(/eurointervention/textbook/pcr-textbook/table-of-contents/)

PART II CHAPTER 12

OPTICAL COHERENCE TOMOGRAPHY

Evelyn Regar, Francesco Prati

SUMMARY
Optical coherence tomography (OCT) is a light-based imaging modality which shows tremen-
dous potential in the setting of coronary imaging. Compared to intravascular ultrasound (IVUS),
OCT (optical coherence tomography) has a ten-fold higher image resolution. OCT (optical coher-
ence tomography) has the ability to characterise the structure and extent of coronary artery dis-
ease in unprecedented detail as the various components of atherosclerotic plaques have differ-
ent optical properties. Typically, calcified, fibrous and lipid-rich plaque components can be dis-
tinguished, 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 (acute coronary syndrome) and STEMI (ST-elevation myocardial infarction) in order to
improve our understanding of the pathophysiology and progression of atherosclerosis. Like-
wise, OCT (optical coherence tomography) allows the detailed analysis of coronary stents, their
interaction with the vessel wall and their long-term outcome. In daily clinical practices, OCT (op-
tical coherence tomography) may be efficient in complex interventions. Preliminary data indi-
cates that OCT (optical coherence tomography) 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 (optical coherence tomography) as an
instrumental tool to ameliorate stent deployment and improve clinical outcome after coronary

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 interventions. As such, OCT (optical coherence tomography) may emerge, along with its undis-
puted 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 tremen-
dous potential in the coronary circulation. Compared to intravascular ultrasound (IVUS), OCT
(optical coherence tomography) has a ten-fold higher image resolution given the use of near in-
frared light rather than sound in the megahertz range. This advantage has seen OCT (optical co-
herence tomography) 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 (optical coherence tomography) 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 measure-
ments 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 scan-
ning to OCDR graphs one could create an image which would be much easier for a human to in-
terpret than a set of OCDR waveforms. All that was required was to add a translation stage and
a software package to convert a data matrix into an image. The central problem in making to-
mographic 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 interfer-
ometer 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 (optical coherence tomography) technology has generated over 5,000 arti-
cles in academic journals. The first manuscript from MIT (Massachusetts Institute of Technolo-
gy), published in 1991, describes the basic concept of an OCT (optical coherence tomography)
imaging system and discusses its possible applications in both retinal and arterial imaging [1].
In 1996, a second manuscript was published, which dealt specifically with the possibility of
imaging coronary arteries with an OCT (optical coherence tomography) device [2]. It became
clear early on that OCT (optical coherence tomography) could contribute to the diagnosis of oc-
ular 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 (Massachusetts Institute of Technology) 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

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 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 (optical co-
herence tomography) research programmes throughout the United States.

Compared to an OCT (optical coherence tomography) microscope, used in ophthalmology and

in most experimental settings, the application of OCT (optical coherence tomography) within
the human vascular system, particularly within coronary arteries, represents a specific chal-
lenge, as a number of principal problems need to be overcome [3]. Therefore, the intracoronary
application of OCT (optical coherence tomography) 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 devel-
opment from “time domain OCT” to “Fourier domain OCT” has the potential to change dramati-
cally the research landscape allowing for a widespread clinical intracoronary application in re-
search and patient care. The chapter will discuss the technical principles of intracoronary OCT
(optical coherence tomography), summarise the preclinical and clinical research, discuss poten-
tial clinical applications and explain the practical performance in the catheterisation laboratory.
Differences in time domain versus Fourier domain OCT (optical coherence tomography) will be
pointed out when relevant.

! FOCUS BOX 1
Introduction
Optical coherence tomography (OCT) is a light-based imaging modality offering
a 10 times higher image resolution (axial resolution 15 μm) compared to in-
travascular ultrasound (IVUS) by using near infrared light with a centre wave-
length of 1,300 nm rather than sound in the megahertz range
This high resolution, however, is at the expense of a reduced penetration depth
into tissue and the need transiently to create a blood-free field of view during
image acquisition

Protoypic “time domain OCT” has been replaced by “Fourier domain OCT” de-
vices

Image acquisition only requires a couple of seconds (typically 3 sec for a pull-
back through an artery segment of 60 mm (millimetre) length), thus alleviating
imaging-related ischaemia seen with time-domain OCT

PHYSICAL PRINCIPLES
The principle of OCT (optical coherence tomography) 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 (optical coherence tomography) 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 ( (/eurointervention/text-
book/media/90_951_figure%201.png)" Figure 1 (90_951_figure 1.png) ); however, this is at the
expense of a reduced penetration depth and the need to create a blood-free environment for

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 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 (optical coherence tomography) 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 ultra-
sound. The resulting resolution depends primarily on the ratio of these parameters, and is one
order of magnitude larger than that of IVUS (intravascular ultrasound); the axial resolution of
OCT (optical coherence tomography) is about 15 μm. The lateral resolution is mainly deter-
mined by the imaging optics in the catheter and is approximately 25 μm. The imaging depth of
approximately 1.0-1.5 mm (millimetre) within the coronary artery wall is limited by the attenua-
tion 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 [4]. The interfer-
ometer splits the light source into two “arms” – a reference arm and a sample arm, which is di-
rected 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 [5, 6].

TIME DOMAIN OCT

In time domain OCT (optical coherence tomography), the length of the reference arm is
scanned over a distance of, typically, a few millimeters, 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
neighboring lines (St. Jude/LightLab Imaging Inc., Westford, MA, USA).

Time domain OCT (optical coherence tomography) has been replaced by the new generation of
OCT (optical coherence tomography) systems: the Fourier domain OCT (optical coherence to-
mography).

FOURIER DOMAIN OCT

Fourier domain OCT (optical coherence tomography) operate in the frequency (rather than
time) domain, also called Fourier domain ( (/eurointervention/textbook/media/90_952_fig-
ure%202.png)" Figure 2 (90_952_figure 2.png) ). 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 [7,
8]. 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 (optical coherence tomography) systems.
From the signal received in one wavelength sweep, the depth profile can be constructed by the

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 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 (optical coherence to-
mography) system.

The scan speed, or line rate, in a time domain OCT (optical coherence tomography) system is
limited by the achievable mechanical scan speed of the reference arm mirror, and by the sensi-
tivity of the signal detection. The source wavelength in Fourier domain OCT (optical coherence
tomography) can be swept at a much higher rate than the position scan of the reference arm
mirror in a time domain OCT (optical coherence tomography) system. In addition, Fourier do-
main OCT (optical coherence tomography) has a higher sensitivity than time domain OCT (opti-
cal coherence tomography) at large line rates and scan depths [9, 10, 11]. 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 (optical coherence tomography) system, the wavelength range of the sweep deter-
mines the resolution of the image, while the imaging depth is inversely related to the instanta-
neous spectral width of the source.

The increased sensitivity of Fourier domain OCT (optical coherence tomography) also allows for
larger imaging depths. The attenuation of light by the tissue is the same for time domain and
for Fourier domain OCT (optical coherence tomography), but the lower noise of the latter
makes it possible to discern weaker signals which would be indistinguishable from the back-
ground in time domain OCT (optical coherence tomography). The depth range from which use-
ful anatomical information can be extracted is extended by a factor of approximately 3 [12].
Clinically, this advantage enables the assessment of coronary microstructures, well beyond the
arterial-lumen border.

Fourier domain OCT (optical coherence tomography) systems produce images much faster than
standard video-rate, so recorded data has to be replayed for inspection by the operator. Cur-
rently, OCT (optical coherence tomography) systems scan 200-500 angles per revolution (frame),
and 5-10 images per mm (millimetre) 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 (optical coherence tomography) data. The high scan speeds have
been employed for real-time volumetric imaging of dynamic phenomena including fast pull-
backs for intracoronary imaging with minimal ischaemia, and retinal scans with minimal motion
artifacts [13]. Imaging of dynamic phenomena in time, or rather removing motion artifacts, are
the prime applications of high-speed OCT (optical coherence tomography). Three-dimensional
rendering of volumes becomes possible if motion during the scan is limited.

