Optical coherence tomography

Summary

Optical coherence tomography (OCT) is a light-based imaging modality which shows tremendous potential in the setting of coronary imaging. Compared to intravascular ultrasound (IVUS), OCT has a ten-fold higher image resolution. OCT has the ability to characterise the structure and extent of coronary artery disease in unprecedented detail as the various components of atherosclerotic plaques have different optical properties. Typically, calcified, fibrous and lipid-rich plaque components can be distinguished, as well as the presence of dense macrophage infiltration, neovascularisation and mural or intraluminal thrombi.

These diagnostic capabilities are being applied to study patients with ACS and STEMI in order to improve our understanding of the pathophysiology and progression of atherosclerosis. Likewise, OCT allows the detailed analysis of coronary stents, their interaction with the vessel wall and their long-term outcome. In daily clinical practices, OCT may be efficient in complex interventions. Preliminary data indicates that OCT can change the operator’s intention-to-treat and modify the overall revascularisation strategy, potentially avoiding unnecessary interventional procedures. Recent studies shed light on the role of OCT as an instrumental tool to study plaque composition, particularly the extension of calcific components and select the most appropriate interventional device. This burden of information can ameliorate stent deployment and improve clinical outcome after coronary interventions. As such, OCT may emerge, along with its undisputed position in research, as the tool of choice in all clinical scenarios where angiography is limited by its nature as a two-dimensional luminogram.

Introduction

Optical coherence tomography (OCT) is a light-based imaging modality which shows tremendous potential in the coronary circulation. Compared to intravascular ultrasound (IVUS), OCT has a ten-fold higher image resolution given the use of near infrared light rather than sound in the megahertz range. This advantage has seen OCT successfully applied to the assessment of atherosclerotic plaque, stent apposition and tissue coverage, introducing a new era in intravascular coronary imaging.

The origins of OCT date back to 1990. David Huang was in his fourth year of an MD-PhD programme at Massachusetts Institute of Technology (MIT). He had been studying optical coherence domain reflectometry (OCDR) to perform ranging measurements in the eye. The OCDR project was an offshoot of femtosecond ranging projects which had been ongoing in Professor James Fujimoto’s laboratory. However, the retinal OCDR scans were very hard to interpret. The thought occurred to Dr Huang that by adding transverse scanning to OCDR graphs one could create an image which would be much easier for a human to interpret than a set of OCDR waveforms. All that was required to add a translation stage and a software package to convert a data matrix into an image. The central problem in making tomographic images using light was to develop a technique which would permit reflections from various depths to be measured and recorded in a fashion analogous to ultrasonic imaging. In the case of sound, electronic circuits are fast enough to separate the echoes from structures which are within the resolution cell of the ultrasonic transducer. In the case of light, an interferometer has to be employed to overcome measurement difficulties caused by the speed of light which is much faster than the speed of sound. By using an interferometer, for the first time it was possible to record reflections from various depths in a biological tissue.

Since 1990, the OCT technology has generated over 5,000 articles in academic journals. The first manuscript from MIT, published in 1991, describes the basic concept of an OCT imaging system and discusses its possible applications in both retinal and arterial imaging [11. Huang D, Swanson EA, Lin CP, Schuman JS, Stinson WG, Chang W, Hee MR, Flotte T, Gregory K, Puliafito CA, Fujimoto JG. Optical coherence tomography. Science (80- ). 1991;254:1178–81. ]. In 1996, a second manuscript was published, which dealt specifically with the possibility of imaging coronary arteries with an OCT device [22. Brezinski ME, Tearney GJ, Bouma BE, Boppart SA, Hee MR, Swanson EA, Southern JF, Fujimoto JG. Imaging of coronary artery microstructure (in vitro) with optical coherence tomography. Am J Cardiol. 1996;77:92–3. ]. It became clear early on that OCT could contribute to the diagnosis of ocular diseases. It was believed that the new technology had the potential to serve as an in vivo microscope which could obtain non-excisional biopsy information from locations at which a conventional biopsy was either impossible or impractical to perform. A second research thrust from the MIT group was to push the resolution of the technology to increasingly higher levels using wider bandwidth optical sources. With sufficiently wide bandwidth sources, one may be able to resolve sub-cellular structures and measure the ratio of the nuclear volume to the total cell volume in a manner similar to the way a pathologist does when diagnosing cancer. In the days since the initial discussions in Professor Fujimoto’s office, several members of the MITOCT team have gone on to start academic OCT research programmes throughout the United States.

Compared to an OCT microscope, used in ophthalmology and in most experimental settings, the application of OCT within the human vascular system, particularly within coronary arteries, represents a specific challenge, as a number of principal problems need to be overcome [33. Regar E van LASP eds., editor. Optical Coherence Tomography in Cardiovascular Research. London: Informa Healthcare. 2007; 2007. ]. Therefore, the intracoronary application of OCT has slowly but steadily increased over the last decade, with a commercially available system for clinical use (St. Jude/LightLab Imaging Inc., Westford, MA, USA) being approved in Europe, Japan and the USA. Today, the technology development from “time domain OCT” to “Fourier domain OCT” has the potential to change dramatically the research landscape allowing for a widespread clinical intracoronary application in research and patient care. The chapter will discuss the technical principles of intracoronary OCT, summarise the preclinical and clinical research, discuss potential clinical applications and explain the practical performance in the catheterisation laboratory. Differences in time domain versus Fourier domain OCT will be pointed out when relevant.

Physical principles

The principle of OCT is analogous to pulse-echo ultrasound imaging, except that light is used rather than sound to create the image. Whereas ultrasound produces images from backscattered sound “echoes”, OCT uses infrared light waves which reflect off the internal microstructure within the biological tissues. The use of near infrared light allows a ten-fold higher image resolution ( Figure 1 ); however, this is at the expense of a reduced penetration depth and the need to create a blood-free environment for imaging. In coronary arteries, blood (namely red blood cells) represents that non-transparent tissue, causing multiple scattering and substantial signal attenuation. As a consequence, blood must be displaced during OCT imaging.

OCT utilises a near infrared light source (approximately 1,300 nm wavelength) in combination with advanced fiber optics to create a dataset of the coronary artery. Both the bandwidth of the infrared light used and the wave velocity are orders of magnitude higher than in medical ultrasound. The resulting resolution depends primarily on the ratio of these parameters and is one order of magnitude larger than that of IVUS; the axial resolution of OCT is about 15 μm. The lateral resolution is mainly determined by the imaging optics in the catheter and is approximately 25 μm. The imaging depth of approximately 1.0-1.5 mm within the coronary artery wall is limited by the attenuation of light in the tissue. Analogous to ultrasound imaging, the echo time delay of the emitted light is used to generate spatial image information: the intensity of the received (reflected or scattered) light is translated into a (false) color scale. As the speed of light is much faster than that of sound, an interferometer is required to measure the backscattered light [44. Michelson A, Morley E. On the relative motion of the earth and the luminiferous aether. Philos. Mag. 1887;S5:449-63. ]. The interferometer splits the light source into two “arms” – a reference arm and a sample arm, which is directed into the tissue. The light from both arms is recombined at a detector, which registers the so-called interferogram, the sum of reference and sample arm fields. Because of the large source bandwidth, the interferogram is non-zero only if the sample and reference arms are of equal length, within a small window equal to the coherence length of the light source [55. Schmitt JM, Knuttel A, Yadlowsky M, Eckhaus MA. Optical-coherence tomography of a dense tissue: Statistics of attenuation and backscattering. Phys Med Biol. 1994;39:1705–20. , 66. Schmitt JM. Optical Coherence Tomography (OCT): a review. IEEE J Sel Top Quantum Electron. 1999;5:1205–15. ].

TIME DOMAIN OCT

In time domain OCT, the length of the reference arm is scanned over a distance of, typically, a few millimetres by moving a mirror. By scanning the beam along the tissue, in a rotary fashion for intravascular imaging, an image is built up out of neighbouring lines (St. Jude/LightLab Imaging Inc., Westford, MA, USA).

Time domain OCT has been replaced by the new generation of OCT systems, the Fourier domain OCT, in the 2008 due to slow data acquisition and the need to clear the artery from blood during image acquisition [77. Gonzalo N, Tearney GJ, Serruys PW, van Soest G, Okamura T, García-García HM, Jan van Geuns R, van der Ent M, Ligthart J, Boum BE, Regar E. Second-Generation Optical Coherence Tomography in Clinical Practice. High-Speed Data Acquisition is Highly Reproducible in Patients Undergoing Percutaneous Coronary Intervention. Rev Española Cardiol (English Ed. 2010;63:893–903. ].

FOURIER DOMAIN OCT

Fourier domain OCT operate in the frequency (rather than time) domain, also called Fourier domain ( Figure 2 ). The interferogram is detected as a function of wavelength, either by using a broadband source as in the time domain systems, and spectrally resolved detection, or alternatively by incorporating a novel wavelength-swept laser source [88. Je HG, Song H, Jung SH, Choo SJ, Song JM, Kang DH, Yun SC, Chung CH, Song JK, Lee JW. Impact of the Maze operation on the progression of mild functional tricuspid regurgitation. J Thorac Cardiovasc Surg. 2008;136:1187–92. , 99. Chinn SR, Swanson EA, Fujimoto JG. Optical coherence tomography using a frequency-tunable optical source. Opt Lett. 1997;22:340. ]. This latter technique is also called “swept source OCT”, or optical frequency domain imaging (OFDI), and capitalises most effectively on the higher sensitivity and lower signal-to-noise ratio offered by Fourier domain detection. This development has led to faster image acquisition speeds, with greater penetration depth, without loss of vital detail or resolution, and represents a great advancement on current conventional OCT systems. From the signal received in one wave length sweep, the depth profile can be constructed by the Fourier transform operation which is performed electronically in the data processing unit. All other components of a Fourier domain system (the interferometer, the catheter, including the imaging optics, display) are comparable to those in a time domain OCT system.

The scan speed, or line rate, in a time domain OCT system is limited by the achievable mechanical scan speed of the reference arm mirror, and by the sensitivity of the signal detection. The source wave length in Fourier domain OCT can be swept at a much higher rate than the position scan of the reference arm mirror in a time domain OCT system. In addition, Fourier domain OCT has a higher sensitivity than time domain OCT at large line rates and scan depths [1010. Leitgeb R, Hitzenberger C, Fercher A. Performance of fourier domain vs time domain optical coherence tomography. Opt Express. 2003;11:889. , 1111. Choma M, Sarunic M, Yang C, Izatt J. Sensitivity advantage of swept source and Fourier domain optical coherence tomography. Opt Express. 2003;11:2183. , 1212. de Boer JF, Cense B, Park BH, Pierce MC, Tearney GJ, Bouma BE. Improved signal-to-noise ratio in spectral-domain compared with time-domain optical coherence tomography. Opt Lett. 2003;28:2067. ]. These features can be put to good use with larger scan speeds, of the order of 10^5 A-lines per second. In a Fourier domain OCT system, the wave length range of the sweep determines the resolution of the image, while the imaging depth is inversely related to the instantaneous spectral width of the source.

The increased sensitivity of Fourier domain OCT also allows for larger imaging depths. The attenuation of light by the tissue is the same for time domain and for Fourier domain OCT, but the lower noise of the latter makes it possible to discern weaker signals which would be indistinguishable from the background in time domain OCT. The depth range from which useful anatomical information can be extracted is extended by a factor of approximately three [1313. Lim H, Mujat M, Kerbage C, Lee ECW, Chen Y, Chen TC, de Boer JF. High-speed imaging of human retina in vivo with swept-source optical coherence tomography. Opt Express. 2006;14:12902. ]. Clinically, this advantage enables the assessment of coronary microstructures, well beyond the arterial-lumen border.

Fourier domain OCT systems produce images much faster than standard video-rate, so recorded data has to be replayed for inspection by the operator. Currently, OCT systems scan 200-500 angles per revolution (frame), and 5-10 images per mm in a pullback. If these parameters are maintained with high-speed systems, 20 mm/sec (or higher) pullback speeds are possible at the same sampling density as conventional OCT data. The high scan speeds have been employed for real-time volumetric imaging of dynamic phenomena including fast pullbacks for intracoronary imaging with minimal ischaemia, and retinal scans with minimal motion artifacts [1313. Lim H, Mujat M, Kerbage C, Lee ECW, Chen Y, Chen TC, de Boer JF. High-speed imaging of human retina in vivo with swept-source optical coherence tomography. Opt Express. 2006;14:12902. ]. Imaging of dynamic phenomena in time, or rather removing motion artifacts, are the prime applications of high-speed OCT. Three-dimensional rendering of volumes becomes possible if motion during the scan is limited.

Practical application in the catherisation laboratory

OCT IMAGING DEVICES

The equipment for intracoronary OCT generally consists of an OCT imaging catheter, a motorised pullback device and an imaging console, which contains the light source, signal processing units, data storage and display [1414. Regar E, Schaar J., Mont E, Virmani R, Serruys P. Optical coherence tomography. Cardiovasc Radiat Med. 2003;4:198–204. ]. The imaging catheter is part of the sample arm of the interferometer described above. The optical signal is transmitted by a single-mode fiber, which is fitted with an integrated lens microprism assembly to focus the beam and direct it towards the tissue. The focus is approximately 1 mm outside the catheter. In order to scan the vessel lengthwise, the catheter-imaging tip is pulled back while rotating, usually inside a transparent sheath, allowing it to collect a three-dimensional dataset of the coronary artery. Both rotary and pullback motion are driven proximally by a motor outside the patient. We will describe the currently commercially available equipment for Fourier domain OCT and the imaging procedure in detail. As many early studies of intracoronary OCT employed time domain OCT, we also summarise the equipment and imaging procedure for time domain OCT.

IMAGING PROCEDURE FOURIER DOMAIN OCT

Currently, there are two commercially available Fourier domain OCT systems: the Dragon-Fly (St. Jude, Westford, MA, USA) and the Fastview catheter (Terumo, Japan) ( Figure 3). The optical probe is integrated with a 2.7 Fr short monorail catheter that can be advanced in the coronary artery over any conventional 0.014” guidewire, and is compatible with 6 Fr guiding catheters. The usable length is around 140 cm.

The OCT imaging catheter is advanced using monorail technique distally into the coronary artery via a standard angioplasty guidewire (0.014”). Care should be taken to position the guide catheter coaxially and deep into the coronary ostium. Correct guide catheter position can be confirmed by manual injection of a small flush bolus through the guide catheter prior to imaging (if needed). During automated OCT pullback (pullback speed is typically in the range of 20 mm/sec to 40 mm/sec) blood needs to be cleared from the lumen by injection of a flush solution through the guide catheter, applying a non-occlusive technique that was set up for the time domain probe [1515. Prati F, Cera M, Ramazzotti V, Imola F, Giudice R, Albertucci M. Safety and feasibility of a new non-occlusive technique for facilitated intracoronary optical coherence tomography (OCT) acquisition in various clinical and anatomical scenarios. EuroIntervention. 2007;3:365–70. ]. A variety of solutions are being used as flush media, including viscous iso-osmolar contrast media, and mixtures of lactated Ringer’s solution and contrast media or low molecular weight dextrose. Flush injection can be performed manually, with assist systems or by using a power injector. Usually, an iso-osmolar contrast medium at room temperature is used via a power injection at a rate of 3 ml/sec or 4 ml/sec through the guide catheter, depending on the vessel diameter. Flushing should be terminated when the region of interest has been imaged, when the OCT catheter optics enter the guide catheter, or in the case of any complications.

CONCOMITANT MEDICATION

Similar to other diagnostic coronary instrumentation, such as FFR or IVUS, patients should be anticoagulated, typically with heparin, before inserting the guidewire into the coronary artery. The OCT catheter should preferably only be introduced into the coronary artery after the administration of intracoronary nitro-glycerine, to minimise the potential for catheter-induced vasospasm.

