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Vascular applications of quantitative optical coherence tomography
van der Meer, F.J.
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van der Meer, F. J. (2005). Vascular applications of quantitative optical coherence tomography
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Download date: 16 Jun 2017
GENERAL INTRODUCTION
GENERAL INTRODUCTION
ardiovascular disease is the leading cause of death in developed countries and is
rapidly becoming the number one killer in the developing countries.' In 2002, it
accounted for 34% of all mortality in the Netherlands, translating to 134 deaths
per day.2 Moreover, 231 patients per day were submitted to a hospital with a cardiac event
in that year. Atherosclerosis, a disease that can lead to these chronic vascular obstruction
and acute coronary and cerebrovascular syndromes, damages the lining of the coronary
arteries, making them susceptible to the formation of blood clots and stenoses.
Atherosclerotic plaque can build up for years before vessel narrowing becomes apparent: a
debilitating or fatal heart attack is often the first indication of the underlying disease.
C
ATHEROSCLEROSIS
Previously, atherosclerosis was regarded as a straightforward plumbing problem: fat
deposits on the surface of static arterial walls, eventually blocking the pipe.' Nowadays it
is recognized that the lesions result from an excessive, inflammatory-fibroproliferative
response to various forms of insult to the endothelium and smooth muscle of the arterial
wall.4'5 Atherosclerotic lesions do not occur in a random fashion; the coronary arteries, the
major branches of the aortic arch, the abdominal aorta and its visceral and major lower
extremity branches are particularly susceptible sites. Hemodynamic forces interacting with
an active vascular endothelium are responsible for localizing lesions in this nonrandom
pattern of distribution. Shear stress and cyclic circumferential strain are the predominant
forces that for example modify the endothelial cell structure and function/'
The normal arterial wall (figure 1-1 A) is composed of three layers, which are separated
by elastic laminas. The innermost layer, the intima, is separated from the blood stream by
endothelial cells and is in normal condition a thin layer of extracellular matrix and an
11
CHAPTER 1
• •
•*•
adventitia
media
intima
lipid pool
calcification
thrombus
macrophages
F i g u r e 1-1. S c h e m a t i c d r a w i n g of the n o r m a l arterial wall A and of
atherosclerotic lesions, showing lipid accumulation (B), ruptured lipid rich plaque
with non-occlusive t h r o m b u s (C), t h r o m b o s i s due to erosion, endothelial
denudation (D), calcification (E) and chronic occlusion I .
i n c i d e n t a l s m o o t h m u s c l e cell (SMC). The intima is separated from the media by the
internal elastic lamina. T h e media c o n s i s t of S M C s , b u n d l e s of collagen fibers and elastic
fibrils, e m b e d d e d in an extracellular matrix, li is separated from the o u t e r m o s t adventitia
b\ the external elastic lamina. T h e adventitia is a layer of c o n n e c t i v e tissue, collagen a n d
elastic libers e m b e d d i n g the e n u r e vessel within its s u r r o u n d i n g s .
In general, a t h e r o s c l e r o s i s starts with lipid deposition in the intima, the so-called 'fatty
streak'. T h e lipid d e p o s i t i o n gradually increases and the intima thickens due to migrating
S M C s t r o m the m e d i a a n d m o n o c y t e s that e n t e r from the b l o o d . T h e
monocytes
differentiate into m a c r o p h a g e s that internalize the lipid deposition, b e c o m i n g lipid loaden
foam cells, w h e r e a s S M C c h a n g e from migrating into a secreting p h e n o t y p e , p r o d u c i n g
collagen to form a p r o t e c t i v e cap figure 1 - IB). D u e to c o m p e n s a t o r } e n l a r g e m e n t of the
12
GENERAL INTRODUCTION
vessel, early lesions can continue to develop without compromising the lumen
('remodeling'). 7 However, some plaques with a large lipid core, which by now contain both
apoptotic and necrotic cells and cellular debris and have a thin fibrous cap, are prone to
rupture. Further lipid deposition and necrosis of foam cells result in a lipid pool, which
thrombogenic contents cause thrombus formation when cap rupture occurs (figure 1-1C).
