(Stroke. 1997;28:2195-2200.)
© 1997 American Heart Association, Inc.
Articles |
A New Automated Computerized Analyzing System Simplifies Readings and Reduces the Variability in Ultrasound Measurement of Intima-Media Thickness
From the Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital, Göteborg University (I.W., J.W.), and the Department of Applied Electronics, Chalmers University of Technology (Q.L., T.G.), Gothenburg, Sweden.
Correspondence to Inger Wendelhag, Wallenberg Laboratory, Fack 16, Sahlgrenska University Hospital, S-413 45 Gothenburg, Sweden. E-mail inger.wendelhag{at}wlab.wall.gu.se
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Abstract |
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Background and Purpose A computerized analyzing system with manual tracing of echo interfaces for measurement of intima-media thickness and lumen diameter in carotid and femoral arteries was previously developed by our research group and has been used for many years in several laboratories. However, manual measurements are not only time consuming, but the results from these readings are also dependent on training and subjective judgement. A further problem is the observed drift in measurements over time. A new computerized technique for automatic detection of echo interfaces was therefore developed. The aim of this study was to evaluate the new automated computerized analyzing system.
Methods The new system is based on dynamic programming and includes optional interactive modification by the human operator. Local measurements of vessel echo intensity, intensity gradient, and boundary continuity are extracted by image analysis techniques and included as weighed terms in a cost function. The dynamic programming procedure is used for determining the optimal location of the vessel interfaces in a way that the cost function is minimized.
Results With the new automated computerized analyzing system the measurement results were less dependent on the reader's experience, and the variability between readers was less compared with the old manual analyzing system. The measurements were also less time consuming.
Conclusions The new automated analyzing system will not only greatly increase the speed of measurements but also reduce the variability between readers. It should also reduce the variability between different laboratories if the same analyzing program is used. Furthermore, the new system will probably prevent the problem with drift in measurements over time.
Key Words: atherosclerosis • ultrasonics • carotid arteries • computer-assisted image processing
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Introduction |
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B-mode ultrasound allows direct noninvasive measurement of the intima-media complex in carotid and femoral arteries. The noninvasive ultrasound method is increasingly used in clinical research relating to the pathophysiology of atherosclerosis and also for the evaluation of preventive measures in randomized clinical trials.1 2 3 4 5 6 For measurement of IMT, most research groups use some kind of computerized analyzing system. These systems are usually based on manual tracing of the different echo interfaces in the ultrasound image.7 8 9 However, manual measurements are not only time consuming, but the results from these readings are also dependent on training and subjective judgement. A further problem is the observed drift in measurements over time.10 11
In previous studies of reproducibility the CVs for interobserver and intraobserver variability in measurement of mean IMT of the common carotid artery were 10.2% and 10.6%, respectively.7 10 This includes both recording and analysis of images with the manual analyzing system. Rereading variability, when the same images were measured twice but 12 months apart, was 3.8%. This means that approximately one third of the variability in the ultrasound method is due to variability in measurements. In accordance with other research groups, the data from rereading of IMT also showed that a small but significant drift may occur when readings are done a long time apart.10 11
To reduce the variability in IMT measurements, an automated analyzing system was designed and implemented in a PC/Microsoft Windows environment. The objective was to develop a boundary detection technique that not only is as accurate as possible but also robust, simple to handle, and less time consuming compared with manual tracing measurements. A dynamic programming procedure is used for the automatic detection of echo interfaces, which combines multiple measurements of echo intensity, intensity gradient, and boundary continuity. The system also includes optional interactive modification by the human operator. Analyzing systems based on automatic detection have previously been presented.12 13 14 However, in these systems the automatic reading is based on single measurements of echo intensity or intensity gradient (edge strength) along the vessel boundary, not taking boundary continuity into account.
The aim of this study was to evaluate the new automated analyzing system for measurement of IMT and LD in predefined sections of the carotid and femoral arteries.
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Methods |
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Development and Validation Procedure
The development of the automated computerized analyzing system was part of a PhD thesis work at Chalmers University of Technology15 and has been in progress for approximately 3 years. All ultrasound images used for the development of the technique were recorded and analyzed at the Wallenberg Laboratory (see below). The research and programming of the automated analyzing system and also the present evaluation of the program were performed in a UNIX computer system. The program was thereafter reimplemented into a PC system with Microsoft Windows.