! FOCUS BOX 2
Physical principles
The basic imaging principle is analogous to pulse-echo ultrasound
imaging.OCT uses infrared light waves to reflect off the internal microstructure
within the biological tissues
The echo time delay of the emitted light is used to generate spatial image infor-
mation, and the intensity of the received (reflected or scattered) light is translat-
ed into a (false) color map

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 As the speed of light is much faster than that of sound, an interferometer is re-
quired to measure the backscattered light
The interferogram is detected as a function of wavelength, either by using a
broadband source as in the time domain systems, and spectrally resolved de-
tection, or alternatively by incorporating a novel wavelength-swept laser source
called “swept source OCT”, or optical frequency domain imaging (OFDI)
Current Fourier domain OCT (optical coherence tomography) systems produce
images much faster than standard video-rate. and can scan 200-500 angles per
revolution (frame), and 5-10 images per mm (millimetre) in a pullback,
with 20 mm/sec (or higher) pullback speeds

PRACTICAL APPLICATION IN THE CATHERISATION LABORATORY

OCT IMAGING DEVICES

The equipment for intracoronary OCT (optical coherence tomography) generally consists of an
OCT (optical coherence tomography) imaging catheter, a motorised pullback device and an
imaging console, which contains the light source, signal processing units, data storage and dis-
play [14]. 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 ap-
proximately 1 mm (millimetre) 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 commercial-
ly available equipment for Fourier domain OCT (optical coherence tomography) and the imag-
ing procedure in detail. As many early studies of intracoronary OCT (optical coherence tomogra-
phy) employed time domain OCT (optical coherence tomography), we also summarise the
equipment and imaging procedure for time domain OCT (optical coherence tomography).

IMAGING PROCEDURE FOURIER DOMAIN OCT

Currently, there are two commercially available Fourier domain OCT (optical coherence tomog-
raphy) systems: the Dragon-Fly (St. Jude, Westford, MA, USA) and the Fastview catheter (Terumo,
Japan) ( (/eurointervention/textbook/media/90_953_figure%203.png)" Figure 3 (90_953_figure
3.png)). The optical probe is integrated with a 2.7 Fr short monorail catheter that can be ad-
vanced 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 (centimeter).

The OCT (optical coherence tomography) imaging catheter is advanced using monorail tech-
nique 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 (optical coher-

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 ence tomography) 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 [15]. A
variety of solutions are being used as flush media, including viscous iso-osmolar contrast me-
dia, and mixtures of lactated Ringer’s solution and contrast media or low molecular weight dex-
trose. Flush injection can be performed manually, with assist systems or by using a power injec-
tor. At the Thoraxcenter, we prefer iso-osmolar contrast medium (Iodixanol 370, Visipaque™,
GE Healthcare, Ireland) warmed to 37°C with 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 (optical coherence tomography)
catheter optics enter the guide catheter, or in the case of any complications.

CONCOMITANT MEDICATION
Similar to other diagnostic coronary instrumentation, such as FFR (fractional flow reserve) or
IVUS (intravascular ultrasound), patients should be anticoagulated, typically with heparin, be-
fore inserting the guidewire into the coronary artery. The OCT (optical coherence tomography)
catheter should preferably only be introduced into the coronary artery after the administration
of intracoronary nitroglycerin, 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 (optical coherence tomography) imaging.

Considerations regarding anatomy and patient characteristics arise (a) from the fact that OCT
(optical coherence tomography) imaging requires a blood-free environment, and (b) from the
OCT (optical coherence tomography) catheter design. As the imaging procedure demands tem-
porary 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 haemodynamically
compromised. Further, OCT (optical coherence tomography) should be used with caution in pa-
tients 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 oc-
clusion and thus a non-occlusive technique may be preferred in these circumstances. Large cal-
iber vessels or very tortuous vessels often preclude complete circumferential imaging as a re-
sult of a non-central, non-coaxial position of the OCT (optical coherence tomography) imaging
probe within the vessel.

These anatomical limitations are reduced significantly in Fourier domain OCT (optical coherence
tomography), 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 select-
ing an appropriate standard guidewire.

! FOCUS BOX 3

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 Practical application in the catheter laboratory
The only commercially Fourier domain OCT (optical coherence tomography)
systems integrates the optical probe in a 2.7 Fr short monorail catheter com-
patible with 6 Fr guiding catheters
After administration of intracoronary nitrates, the OCT (optical coherence to-
mography) imaging catheter is advanced distally into the coronary artery over
the angioplasty guidewire (0.014”)
Care should be taken to position the guide catheter coaxially
Automated OCT (optical coherence tomography) pullback (20 mm/sec) is per-
formed during flush administration
The preferred flush is iso-osmolar contrast medium at 37 °C using a power in-
jector (flow rate 3 ml/sec) connected to the standard Y-piece of the guiding
catheter

OCT - ROLE FOR THE ASSESSMENT OF ATHEROSCLEROTIC LESIONS

OCT has the ability to characterise the structure and extent of coronary artery disease in un-
precedented detail ( (/eurointervention/textbook/media/90_954_figure%204.png)" Figure 4
(90_954_figure 4.png) ). OCT (optical coherence tomography) images can be interpreted by vis-
ual assessment of the signal intensity and geometry [16] as various components of atheroscle-
rotic plaques have different optical properties ( (/eurointervention/textbook/media/90_955_fig-
ure%205.png)" Figure 5 (90_955_figure 5.png) ). Attenuation and backscatter affect the re-
ceived signal intensity and penetration depth into the tissue. OCT (optical coherence tomogra-
phy) signal intensity is displayed using a false color map. A popular color map is the “sepia”
scale, ranging from black (low OCT (optical coherence tomography) signal) through to brown,
yellow and white (high OCT (optical coherence tomography) signal); alternatively, grey scale (low
is black, high is white), or inverted grey scale maps are being used ( (/eurointervention/text-
book/media/90_956_figure%206.png)" Figure 6 (90_956_figure 6.png) ). The depth of penetra-
tion is greatest for fibrous tissue and least for thrombi, with calcium and lipid tissue having in-
termediate values [17, 18, 19, 20, 21]. Correct identification of plaque components by OCT (opti-
cal coherence tomography) 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 (optical coherence
tomography). The media is seen as a dark band delineated by the internal elastic lamina and ex-
ternal elastic lamina. As the mean media thickness is 200 μm, it can easily be visualised by OCT
(optical coherence tomography) [22, 23]. In the presence of vessel remodeling (where there is
an expansion of the vessel wall at the sites of plaque accumulation) the media typically be-
comes thinner. Unfortunately, because of its limited tissue penetration (1-1.5 mm (millimetre))
OCT (optical coherence tomography) is not suited to study vessel remodeling, as often the pres-
ence of atherosclerotic vessel wall thickening obscures visualisation of the media.

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 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 (optical coherence tomography). However, OCT (optical coherence tomography) can de-
tect early stages of intimal thickening, depicted as a signal-rich, homogeneous, thin rim of tis-
sue. Thus, OCT (optical coherence tomography) can confirm the absence of significant ath-
erosclerosis or indicate the degree of subclinical atherosclerotic lesion formation. Serial mea-
surements 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 incipi-
ent plaque [21, 22, 23].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
[24] (" Figure 1 (90_951_figure 1.png)A). The use of dedicated software to identify with accura-
cy the same cross-section in serial studies [25] or the application of a volumetric approach are
possible solutions to this problem [26].

QUALITATIVE DESCRIPTION OF ATHEROSCLEROSIS

Fibrous plaques
These are typically rich in collagen or muscle cells and have a homogeneous OCT (optical coher-
ence tomography) 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 backscat-
tering, signal-poor heterogeneous regions. In general, superficial calcium deposits can be stud-
ied and measured by OCT (optical coherence tomography) unless their thickness is greater than
1.0-1.5 mm (millimetre) whereupon the penetration limit of OCT (optical coherence tomogra-
phy) 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 [25]. Reviewing
consecutive OCT (optical coherence tomography) 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 re-
ported a higher sensitivity and specificity of OCT (optical coherence tomography) for lipid-rich
plaque detection when comparing OCT (optical coherence tomography), IVUS (intravascular ul-
trasound) and IVUS- derived techniques for plaque composition analysis [22, 27]. In the majority
of cases, the thickness of the lipid-rich plaque component cannot be measured by OCT (optical
coherence tomography) 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, vulnera-

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 ble 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 (three-dimensional) longitu-
dinal 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
(optical coherence tomography) 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 sub-
tend an arc which is greater than 90°or comprise more than one quadrant [27, 28].