Thrombus formation may also occur when the endothelial lining is damaged (erosion)
(figure 1-1D). The thrombus can embolize in other vessels causing symptoms of acute
syndromes, such as the abrupt reduction in flow to a region of the myocardium (myocardial
infarction), or strokes. Further advanced plaques show calcifications (figure 1-1E) which
can result in thrombus formation by protruding into the lumen through a disrupted thin
fibrous cap. Healing of cap rupture and further accumulation of lipid, calcifications, SMCs
and fibrous tissue can eventually compromise the vascular lumen (figure 1-1F).
VULNERABLE PLAQUE
Vulnerable plaques have been defined as precursors to lesions that rupture. A large
number of vulnerable plaques are relatively uncalcified, relatively nonstenotic, and similar
to type IV atherosclerotic lesions described in the American Heart Association classification.''
They are morphologically characterized by a lipid core covered by a thin fibrous cap (thickness
< 65 / um). l o r > These unstable plaques are very prone to rupture or fissure, especially in the
Morphology/structure
Activity/'function
Cap thickness
Inflammation (macrophage density)
I jpid core size
Endothelial denudation or dysfunction
Stenosis
Plaque oxidative stress
Remodelling
Superficial platelet aggregation/fibrin
deposition
Color
Rate of apoptosis
Collagen content vs. lipid content, mechanical
stability
Angiogenesis, intraplaque hemorrhage,
leaking vasa vasorum
Calcification burden and pattern
Matrix-digesting enzyme activity (MM I')
Shear stress
Certain microbial agents (HSP60,
C. Pneumoniae)
Adapted from ret. H
Table 1-1 Overview of markers for plaque vulnerability, categorized into
morphological or functional markers.
13
CHAPTER 1
s h o u l d e r s of the fibrous cap, with subsequent e x p o s u r e o f the t h r o m b o g e n i c lipid c o r e t o
t h e flowing b l o o d , resulting in t h r o m b o s i s . H o w e v e r , different types of vulnerable plaque
exist. C o r o n a r y t h r o m b o s i s m a y o c c u r from o t h e r lesions like plaque e r o s i o n and calcified
n o d u l e s , a l t h o u g h to a lesser frequency than c a p r u p t u r e . I n a r e c e n t publication, N a g h a v i
i't a/, s u m m a r i z e d the c h a r a c t e r i s t i c s o f a t h e r o s c l e r o t i c lesions that resulted in vascular
o c c l u s i o n and o t h e r clinical s y m p t o m s (table 1-1). u
IMAGING OF THE VULNERABLE PLAQUE
S e v e r a l i m a g i n g t e c h n i q u e s are currently available for the d e t e c t i o n o f s t e n o s i s a n d
p l a q u e s , r a n g i n g f r o m n o n - i n v a s i v e to catheter b a s e d invasive s y s t e m s , u s i n g e l e c t r o m a g n e t i c o r u l t r a s o u n d waves. 13 " 18 For non-invasive imaging, the radiation which is minimally
a b s o r b e d by tissue can b e utilized. I n figure 1-2, t h e a b s o r p t i o n s p e c t r u m of w a t e r for
e l e c t r o - m a g n e t i c w a v e s is p l o t t e d . F r o m this g r a p h it is clear that for X-rays, y-rays a n d
r a d i o w a v e s the a b s o r p t i o n coefficient is smaller t h a n 1 cm"' a n d therefore t h e s e are very
s u i t a b l e for i m a g i n g t h r o u g h c e n t i m e t r e s o f tissue. X-rays h a v e b e e n utilized for m o r e
t h a n h u n d r e d years for n o n - i n v a s i v e imaging. T h e c o n t r a s t is b a s e d o n differences in
a b s o r p t i o n for t h e X-rays by t h e tissue. H o w e v e r , d u e t o the l o w a b s o r p t i o n differences
b e t w e e n b l o o d a n d vascular wall c o m p o n e n t s , highly a b s o r b i n g contrast agents have to b e
i n j e c t e d to visualize t h e l u m e n . C o n s e q u e n t l y , a n g i o g r a p h y visualizes, albeit with a g o o d
r e s o l u t i o n , the v a s c u l a r l u m e n b u t is n o t able to i m a g e the vascular wall and its c o n t e n t s .