The first step in the programming of the new automated analyzing system was to measure a number of ultrasound images of good quality from the common carotid artery (27 images) with the manual analyzing system. The measurement contours from these measurements were saved and served as reference for the automatic outlining. Manual contours from a further set of 42 images of different qualities were added for refinement and validation of the automatic procedure. Another 60 images from the common carotid artery were used in an evaluation of the first version of the program. The manual contours from these images were thereafter added to the first 27+42 images to further improve the automatic outlining. This procedure was repeated a second and a third time with continuous refinement of the program. Manual contours from measurements in the carotid artery bulb and in the common femoral artery were also used to adjust the program to be applicable to these measurement areas as well. A total of approximately 500 images were used for the refinement and validation of the automatic detection system.
The final program version was thereafter tested in the present evaluation study. Images (not earlier used) from a consecutive group of patients and control subjects (n=50) were analyzed in both the old manual tracing analyzing system and the new automated analyzing system. Furthermore, the same images were independently analyzed by three technologists with different experience in reading of ultrasound images.
Ultrasonography
Examination was performed with an ultrasound scanner
(Acuson 128) with a 7-MHz linear transducer and a transducer aperture
of 38 mm. The electrocardiographic signal (lead II) was
simultaneously recorded to synchronize the image
capture to the top of the R wave to minimize variability during the
cardiac cycle.
The carotid arteries were scanned at the level of the bifurcation, and the femoral arteries were examined distal to the inguinal ligament, at the site where the artery divides into the superficial femoral artery and the profound femoral artery. Images for IMT measurements were recorded from the carotid bulb, the common carotid artery, and the common femoral artery, respectively. At the position of the thickest part of the far wall (visually judged), a frozen longitudinal image was captured and recorded on videotape. The procedure was repeated three times to achieve three separate images for analysis (see below). A short sequence of real-time images was also recorded on videotape to assist in the interpretation of the frozen images.
Manual Measurement of IMT and LD
The ultrasound images from the videotape were first
analyzed in the computerized analyzing system based on manual
tracing of the echo interfaces described by our group in an earlier
report.7 IMT was defined as the distance from the leading
edge of the lumen-intima interface to the leading edge of the
media-adventitia interface of the far wall. The measurement of IMT in
the carotid artery was made in two separate segments: along a
10-mm-long segment in the common carotid artery and also along a
10-mm-long segment in the carotid artery bulb. Approximately 10
boundary points were marked along each echo interface by use of a
digitizer table and a mouse. Between these marked points the echo
interfaces were interpolated by the computer, so that 100 boundary
points were analyzed for each 10-mm section. The computer
program calculated the average thickness along the 10-mm-long section
(IMTmean) and also the maximum thickness of the
analyzed section (IMTmax). Mean and minimum LD of
the common carotid artery (LDmean and LD min)
were defined by the distance between the leading edges of the
intima-lumen interfaces of the near and lumen-intima of the far
wall.16 Measurements in the common femoral artery were
made in a way similar to that for the carotid artery but along a
15-mm-long section proximal to the bifurcation into the superficial
femoral artery and the profound femoral artery.4
Automated Measurement of IMT and LD
The images were also measured in the new analyzing system based
on automatic detection of the echo structures in the ultrasound image
but with the option to make manual corrections by the operator. In the
new analyzing system, the digitized image and the program functions are
shown on the same PC monitor (Fig 1
). An
extra monitor is also directly connected to the tape recorder for
visual evaluation of the real-time images on the videotape. This is
done to assist in a correct interpretation of the interfaces in the
frozen ultrasound images.
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Measurement Procedure
The starting point of the measurement area is set by the
operator, and a 10- or 15-mm box is automatically drawn. The different
echo interfaces are initially outlined fully automatically. If obvious
errors are detected by the reader, it is possible to modify the
measurement by marking a correct echo in the ultrasound image. In this
case only one or two manually marked points are often needed to guide
the automatic outlining to the correct interface in the whole segment.