PATIENT SELECTION AND ANATOMICAL CONSIDERATIONS

In principle, all epicardial coronary arteries, venous or arterial grafts accessible by a guiding catheter are eligible for OCT imaging.

Considerations regarding anatomy and patient characteristics arise (a) from the fact that OCT imaging requires a blood-free environment, and (b) from the OCT catheter design. As the imaging procedure demands temporary blood removal and flush (e.g., lactated Ringer’s or x-ray contrast medium), it should not be performed in patients with severely impaired left ventricular function or hemodynamically compromised. Further, OCT should be used with caution in patients with a single remaining vessel or those with markedly impaired renal function. Lesions that are ostially or proximally located cannot be adequately imaged using proximal balloon occlusion and thus a non-occlusive technique may be preferred in these circumstances. Large caliber vessels or very tortuous vessels often preclude complete circumferential imaging as a result of a non-central, non-coaxial position of the OCT imaging probe within the vessel.

These anatomical limitations are reduced significantly in Fourier domain OCT, as the pullback speed is much higher and, as a result, the duration of ischaemia and the amount of potentially nephrotoxic flush is much lower. Increased penetration depth and scanning range allow imaging of the complete circumference of large and tortuous vessels. The design of a short monorail catheter enables negotiation even of complex lesions by selecting an appropriate standard guidewire.

OCT - Role for the assessment of atherosclerotic lesions

OCT has the ability to characterise the structure and extent of coronary artery disease in unprecedented detail ( Figure 4 ). OCT images can be interpreted by visual assessment of the signal intensity and geometry [1616. Prati F, Regar E, Mintz GS, Arbustini E, Di Mario C, Jang IK, Akasaka T, Costa M, Guagliumi G, Grube E, Ozaki Y, Pinto F, Serruys PWJ. Expert review document on methodology, terminology, and clinical applications of optical coherence tomography: Physical principles, methodology of image acquisition, and clinical application for assessment of coronary arteries and atherosclerosis. Eur Heart J. 2010;31:401–15. ] as various components of atherosclerotic plaques have different optical properties ( Figure 5 ). Attenuation and backscatter affect the received signal intensity and penetration depth into the tissue. OCT signal intensity is displayed using a false color map. A popular color map is the “sepia” scale, ranging from black (low OCT signal) through to brown, yellow and white (high OCT signal); alternatively, grey scale (low is black, high is white), or inverted grey scale maps are being used ( Figure 6 ). The depth of penetration is greatest for fibrous tissue and least for thrombi, with calcium and lipid tissue having intermediate values [1717. Yabushita H, Bouma BE, Houser SL, Aretz HT, Jang IK, Schlendorf KH, Kauffman CR, Shishkov M, Kang DH, Halpern EF, Tearney GJ. Characterization of human atherosclerosis by optical coherence tomography. Circulation. 2002;106:1640–5. , 1818. Kubo T, Imanishi T, Takarada S, Kuroi A, Ueno S, Yamano T, Tanimoto T, Matsuo Y, Masho T, Kitabata H, Tsuda K, Tomobuchi Y, Akasaka T. Assessment of Culprit Lesion Morphology in Acute Myocardial Infarction. Ability of Optical Coherence Tomography Compared With Intravascular Ultrasound and Coronary Angioscopy. J Am Coll Cardiol. 2007;50:933–9. , 1919. Kume T, Akasaka T, Kawamoto T, Ogasawara Y, Watanabe N, Toyota E, Neishi Y, Sukmawan R, Sadahira Y, Yoshida K. Assessment of Coronary Arterial Thrombus by Optical Coherence Tomography. Am J Cardiol. 2006;97:1713–7. , 2020. Prati F, Zimarino M, Stabile E, Pizzicannella G, Fouad T, Rabozzi R, Filippini A, Pizzicannella J, Cera M, De Caterina R. Does optical coherence tomography identify arterial healing after stenting? An in vivo comparison with histology, in a rabbit carotid model. Heart. 2008;94:217–21. , 2121. Zimarino M, Prati F, Stabile E, Pizzicannella J, Fouad T, Filippini A, Rabozzi R, Trubiani O, Pizzicannella G, De Caterina R. Optical coherence tomography accurately identifies intermediate atherosclerotic lesions-An in vivo evaluation in the rabbit carotid artery. Atherosclerosis. 2007;193:94–101. ]. Correct identification of plaque components by OCT depends on the penetration depth of the incident light beam into the vessel wall.

NORMAL CORONARY MORPHOLOGY AND PLAQUE COMPOSITION

The normal coronary artery wall appears as a three-layer structure by OCT. The media is seen as a dark band delineated by the internal elastic lamina and external elastic lamina. As the mean media thickness is 200 μm, it can easily be visualised by OCT [2222. Kawasaki M, Bouma BE, Bressner J, Houser SL, Nadkarni SK, MacNeill BD, Jang IK, Fujiwara H, Tearney GJ. Diagnostic Accuracy of Optical Coherence Tomography and Integrated Backscatter Intravascular Ultrasound Images for Tissue Characterization of Human Coronary Plaques. J Am Coll Cardiol. 2006;48:81–8. , 2323. Kume T, Akasaka T, Kawamoto T, Watanabe N, Toyota E, Neishi Y, Sukmawan R, Sadahira Y, Yoshida K. Assessment of coronary intima - Media thickness by optical coherence tomography: Comparison with intravascular ultrasound. Circ J. 2005;69:903–7. ]. In the presence of vessel remodeling (where there is an expansion of the vessel wall at the sites of plaque accumulation) the media typically becomes thinner. Unfortunately, because of its limited tissue penetration (1-1.5 mm) OCT is not suited to study vessel remodeling, as often the presence of atherosclerotic vessel wall thickening obscures visualisation of the media.

The normal intima consists of a thin sub-endothelial collagen layer covered towards the lumen by a single layer of endothelial cells. This normal anatomical structure is beyond the resolution of OCT. However, OCT can detect early stages of intimal thickening, depicted as a signal-rich, homogeneous, thin rim of tissue. Thus, OCT can confirm the absence of significant atherosclerosis or indicate the degree of subclinical atherosclerotic lesion formation. Serial measurements can be performed to monitor the structural changes that occur in the vessel wall over time. This information could be clinically relevant to study the natural history of coronary atherosclerosis and the effect of different therapies on the regression/progression of the incipient plaque [2121. Zimarino M, Prati F, Stabile E, Pizzicannella J, Fouad T, Filippini A, Rabozzi R, Trubiani O, Pizzicannella G, De Caterina R. Optical coherence tomography accurately identifies intermediate atherosclerotic lesions-An in vivo evaluation in the rabbit carotid artery. Atherosclerosis. 2007;193:94–101. , 2222. Kawasaki M, Bouma BE, Bressner J, Houser SL, Nadkarni SK, MacNeill BD, Jang IK, Fujiwara H, Tearney GJ. Diagnostic Accuracy of Optical Coherence Tomography and Integrated Backscatter Intravascular Ultrasound Images for Tissue Characterization of Human Coronary Plaques. J Am Coll Cardiol. 2006;48:81–8. , 2323. Kume T, Akasaka T, Kawamoto T, Watanabe N, Toyota E, Neishi Y, Sukmawan R, Sadahira Y, Yoshida K. Assessment of coronary intima - Media thickness by optical coherence tomography: Comparison with intravascular ultrasound. Circ J. 2005;69:903–7. ]. In this regard the exact selection of the same frame in serial study is key. However, some inconsistency in selecting the frame with the thinnest fibrous cap was found [2424. Kim SJ, Lee H, Kato K, Yonetsu T, Xing L, Zhang S, Jang IK. Reproducibility of in vivo measurements for fibrous cap thickness and lipid Arc by OCT. JACC Cardiovasc Imaging. 2012;5:1072–4. ] ( Figure 1 A ). The use of dedicated software to identify with accuracy the same cross-section in serial studies [2525. Gabriele A, Marco V, Gatto L, Paoletti G, Di Vito L, Castriota F, Romagnoli E, Ricciardi A, Prati F. Reproducibility of the Carpet View system: a novel technical solution for display and off line analysis of OCT images. Int J Cardiovasc Imaging. 2014;30:1225–33. ] or the application of a volumetric approach are possible solutions to this problem [2626. Wang Z, Chamie D, Bezerra HG, Yamamoto H, Kanovsky J, Wilson DL, Costa MA, Rollins AM. Volumetric quantification of fibrous caps using intravascular optical coherence tomography. Biomed Opt Express. 2012;3:1413. ].

QUALITATIVE DESCRIPTION OF ATHEROSCLEROSIS

Fibrous plaques

These are typically rich in collagen or muscle cells and have a homogeneous OCT signal with high backscatter and low attenuation, resulting in a bright, signal-intense appearance.

Calcifications

These occur within plaques and are identified by the presence of well-delineated, low backscattering, signal-poor heterogeneous regions. In general, superficial calcium deposits can be studied and measured by OCT unless their thickness is greater than 1.0-1.5 mm whereupon the penetration limit of OCT is reached. In these circumstances, the diagnosis of focal calcification can be challenging. Signal-poor calcifications might be confused with signal-poor lipid-rich tissue [2525. Gabriele A, Marco V, Gatto L, Paoletti G, Di Vito L, Castriota F, Romagnoli E, Ricciardi A, Prati F. Reproducibility of the Carpet View system: a novel technical solution for display and off line analysis of OCT images. Int J Cardiovasc Imaging. 2014;30:1225–33. ]. Reviewing consecutive OCT images instead of single frames, still images might increase diagnostic accuracy.

Necrotic cores or lipid-rich tissues

These are less well delineated than calcifications, appearing as diffusely-bordered, signal-poor regions with overlying signal-rich bands, corresponding to fibrous caps. Some authors have reported a higher sensitivity and specificity of OCT for lipid-rich plaque detection when comparing OCT, IVUS and IVUS- derived techniques for plaque composition analysis [2222. Kawasaki M, Bouma BE, Bressner J, Houser SL, Nadkarni SK, MacNeill BD, Jang IK, Fujiwara H, Tearney GJ. Diagnostic Accuracy of Optical Coherence Tomography and Integrated Backscatter Intravascular Ultrasound Images for Tissue Characterization of Human Coronary Plaques. J Am Coll Cardiol. 2006;48:81–8. , 2727. Jang IK, Tearney GJ, MacNeill B, Takano M, Moselewski F, Iftima N, Shishkov M, Houser S, Aretz HT, Halpern EF, Bouma BE. In vivo characterization of coronary atherosclerotic plaque by use of optical coherence tomography. Circulation. 2005;111:1551–5. ]. In the majority of cases, the thickness of the lipid-rich plaque component cannot be measured by OCT because the penetration depth is insufficient. However, the thickness of the fibrous cap covering superficial lipid towards the lumen can be measured accurately. Pathological studies of plaques leading to cardiac death and acute myocardial infarction have established 65 μm as the threshold of fibrous cap thickness which best identifies thin, vulnerable caps with a propensity to rupture and to cause coronary thrombosis. The thickness of the fibrous cap is not homogeneous throughout the plaque and its 3D longitudinal distribution should not be ignored. The size of a lipid necrotic-rich plaque can be graded semi-quantitatively according to the number of involved quadrants on the cross-sectional OCT images, and an estimate of the lipid content of a lesion can be derived from the number of quadrants occupied by necrotic lipid pool. By applying such semi-quantitative grading, necrotic lipid pools can be classified as absent or subtending 1, 2, 3 or 4 quadrants. Some studies have used an additional parameter that the necrotic core should subtend an arc which is greater than 90°or comprise more than one quadrant [2727. Jang IK, Tearney GJ, MacNeill B, Takano M, Moselewski F, Iftima N, Shishkov M, Houser S, Aretz HT, Halpern EF, Bouma BE. In vivo characterization of coronary atherosclerotic plaque by use of optical coherence tomography. Circulation. 2005;111:1551–5. , 2828. Barlis P, Serruys PW, Gonzalo N, van der Giessen WJ, de Jaegere PJ, Regar E. Assessment of Culprit and Remote Coronary Narrowings Using Optical Coherence Tomography With Long-Term Outcomes. Am J Cardiol. 2008;102:391–5. ].

Thrombi

These are identified as masses protruding into the vessel lumen, frequently discontinuous from the surface of the vessel wall. Red thrombi consist mainly of red blood cells. OCT images are characterised as high-backscattering protrusions with signal-free shadowing. White thrombi consist mainly of platelets and white blood cells and are characterised by signal-rich, low-backscattering billowing projections protruding into the lumen [1919. Kume T, Akasaka T, Kawamoto T, Ogasawara Y, Watanabe N, Toyota E, Neishi Y, Sukmawan R, Sadahira Y, Yoshida K. Assessment of Coronary Arterial Thrombus by Optical Coherence Tomography. Am J Cardiol. 2006;97:1713–7. ]. In reality, pure white or red thrombi are rarely found. The aspect of thrombus at OCT changes over time. The irregular inner border of the thrombus in the acute phase evolves to a homogeneous and smooth profile in the following weeks [2929. Souteyrand G, Arbustini E, Motreff P, Gatto L, Di Vito L, Marco V, Amabile N, Chisari A, Kodama T, Romagnoli E, Tavazzi L, Crea F, Narula J, Prati F. Serial optical coherence tomography imaging of ACS-causing culprit plaques. EuroIntervention. 2015;11:319–24. ]. The identification of fresh thrombus is key for diagnosing acute coronary syndromes. Thrombi are frequently found within culprit lesions of patients with acute coronary syndromes [1616. Prati F, Regar E, Mintz GS, Arbustini E, Di Mario C, Jang IK, Akasaka T, Costa M, Guagliumi G, Grube E, Ozaki Y, Pinto F, Serruys PWJ. Expert review document on methodology, terminology, and clinical applications of optical coherence tomography: Physical principles, methodology of image acquisition, and clinical application for assessment of coronary arteries and atherosclerosis. Eur Heart J. 2010;31:401–15. , 1818. Kubo T, Imanishi T, Takarada S, Kuroi A, Ueno S, Yamano T, Tanimoto T, Matsuo Y, Masho T, Kitabata H, Tsuda K, Tomobuchi Y, Akasaka T. Assessment of Culprit Lesion Morphology in Acute Myocardial Infarction. Ability of Optical Coherence Tomography Compared With Intravascular Ultrasound and Coronary Angioscopy. J Am Coll Cardiol. 2007;50:933–9. ]. A fresh or large thrombus may hamper the visualisation of plaque features such as ulceration beneath the thrombus itself. To solve this problem, when thrombus is present, OCT cross-sections acquired within the coronary segment with thrombus should be searched one by one for sites where vessel wall and plaque morphology can be seen.

Vasa vasorum and neovascularisation

(Neo) vessels within the intima appear as signal-poor voids which are sharply delineated and usually contiguous and seen on multiple frames [1616. Prati F, Regar E, Mintz GS, Arbustini E, Di Mario C, Jang IK, Akasaka T, Costa M, Guagliumi G, Grube E, Ozaki Y, Pinto F, Serruys PWJ. Expert review document on methodology, terminology, and clinical applications of optical coherence tomography: Physical principles, methodology of image acquisition, and clinical application for assessment of coronary arteries and atherosclerosis. Eur Heart J. 2010;31:401–15. ].

Macrophages

Macrophages are seen by OCT as signal-rich, distinct or confluent punctate dots which exceed the intensity of background speckle noise. Macrophages may often be seen at the boundary between the bottom of the cap and the top of a necrotic core. Dedicated softwares have been developed to identify macrophage bands with a higher accuracy than simple visual inspection [3030. Tearney GJ, Yabushita H, Houser SL, Aretz HT, Jang IK, Schlendorf KH, Kauffman CR, Shishkov M, Halpern EF, Bouma BE. Quantification of macrophage content in atherosclerotic plaques by optical coherence tomography. Circulation. 2003;107:113–9. , 3131. Di Vito L, Agozzino M, Marco V, Ricciardi A, Concardi M, Romagnoli E, Gatto L, Calogero G, Tavazzi L, Arbustini E, Prati F. Identification and quantification ofmacrophage presence in coronary atherosclerotic plaques by optical coherence tomography. Eur Heart J Cardiovasc Imaging. 2015;16:807–13. ].