D u e to t h e fact t h a t v u l n e r a b l e p l a q u e s are o f t e n h e m o d y n a m i c a l l v insignificant, they are
difficult to detect with angiography. v> ~" Still, angiography was the gold standard for c o r o n a r y
i m a g i n g l o r d e c a d e s . C o m p u t e d t o m o g r a p h y of m u l t i d i r e c t i o n a l X-ray p r o j e c t i o n s (CT)
a l l o w s 3 D v i s u a l i z a t i o n of m o r p h o l o g i c s t r u c t u r e s . H o w e v e r , d u e to limited r e s o l u t i o n
(up t o 0.6 x 0.75 m m ) a n d limited contrast, a l t h o u g h m u c h better than for X-ray projection
i m a g i n g , only calcifications can b e clearly d e t e c t e d .
2I
F o r the m o r e e n e r g e t i c p a r t of t h e
e l e c t r o - m a g n e t i c s p e c t r u m , the imaging techniques like P E T a n d S P E C T a r e h a m p e r e d by
t h e i r l o w r e s o l u t i o n ( a p p r o x i m a t e l y 3-10 m m ) . ~
A t t h e o t h e r side o f the s p e c t r u m , radio w a v e s in c o m b i n a t i o n with a high m a g n e t i c
field are u s e d to non-invasively i m a g e tissues. In this so called nuclear magnetic r e s o n a n c e
i m a g i n g (MRI), radio w a v e s are used to excite the m a g n e t i c field induced split g r o u n d state
o f h y d r o g e n a t o m s in the tissue. After excitation, r a d i o w a v e s are e m i t t e d w h i c h can b e
c h a r a c t e r i z e d t h r e e p a r a m e t e r s : the signal s t r e n g t h , w h i c h d e p e n d s o n the density of the
p r o t o n s , t h e t i m e T , n e e d e d for recovery o f the excited spins to the e q u i l i b r i u m , w h i c h
d e p e n d s o n the spin-lattice i n t e r a c t i o n and the decay t i m e T 7 of the R F signal, w h i c h
d e p e n d s o n the s p i n - s p i n i n t e r a c t i o n . These p a r a m e t e r s are tissue specific a n d t h e r e f o r e
c a n b e u s e d t o differentiate the tissue c o m p o n e n t s . T h u s M R I has t h e p o t e n t i a l to
d i s t i n g u i s h a t h e r o s c l e r o t i c p l a q u e a n d to d e t e r m i n e its c o m p o s i t i o n a n d m i c r o a n a t o m y 2 ' .
I n p a t i e n t s , M R I is able to identify u n s t a b l e p l a q u e s in the aorta. 2 4 H o w e v e r , t h e
r e s o l u t i o n of M R I , w h i c h is approximately 0.4 m m i n - p l a n e r e s o l u t i o n with a 3 - m m slice
14
GENERAL INTRODUCTION
Frequency [Hz]
FIGURE 1-2 The absorption coefficient of water as a function of the frequency
of the electro magnetic waves. Note the logarithmic scales and the regions in
which the absorption coefficient is less than 1 cm"1: Radio waves, visible light, X
and y rays.
