Atherosclerosis: the evolving role of vascular image analysis
Computerized Medical Imaging and Graphics
Atherosclerosis: The evolving role of vascular image analysis
National Technical University of Athens, School of Electrical and Computer Engineering, Biomedical Simulations and Imaging (BIOSIM) Laboratory,
Iroon Polytechniou 9, Zografos 15780, Athens, Greece
Atherosclerosis, a chronic systemic degenerative disease involv-
hemorrhage, large lipid cores, and heterogeneous material distri-
ing the aorta, coronary, carotid, and peripheral arteries, has plagued
bution are among the candidate “suspects” for abrupt progression
mankind since the beginning of time. Surprisingly enough, it
of the disease and plaques prone to rupture. Plaque inﬂammation
has been recently proved that even Egyptian mummies, ancient
is also believed to be a main driver of clinical events
humans of high social status, had established atherosclerosis in
The aforementioned difﬁculties in current decision making for
atherosclerosis hold major risks for patient safety considering that
Although atherosclerotic lesions (plaques) may remain “silent”
atherosclerosis may not be detected at an early stage, vulnerable
for decades, they are considered the leading underlying cause of
plaques may not be identiﬁed, while patients with stable plaques
cardiovascular disease (CVD) which covers a wide range of fatal
may unnecessarily undergo a surgical procedure with potential
disorders related to the circulatory system, such as coronary heart
complications. Furthermore, due to the high cost of revascula-
disease (CHD) and stroke. Each year, CVD causes over 1.9 million
rization and bypass surgery already unbearable cost of
deaths in the European Union (EU); CHD by itself accounts for 15%
atherosclerosis is further increased; note that it has recently been
and 13% of all deaths among men and women, respectively, while
shown that unnecessary carotid revascularization procedures in
around one in every twelve men (8%) and one in ten women (11%)
asymptomatic patients in the US cost health-care providers US$2
die from stroke same report highlights that CVD costs EU
some D 196 billion a year due to healthcare costs (54%), productivity
With atherosclerosis being a major cause of morbidity and mor-
losses (24%) and spending on informal care (22%). Similar statistics
tality, as well as an economic burden worldwide, it is obvious that
have also been reported for the United States (US) causes
early detection and valid risk stratiﬁcation for the disease consti-
approximately 1.3 million deaths each year in the US, with CHD
tute a crucial public health challenge. In recent decades, advances
and stroke accounting for 17% and 6% of all deaths, respectively.
in medical imaging technology and computer vision have allowed
The annual direct and indirect ﬁnancial cost of CVD in the US is
for valuable contribution of image analysis toward this direction. By
estimated $297.7 billion due to healthcare expenditures (60%) and
continuously revealing several new morphological or composition-
related markers, vascular image analysis plays a multifaceted role
In current clinical practice, atherosclerotic patients are offered
which focuses on accurately detecting the presence of atheroscle-
either an invasive procedure, such as artery revascularization
rosis in individuals, deﬁning the burden of the disease before they
(endarterectomy or angioplasty with stenting) and bypass surgery,
develop clinical events, and evaluating the efﬁcacy of therapies.
or a more conservative therapy with medications, physical exercise
Computed tomography (CT) of the chest, in particular, has pro-
and dietary therapeutic decision is traditionally made judg-
vided a real breakthrough in the evaluation of coronary artery
ing on symptom status and the image-measured degree of artery
calciﬁcation (CAC) used for detecting the presence of atheroscle-
stenosis, which, however, is not always sufﬁcient Speciﬁ-
rosis in the artery. Furthermore, CAC score has been shown to be
cally, it has been observed that severe carotid artery stenosis may
able to assess cardiovascular risk, adding prognostic information
remain asymptomatic carotid atherosclerotic plaques
to the Framingham risk score CT image analy-
causing a low degree of stenosis can result in symptoms
sis has also shown great potential in detecting signiﬁcant coronary
nary atherosclerotic plaques being less than 50% occlusive have
artery stenoses identifying the composition of plaques
also been reported to cause acute coronary and cerebrovascular
and assessing the response to anti-inﬂammatory drugs
syndromes observations arise from the fact that plaque’s
Similar ﬁndings have been reported regarding the role of mag-
material (calcium, ﬁbers, blood components, lipids, etc.) composi-
netic resonance imaging (MRI) in optimal management of the
tion appears to be a critical determinant of the risk for future events
disease. Besides the ability of MRI image analysis to clearly identify
the absence of calciﬁcation, thin ﬁbrous caps, intra-plaque
vessel boundaries, thereby allowing highly accurate measurements
of plaque burden histological studies have shown that it
also offers a comprehensive structural plaque characterization
More interestingly, experiments have associated the iden-
tiﬁcation of a ruptured ﬁbrous cap in MRI images with a recent
K.S. Nikita / Computerized Medical Imaging and Graphics 37 (2013) 1–3
history of ischemic event MRI image analysis of
would offer optimal data management, knowledge discovery and
atherosclerosis can also provide useful information about the effect