Generally, good inter- and intra-observer agreement for visual plaque characterisation have been reported with TD-OCT [1717. Yabushita H, Bouma BE, Houser SL, Aretz HT, Jang IK, Schlendorf KH, Kauffman CR, Shishkov M, Kang DH, Halpern EF, Tearney GJ. Characterization of human atherosclerosis by optical coherence tomography. Circulation. 2002;106:1640–5. ]. Recent studies showed a good reproducibility for measurements of OCT features, including FC thickness [3232. Romagnoli E, Paoletti G, Marco V, Gatto L, Calligaris G, Fabbiocchi F, Fineschi M, Boi A, Albertucci M, Nicholls SJ, Prati F. Comparison between different approaches to evaluate fibrous cap thickness in sequential OCT studies. Minerva Cardioangiol. 2020. ] and macrophage circumferential extension and superficiality (distance to the lumen) [3333. Gatto L, Paoletti G, Marco V, La Manna A, Fabbiocchi F, Cortese B, Vergallo R, Boi A, Fineschi M, Di Giorgio A, Taglieri N, Calligaris G, Budassi S, Burzotta F, Isidori F, Lella E, Ruscica G, Albertucci M, Tamburino C, Ozaki Y, Alfonso F, Arbustini E, Prati F. Prevalence and quantitative assessment of macrophages in coronary plaques. Int J Cardiovasc Imaging. 2021;37:37–45. ].

PLAQUE VULNERABILITY AND INTRACORONARY THROMBOSIS

Acute coronary syndromes (ACS) caused by the rupture of a coronary plaque and thrombosis are common initial, and often fatal, manifestations of coronary atherosclerosis in otherwise apparently healthy subjects. The detection of a lesion with high risk of rupture (the so-called “vulnerable plaque”) would be of prime importance for the prevention of future ACS. OCT has emerged as one of the most promising tools to assess patients with ACS ( Figure 7) ( Figure 8) ( Figure 9) and to detect key features of plaques at high risk for rupture.

OCT for diagnosis of vulnerable plaques

Thin fibrous cap atheromas are considered the most important morphological substrate for a plaque at high risk of rupture. The thickness and structure of the fibrous cap, as well as the size and extent of the underlying necrotic core, are major determinants of plaque vulnerability. OCT allows the diagnosis of thin cap fibro-atheroma (TCFA) with a sensitivity of 90% and a specificity of 79% when compared to histopathology [3434. Kume T, Okura H, Yamada R, Kawamoto T, Watanabe N, Neishi Y, Sadahira Y, Akasaka T, Yoshida K. Frequency and spatial distribution of thin-cap fibroatheroma assessed by 3-vessel intravascular ultrasound and optical coherence tomography - An ex vivo validation and an initial in vivo feasibility study. Circ J. 2009;73:1086–91. ].

OCT is suited for the in vivo detection of TCFA [3434. Kume T, Okura H, Yamada R, Kawamoto T, Watanabe N, Neishi Y, Sadahira Y, Akasaka T, Yoshida K. Frequency and spatial distribution of thin-cap fibroatheroma assessed by 3-vessel intravascular ultrasound and optical coherence tomography - An ex vivo validation and an initial in vivo feasibility study. Circ J. 2009;73:1086–91. , 3535. Kubo T, Imanishi T, Takarada S, Kuroi A, Ueno S, Yamano T, Tanimoto T, Matsuo Y, Masho T, Kitabata H, Tanaka A, Nakamura N, Mizukoshi M, Tomobuchi Y, Akasaka T. Implication of Plaque Color Classification for Assessing Plaque Vulnerability A Coronary Angioscopy and Optical Coherence Tomography Investigation. 2008. ]. Several studies have demonstrated a good correlation between fibrous cap thickness measurements with OCT and histology [3434. Kume T, Okura H, Yamada R, Kawamoto T, Watanabe N, Neishi Y, Sadahira Y, Akasaka T, Yoshida K. Frequency and spatial distribution of thin-cap fibroatheroma assessed by 3-vessel intravascular ultrasound and optical coherence tomography - An ex vivo validation and an initial in vivo feasibility study. Circ J. 2009;73:1086–91. , 3535. Kubo T, Imanishi T, Takarada S, Kuroi A, Ueno S, Yamano T, Tanimoto T, Matsuo Y, Masho T, Kitabata H, Tanaka A, Nakamura N, Mizukoshi M, Tomobuchi Y, Akasaka T. Implication of Plaque Color Classification for Assessing Plaque Vulnerability A Coronary Angioscopy and Optical Coherence Tomography Investigation. 2008. ]. Moreover, a good reproducibility (confidence intervals less than 0.04 mm) of the fibrous cap thickness has been demonstrated performing longitudinal measurements in multiple adjacent frames [3232. Romagnoli E, Paoletti G, Marco V, Gatto L, Calligaris G, Fabbiocchi F, Fineschi M, Boi A, Albertucci M, Nicholls SJ, Prati F. Comparison between different approaches to evaluate fibrous cap thickness in sequential OCT studies. Minerva Cardioangiol. 2020. ]. In a study comparing OCT, IVUS and angioscopy in patients with acute myocardial infarction, OCT was the only imaging technology able to estimate the fibrous cap thickness (mean 49±21 μm) [3535. Kubo T, Imanishi T, Takarada S, Kuroi A, Ueno S, Yamano T, Tanimoto T, Matsuo Y, Masho T, Kitabata H, Tanaka A, Nakamura N, Mizukoshi M, Tomobuchi Y, Akasaka T. Implication of Plaque Color Classification for Assessing Plaque Vulnerability A Coronary Angioscopy and Optical Coherence Tomography Investigation. 2008. ]. Angioscopy does not allow the measurement of the fibrous cap but there is evidence of a relation between the plaque color by angioscopy and the thickness of the fibrous cap as measured by OCT [1616. Prati F, Regar E, Mintz GS, Arbustini E, Di Mario C, Jang IK, Akasaka T, Costa M, Guagliumi G, Grube E, Ozaki Y, Pinto F, Serruys PWJ. Expert review document on methodology, terminology, and clinical applications of optical coherence tomography: Physical principles, methodology of image acquisition, and clinical application for assessment of coronary arteries and atherosclerosis. Eur Heart J. 2010;31:401–15. ].

Based on OCT studies fibrous cap thickness can change in response to drug therapy. A study evaluating the baseline plaque characteristics in patients undergoing cardiac catheterisation demonstrated a trend towards an increased fibrous cap thickness in patients on statin therapy. Furthermore, ruptured plaques were significantly less frequent in the statin group [3636. Chia S, Raffel OC, Takano M, Tearney GJ, Bouma BE, Jang IK. Association of statin therapy with reduced coronary plaque rupture: An optical coherence tomography study. Coron Artery Dis. 2008;19:237–42. ]. Takarada et al studied non-culprit lipid-rich lesion in patients with acute myocardial infarction and showed a marked increase in the fibrous cap thickness in patients treated with statins [3737. Takarada S, Imanishi T, Kubo T, Tanimoto T, Kitabata H, Nakamura N, Tanaka A, Mizukoshi M, Akasaka T. Effect of statin therapy on coronary fibrous-cap thickness in patients with acute coronary syndrome: Assessment by optical coherence tomography study. Atherosclerosis. 2009;202:491–7. ]. More recently Habara et al showed in an OCT study that lipid-lowering therapy with ezetimibe + fluvastatin further increases the fibrous cap thickness of lipid-rich plaques compared with fluvastatin monotherapy [3838. Habara M, Nasu K, Terashima M, Ko E, Yokota D, Ito T, Kurita T, Teramoto T, Kimura M, Kinoshita Y, Tsuchikane E, Asakura Y, Matsubara T, Suzuki T. Impact on optical coherence tomographic coronary findings of fluvastatin alone versus fluvastatin + ezetimibe. Am J Cardiol. 2014;113:580–7. ].

The stability of the fibrous cap depends not only on its thickness but also on the collagen content and organisation. Several investigations have shown lower collagen content, thinner collagen fibers, and fewer smooth muscle cells (SMC) in unstable plaques. Polarisation-sensitive OCT (PSOCT) is a new technology that enhances OCT by measuring birefringence, a property which is elevated in tissues containing proteins with an ordered structure such as collagen and SMC’s actin/myosin. PSOCT is potentially able to evaluate collagen content, collagen fiber thickness and SMC density in fibro-atheroma plaques [3939. Nadkarni SK, Pierce MC, Park BH, de Boer JF, Whittaker P, Bouma BE, Bressner JE, Halpern E, Houser SL, Tearney GJ. Measurement of Collagen and Smooth Muscle Cell Content in Atherosclerotic Plaques Using Polarization-Sensitive Optical Coherence Tomography. J Am Coll Cardiol. 2007;49:1474–81. ]. This information is related to the mechanical stability of the fibrous cap and could help improve the identification of lesions at high risk of rupture in patients.

Xing et al. explored in 1,474 patients from the Massachusetts General Hospital (MGH) OCT Registry the clinical impact of plaques in non-culprit regions of target vessels [4040. Xing L, Higuma T, Wang Z, Aguirre AD, Mizuno K, Takano M, Dauerman HL, Park SJ, Jang Y, Kim CJ, Kim SJ, Choi SY, Itoh T, Uemura S, Lowe H, Walters DL, Barlis P, Lee S, Lerman A, Toma C, Tan JWC, Yamamoto E, Bryniarski K, Dai J, Zanchin T, Zhang S, Yu B, Lee H, Fujimoto J, Fuster V, Jang IK. Clinical Significance of Lipid-Rich Plaque Detected by Optical Coherence Tomography: A 4-Year Follow-Up Study. J Am Coll Cardiol. 2017;69:2502–13. ]. Major adverse cardiac events (MACE), defined as a composite of cardiac death, acute myocardial infarction, and ischemia-driven revascularization were significantly more common in patients with lipid-rich plaques (3.5% vs. 1.8% at two years). In addition, lipid rich plaques in patients with MACE had longer lipid lengths (p < 0.001), wider maximal lipid arcs (p = 0.023), and smaller minimal lumen areas (p = 0.003).

A recent study [4141. Prati F, Gatto L, Romagnoli E, Limbruno U, Fineschi M, Marco V, Albertucci M, Tamburino C, Crea F, Alfonso F, Arbustini E. In vivo vulnerability grading system of plaques causing acute coronary syndromes: An intravascular imaging study. Int J Cardiol. 2018;269:350–5. ] highlighted the role of superficial macrophages as a feature related to plaque vulnerability, studying 99 lesions by means of IntraVascular-Ultrasound Near-Infrared-Spectroscopy (IVUS-NIRS) and OCT. OCT was able to identify at the culprit site of ACS the co-presence of 3 features of vulnerability (MLA<4 mm², FCT<75µm and superficial macrophages) in the vast majority of findings. This finding set the basis for a new OCT vulnerability grading system including superficial macrophages that was applied later on in the CLIMA study, [4242. Prati F, Romagnoli E, Gatto L, Manna A La, Burzotta F, Ozaki Y, Marco V, Boi A, Fineschi M, Fabbiocchi F, Taglieri N, Niccoli G, Trani C, Versaci F, Calligaris G, Ruscica G, Di Giorgio A, Vergallo R, Albertucci M, Biondi-Zoccai G, Tamburino C, Crea F, Alfonso F, Arbustini E. Relationship between coronary plaque morphology of the left anterior descending artery and 12 months clinical outcome: The CLIMA study. Eur Heart J. 2020;41:383–91. ] that enrolled 1003 patients undergoing OCT evaluation of an untreated proximal left anterior descending coronary artery. Overall, 1776 lipid plaques were studied. Presence of MLA <3.5mm² (HR 2.1, confidence interval [CI] 95% 1.1-4.0), FCT <75µm (HR 4.7, CI 95% 2.4-9.0), lipid arc circumferential extension >180° (HR 2.4, CI 95% 1.2-4.8), and macrophages (HR 2.7, CI 95% 1.2-6.1) were all associated with increased risk of clinical events. The simultaneous presence of the 4 OCT criteria in the same plaque was observed in 19.4% of patients experiencing the primary hard end-point (Death and or target segment myocardial infarction) and was an independent predictor of events (HR 7.54, CI 95% 3.1-18.6).

Based on histology data, over 5% of acute coronary syndromes (ACS) are caused by acute thrombosis occurring at the site of calcific nodules. In a post-hoc analysis of the CLIMA study the presence of calcific nodules with disruption, characterized by loss of integrity of the intimal fibrous layer and possible superficial thrombus apposition, are associated with a higher one-year incidence of cardiac death and/ or target lesion MI, compared with the group without disrupted calcific nodules [4343. Prati F, Gatto L, Fabbiocchi F, Vergallo R, Paoletti G, Ruscica G, Marco V, Romagnoli E, Boi A, Fineschi M, Calligaris G, Tamburino C, Crea F, Ozaki Y, Alfonso F, Arbustini E. Clinical outcomes of calcified nodules detected by optical coherence tomography: a sub-analysis of the CLIMA study. EuroIntervention. 2020;16:380–6. ].

Clinical observations in patients with ACS

Pathological data has shown differences in the characteristics of the underlying plaque in patients with stable and unstable coronary syndromes [4444. Virmani R, Burke AP, Farb A, Kolodgie FD. Pathology of the Vulnerable Plaque. J Am Coll Cardiol. 2006;47. ]. The ability of OCT to characterise fibrous cap has enabled pathophysiological studies on the prevalence, distribution and mechanism of rupture of thin-cap fibro-atheromas in different clinical scenarios. Jang et al evaluated the culprit lesion characteristics as assessed by OCT in patients with stable and unstable clinical presentation. The percentage of lipid-rich plaque in acute myocardial infarction, ACS and stable angina was 90%, 75%, and 59% respectively (p=0.09). The authors also reported differences in the thickness of the fibrous cap, which was lower in the patients with unstable syndromes. Consistently, the frequency of TCFA was higher in the acute myocardial infarction population (72%) and in the ACS group (50%) than in the stable angina group (20%) [2727. Jang IK, Tearney GJ, MacNeill B, Takano M, Moselewski F, Iftima N, Shishkov M, Houser S, Aretz HT, Halpern EF, Bouma BE. In vivo characterization of coronary atherosclerotic plaque by use of optical coherence tomography. Circulation. 2005;111:1551–5. ]. These results are in line with another study from Kubo et al showing a higher incidence of lipid-rich plaques (71% vs. 42%, p=0.03), plaque rupture (42% vs. 3%, p<0.001), intracoronary thrombus (67% vs. 3%, p <0.001) and TCFA (46% vs. 3%, p=0.001) in patients with unstable angina vs. patients with stable presentation [4545. Kubo T, Imanishi T, Kitabata H, Kuroi A, Ueno S, Yamano T, Tanimoto T, Matsuo Y, Masho T, Takarada S, Tanaka A, Nakamura N, Mizukoshi M, Tomobuchi Y, Akasaka T. Comparison of Vascular Response After Sirolimus-Eluting Stent Implantation Between Patients With Unstable and Stable Angina Pectoris. A Serial Optical Coherence Tomography Study. JACC Cardiovasc Imaging. 2008;1:475–84. ]. Plaques with TCFA morphology by OCT appear to be highly prevalent in patients with ACS. A study of the culprit lesion in acute myocardial infarction patients revealed an incidence of TCFA of 83% with a mean fibrous cap thickness of 49±21 μm [1818. Kubo T, Imanishi T, Takarada S, Kuroi A, Ueno S, Yamano T, Tanimoto T, Matsuo Y, Masho T, Kitabata H, Tsuda K, Tomobuchi Y, Akasaka T. Assessment of Culprit Lesion Morphology in Acute Myocardial Infarction. Ability of Optical Coherence Tomography Compared With Intravascular Ultrasound and Coronary Angioscopy. J Am Coll Cardiol. 2007;50:933–9. ]. Presence of lesions with thin-cap fibro-atheroma was also investigated by Fuji et al [4646. Fujii K, Kawasaki D, Masutani M, Okumura T, Akagami T, Sakoda T, Tsujino T, Ohyanagi M, Masuyama T. OCT Assessment of Thin-Cap Fibroatheroma Distribution in Native Coronary Arteries. JACC Cardiovasc Imaging. 2010;3:168–75. ]. In a 3-vessel OCT study conducted in 55 patients (165 coronary arteries), the authors identified 94 thin-cap fibro-atheromas. Thin-cap atheromas were found to cluster in the proximal left anterior descending but had an even distribution in the left circumflex and right coronary artery.

