First in-human evaluation of a novel intravascular ultrasound and optical coherence tomography system for intracoronary imaging.

AIMS: We evaluated the first in-human performance of a novel hybrid imaging catheter that permits simultaneous and co-registered acquisition of intravascular ultrasound (IVUS) and optical coherence tomography (OCT) images. METHODS AND RESULTS: A total of 17 patients undergoing planned percutaneous coronary intervention (PCI) were imaged between August 2018 and August 2019. Eleven patients with both pre- and post-PCI IVUS and OCT images were included in the offline image analysis. IVUS and OCT images were analyzed separately then together with co-registered images for pre-stent findings, and only separately for post-stent findings. A total of 926 frames were analyzed (218 pre-PCI, 708 post-PCI). There was substantial agreement to detect calcific plaque between co-registered IVUS-OCT and standalone IVUS (Kappa 0.72 [0.65-0.79]) and standalone OCT (Kappa 0.75 [0.68-0.81]) while standalone imaging modalities showed lower agreement to detect lipidic and fibrotic plaques compared with co-registered IVUS-OCT. There were more frames with stent underexpansion on IVUS than OCT [72 (28.7%) vs. 58 (23.1%), respectively, p = 0.039]. Detection rates of incomplete stent apposition (present on 20 OCT frames vs. 2 IVUS frames, p < 0.001) and tissue protrusion (40 vs. 27 frames, p < 0.001) were higher on OCT than IVUS. One stent edge dissection was detected in the image analysis and was seen on OCT but not IVUS. All 177 frames with image artifacts contained at least one co-registered imaging modality with interpretable diagnostic content. There were no study device-related adverse events. CONCLUSIONS: Hybrid image acquisition was safe. The availability of both IVUS and OCT changed image interpretation compared to either modality alone, suggesting a complementary role of these two techniques.

Multi-modality intravascular imaging for guiding coronary intervention and assessing coronary atheroma: the Novasight Hybrid IVUS-OCT system.

Intravascular imaging has evolved alongside interventional cardiology as an adjunctive tool for assessing plaque pathology and for guiding and optimizing percutaneous coronary intervention (PCI) in challenging lesions. The two modalities which have dominated the field are intravascular ultrasound (IVUS), which relies on sound waves and optical coherence tomography (OCT), relying on light waves. These approaches however have limited efficacy in assessing plaque morphology and vulnerability that are essential for guiding PCI in complex lesions and identifying patient at risk that will benefit from emerging therapies targeting plaque evolution. These limitations are complementary and, in this context, it has been recognized and demonstrated in multi-modality studies that the concurrent use of IVUS and OCT can help overcome these deficits enabling a more complete and accurate plaque assessment. The Conavi Novasight Hybrid IVUS-OCT catheter is the first commercially available device that is capable of invasive clinical coronary assessment with simultaneously acquired and co-registered IVUS and OCT imaging. It represents a significant evolution in the field and is expected to have broad application in clinical practice and research. In this review article we present the limitations of standalone intravascular imaging techniques, summarize the data supporting the value of multimodality imaging in clinical practice and research, describe the Novasight Hybrid IVUS-OCT system and highlight the potential utility of this technology in coronary intervention and in the study of atherosclerosis.

Advances in IVUS/OCT and Future Clinical Perspective of Novel Hybrid Catheter System in Coronary Imaging.

Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) have been developed and improved as both diagnostic and guidance tools for interventional procedures over the past three decades. IVUS has a resolution of 100 µm with a high tissue penetration and capability of assessing the entire structure of a coronary artery including the external elastic membrane, whereas OCT has a higher resolution of 10-20 µm to assess endoluminal structures with a limited tissue penetration compared to IVUS. Recently, two companies, CONAVI and TERUMO, integrated IVUS and OCT into a single catheter system. With their inherent strength and limitations, the combined IVUS and OCT probes are complementary and work synergistically to enable a comprehensive depiction of coronary artery. In this review, we summarize the performance of the two intracoronary imaging modalities-IVUS and OCT-and discuss the expected potential of the novel hybrid IVUS-OCT catheter system in the clinical field.

30/80 MHz Bidirectional Dual-Frequency IVUS Feasibility Evaluated In Vivo and for Stent Imaging.