The analyzing system also has an option for manual marking along the
whole echo interfaces in the segment. The program gives the average and
also the maximum thickness of the intima-media complex
(IMTmean and IMTmax) as well as
LDmean and LDmin, as in the manual analyzing
system. It is possible to save both the measurement results and the
contours of the measurement lines. This option makes it possible to
later reload the ultrasound image and also reload the measurement
contours.
Automatic Detection of Echo Interfaces by Use of a Dynamic
Programming Procedure
The automatic searching starts with an estimation of the
approximate positions of the echo interfaces and finishes with the
refined interface positions. The criterion for the optimized search is
based on a cost function that contains three terms, each of which has a
unique weight factor. The three terms reflect typical image features
that can be associated with the interface between different anatomic
structures. For a detailed description of general dynamic programming
procedures, see Reference 1717 .
Cost Function and Determination of Weight Factors
An essential step in the development of the new automated
analyzing system was to determine the terms to be included in the cost
function and their weight factors (Fig 2). These weight factors direct the
relative importance of the terms: echo intensity, intensity gradient,
and boundary continuity. For example, a low value of the weight factor
for boundary continuity will allow for a more irregular boundary,
whereas a high value forces the system to detect a more straight
boundary. This has important implications for the handling of echo
dropouts and irregularities along the vessel interface. Therefore, it
is important that the weight factors are tuned to the specific image
characteristics of each segment and each interface. The tuning is
performed in a trimming procedure and should thereafter not be
modified. If other ultrasonic instrumentations give other
characteristics, the weight factors might need some adjustments.
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Dynamic Programming Procedure
The estimated values of the three boundary features (echo
intensity, intensity gradient, and boundary continuity) are included as
weighed terms in the cost function so that each image point is
associated with a specific cost that in turn correlates with the
likelihood of that point being located at the echo interface. The
boundary detection algorithm inspects all points (pixels) in the image
(Fig 2
), considering all possible lines that may form the echo
interface, and gives favor to that which minimizes the cost function.
The number of all possible ways of forming a boundary in this manner is
enormous, and therefore an exhaustive search cannot be applied.
However, the optimization procedure referred to as dynamic programming
can solve this problem with dramatically fewer
operations.17
Statistical Analysis
All statistics were analyzed with the use of SPSS for
Windows 6.1. Means and SDs for differences between the readers were
calculated. Interobserver error (s) was then calculated
according to the formula s=SD/
2. The CV describes the
difference as a percentage of the pooled mean value
(¯x) and was calculated according to the formula
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Results |
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Comparison Between the Manual and Automated Analyzing Systems
The relationships between the two analyzing methods were highly significant (Table 1
). However, the
automated analyzing system gave higher mean values of carotid IMT than
the manual system (Table 1). See "Discussion" and Fig 3.
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Variability Between Readers
The same images were measured by three laboratory technologists
with different experience regarding analysis of ultrasound
images. When two experienced technologists used the manual analyzing
system, there was a significant difference in mean values of common
carotid IMT. When the automated analyzing system was used, the mean
values of IMT and LD were similar (Table 2).
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The CVs for IMT measurements between a technologist with long
experience and a technologist without previous experience of
analysis of ultrasound images were 1.2%, 3.8%, and 6.9% for
common carotid IMTmean, carotid bulb IMTmean,
and common femoral IMTmean, respectively (Fig 4).
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Manual Corrections
Manual corrections of the automatic outlining of the lumen-intima
or the media-adventitia interfaces of the far wall were performed in
17% of all images from the common carotid artery. Most corrections
were minor in nature (12%). Manual corrections of the interfaces in
the far wall of the carotid artery bulb were performed in 58% (minor
changes in 21%) of all images and in 67% (minor changes in 13%) of
all images from the common femoral artery.
Comparison of Time for Analysis
Analysis of one subject included measurement of 3 images
from the common carotid artery, 3 images from the carotid bulb, and 3
images from the common femoral artery. A complete analysis also
included the choice of frozen images from the videotape and image
digitization and also the evaluation of the real-time images on the
tape. This whole procedure takes approximately 45 minutes with the
manual analyzing system compared to 15 to 18 minutes with the new
automated analyzing system. The measurement procedure for 3 images from
common carotid artery and 3 images from the carotid artery bulb takes
approximately 4 minutes.
