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INTRODUCTION
Optical coherence tomography (OCT) is a new intracoronary imaging modality
that provides in vivo high-resolution images of the coronary artery.1
The OCT imaging technique is, in general, similar to that of intravascular
ultrasound (IVUS), but whereas IVUS works by applying radiofrequency radiation,
OCT uses light radiation. In both techniques the imaging probe is automatically
pulled back through the coronary segment of interest. In contrast to IVUS, in
OCT acquisition the coronary vessel needs to be cleared of blood. This is
necessary since red blood cells are non-transparent causing multiple light
scattering and substantial signal attenuation. This was achieved in the first
commercially available OCT system by proximal occlusion of the vessel with a
dedicated low-pressure balloon and simultaneous distal flush delivery (occlusive
technique) during OCT probe pullback.2 However, the recent increase
in pullback speed (from 1 mm/s to 3 mm/s) enabled OCT pullback while displacing
blood by continuous flush (x-ray contrast medium) delivery through the guide
catheter without the need for vessel occlusion (non-occlusive technique).3
The impact of these 2 different acquisition techniques on lumen dimension when
measured by OCT has not yet been reported.
The present study had 2 aims: to compare lumen size when measured by IVUS,
OCT and histology in human coronary arteries ex vivo; to compare, in vivo,
intracoronary lumen size when measured in patients by OCT with balloon
occlusion, OCT without balloon occlusion, and IVUS.
METHODS
Ex Vivo Human Coronary Arteries
Specimens
Ten left anterior descending coronary artery (LAD) segments were excised
within 24 h postmortem, 1 cm proximal to the bifurcation with the left
circumflex artery (LCX) and fixed in 4% formaldehyde. Standard 6 F coronary
sheaths (Arrow, Reading, PA, USA) were introduced and fixed at the distal and
proximal ends of the arteries.
Intracoronary Imaging
For intracoronary imaging, the specimens were immersed in a saline bath at
room temperature and perfused with saline at physiologic pressure. IVUS data
were acquired using the AtlantisTM 40 MHz catheter
with an automated motorized pullback device at a constant speed of 0.5 mm/s. OCT
data were acquired using a commercially available system for intracoronary
imaging and a 0.019" ImageWireTM (LightLab Imaging,
Westford, MA, USA) with automated pullback at 1 mm/s. Lumen measurements in both
IVUS and OCT were performed with the same dedicated coronary vessel analysis
software (CURAD, Wijk bij Duurstede, Netherlands).4-6
Histology Preparation and Analysis
Following the intracoronary imaging procedures, the specimens were sectioned
for histological analysis. The distal side of the bifurcation of the LAD to the
LCX was used as the starting point for the first histology section. From this
point to the distal and proximal side, histology sections were taken at 5-mm
intervals to the end of the specimen.7
Matching Procedure
The OCT and IVUS pullbacks were matched by vessel analysis software (CURAD),
which can synchronize image data acquired with different modalities onto a
single computer screen. The proximal and distal sheaths were used as
longitudinal landmarks. After histology tissue processing, the sections (eg,
microscopic images) were used to identify the corresponding location in the OCT
image data set based on the similar visual appearance of the lumen morphology.
Following this identification process, the visualization software synchronized
the OCT and the IVUS image data sets and identified the corresponding IVUS image8
(Figure 1). To avoid the Dotter effect, only cross-sections where the IVUS
catheter was moving freely in the lumen were selected.
Figure 1.Matching of IVUS, OCT, and histology
ex vivo. The distal side of the bifurcation of the LAD to the LCX (*) was used
as the starting point for the first histology section. From this point to the
distal and proximal side, histology sections were taken at 5-mm intervals to the
end of the specimen (A). The histology sections (B) were used to identify the
corresponding location in the OCT image data set (C) based on the similar visual
appearance of the lumen morphology. Following this identification, the
visualization software synchronized the OCT and IVUS image data sets and
identified the corresponding IVUS image (D).
In Vivo Human Coronary Arteries
Study Population
Patients who were undergoing OCT examination of 1 coronary artery were
included in the study. The medical ethics committee of the Erasmus MC approved
the study and all patients gave written informed consent.
IVUS Acquisition and Analysis
IVUS was acquired after intracoronary nitroglycerine administration using the
Eagle Eye 20 MHz catheter (Volcano, Rancho Cordova, USA) with automatic
continuous pullback at 0.5 mm/s. Before analysis, the IVUS data were
retrospectively processed with an image-based gating system (Intelligate).9
The lumen was measured with the dedicated quantitative analysis software
(CURAD).4,5
OCT Acquisition and Analysis
Optical coherence tomography acquisition was performed using the same system
as described for the ex vivo study. Firstly, pullback was performed with
proximal balloon occlusion and distal flush delivery, after which pullback was
performed in the same segment without occlusion.