Although intravascular ultrasound (IVUS) is an important tool in guiding complex coronary interventions, the resolution of existing commercial IVUS devices is considerably poorer than that of optical coherence tomography. Dual-frequency IVUS (DF IVUS), incorporating a second, higher frequency transducer, has been proposed as a possible method of overcoming this limitation. Although preliminary studies have shown that DF IVUS can produce complementary images, including large-scale morphology and high detail of superficial features, it has not yet been determined that this approach would be feasible in a more clinically relevant environment. The purpose of this study was to demonstrate the first in vivo use of a 30/80 MHz DF IVUS catheter in visualizing coronary vessels in a porcine model. In addition, two commercially available stents were studied in vitro and in vivo. Clear subjective improvement of visualization of superficial structures is demonstrated, and sufficient dynamic range is achieved to image through both the catheter sheath and blood in vivo.

Cardiac Tissue-Mimicking Ballistic Gel Phantom for Ultrasound Imaging in Clinical and Research Applications.

Ballistic gel was investigated as a tissue-mimicking material in an anthropomorphic cardiac phantom for ultrasound imaging. The gel was tested for its acoustic properties and its compatibility with conventional plastics molding techniques. Speed of sound and attenuation were evaluated in the range 2-12 MHz. The speed of sound was 1537 ± 39 m/s, close to typical values for cardiac tissue (∼1576 m/s). The attenuation coefficient was 1.07 dB/cm·MHz, within the range of values previously reported for cardiac tissue (0.81-1.81 dB/cm·MHz). A cardiac model based on human anatomy was developed using established image segmentation processes and conventional plastic molding techniques. Key anatomic features were observed, captured and identified in the model using an intracardiac ultrasound imaging system. These favorable results along with the material's durability and processes that allow for repetitive production of detailed whole-heart models at low cost are promising. There are numerous applications for geometrically complex phantoms in research, training, device development and clinical use.

Essential requirements for establishing and operating data trusts: practical guidance co-developed by representatives from fifteen canadian organizations and initiatives.

INTRODUCTION: Increasingly, the label "data trust" is being applied to repeatable mechanisms or approaches to sharing data in a timely, fair, safe, and equitable way. However, there is an absence of practical guidance regarding how to establish and operate a data trust. AIM AND APPROACH: In December 2019, the Canadian Institute for Health Information and the Vector Institute for Artificial Intelligence convened a working meeting of 19 people representing 15 Canadian organizations/initiatives involved in data sharing, most of which focus on public sector health data. The objective was to identify essential requirements for the establishment and operation of data trusts in the Canadian context. Preliminary requirements were discussed during the meeting and then refined as authors contributed to this manuscript. RESULTS: Twelve minimum specification requirements ("min specs") for data trusts were identified. The foundational min spec is that data trusts must meet all legal requirements, including legal authority to collect, hold or share data. In addition, there was agreement that data trusts must have (i) an accountable governing body to ensure that the data trust achieves its stated purpose and is transparent, (ii) comprehensive data management including clear processes and qualified individuals responsible for the collection, storage, access, disclosure and use of data, (iii) training and accountability requirements for all data users and (iv) ongoing public and stakeholder engagement. CONCLUSIONS: Practical guidance for the establishment and operation of data trusts was articulated in the form of 12 min specs requirements. The 12 min specs are a starting point. Future work to refine and strengthen them with members of the public, companies, and additional research data stakeholders from within and outside of Canada, is recommended.

Polycythemia Vera Presenting as Cardiac Arrest: Novel Management Strategies.

Acute coronary syndromes (ACS) usually occur in patients with multiple cardiac risk factors. In young adults, drug use and hypercoagulable states are common causes for ACS presentations. We report a case of a man in his early 30s who was diagnosed with polycythemia vera (PV) and had a cardiac arrest due to an anterolateral ST elevation myocardial infarction. We discuss his unique management and review the evidence on the management of arterial thromboembolism in PV patients.

Development of a 3 French Dual-Frequency Intravascular Ultrasound Catheter.