sharing, as well as easy comparisons with similar prior cases for
Nuclear imaging modalities, i.e. positron emission tomogra-
However, translating biomedical research into beneﬁcial com-
phy (PET) and single-photon emission computed tomography
mercial and proﬁtable products is often difﬁcult due to different
(SPECT), can provide a valuable tool for functional evaluation of
expertise and the mutual understanding of objectives and
the atherosclerotic disease. PET and SPECT can demonstrate signif-
requirements of the scientiﬁc community, clinicians and indus-
icant artery stenoses, while co-registration with other modalities
try. Therefore, partnerships and information exchange among
(PET-CT, PET-MRI, SPECT-CT) is widely used enabling a com-
academic, medical and industrial institutions are necessary in
bined study of plaques’ structure and function
developing systems which will be incorporated in current clin-
18F-ﬂuorodeoxyglucose nuclear image analysis has been used to
ical practice, thereby optimizing the delivery of healthcare for
identify inﬂamed atherosclerotic plaques detect signs of
atherosclerosis. Such systems are expected to signiﬁcantly con-
biological effects of experimental drugs
tribute to the vision of occidental countries to manage prevalent
Intravascular ultrasound (IVUS) has emerged as a valuable imag-
chronic diseases, enhance patient safety through prediction, opti-
ing modality for atherosclerosis, especially for the assessment of
mized treatments, and fewer medical errors, halt the rising cost of
ambiguous lesions, as those located in the left main coronary artery
healthcare without compromising quality and efﬁciency, bridge the
or at bifurcation sites. Measurements on IVUS images are able to
gap between research and medical practice, and realize the health
demonstrate changes in plaque lesion size with time and treatment
IVUS studies are more limited because of the ﬁnan-
To conclude, given that atherosclerosis holds a major risk for
cial cost, the increase in the time of the procedure, and the fact that
both public health and state economies, and the current ‘one-size-
it is considered an interventional procedure.
ﬁts-all’ approach has been shown to be inadequate and inefﬁcient,
Because of its low cost, non-invasiveness and short time of
it is crucial to reveal novel, personalized and low-cost markers that
examination, duplex ultrasound is commonly used in monitor-
will upgrade the medical practice for the disease. Computerized
ing and tracking progression of atherosclerotic disease. Analysis of
analysis of vascular images, and particularly ultrasound ones, plays
ultrasound images of the neck allows measurements of (i) the thick-
a valuable role in this ﬁeld and is expected to continue receiving
ness of two layers of the wall of the carotid artery (the so-called
signiﬁcant attention by future research.
carotid intima-media thickness) which has emerged as one of the
most powerful tools for the evaluation of subclinical atherosclero-
sis drug response (ii) texture indices of carotid
plaques which in several studies have been correlated with plaque
stability symptom status motion-based features
 Allam AH, Thompson RC, Wann LS, Miyamoto MI, Thomas GS. Computed tomo-
which can discriminate between symptomatic and asymptomatic
graphic assessment of atherosclerosis in ancient Egyptian mummies. J Am Med
patients can also quantify arterial stiffness and shear strain
 Nichols M, Townsend N, Luengo-Fernandez R, Leal J, Scarborough P, Rayner M.
within the carotid arterial wall plaque volume changes
European cardiovascular disease statistics. Sophia Antipolis: European Heart
for evaluating new therapies and (v) plaque surface varia-
Network and European Society of Cardiology; 2012, ISBN 978-2-9537898-1-2.
 Roger VL, Go AS, Lloyd-Jones DM, Benjamin EJ, Berry JD, Borden WB, et al.
tion/roughness to examine the regression/progression of carotid
Heart disease and stroke statistics—update. A report from the American Heart
Association. Circulation 2012;125(1):e2–220.
In all cases, vascular image analysis and quantiﬁcation of
 Tendera M, Aboyans V, Bartelink ML, Baumgartner I, Clément D, Collet JP, et al.
ESC guidelines on the diagnosis and treatment of peripheral artery diseases:
plaque morphology and composition depend primarily on image
document covering atherosclerotic disease of extracranial carotid and verte-
processing methods. This leads to several challenging steps in cur-
bral, mesenteric, renal, upper and lower extremity arteries: the Task Force on
rent related research, including improvement of image quality
the Diagnosis and Treatment of Peripheral Artery Diseases of the European
valid and user-independent identiﬁcation of plaque region
Society of Cardiology (ESC). Eur Heart J 2011;32(22):2851–906.
 Inzitari D, Eliasziw M, Gates P. The causes and risk of stroke in
enhancement of accuracy in feature extraction
patients with asymptomatic internal carotid artery stenosis. N Engl J Med
implementation of proper statistical analysis and artiﬁcial intelli-
gence tools importantly, ongoing research focuses
 Polak JF, Shemanski L, O’Leary DH. Hypoechoic plaque at US of the carotid
artery: an independent risk factor for incident stroke in adults aged 65 years
on the identiﬁcation, and evaluation in large data samples, of novel
or older. Cardiovascular Health Study. Radiology 1998;208:649–54.
markers for detecting the presence of atherosclerosis and assessing
 Schoenhagen P, Ziada KM, Kapadia SR, Crowe TD, Nissen SE, Tuzcu EM.
plaque vulnerability before noticeable symptoms develop.