thickness, 2526 and the imaging time (several minutes) limit its application for the detection
of the specific morphological characteristics of unstable plaques in coronary arteries. 2
Tn the visible part of the electro-magnetic spectrum, the absorption by water is also
low (figure 1 -2). However, in this part the scattering of the light by the tissue constituents
hampers the utilisation of these electro-magnetic waves for non-invasive imaging. Using
fiber-optics, light can be used in catheter based systems for intravascular imaging. In
angioscopy, via a coherent bundle of optical fibers, an intra-luminal image is obtained
while the blood is removed with flushing saline or C O , gas. 28 Angioscopy is a straightforward imaging technique that only provides information on the morphology of the
endo-luminal surface and is therefore, like angiography, unable to identify the extent of an
atherosclerotic plaque into the vessel wall. In some cases, angioscopy can indirectly detect
the position of a fibroatheromatous plaque. 2 '' The yellow color intensity of plaque
determined by angioscopy can indicate the prevalence of thrombosis on the plaque and
thus be a marker of plaque vulnerability.1" Finally, the plaque cap thickness is a determinant
of plaque color and quantitative colorimetry might be useful for the detection of vulnerable
plaques.''Instead of electro-magnetic waves, also acoustic waves can be used for medical
imaging. In ultrasound (US) imaging, the intensity of back-reflected acoustic pulses is
depicted as a function of the time of flight. The contrast of US imaging is based on
differences in the acoustic impedance of the different tissue layers. Both the axial resolution
and the attenuation of the US in tissue are proportional to the frequency of the US waves
15
CHMM!K1
(figure 1 -3). Therefore, for high resolution imaging of the arterial wall, the I S signals of
frequencies around 311 MI 1/ have t< > be delivered and detected intravascular. This intravascular
ultrasound (IVUS) imaging, which lias an axial resolution of approximately 100 fivn,
currently represents the gold standard in the assessment of atherosclerotic disease. [VI S
facilitated in-depth understanding of coronary artery disease. like arterial remodelling and
therapeutic strategies like stent implantation and coronary brachv ihcrapv. [VUS imaging,
although being able to image the vascular wall, is limited in specifically identifying lipidrich plaques, thus the contrast and the res. >lution are not suitable for directly detecting
the vulnerable plaque.
I sing a sophisticated analysis of the I S signals obtained during systole, the local
mechanical properties can be assessed. This so called elastography can distinguish the
weaker and stiffer regions in the arterial wall and therefore can identify the vulnerable
plaque. Intravascular elastography is a unique tool to assess lesion composition and
vulnerability, ' ; S(' which has proven to detect vulnerable plaques in vitro v With the
development of three-dimensional elastography, palpography, in vivo identification of
weak spots over the full length of human coronary arteries has become possible."
An entirely different approach to deteel plaque vulnerability is the measurement of the
temperature of the arterial wall, which may be increased by the local inflammation. With a
precise thermography catheter, the heal or metabolic activity can be localised and correlated
with plaques at high risk to rupture or thrombosis. Indeed, an increased thermal
heterogeneity within human atherosclerotic coronan arteries was observed in patients
10
Tomography:
SPECT & PET
SE"
US: 3-5 Mhz
^
CL
Q
US: 7.5-20 Mhz . ^
C^
20-40 Mhz
0.1
10
o
—
w
E
5,
o.
0)
D
0 1
1
10
100
Depth \prr\]
1
10
100
1000
Depth [mm]
Figure 1-3 Axial (depth) resolution and obtainable imaging depth for I S imaging
devices with different frequencies compared with other imaging techniques as
SPECT, PET, CT, MR1. I S, OCT and (confocal) microscopy C)M .
16
GENERAL IXTRODI O K >\
with u n s t a b l e angina a n d acute myocardial i n f a r c t i o n , s u g g e s t i n g that it may be related to
t h e p a t h o g e n e s i s . 4 " H o w e v e r , t h e spatial r e s o l u t i o n ( a p p r o x i m a t e l y 0.5 m m ) and t h e
p o t e n t i a l in v i v o u n d e r e s t i m a t i o n of h e a t p r o d u c t i o n locally in h u m a n a t h e r o s c l e r o t i c
plaque d u e t o t h e " c o o l i n g effect" of c o r o n a r y b l o o d flow 41 currently limits the applicability
o f this t e c h n i q u e .