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 (optical coher-
ence tomography) images are characterised as high-backscattering protrusions with signal-free
shadowing. White thrombi consist mainly of platelets and white blood cells and are charac-
terised by signal-rich, low-backscattering billowing projections protruding into the lumen [29]. In
reality, pure white or red thrombi are rarely found; mixed thrombi, on the other hand

Vasa vasorum and neovascularisation

(Neo) vessels within the intima appear as signal-poor voids that are sharply delineated, usually
contiguous and seen on multiple frames [16].

Thrombi are frequently found within culprit lesions of patients with acute coronary syndromes
[16, 18]. A fresh or large thrombus may hamper the visualisation of plaque features such as ul-
ceration beneath the thrombus itself. To solve this problem when thrombus is present, OCT (op-
tical coherence tomography) cross-sections acquired within the coronary segment with throm-
bus should be examined one by one for sites where vessel wall and plaque morphology can be
seen.

Macrophages
Macrophages are seen by OCT (optical coherence tomography) as signal-rich, distinct or conflu-
ent 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 software have been developed to identify macrophage bands with a higher accuracy
than simple visual inspection [30, 31].

Generally, good inter- and intra-observer agreement for visual plaque characterisation was re-
ported with TD-OCT (time domain optical coherence tomography) [17]. Similar results have re-
cently been reported with the second-generation, FD-OCT (Fourier domain optical coherence to-
mography) systems [17, 32]. However, whilst visual inspection of OCT (optical coherence tomog-
raphy) images allows for fast plaque characterisation, correct image interpretation depends on
the experience of the observer and on the penetration depth into the tissue.

PLAQUE RUPTURE AND INTRACORONARY THROMBOSIS

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 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 ap-
parently healthy subjects. The detection of a lesion with high risk of rupture (the so-called “vul-
nerable plaque”) would be of prime importance for the prevention of future ACS (acute coro-
nary syndrome). OCT (optical coherence tomography) has emerged as one of the most promis-
ing tools to assess patients with ACS (acute coronary syndrome) ( (/eurointervention/text-
book/media/90_957_figure%207.png)" Figure 7 (90_957_figure 7.png)) ( (/eurointerven-
tion/textbook/media/90_958_figure%208.png)" Figure 8 (90_958_figure 8.png)) ( (/eurointer-
vention/textbook/media/90_959_figure%209.png)" Figure 9 (90_959_figure 9.png)) and to de-
tect key features of plaques at high risk for rupture.

Diagnosis of fibrous cap atheroma

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
(optical coherence tomography) allows the diagnosis of thin cap fibro-atheroma (TCFA) with a
sensitivity of 90% and a specificity of 79% when compared to histopathology [33].

At present, OCT (optical coherence tomography) is the only imaging technique that allows an ac-
curate evaluation of the fibrous cap in vivo. Several studies have demonstrated a good correla-
tion between fibrous cap thickness measurements with OCT (optical coherence tomography)
and histology [33, 34]. This ability to assess the fibrous cap indicates that OCT (optical coher-
ence tomography) may be well-suited for the in vivo detection of TCFA (thin-cap fibroatheroma)
[33, 34]. In a study comparing OCT (optical coherence tomography), IVUS (intravascular ultra-
sound) and angioscopy in patients with acute myocardial infarction, Kubo et al [34] reported
that OCT (optical coherence tomography) was the only imaging technology able to estimate the
fibrous cap thickness (mean 49±21 μm). Angioscopy does not allow the measurement of the fi-
brous 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 (optical coherence tomography) [16].

OCT studies have been carried on to monitor changes in the fibrous cap thickness, with the goal
to address the effect of therapeutic agents aiming at plaque stabilisation. 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 [35]. 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 [36]. More recently Habara
et al showed in an OCT (optical coherence tomography) study that lipid-lowering therapy with
ezetimibe + fluvastatin further increases the fibrous cap thickness of lipid-rich plaques com-
pared with fluvastatin monotherapy [37].

The stability of the fibrous cap depends not only on its thickness but also on the collagen con-
tent and organisation. Several investigations have shown lower collagen content, thinner colla-
gen fibers, and fewer smooth muscle cells (SMC) in unstable plaques. Polarisation-sensitive OCT
(optical coherence tomography) (PSOCT) is a new technology that enhances OCT (optical coher-

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 ence tomography) by measuring birefringence, a property which is elevated in tissues contain-
ing proteins with an ordered structure such as collagen and SMC’s actin/myosin. It has been
demonstrated that PSOCT (polarisation sensitive optical coherence tomography) is able to eval-
uate collagen content, collagen fibre thickness and SMC (smooth muscle cells) density in
plaques and in fibrous caps of fibro-atheromas [38]. This information is related to the mechani-
cal stability of the fibrous cap and could help improve the identification of lesions at high risk of
rupture in patients.

Clinical observations in patients with ACS

Pathological data has shown differences in the characteristics of the underlying plaque in pa-
tients with stable and unstable coronary syndromes [39, 40]. The ability of OCT (optical coher-
ence tomography) to characterise fibrous cap has enabled pathophysiological studies on the
prevalence, distribution and mechanism of rupture of thin-cap fibro-atheromas in different clin-
ical scenarios. Jang et al evaluated the culprit lesion characteristics as assessed by OCT (optical
coherence tomography) in patients with stable and unstable clinical presentation. The percent-
age of lipid-rich plaque in acute myocardial infarction, ACS (acute coronary syndrome) and sta-
ble 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 (thin-cap fibroatheroma) was higher in the acute myocardial
infarction population (72%) and in the ACS (acute coronary syndrome) group (50%) than in the
stable angina group (20%) [27]. 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 (thin-cap fibroatheroma)
(46% vs. 3%, p=0.001) in patients with unstable angina vs. patients with stable presentation [41].
Plaques with TCFA (thin-cap fibroatheroma) morphology by OCT (optical coherence tomogra-
phy) appear to be highly prevalent in patients with ACS (acute coronary syndrome). A study of
the culprit lesion in acute myocardial infarction patients revealed an incidence of TCFA (thin-cap
fibroatheroma) of 83% with a mean fibrous cap thickness of 49±21 μm [18]. Presence of lesions
with thin-cap fibro-atheroma was also investigated by Fuji et al [42]. In a 3-vessel OCT (optical
coherence tomography) 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 proxi-
mal left anterior descending but had an even distribution in the left circumflex and right coro-
nary artery.

Tanaka et al [43] suggest that morphologies of exertion-triggered and rest-onset ruptured

plaques differ in patients with ACS (acute coronary syndrome) 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 (acute coronary syndrome) during exertion, whilst in the
group with ACS (acute coronary syndrome) 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 athero-
sclerotic plaque and its dynamic changes in a longitudinal way.

! FOCUS BOX 4

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 OCT assessment of atherosclerotic lesions
OCT has the ability to characterise the structure and extent of coronary artery
disease in unprecedented detail
OCT is capable of reliably differentiating normal vessel wall from various com-
ponents of atherosclerotic plaques, including fibrous, calcified or lipid-rich tis-
sues
OCT can visualise features associated with risk of plaque rupture, including
thin-cap fibro-atheroma, thin fibrous cap, necrotic core, macrophage infiltra-
tion, ruptured plaque and intracoronary thrombosis

GUIDANCE OF STENT DEPLOYMENT.

