molecular-structural near-infrared fluorescence (NIRF)-optical coherence tomography (OCT) imaging. Methods: Rabbits implanted with clinical-grade bare-metal stents (3.5x12 mm) received oral colchicine 0.6 mg or placebo daily (N=5 rabbits, 15 stents per group) and were imaged at 2 and 6 weeks with intravascular NIRF-OCT 24 hours following ProSense VM110 (4 mg/kg IV; ex/em 750/780 nm) for molecular NIRF imaging of cathepsin protease inflammatory activity. Neointimal formation was measured every 400 μm by co-registered structural OCT. Stents were analyzed by ex vivo fluorescence microscopy, histology, and cathepsin mRNA expression. Results: In controls, NIRF inflammation at 2 weeks was significantly enhanced at the stent edges (edge 32.6±7.3 vs. mid 20.1±2.6 nM; p Conclusion: We demonstrate that in vivo NIRF inflammatory protease activity predicts stent locations that develop greater restenosis, and that colchicine, an FDA-approved agent, decreases stent-induced inflammation and subsequent restenosis in vivo. lntravascular NIRF-OCT is a novel translatable approach to predict site-specific coronary stent restenosis based on the local inflammatory profile and monitor the effects of anti-restenosis therapeutics.