Tanaka et al [4747. Tanaka A, Imanishi T, Kitabata H, Kubo T, Takarada S, Tanimoto T, Kuroi A, Tsujioka H, Ikejima H, Ueno S, Kataiwa H, Okouchi K, Kashiwaghi M, Matsumoto H, Takemoto K, Nakamura N, Hirata K, Mizukoshi M, Akasaka T. Morphology of exertion-triggered plaque rupture in patients with acute coronary syndrome: An optical coherence tomography study. Circulation. 2008;118:2368–73. ] suggested that morphologies of exertion-triggered and rest-onset ruptured plaques differ in patients with ACS who presented with a ruptured plaque at the culprit site. The culprit plaque tended to rupture at the fibrous cap shoulder more frequently in patients who had ACS during exertion, whilst in the group with ACS developing at rest, the rupture of fibrous cap was more commonly located in non-shoulder regions. These clinical observations are important, as they not only confirm histopathology observations but also offer the potential to assess atherosclerotic plaque and its dynamic changes in a longitudinal way.

More recently OCT studies confirmed past histology findings showing calcified nodules with disruption at the culprit site of patients with ACS in 3.1% to 8.0% of cases [4848. Higuma T, Soeda T, Abe N, Yamada M, Yokoyama H, Shibutani S, Vergallo R, Minami Y, Ong DS, Lee H, Okumura K, Jang IK. A Combined Optical Coherence Tomography and Intravascular Ultrasound Study on Plaque Rupture, Plaque Erosion, and Calcified Nodule in Patients with ST-Segment Elevation Myocardial Infarction Incidence, Morphologic Characteristics, and Outcomes after Percutaneous Coronary Intervention. JACC Cardiovasc Interv. 2015;8:1166–76. , 4949. Kajander OA, Pinilla-Echeverri N, Jolly SS, Bhindi R, Huhtala H, Niemelä K, Fung A, Vijayaraghavan R, Alexopoulos D, Sheth T. Culprit plaque morphology in STEMI-an optical coherence tomography study: Insights from the TOTAL-OCT substudy. EuroIntervention. 2016;12:716–23. , 5050. Wang L, Parodi G, Maehara A, Valenti R, Migliorini A, Vergara R, Carrabba N, Mintz GS, Antoniucci D. Variable underlying morphology of culprit plaques associated with ST-elevation myocardial infarction: An optical coherence tomography analysis from the SMART trial. Eur Heart J Cardiovasc Imaging. 2015;16:1381–9. ].

Coronary plaque progression

Uemura et al [5151. Uemura S, Ishigami KI, Soeda T, Okayama S, Sung JH, Nakagawa H, Somekawa S, Takeda Y, Kawata H, Horii M, Saito Y. Thin-cap fibroatheroma and microchannel findings in optical coherence tomography correlate with subsequent progression of coronary atheromatous plaques. Eur Heart J. 2012;33:78–85. ] identified for the first time the lesions that exhibited rapid progression. TCFA and microchannel images were the plaque features more commonly present in plaques with progressions at the univariate regression analysis.

More recently plaques with rapid progression exhibited a significantly higher prevalence of lipid-rich plaque (thin-cap fibroatheroma, layered plaque, macrophage accumulation, microvessel plaque rupture and thrombus) at baseline compared with those without rapid progression. Multivariate analysis identified lipid-rich plaque (OR 2.17 ), TCFA (OR: 5.85) and layered plaque (OR: 2.19) as predictors of subsequent rapid lesion progression. [5252. Araki M, Yonetsu T, Kurihara O, Nakajima A, Lee H, Soeda T, Minami Y, McNulty I, Uemura S, Kakuta T, Jang IK. Predictors of Rapid Plaque Progression: An Optical Coherence Tomography Study. JACC Cardiovasc Imaging. 2020. ].

Guidance of stent deployment

Pre-implantation assessment

The ILUMIEN observational OCT trial [5353. Wijns W, Shite J, Jones MR, Lee SWL, Price MJ, Fabbiocchi F, Barbato E, Akasaka T, Bezerra H, Holmes D. Optical coherence tomography imaging during percutaneous coronary intervention impacts physician decision-making: ILUMIEN i study. Eur Heart J. 2015;36:3346–55. ] was the first study to focus on the role of pre-intervention OCT assessment. Based on pre-PCI OCT, the procedure was altered in 55% of patients as led to selection of different stent lengths, that were shorter in 25% and longer in 43%. Based on postintervention OCT further stent optimization was done in 25% of patients with further in-stent post-dilatation (81%) or placement of new stents (12%). MACE incidence at 30 days was low, with death occurring in 0.25%, myocardial infarction in 7.7%, repeat PCI in 1.7%, and stent thrombosis in 0.25%.

In the randomised controlled trial ILUMIEN III [5454. Ali ZA, Landmesser U, Galougahi KK, Maehara A, Matsumura M, Shlofmitz RA, Guagliumi G, Price MJ, Hill JM, Akasaka T, Prati F, Bezerra HG, Wijns W, Mintz GS, Ben-Yehuda O, McGreevy RJ, Zhang Z, Rapoza RJ, West NEJ, Stone GW. Optical coherence tomography-guided coronary stent implantation compared to angiography: A multicentre randomised trial in PCI – Design and rationale of ILUMIEN IV: OPTIMAL PCI. EuroIntervention. 2021;16:1092–9. ] Ziad et al. proved the non-inferiority of OCT guidance vs IVUS guidance in term of final minimum stent area 5.79 mm² (IQR 4.54–7.34) vs 5.89 mm² (4.67–7.80) respectively. They applied a novel approach for stenting sizing, based on pre-intervention measurement of the media to media border. According to the core lab centralized analysis a correct measurement was deemed possible in 95% of cases, despite the limited penetration of OCT. Such approach is being tested in the ongoing large-scale, randomized ILUMIEN IV trial, which will evaluate the OCT guided compared to the Angio-guided PCI in terms of post-PCI lumen dimensions and clinical outcomes in patients with diabetes and/or with complex coronary lesions [5454. Ali ZA, Landmesser U, Galougahi KK, Maehara A, Matsumura M, Shlofmitz RA, Guagliumi G, Price MJ, Hill JM, Akasaka T, Prati F, Bezerra HG, Wijns W, Mintz GS, Ben-Yehuda O, McGreevy RJ, Zhang Z, Rapoza RJ, West NEJ, Stone GW. Optical coherence tomography-guided coronary stent implantation compared to angiography: A multicentre randomised trial in PCI – Design and rationale of ILUMIEN IV: OPTIMAL PCI. EuroIntervention. 2021;16:1092–9. ].

Plaque composition and risk of periprocedural complications

OCT can be used to confirm the presence of atherosclerotic plaque and to characterise its composition. The assessment of plaque composition can be helpful in clinical practice to guide percutaneous coronary interventions, as plaque composition has been related to the outcome after percutaneous interventions (e.g., heavily calcified lesions which have lower distensibility or necrotic core plaques with their propensity to rupture).

Fujino et al [5555. Fujino A, Mintz GS, Lee T, Hoshino M, Usui E, Kanaji Y, Murai T, Yonetsu T, Matsumura M, Ali ZA, Jeremias A, Moses JW, Shlofmitz RA, Kakuta T, Maehara A. Predictors of Calcium Fracture Derived From Balloon Angioplasty and its Effect on Stent Expansion Assessed by Optical Coherence Tomography. JACC Cardiovasc Interv. 2018;11:1015–7. ] developed an OCT based calcium scoring system to predict stent underexpansion. The multivariable model showed that maximum calcium angle per 180°, maximum calcium thickness per 0.5 mm, and calcium length per 5 mm are independent predictors of stent expansion. A calcium score was then defined as 2 points for maximum angle >180°, 1 point for maximum thickness >0.5 mm, and 1 point for length >5 mm. Lesions with a score of 4 had poor stent expansion (96% versus 78%, p<0.01).

Recently, several devices have become available, expanding the possibilities of treatment in calcified lesions through different mechanisms. OCT assessment of the calcification score enables the selection of the most effective technology for treating highly calcified lesions. [55–58]. Rotational, orbital and excimer laser atherectomy, cutting, scoring balloon and intravascular lithotripsy (IVL; [Shockwave Medical, Inc. Coronary Lithoplasty® System]) are valuable solutions to improve lesion preparation [5656. Karimi Galougahi K, Shlofmitz E, Jeremias A, Gogia S, Kirtane AJ, Hill JM, Karmpaliotis D, Mintz GS, Maehara A, Stone GW, Shlofmitz RA, Ali ZA. Therapeutic Approach to Calcified Coronary Lesions: Disruptive Technologies. Curr Cardiol Rep. 2021;23. ]. A deep calcification or a score ≤2 may suggest the adoption of a non-Compliant (NC; high-pressure), scoring or cutting balloon. A score ≥3 favours a different approach with IVL and orbital or rotational atherectomy. These last two technologies are particularly recommended in presence of nodular and uncrossable lesion [5656. Karimi Galougahi K, Shlofmitz E, Jeremias A, Gogia S, Kirtane AJ, Hill JM, Karmpaliotis D, Mintz GS, Maehara A, Stone GW, Shlofmitz RA, Ali ZA. Therapeutic Approach to Calcified Coronary Lesions: Disruptive Technologies. Curr Cardiol Rep. 2021;23. ].

The relation between the lipid content of the plaque and the presence of no-reflow phenomenon after stent implantation has been shown in an IVUS-virtual histology study [5959. Bae JH, Kwon TG, Hyun DW, Rihal CS, Lerman A. Predictors of slow flow during primary percutaneous coronary intervention: An intravascular ultrasound-virtual histology study. Heart. 2008;94:1559–64. ]. This observation has been confirmed by OCT. According to Ohshima et al the frequency of no-reflow phenomenon increases according to the lipid content of the plaque [6060. Tanaka A, Imanishi T, Kitabata H, Kubo T, Takarada S, Tanimoto T, Kuroi A, Tsujioka H, Ikejima H, Komukai K, Kataiwa H, Okouchi K, Kashiwaghi M, Ishibashi K, Matsumoto H, Takemoto K, Nakamura N, Hirata K, Mizukoshi M, Akasaka T. Lipid-rich plaque and myocardial perfusion after successful stenting in patients with non-ST-segment elevation acute coronary syndrome: An optical coherence tomography study. Eur Heart J. 2009;30:1348–55. ].

Consistently with these findings, Imola et al compared 15 patients with post-procedural myocardial infarctions with 15 controls without infarctions and showed that incomplete stent coverage of coronary lipid pools is associated with an increased risk of post-procedural myocardial infarction [6161. Imola F, Occhipinti M, Biondi-Zoccai G, Di Vito L, Ramazzotti V, Manzoli A, Pappalardo A, Cremonesi A, Albertucci M, Prati F. Association between proximal stent edge positioning on atherosclerotic plaques containing lipid pools and postprocedural myocardial infarction (from the CLI-POOL Study). Am J Cardiol. 2013;111:526–31. ].

Post implantation assessment

The high resolution of the OCT technique permits detection of features that may be missed by IVUS, such as malapposition, intra stent plaque/thrombus protrusion, or dissections at the stent edges and inside the stents. This aspect is instrumental to better understand how to obtain optimal stenting, however it provides operators with an excess of information that may lead to an over-reaction, in the effort to correct innocent, but ominous looking anatomical issues. The CLI-OPCI studies [6262. Prati F, Di Vito L, Biondi-Zoccai G, Occhipinti M, La Manna A, Tamburino C, Burzotta F, Trani C, Porto I, Ramazzotti V, Imola F, Manzoli A, Materia L, Cremonesi A, Albertucci M. Angiography alone versus angiography plus optical coherence tomography to guide decision-making during percutaneous coronary intervention: The Centro per la Lotta contro l’Infarto-Optimisation of Percutaneous Coronary Intervention (CLI-OPCI) study. EuroIntervention. 2012;8:823–9. , 6363. Prati F, Romagnoli E, Burzotta F, Limbruno U, Gatto L, La Manna A, Versaci F, Marco V, Di Vito L, Imola F, Paoletti G, Trani C, Tamburino C, Tavazzi L, Mintz GS. Clinical impact of OCT findings during PCI the CLI-OPCI II study. JACC Cardiovasc Imaging. 2015;8:1297–305. ] were specifically designed to answer these crucial questions in “every day” practice.

The multicenter CLI-OPCI study [6262. Prati F, Di Vito L, Biondi-Zoccai G, Occhipinti M, La Manna A, Tamburino C, Burzotta F, Trani C, Porto I, Ramazzotti V, Imola F, Manzoli A, Materia L, Cremonesi A, Albertucci M. Angiography alone versus angiography plus optical coherence tomography to guide decision-making during percutaneous coronary intervention: The Centro per la Lotta contro l’Infarto-Optimisation of Percutaneous Coronary Intervention (CLI-OPCI) study. EuroIntervention. 2012;8:823–9. ] aimed at verifying whether the use of OCT can improve the 1-year composite event of cardiac death or nonfatal myocardial infarction after PCI in a real-world population. Results from 335 patients who underwent OCT-guided intervention were compared with those from a control group by means of propensity score adjustment. Conclusions were very promising, in-fact OCT guided intervention halved the rate of death and myocardial infarction from 13% to 6.6% (p=0.006).

The study showed that OCT could potentially improve the clinical outcomes after coronary intervention in a real-world population. However, its promising conclusions were approached with caution due to its non-randomized design and relatively small population size.

The CLI-OPCI II [6464. Prati F, Romagnoli E, Gatto L, La Manna A, Burzotta F, Limbruno U, Versaci F, Fabbiocchi F, Di Giorgio A, Marco V, Ramazzotti V, Di Vito L, Trani C, Porto I, Boi A, Tavazzi L, Mintz GS. Clinical impact of suboptimal stenting and residual intrastent plaque/thrombus protrusion in patients with acute coronary syndrome. Circ Cardiovasc Interv. 2016;9. ] corroborated the findings obtained in the CLI-OPCI registry testing the role of OCT findings after PCI in a much larger population comprising 832 patients and 1002 lesions with a median follow-up of 319 days. Consistent with previous data [6262. Prati F, Di Vito L, Biondi-Zoccai G, Occhipinti M, La Manna A, Tamburino C, Burzotta F, Trani C, Porto I, Ramazzotti V, Imola F, Manzoli A, Materia L, Cremonesi A, Albertucci M. Angiography alone versus angiography plus optical coherence tomography to guide decision-making during percutaneous coronary intervention: The Centro per la Lotta contro l’Infarto-Optimisation of Percutaneous Coronary Intervention (CLI-OPCI) study. EuroIntervention. 2012;8:823–9. ] the CLI-OPCI II showed that OCT-defined suboptimal stent deployment was a relatively common finding (31.0% of cases) with a significantly higher prevalence in patients experiencing MACE in the first year of follow up (59.2% vs. 26.9%, p<0.001) and was an independent predictor of worse outcome (HR=3.53, p<0.001).