T h e r e a r e t w o factors that h a m p e r t h e d e t e c t i o n o f t h e v u l n e r a b l e p l a q u e using t h e
a b o v e d e s c r i b e d t e c h n i q u e s : they are e i t h e r (1) en face i m a g i n g t e c h n i q u e s , w h i c h are n o t
able t o s h o w t h e d e p t h resolved m o r p h o l o g y (angioscopy, t h e r m o g r a p h y ) or (2) h a v e a
r e s o l u t i o n t h a t d o e s n o t p e r m i t detailed i m a g i n g ( I V U S , M R I a n d C T ) . T h e n e e d for a
high resolution imaging technique that can detect u n s t a b l e c o r o n a r y atherosclerotic plaques
b e f o r e they b e c o m e clinically significant is p a r a m o u n t . T h i s imaging lacuna could be filled
by optical c o h e r e n c e t o m o g r a p h y ( O C T ) . Intravascular O C T may plav an i m p o r t a n t role in
guiding therapeutic interventions, diagnosing atherosclerosis and researching the causes
of c o r o n a r y artery disease.
OCT
Since its i n t r o d u c t i o n in t h e early 1990s, O C T has b e c o m e a p o w e r f u l m e t h o d f o r
i m a g i n g t h e i n t e r n a l s t r u c t u r e of biological s y s t e m s a n d materials. 4 2 O C T is a n a l o g o u s t o
B - m o d e u l t r a s o u n d , e x c e p t that it uses light r a t h e r t h a n s o u n d . W h e r e a s in u l t r a s o u n d t h e
l o c a t i o n o f reflecting o b j e c t is d e t e r m i n e d by m e a s u r i n g e c h o delay t i m e s , in O C T d e p t h
r e s o l v e d m e a s u r e m e n t o f t h e b a c k s c a t t e r e d light is a c h i e v e d t h r o u g h l o w - c o h e r e n c e
i n t e r f e r o m e t r y . T h e h e a r t o f the O C T s e t u p is a M i c h e l s o n i n t e r f e r o m e t e r (figure 1-4);
light e m i t t e d by a light s o u r c e is split by a b e a m splitter in t w o b e a m s . O n e is directed i n t o
t h e r e f e r e n c e a r m a n d is reflected by a t r a n s l a t i n g r e f e r e n c e m i r r o r . T h e o t h e r b e a m is
directed i n t o t h e s a m p l e a r m a n d is reflected by a tissue s a m p l e . T h e back reflected b e a m s
r e c o m b i n e at t h e b e a m splitter a n d are g u i d e d to a d e t e c t o r . It is i m p o r t a n t to n o t e t h a t
i n t e r f e r e n c e b e t w e e n t h e t w o light b e a m s will only b e d e t e c t e d w h e n t h e difference in
optical p a t h l e n g t h s travelled by the light in b o t h a r m s is less t h a n t h e so-called c o h e r e n c e
length o f t h e light s o u r c e . T h i s p h e n o m e n o n is used t o d e t e r m i n e t h e optical p a t h l e n g t h
t h e light has travelled in t h e s a m p l e a r m : if i n t e r f e r e n c e is o b s e r v e d while s c a n n i n g t h e
p a t h length in t h e reference a r m (i.e. m o v i n g t h e reference m i r r o r ) , the back scattered light
f r o m d i f f e r e n t p o s i t i o n s w i t h i n t h e s a m p l e (i.e. in d e p t h ) can b e m e a s u r e d ( ' c o h e r e n c e
gating'). C o n s e q u e n t l y , t h e axial r e s o l u t i o n is directly related t o the c o h e r e n c e length (/) o f
the light s o u r c e (with a c e n t e r w a v e l e n g t h Xr), w h i c h is inversely related t o t h e b a n d w i d t h
(ZlA) of t h e light s o u r c e ( e q u a t i o n 1-1).
