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Activity Index: A Tool to Identify Active Carotid Plaques 175
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Coronary Atherosclerotic Plaque Characterization By Intravascular Ultrasound
Francesco Ciompi, Oriol Pujol, Josepa Mauri Ferr´e, and Petia Radeva
Abstract The accurate characterization of in vivo atherosclerotic plaques
represents an important task during percutaneous intervention. Intravascular Ultrasound (IVUS) is a catheter-based imaging technique that provides a detailed cross-sectional representation of the internal morphology of the vessel, thus allowing to assess plaque amount and composition. In this chapter the state of the art methods for automatic plaque characterization in IVUS are analyzed. The main classification techniques as well as the most discriminative features are illustrated. Furthermore, a recently presented technique for the fusion of in vivo and in vitro IVUS data is illustrated.
1 Introduction
Coronary heart disease represents the 21% of mortality cause and accounts for 2 millions of lives in Europe. Atherosclerotic plaque formation results from the thickening of the intimal-medial segments and an overall thickening of the vessel wall. The term vulnerable plaque is commonly attributed to an atherosclerotic plaque that is likely to rupture or fissure, leading to thrombosis, and then to acute coronary syndrome: myocardial infarction, unstable angina pectoris, or sudden cardiac death [1–6]. An accurate analysis of in vivo plaque composition is then an important task in diagnosis and detection of vulnerable atheroma before plaque rupture.
F. Ciompi ()•O.Pujol•P.Radeva Computer Vision Center, Campus UAB, Edifici O, Bellaterra, Spain
University of Barcelona, Gran Via de Les Cortes Catalanes, 585, 08007 Barcelona, Spain e-mail: fciompi@maia.ub.es; oriol@maia.ub.es; petia@cvc.uab.es
J.M. Ferr´e University Hospital Germans Trias i Pujol, Carretera de Canyet s/n. 08916 Badalona, Spain e-mail: mauritri@gmail.com
J.M. Sanches et al. (eds.), Ultrasound Imaging: Advances and Applications, DOI 10.1007/978-1-4614-1180-2
8, © Springer Science+Business Media, LLC 2012
177
178 F. Ciompi et al.
Fig. 1 (a) In vivo IVUS image in cartesian coordinates, representing the cross-sectional IVUS image and (b) in polar coordinates
Fig. 2 Histological image (at the microscope) of ex vivo coronary section (a). The three layers are marked and (b) the detail of the interfaces (internal and external elastic lamina) is shown
Intravascular Ultrasound (IVUS) is a catheter-based imaging modality that provides an accurate luminal and transmural image of vascular structures [7]. It allows the visualization of the full circumference of the vessel wall, thus showing the tissue morphology and composition [8,9](seeFig.1).
The use of IVUS facilitates direct measurements of lumen size, including mini­mum and maximumdiameter and cross-sectionalarea as well as the characterization of atheroma size, plaque distribution, and lesion composition [10]. Three main regions, surrounding the luminal area of the vessel, can be distinguished in an IVUS image: the intima,themedia,andtheadventitia (see Fig. 2).
Coronary Atherosclerotic Plaque Characterization By Intravascular Ultrasound 179
The intima is normally a thin layer of endothelial cells: this layer substantially and often unevenly thickens into atherosclerosis. The media consists of multiple layers of smooth muscle cells arranged helically and circumferentially around the lumen of the artery. Finally, the adventitia is the external layer, essentially composed by fibrous tissue, i.e., collagen and elastin [11]. Estimation ofthe vessel area is based on the measurements of the media-adventitia border, and plaque area is derived by subtracting lumen area from vessel area.
Several IVUS-based approaches for the automatic assessment of plaque composition have been proposed in the last ten years, mainly based on image texture analysis [12–14] as well as on raw Radio Frequency (RF) signals processing [15–20]. Some approaches use Autoregressive Models (ARM) [15–17]orthe Fourier Transform [18, 20] to obtain a description of the tissue in the frequency domain, from whichspectral features are extracted. Approachesusing the Integrated Backscatter parameter [21–23]ortheWavelet coefficients [24] have been also proposed.
Most of the proposed methods for the automatic plaque characterization are based on a model that learns the plaque properties by labeled IVUS examples. In order to correctly train a model, reliable labeled IVUS data are necessary. The reliable correspondence between an atherosclerotic plaque and the corresponding IVUS data can only be obtained by histological analysis of post-mortem coronary arteries. Histology is in fact the only procedure that allows to know the real plaque nature in a certain position of the vessel. Unfortunately this methodology suffers from the complicated procedure of obtaining in vitro data: scarce arteries availability, frequent tissue spoiling during analysis and the difficulty in finding the right correspondence between IVUS and histological image.