Pre-implantation assessment
The ILUMIEN observational OCT (optical coherence tomography) trial [44] was the first study to
focus on the role of pre-intervention OCT (optical coherence tomography) assessment. Based
on the study design , OCT (optical coherence tomography) and documentary FFR (fractional flow
reserve) were performed pre-and post-PCI in 418 patients with stable or unstable angina or
NSTEMI (non-ST-elevation myocardial infarction). Based on pre-PCI OCT (optical coherence to-
mography), 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%. After clinically stent implantation using an-
giographic guidance, post-PCI FFR (fractional flow reserve) and OCT (optical coherence tomogra-
phy) were repeated. OCT (optical coherence tomography) malapposition, edge dissection, and
stent under-expansion that were not apparent on angiography were the main reasons driving
additional reaction by operators. Further work was required to treat malapposition (14.5%) un-
der-expansion (7.6%), edge dissection ( 2.7%) and led to further stent optimisation based on
OCT (optical coherence tomography) in 25% of patients with further in-stent post-dilatation
(81%) or placement of new stents (12%). MACE (major adverse cardiac events) incidence at 30
days was low, with death occurring in 0.25%, myocardial infarction in 7.7%, repeat PCI (percuta-
neous coronary intervention) in 1.7%, and stent thrombosis in 0.25%.

Plaque composition and risk of periprocedural complications

OCT can be used to confirm the presence of atherosclerotic plaque and to characterise its com-
position. The assessment of plaque composition can be helpful in clinical practice to guide per-
cutaneous coronary interventions, as plaque composition has been related to the outcome af-
ter percutaneous interventions (e.g., heavily calcified lesions which have lower distensibility or
necrotic core plaques with their propensity to rupture). Several IVUS-VH (intravascular ultra-
sound – virtual histology) studies suggested a relation between the lipid content of the plaque
and the presence of no-reflow phenomenon after stent implantation [45, 46]. This observation
has been confirmed by OCT (optical coherence tomography). Tanaka et al evaluated 83 patients
with non-ST elevation acute coronary syndromes. Composition of the culprit plaque analysed
with OCT (optical coherence tomography) demonstrated that the frequency of no-reflow phe-

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 nomenon increases according to the lipid content of the plaque. Similarly, the final TIMI (throm-
bolysis in myocardial infarction) blush grade was worse when the lipid content was higher. In a
multivariate analysis, the size of the lipid arc was an independent predictor of no-reflow [47].

Consistently with these findings, Imola et al compared 15 patients with post-procedural myocar-
dial infarctions with 15 controls without infarctions and showed that incomplete stent coverage
of coronary lipid pools is associated with an increased risk for post-procedural myocardial in-
farction [48].

Post implantation assessment

The high resolution of the OCT (optical coherence tomography) technique permits detection of
features that may be missed by IVUS (intravascular ultrasound), 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 cor-
rect innocent, but ominous looking anatomical issues. The CLI-OPCI studies [49, 50] were specif-
ically designed to answer these crucial questions in “everyday” practice.

The multicentre CLI-OPCI study [49] aimed at verifying whether the use of OCT (optical coher-
ence tomography) can improve the 1-year composite event of cardiac death or nonfatal myocar-
dial infarction after PCI (percutaneous coronary intervention) 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 (optical coherence tomography) guided intervention halved the rate of death and my-
ocardial infarction from 13% to 6,6% (p=0.006).

The study showed that OCT (optical coherence tomography) could potentially improve the clini-
cal outcomes after coronary intervention in a real-world population. However, its promising
conclusions were approached with caution due to its non-randomised design and relatively
small population size.

The CLI-OPCI II [50] corroborated the findings obtained in the CLI-OPCI registry testing the role
of OCT (optical coherence tomography) findings after PCI (percutaneous coronary intervention)
in a much larger population comprising 832 patients and 1002 lesions with a median follow-up
of 319 days. Consistent with previous data [49] the CLI-OPCI II showed that OCT-defined subop-
timal stent deployment was a relatively common finding (31.0% of cases) with a significantly
higher prevalence in patients experiencing MACE (major adverse cardiac events) 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).

Specific OCT (optical coherence tomography) findings of suboptimal stenting.

In both CLI-OPCI and CLI-OPCI II studies quantitative metrics to indicate good stent positioning
were applied.
Lesion coverage

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 Incomplete lesion coverage and residual reference segment stenosis have been associated with
stent thrombosis in IVUS (intravascular ultrasound) studies. The presence of residual lumen
stenosis and incomplete lesion coverage can readily be identified by OCT (optical coherence to-
mography).

Consistently with IVUS (intravascular ultrasound) data [51] presence of residual reference seg-
ment disease was of utmost importance. The CLIO-PCI II study stented segments exhibiting a
narrowing at the reference (lumen area <4.5mm2 in the presence of significant plaque) experi-
enced a worse outcome with a risk of MACE (major adverse cardiac events) approximately five
times higher regardless of the location (proximal or distal reference segment).

Distal Dissections >200µm at the distal stent edge also conveyed a higher risk of MACE (major
adverse cardiac events) (HR 2.54, p=0.004), while proximal dissections had no clinical impact.
The same conclusion was reached by Bouki et a [52]. According to authors, who studied 74 pa-
tients with ACS (acute coronary syndrome), the presence of a residual dissection flap > 0.31 mm
(millimetre), carried an adverse long term clinical impact. In contrast with these data Soeda et al
[53] did not relate the presence of dissection with the clinical outcome. Of note authors, did not
introduce a quantitative threshold for dissection width, including within the study mild dissec-
tions, a common and benign OCT (optical coherence tomography) 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 [54] who showed in a serial OCT (optical coherence tomography) study that dissections
tend to heal at late follow-up. In fact at one year 90% of edge dissections were completely
healed on OCT (optical coherence tomography).

In-stent under-expansion, using absolute dimensions expressed as in-stent MLA (minimal lu-
men area), was significantly related to clinical outcome in the CLI-OPCI II. The absolute in-stent
MLA (minimal lumen area) <4.5mm2 was the best OCT (optical coherence tomography) MACE
(major adverse cardiac events) predictor. A different approach, based on the stent percentage
of under-expansion (MLA less than 70% of reference lumen areas), would guarantee an inferior
clinical benefit, as pointed out by IVUS (intravascular ultrasound) studies. [51].

STENT MALAPPOSITION
For the past two decades, IVUS (intravascular ultrasound) has been used to assess the acute re-
sult following stent implantation, giving valuable information on stent expansion, strut apposi-
tion and signs of vessel trauma including dissections and tissue prolapse. IVUS (intravascular ul-
trasound) studies [55, 56] have suggested that stent strut malapposition is a relatively uncom-
mon finding, observed in approximately 7% of cases, and that strut malapposition does not in-
crease the risk of subsequent major adverse cardiac events. By contrast, OCT (optical coherence
tomography) can visualise in much greater detail the complex coronary arterial wall structure
after stenting [57]. As a result, OCT (optical coherence tomography) studies in the acute post-
stent setting [58, 59] have demonstrated a relatively high proportion of stent struts not com-
pletely apposed to the vessel wall contact even after high pressure post-dilatation, with this

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 phenomenon being particularly evident in regions of stent overlap. In an evaluation of OCT (op-
tical coherence tomography) findings following stent implantation to complex coronary lesions,
Tanigawa et al [59] examined a total of 6,402 struts from 23 patients (25 lesions) and found
9.1±7.4% of all struts in each lesion treated were malapposed. Univariate predictors of malap-
position on multilevel logistic regression analysis were the implantation of a sirolimus-eluting
stent (probably due to its thick struts and closed cell design) together with the presence of over-
lapping stents, a longer stent length and a type C lesion. Probable mechanical explanations for
stent malapposition include strut thickness, closed cell design or acute stent recoil [60].The me-
chanical result after stent implantation is of special interest in bifurcation lesions ( (/eurointer-
vention/textbook/media/90_960_figure%2010.png)" Figure 10 (90_960_figure 10.png) ). OCT
(optical coherence tomography) is able to visualise the stent strut/vessel wall interaction in
great detail and thus allows the evaluation of specific treatment strategies, such as dedicated
bifurcation stents. Malapposed struts were found to be frequent in bifurcations despite the use
a dedicated stents. [61].

While these findings are impressive and helpful for the improvement of future stent designs, to-
day 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 (drug-eluting stent) thrombosis. Postulated causes of stent strut malappo-
sition are numerous and include incomplete stent expansion, stent recoil or fracture, late out-
ward vessel remodeling or the dissolution of thrombus which was compressed during PCI (per-
cutaneous coronary intervention) between the stent strut and the vessel wall. Regardless of the
pathophysiological mechanism, the major concern in stent malapposition remains the assump-
tion that areas of strut malapposition cause non-laminar and turbulent blood flow characteris-
tics, which in turn can trigger platelet activation and thrombosis. Here, prospective, serial OCT
(optical coherence tomography) 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.