TTAA
r
CHAPTER 1
reference arm
m
RM
*->
BS
Is
EH
sample an
d
Figure 1-4 A schematic drawing of an OCT setup. Light emitted by a light
source (Is) is split by a beam splitter (BS) into two beams, travelling through the
reference arm or the sample arm. Via mirror (m), the light in the sample arm, is
focused into a sample (S) using a lens (L). In the reference arm, the light is
directed to a translating reference mirror (RM). Back reflected light from both
arms is recombined by the beam splitter (BS) and the interference signal is
monitored bv the detector (d).
The transverse resolution for O C T imaging is determined by the focused spot size, as
in microscopy. In contrast to conventional microscopy, the lateral resolution is decoupled
from the axial resolution. Furthermore, OCT provides cross-sectional images of structure
below the tissue surface in analogy to histopathology. Standard-resolution O C T can achieve
axial resolutions of 10-15 /urn.
In accordance with the terminology of ultrasound imaging, a measurement of reflectivity
vs. depth is called an A-scan. The O C T image, or B-scan, is constructed from adjacent Ascans, with the reflectivity now plotted as a grey or color scale. The contrast of an O C T
image is determined by differences in the optical properties (e.g. scattering and absorption)
of different tissue layers and their components. The imaging depth is also determined by
the optical properties of the tissue. Using wavelengths in the near infrared, where
hemoglobin and melanin absorption arc low and scattering is reduced, permits imaging
depths of up to 2 mm in tissues.43-4"1 Although this depth is shallow compared with other
clinical imaging techniques like US (figure 1-3), the image resolution of O C T is 1 to 2
orders of magnitude better than conventional ultrasound imaging, magnetic resonance
imaging or computed tomography. Recently, using state-of-the-art lasers as light sources,
IS
GENERAL INTRODUCTION
ultrahigh-resolution imaging with axial resolutions as fine as 1— 2ium has been d e m o n s t r a t e d
(table 1-2).45
VASCULAR APPLICATION O F
OCT
T o d a t e , O C T i m a g i n g is r o u t i n e l y used in ophthalmology, 4 6 ' 1 b u t has g r e a t p o t e n t i a l
as an ' o p t i c a l b i o p s y ' t o o l in o t h e r fields o f m e d i c i n e , i.e. g a s t r o - e n t e r o l o g y , 4 8 " 5
d e r m a t o l o g y , M urology, 5 2 ' 5 4 gynaecology,"'"' a n d cardiology."''' A p a r t from a p p l i c a t i o n as a
d i a g n o s t i c tool, O C T can also b e u s e d for feedback d u r i n g surgical procedures' 1 " e.g. in
laser a b l a t i o n of tissues, , x a n d for g u i d a n c e in clearing a totally o c c l u d e d vessel."' 9 I n
cardiology, O C T c o u l d b e u s e d t o d e t e c t a n d analyze a t h e r o s c l e r o t i c lesions, d u e to its
capacity o f high r e s o l u t i o n i m a g i n g of superficial s t r u c t u r e s . As P a s t e r k a m p et al. s t a t e ,
t h i c k n e s s o f t h e c a p as well as t h e size a n d c o m p o s i t i o n o f t h e u n d e r l y i n g a t h e r o m a t o u s
lipid c o r e , are major c o n t r i b u t o r s t o p l a q u e vulnerability, a n d O C T is t h e only i m a g i n g
m o d a l i t y c a p a b l e of m e a s u r i n g this c a p t h i c k n e s s . 6 0 By accurately m e a s u r i n g t h e c a p
t h i c k n e s s , O C T c o u l d b e a tool in d e t e c t i o n o f r u p t u r e - p r o n e v u l n e r a b l e plaques. 6 i r ' 2