In addition, in almost all the known plaque characterization methods, the discriminative power is assessed on in vitro plaques, then implicitly extending the discriminative property to in vivo data as well. This erroneous assumption is implicitly based on the hypothesis that differences between in vivo and in vitro IVUS data are negligible.
In this chapter some of the most important state-of-the-art techniques for automatic plaque characterization in Intravascular Ultrasound are presented. Fur­thermore, recent advances in the research topic of fusing in vivo and in vitro IVUS data for plaque characterization are described, and some results are provided.
2 In Vitro Data Validation Procedure
A possible procedure for the acquisition and validation of post-mortemIVUS data is now described. The coronary artery (separated from the heart) is first put on a mid­soft plane and filled (using a catheter) with physiological saline solution at constant pressure (around 100 mmHg), simulating blood pressure (see Fig.3). In the panel the distal and proximal position, together with left and right hand are marked to be used as a reference during histology. The probe is then introduced and RF data are
180 F. Ciompi et al.
Fig. 3 Set up for IVUS acquisition from post-mortem artery. (a) Coronary artery on the plane with marked positions clearly shown; (b) plaque segmentation on histological image and (c) segmentation on corresponding IVUS image
acquired in correspondence of plaques. These positions can be clearly marked on the externalpart of the artery. The artery is then cut in correspondenceof previously marked positions and plaque composition is determined by histological analysis.
As an alternative, a specially designed box containing the artery can be used, allowing the automatic cut of the vessel at a fixed number of positions by superimposing a dedicated set of knives [18]. With this procedure, a set of equally- spaced artery cuts of the artery are obtained.
For each cut, an image of the tissue at the microscope is obtained. Given the reference points in the paneland in the IVUS image orientation itis possibleto put in correspondence the plaques detected by histology with their respective areas in the IVUS image. The different conditions and modalities in which the two images are acquired are profoundly different. The mechanical consistence given to the artery while acquiring IVUS data is lost when cutting the vessel. Phenomena of tissue spoiling and a certain error in finding the exact correspondence between the IVUS and histological image make hard to get a good registration and, consequently, a reliable automatic labeling. Hence, the labeling process can be performed manually by joint cooperation of expertsand pathologist or by using a dedicated software able to register the two images obtained by different modalities and different approaches [16,17]. The plaques in IVUS data are thus validated and a groundtruth is obtained.
3 Plaque Characterization by Intravascular Ultrasounds
Different tissue types exhibit different acoustic properties and, consequently, different intensity and shape of the reflected ultrasonic wave; furthermore, the contribution of the scattered component is also different for each tissue. As a result, in the IVUS image, areas corresponding to different tissues exhibit different grey-level intensity and textures.
Most of the proposed plaque characterization methods are formulated as pattern recognition problems. For this reason, two main steps can be identified in each method: (1) the definition and extraction of discriminative features, describing the properties of different tissues; (2) the training of a classifier, used to characterize
Coronary Atherosclerotic Plaque Characterization By Intravascular Ultrasound 181
RF
Signals
Fig. 4 Schematic example of IVUS image formation from RF signals
TGC BP EV Log
IVUS
image
each position of the IVUS frame as belonging to one of the known plaque types. In this section the features used in the state-of-the-art methods are first presented, then the most common classification techniques used in the plaque characterization field are described.
3.1 Features Extraction
In the state-of-the-art plaque characterization methods, two main groups can be recognized: the methods based on image analysis and the methods based on radio frequency analysis. In this section, the features used in the two approaches are presented.
3.1.1 Image-Based Features
The first plaque characterization method based on the analysis of the texture in the IVUS image has been presented in [12]. The features used in this approach are: (1) radial profile,(2)long-run emphasis,and(3)fractal dimension. Despite of the high accuracy achieved, the main problem of using the IVUS images obtained with the IVUS equipment is the lack of normalization in data they provide. In order to improve the tissue visualization, physicians are used to change the imaging parameters of the IVUS equipment, thus making the set of images and, consequently, image-based features, not comparable. In order to avoid this problem, the raw radio frequency signals captured by the IVUS equipment can be used to reproduce the image formation process [14]. A common approach to IVUS image formation from RF data foresees, at least, the following steps (see Fig. 4):
• Time Gain Compensation (TGC): as the US propagating in the tissue is af-
fected by an attenuation due to depth, it is necessary to compensate it by a
TGC function. One possible TGC function could be: T (r)=1 −e
α
β
= ln10
f /20
,αis the attenuation factorof the tissue measured in dB/MHz·cm,
−βr
,where
f is the frequency of the transducer in MHz,andr is the radial distance from the
catheter in cm.
