(Circulation. 1997;96:2944-2952.)
© 1997 American Heart Association, Inc.
Articles |
From the Thoraxcenter, Division of Cardiology, University Hospital Rotterdam-Dijkzigt and Erasmus University, Rotterdam (C. von B., E. de V., A.N., N.B., W.L., C.J.S., J.R.T.C.R., P.W.S., P.J. de F.), and the Interuniversity Cardiology Institute (W.L., P.W.S.), Netherlands; and the Washington (DC) Hospital Center (G.S.M.). Dr von Birgelen is now at the Department of Cardiology, University Hospital Essen, Germany.
Correspondence to Pim J. de Feyter, MD, PhD, Thoraxcenter, Bd 381, PO Box 1738, 3000 DR Rotterdam, Netherlands.
| Abstract |
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Methods and Results We used an ECG-gated 3D IVUS image acquisition workstation and a dedicated pullback device in atherosclerotic coronary segments of 30 patients to evaluate (1) the feasibility of this approach of image acquisition, (2) the reproducibility of an automated contour detection algorithm in measuring lumen, external elastic membrane, and plaque+media cross-sectional areas (CSAs) and volumes and the cross-sectional and volumetric plaque+media burden, and (3) the agreement between the automated area measurements and the results of manual tracing. The gated image acquisition took 3.9±1.5 minutes. The length of the segments analyzed was 9.6 to 40.0 mm, with 2.3±1.5 side branches per segment. The minimum lumen CSA measured 6.4±1.7 mm2, and the maximum and average CSA plaque+media burden measured 60.5±10.2% and 46.5±9.9%, respectively. The automated contour-detection required 34.3±7.3 minutes per segment. The differences between these measurements and manual tracing did not exceed 1.6% (SD<6.8%). Intraobserver and interobserver differences in area measurements (n=3421; r=.97 to.99) were <1.6% (SD<7.2%); intraobserver and interobserver differences in volumetric measurements (n=30; r=.99) were <0.4% (SD<3.2%).
Conclusions ECG-gated acquisition of 3D IVUS image sets is feasible and permits the application of automated contour detection to provide reproducible measurements of the lumen and atherosclerotic plaque CSA and volume in a relatively short analysis time.
Key Words: ultrasonics coronary disease imaging
| Introduction |
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As a consequence, we have developed an analysis system that (1) uses 3D IVUS image sets acquired with an ECG-gated image acquisition workstation and pullback device to limit cyclic artifacts28 and (2) detects both the luminal and external vascular boundaries of atherosclerotic coronary arteries to permit plaque volume measurement.10 29 30 31 We report the feasibility of IVUS image acquisition and the reproducibility of analysis with this methodology.
| Methods |
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Thirty atherosclerotic coronary segments located in the left
anterior descending coronary artery (n=15), right
coronary artery (n=12), and left circumflex coronary
artery (n=3) were analyzed; 13 segments were proximal, 15 mid,
and 2 distal. As a condition for inclusion, segments had to be
angiographically relatively straight (in at least two angiographic
views from opposite projections). An exclusion criterion was
calcification encompassing >180° of the arterial
circumference over a
5-mm-long axial segment. This study was approved
by the Local Council on Human Research. All patients signed a written
informed consent form approved by the Medical Ethical Committee of the
University Hospital Rotterdam-Dijkzigt.
IVUS Imaging
All patients received 250 mg aspirin and 10 000 U heparin IV.
If the duration of the entire catheterization procedure
exceeded 1 hour, the activated clotting time was measured, and
intravenous heparin was administered to maintain an
activated clotting time of >300 seconds. After
intracoronary injection of 0.2 mg
nitroglycerin, the atherosclerotic coronary
segment to be reconstructed was examined with a mechanical IVUS system
(ClearView, CardioVascular Imaging Systems Inc) and a sheath-based IVUS
catheter incorporating a 30-MHz beveled, single-element transducer
rotating at 1800 rpm (MicroView, CardioVascular Imaging Systems Inc).
This catheter is equipped with a 2.9F 15-cm-long sonolucent distal
sheath with a common lumen that alternatively houses the guidewire
(during catheter introduction) or the transducer (during imaging after
the guidewire has been pulled back), but not both. This design avoids
direct contact of the IVUS imaging core with the vessel wall. The IVUS
transducer was withdrawn through the stationary imaging sheath by an
ECG-triggered pullback device with a stepping motor developed at the
Thoraxcenter Rotterdam.28
ECG-Gated 3D IVUS Image Acquisition
The ECG-gated image acquisition and image digitization was
performed by a workstation initially designed for the 3D reconstruction
of echocardiographic images28 (Echoscan,
TomTec). This workstation received input from the IVUS machine (video)
and the patient (ECG signal) and on the other hand, controlled the
motorized transducer pullback device.