More recently the Pan-London PCI registry [6565. Jones DA, Rathod KS, Koganti S, Hamshere S, Astroulakis Z, Lim P, Sirker A, O’Mahony C, Jain AK, Knight CJ, Dalby MC, Malik IS, Mathur A, Rakhit R, Lockie T, Redwood S, MacCarthy PA, Desilva R, Weerackody R, Wragg A, Smith EJ, Bourantas C V. Angiography Alone Versus Angiography Plus Optical Coherence Tomography to Guide Percutaneous Coronary Intervention: Outcomes From the Pan-London PCI Cohort. JACC Cardiovasc Interv. 2018;11:1313–21. ], conceived as an observational study including 123,764 patients, confirmed data emerged from the CLIO-PCI study. OCT guidance was used in 1,149 (1.3%) patients, IVUS in 10,971 (12.6%) and angiography alone in the remaining 75,046 patients. OCT-guided PCI was associated with improved procedural outcomes, in-hospital events, and long-term survival, compared with standard angiography-guided PCI.

Other studies, performed with a randomized design and mainly exploring surrogate clinical end-points, confirmed the effectiveness of an OCT guidance strategy of stent deployment.

The DOCTORS study [6666. Meneveau N, Souteyrand G, Motreff P, Caussin C, Amabile N, Ohlmann P, Morel O, Lefrançois Y, Descotes-Genon V, Silvain J, Braik N, Chopard R, Chatot M, Ecarnot F, Tauzin H, Van Belle E, Belle L, Schiele F. Optical coherence tomography to optimize results of percutaneous coronary intervention in patients with Non-ST-elevation acute coronary syndrome. Circulation. 2016;134:906–17. ] was a multicenter, randomized study, carried on in 240 patients with non–ST-segment elevation ACS, for comparison of OCT-guided PCI vs fluoroscopy-guided PCI. In the OCT arm pre- and post-PCI imaging was performed. OCT-guided PCI was found to be associated with higher postprocedural fractional flow reserve, which was the primary study end-point.

The OPINION study [6767. Kubo T, Shinke T, Okamura T, Hibi K, Nakazawa G, Morino Y, Shite J, Fusazaki T, Otake H, Kozuma K, Ioji T, Kaneda H, Serikawa T, Kataoka T, Okada H, Akasaka T. Optical frequency domain imaging vs. intravascular ultrasound in percutaneous coronary intervention (OPINION trial): One-year angiographic and clinical results. Eur Heart J. 2017;38:3139–47. ] was a prospective, multicentre, randomized (ratio 1:1), non-inferiority comparative study that allocated 829 patients to receive OCT-guided PCI or IVUS-guided PCI. Both OCT-guided and IVUS-guided PCI yielded excellent angiographic and clinical results at 12 months, with very low rates of 8-month angiographic binary restenosis and 12-month target vessel failure.

The ILUMIEN III study [5454. Ali ZA, Landmesser U, Galougahi KK, Maehara A, Matsumura M, Shlofmitz RA, Guagliumi G, Price MJ, Hill JM, Akasaka T, Prati F, Bezerra HG, Wijns W, Mintz GS, Ben-Yehuda O, McGreevy RJ, Zhang Z, Rapoza RJ, West NEJ, Stone GW. Optical coherence tomography-guided coronary stent implantation compared to angiography: A multicentre randomised trial in PCI – Design and rationale of ILUMIEN IV: OPTIMAL PCI. EuroIntervention. 2021;16:1092–9. ] was designed as a randomised non-inferiority trial, like the OPINION trial. The trial proved the non-inferiority of OCT guidance vs IVUS guidance in term of final minimum stent area 5.79 mm² in the OCT group vs 5.89 mm² in the IVUS group.

Specific OCT findings of suboptimal stenting.

Lesion coverage

Incomplete lesion coverage and residual reference segment stenosis have been associated with stent thrombosis in IVUS studies [6868. Maehara A, Mintz GS, Witzenbichler B, Weisz G, Neumann FJ, Rinaldi MJ, Christopher Metzger D, Henry TD, Cox DA, Duffy PL, Brodie BR, Stuckey TD, Mazzaferri EL, McAndrew T, Généreux P, Mehran R, Kirtane AJ, Stone GW. Relationship between intravascular ultrasound guidance and clinical outcomes after drug-eluting stents: Two-year follow-up of the ADAPT-DES study. Circ Cardiovasc Interv. 2018;11. ]. The presence of residual lumen stenosis and incomplete lesion coverage can readily be identified by OCT.

In the CLIO-PCI II study [6363. Prati F, Romagnoli E, Burzotta F, Limbruno U, Gatto L, La Manna A, Versaci F, Marco V, Di Vito L, Imola F, Paoletti G, Trani C, Tamburino C, Tavazzi L, Mintz GS. Clinical impact of OCT findings during PCI the CLI-OPCI II study. JACC Cardiovasc Imaging. 2015;8:1297–305. ] stented segments exhibiting a narrowing at the reference (lumen area <4.5mm² in the presence of significant plaque) experienced a worse outcome with a risk of MACE approximately five times higher regardless of the location (proximal or distal reference segment).

Edge dissections

OCT with its high resolution can identify less-extensive edge dissections which are missed by IVUS. Whilst minor edge dissections are unlikely to convey a worse outcome, large ones were found to be related to a higher incidence of MACE. In the CLI-OPCI II Study [6363. Prati F, Romagnoli E, Burzotta F, Limbruno U, Gatto L, La Manna A, Versaci F, Marco V, Di Vito L, Imola F, Paoletti G, Trani C, Tamburino C, Tavazzi L, Mintz GS. Clinical impact of OCT findings during PCI the CLI-OPCI II study. JACC Cardiovasc Imaging. 2015;8:1297–305. ], dissections >200 µm at the distal (but not proximal) stent edge by OCT emerged as an independent predictor of MACE (HR 2.5).

The same conclusion was reached by Bouki et a [6969. Bouki KP, Sakkali E, Toutouzas K, Vlad D, Barmperis D, Phychari S, Riga M, Apostolou T, Stefanadis C. Impact of coronary artery stent edge dissections on long-term clinical outcome in patients with acute coronary syndrome: An optical coherence tomography study. Catheter Cardiovasc Interv. 2015;86:237–46. ]. According to authors, who studied 74 patients with ACS, presence of a residual dissection flap > 0.31 mm, carried an adverse long-term clinical impact. In contrast with these data Soeda et al [7070. Soeda T, Uemura S, Park SJ, Jang Y, Lee S, Cho JM, Kim SJ, Vergallo R, Minami Y, Ong DS, Gao L, Lee H, Zhang S, Yu B, Saito Y, Jang IK. Incidence and clinical significance of poststent optical coherence tomography findings: One-year follow-up study from a multicenter registry. Circulation. 2015;132:1020–9. ] did not relate presence of dissection with the clinical outcome. Of note authors, did not introduce a quantitative threshold for dissection width, including in the study mild dissections, a common OCT finding after stenting.

The negative clinical impact of stent edge dissection, shown in the CLI-OPCI study, was exerted in the early phase after intervention with the vast majority of MACEs occurring during the first 3 months after the procedure. This finding does not contradict the conclusions reached by Radu et al [7171. Radu MD, Räber L, Heo J, Gogas BD, Jørgensen E, Kelbæk H, Muramatsu T, Farooq V, Helqvist S, Garcia-Garcia HM, Windecker S, Saunamäki K, Serruys PW. Natural history of optical coherence tomography-detected non-flow-limiting edge dissections following drug-eluting stent implantation. EuroIntervention. 2014;9:1085–94. ] who showed in a serial OCT study the late dissection tends to heal at late follow-up: In fact, at one year 90% of edge dissections were completely healed on OCT.

According to the ECS consensus document on the clinical use of intracoronary imaging [7272. Räber L, Mintz GS, Koskinas KC, Johnson TW, Holm NR, Onuma Y, Radu MD, Joner M, Yu B, Jia H, Meneveau N, De La Torre Hernandez JM, Escaned J, Hill J, Prati F, Colombo A, Di Mario C, Regar E, Capodanno D, Wijns W, Byrne RA, Guagliumi G, Alfonso F, Bhindi R, Ali Z, Carter R. Clinical use of intracoronary imaging. Part 1: Guidance and optimization of coronary interventions. An expert consensus document of the European Association of Percutaneous Cardiovascular Interventions. Eur Heart J. 2018;39:3281–300. ]

dissections with: 1) arc grade > 60, 2) longitudinal extension >2 mm, 3) involvement of deeper layers (medial or adventitia) and 4) localization distal to the stent are related to a higher risk for adverse events.

In-stent under-expansion, using absolute dimensions expressed as in-stent MLA, was significantly related to clinical outcome. The CLI-OPCI II registries identified an MLA of 4.5 mm2 as a threshold for discriminating patients with MACEs, whilst in the DOCTORS trial the optimal luminal cut-off to predict post-procedural FFR >0.90 was 5.44 mm² by OCT [6363. Prati F, Romagnoli E, Burzotta F, Limbruno U, Gatto L, La Manna A, Versaci F, Marco V, Di Vito L, Imola F, Paoletti G, Trani C, Tamburino C, Tavazzi L, Mintz GS. Clinical impact of OCT findings during PCI the CLI-OPCI II study. JACC Cardiovasc Imaging. 2015;8:1297–305. ].

A different approach to address under expansions resides on the stent percentage of under-expansion. The ESC consensus doc on clinical use of intracoronary imaging by Räber et al [7272. Räber L, Mintz GS, Koskinas KC, Johnson TW, Holm NR, Onuma Y, Radu MD, Joner M, Yu B, Jia H, Meneveau N, De La Torre Hernandez JM, Escaned J, Hill J, Prati F, Colombo A, Di Mario C, Regar E, Capodanno D, Wijns W, Byrne RA, Guagliumi G, Alfonso F, Bhindi R, Ali Z, Carter R. Clinical use of intracoronary imaging. Part 1: Guidance and optimization of coronary interventions. An expert consensus document of the European Association of Percutaneous Cardiovascular Interventions. Eur Heart J. 2018;39:3281–300. ] suggested a cut-off >80% for the MSA (relative to average reference lumen area), that appears to be a reasonable solution, keeping in mind that values of in stent expansion greater than 90% are difficult to achieve [6666. Meneveau N, Souteyrand G, Motreff P, Caussin C, Amabile N, Ohlmann P, Morel O, Lefrançois Y, Descotes-Genon V, Silvain J, Braik N, Chopard R, Chatot M, Ecarnot F, Tauzin H, Van Belle E, Belle L, Schiele F. Optical coherence tomography to optimize results of percutaneous coronary intervention in patients with Non-ST-elevation acute coronary syndrome. Circulation. 2016;134:906–17. ].

Stent malapposition

For the past two decades, IVUS has been used to assess the acute result following stent implantation, giving valuable information on stent expansion, strut apposition and signs of vessel trauma including dissections and tissue prolapse. IVUS studies [7373. Hong MK, Mintz GS, Lee CW, Park DW, Park KM, Lee BK, Kim YH, Song JM, Han KH, Kang DH, Cheong SS, Song JK, Kim JJ, Park SW, Park SJ. Late stent malapposition after drug-eluting stent implantation: An intravascular ultrasound analysis with long-term follow-up. Circulation. 2006;113:414–9. , 7474. Tanabe K, Serruys PW, Degertekin M, Grube E, Guagliumi G, Urbaszek W, Bonnier J, Lablanche JM, Siminiak T, Nordrehaug J, Figulla H, Drzewiecki J, Banning A, Hauptmann K, Dudek D, Bruining N, Hamers R, Hoye A, Ligthart JMR, Disco C, Koglin J, Russell ME, Colombo A. Incomplete stent apposition after implantation of paclitaxel-eluting stents or bare metal stents: Insights from the randomized TAXUS II trial. Circulation. 2005;111:900–5. ] have suggested that stent strut malapposition is a relatively uncommon finding, observed in approximately 7% of cases, and that strut malapposition does not increase the risk of subsequent major adverse cardiac events. By contrast, OCT can visualise in much greater detail the complex coronary arterial wall structure after stenting. As a result, OCT studies in the acute post-stent setting [7575. Tanigawa J, Barlis P, Dimopoulos K, Di Mario C. Optical coherence tomography to assess malapposition in overlapping drug-eluting stents. EuroIntervention. 2008;3:580–3. ] have demonstrated a relatively high proportion of stent struts not completely apposed to the vessel wall contact even after high pressure post-dilatation, with this phenomenon being particularly evident in regions of stent overlap. The mechanical result after stent implantation is of special interest in bifurcation lesions ( Figure 10). Malapposed struts were found to be frequent in bifurcations despite the use dedicated stents [7676. Tyczynski P, Ferrante G, Kukreja N, Moreno-Ambroj C, Barlis P, Ramasami N, De Silva R, Beatt K, Di Mario C. Optical coherence tomography assessment of a new dedicated bifurcation stent. EuroIntervention. 2009;5:544–51. ].

While these findings are impressive and helpful for the improvement of future stent designs, today the clinical relevance of malapposed struts is questionable.

Stent strut malapposition has been proposed as a cause of drug-eluting stent (DES) failure. Anecdotal cases shed light on the role of acute and late malapposition as a possible cause of first-generation DES thrombosis. Postulated causes of stent strut malapposition are numerous and include incomplete stent expansion, stent recoil or fracture, late outward vessel remodeling or the dissolution of thrombus which was compressed during PCI between the stent strut and the vessel wall. Regardless of the pathophysiological mechanism, the major concern in stent malapposition remains the assumption that areas of strut malapposition cause non-laminar and turbulent blood flow characteristics, which in turn can trigger platelet activation and thrombosis. Here, prospective, serial OCT observations, both immediately and at longer-term follow-up after stenting, may improve our understanding of these complex mechanisms and shed light on the likely clinical significance of this phenomenon.

IVUS and OCT studies [77–80] failed to relate acute stent-vessel wall malapposition with clinical outcome. It is likely that the innovative technology adopted for the new DES minimizes the consequences of acute malapposition.

Plaque- Tissue prolapse

Tissue prolapse after stent implantation has been identified as an OCT predictor of early stent thrombosis and has been related to adverse short-term prognosis following PCI [8181. Porto I, Di Vito L, Burzotta F, Niccoli G, Trani C, Leone AM, Biasucci LM, Vergallo R, Limbruno U, Crea F. Predictors of periprocedural (Type IVa) myocardial infarction, as assessed by frequency-domain optical coherence tomography. Circ Cardiovasc Interv. 2012;5:89–96. ].

Tissue prolapse at OCT is rather common in ACS patients. In the CLI-OPCI ACS registry [6464. Prati F, Romagnoli E, Gatto L, La Manna A, Burzotta F, Limbruno U, Versaci F, Fabbiocchi F, Di Giorgio A, Marco V, Ramazzotti V, Di Vito L, Trani C, Porto I, Boi A, Tavazzi L, Mintz GS. Clinical impact of suboptimal stenting and residual intrastent plaque/thrombus protrusion in patients with acute coronary syndrome. Circ Cardiovasc Interv. 2016;9. ] including 780 patients (50% with ACS), irregular protrusion was more common in patients treated for MI and was an independent predictor of 1-year clinical outcomes, Of note tissue prolapse in the context of ACS is more likely to have consequences than in more stable clinical setting as shown by the CLI-OPCI study.

Ambiguous images after stent implantation

Occasionally, ambiguous angiographic images can be observed after stent implantation and can create doubts about the need for further interventions. OCT may be helpful in clarifying the origin of these findings. Hazy regions at the borders of the stent can correspond to edge dissections, thrombus or residual uncovered plaque. When they are located inside the stent, they can be associated with the presence of intracoronary thrombus or intra-stent dissections [8282. Gonzalo N, Serruys PW, Okamura T, Shen ZJ, Garcia-Garcia HM, Onuma Y, Van Geuns RJ, Ligthart J, Regar E. Relation between plaque type and dissections at the edges after stent implantation: An optical coherence tomography study. Int J Cardiol. 2011;150:151–5. ].