• Band Pass filtering: data can be then filtered by a band-pass filter in order to
reduce the noise effect and spurious harmonic components outside the band of
interest. For this purpose, a Butterworth filter is suitable, given that its frequency
response is as flat as mathematically possible in the passband.
182 F. Ciompi et al.
• Envelope: after filtering, the envelope of the signal has to be recovered, in order
to change from bipolar to unipolar signal and to achieve the final conversion
between 0 and 255. This can be done for example by taking the absolute value of
the Hilbert transform of the signal.
• Logarithmic compression: This transformationmaps a narrow range of lowgray-
level values in the input image into a wider range of output levels; the following
log(1+(et−1)RF
formula can be used [25]: RF
log
=
t
RF data after the envelope computation, and RF
)
env
,whereRF
the output of the logarithmic
log
represents the
env
compression.
In [14] the reconstruction process is used to create a set of IVUS images of in vivo cases. Textural features are then extracted by using: (1) co-occurrence matrix, (2) local binary patterns,and(3)gabor filters.
3.1.2 Radio Frequency-Based Features
RF data from the unprocessed backscattered ultrasound signal provide an alter­native to greyscale image analysis. Theoretically, the analysis of the IVUS-RF data provides a more accurate and reproducible technique for measuring tissue properties because it is not subject to machine-dependent processing, subsampling, interpolation, quantization, and even operator-dependent settings [26].
The most important approaches based on RF data processing are now analyzed by focusing on the analysis of the used features. Most of the methods process the RF data frame, formed by N A-lines and M samples.
Acoustic Impedance (Z)
It is known that the US wave propagates with different velocity in different tissues; this comes from the equation of the wave propagating through a tissue with density
ρ
and with acoustic impedanceζ. Then, the information on the relative acoustic impedance can beused as a parameterto classify plaque types, since they are consid­ered as different tissues. The method presented in [19] is based on this phenomenon. It assumes that ultrasound pulse is well approximated by using the Plane Wave Born Approximation (PWBA) deconvolved inverse scattering technique [27].
Integrated Backscatter (IB)
The first methodbased on IB wasproposed in 1989 and wasoriented to the detection of acute myocardial infarction and re-perfusionvia M-mode echocardiography [28].
Coronary Atherosclerotic Plaque Characterization By Intravascular Ultrasound 183
Tabl e 1 Integrated backscatter values obtained by histological analysis of post-mortem tissues. The values are provided as mean value ±1 dB. Data extracted from [22]
Histology IB [dB] Calcified tissue −30 < IB ≤−23
Mixed lesion −55 < IB ≤−30 Fibrotic tissue −63 < IB ≤−55 Lipidic core −73 < IB ≤−63 Thrombus −88 < IB ≤−80
The IB is an intrinsic parameter of the electrical US signal and can be computed as [21]:
IB = 20log
1
T
1
T
T
2
V
∑
0
, (1)
T
2
V
∑
0
0
where V is the signal voltage from a selected Region of Interest (ROI) in the RF data frame, V
is the smallest signal voltage that the system can detect, and T is the
0
integration interval.
It has been shown that the IB parameter combined with two-dimensional echo can differentiatethe tissue characteristics in both in vivo and ex vivo studies [21,22]. In Table 1 the computed value of the IB parameter when characterizing tissues in in vitro cases are presented when discriminating calcifications, mixed lesions, fibrous tissue, lipidic core, and thrombus. Since no overlaps in the obtained values are encountered, the discriminative power of this parameter is confirmed (see Table 1).
A plaque characterization system based only on IB parameter is now distributed only in Japan (YD Co. Ltd, Tokyo).
Power Spectrum
Based on the hypothesis that different tissues behave differently in the frequency domain, several approaches based on the analysis of power spectrum have been proposed. Mainly, given the RF representation of an IVUS frame, for each ROI of
N
samples and Mrcontiguous A-lines, a power spectrum is associated to each point
r
by averaging the power spectra computed in the lines belonging to the ROI. The power spectrum can be computed by means of the Fast Fourier Transform (FFT) [15,18, 20] or by using the AutoRegressive Model (ARM) [14,16,17, 29].