Coronary plaque morphology, including plaque size and fibrous cap thickness, is thought to contribute to the risk of plaque rupture and future cardiac events. Dual-frequency intravascular ultrasound has been proposed as a possible technique to visualize both large-scale features and superficial detail of coronary plaque; however, it has not been found to be feasible within the constraints of a clinically functional intravascular ultrasound catheter. In this study, we describe the design and fabrication of a dual-frequency catheter using a bidirectional transducer stack with center frequencies of approximately 30 and 80 MHz. We describe how the high-frequency transducer achieves significantly improved axial and lateral resolution (16 and 120 µm, respectively, vs. 50 and 220 µm) at the expense of penetration depth. Finally, imaging of ex vivo human coronary artery segments reveals that the catheter can provide complementary images of the deeper arterial wall and superficial plaque features.

Hybrid intravascular imaging: recent advances, technical considerations, and current applications in the study of plaque pathophysiology.

Cumulative evidence from histology-based studies demonstrate that the currently available intravascular imaging techniques have fundamental limitations that do not allow complete and detailed evaluation of plaque morphology and pathobiology, limiting the ability to accurately identify high-risk plaques. To overcome these drawbacks, new efforts are developing for data fusion methodologies and the design of hybrid, dual-probe catheters to enable accurate assessment of plaque characteristics, and reliable identification of high-risk lesions. Today several dual-probe catheters have been introduced including combined near infrared spectroscopy-intravascular ultrasound (NIRS-IVUS), that is already commercially available, IVUS-optical coherence tomography (OCT), the OCT-NIRS, the OCT-near infrared fluorescence (NIRF) molecular imaging, IVUS-NIRF, IVUS intravascular photoacoustic imaging and combined fluorescence lifetime-IVUS imaging. These multimodal approaches appear able to overcome limitations of standalone imaging and provide comprehensive visualization of plaque composition and plaque biology. The aim of this review article is to summarize the advances in hybrid intravascular imaging, discuss the technical challenges that should be addressed in order to have a use in the clinical arena, and present the evidence from their first applications aiming to highlight their potential value in the study of atherosclerosis.

Hybrid intravascular ultrasound and optical coherence tomography catheter for imaging of coronary atherosclerosis.

OBJECTIVE: To demonstrate the feasibility of imaging human coronary atherosclerosis using a novel hybrid intravascular ultrasound (IVUS) and optical coherence tomography (OCT) imaging catheter. BACKGROUND: IVUS and OCT have synergistic advantages and recent studies involving both modalities suggest the use of a hybrid imaging catheter may offer improved guidance of coronary interventions and plaque characterization. METHODS: A 1.3 m custom hybrid IVUS-OCT imaging probe was built within a 4F catheter using a 42 MHz ultrasound transducer and an OCT imaging fiber. Coplanar images were simultaneously acquired ex vivo by both modalities in 31 arterial segments from 11 cadaveric human coronaries. IVUS and OCT images were acquired at 250 µm intervals, of which 13 of the arterial segments were selected as representative of a diverse set of pathological findings. The selected segments were then imaged with either digital X-ray or micro-CT, processed for histological analysis and compared with the corresponding IVUS and OCT images. RESULTS: Images of human coronary atherosclerosis using the hybrid IVUS-OCT catheter demonstrated a range of vascular pathologies that were confirmed on histology. The anticipated synergistic advantages of each modality were qualitatively apparent, including the deeper tissue penetration of IVUS and the superior contrast, resolution and near-field image quality of OCT. CONCLUSIONS: Preliminary ex vivo images using a hybrid IVUS-OCT catheter demonstrated feasibility in using the device for intracoronary imaging of atherosclerosis. Future studies will include in vivo imaging and larger samples sizes to enable quantitative comparisons of tissue characterization and feature identification using hybrid imaging catheters versus standalone IVUS and OCT imaging techniques. © 2012 Wiley Periodicals, Inc.

Intraoperative handheld optical coherence tomography forward-viewing probe: physical performance and preliminary animal imaging.

A prototype intraoperative hand-held optical coherence tomography (OCT) imaging probe was developed to provide micron resolution cross-sectional images of subsurface tissue during open surgery. This new ergonomic probe was designed based on electrostatically driven optical fibers, and packaged into a catheter probe in the form factor of clinically accepted Bayonet shaped neurosurgical probes. Optical properties of the probe were measured to have a ~20 µm spot size, 5 mm working distance and 4 mm field of view. Feasibility of this probe for structural and Doppler shift imaging was tested on porcine femoral blood vessel imaging.

Intravascular ultrasound results from the NEVO ResElution-I trial: a randomized, blinded comparison of sirolimus-eluting NEVO stents with paclitaxel-eluting TAXUS Liberté stents in de novo native coronary artery lesions.