The steering logic of the workstation considered the heart rate
variability and checked for the presence of extrasystoles during image
acquisition and digitization (Fig 1
).
First, the RR intervals were measured over a 2-minute period to define
the upper and lower limits of the range of acceptable RR intervals
(mean value±50 ms). IVUS images were acquired 40 ms after the peak of
the R wave. When the length of the RR interval met the preset range,
the IVUS image was stored in the computer memory. Consecutively, the
IVUS transducer was withdrawn 200 µm to acquire the next image.
Although the longitudinal resolution available with this technical
setup is 100 µm,28 in the present study only
one IVUS image per 200 µm axial arterial length was
acquired. Thus, an average of 114 images per segment were digitized and
analyzed (range, 48 to 200 images per segment; corresponding
segment length, 9.6 to 40.0 mm).
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IVUS Analysis Protocol
Each set of digitized IVUS images was analyzed off-line
by two independent observers using an automated, computerized contour
detection algorithm.29 30 31 These measurements (Ia and II)
were compared to study the interobserver variability. Blinded
analyses were repeated by the first observer after an interval
of at least 6 weeks. These measurements (Ia and Ib) were compared to
study the intraobserver variability.
Two hundred planar images were randomly selected for "manual" analysis by a third investigator (MA-III) who was experienced in IVUS image analysis but blinded to the (above) automated contour detection results. This analyst could review the videotape to ensure a maximum accuracy of contour tracing, performed within an average of 4.1 minutes per image. Validation of manual CSA measurements by IVUS has been reported previously.32 33 34 These measurements were compared with the automated contour detection analysis made by observer I.
Data Analysis
The CSA measurements included the lumen and EEM CSA.
Plaque+media CSA was calculated as EEM minus lumen CSA, and the CSA
plaque+media burden was calculated as plaque+media CSA divided by EEM
CSA. The EEM CSA (which represents the area within the border
between the hypoechoic media and the echoreflective adventitia) has
been shown to be a reproducible measure of the total
arterial CSA. As in many previous studies using IVUS,
plaque+media CSA was used as a measure of atherosclerotic plaque,
because ultrasound cannot measure media thickness
accurately.35 Lumen, EEM, and plaque+media volumes were
calculated as
![]() |
where H is the thickness of a coronary artery slice, represented by a single tomographic IVUS image, and n is the number of IVUS images in the 3D data set. The volumetric plaque+media burden was calculated as plaque+media volume divided by EEM volume.
Plaque composition was assessed visually to identify lesion calcium. Calcium produced bright echoes (brighter than the reference adventitia), with acoustic shadowing of deeper arterial structures. The largest arc(s) of target lesion calcium was identified and measured in degrees with a protractor centered on the lumen. The overall length (in mm) of lesion calcium was measured by use of the length measurements provided by the 3D reconstruction.
Computerized Contour Detection in ECG-Gated 3D IVUS
Steps Involved in Image Analysis
Two longitudinal sections were constructed, and contours
corresponding to the lumen-tissue and media-adventitia interfaces were
automatically identified (Fig 1
). The necessity to manually edit these
contours was significantly reduced, because cyclic "saw-shaped"
image artifacts that can hamper the automated detection in nongated
image sets were virtually abolished (Fig 2
). The sufficiency of the contour
detection was visually checked, requiring an average of 5 minutes. If
necessary, these longitudinal contours were edited with computer
assistance (see below) within <1 minute. The longitudinal contours
were transformed to individual edge points on the planar images,
defining center and range of the automated boundary search on the
planar images.
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Subsequently, contour detection of the planar images was performed. The axial location of an individual planar image was indicated by a cursor, which was used to scroll through the entire set of planar images while the detected contours were visually checked. Correct detection of the longitudinal contours minimized the need for computer-assisted editing of the cross-sectional contours. Careful checking and editing of the contours of the planar images was performed within an average of 25 minutes. Finally, the contour data of the planar images were used for the computation of the results.