Given the power spectrum, a set of spectral features can be extracted. Some features have been successfully used in plaque characterization techniques, as the mean power (dB), maximum power (dB), spectral slope (dB/MHz) (a least­squares linear regression over the given bandwidth), y-axis intercept of spectral slope (dB) (intercept of the straight line with the y-axis at 0 Hz) [15]. In addition, the value of the frequencies corresponding to maximum and minimum power can be used [16, 17]. In [16, 17] these features are extracted in a frequency range of
184 F. Ciompi et al.
17–42MHz, corresponding to the −20 dB bandwidth of the system. This set of features, commonly known in literature as the seven-features approach, together with the Integrated Backscatter (IB) represent the basis of a commercial product called Virtual Histology (VH), implemented in the Volcano (Rancho Cordova, CA) IVUS clinical scanners that offer near-realtime tissue characterization in vivo [30].
Alternatively to the presented spectral features, a full-spectrum approach can be considered, where the Fourier Transform is used [18, 20]. The use of a full­spectrum analysis demonstrated to produce more accurate results, compared with the seven-features approach, classifying fibrolipidic, lipidic, fibrotic, and calcified tissue: when using a 40MHz catheter in fact, a lot of variations can be found in the main bandwidth of the signal (20–60 MHz), thus justifying a full-spectrum analysis [18]. In the full-spectrum approach the power spectrum, with frequency range from 0 to 100MHz, is discretized using a certain number of bins and then used as feature vector for each point (the center of a ROI) of the IVUS frame. This approach is implemented in the iMap Plaque Characterization software provided with the iLab IVUS equipment (Boston Scientific).
Wavelet-Based Approach
The wavelet analysis of RF signals has been also studied in recent years [24, 31]. A wavelet is mainly a waveform of limited duration and zero average amplitude [32]. The wavelet analysis, applied to IVUS-RF signal, consists in the computation of wavelet coefficients, localized by the amplitude and the position of wavelets.
The hypothesis in this kind of approach is that the IVUS-RF signal belonging to different tissues exhibits different behavior when analyzed by wavelet, and that the wavelet coefficients, computed at different scales, could be the discriminative measures to be used in the tissue characterization [26].
This approach has been proved to be appropriate in discriminating the fibrous from the fatty areas within atherosclerotic plaques [24].
Joining Textural and Spectral Features
Recently [29], an approach that proposes to combine both textural and spectral features provided interesting results in the field of plaque characterization. The used feature vector is constructed by concatenating image textural and spectral features with the aim of blending the appearance of the tissues with information obtained from their spectral content. Themain idea is thatimage-based andRF signal analysis provide complementary data for the accurate description of tissue composition and leads to a rich set of features to be selected and weighted by the classifier. The approach leads to an overall accuracy A = 89.93% in classifying fibrotic, lipidic, and calcified plaques in vitro [29].
Coronary Atherosclerotic Plaque Characterization By Intravascular Ultrasound 185
2000
1800
1600
3
1400
1200
feature
1000
800
600
1
0.8
Fig. 5 Feature space. A set of point acquired from four different tissue types are represented in the space of three discriminant features
tissue1 tissue2 tissue3 tissue4
0.6
feature
2
0.4
0.2
20
15
10
5
0
0
feature
1
3.2 Tissue Classification
A classifier is a probabilistic model (discriminative or generative) with a set of parameters determined (learned) during the training process. The model is in fact able to learn the features of the input data, and to tune its parameters according to data. When the training process is over, the set of learned parameter is finally saved and the classifier is ready to be used to characterize unknown examples.
The atherosclerotic plaque characterization problem implies the definition of a multi-class classifier. Except for some approaches that discriminate for example fibrotic from fatty (lipidic) plaques, the main scenario implies in fact the discrim­ination among fibrotic, lipidic, and calcified plaques. Furthermore, the necrotic core, fibrolipidic, and lipidic with calcifications tissues are also considered in some approaches. The characterization problem consists in separating, in the feature space, clouds of points belonging to multiple classes (Fig.5).
Several approaches have been presented to solve the multi-class tissue character­ization problem: we will refer to them with the word “architecture,” since they often consist in combining a set of simple classifiers into a more complex framework.
3.2.1 Decision Tree
One simple architecture for the discrimination of different tissues is the decision tree [16,17]. Starting from the main node (root), during the training process, at each
node the input data are split into sub-groups according to the most discriminative feature in that node.