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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5528_Библиотеки_им_академика_М_И_Перельмана.pdf
30 S. Torii
et al.
Optical coherence tomography (OCT) provides high-resolution
images (10–20 µm axial resolution), allowing assessment of plaque composition mostly limited to the superficial regions of plaques and microstructures that far exceeds existing standard intravascular imaging techniques,
such as intravascular ultrasound (IVUS).
3
OCT processes backscattering infrared light to generate real-time tomographic images. The imaging
catheter is made up of an inner imaging core surrounded by an outer sheath.
The imaging core is comprised of an optic fiber with a prism and micro
lens at the distal tip that generate a scanning beam perpendicular to the axis
of the inner core, which rotates within the outer sheath to produce a cross-
4
sectional image.
The older versions of this technology used time-domain
detection. The current version of OCT uses frequency-domain detection,
that allows the backscattering light from different locations to be measured
simultaneously, enabling a rapid pullback and shorter acquisition time during non-occlusive luminal flush with contrast.One of the limitations of OCT
is poor penetration depth (to 1–3 mm) of the light beam through blood and
tissue resulting in the incomplete reflection from the deeper arterial layers,
preventing the determination of exact vessel dimensions in areas where the
plaque burden is large.
5
OCT has been successfully used to identify different stages
of atherosclerotic coronary plaques, including thin cap fibroatheroma
(TCFA).
6
In this chapter, we will discuss how OCT can identify the stepwise pathological progression of atherosclerotic plaques similar to histology. We will also highlight how OCT can potentially be used to identify
high-risk plaques and aid in the management of acute coronary syndromes
(ACSs).
5
Normal vessel wall, intimal thickening, and intimal xanthoma (fatty streak)
The normal vessel wall is characterized by a layered architecture, comprising a highly backscattering or signal-rich intima (thin), a media that
frequently has low backscattering or is signal poor, and a heterogeneous
and frequently highly backscattering adventitia. With OCT, the internal
elastic membrane (IEM) is defined as the border between the intima and
Coronary Arteries 31
inma
Figure 1. Normal coronary arterial wall. The normal vessel wall is characterized by a layered
architecture, comprising a highly backscattering or signal-rich intima (thin), a low backscattering
media, and a heterogeneous and frequently highly backscattering adventitia.
media
advena
media, and the external elastic membrane (EEM) is defined as the border
between the media and the adventitia (Figure 1).
Intimal thickening is observed in all arteries, especially near branch
7
points,
and is considered a physiological response to blood flow rather
than an atherosclerotic process. Intimal thickening lesions may regress over
time; however, these lesions are thought to evolve early and, in children,
are seen at similar locations to where more-advanced lesions develop in
8
adults.
Histologically, regions of intimal thickening contain focal accumulation of smooth muscle cells, with proteoglycan- and collagen-rich
extracellular matrix with an absence of inflammation. Although there is
some evidence that supports the idea that intimal proliferation is a precursor of a more-advanced atherosclerotic lesion,
2,8
another theory is that
intimal proliferation is an adaptive vascular process to altered blood flow
in coronary arteries.
2
Intimal xanthomas, or so-called “fatty streaks”, are lesions primarily
composed of infiltrating macrophage foam cells and, to a lesser extent,
lipid-laden SMCs within the intima.
9
Intimal xanthomas do not always
lead to more-advancedatherosclerotic plaques and in fact have been shown
to regress and, therefore, are not considered as progression-prone diseases.
32 S. Torii
et al.
(a) (b) (c)
(d) (e)
c
b
I
M
A
I
M
A
I
M
A
I
M
A
Figure 2. Intimal thickening and intimal xanthoma. (a) Low-power and (b, c) high-power ex vivo
OCT images showing i ntimal thickening (panels a and b) and intimal xanthoma (panels a and
c) in a human coronary artery. Three layers — A, I, and M — are apparent in the arterial wall.
A focal signal-rich confluent punctate region (white arrows in panel c) is observed close to the
luminal surface, which is accompanied by signal attenuation (white arrowheads in panel c). (d, e)
Corresponding histological images showing intimal thickening without macrophages (panel d), and
intimal xanthoma characterized by the presence of foamy macrophages (black arrows) within the
thin neointima (panel e). Abbreviations: A, adventitia; I, intima; M, media; OCT, optical coherence
tomography. Histological image in panel a reprinted with permission from Nature Publishing Group
© Otsuka, F., et al. Clinical classification of plaque morphology in coronary disease. Nature Reviews
Cardiology, 11(7): 379–389 (2014).
Correlative histopathological imaging clinical data showing the fate
of intimal thickening is lacking, especially data from observational studies.
From our experience, intimal thickening is most often seen by OCT as a
high backscattering signal-rich appearance in the a bsence of shadowing or
severe attenuation of the light beam situated just above the media which
has a signal-poor appearance as compared to the intima and adventitia
(Figure 2).