Minimum-Cost Algorithm and Computer-Assisted Contour
Editing
A minimum-cost algorithm was used to detect the luminal and
external vessel boundaries.29 Each digitized IVUS image
was resampled in a radial format (64 radii per image); a cost matrix
representing the edge strength was calculated from the
image data. For the boundary between lumen and plaque, the cost value
was defined by the spatial first derivative.36 For the
external vessel boundary, a cross-correlation pattern matching process
was used for the cost calculations. The path with the smallest
accumulated value was determined by dynamic programming
techniques.29 The computer-assisted editing differed
considerably from conventional manual contour tracing. The computer
mouse was pointed on the correct boundary to give that site a very low
value in the cost matrix, and subsequently the automated detection of
the minimum cost path was updated within <1 second. Editing the
contour of a single slice caused the entire data set to be updated
(dynamic programming).
Handling of Side Branches and Calcification
Side branches with a relatively small ostium were generally
ignored by the algorithm as a result of its robustness, which means
that the automated contour detection did not follow every abrupt change
in the cost path. However, in branches with a large ostium, the contour
did follow the lumen and vessel boundaries of the side branch. This was
corrected by displaying the side branch in one of the longitudinal
sections and interpolating the longitudinal vessel contours as straight
lines. As a result, the side branch was outside the region of interest
on the planar images. Similarly, small calcific portions of the plaque
did not affect the detection of the external vessel boundary because of
the robustness of the algorithm. In case of marked vessel wall
calcification, the automated approach fails to detect the external
vessel boundary. However, the 3D approach of the analysis
system allowed interpretation of the external vessel boundary in the
longitudinal dimension and facilitated tracing of a straight contour
line behind the calcium.
Previous Validation In Vitro and In Vivo
In vitro, the algorithm has been validated in a tubular phantom
consisting of several segments. The automated measurements revealed a
high correlation with the true phantom areas and volumes
(r=.99); mean differences were -0.7% to 3.9% (SD<2.6%)
for the areas and 0.3% to 1.7% (SD<3.8%) for the volumes of the
various segments.30 A comparison between automated 3D IVUS
measurements in 13 atherosclerotic coronary specimen (area
plaque+media burden <40%) in vitro and morphometric measurements on
the corresponding histological sections revealed good
correlations for measurements of lumen, EEM, plaque+media, and
plaque+media burden (r=.94,.88,.80, and.88 for areas
and.98,.91,.83, and.91 for volumes).31 In vitro, both area
and volume measurements by the automated system agreed well with
results obtained by manual tracing of IVUS images, showing low (-3.7%
to 0.3%) mean between-method differences with SD <6% and high
correlation coefficients (r
.97 for areas and
r=.99 for volumes).31 In vivo, using 3D IVUS
image sets acquired during nongated continuous pullbacks through 20
diseased coronary segments, intraobserver and interobserver
comparisons revealed high correlations (r=.95 to.98 for area
and r=.99 for volume)30 and small mean
differences (-0.9% to 1.1%), with SD of lumen, EEM, and plaque+media
not exceeding 7.3%, 4.5%, and 10.9% for areas and 2.7%, 0.7%, and
2.8% for volumes. The time of (automated) analysis in that
study was 69±19 minutes. Importantly, that study did not include
segments with more than focal calcification, more than one side branch,
or extensive systolic-diastolic movement artifacts
in the longitudinally constructed images.
Statistical Analysis
Quantitative data were given as mean±SD; qualitative data
were presented as frequencies. According to Bland and
Altman,37 the intraobserver and interobserver agreement
(reproducibility) of the contour detection method was assessed by
determining the mean and SD of the between-observation and
between-observer differences, respectively. The results of the repeated
contour analyses (Ia versus Ib), the independent contour
detection analyses (Ia versus II), and the manual versus the
contour analyses (III-MA versus Ia) were compared by the
two-tailed Student's t test for paired data
analysis and linear regression analysis; values of
P<.05 were considered statistically significant.
| Results |
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IVUS Segment Characteristics
All but two of the segments (93%) contained at least one side
branch (Table 2
). The average number of
side branches per segment was 2.3±1.5 (range, 0 to 6). Calcification
was present in 17 segments (57%), 11 (37%) showed a single
calcium deposit, and 6 (20%) contained multiple calcium deposits. The
maximum arc of calcium was 114±49° (50° to 190°); in 6 segments,
the length of the calcified portion exceeded 1 mm.
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The minimal lumen CSA as measured by the contour detection system was 6.4±1.7 mm2 (3.5 to 9.7 mm2). The maximum and average CSA plaque+media burden were 60.5±10.2% (31.7% to 77.7%) and 46.5±9.9% (22.8% to 65.9%).