Recent studies [49, 50, 53, 62] failed to relate acute stent-vessel wall malapposition with clinical
outcome. It is likely that the innovative technology adopted by the new DES (drug-eluting stent)
platforms minimise the consequences of acute malapposition. Importantly these OCT (optical
coherence tomography) findings are also in line with IVUS (intravascular ultrasound) data [63,
64].

Such conclusions are also supported by an OCT (optical coherence tomography) study on the
mechanism of stent thrombosis [65]. Authors compared DES (drug-eluting stent) with sub-acute
thrombosis, with a control arm. Unlike significant under-expansion, residual disease or dissec-
tion, the incidence of malapposition was not higher in the group with stent thrombosis.

Periprocedural vessel injury

High-pressure deployment is necessary for an adequate stent expansion but it can induce
periprocedural vessel damage. Experimental data has related the vessel response to injury after
implantation with stent restenosis. Given its high resolution, OCT (optical coherence tomogra-

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 phy) allows a detailed visualisation of vessel damage after stent implantation and can distin-
guish different types of injury ( (/eurointervention/textbook/media/90_968_figure%2018.png)"
Figure 18 (90_968_figure 18.png)). Furthermore, the technique allows the quantification of
these findings [66]. A recent study showed that the frequency of tissue prolapse or intra-stent
dissections after stenting was high, irrespective of the clinical presentation of the patients [66].
Dedicated assessment of the reference segments at the extremities of the stents revealed a
high proportion of patients with lipid-rich plaques at the stent borders [67]. Fibroatheroma was
observed in 15.3% of the distal and 28.9% of the proximal edges, and thin-cap fibroatheroma
(TCFA) in 7%. Plaque type at the stent borders affected the incidence of edge dissections. In the
distal edge, the presence of edge dissection was significantly more frequent when the plaque
type at the border was fibrocalcific (43.8%) or lipid-rich (37.5%) than when the plaque was fi-
brous (10%), p=0.009.

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 (optical coherence tomography)
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 lo-
cated inside the stent, they can be associated with the presence of intracoronary thrombus or
intra-stent dissections [66, 67].

! FOCUS BOX 5
Use of OCT (optical coherence tomography) to guide coronary interventions
The baseline use of OCT (optical coherence tomography) alter the intervention-
al strategy, leading to selection of different stent lengths and diameters
The use of OCT (optical coherence tomography) post-intervention can reveal
suboptimal stent deployment
The application of OCT (optical coherence tomography) metrics of suboptimal
stenting identifies patients at higher risk of major cardiovascular events during
follow-up

ASSESSMENT OF LONG-TERM OUTCOME

Visualisation and quantification of stent strut tissue coverage
OCT can reliably detect very thin layers of tissue coverage on stent struts. Several small studies
have been published highlighting the ability of OCT (optical coherence tomography) to detect
stent tissue coverage at follow-up ( (/eurointervention/textbook/media/90_961_fig-
ure%2011.png)" Figure 11 (90_961_figure 11.png)) ( (/eurointervention/textbook/me-
dia/90_962_figure%2012.png)" Figure 12 (90_962_figure 12.png)). Importantly, OCT (optical co-
herence tomography) permits the quantification of tissue coverage with high reliability [68].
Matsumoto et al [69] 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 neoin-
tima undetectable by IVUS (intravascular ultrasound) was 64%. The average rate of neointima-
covered struts in an individual SES (sirolimus-eluting stent) was 89%. Takano et al [70] showed

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 that rates of exposed struts and exposed struts with malapposition were 15% and 6% respec-
tively at 3 months and were more frequent in presence of ACS (acute coronary syndrome) (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 (optical coherence tomography) findings [71]. 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 [72]
used OCT (optical coherence tomography) to image SES (sirolimus-eluting stent) and bare metal
stents (BMS) at different time points following implantation. The authors identified a significant-
ly higher number of incompletely apposed and uncovered stent struts in patients receiving SES
(sirolimus-eluting stent) compared to BMS (bare metal stent). More recently, the OCT (optical co-
herence tomography) 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
(optical coherence tomography) substudy was performed in 56 consecutive patients who un-
derwent OCT (optical coherence tomography) during angiographic follow-up at 9 months. Strut
coverage at an average follow-up of 9 months appeared to be more complete in patients allo-
cated to BESs as compared to SESs. Results were similar after adjustment for pre-procedural le-
sion length, reference vessel diameter, number of implanted study stents, and presence of
stent overlap. [73]. The clinical impact of these small but measurable differences in tissue cover-
age is unclear as it did not translate into a difference in clinical event rates in the substudy co-
hort. The 4-year follow-up data of the overall LEADERS cohort BES (biolimus-eluting stent) with
biodegradable polymer was proven non-inferior to SES (sirolimus-eluting stent) with durable
polymer. Interestingly, BES (biolimus-eluting stent) showed a reduction in the risk of very late
stent thrombosis at 4-year follow-up (RR 0.20, 95% CI (confidence intervals) 0.06-0.67, p=0.004)
[74]. In the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial In-
farction (HORIZONS-AMI) trial, patients with STEMI (ST-elevation myocardial infarction) were
randomised to PES (paclitaxel-eluting stent) for BMS (bare metal stent) implantation [75]. In a
formal sub-study, OCT (optical coherence tomography) at 13 months was performed in 118 con-
secutive randomised patients. OCT (optical coherence tomography) revealed that implantation
of PES (paclitaxel-eluting stent) as compared with BMS (bare metal stent) 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 (bare metal stent) lesions versus 5.7±7.0% in PES (pacli-
taxel-eluting stent) 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 (optical coherence tomography) was employed to study tissue coverage at follow-
up in bioresorbable scaffolds [76, 77, 78]. OCT (optical coherence tomography) was able to visu-
alise 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 ( (/eu-
rointervention/textbook/media/90_963_figure%2013.png)" Figure 13 (90_963_figure 13.png)) (

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 (/eurointervention/textbook/media/90_964_figure%2014.png)" Figure 14 (90_964_figure
14.png)) ( (/eurointervention/textbook/media/90_965_figure%2015.png)" Figure 15 (90_965_-
figure 15.png)). The OCT (optical coherence tomography) sub-studies demonstrated differences
in the two generations of everolimus-eluting bioresorbable vascular scaffolds at 6-month fol-
low-up as used in the ABSORB Cohort A (1.0 BVS (bioresorbable vascular scaffold)) vs. Cohort B
(1.1 BVS (bioresorbable vascular scaffold)) trials. The appearances of the polymeric struts of the
1.1 BVS (bioresorbable vascular scaffold) were preserved in all the patients at 6 months and the
strut central core remained unchanged over time. Specifically, the 1.1 BVS (bioresorbable vascu-
lar scaffold) did not show late shrinkage at six months with respect to the baseline scaffold
area; the 1.0 BVS (bioresorbable vascular scaffold) had higher neointimal growth and large in-
device area obstruction than the 1.1 BVS (bioresorbable vascular scaffold). These changes re-
sulted in a higher OCT (optical coherence tomography) luminal loss and angiographic late loss
in the 1.0 BVS (bioresorbable vascular scaffold) than in the 1.1 BVS (bioresorbable vascular scaf-
fold). The overall strut appearance at 6-month follow-up was markedly different between the
two generations of BVS (bioresorbable vascular scaffold), with the absence of optically demon-
strable alteration of the polymeric struts of the 1.1 BVS (bioresorbable vascular scaffold) 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 (bioresorbable vascular scaffold) revision 1.0
(Cohort A) and BVS (bioresorbable vascular scaffold) revision 1.1 (Cohort B) designs revealed
that the revision 1.1 BVS (bioresorbable vascular scaffold) design has a different longitudinal
strut distribution pattern, indicating that the new design has a reduced maximum circular un-
supported cross-sectional area. By contrast, there was no significant difference between the 1.0
BVS (bioresorbable vascular scaffold) and the 1.1 BVS (bioresorbable vascular scaffold) 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 [79].