Pathological intimal thickening
Pathological intimal thickening is the earliest progressive atherosclerotic
lesion and is characterized by the presence of an acellular lipid pool,
Coronary Arteries 33
consisting of proteoglycans and lipids, with the absence of both smooth
muscle cells and macrophages that are often located close to the medial
8,10
wall
(Figure 3). It is the presence of lipid pool that separates intimal
thickening from pathologic intimal thickening. The luminal intima consists
of smooth muscle cells in a proteoglycan- and collagen-rich extracellular
matrix and may or may not contain macrophages and T-lymphocytes,which
are usually remote from the lipid pool, i.e. close to the lumen. Pathological intimal thickening is the earliest type of atherosclerotic lesion that
exhibits calcification, visualized by either von Kossa or Alizarin red staining, on non-decalcified paraffin-embedded sections as microcalcifications
(≥ 0.5 µm and typically <15 µm) and likely originates from the death of
smooth muscle cells or from matrix vesicles, but these are characteristically 100–700 nm with calcium phosphates appearing inside these matrix
vesicles, forming hydroxyapatite crystals, akin to bone formation.
11
Pathological intimal thickening in the absence of macrophages typically appears as focal thickening of the intimal layer exhibiting high
backscattering signal by OCT with moderate attenuation of the light beam
in the deeper intimal layers (Figure 3). However, the ability of OCT to
separate lipid pools from necrotic core remains difficult, probably because
the lipid pool usually forms within the deeper intimal regions, close to the
medial layer, where the attenuated light beam results in insufficient penetration to illustrate anatomical details. Also, when macrophages are present in
the superficial intimal layers as signal-rich, distinct, or confluent punctate
areas, they are accompanied by s hadowing of the underlying tissuestructure
as observed by OCT.
3,12
Rapid attenuation of the penetrating light beam is
a key component of macrophage-rich lesions, and because of the rapid drop
in signal, it is difficult to separate lipid pool from necrotic core (Figure 3),
which are important features of fibroatheroma and TCFA (described in the
following).
Fibroatheroma
Fibroatheroma is considered a more advanced stage of atherosclerosis
progression and is characterized by the presence of an acellular necrotic
core formed by the infiltration of the lipid pool by macrophages, the
latter releasing MMPs that are responsible for the breakdown of the
34 S. Torii
(a) (b) (c)
Movat
(d) (e) (f )
Movat
Figure 3. Pathological intimal thickening. (a–c) Images showing macrophage-poor pathological intimal thickening. (d–f) Images showing pathological intimal thickening containing macrophages. Focal
signal-poor region with diffuse border (white arrowheads) in ex v ivo OCT images (panels a and d)
correspond with the presence of LP in low-powered (panels b and e) and high-powered (panels
c and f) images of histological sections of human coronary plaques (all sections are stained with
Movat pentachrome). Signal-rich confluent punctate area with attenuation is observed in the OCT
image in panel d (white arrows), which corresponds with the presence of foamy macrophages in the
histology in panel f (black arrows). Abbreviations: LP, lipid pool; OCT, optical coherence tomography.
Histological image in panel a reprinted with permission from Nature Publishing Group © Otsuka, F.,
et al. Clinical classification of plaque morphology in coronary disease. Nature Reviews Cardiology,
11(7): 379–389 (2014).
et al.
LP
LP
proteoglycan–collagenousmatrix (Figure 4). Fibroatheroma can be further
subdivided into early and late stages, based mainly on the relative extent to
which the proteoglycan–collagenous matrix isbroken down. The early stage
of fibroatheroma is characterized by the presence of the lipid pool with focal
areas showing macrophage infiltration as well as breakdown of the matrix,
while in the late stage, the lipid pool is replaced by necrotic tissues and there
are discreet areas of lack of necrosis containing large cholesterol clefts. In
lesions with late fibroatheroma, there may be a sudden increase in luminal
stenosis from episodes of intraplaque hemorrhage which can occur from
Coronary Arteries 35
(a) (b) (c)
LP
NC
Movat
(d) (e) (f)
NC
Movat
Figure 4. Fibroatheroma. (a–c) Images showing early fibroatheroma. (d–f) Images showing late
fibroatheroma. Low backscattering, signal-poor regions with diffuse border (white arrowheads) in
ex vivo optical coherence tomography images (panels a and d) correspond with the presence of LP or
NC in low-powered (panels b and e) and high-powered (panels c and f) images of histological sections
of human coronary plaques (all sections are stained with Movat pentachrome). Early NC in panel c
is characterized by the infiltration of foamy macrophages into the LP, with focal loss of proteoglycan
and/or collagen matrix and cholesterol cleft. Late NC in panel f consists of discrete collections of
cellular debris with extensive cholesterol cleft and intraplaque hemorrhage (black arrows) where
extracellular matrix is almost completely depleted. Abbreviations: LP, lipid pool; NC, necrotic core.