Occlusive technique: the occlusion balloon (Helios, Goodman, Japan) was
advanced distal to the region of interest over a conventional angioplasty
guidewire (0.014''). The conventional guidewire was then replaced by the OCT
ImageWire and the occlusion balloon catheter was positioned proximal to the
segment of interest. Pullback of the ImageWire was performed during inflation of
the proximal occlusion balloon catheter at low pressure (0.4 atm) with
simultaneous distal flush delivery (lactated Ringer's solution at 37oC;
flow rate 0.8 mL/s). Images were acquired during pullback at 1 mm/s.
Non-occlusive technique: the ImageWire was placed in the artery using a
double lumen catheter (Twin Pass catheter, Vascular Solutions). Pullback was
performed during continuous injection of contrast medium (3 mL/s, Iodixanol
370, Visipaque, GE Health Care, Cork, Ireland) through the guide catheter
with an injection pump. In this case, the automated pullback rate was 3
mm/s.
The lumen measurements were performed with proprietary software for offline
analysis (LightLab Imaging, Westford, MA, USA). For all OCT studies, the
settings for the refraction index were adjusted to the flush solution used
(saline, Ringer's lactate, and x-ray contrast, respectively).
Matching of OCT and IVUS Pullbacks
The region of interest was matched in the 3 pullbacks (occlusive OCT,
non-occlusive OCT, and IVUS) using landmarks such as side branches (Figure 2).
Differences in pullback speed were adjusted to appropriately compare the 2 OCT
pullbacks per frame.
Figure. 2.Selection of the region of interest
in OCT pullbacks acquired with and without occlusion. PB1 and PB2 show the
longitudinal view of the pullbacks acquired with and without occlusion,
respectively. The white arrows indicate the side branches (SBA and SBB) used for
matching of the region of interest. 1A and 2A show corresponding cross-sections
of SBA with and without occlusion. 1B and 2B show corresponding cross-sections
of the SBB with and without occlusion.
Statistical Analysis
Statistical analysis was performed using SPSS 12.0.1 for Windows (SPSS,
Chicago, IL, USA). Continuous variables are expressed as mean (standard
deviation) and categorical variables are expressed as percentages. The absolute
and relative differences between measurements obtained with the different
techniques were calculated. The relative difference was defined as the absolute
difference divided by the average. Data are also expressed in Bland-Altman plots
showing the absolute difference between corresponding lumen measurements for
both techniques (y-axis) versus the average of both techniques (x-axis). The
limits of agreement were calculated as the mean difference (+2SD).
RESULTS
Ex Vivo Human Coronary Arteries
Intravascular ultrasound and OCT were successfully performed in 8 out of 10
specimens. Intracoronary imaging was not possible in 2 cases due to the lumen
being totally occluded. A good match between OCT, IVUS, and histology images was
obtained in 35 frames. Overall, the mean lumen, plaque and vessel area when
measured by histomorphometry were 2.5 (1.7) mm2, 3.7 (1.9) mm2,
and 7.6 (3.2) mm2, respectively. The mean percentage of stenosis was
59% (18%).
Bland-Altman and regression analyses were performed on the lumen area
measurements between the 3 imaging modalities (Figure 3). The average relative
differences of the lumen measurements were 28% between OCT and histology, 40%
between IVUS and histology, and 11% between IVUS and OCT.
Figure 3. Lumen measurements in ex vivo
coronary arteries. Bland-Altman plots showing the differences in lumen
measurements between OCT and histology (A), IVUS and histology (B), and OCT and
IVUS (C). Correlation for lumen measurements between OCT and histology (A'),
IVUS and histology (B'), and OCT and IVUS (C').
In Vivo Human Coronary Arteries
Clinical and Procedural Characteristics
Five patients (5 vessels) were included in the study. The average age was
61.2 (8.9) years and 4/5 were male. Three out of 5 had hypertension, 1 of 5 had
diabetes, 4 of 5 had hyperlipidemia, and none were smokers. The imaged vessel
was the LAD in 1 case and the LCX in the other 4 cases. Only 1 patient presented
chest pain and ST depression during acquisition with balloon occlusion, which
disappeared immediately after balloon deflation.
Comparison Lumen Measurements With OCT and IVUS
Overall, the mean lumen, plaque, and vessel area measured by IVUS were 6.3
(1.0) mm2, 6.9 (1.4) mm2, and 13.3 (1.7) mm2,
and mean cross-sectional area stenosis was 52% (6%).
Comparison IVUS and OCT With Occlusion
The mean relative difference for the mean lumen area was 33.7%, and the mean
absolute difference for the mean lumen area was 1.67 (0.54) mm2, with
limits of agreement of 0.62-2.73 mm2 (Table 1). The mean relative
difference for the minimum lumen area (MLA) between IVUS and OCT with occlusion
was 55.5%, and the mean absolute difference was 1.90 (0.37) mm2, with
limits of agreement of 1.17-2.63 mm2.