I n 1996, Brezinski et al. w e r e t h e first t o r e p o r t t h e u s e of O C T for i m a g i n g v a s c u l a r
pathology. 6 1 , 6 3 T h i s g r o u p also d e v e l o p e d d e v e l o p m e n t of an e x p e r i m e n t a l c a t h e t e r for in
vivo imaging. 6 4 T h e c a t h e t e r - b a s e d i m a g e s w e r e p r o v e n t o identify p l a q u e s b o t h in vitro,65
a n d in vivo.1'''-'' I n an in vitro e x p e r i m e n t , Y a b u s h i t a et al. d e m o n s t r a t e d the abilitv o f O C T
to d e t e c t different types of a t h e r o s c l e r o t i c lesions, defined as
fibrous,
fibrocalcific
and
lipid-rich atheroma's. 6 " U s i n g a p r o t o t y p e c a t h e t e r , J a n g et al. recently s h o w e d t h a t in vivo
i n t r a c o r o n a r y O C T a p p e a r s t o b e feasible a n d safe. 6 " W i t h O C T they identified m o s t
a r c h i t e c t u r a l features d e t e c t e d by I V U S a n d s u g g e s t e d t h a t O C T may p r o v i d e a d d i t i o n a l
detailed structural i n f o r m a t i o n .
light s o u r c e
"k ( n m )
Ak ( n m )
Pm ,x ( m W )
/c (Mm)
d\ ( m m )
SLD
825
-25
- 5
- 12
0.5- 1.0
SLD
1300
- 50
- 5
- 15
1.0-2.0
AF
1300
- 60
-20
- 12
1.0-2.0
Ti:Al 2 0 3
800
- 100 - 250
- 1000
-1-3
0.5- 1.5
T a b l e 1-2 Overview of light sources and their specifications. T h e center
wavelength (A) is proportional to the imaging depth (d). The bandwidth of the
light source (AX) is inversely proportional to the coherence length (/.). The maximal
power (P |lla J is also given. SLD: super luminescent diode; AF: autofluorescent
fiber; Ti:Al,0. : titanium sapphire laser
19
CHAPTER 1
SCOPE OF THIS THESIS
Currently, the interpretation of vascular O C T images is based on the qualitative
interpretation of the O C T images, without further quantitative data analysis of the O C T
signals. In this thesis, the possibilities of quantitative analysis of vascular O C T signals are
explored for the identification of vulnerable plaques. To distinguish the constituents of
these plaques, reflection spectroscopy on components will be performed, furthermore,
the effect of the light source, with consequently the effect of axial resolution and contrast,
on the O C T data analysis is studied.
In CHAPTER 2 we explore the possibility to extract quantitative data from the O C T
image, i.e. the attenuation coefficient (ju ). Subsequently, the algorithm for measurement
of fx is applied to O C T images of human atherosclerotic tissue and the possibility of
discrimination of plaque components, based on the quantitative basis is explored. The
results are presented in CHAPTER 3. A comparison between two O C T setups, operating
with different light sources (and thus different contrast and resolution), the effect on
quantitative measurement is presented in CHAPTER 4 as well as the correlation between
O C T and histology. To determine the effect of the surrounding tissue and to further
quantify the optical properties precisely, ,a and the index of refraction (n) was measured in
isolated vessel wall and plaque components (CHAPTER 5). The dependence on temperature
of /u and n, important to relate in vitro and /'// vivo measurements, was also determined. In
CHAPTER 6, the measurement of// is applied to living, apoptotic and necrotic cells. Since
the morphological changes during necrosis and apoptosis would result in changes of ji ,
enabling detection of cellular death using OCT. Finally, in CI IAPTER 7 a general discussion
on the role of vascular O C T is given.
20
GENERAL INTRC «DUCTION
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23