Assessment of structural details of tissue coverage

OCT also permits the characterisation of neointimal tissue in a qualitative way [20]. This is a
great advantage as such information has not been available in vivo until now. The limited reso-
lution, together with artifacts induced by metallic stent struts, does not allow the characterisa-
tion of such details by IVUS (intravascular ultrasound). With OCT (optical coherence tomogra-
phy), neointimal tissue can show a variety of morphologies ranging from homogenous, bright,
uniform tissue to optically heterogeneous tissue or eccentric tissue of various thicknesses. Fur-
thermore, structural details within the tissue can be observed such as intimal neovascularisa-
tion [31] or a layered appearance [80], 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 [81]. Howev-
er, there is a paucity of data directly demonstrating the OCT (optical coherence tomography) ap-
pearance of different components in neointimal tissue as defined by histology. Post-mortem
imaging of DES (drug-eluting stent) in human coronaries is difficult and might be limited by the

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 fact that the optical tissue properties show variations with temperature and fixation [82]. Long-
term animal OCT (optical coherence tomography) observations in DES (drug-eluting stent) are
scarce.

The neointima can develop atherosclerotic lesions over time, a phenomenon dubbed “neoath-
erosclerosis”. OCT (optical coherence tomography) can visualise these lesions and add to our
understanding of the incidence and role of neoatherosclerosis in relation to stent failure. Accel-
erated neoatherosclerosis has been described in drug-eluting stents [83, 84].

Stent strut tissue coverage and thrombosis

Stent thrombosis tended to occur at a yearly rate >0.5% after deployment of first generation
DES (drug-eluting stent). However acute and late thrombosis represent a rare finding after posi-
tioning of new DES. The mechanism of DES (drug-eluting stent) 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 (optical coherence tomography) 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 [85, 86].
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 en-
dothelialisation. However, OCT (optical coherence tomography) observations need to be inter-
preted with caution. OCT (optical coherence tomography) 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 en-
dothelium [87]. Early experimental stent data showed that endothelial function can vary consid-
erably 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 [88]. However, OCT (optical coher-
ence tomography) is the only imaging modality to date which offers, within the discussed limits,
the possibility to understand tissue coverage and neointima formation in DES (drug-eluting
stent) over time. Clearly, larger stent trials with OCT (optical coherence tomography) at different
time periods are needed to obtain a representative assessment of the true time course of en-
dothelial stent coverage. FD-OCT (Fourier domain optical coherence tomography) 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 deploy-
ment, vascular healing, the true time course of endothelial stent coverage and late stent throm-
bosis. This may also better guide the optimal duration of dual antiplatelet therapy which cur-
rently remains unclear and rather empiric.

Stent strut tissue coverage and DES (drug-eluting stent) restenosis

OCT can be useful in the evaluation of the causes that contribute to restenosis after DES (drug-
eluting stent) 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 incom-

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 plete healing. The clinical significance of these findings is currently poorly understood [89, 90].

Stent fracture has also been related to restenosis in DES (drug-eluting stent) and could be visu-
alised with OCT (optical coherence tomography) [91]. 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 (drug-eluting stent) [92]. This has been confirmed in preclinical and IVUS (in-
travascular ultrasound) studies. OCT (optical coherence tomography) allows the assessment of
strut distribution in vivo with high accuracy. A study with phantom models showed how the
strut distribution of SES (sirolimus-eluting stent) and paclitaxel-eluting stents (PES) assessed by
OCT (optical coherence tomography) were significantly different, suggesting that SES (sirolimus-
eluting stent) maintained a more regular strut distribution despite expansion [93].

Another field of clinical use for OCT (optical coherence tomography) might be the assessment
of the performance of DES (drug-eluting stent) in complex coronary interventions such as bifur-
cations. Buellesfeld et al [94] reported the 9-month OCT (optical coherence tomography) follow-
up in a case of crush stenting with PES (paclitaxel-eluting stent). 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 ad-
verse effect of delayed endothelialisation. In this report, OCT (optical coherence tomography)
imaging showed the overlapping strut layers in the crushed segment completely covered by tis-
sue. Furthermore, OCT (optical coherence tomography) 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-elut-
ing stent overlap, revealed a more complex interaction between strut overlap, underlying
plaque and tissue coverage [95]. ODESSA was a prospective, randomised controlled trial de-
signed to evaluate healing of overlapping stents. Overlapping drug-eluting stents in normal-ap-
pearing coronary segments showed a higher incidence of uncovered or malapposed struts,
while restenosis occurred exclusively in overlapping stents at high-grade stenosis. Any uncov-
ered 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).

! FOCUS BOX 6
OCT assessment of coronary stents follow-up
OCT the gold standard for the assessment of coronary stents, including novel
stents such as bioresorbable stents
At baseline stent expansion, strut apposition, extent of lesion coverage and ref-
erence segments can be analysed
Mechanical vessel injury and edge dissections can be observed with high sensi-
tivity and specificity
At follow-up, OCT (optical coherence tomography) can identify strut apposition
and strut coverage even with very thin layers of tissue with high reproducibility
OCT permits the assessment of structural composition and extent of strut cov-
erage

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 GUIDANCE OF STENT IMPLANTATION IN COMPLEX LESIONS
OCT seems particularly efficient in complex interventions, including treatment of left main
stem, 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.

A technical drawback consists of the fact that plaques located at the very ostium of the left or
right coronaries cannot be accurately addressed by OCT (optical coherence tomography) as it is
difficult to clear the artery from blood during a non-selective guide catheter position, required
for the visualisation of the ostium.

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 (drug-
eluting stent) has reduced the incidence of restenosis in coronary bifurcations, but concerns re-
main about the risk of stent thrombosis. OCT (optical coherence tomography) can visualise ma-
lapposition (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 bifurca-
tions. Further, OCT (optical coherence tomography) can characterise the atherosclerotic plaque
in bifurcations, another important factor which could potentially contributeto the higher risk of
stent failure in these lesions [96].

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 (optical coherence
tomography) can provide useful additional information which may potentially be useful to guide
the procedure safely. Preliminary ex vivo experience with forward-looking OCT (optical coher-
ence tomography) systems which use multiple longitudinal OCT (optical coherence tomogra-
phy) slices to generate cross-sectional images of occluded arteries have been reported [97].
OCT (optical coherence tomography) was able to differentiate between occluded lumen and dif-
ferent layers of the arterial wall, and showed potential to identify micro-channels ( (/eurointer-
vention/textbook/media/90_966_figure%2016.png)" Figure 16 (90_966_figure 16.png)). This in-
formation 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 (optical coherence tomography) can pro-
vide useful information about the composition of the plaque causing the occlusion. Further,
when a dissection occurs, OCT (optical coherence tomography) can be used to differentiate true
from false lumen [98]. Future developments such as OCT-based Doppler techniques could, po-
tentially, be used to assess the presence of micro-channels [99].

GUIDANCE OF CORONARY INTERVENTIONS IN AMBIGUOUS CASES AND

ACS
Ambiguous lesions
Suboptimal angiographic lesion visualisation may happen in the presence of intermediate le-
sions 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 le-

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 sions, often caused by the presence of thrombus or calcifications. The use of OCT (optical co-
herence tomography) is particularly worthwhile in these cases as OCT (optical coherence to-
mography) provides an accurate visualisation of the luminal structure and dimensions, because
of its excellent delineation of the lumen-wall interface.

Patients with ACS (acute coronary syndrome) 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 (electrocardiogram) changes or by the
finding of a thrombotic, hazy lesion by angiography. However, the identification of the culprit le-
sion can be challenging in individual patients, especially in the presence of multi vessels dis-
ease. Similarly, in 15% of the patients undergoing primary PCI (percutaneous coronary interven-
tion), angiography shows a patent infarct-related vessel with TIMI (thrombolysis in myocardial
infarction) 3 flow [100]. OCT (optical coherence tomography) can provide accurate information
on the superficial composition of the plaque, can identify ruptured plaques and, most impor-
tantly, can reveal thrombosed lesions, and thus identify the culprit lesion, namely the most like-
ly pathophysiologic substrate for the acute coronary syndrome.