ASSESSMENT OF LONG-TERM OUTCOME

Visualisation and quantification of stent strut tissue coverage

Several small studies have been published highlighting the ability of OCT to detect stent tissue coverage at follow-up ( Figure 11) ( Figure 12). Matsumoto et al [8383. Matsumoto D, Shite J, Shinke T, Otake H, Tanino Y, Ogasawara D, Sawada T, Paredes OL, Hirata K -i., Yokoyama M. Neointimal coverage of sirolimus-eluting stents at 6-month follow-up: evaluated by optical coherence tomography. Eur Heart J. 2007;28:961–7. ] studied 34 patients following sirolimus-eluting stent (SES) implantation. The mean neointima thickness was 52.5 μm, and the prevalence of struts covered by thin neointima undetectable by IVUS was 64%. The average rate of neointima-covered struts in an individual SES was 89%. Takano et al [8484. Takano M, Inami S, Jang IK, Yamamoto M, Murakami D, Seimiya K, Ohba T, Mizuno K. Evaluation by Optical Coherence Tomography of Neointimal Coverage of Sirolimus-Eluting Stent Three Months After Implantation. Am J Cardiol. 2007;99:1033–8. ] showed that rates of exposed struts and exposed struts with malapposition were 15% and 6% respectively at 3 months and were more frequent in presence of ACS (18% vs.13%, p<0.001; 8% vs. 5%, p<0.005 respectively). The same group reported for the first time on long term 2-year follow-up OCT findings [8585. Takano M, Jang IK, Inami S, Yamamoto M, Murakami D, Okamatsu K, Seimiya K, Ohba T, Mizuno K. In Vivo Comparison of Optical Coherence Tomography and Angioscopy for the Evaluation of Coronary Plaque Characteristics. Am J Cardiol. 2008;101:471–6. ]. The frequency of uncovered struts was found to be lower in the 2-year group compared to the 3-month group (5% vs. 15% respectively; p<0.001). However, the prevalence of patients with uncovered struts did not differ between the 3-month and the 2-year follow-up study (95% vs. 81% respectively) highlighting that exposed struts continued to persist at long-term follow-up. Chen et al [8686. Chen BX, Ma FY, Luo W, Ruan JH, Xie WL, Zhao XZ, Sun SH, Guo XM, Wang F, Tian T, Chu XW. Neointimal coverage of bare-metal and sirolimus-eluting stents evaluated with optical coherence tomography. Heart. 2008;94:566–70. ] used OCT to image SES and bare metal stents (BMS) at different time points following implantation. The authors identified a significantly higher number of incompletely apposed and uncovered stent struts in patients receiving SES compared to BMS. More recently, the OCT observations in prospective, multicentre clinical trials were reported. More recently, the results of larger-scale clinical trials have become available. The LEADERS trial was a multicentre, randomised comparison of a biolimus-eluting stent (BES) with biodegradable polymer with a sirolimus-eluting stent (SES) using a durable polymer in 1,707 patients. An OCT substudy was performed in 56 consecutive patients who underwent OCT during angiographic follow-up at 9 months. Strut coverage at an average follow-up of 9 months appeared to be more complete in patients allocated to BESs as compared to SESs. Results were similar after adjustment for pre-procedural lesion length, reference vessel diameter, number of implanted study stents, and presence of stent overlap [8686. Chen BX, Ma FY, Luo W, Ruan JH, Xie WL, Zhao XZ, Sun SH, Guo XM, Wang F, Tian T, Chu XW. Neointimal coverage of bare-metal and sirolimus-eluting stents evaluated with optical coherence tomography. Heart. 2008;94:566–70. ]. The clinical impact of these small but measurable differences in tissue coverage is unclear as it did not translate into a difference in clinical event rates in the substudy cohort. The 4-year follow-up data of the overall LEADERS cohort BES with biodegradable polymer was proven non-inferior to SES with durable polymer. Interestingly, BES showed a reduction in the risk of very late stent thrombosis at 4-year follow-up (RR 0.20, 95% CI 0.06-0.67, p=0.004) [8787. Barlis P, Regar E, Serruys PW, Dimopoulos K, Van Der Giessen WJ, Van Geuns RJM, Ferrante G, Wandel S, Windecker S, Van Es GA, Eerdmans P, Jüni P, Di Mario C. An optical coherence tomography study of a biodegradable vs. durable polymer-coated limus-eluting stent: A LEADERS trial sub-study. Eur Heart J. 2010;31:165–76. ]. In the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial, patients with STEMI were randomised to PES for BMS implantation [8888. Stefanini GG, Kalesan B, Serruys PW, Heg D, Buszman P, Linke A, Ischinger T, Klauss V, Eberli F, Wijns W, Morice MC, Di Mario C, Corti R, Antoni D, Sohn HY, Eerdmans P, Van Es GA, Meier B, Windecker S, Jüni P. Long-term clinical outcomes of biodegradable polymer biolimus-eluting stents versus durable polymer sirolimus-eluting stents in patients with coronary artery disease (LEADERS): 4 year follow-up of a randomised non-inferiority trial. Lancet. 2011;378:1940–8. ]. In a formal sub-study, OCT at 13 months was performed in 118 consecutive randomised patients. OCT revealed that implantation of PES as compared with BMS significantly reduced neointimal hyperplasia but resulted in higher rates of uncovered and malapposed stent struts at 13-month follow-up (1.1±2.5% in BMS lesions versus 5.7±7.0% in PES lesions, p<0.0001). While these observations are important to understand differences in stent design, further studies are required to determine the clinical significance of these findings. As yet, no threshold for coverage has been established.

Likewise, OCT was employed to study tissue coverage at follow-up in bioresorbable scaffolds [86–88]. OCT was able to visualise the particular structure of the scaffold struts, the tissue coverage over time as well as the changes in the optical properties of the vascular tissue during the bioresorption process ( Figure 13) ( Figure 14) ( Figure 15). The OCT sub-studies demonstrated differences in the two generations of everolimus-eluting bioresorbable vascular scaffolds at 6-month follow-up as used in the ABSORB Cohort A (1.0 BVS) vs. Cohort B (1.1 BVS) trials. The appearances of the polymeric struts of the 1.1 BVS were preserved in all the patients at 6 months and the strut central core remained unchanged over time. Specifically, the 1.1 BVS did not show late shrinkage at six months with respect to the baseline scaffold area; the 1.0 BVS had higher neointimal growth and large in-device area obstruction than the 1.1 BVS. These changes resulted in a higher OCT luminal loss and angiographic late loss in the 1.0 BVS than in the 1.1 BVS. The overall strut appearance at 6-month follow-up was markedly different between the two generations of BVS, with the absence of optically demonstrable alteration of the polymeric struts of the 1.1 BVS at six months which may reflect differences in the bioresorption state at that point in time. Analysis of the strut distribution patterns between the BVS revision 1.0 (Cohort A) and BVS revision 1.1 (Cohort B) designs revealed that the revision 1.1 BVS design has a different longitudinal strut distribution pattern, indicating that the new design has a reduced maximum circular unsupported cross-sectional area. By contrast, there was no significant difference between the 1.0 BVS and the 1.1 BVS in the number of analysed struts corrected for the length of the scaffold, the number of struts per frame or the maximum inter-strut angle [8989. Guagliumi G, Costa MA, Sirbu V, Musumeci G, Bezerra HG, Suzuki N, Matiashvili A, Lortkipanidze N, Mihalcsik L, Trivisonno A, Valsecchi O, Mintz GS, Dressler O, Parise H, Maehara A, Cristea E, Lansky AJ, Mehran R, Stone GW. Strut coverage and late malapposition with paclitaxel-eluting stents compared with bare metal stents in acute myocardial infarction: Optical coherence tomography substudy of the harmonizing outcomes with revascularization and stents in acute myocardial infarction (HORIZONS-AMI) trial. Circulation. 2011;123:274–81. ].

Assessment of structural details of tissue coverage

OCT also permits the characterisation of neointimal tissue in a qualitative way [2020. Prati F, Zimarino M, Stabile E, Pizzicannella G, Fouad T, Rabozzi R, Filippini A, Pizzicannella J, Cera M, De Caterina R. Does optical coherence tomography identify arterial healing after stenting? An in vivo comparison with histology, in a rabbit carotid model. Heart. 2008;94:217–21. ]. This is a great advantage as such information has not been available in vivo until now. The limited resolution, together with artifacts induced by metallic stent struts, does not allow the characterisation of such details by IVUS. With OCT, neointimal tissue can show a variety of morphologies ranging from homogenous, bright, uniform tissue to optically heterogeneous tissue or eccentric tissue of various thicknesses. Furthermore, structural details within the tissue can be observed such as intimal neovascularisation or a layered appearance [9090. Shouzou Tanimoto; Jiro Aoki; Patrick W Serruys; Evelyn Regar. Paclitaxel-eluting stent restenosis shows three-layer appearance by optical coherence tomography. EuroIntervention. 2006. ], often observed in restenotic regions. Variations in the appearance of strut coverage can be seen within an individual patient, within an individual stent or within stents of different design.

OCT findings, such as dark, signal-poor halos around stent struts, may reflect fibrin deposition and incomplete healing, as described in pathologic and animal experimental series [9191. Van Beusekom HMM, Saia F, Zindler JD, Lemos PA, Hoor SLS Ten, Van Leeuwen MAH, De Feijter PJ, Serruys PW, Van Der Giessen WJ. Drug-eluting stents show delayed healing: Paclitaxel more pronounced than sirolimus. Eur Heart J. 2007;28:974–9. ]. However, there is a paucity of data directly demonstrating the OCT appearance of different components in neointimal tissue as defined by histology. Post-mortem imaging of DES in human coronaries is difficult and might be limited by the fact that the optical tissue properties show variations with temperature and fixation [9292. van der Meer FJ, Faber DJ, Çilesiz I, van Gemert MJC, van Leeuwen TG. Temperature-dependent optical properties of individual vascular wall components measured by optical coherence tomography. J Biomed Opt. 2006;11:041120. ]. Long-term animal OCT observations in DES are scarce.

The neointima can develop atherosclerotic lesions over time, a phenomenon dubbed “neoatherosclerosis”. OCT can visualise these lesions and add to our understanding of the incidence and role of neoatherosclerosis in relation to stent failure. Accelerated neoatherosclerosis has been described in drug-eluting stents [9393. Kang SJ, Mintz GS, Akasaka T, Park DW, Lee JY, Kim WJ, Lee SW, Kim YH, Lee CW, Park SW, Park SJ. Optical coherence tomographic analysis of in-stent neoatherosclerosis after drug-eluting stent implantation. Circulation. 2011;123:2954–63. , 9494. Nakazawa G, Otsuka F, Nakano M, Vorpahl M, Yazdani SK, Ladich E, Kolodgie FD, Finn A V., Virmani R. The pathology of neoatherosclerosis in human coronary implants: Bare-metal and drug-eluting stents. J Am Coll Cardiol. 2011;57:1314–22. ].

Stent strut tissue coverage and thrombosis

Stent thrombosis tended to occur at a yearly rate >0.5% after deployment of first generation DES. However acute and late thrombosis represent a rare finding after positioning of new DES. The mechanism of DES thrombosis is multifactorial with premature discontinuation of dual antiplatelet therapy, stent underexpansion, hypersensitivity (e.g., to the polymer), and lack of endothelial tissue coverage and strut malapposition all being implicated. The results of small observational OCT studies, as described above, are compatible with evidence from animal and human post-mortem series showing that DESs cause impairment in arterial healing, with some suggesting incomplete re-endothelialisation and persistence of fibrin possibly triggering late stent thrombosis [9595. Finn A V., Joner M, Nakazawa G, Kolodgie F, Newell J, John MC, Gold HK, Virmani R. Pathological correlates of late drug-eluting stent thrombosis: Strut coverage as a marker of endothelialization. Circulation. 2007;115:2435–41. , 9696. Finn A V., Nakazawa G, Ladich E, Kolodgie FD, Virmani R. Does Underlying Plaque Morphology Play a Role in Vessel Healing After Drug-Eluting Stent Implantation?**Editorials published in JACC: Cardiovascular Imaging reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Imaging or the American College of Cardiology. JACC Cardiovasc Imaging. 2008;1:485–8. ]. Pathological data in humans suggests that neointimal coverage of stent struts could be used as a surrogate marker of endothelialisation due to the correlation between strut coverage and endothelialisation. However, OCT observations need to be interpreted with caution. OCT is limited by its resolution of 15 μm which is lower than the thickness of an individual layer of endothelial cells. Furthermore, the presence of tissue coverage does not necessarily imply the presence of a functionally intact endothelium [9797. van Beusekom HMM, Serruys PW. Drug-Eluting Stent Endothelium. Presence or Dysfunction. JACC Cardiovasc Interv. 2010;3:76–7. ]. Early experimental stent data showed that endothelial function can vary considerably and can show evidence of damage when subjected to the Evan’s blue dye exclusion test, even in the presence of a well-structured neointimal layer [9898. Van Beusekom HM m., Whelan DM, Hofma SH, Krabbendam SC, Van Hinsbergh VW m., Verdouw PD, Van Der Giessen WJ. Long-term endothelial dysfunction is more pronounced after stenting than after balloon angioplasty in porcine coronary arteries. J Am Coll Cardiol. 1998;32:1109–17. ]. However, OCT is the only imaging modality to date which offers, within the discussed limits, the possibility to understand tissue coverage and neointima formation in DES over time. Clearly, larger stent trials with OCT at different time periods are needed to obtain a representative assessment of the true time course of endothelial stent coverage. FD-OCT is a simple imaging procedure that offers the potential for large-scale, prospective studies, indispensable for addressing vexing clinical questions such as the relationship of drug-eluting stent deployment, vascular healing, the true time course of endothelial stent coverage and late stent thrombosis. This may also better guide the optimal duration of dual antiplatelet therapy which currently remains unclear and rather empiric.

Stent strut tissue coverage and DES restenosis

OCT can be useful in the evaluation of the causes that contribute to restenosis after DES implantation, such as incomplete lesion coverage or gaps between stents.

OCT is able to visualise tissue coverage, including restenotic tissue, in great detail. Neointimal tissue shows great optical variability, most probably reflecting pathophysiology such as incomplete healing. The clinical significance of these findings is currently poorly understood [9090. Shouzou Tanimoto; Jiro Aoki; Patrick W Serruys; Evelyn Regar. Paclitaxel-eluting stent restenosis shows three-layer appearance by optical coherence tomography. EuroIntervention. 2006. , 9999. Gonzalo N, Serruys PW, Okamura T, van Beusekom HM, Garcia-Garcia HM, van Soest G, van der Giessen W, Regar E. Optical coherence tomography patterns of stent restenosis. Am Heart J. 2009;158:284–93. ].

Stent fracture has also been related to restenosis in DES and could be visualised with OCT [100100. Shite J, Matsumoto D, Yokoyama M. Sirolimus-eluting stent fracture with thrombus, visualization by optical coherence tomography. Eur Heart J. 2006;27:1389–1389. ]. Non-uniform distribution of stent struts can affect the drug concentration within the arterial wall and may therefore play a role in restenosis in DES [101101. Suzuki Y, Ikeno F, Yeung AC. Drug-eluting stent strut distribution: A comparison between cypherTM and taxus® by optical coherence tomography. J Invasive Cardiol. 2006;18:111–4. ]. This has been confirmed in preclinical and IVUS studies. OCT allows the assessment of strut distribution in vivo with high accuracy. A study with phantom models showed how the strut distribution of SES and paclitaxel-eluting stents (PES) assessed by OCT were significantly different, suggesting that SES maintained a more regular strut distribution despite expansion [102102. Takao Hasegawa, Junya Ako, Fumiaki Ikeno, Katsuhisa Waseda, Ypriyasu Suzuji, Yasuhiro Honda, Peter J. Fitzgerarld. Comparison of nonuniform strut distribution between two drug-eluting stent platforms - PubMed 2008. https://pubmed.ncbi.nlm. nih. gov/17541122/ (accessed 7 April 2021). ].