Comparison IVUS and OCT Without Occlusion
The average relative difference for the mean lumen area was 21.5%, and the
absolute difference was 1.11 (0.53) mm2, with limits of agreement of
0.05-2.14 mm2 (Table 2). The average relative difference for MLA was
29%, and the average absolute difference was 1.10 (0.37) mm2, with
limits of agreement 0.37-1.83 mm2.
Comparison of the Lumen Measurements by OCT With and Without Occlusion
For the comparison of lumen dimensions when measured by OCT, 373 matched
frames obtained with and without occlusion were analyzed (Figure 4). The mean
length of the region analyzed was 11.34 (3.87) mm with occlusion and 11.23
(3.86) mm without occlusion (P=.96). Bland-Altman and regression analyses
were also performed for these measurements (Figure 5).
Figure 4.Example of differences in lumen
measurements between OCT with and without occlusion. The figure shows
corresponding images acquired with occlusion (A, B, and C) and without occlusion
(A', B', and C'). The white arrows indicate the landmarks used for matching of
the pullbacks (side branches in A and C and calcium spot in B). In all the
examples, the lumen dimensions are smaller in the pullback acquired with
occlusion.
Figure 5. Comparison of lumen measurements with
optical coherence tomography (OCT) with and without occlusion. Bland-Altman plot
showing the differences between lumen measurements in OCT pullbacks acquired
with the occlusive and nonocclusive technique (A). Correlation between the lumen
measurements in the OCT pullbacks acquired with and without occlusion (B).
The mean absolute and relative differences for mean lumen area were 0.61
(0.23) mm2 (13%) (limits of agreement, 0.15-1.07 mm2). The
mean absolute and relative differences for MLA were 0.80 (0.21) mm2
(28%) (limits of agreement, 0.37-1.23 mm2) (Tables 3 and 4).
The mean lumen volumes were 55 (29.5) and 60.4 (30.4) mL3 with and
without occlusion, respectively, with a relative difference of 11.7%. The mean
absolute difference was 5.4 (2.7) mL3 and the limits of agreement
were 0.0-10.7 mm3.
DISCUSSION
Optical coherence tomography is emerging as one of the most promising
intracoronary imaging modalities due to its capacity to provide very
high-resolution images of the coronary vessel wall. It enables the very detailed
assessment of atherosclerotic plaque and the interaction between implanted
coronary stents and the vessel wall.10,11 In recent years, there has
been continuous technical development that has led to changes in the OCT
acquisition technique (changing from the need to occlude the vessel to a
non-occlusive procedure) which have simplified the use of the technology and
reduced patient discomfort.12,13 However, even though the
non-occlusive technique is currently gradually replacing the occlusive technique
in many centers, it remains "off-label." Furthermore, many of the recently
published OCT data were obtained by using the occlusive technique.14-20
The impact of the acquisition technique in relation to quantitative lumen
measurements obtained by OCT and compared to quantitative IVUS has not yet been
reported. The present study showed the following: a) in fixed human
coronary arteries, both OCT and IVUS overestimated the lumen area compared to
histology; b) lumen dimensions when measured by IVUS are larger than
those when measured by OCT with or without occlusion in vivo; and c) the
OCT acquisition technique (occlusive or non-occlusive) has an impact on lumen
dimension measurements.
Differences in Lumen Measurements Between IVUS, OCT, and Histology
In the present study, the lumen areas when measured by IVUS and OCT were
larger than those measured by histology in fixed human coronary arteries. The
mean differences with histomorphometry were 0.8 mm2 (28%) for OCT and
1.3 mm2 (40%) for IVUS. These results are in line with a previous
study in stented porcine coronary arteries that showed that lumen area was
largest when measured by IVUS, followed by OCT, and was smallest when measured
by histology.21 However, it should be borne in mind that the ex vivo
processing of the specimen for histology analysis may have had an influence on
lumen size. It is well established that tissue shrinkage occurs in different
phases when preparing specimens for histology.22
Regarding the comparison of IVUS and OCT, our in vivo data are in agreement
with the ex vivo findings. In our study, the lumen dimensions measured by IVUS
in living patients were always higher than those measured by OCT with or without
balloon occlusion. There are several studies in the literature comparing lumen
dimensions measured by IVUS and OCT with occlusion that show contrasting
results. Kawase et al, performed IVUS and OCT with occlusion in vivo in 6
coronary arteries in pigs and reported no differences in lumen areas and volumes
between IVUS and OCT with occlusion.23 However, another study in pigs
with a larger sample size reported an absolute difference of 0.49 mm2
between mean lumen area by IVUS and OCT acquired with the occlusive technique in
stented segments.21 Yamaguchi et al evaluated in vivo differences in
humans and found that the MLA was significantly smaller when measured by OCT
with occlusion than when measured with IVUS (mean difference, 0.4 mm2).