Manual Tracing Versus Automated Contour Detection
In the 200 randomly selected image slices, the measurements
of the lumen, EEM, and plaque+media CSAs and the CSA plaque+media
burden obtained with the automated contour detection system
(9.37±3.09 mm2, 18.33±6.70 mm2,
8.95±5.16 mm2, and 46.03±13.46%, respectively) were
similar to the results obtained by manual tracing (9.35±3.18
mm2, 18.37±6.62 mm2, 9.02±5.08
mm2, and 46.53±13.41%; n=200). Between-method differences
were 0.4±4.3%, -0.4±3.6%, -1.6±9.1%, and -1.2± 6.8%,
respectively (all P=NS). The correlations between the
measurements provided by both methods were high (r
.98; Fig 3
).
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Reproducibility of the Contour Detection Analysis
For measurements of lumen, EEM, and plaque+ media CSA and the CSA
plaque+media burden (n=3421), both intraobserver (-0.4±2.7%, -0.4±
1.8%, -0.4±5.1%, and -0.0±4.2%) and interobserver (0.4±5.2%,
-0.9±2.7%, -1.5±7.2%, and -1.5±6.9%; all P<.001)
differences were low. Correlation coefficients were high for repeated
measurements by the same observer (r=.99) and measurements
by the two observers (r
.97; Fig 4
). For the corresponding volumetric
measurements (n=30), the intraobserver (-0.4±1.1%, -0.4±0.6%,
-0.3±1.0%, and 0.0±0.4%) and interobserver (0.6±2.9%,
-0.8±1.0%, -2.5±3.2%, and 0.8±1.5%; P<.05)
differences were also low, and high correlations were found for both
intraobserver and interobserver comparisons (r=.99; Fig 5
).
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| Discussion |
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3D reconstruction of IVUS images was first used to visually assess the spatial configuration of plaques, dissections, and stents and to perform basic measurements.16 17 19 More recently, the 3D reconstruction systems have included algorithms for automated quantification of lumen dimensions.16 17 18 19 20 21 25 26 27 The contour detection system used in the present study can be used for the detection of both the tissue-lumen boundary and the media-adventitia (EEM) boundary, and therefore plaque volume can be measured.
Feasibility
NonECG-gated image acquisition is frequently marred by cardiac
cyclelinked coronary artery vasomotion and IVUS catheter
motion, which produce sawtooth artifacts in the reconstructed 3D images
that can interfere with automated contour detection (both the ease of
use and, presumably, reproducibility). Conversely, in the present
ECG-gated image sets, the longitudinal contours were smooth and without
such artifacts. Therefore, there was much less need to manually edit
the automatically detected longitudinal contours. Moreover, the
accuracy of the derived edge information improved the
performance of the second automated contour detection step on
the planar IVUS images. This reduction in manual editing time on both
longitudinal and planar images accounts for the low time of
analysis compared with a previous study using nongated image
acquisition30 (34 minutes and 69 minutes, respectively).
Indeed, this represents a significant reduction in
analysis time and as a consequence reduces the cost of the
analysis. However, the ECG-gated 3D IVUS acquisition in the
present study required a longer acquisition time than conventional
motorized pullback (eg, nonECG-triggered pullback at 0.5 mm/s).
On average, only a 6-mm-long coronary segment could be imaged
in 1 minute.
Reproducibility of the Contour Detection
In the present study, the measurement of the lumen, EEM, and
plaque+media CSA differed little from the results obtained by manual
contour tracing of these borders; there were only small interobserver
and intraobserver differences in both the planar and volumetric
analyses. However, the reproducibility of the plaque+media
measurements was lower than for the other measures, which may reflect
the combined variability of both the luminal and the EEM contours,
confirming previous in vitro31 and in vivo data (nongated
patient data)30 and findings of others.38 The
reproducibility of the volumetric measurements was higher than for the
CSA measurements, which may be a result of an averaging of the
differences between the individual CSA measurements.
Although the segments in this ECG-gated contour detection study were nonselected and included calcified segments with some side branches, the reproducibility of the CSA measurements was consistently better than observed in a previous study using nongated contour detection.30 We believe that the key factors explaining the overall high reproducibility of automated contour detection observed in this study are (1) the integrated analyses of the conventional cross-sectional image slices with two longitudinal sections and (2) the facilitated and improved detection as a result of the smoothness of the contours on the ECG-gated longitudinal IVUS sections.
Reproducibility of Alternative Methods of Quantitative 3D
IVUS
There is very little information on the reproducibility of 3D IVUS
measurements using other measurement systems and algorithms. Matar and
colleagues21 reported a Pearson's correlation coefficient
of .98 for an intraobserver study of lumen volume measurement by an
automated threshold-based IVUS analysis system, confirming the
low variability of the volumetric measurements observed in the
present study. Another acoustic quantification
system25 performs measurements of lumen CSA and volume,
based on the automated detection of the blood pool in single IVUS
images acquired at random during the cardiac cycle.21 25
Because the measurements are based on single-frame analysis,
ECG-gated image acquisition may not influence the reproducibility of
such systems.