In patients with coronary thrombosis, distinct OCT (optical coherence tomography) morpholo-
gies 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 indica-
tive of erosion.

Acute plaque ulceration or rupture can be detected by OCT (optical coherence tomography) as a
ruptured fibrous cap which connects the lumen with the necrotic core. These ulcerated or rup-
tured 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 cer-
tainty, unless clinical criteria provide some evidence that the lesion is responsible for the acute
events.

Detection of erosion versus ulceration

OCT is capable of identifying the pathophysiology of ACS (acute coronary syndrome), showing
presence of plaque ulceration vs. erosion. This finding has clinical implications.

Niccoli et al [101] studied the mechanism of ACS (acute coronary syndrome) (plaque rupture vs.
intact fibrous cap) in 139 consecutive ACS (acute coronary syndrome) 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

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 The ability of OCT (optical coherence tomography) identify ACS (acute coronary syndrome) cul-
prit lesions with intact fibrous cap can be used to select lesions that can be treated using a less
aggressive approach, without balloon dilatation or stenting. In a preliminary study, Prati et al
applied this strategy in 12 patients with intact fibrous cap and showed that such a strategy can
be accomplished with a good clinical outcome at 2 years [102]. More recently Souteyrand et al.
suggested a deferred strategy of stent deployment in patients with ACS (acute coronary syn-
drome) in presence of plaque ulceration [103].

ASSESSMENT OF STENT FAILURE

The causes of DES (drug-eluting stent) failure are poorly understood. In the catheterisation lab-
oratory, OCT (optical coherence tomography) 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 (optical coherence tomography) 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
( (/eurointervention/textbook/media/90_969_figure%2019.png)" Figure 19 (90_969_figure
19.png) ).

While OCT (optical coherence tomography) offers a number of potential clinical applications, it
can be challenging to consolidate the information gained by OCT (optical coherence tomogra-
phy) 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 over-
lap, 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 proto-
type, Erlangen, Germany) or the software-enabled synchronisation of three-dimensional angiog-
raphy with OCT (optical coherence tomography) pullback (Medis medical imaging systems bv
prototype, Leiden, The Netherlands) ( (/eurointervention/textbook/media/90_970_fig-
ure%2020.png)" Figure 20 (90_970_figure 20.png)). The ultimate goal is an on-line co-registra-
tion 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 in-
formation of the complementary imaging modality just by pointing at any region of interest ei-
ther on the angiogram or on the OCT (optical coherence tomography).

Another approach which could overcome limitations of spatial orientation and orientation with
respect to angiography is the three- dimensional (3D) reconstruction of the OCT (optical coher-
ence tomography) dataset. Fourier domain OCT (optical coherence tomography) is particularly
well-suited for 3D (three-dimensional) rendering as the high frame rate allows for dense sam-
pling and the fast pullback limits motion artifacts as the complete pullback is acquired in a few

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 cardiac cycles ( (/eurointervention/textbook/media/90_971_figure%2021.png)" Figure 21
(90_971_figure 21.png)). The preliminary experience with 3D (three-dimensional) reconstruction
of Fourier domain datasets demonstrates that this data display format can facilitate the under-
standing of complex anatomy [104, 105, 106]. However, today there is no standard for 3D
(three-dimensional) rendering available, covering aspects such as cut planes, calibration and
quantification.

! FOCUS BOX 7
OCT potential to guide complex procedures and ACS
OCT can be of clinical value and can guide clinical decision-making, at least in
individual patients and in specific clinical scenarios
Preliminary data on OCT (optical coherence tomography) indicates that it can
change the operator’s intention-to-treat and modify the overall revascularisa-
tion strategy, potentially avoiding unnecessary interventional procedures
OCT might be efficient in complex interventions including treatment of left
main stem, ostial left anterior descending or left circumflex artery lesions or bi-
furcations as well as in all cases of angiographically ambiguous lesions and in
stent failures
In the setting of ACS (acute coronary syndrome), OCT (optical coherence tomog-
raphy) information can be adopted to identify the underlying mechanism and
defer stenting

SAFETY
The applied energies in intravascular OCT (optical coherence tomography) are relatively low
(output power in the range of 5.0-8.0 mW) and are not considered to cause functional or struc-
tural 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 (optical coherence tomography) 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 tachy-
cardia, 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 pro-
cedure-related artery, were not observed [107]. 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 (electrocardiogram) changes during image acquisition [108]. These side
effects are expected to be reduced further by the introduction of Fourier domain OCT (optical
coherence tomography). In Fourier domain OCT (optical coherence tomography), high pullback
speeds of up to 40 mm/sec allow data acquisition of a long coronary segment within a few sec-
onds and without introducing relevant ischaemia. Imola et al [109] addressed the safety of FD-
OCT (Fourier domain optical coherence tomography) in 114 OCT (optical coherence tomogra-
phy) acquisitions, performed in 90 patients. In 99% of cases the procedure was successful. No

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 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 (Fourier domain optical coherence tomography) image acquisition no ischaemic
ECG (electrocardiogram) changes occurred. Ventricular ectopic beats were found in only 3 pa-
tients while other major arrhythmias (ventricular tachycardia or fibrillation) were not observed.

! FOCUS BOX 7
Safety
Imaging-related complications used to be caused by the ischaemia transiently
created during imaging with. Time domain OCT systems. These devices re-
quired proximal balloon occlusion and distal flushing as well as slow data acqui-
sition thus limiting their clinical application
Fourier domain OCT is a safe, easy to use and fast imaging modality
Fourier domain OCT has high pullback speeds of up to 40 mm/sec to allow data
acquisition of a long coronary segment within a few seconds without the need
to occlude the artery and, thus, without introducing any relevant ischaemia
Fourier domain OCT has a broad applicability and high imaging success (99%)
without ischaemic ECG changes or clinically significant arrhythmias

LIMITATIONS
Generally, the main limitations of intracoronary OCT (optical coherence tomography) as com-
pared to intravascular ultrasound consist, firstly, in the fact that light cannot penetrate blood.
Thus, OCT (optical coherence tomography) requires clearing of the artery from blood as an ad-
ditional step during the imaging procedure. Secondly, the high resolution of OCT (optical coher-
ence tomography) is at the expense of penetration depth. However, additional issues can influ-
ence intracoronary OCT (optical coherence tomography) quality and interpretation in clinical in-
tracoronary OCT (optical coherence tomography) application. The most important practical limi-
tations and artifacts are summarised below.

IMAGING ARTIFACTS
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 re-
quires 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 centered position within the
target artery, which may affect penetration depth, brightness and resolution of the imaged
structure.

Coronary calibre

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 Coronary arteries represent relatively small structures for in vivo imaging; they are, however,
relatively big structures compared to experimental OCT (optical coherence tomography) ap-
plications which often focus on much smaller sample volumes. Epicardial arteries have a maxi-
mal lumen diameter of approximately 4-5 mm (millimetre) in their proximal portion and taper
distally. Typically, arteries with a lumen diameter down to approximately 1.0 mm (millimetre)
are considered clinically relevant and accessible to standard imaging equipment, such as coro-
nary angiography and intravascular ultrasound. Ideally, the penetration depth of intravascular
OCT (optical coherence tomography) 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 af-
fects the vascular dimensions (with a variability of lumen area of approximately 8% between
systole and diastole [110]) and the OCT (optical coherence tomography) device position within
the artery (transversal and longitudinal motion), typically resulting in a saw-tooth appearance of
the longitudinal data reconstruction. Fourier domain OCT (optical coherence tomography) 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 (optical coherence to-
mography), a pullback might include 20-30 heart beats ( (/eurointervention/textbook/me-
dia/90_972_figure%2022.png)" Figure 22 (90_972_figure 22.png)) ( (/eurointervention/text-
book/media/90_973_figure%2023.png)" Figure 23 (90_973_figure 23.png)).