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Discussion |
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The development of a new automated analyzing system improves and facilitates the ultrasound measurement of IMT and LD in carotid and femoral arteries. The analyzing program is built in a PC/Windows environment with the program functions and the digitized ultrasound image on the same monitor and with the different steps in the program mouse controlled. This makes the new analyzing station more compact than the earlier system, and it also has ergonomic advantages compared with the old manual analyzing system. The automatic outlining of the echo structures and the easy handling of the program functions make the measurements much faster compared with manual tracing of the echo interfaces.
A thorough evaluation of the new program has been performed. This
evaluation showed that with the new automated analyzing system the
measurement results were less dependent on the readers experience, and
the variability between readers was also less compared with the old
manual analyzing system. There was still a small difference in common
carotid IMT between the readers (0.007 mm; Table 2), which was due
to the possibility of doing manual corrections. Therefore, when
performing the analyses the readers should be directed to only
correct obvious errors and false gaps in the echo interface defined by
help of the real-time images on videotape.
Few corrections were made in the measurement of common carotid IMT. However, many of the images from the carotid artery bulb and the common femoral artery needed corrections. The main cause was the occurrence of plaques in these areas. One reason for a false detection could be echoes with high intensity within the plaque. To lead the automatic outlining to the correct echo was mostly easy and could sometimes be made by marking one or two points of the correct interface. Other corrections consisted of marking of gaps in the echo interface. Small gaps in the echo interface were mostly outlined correctly since the automatic procedure also includes a boundary continuity term. This also means that artifacts within the blood stream with low continuity are not falsely outlined.
For one of the readers the automated analyzing system gave higher
values of IMT compared with the manual analyzing system. A possible
explanation for this is illustrated in Fig 3. The automatic procedure
always marks the interface at the point of the maximal gradient, that
is, the maximal change in echo intensity (or approximately at the point
of the maximal gradient since the program also takes into account the
other terms included in the cost function). When measurements are
performed manually, the point of the maximal gradient is mostly marked,
but sometimes the threshold for visibility of the echo interface (for
the human eye) is above this point, especially in the weaker
lumen-intima echo. In those cases the operator tends to mark more
closely to the top of the intensity curve for the lumen-intima
interface. This gives a thinner IMT compared with automatic
measurements (Fig 3).
A comparison was made between a technologist with long experience and a technologist without previous experience of analysis of ultrasound images. The CV for measurement of common carotid IMT was less than in previous studies of rereading with the manual analyzing system by the same experienced technologist.10 The CVs for measurement of carotid bulb IMT and common femoral IMT were similar compared with previous rereading studies.10
Automated analyzing systems that use the intensity gradient method (edge strength) for boundary detection have the advantage of applying well-defined measurement points since the algorithm always selects the points associated with the maximal gradient,12 13 14 but they also have some major disadvantages. The most prominent one seems to be the lack of a boundary continuity constraint. This makes the algorithm less robust because it frequently results in irregular boundaries due to echo dropouts and scattering phenomena. If the ultrasound image has smooth and clearly visible vessel interfaces along the whole segment, which is unusual, no major differences will be noticed between the boundaries detected by the intensity gradient method and the dynamic programming method. The reason for this is that both algorithms include a mechanism for searching points with high gradient, or edge strength, and the fact that the dynamic programming algorithm also includes a continuity term has no meaning in cases of images with smooth and clearly visible interfaces. But in the case of a partly irregular surface of the intima-media complex with echo dropouts, the dynamic programming algorithm will mostly bridge the gaps in the way a trained reader would have traced the interface. This is because the automatic program was trimmed, or tuned, to allow for the same amount of flexibility as shown by an experienced technologist. However, in cases in which the gap is wide or where there are several possible routes that the boundary detection could follow, even the dynamic programming algorithm may fail.
In conclusion, automatic measurement of IMT and LD is less time consuming. It also reduces the variability between readers and will probably also reduce the variability between different laboratories if the same analyzing program is used. Furthermore, the new automated analyzing system will probably prevent the problem with drift in measurements over time in a longitudinal study.