BACKGROUND: The NEVO sirolimus-eluting stent (NEVO SES) is a novel cobalt-chromium stent combining sirolimus release from reservoirs with bioabsorbable polymer to reduce spatial and temporal polymer exposure. The aim of this study was to assess the arterial response to the NEVO SES in a randomized, blinded comparison versus the surface-coated TAXUS Liberte paclitaxel-eluting stent (TAXUS Liberté PES) in human native coronary lesions using intravascular ultrasound (IVUS). METHODS AND RESULTS: The NEVO ResElution-I IVUS substudy enrolled 100 patients (1:1 randomization). In addition to standard IVUS variables, uniformity of neointimal distribution within stents was evaluated in 3 dimensions by computing mean neointimal thickness within 12 equally spaced radial sectors on every 1-mm cross section along the stented segment. The NEVO SES showed significantly less neointimal proliferation (neointimal obstruction: 5.5±11.0% versus 11.5±9.7%, P=0.02), resulting in less late lumen area loss and smaller maximum cross-sectional narrowing at 6 months. The absolute variability of neointima distribution, assessed by the standard deviation of neointimal thickness within each stent, was significantly reduced with the NEVO SES compared with the TAXUS Liberté PES(0.04±0.04 mm versus 0.10±0.07 mm, P<0.0001). TAXUS Liberté PES showed significantly greater positive vessel remodeling than the NEVO SES (Δvessel volume index: 1.30±1.36 mm(3)/mm versus 0.36±0.63 mm(3)/mm, respectively, P=0.003). CONCLUSIONS: The NEVO SES with focal release of sirolimus from reservoirs achieved significantly greater and more consistent suppression of neointimal hyperplasia than the surface-coated TAXUS Liberté PES. This was associated with less positive remodeling and no increased morphological or morphometric abnormalities surrounding the stent or at the stent margins. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00714883.

Intravascular ultrasound results from the NEVO ResElution-I trial: a randomized, blinded comparison of sirolimus-eluting NEVO stentswith paclitaxel-eluting TAXUS Liberté stents in de novo native coronaryartery lesions

Background—The NEVO sirolimus-eluting stent (NEVO SES) is a novel cobalt-chromium stent combining sirolimusrelease from reservoirs with bioabsorbable polymer to reduce spatial and temporal polymer exposure. The aim of thisstudy was to assess the arterial response to the NEVO SES in a randomized, blinded comparison versus thesurface-coated TAXUS Liberte paclitaxel-eluting stent (TAXUS Liberte´ PES) in human native coronary lesions usingintravascular ultrasound (IVUS).Methods and Results—The NEVO ResElution-I IVUS substudy enrolled 100 patients (1:1 randomization). In addition tostandard IVUS variables, uniformity of neointimal distribution within stents was evaluated in 3 dimensions bycomputing mean neointimal thickness within 12 equally spaced radial sectors on every 1-mm cross section along thestented segment. The NEVO SES showed significantly less neointimal proliferation (neointimal obstruction: 5.5 11.0%versus 11.5 9.7%, P 0.02), resulting in less late lumen area loss and smaller maximum cross-sectional narrowing at6 months. The absolute variability of neointima distribution, assessed by the standard deviation of neointimal thicknesswithin each stent, was significantly reduced with the NEVO SES compared with the TAXUS Liberte´PES(0.04 0.04 mm versus 0.10 0.07 mm, P 0.0001). TAXUS Liberte´ PES showed significantly greater positivevessel remodeling than the NEVO SES ( vessel volume index: 1.30 1.36 mm3/mm versus 0.36 0.63 mm3/mm,respectively, P 0.003).Conclusions—The NEVO SES with focal release of sirolimus from reservoirs achieved significantly greater and moreconsistent suppression of neointimal hyperplasia than the surface-coated TAXUS Liberte´ PES. This was associated withless positive remodeling and no increased morphological or morphometric abnormalities surrounding the stent or at thestent margins.

Doppler optical coherence tomography for interventional cardiovascular guidance: in vivo feasibility and forward-viewing probe flow phantom demonstration.