Another field of clinical use for OCT might be the assessment of the performance of DES in complex coronary interventions such as bifurcations. Buellesfeld et al [103103. Buellesfeld L, Lim V, Gerckens U, Mueller R, Grube E. Comparative endoluminal visualization of TAXUS crush-stenting at 9 months follow-up by intravascular ultrasound and optical coherence tomography. Z Kardiol. 2005;94:690–4. ] reported the 9-month OCT follow-up in a case of crush stenting with PES. Crush stenting results in three layers of metal in the segment of the main vessel proximal to the stented side branch. There has been concern that this could release a higher dose of drug locally with the potential adverse effect of delayed endothelialisation. In this report, OCT imaging showed the overlapping strut layers in the crushed segment completely covered by tissue. Furthermore, OCT allowed clear visualisation of the struts located in the ostium, demonstrating a non-uniform distribution and different patterns of tissue coverage. By contrast, a sub-study of the ODESSA trial, specifically designed to assess drug-eluting stent overlap, revealed a more complex interaction between strut overlap, underlying plaque and tissue coverage [104104. Tahara S, Bezerra HG, Sirbu V, Kyono H, Musumeci G, Rosenthal N, Guagliumi G, Costa MA. Angiographic, IVUS and OCT evaluation of the long-term impact of coronary disease severity at the site of overlapping drug-eluting and bare metal stents: A substudy of the ODESSA trial. Heart. 2010;96:1574–8. ]. ODESSA was a prospective, randomised controlled trial designed to evaluate healing of overlapping stents. Overlapping drug-eluting stents in normal-appearing coronary segments showed a higher incidence of uncovered or malapposed struts, while restenosis occurred exclusively in overlapping stents at high-grade stenosis. Any uncovered or malapposed struts occurred more often in overlapping drug-eluting stents at low-grade stenosis regions than at high-grade stenosis regions (59.4% vs. 32.6%, p=0.03).

Guidance of stent implantation in complex lesions

OCT seems particularly efficient in complex interventions, including treatment of left main (LM), ostial left anterior descending or left circumflex artery lesions or bifurcations, as well as in all cases of angiographically ambiguous lesions and in stent failures.

As a technical drawback plaque located at the very ostium of the left or right coronaries cannot be accurately addressed by OCT as it is difficult to clear the artery from blood during a non-selective guide catheter position, required for the visualisation of the ostium.

Despite that recent studies addressed the role of OCT guidance for LM lesions. A systematic OCT guidance during LM PCI enabled detection of acute stent underexpansion (7.2%) and malapposition (10.9%). and led to a reduced late follow-up lumen loss [105105. Cortese B, Burzotta F, Alfonso F, Pellegrini D, Trani C, Aurigemma C, Rivero F, Antuña P, Orrego PS, Prati F. Role of optical coherence tomography for distal left main stem angioplasty. Catheter Cardiovasc Interv. 2020;96:755–61. ].

The LEMON study proved the effectiveness of OCT-guided PCI for middle or distal LM according to a pre-specified protocol. The main study end-point (residual angiographic stenosis <50% + TIMI 3 flow in all branches + adequate OCT stent expansion) was achieved in 86% of cases and the one-year survival free from major clinical adverse events was observed in 98.6% of cases [106106. Amabile N, Rangé G, Souteyrand G, Godin M, Boussaada MM, Meneveau N, Cayla G, Casassus F, Lefèvre T, Hakim R, Bagdadi I, Motreff P, Caussin C. Optical Coherence Tomography to Guide Percutaneous Coronary Intervention of the Left Main Coronary Artery: the LEMON study. EuroIntervention. 2020. ].

Bifurcations represent a complex subset of coronary lesions with higher rates of stent failure, with no general consensus about the optimal treatment strategy for these lesions. DES has reduced the incidence of restenosis in coronary bifurcations, but concerns remain about the risk of stent thrombosis. OCT can visualise malapposition (a common phenomenon in the ostium of the side branch), as well as overlapping struts in the main vessel when a two-stent approach is employed. Both phenomena can delay endothelialisation and potentially contribute to the higher risk of stent thrombosis in bifurcations. Further, OCT can characterise the atherosclerotic plaque in bifurcations, another important factor which could potentially contribute to the higher risk of stent failure in these lesions [107107. Gonzalo N, Garcia-Garcia HM, Regar E, Barlis P, Wentzel J, Onuma Y, Ligthart J, Serruys PW. In Vivo Assessment of High-Risk Coronary Plaques at Bifurcations With Combined Intravascular Ultrasound and Optical Coherence Tomography. JACC Cardiovasc Imaging. 2009;2:473–82. ].

Chronic total occlusions (CTO) represent a subgroup of lesions with a lower procedural success rate, and their treatment remains challenging. In this complex scenario, OCT can provide useful additional information which may potentially be useful to guide the procedure safely. Preliminary ex vivo experiences with forward-looking OCT systems which use multiple longitudinal OCT slices to generate cross-sectional images of occluded arteries have been reported [108108. Munce NR, Yang VXD, Standish BA, Qiang B, Butany J, Courtney BK, Graham JJ, Dick AJ, Strauss BH, Wright GA, Vitkin IA. Ex vivo imaging of chronic total occlusions using forward-looking optical coherence tomography. Lasers Surg Med. 2007;39:28–35. ]. OCT was able to differentiate between occluded lumen and different layers of the arterial wall, and showed potential to identify micro-channels ( Figure 16 ). This information could be used to direct the guidewire in order to cross the cap of the occlusion. Once the guidewire has been advanced into the lesion, OCT can provide useful information about the composition of the plaque causing the occlusion. Further, when a dissection occurs, OCT can be used to differentiate true from false lumen [109109. Schultz C, van der Ent M, Serruys PW, Regar E. Optical Coherence Tomography to Guide Treatment of Chronic Occlusions? JACC Cardiovasc Interv. 2009;2:366–7. ]. Future developments such as OCT-based Doppler techniques could, potentially, be used to assess the presence of micro-channels [110110. Munce NR, Wright GA, Mariampillai A, Standish BA, Leung MKK, Tan L, Lee K, Courtney BK, Teitelbaum AA, Strauss BH, Vitkin IA, Yang VXD. Doppler optical coherence tomography for interventional cardiovascular guidance: in vivo feasibility and forward-viewing probe flow phantom demonstration. J Biomed Opt. 2010;15:011103. ].

Guidance of coronary interventions in ambiguous cases and ACS

Ambiguous lesions

Suboptimal angiographic lesion visualisation may happen in the presence of intermediate lesions of uncertain severity, very short lesions, pre- or post-aneurysmal lesions, ostial or left main stenoses, disease at branching sites, sites with focal spasm, or angiographically hazy lesions, often caused by the presence of thrombus or calcifications. The use of OCT is particularly worthwhile in these cases as OCT provides an accurate visualisation of the luminal structure and dimensions, because of its excellent delineation of the lumen-wall interface.

OCT proved to be useful in presence of intermediate angiographic narrowing. The randomized FORZA (FFR or OCT Guidance to Revascularize Intermediate Coronary Stenosis Using Angioplasty) trial [111111. Burzotta F, Leone AM, Aurigemma C, Zambrano A, Zimbardo G, Arioti M, Vergallo R, De Maria GL, Cerracchio E, Romagnoli E, Trani C, Crea F. Fractional Flow Reserve or Optical Coherence Tomography to Guide Management of Angiographically Intermediate Coronary Stenosis: A Single-Center Trial. JACC Cardiovasc Interv. 2020;13:49–58. ], compared optical coherence tomographic and FFR guidance in patients with angiographically intermediate coronary lesions. Patients allocated to the FFR arm experienced less often FU MACE or significant angina [111111. Burzotta F, Leone AM, Aurigemma C, Zambrano A, Zimbardo G, Arioti M, Vergallo R, De Maria GL, Cerracchio E, Romagnoli E, Trani C, Crea F. Fractional Flow Reserve or Optical Coherence Tomography to Guide Management of Angiographically Intermediate Coronary Stenosis: A Single-Center Trial. JACC Cardiovasc Interv. 2020;13:49–58. ]. The study is in support of a comprehensive plaque imaging strategy, capable of exploring multiple features of vulnerability, including FCT. This approach seems to have more potential than isolated functional assessment to guide prophylactic percutaneous coronary interventions to prevent hard cardiac event [112112. Alfonso F, Antuña P, Prati F. Value of Optical Coherence Tomography in Angiographically Intermediate Coronary Lesions. JACC Cardiovasc Interv. 2020;13:268–9. ].

Patients with ACS and unclear culprit

The management of acute coronary syndrome relies on rapid treatment of the culprit vessel. The culprit vessel is indicated by the nature of the ECG changes or by the finding of a thrombotic, hazy lesion by angiography. However, the identification of the culprit lesion can be challenging in individual patients, especially in the presence of multi vessels disease. Similarly, in 15% of the patients undergoing primary PCI, angiography shows a patent infarct-related vessel with TIMI 3 flow [113113. Van De Werf F, Bax J, Betriu A, Blomstrom-Lundqvist C, Crea F, Falk V, Filippatos G, Fox K, Huber K, Kastrati A, Rosengren A, Steg PG, Tubaro M, Verheugt F, Weidinger F, Weis M, Vahanian A, Camm J, De Caterina R, Dean V, Dickstein K, Funck-Brentano C, Hellemans I, Kristensen SD, McGregor K, Sechtem U, Silber S, Tendera M, Widimsky P, Zamorano JL, Aguirre F V., Al-Attar N, Alegria E, Andreotti F, Benzer W, Breithardt O, Danchin N, Di Mario C, Dudek D, Gulba D, Halvorsen S, Kaufmann P, Kornowski R, Lip GYH, Rutten F. Management of acute myocardial infarction in patients presenting with persistent ST-segment elevation. Eur Heart J. 2008;29:2909–45. ]. OCT can provide accurate information on the superficial composition of the plaque, can identify ruptured plaques and, most importantly, can reveal thrombosed lesions, and thus identify the culprit lesion, namely the most likely pathophysiologic substrate for the acute coronary syndrome.

In patients with coronary thrombosis, distinct OCT morphologies can be appreciated:

1) massive thrombosis or any amount of red thrombus which does not permit assessment of vessel and plaque morphology;

2) thrombosis with signs of plaque rupture as visualised by a dissection flap representing the remnant of a fibrous cap;

3) thrombosis with signs of ulceration underneath; or

4) thrombosis with apparently normal endothelial lining underneath, which is likely to be indicative of erosion.

Acute plaque ulceration or rupture can be detected by OCT as a ruptured fibrous cap which connects the lumen with the necrotic core. These ulcerated or ruptured plaques may occur with or without a superimposed thrombus. When signs of ulceration are present without evidence of thrombosis, the lesion cannot be defined as a “culprit” with certainty, unless clinical criteria provide some evidence that the lesion is responsible for the acute events.

Detection of erosion versus ulceration

Niccoli et al [114114. Niccoli G, Montone RA, Di Vito L, Gramegna M, Refaat H, Scalone G, Leone AM, Trani C, Burzotta F, Porto I, Aurigemma C, Prati F, Crea F. Plaque rupture and intact fibrous cap assessed by optical coherence tomography portend different outcomes in patients with acute coronary syndrome. Eur Heart J. 2015;36:1377–84. ] studied the mechanism of ACS (plaque rupture vs. intact fibrous cap) in 139 consecutive ACS patients. Major adverse cardiac events occurred more frequently in patients with plaque rupture (39.0 vs. 14.0%, p=0.001), that was an independent predictor of outcome at multivariable analysis.

The ability of OCT identify ACS culprit lesions with intact fibrous cap can be used to select lesions to be treated with a less aggressive approach, without balloon dilatation or stenting. In a first pilot study it was shown that such strategy can be accomplished with a good clinical outcome at 2 years [115115. Prati F, Uemura S, Souteyrand G, Virmani R, Motreff P, Di Vito L, Biondi-Zoccai G, Halperin J, Fuster V, Ozaki Y, Narula J. OCT-based diagnosis and management of STEMI associated with intact fibrous cap. JACC Cardiovasc Imaging. 2013;6:283–7. ]. These preliminary data were confirmed later on by two studies [116116. Souteyrand G, Amabile N, Combaret N, Hammas S, Prati F, Berry C, Pereira B, Lusson JR, Caussin C, Motreff P. Invasive management without stents in selected acute coronary syndrome patients with a large thrombus burden: A prospective study of optical coherence tomography guided treatment decisions. EuroIntervention. 2015;11:895–904. , 117117. Jia H, Dai J, Hou J, Xing L, Ma L, Liu H, Xu M, Yao Y, Hu S, Yamamoto E, Lee H, Zhang S, Yu B, Jang I-K. Effective anti-thrombotic therapy without stenting: intravascular optical coherence tomography-based management in plaque erosion (the EROSION study). Eur Heart J. 2016;38:ehw381. ].

The Erosion study [117117. Jia H, Dai J, Hou J, Xing L, Ma L, Liu H, Xu M, Yao Y, Hu S, Yamamoto E, Lee H, Zhang S, Yu B, Jang I-K. Effective anti-thrombotic therapy without stenting: intravascular optical coherence tomography-based management in plaque erosion (the EROSION study). Eur Heart J. 2016;38:ehw381. ] showed that a further decrease in thrombus volume occurs between 1-month and 1-year follow-up using a strategy of stenting deferral. These finding may have clinical implications, but more robust data are needed to confirm these preliminary studies.

ASSESSMENT OF STENT FAILURE

The causes of DES failure are poorly understood. In the catheterisation laboratory, OCT can be very useful in the evaluation of the causes for stent failure in any given patient and can help guide treatment decisions. This is of note, as potential reasons for stent failure are manifold. OCT is able to differentiate mechanical stent failure, such as incomplete stent expansion or stent fracture, from impaired healing such as absence of strut coverage, absence of homogenous coverage or (late) strut malapposition frequently associated with inflammation and hypersensitivity reaction ( Figure 19 ).

While OCT offers a number of potential clinical applications, it can be challenging to consolidate the information gained by OCT with the angiogram, and especially to ensure correct spatial orientation. This is true for all angiographically silent lesions, since this phenomenon might be a consequence of vessel overlap, foreshortening or the inability to visualise a complex three-dimensional structure correctly in a two-dimensional image. Often, operators use side branches, as observed in both imaging modalities, as landmarks. This, however, can be challenging, as the side branch ostium is often not clearly visible by angiography. In addition, the assumed caliber of a particular side branch can be underestimated.

Currently, a number of technical solutions to this problem are being developed, including the use of pulsed fluoroscopy to track the imaging catheter in real time (Siemens Medical prototype, Erlangen, Germany) or the software-enabled synchronisation of three-dimensional angiography with OCT pullback (Medis medical imaging systems bv prototype, Leiden, The Netherlands) ( Figure 20). The ultimate goal is an on-line co-registration of the invasive imaging modality with the coronary angiogram, allowing the operator to scroll through a synchronised dataset. The operator should be able to see the corresponding information of the complementary imaging modality just by pointing at any region of interest either on the angiogram or on the OCT.