Histological image in panel a reprinted with permission from Nature Publishing Group © Otsuka, F.,
et al. Clinical classification of plaque morphology in coronary disease. Nature Reviews Cardiology,
11(7): 379–389 (2014).
NC
NC
two sources either from hemorrhage from rupture of intraplaque/plaque fissure or from leaky vasa vasorum with an incompetent endothelium. These
fibroatheromas are often accompanied by focal calcification, which is more
prominent in the necrotic cores that show hemorrhage.
Fibroatheromas on OCT have a superficial high backscattering bright
signal (Figure 4), with pronounced signal a ttenuation of light in the deeper
plaque regions. The signal attenuation is most pronounced in the presence
of macrophages with gradual signal attenuation of light, whereas if there is
calcification, the signal attenuation is sudden. The major drawback of OCT
36 S. Torii
et al.
technology is the limited tissue penetration (1–3 mm), which precludes
the determination of exact vessel dimensions in areas with large plaque
burden,
5
and in the cases of calcification, one may not be able to see the
outer rim of the calcium. As such, OCT is more accurate for identifying
necrotic cores that are in close proximity to the intimal surface. It is not possible to distinguish early fibroatheromas from late fibroatheromas by OCT
nor is it possible to differentiate lipid pool, necrotic core, and intraplaque
hemorrhage from one another by OCT.
Thin-cap fibroatheroma
Retrospective angiographic studies of patients presenting with AMI
promoted the idea that MI frequently develops in previously non-severe
lesions.
hemodynamically insignificant plaques as vulnerable plaques, defined as
lesions that have a susceptibility to rupture.
that there are other etiologies of luminal thrombosis such as plaque erosion
and calcified nodule and that to define the precursor lesion of plaque rupture,
the definition had to be more specific, and the term “thin-cap fibroatheroma”
(TCFA; Figure 5) was used and not vulnerable plaque as this term includes
precursor lesions of all luminal thrombi, i.e. erosion and calcified nodule.
TCFA has a large necrotic core (usually occupying >25% of the plaque
area
measurement of the thickness of the fibrous cap near sites of rupture which
was 23 ± 19 µm with 95% of caps measuring <64 µm.
cap is composed predominantly of collagen type I with varying degrees of
macrophages and lymphocyte infiltration, and there is paucity or absence
of smooth muscle cells. The thinning or weakening of the fibrous cap is an
important precursor for plaque rupture.
from ruptured plaques, as they tend to have a smaller necrotic core, fewer
macrophages within the fibrous cap, less plaque burden, and less luminal
encroachment than ruptured plaques.
has been employed to identify TCFA using a <85 µm cut-off for the thin
cap.
criteria developed from histopathological studies should be adjusted for
13
This concept led James E. Muller et al. in 1989 to name these
14
Morerecently,wehaveshown
15
) encased by a thin fibrous cap. The 65uM threshold is based on the
16
The thin fibrous
2,17
Although similar, TCFAs differ
18
OCT can be used to measure fibrous cap thickness and, therefore,
19,20
This cut-off has been chosen on the basis that the well-established
Coronary Arteries 37
(a) (b) (c)
NC
NC
Movat
(d) (e) (f)
NC
Figure 5. Thin-cap fibroatheroma with extensive hemorrhage. Thin-cap fibroatheroma with extensive
hemorrhage. (a–c) Low-powered images. (d–f) High-powered images. A low backscattering, signalpoor region with diffuse border (white arrow heads) in an ex vivo OCT image (panel a) corresponds
with a large NC with extensive intraplaque hemorrhage in histological sections of human coronary
plaques (panel b; section stained with Movat Pentachrome). A high-power OCT image in panel
c shows distinct superficial high backscattering, signal-rich region (white arrows) and thin fibrous
cap (double arrow = 70µm). A corresponding high-power histological image in panel d shows thin
fibrous cap that is heavily infiltrated by macrophages. The infiltrated macrophages in the black square
are further highlighted in an even higherpower image (panel e) and also confirmed in panel f by
immunostaining for CD68+ macrophages (black arrows). Abbreviations: NC, necrotic core; OCT,
optical coherence tomography. Histological image in panel a reprinted with permission from Nature
Publishing Group © Otsuka, F., et al. Clinical classification of plaque morphology in coronary disease.
Nature Reviews Cardiology, 11(7): 379–389 (2014).
NC
CD68
shrinkage (20–25%) that occurs both from fixation and dehydration and is
applied to OCT images to determine the in vivo cap thickness.