STENT-RELATED IMAGING ARTIFACTS

Shadowing behind stent struts
The light source used for OCT (optical coherence tomography) is unable to penetrate metal re-
sulting in dorsal shadowing behind the stent strut. When interpreting OCT (optical coherence
tomography) 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 (optical coherence tomography), particularly also given its poor tissue penetra-
tion (< 1.5 mm (millimetre)). Furthermore, the OCT (optical coherence tomography) imaging
plane rarely intersects the stent struts perpendicularly, thereby resulting in shadows much larg-
er 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 interfer-
ogram, 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 re-

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 flection. 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 [111]. Intravascular OCT (optical coherence tomography)
is unable to penetrate advanced, thick plaque, irrespective of the position of the OCT (optical
coherence tomography) imaging device within the lumen. This leads to a major limitation of
OCT (optical coherence tomography), namely the inability to measure plaque burden in ad-
vanced atherosclerosis. This drawback may have some clinical implications, especially in diffuse
disease where IVUS (intravascular ultrasound) has been used in the past to assess the longitudi-
nal extension of plaque burden and to select the most appropriate stent length. The most es-
tablished criterion to identify reference segments is a plaque burden less than 40% by IVUS (in-
travascular ultrasound) [112]. This definition originates from the IVUS (intravascular ultrasound)
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 (optical coherence tomography) 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
(Fractional flow reserve versus Angiography for Multivessel Eva) study, highlighting the link be-
tween physiological assessment of lesion severity by means of fractional flow reserve and pa-
tient clinical outcome [113].

Plaque composition
The limited penetration depth into the vessel wall can reduce the sensitivity of OCT (optical co-
herence tomography) for different plaque components. An ex vivo comparison with histology
suggested that even experienced observers could have difficulties differentiating lipid and calci-
fied tissue by visual evaluation of OCT (optical coherence tomography) images. The misclassifi-
cations between lipid pools and calcium deposits described in the study were related to limita-
tion of the technology, such as the limited penetration or the presence of artifacts but also to
the heterogeneity of the plaque components [25]. Calcium deposits as well as lipid-rich tissues
appear signal- poor by OCT (optical coherence tomography). These two tissue types can be dis-
criminated 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 (optical coherence tomography) image analysis are being de-
veloped in centers around the world to extract anatomical and compositional tissue properties
in a more objective, user-independent way [114, 115, 116]. Recently, Faber et al have demon-

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 strated in vitro that the optical attenuation coefficient (μt) is principally a useful parameter to
distinguish different tissue types when using an OCT (optical coherence tomography) micro-
scope. van Soest et al have confirmed that the optical attenuation coefficient (μt) can distin-
guish 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 [117]. Likewise, three-dimensional reconstructions, including
tissue characterisation employing attenuation coefficient but also other parameters, have been
described with the second generation FD-OCT (Fourier domain optical coherence tomography)
systems [118].

! FOCUS BOX 8
Limitations
The main limitation of intracoronary OCT (optical coherence tomography) arises
from the fact that light can not penetrate blood
OCT requires clearing of the artery from blood during the imaging procedure
Visualisation of the ostium of the left main stem or the right coronary artery is
difficult
OCT should not be performed in patients with severely impaired left ventricular
function or those presenting with haemodynamic compromise
OCT should be used with caution in patients with a single remaining vessel or
those with markedly impaired renal function
OCT is not able to visualise the media or adventitia in advanced coronary
plaque with intimal thickening exceeding 1.5-2 mm

PERSONAL PERSPECTIVE – EVELYN REGAR

At the Thoraxcenter, we initiated the academic intracoronary OCT (optical coherence tomogra-
phy) programme a decade ago. Back then, the first generation, time domain OCT (optical coher-
ence tomography) required a rather cumbersome imaging procedure as blood had to be
cleared from the field of view during imaging: a standard angioplasty balloon was inflated with
the transparent mixture of x-ray contrast and saline, while the OCT (optical coherence tomogra-
phy) image wire was introduced into the guidewire lumen and a pullback was performed within
the balloon during brief inflation. Further stepwise improvement of the imaging procedure es-
tablished OCT (optical coherence tomography) for in vivo imaging of coronary stents, with the
ODESSA and the LEADERS trials pioneering OCT (optical coherence tomography) in multicentre,
randomised, clinical settings. In 2008, the introduction of the second generation, Fourier do-
main OCT (optical coherence tomography) enabled a paradigm shift: this remarkable innovation
transformed OCT (optical coherence tomography) from a niche technology applied by experts in
selected patients to a robust, user-friendly and reliable clinical research modality. Fourier do-
main OCT (optical coherence tomography), 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 (optical coherence tomography) is the widely accepted gold
standard for the assessment of coronary stents. Future applications will include tissue charac-
terisation, sub-cellular resolution imaging and the 3D (three-dimensional) representation of

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 complex biological structures. When it comes to broad clinical application, OCT (optical coher-
ence tomography) offers a considerable number of potential clinical applications to facilitate
clinical decision-making. However, there are still a number of issues (besides lack of evidence
from well-controlled trials basically reflecting the novelty of the technology) which can challenge
clinical application. OCT (optical coherence tomography) gives detailed structural, anatomical
information; however, it is currently not capable of providing the operator with functional infor-
mation to assess, e.g. (exempli gratia / for example), the haemodynamic relevance of stenoses
in patients presenting with stable angina. On the other hand, OCT (optical coherence tomogra-
phy) can recognise many features associated with plaque instability. However, it is limited by its
penetration depth into the tissue. A number of research groups have successfully combined
OCT (optical coherence tomography) with an ultrasound transducer, allowing the combination
of the high resolution of OCT (optical coherence tomography) in the near field with the penetra-
tion depth of IVUS (intravascular ultrasound) to visualise the complete plaque as well as to as-
sess plaque burden. While the excellent resolution and the high contrast between lumen and
vessel wall allow for easy image interpretation and a remarkably steep learning curve, interpre-
tation 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 (optical coher-
ence tomography) signal. Promising concepts for quantitative tissue characterisation might fur-
ther improve the diagnostic capabilities in the future. Finally, OCT (optical coherence tomogra-
phy) 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 en-
sure that knowledge gain in different clinical scenarios all over the world can be shared and
used to improve our clinical practice [119].

The authors recommend for further reading: The Clinical Atlas of Intravascular Optical Coher-
ence Tomography (OCT) by Maria D (days). Radu, Lorenz Räber, Hector M. Garcia-Garcia, Patrick
W. Serruys (Editors). PCR 2012. via the following link: http://www.pcrpublishing.com/octatlas
(http://www.pcrpublishing.com/octatlas)

ONLINE DATA SUPPLEMENT

" MOVING IMAGE 1 (90_1084_2_07_Regar_Video_01_090793OCT-acute-post-stent.mp4)
“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 (90_1085_2_07_Regar_Video_02_Animation-of-C7-Deployment.mp4)

“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 with-
drawn during simultaneous flush delivery through the guide catheter.

" MOVING IMAGE 3 (90_1086_2_07_Regar_Video_03_C7-pullback-real-time.mp4)

“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

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 cause ischaemia and shows few motion artifacts.

" MOVING IMAGE 4 (90_1087_2_07_Regar_Video_04_NCLCX-OCT-fup-post-stent.mp4)

“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 lo-
cated at the side branch ostium are clearly visible.

" MOVING IMAGE 5 (90_1088_2_07_Regar_Video_05_St_Jude_C7XR.mp4)

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

! REFERENCES

RECOMMENDED REFERENCES

1. Huang D, Swanson EA, Lin CP, Schuman JS, Stinson WG, Chang W, Hee MR, Flotte T, Gregory
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(http://www.ncbi.nlm.nih.gov/pubmed?term=Science. 1991;254:1178-81.)
Landmark publication on the principle of optical coherence tomography
3. Regar E, van Leeuwen AMGJ, Serruys PW, eds. Optical coherence tomography in cardiovas-
cular research. London: Informa Healthcare; 2007. % (http://www.ncbi.nlm.nih.gov/pubmed?
term=Informa Healthcare. 2007.)
In-depth description of the physical principle, practical application in the cathlab, pitfalls, research ap-
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Grube E, Ozaki Y, Pinto F, Serruys PW; Expert’s OCT Review Document. Expert review document
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