Conversely, 3D contour detectionbased analysis approaches benefit from an ECG-gated image acquisition.20 Sonka and associates39 40 developed an alternative 3D contour detection system that performs computerized detection of the luminal and external vascular boundaries in 3D sets of planar IVUS images without the additional information provided by the longitudinal contours. In their study,39 the correlation between automated and manually traced CSA measurements was quite good (r=.91 and.83 for lumen and plaque CSA, respectively). Using ECG-gated 3D IVUS, they found significantly improved results (r=.98 and.94 for lumen and plaque+media CSA, respectively),40 underlining the significance of ECG-gated IVUS image acquisition. Most likely, other promising contour detection algorithms41 42 for 3D analyses may also benefit from an ECG-gated image acquisition.
Potential Sources of Error and Study Limitations
Problems related to IVUS in general43 and to 3D
reconstruction in particular22 23 may influence the
contour detection process. The quality of the basic IVUS images is
crucial to both planar and 3D image analysis.22
Incomplete visualization of the vessel wall, for example as caused by
acoustic shadowing6 from lesion-associated calcium,
hampers conventional planar IVUS analyses; however, 3D IVUS
allows interpretation in the axial dimension and estimated contour
tracing of the external vascular boundary. Image distortion caused by
nonuniform transducer rotation or noncoaxial IVUS catheter position in
the lumen may create artifacts both in planar images and in 3D
reconstruction.22
Vessel curvatures may cause differences between the movement of the distal transducer tip and the proximal part of the catheter (although the use of sheath-based IVUS catheters reduces the latter problem) and a significant distortion of the 3D image reconstruction.
Most importantly, linear 3D systems such as used in this study can provide only approximate values of the volumetric parameters44 because they do not account for vascular curvatures and the real spatial geometry. In curved vascular segments, this results in an overestimation of plaque volume at the inner side (expansion) and an underestimation of plaque volume at the outer side (compression) of the curve.22 Approaches combining data obtained from angiography and IVUS45 46 47 48 can provide information on the real spatial geometry of the vessel. Unquestionably, the combined approaches have a unique potential, but currently these sophisticated techniques are still laborious, restricted to research applications, and not yet useful for routine off-line analysis of clinical IVUS examinations. In the present study, only relatively straight coronary segments, showing no more than mild vessel curvatures, were included. We felt that this premise was important to limit curve distortioninduced deviation of volumetric measurement,44 because linear 3D analysis systems do not account for vascular curvatures.
Compared with conventional motorized transducer pullback at a uniform speed, ECG-gated image acquisition takes longer, which may limit its use before intervention, especially in patients with very severe coronary stenoses. Therefore, we currently perform ECG-gated IVUS examinations during diagnostic or follow-up catheterizations and at the presumed end point of coronary interventions.
Clinical Implications
The examination of coronary arteries by IVUS permits the
comprehensive assessment of
atherosclerosis1 2 3 6 7 10 11 and the
evaluation of the instantaneous27 49 and long-term effects
of catheter-based interventions on the coronary lumen and
plaque. To quantify these changes, anatomic landmarks such as side
branches or spots of calcium can be used to define specific anatomic
image slices for comparative analysis in serial studies.
The proposed 3D IVUS method, which permits reproducible and reliable contour detection of both lumen and plaque, may facilitate volumetric measurements10 30 31 and obviate the need for laborious analyses based on Simpson's rule.15 Furthermore, the use of ECG-gated image acquisition28 increases the applicability of the contour detection algorithm by shortening the analysis time49 and increasing the reproducibility of the method. These advantages may be most significant in studies that are expected to show only small changes in plaque and/or lumen over time (eg, in trials evaluating the progression or regression of atherosclerosis during pharmacological therapy10 ). In addition, because the time from the peak of the R wave to image acquisition can be varied, this method can be used to study the cyclic (systole versus diastole) changes in vessel dimensions.
Conclusions
ECG-gated acquisition of 3D IVUS image sets is feasible and
permits the application of automated contour detection to provide
reproducible measurements of the lumen and atherosclerotic plaque CSA
and volume in a relatively short analysis time.
| Selected Abbreviations and Acronyms |
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| Acknowledgments |
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Received January 8, 1997; revision received May 8, 1997; accepted May 28, 1997.
| References |
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