3, 21
Others
have reported a threshold of 65 µm for establishing the diagnosing TCFA,
which is similar to that established by histopathology.
22
Nevertheless, an
appropriate in vivo threshold remains to be validated and several OCT studies have also used the arc of necrotic core as an additional parameter for
detecting TCFA
death demonstrate arcs of necrotic core that exceed 120
3
; most TCFA in the autopsy cases of sudden coronary
◦.23
Indeed, the
definition of necrotic core arc to detect TCFA as an adjunct to measuring
fibrous cap thickness seems reasonable, although artificial attenuation of
OCT signal with feint of TCFA secondary to tangential signal dropout in
38 S. Torii
et al.
case of eccentric catheter position close to the vessel wall must be considered.
24
A change in OCT catheter position may help distinguish signal
attenuation due to the necrotic core formation from artificial signal dropout.
Ruptured plaques
Plaque rupture (PR)is the commonest pathological substrateresponsible for
acute coronary syndromes (ACSs), accounting for ∼75% of acute myocar-
2
dial infarctions.
with an overlying disrupted thin fibrous cap and can be distinguished from
TCFA by the presence of a luminal thrombus. At the rupture site, the luminal
thrombus is usually platelet-rich and grossly appears as a white thrombus;
a predominance of red thrombus is apparent at the proximal and distal
propagation sites. Organizing thrombus is characterized by an infiltration
of inflammatory cells, smooth muscle cells, and endothelial cells, with surrounding extracellular matrix (that is, mostly proteoglycans and type III
collagen-rich).
Ruptured plaques, usually have an underlying necrotic core which is
large in size (usually occupying >30% of the plaque area).
cap as stated above consists mainly of type I collagen, with greater degrees
of macrophages and lymphocytes than in TCFAsand with sparse or absence
of smooth muscle cells. The thickness of the fibrous cap at the rupture
site is 23 ± 19 µm, and 95% of the cap measures <64 µm.
fibrous cap rupture is mostly thought to occur at its weakest point, often
near shoulder regions, autopsy studies using serial sectioning demonstrate
an equal number of ruptures are located at the mid-portion of the fibrous
cap, especially when rupture occurs following exercise.
disrupted cap, the circulating cellular and non-cellular elements come in
direct contact with the highly thrombogenic components of the necrotic
core and result in the formation of a platelet-rich thrombus (Figure 6).
Focal calcification or larger calcified sheets are frequently observed around
the necrotic core of ruptured plaques. We have observed its presence in
over 80% of ruptured lesions with the calcium mostly located toward the
abluminal surface of the necrotic core.
Previousclinical OCT imaging studies have shownthat the presenceof
plaque rupture is the most frequently identified cause of ACS.
Ruptured plaques (Figure 6) consist of a necrotic core
2,18
The fibrous
25
Although
26
At the site of the
27
20,28
In these
Coronary Arteries 39
https://avxhm.se/blogs/hill0
(a) (b) (c)
LM
LAD
(d) (e)
LCX
RI
b
c
d, e
(f)
NC
Thr
CD68
Movat
Thr
Figure 6. Ruptured plaque associated with nonocclusive luminal thrombus. A man aged 45 years
with a history of hypertension, diabetes mellitus, and hyperlipidaemia died suddenly after jogging
during his lunch break. (a) Postmortem angiography showed mild luminal narrowing with haziness at
proximal RI. (b–d) Serial OCT images revealed the presence of plaque rupture (in panels c and d)
with nonocclusive luminal thrombus (white arrowhead in panel d) and an adjacent distinct superficial
signal-rich region (white arrows in panel b) with rapid attenuation (white arrowheads in panel b)
indicating thin-cap fibroatheroma. Disrupted fibrous cap also shows distinct superficial signal-rich
region (white arrows in panels c and d). (e) Histology confirmed the presence of plaque rupture
with an acute fibrin-rich thrombus (shown as Thr) overlying the NC (section stained with Movat
pentachrome). (f) Immunostaining for CD68+ macrophages demonstrated substantial infiltration
of macrophages within the disrupted fibrous cap (black arrows). Abbreviations: LAD, left anterior
descending coronary artery; LCX, left circumflex coronary artery; LM, left main coronary artery; NC,
necrotic core; OCT, optical coherence tomography; RI, ramus intermedius. Histological image in panel
a reprinted with permission from Nature Publishing Group © Otsuka, F., et al. Clinical classification
of plaque morphology in coronary disease. Nature Reviews Cardiology, 11(7): 379–389 (2014).
studies, the disrupted fibrous cap was < 70 µm thick and was observed
in 67% of cases; median cap thickness was 54 µm (interquartile range
[IQR] 50–60 µm), and 95% of the thinnest cap measured <80 µm. These
clinical observations confirm our pathology data as stated above. One of