The greater differences found in our data could be explained by the fact that we
did not include coronary segments treated with bare-metal stents. Bare-metal
stents are probably less affected by variations in intracoronary pressure caused
by proximal vessel occlusion as they have considerable radial strength.
To our knowledge, no published studies have reported differences in
measurements between IVUS and OCT acquired with the non-occlusive technique. In
the present study, the lumen dimensions were even larger by IVUS, but the
differences, as expected, were smaller than with occlusion.
The greater overestimation of lumen dimensions when measured by IVUS compared
to OCT could be related to the difficulty in differentiating the lumen border by
IVUS due to blood speckle or presence of artefacts.24 OCT shows the
lumen-intima interface as a sharply defined border, clearly visible in most
cases.25 IVUS also overestimates the lumen area compared to
quantitative angiography measurements (both by videodensitometry and edge
detection).26-28 In our study, the differences between lumen
measurements by IVUS and OCT were higher in vivo than ex vivo. This could be
related to the frame selection for in vivo analysis. The IVUS pullback obtained
in vivo was processed with a gating system that selects enddiastolic frames (the
moment in the cardiac cycle when the vessel is biggest), whereas OCT pullback is
not gated and therefore the frames could correspond to any moment in the cardiac
cycle. Previous IVUS studies have suggested a variation in lumen area during the
cardiac cycle in the range of 8%.29
The differences found between lumen size when measured by IVUS and OCT may
have clinical implications if OCT is going to be used to define lesion severity.
An MLA <4 mm2 has been associated with myocardial ischemia and has
been considered a criterion for coronary lesion revascularization. In the
present study, whereas all the patients had an MLA >4 mm2 when
measured by IVUS, 4 out of 5 patients had an MLA <4 mm2 when measured
by OCT with occlusion. All the patients were asymptomatic and were not treated.
This reinforces the idea that IVUS criteria cannot be directly translated to OCT
and emphasizes the need for new specific cut-off points to define lesion
severity by OCT.
Impact of OCT Acquisition Technique on Lumen Measurements
The present report consistently shows that the mean and minimum lumen areas
were smaller when OCT was performed with balloon occlusion than acquisitions
without occlusion. These differences could be related to the decrease of
intracoronary pressure due to the vessel occlusion that is not completely
compensated by continuous flush injection. Furthermore, the injection of
contrast medium during the non-occlusive procedure increases intracoronary
pressure (Figure 6). These phenomena are likely to be more accentuated in
healthy arteries and in coronary segments not treated with bare-metal stents (as
in this study). The relative differences were higher in smaller vessels,
suggesting that they may have a greater tendency to collapse after occlusion.
Figure 6.Intracoronary pressure recorded during
saline or contrast injection. The figure shows the ECG (red) and intracoronary
pressure (blue) records obtained in a left anterior descending coronary artery
during injection of saline or contrast medium (Iodixanol 370). The distal
intracoronary pressure was registered using the RADI pressure wire. The saline
injection at 3 mL/s did not significantly modify intracoronary pressure (A).
However, an increase in intracoronary pressure can be observed during contrast
injection at 3 mL/s, (B). *Ventricular extrasystole.
Limitations
Even though a complex matching process was used, the difference in slice
thickness between IVUS, OCT, and histology cross-sections may have influenced
the results of the ex vivo study. The main limitations of the in vivo study are
the small sample size and the limited type of coronary segments that could be
analyzed. More data are needed to evaluate the quantitative differences between
OCT pullbacks acquired with different techniques and IVUS in human coronary
arteries treated with bare-metal stents. Further studies with a larger sample
size and using different types of coronary segments are warranted before
definite conclusions can be drawn.
CONCLUSION
In fixed human coronary arteries, both OCT and IVUS overestimated lumen areas
compared to histomorphometry. Lumen dimensions measured by IVUS are larger than
those measured by OCT with or without occlusion in vivo. The OCT acquisition
technique (occlusive or non-occlusive) has an impact on quantitative lumen
dimension measurements.
ABBREVIATIONS
IVUS: intravascular ultrasound
LAD: left anterior descending coronary artery
LCX: left circumflex artery
MLA: minimum lumen area
OCT: optical coherence tomography
SEE EDITORIAL ON PAGES 599-602
Correspondence: Dr E. Regar,
Thoraxcenter, Bd 585. 's-Gravendijkwal 230, 3015-CE Rotterdam, The Netherlands
E-mail: e.regar@erasmusmc.nl
Received January 13, 2009.
Accepted for publication February 19, 2009.
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Interventional Cardiology.
Volume 62, Issue 06, June 2009