Another approach which could overcome limitations of spatial orientation and orientation with respect to angiography is the three- dimensional (3D) reconstruction of the OCT dataset. Fourier domain OCT is particularly well-suited for 3D rendering as the high frame rate allows for dense sampling and the fast pullback limits motion artefacts as the complete pullback is acquired in a few cardiac cycles ( Figure 21). The preliminary experience with 3D reconstruction of Fourier domain datasets demonstrates that this data display format can facilitate the understanding of complex anatomy [118118. Okamura T, Onuma Y, García-García HM, Regar E, Wykrzykowska JJ, Koolen J, Thuesen L, Windecker S, Whitbourn R, McClean DR, Ormiston JA, Serruys PW. 3-dimensional optical coherence tomography assessment of jailed side branches by bioresorbable vascular scaffolds: A proposal for classification. JACC Cardiovasc Interv. 2010;3:836–44. , 119119. Farooq V, Serruys PW, Heo JH, Gogas BD, Okamura T, Gomez-Lara J, Brugaletta S, Garca-Garca HM, Van Geuns RJ. New insights into the coronary artery bifurcation: Hypothesis-generating concepts utilizing 3-dimensional optical frequency domain imaging. JACC Cardiovasc Interv. 2011;4:921–31. ]. However, today there is no standard for 3D rendering available, covering aspects such as cut planes, calibration and quantification.

Safety

The applied energies in intravascular OCT are relatively low (output power in the range of 5.0-8.0 mW) and are not considered to cause functional or structural damage to the tissue. Therefore, safety issues seem mainly dependent on the need for blood displacement for image acquisition. One recently published study evaluated the safety and feasibility of time domain OCT in 76 patients in the clinical setting using the occlusive technique. Vessel occlusion time was 48.3 ±13.5 seconds. The most frequent complications were transient events, such as chest discomfort, bradycardia or tachycardia, and ST-T changes on the electrocardiogram, all of which resolved immediately after the procedure. There were no major complications, including myocardial infarction, emergency revascularisation, or death. The authors reported that acute procedural complications such as acute vessel occlusion, dissection, thrombus formation, embolism, or vasospasm along the procedure-related artery, were not observed [120120. Yamaguchi T, Terashima M, Akasaka T, Hayashi T, Mizuno K, Muramatsu T, Nakamura M, Nakamura S, Saito S, Takano M, Takayama T, Yoshikawa J, Suzuki T. Safety and Feasibility of an Intravascular Optical Coherence Tomography Image Wire System in the Clinical Setting. Am J Cardiol. 2008;101:562–7. ]. The introduction of the non-occlusive technique in clinical practice has led to an important reduction in the procedural time and in the incidence of chest pain and ECG changes during image acquisition [121121. Barlis P, Gonzalo N, Di Mario C, Prati F, Buellesfeld L, Rieber J, Dalby MC, Ferrante G, Cera M, Grube E, Serruys PW, Regar E. A multicentre evaluation of the safety of intracoronary optical coherence tomography. EuroIntervention. 2009;5:90–5. ]. These side effects are expected to be reduced further by the introduction of Fourier domain OCT. In Fourier domain OCT, high pullback speeds of up to 40 mm/sec allow data acquisition of a long coronary segment within a few seconds and without introducing relevant ischaemia. Imola et al [122122. Imola F, Mallus MT, Ramazzotti V, Manzoli A, Pappalardo A, Di Giorgio A, Albertucci M, Prati F. Safety and feasibility of frequency domain optical coherence tomography to guide decision making in percutaneous coronary intervention. EuroIntervention. 2010;6:575–81. ] addressed the safety of FD-OCT in 114 OCT acquisitions, performed in 90 patients. In 99% of cases the procedure was successful. No patients suffered renal damage and no major complications were recorded. Only one patient had a transient vessel spasm which was resolved with intracoronary administration of nitrates. During FD-OCT image acquisition no ischaemic ECG changes occurred. Ventricular ectopic beats were found in only 3 patients while other major arrhythmias (ventricular tachycardia or fibrillation) were not observed.

Limitations

Generally, the main limitations of intracoronary OCT as compared to intravascular ultrasound consist, firstly, in the fact that light cannot penetrate blood. Thus, OCT requires clearing of the artery from blood as an additional step during the imaging procedure. Secondly, the high resolution of OCT is at the expense of penetration depth. However, additional issues can influence intracoronary OCT quality and interpretation in clinical intracoronary OCT application. The most important practical limitations and artifacts are summarised below.

IMAGING ARTEFACTS

Vessel tortuosity

Within the human body, peripheral arteries (the vascular access sites) as well as the coronary arteries (imaging target) are more or less tortuous structures. This requires high flexibility and steerability from the imaging device. This is not trivial, given the fact that light transmission requires easily breakable fiber optics. There is also a consequence on the image geometry. In the majority of cases, the imaging device will not be in a coaxial and central position within the target artery, which may affect penetration depth, brightness and resolution of the imaged structure.

Coronary calibre

Coronary arteries represent relatively small structures for in vivo imaging; they are, however, relatively big structures compared to experimental OCT applications which often focus on much smaller sample volumes. Epicardial arteries have a maximal lumen diameter of approximately 4-5 mm in their proximal portion and taper distally. Typically, arteries with a lumen diameter down to approximately 1.0 mm are considered clinically relevant and accessible to standard imaging equipment, such as coronary angiography and intravascular ultrasound. Ideally, the penetration depth of intravascular OCT should be able to cover the complete caliber range.

Motion during the cardiac cycle

Epicardial arteries experience significant three-dimensional motion during heart cycle. This affects the vascular dimensions (with a variability of lumen area of approximately 8% between systole and diastole [123123. Weissman NJ, Palacios IF, Weyman AE. Dynamic expansion of the coronary arteries: Implications for intravascular ultrasound measurements. Am Heart J. 1995;130:46–51. ] and the OCT device position within the artery (transversal and longitudinal motion), typically resulting in a saw-tooth appearance of the longitudinal data reconstruction. Fourier domain OCT is far less susceptible to the latter motion artifact, simply due to the fact that the complete pullback is being acquired within 2 or 3 heart beats, whereas, in a time domain OCT, a pullback might include 20-30 heart beats ( Figure 22) ( Figure 23).

STENT-RELATED IMAGING ARTIFACTS

Shadowing behind stent struts

The light source used for OCT is unable to penetrate metal resulting in dorsal shadowing behind the stent strut. When interpreting OCT images, the thickness of the whole stent strut (including metal and polymer) must be taken into consideration rather than only the visible endoluminal strut surface.

Shadowing also limits the interpretation of structures behind the stent strut and this remains a limitation of OCT, particularly also given its poor tissue penetration (< 1.5 mm). Furthermore, the OCT imaging plane rarely intersects the stent struts perpendicularly, thereby resulting in shadows much larger than the actual width of the stent strut.

Bright reflections saturating an entire line (spikes)

If the imaging beam hits a strut perpendicularly, it reflects a very large fraction of the beam back towards the catheter. This strong signal may saturate the detector registering the interferogram, producing a readily recognisable artifact of bright radial streaks centered on the struts.

Multiple reflections (stent – catheter – stent)

In a similar geometry, near-specular reflection, light may bounce back between the catheter and strut more than once. The optical catheter itself reflects part of the received light back into the tissue. Strong reflectors, such as struts, may produce an appreciable signal in the second reflection. The optical path length of light in the secondary reflections’ doubles that of the primary feature. Hence, a double reflection will show up as an apparent second strut appearing behind the first at twice the distance from the catheter.

IMAGE INTERPRETATION CAVEATS

Plaque geometry and burden

Atherosclerotic coronary arteries contain a highly variable degree of plaque deposition within the artery wall. Atherosclerotic plaque can form a concentric ring encroaching on the lumen but will be eccentric with a normal vessel wall sector or with relatively big differences in vessel wall thickness in the majority of cases [124124. Freudenberg H, Lichtlen P R. [The normal wall segment in coronary stenoses--a postmortal study (author’s transl)] - PubMed. Z Kardiol. 1981. ]. Intravascular OCT is unable to penetrate advanced, thick plaque, irrespective of the position of the OCT imaging device within the lumen. This leads to a major limitation of OCT, namely the inability to measure plaque burden in advanced atherosclerosis. This drawback may have some clinical implications, especially in diffuse disease where IVUS has been used in the past to assess the longitudinal extension of plaque burden and to select the most appropriate stent length. The most established criterion to identify reference segments is a plaque burden less than 40% by IVUS [125125. Mudra H, Regar E, Klauss V, Werner F, Henneke KH, Sbarouni E, Theisen K. Serial follow-up after optimized ultrasound-guided deployment of Palmaz- Schatz stents: In-stent neointimal proliferation without significant reference segment response. Circulation. 1997;95:363–70. ]. This definition originates from the IVUS finding that a plaque burden greater than 40% at stent margin represents a risk factor for late restenosis and thrombosis.

A possible approach of OCT guidance may be the identification of the lumen contour, without attempting to measure the plaque burden, based on the concept that assessment of luminal reduction and not the increase in plaque dimension can cause flow impairment. These concepts are further corroborated by the recent finding from the FAME study, highlighting the link between physiologic assessment of lesion severity by means of fractional flow reserve and patient clinical outcome [126126. Tonino PAL, De Bruyne B, Pijls NHJ, Siebert U, Ikeno F, van `t Veer M, Klauss V, Manoharan G, Engstrøm T, Oldroyd KG, Ver Lee PN, MacCarthy PA, Fearon WF. Fractional Flow Reserve versus Angiography for Guiding Percutaneous Coronary Intervention. N Engl J Med. 2009;360:213–24. ].

Plaque composition

The limited penetration depth into the vessel wall can reduce the sensitivity of OCT for different plaque components. An ex vivo comparison with histology suggested that even experienced observers could have difficulties differentiating lipid and calcified tissue by visual evaluation of OCT images. The misclassifications between lipid pools and calcium deposits described in the study were related to limitation of the technology, such as the limited penetration or the presence of artifacts but also to the heterogeneity of the plaque components [2525. Gabriele A, Marco V, Gatto L, Paoletti G, Di Vito L, Castriota F, Romagnoli E, Ricciardi A, Prati F. Reproducibility of the Carpet View system: a novel technical solution for display and off line analysis of OCT images. Int J Cardiovasc Imaging. 2014;30:1225–33. ]. Calcium deposits as well as lipid-rich tissues appear signal- poor by OCT. These two tissue types can be discriminated by the tissue borders: calcium typically shows very sharp, well-delineated borders, whereas lipid shows poorly defined borders with diffuse transition to the surrounding tissue.

Therefore, new methods for OCT image analysis are being developed in centers around the world to extract anatomical and compositional tissue properties in a more objective, user-independent way [127127. Van Der Meer FJ, Faber DJ, Perrée J, Pasterkamp G, Baraznji Sassoon D, Van Leeuwen TG. Quantitative optical coherence tomography of arterial wall components. Lasers Med Sci. 2005;20:45–51. , 128128. Van Der Meer FJ, Faber DJ, Sassoon DMB, Aalders MC, Pasterkamp G, Van Leeuwen TG. Localized measurement of optical attenuation coefficients of atherosclerotic plaque constituents by quantitative optical coherence tomography. IEEE Trans Med Imaging. 2005;24:1369–76. , 129129. Xu C, Schmitt JM, Carlier SG, Virmani R. Characterization of atherosclerosis plaques by measuring both backscattering and attenuation coefficients in optical coherence tomography. J Biomed Opt. 2008;13:034003. ]. Recently, Faber et al have demonstrated in vitro that the optical attenuation coefficient (μt) is principally a useful parameter to distinguish different tissue types when using an OCT microscope. van Soest et al have confirmed that the optical attenuation coefficient (μt) can distinguish different atherosclerotic tissue types when applied to intracoronary OCT: necrotic core and macrophage infiltration exhibit strong attenuation, μt ≥10 mm–1, while calcific and fibrous tissue have a lower μt ≈ 2-5 mm–1 [130130. Van Soest G, Goderie TPM, Gonzalo N, Koljenović S, Van Leenders GLJH, Regar E, Serruys PW, Van Der Steen AFW. Imaging atherosclerotic plaque composition with intracoronary optical coherence tomography. Netherlands Hear J. 2009;17:448–50. ]. Likewise, three-dimensional reconstructions, including tissue characterisation employing attenuation coefficient but also other parameters, have been described with the second-generation FD-OCT systems [131131. Tearney GJ, Waxman S, Shishkov M, Vakoc BJ, Suter MJ, Freilich MI, Desjardins AE, Oh WY, Bartlett LA, Rosenberg M, Bouma BE. Three-Dimensional Coronary Artery Microscopy by Intracoronary Optical Frequency Domain Imaging. JACC Cardiovasc Imaging. 2008;1:752–61. ].

Conclusion

OCT has the ability to characterise the structure and extent of coronary artery disease in unprecedented detail. OCT is now the widely accepted gold standard for the assessment of coronary stents. It also represents an established method to characterize plaque before intervention and guide stent deployment. Furthermore, with its unique ability to characterize the superficial plaque components, OCT established itself as the ideal method to study MINOCA lesions, and more recently has been utilised as an innovative invasive solution to predict plaque instability.

Personal perspective – Francesco Prati

Since the introduction of the former time domain technique OCT has come a long way. In 2008, the introduction of the second generation, Fourier domain OCT enabled a paradigm shift: this remarkable innovation transformed OCT from a niche technology applied by experts in selected patients to a robust, user-friendly and reliable clinical research modality. Fourier domain OCT, with its extremely fast data acquisition, kept its promise and provided outstanding image quality, ease of use and safety in a variety of clinical studies.

In 2010, intracoronary OCT became the widely accepted gold standard for the assessment of coronary stents. Soon after prospective and retrospective registries set up OCT criteria of optimal stent deployment and more recently randomized trial confirmed the clinical utility of an OCT guided approach. At the same time, with its unique ability to characterize the superficial plaque components, OCT established itself as the ideal method to study MINOCA lesions and more recently has emerged as an innovative invasive solution to predict plaque instability.

Future applications will include the development of multimodality imaging catheters providing a comprehensive tissue characterisation. In the next future OCT will also provide operator with functional information to assess, e.g., the haemodynamic relevance of stenoses in patients presenting with stable angina.

While the excellent resolution and the high contrast between lumen and vessel wall allow for easy image interpretation and a remarkably steep learning curve, interpretation is still observer-dependent and visual assessment of grey scales might not be sensitive and specific enough to exploit fully the information which comes with the OCT signal. Promising concepts for quantitative tissue characterisation might further improve the diagnostic capabilities in the future. Finally, OCT offers an incredible richness of data within one single pullback in the blink of an eye. The challenge here is clearly to handle the amount of information, to establish guidelines for image display, interpretation and analysis (in order to provide the users with a framework), and to ensure that knowledge gain in different clinical scenarios all over the world can be shared and used to improve our clinical practice.

Online data supplement

MOVING IMAGE 1
“090793 OCT acute post stent”: OCT (St. Jude/LightLab Imaging) immediately after coronary stent implantation. Strut malapposition as well as tissue prolapse can be observed.

MOVING IMAGE 2
“Animation of C7 deployment”: schematic (courtesy of St. Jude/LightLab Imaging) illustrating the practical application of Fourier domain OCT in the cath lab. A guidewire is introduced into the coronary, the OCT imaging catheter is advanced distally to the region of interest and then withdrawn during simultaneous flush delivery through the guide catheter.

MOVING IMAGE 3
“C7 pullback real time”: example of an intracoronary Fourier domain OCT pullback (St. Jude/LightLab Imaging). The pullback speed is 20 mm/sec. Therefore, the pullback does not cause ischaemia and shows few motion artifacts.

MOVING IMAGE 4
“NCLCx OCT fuo post stent”: OCT (St. Jude/LightLab Imaging) at long-term after coronary stent implantation. Note the relatively thin tissue coverage and bifurcation region. The stent struts located at the side branch ostium are clearly visible.

MOVING IMAGE 5
“St. Jude C7XR” is a self-explanatory video on the OCT catheter with voice-over.