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Selected Abbreviations and Acronyms |
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Acknowledgments |
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This study was supported by grants from the Swedish Heart-Lung Foundation, the Swedish Medical Research Council (project B96-27X-10880-03A), and the Astra Hässle Cardiovascular Research Laboratories, Mölndal, Sweden. The authors acknowledge the excellent technical assistance of Caroline Schmidt and Anna Frödén. The computer laboratory of the Medical Faculty (MEDNET), Göteborg University, is also acknowledged for providing computing facilities.
Received March 6, 1997; revision received June 20, 1997; accepted July 3, 1997.
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O. Wiklund, J. Hulthe, J. Wikstrand, C. Schmidt, S.-O. Olofsson, and G. Bondjers Effect of Controlled Release/Extended Release Metoprolol on Carotid Intima-Media Thickness in Patients With Hypercholesterolemia: A 3-Year Randomized Study Stroke, February 1, 2002; 33(2): 572 - 577. [Abstract] [Full Text] [PDF]
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R. J. Woodman, D. A. Playford, G. F. Watts, C. Cheetham, C. Reed, R. R. Taylor, I. B. Puddey, L. J. Beilin, V. Burke, T. A. Mori, et al. Improved analysis of brachial artery ultrasound using a novel edge-detection software system J Appl Physiol, August 1, 2001; 91(2): 929 - 937. [Abstract] [Full Text] [PDF]
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P. Lundman, M. J. Eriksson, M. Stuhlinger, J. P. Cooke, A. Hamsten, and P. Tornvall Mild-to-moderate hypertriglyceridemia in young men is associated with endothelial dysfunction and increased plasma concentrations of asymmetric dimethylarginine J. Am. Coll. Cardiol., July 1, 2001; 38(1): 111 - 116. [Abstract] [Full Text] [PDF]
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 B. Hedblad, J. Wikstrand, L. Janzon, H. Wedel, and G. Berglund Low-Dose Metoprolol CR/XL and Fluvastatin Slow Progression of Carotid Intima-Media Thickness : Main Results From the {beta}-Blocker Cholesterol-Lowering Asymptomatic Plaque Study (BCAPS) Circulation, April 3, 2001; 103(13): 1721 - 1726. [Abstract] [Full Text] [PDF]
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J. Hulthe, O. Wiklund, E. Hurt-Camejo, and G. Bondjers Antibodies to Oxidized LDL in Relation to Carotid Atherosclerosis, Cell Adhesion Molecules, and Phospholipase A2 Arterioscler Thromb Vasc Biol, February 1, 2001; 21(2): 269 - 274. [Abstract] [Full Text] [PDF]
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J. Hulthe, L. Bokemark, and B. Fagerberg Antibodies to Oxidized LDL in Relation to Intima-Media Thickness in Carotid and Femoral Arteries in 58-Year-Old Subjectively Clinically Healthy Men Arterioscler Thromb Vasc Biol, January 1, 2001; 21(1): 101 - 107. [Abstract] [Full Text] [PDF]
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J. Hulthe, L. Bokemark, J. Wikstrand, and B. Fagerberg The Metabolic Syndrome, LDL Particle Size, and Atherosclerosis : The Atherosclerosis and Insulin Resistance (AIR) Study Arterioscler Thromb Vasc Biol, September 1, 2000; 20(9): 2140 - 2147. [Abstract] [Full Text] [PDF]
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C. Schmidt, J. Hulthe, J. Wikstrand, H. Gnarpe, J. Gnarpe, S. Agewall, and B. Fagerberg Chlamydia pneumoniae Seropositivity Is Associated With Carotid Artery Intima-Media Thickness Stroke, July 1, 2000; 31(7): 1526 - 1531. [Abstract] [Full Text] [PDF]
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D. Baldassarre, E. Tremoli, M. Amato, F. Veglia, A. Bondioli, and C. R. Sirtori Reproducibility Validation Study Comparing Analog and Digital Imaging Technologies for the Measurement of Intima-Media Thickness Stroke, May 1, 2000; 31(5): 1104 - 1110. [Abstract] [Full Text] [PDF]
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H. S. Markus, M. Sitzer, D. Carrington, M. A Mendall, and H. Steinmetz Chlamydia pneumoniae Infection and Early Asymptomatic Carotid Atherosclerosis Circulation, August 24, 1999; 100(8): 832 - 837. [Abstract] [Full Text] [PDF]
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