We demonstrate the potential of a forward-looking Doppler optical coherence tomography (OCT) probe for color flow imaging in several commonly seen narrowed artery morphologies. As a proof of concept, we present imaging results of a surgically exposed thrombotic occlusion model that was imaged superficially to demonstrate that Doppler OCT can identify flow within the recanalization channels of a blocked artery. We present Doppler OCT images in which the flow is nearly antiparallel to the imaging direction. These images are acquired using a flexible 2.2-mm-diam catheter that used electrostatic actuation to scan up to 30 deg ahead of the distal end. Doppler OCT images of physiologically relevant flow phantoms consisting of small channels and tapered entrance geometries are demonstrated.

Right coronary wall CMR in the older asymptomatic advance cohort: positive remodeling and associations with type 2 diabetes and coronary calcium.

BACKGROUND: Coronary wall cardiovascular magnetic resonance (CMR) is a promising noninvasive approach to assess subclinical atherosclerosis, but data are limited in subjects over 60 years old, who are at increased risk. The purpose of the study was to evaluate coronary wall CMR in an asymptomatic older cohort. RESULTS: Cross-sectional images of the proximal right coronary artery (RCA) were acquired using spiral black-blood coronary CMR (0.7 mm resolution) in 223 older, community-based patients without a history of cardiovascular disease (age 60-72 years old, 38% female). Coronary measurements (total vessel area, lumen area, wall area, and wall thickness) had small intra- and inter-observer variabilities (r = 0.93~0.99, all p < 0.0001), though one-third of these older subjects had suboptimal image quality. Increased coronary wall thickness correlated with increased coronary vessel area (p < 0.0001), consistent with positive remodeling. On multivariate analysis, type 2 diabetes was the only risk factor associated with increased coronary wall area and thickness (p = 0.03 and p = 0.007, respectively). Coronary wall CMR measures were also associated with coronary calcification (p = 0.01-0.03). CONCLUSIONS: Right coronary wall CMR in asymptomatic older subjects showed increased coronary atherosclerosis in subjects with type 2 diabetes as well as coronary calcification. Coronary wall CMR may contribute to the noninvasive assessment of subclinical coronary atherosclerosis in older, at-risk patient groups.

Electrostatic forward-viewing scanning probe for Doppler optical coherence tomography using a dissipative polymer catheter.

A novel flexible scanning optical probe is constructed with a finely etched optical fiber strung through a platinum coil in the lumen of a dissipative polymer. The packaged probe is 2.2 mm in diameter with a rigid length of 6mm when using a ball lens or 12 mm when scanning the fiber proximal to a gradient-index (GRIN) lens. Driven by constant high voltage (1-3 kV) at low current (< 5 microA), the probe oscillates to provide wide forward-viewing angle (13 degrees and 33 degrees with ball and GRIN lens designs, respectively) and high-frame-rate (10-140 fps) operation. Motion of the probe tip is observed with a high-speed camera and compared with theory. Optical coherence tomography (OCT) imaging with the probe is demonstrated with a wavelength-swept source laser. Images of an IR card as well as in vivo Doppler OCT images of a tadpole heart are presented. This optomechanical design offers a simple, inexpensive method to obtain a high-frame-rate forward-viewing scanning probe.

Innovations in imaging for chronic total occlusions: a glimpse into the future of angiography's blind-spot.

Chronic total occlusions (CTOs) are a subset of lesions that present a considerable burden to cardiovascular patients. There exists a strong clinical desire to improve non-surgical options for CTO revascularization. While several techniques, devices, and guide wires have been developed and refined for use in CTOs, the inability of angiography to adequately visualize occluded arterial segments makes interventions in this setting technically challenging. This review describes the current status of several invasive and non-invasive imaging techniques that may facilitate improved image guidance during CTO revascularization, with the goals of improving procedure safety and efficacy while reducing the time required to complete these interventions. Cardiac imaging also has important potential roles in selecting patients most likely to benefit from revascularization as well as pre-procedural planning, post-procedural assessment of revascularized segments and long-term outcomes studies. Modalities discussed include non-invasive techniques, such as CT(computed tomography) angiography and cardiac magnetic resonance imaging (MRI), as well as invasive techniques, such as intravascular ultrasound, optical coherence tomography, intravascular MRI, and conventional angiography. While some of these techniques have some evidence to support their use at present, others are at earlier stages of development. Strategies that combine imaging techniques with the use of interventional therapies may provide significant opportunities to improve results in CTO interventions and represent an active area of investigation.