Extent and direction of arterial remodeling in stable versus unstable coro-
nary syndromes: an intravascular ultrasound study. Circulation 2000;101:
The ultimate outcome of such investigations will hopefully be
the development of integrated systems will assist pre-
 Hellings WE, Peeters W, Moll FL, Piers SR, van Setten J, Van der Spek PJ, et al.
diction, diagnosis and therapy decision for atherosclerosis. Carotid
Composition of carotid atherosclerotic plaque is associated with cardiovascular
outcome: a prognostic study. Circulation 2010;121(17):1941–50.
ultrasound image analysis shows great potential toward this direc-
 Hansson GK, Robertson AK, Söderberg-Nauclér C. Inﬂammation and atheroscle-
tion, considering the cost-effectiveness of ultrasound imaging and
rosis. Annu Rev Pathol 2006;1:297–329.
the fact that it has already revealed valuable markers. A system
 Koechlin F, Lorenzoni L, Schreyer P. Comparing price levels of hospital services
across countries: results of a pilot study. OECD Health Working Papers No. 53;
incorporating the produced knowledge would offer (i) predic-
tion and early diagnosis of carotid atherosclerosis by measuring
 Ross Naylor A. Time to rethink management strategies in asymptomatic carotid
intima-media thickness, (ii) identiﬁcation of plaque presence and
artery disease. Nat Rev Cardiol 2012;9:116–24.
boundaries, which in routine clinical practice depends on the train-
 Arad Y, Goodman KJ, Roth M, Newstein D, Guerci AD. Coronary calciﬁca-
tion, coronary disease risk factors, C-reactive protein, and atherosclerotic
ing, the experience and the expertise of the observer, through
cardiovascular disease events: the St. Francis Heart Study. J Am Coll Cardiol
user-independent segmentation techniques, (iii) objective char-
acterization of arterial areas in terms of texture, motion and
 Leber AW, Knez A, Becker A, Becker C, von Ziegler F, Nikolaou K, et al. Accuracy
of multidetector spiral computed tomography in identifying and differentiating
morphology, (iv) valid assessment of plaque vulnerability, and (v)
the composition of coronary atherosclerotic plaques: a comparative study with
recommendation on treatment selection. Additionally, the com-
intracoronary ultrasound. J Am Coll Cardiol 2004;43:1241–7.
bination of this system with semantic technology would allow
 Heuschmid M, Burgstahler C, Baumbach A, Wehrmann M, Claussen CD.
Reliability of differentiating human coronary plaque morphology using
medical experts to annotate images with formality and retrieve
contrast-enhanced multislice spiral computed tomography: a comparison with
data through complex search queries These functionalities
histology. J Comput Assist Tomogr 2004;28:449–54.
K.S. Nikita / Computerized Medical Imaging and Graphics 37 (2013) 1–3
 Kouz S, Lavoie MA, Paquin J, Brotz TM, Taub R, Pressacco J. Treatment with
 Tsiaparas NN, Golemati S, Andreadis I, Stoitsis JS, Valavanis I, Nikita KS.
5-lipoxygenase inhibitor VIA-2291 (Atreleuton) in patients with recent acute
Comparison of multiresolution features for texture classiﬁcation of carotid
coronary syndrome. Circ Cardiovasc Imaging 2010;3:298–307.
atherosclerosis from B-mode ultrasound. IEEE Trans Inf Technol Biomed
 Yuan C, Beach KW, Smith Jr LH, Hatsukami TS. Measurement of atherosclerotic
carotid plaque size in vivo using high resolution magnetic resonance imaging.
 Meairs S, Hennerici M. Four-dimensional ultrasonographic characterization of
plaque surface motion in patients with symptomatic and asymptomatic carotid
 Cai JM, Hatsukami TS, Ferguson MS, Small R, Polissar NL, Yuan C. Classiﬁcation
artery stenosis. Stroke 1999;30(9):1807–13.
of human carotid atherosclerotic lesions with in vivo multicontrast magnetic
 Golemati S, Stoitsis JS, Gastounioti A, Dimopoulos AC, Koropouli V, Nikita KS.
resonance imaging. Circulation 2002;106:1368–73.
Comparison of block matching and differential methods for motion analysis of
 Yuan C, Zhang SX, Polissar NL, Echelard D, Ortiz G, Davis JW, et al. Identiﬁcation
the carotid artery wall from ultrasound images. IEEE Trans Inf Technol Biomed
of ﬁbrous cap rupture with magnetic resonance imaging is highly associated
with recent TIA or stroke. Circulation 2002;105:181–5.
 Ainsworth CD, Blake CC, Tamayo A, Beletsky V, Fenster A, Spence JD. 3D ultra-
 Corti R, Fuster V, Fayad ZA, Worthley SG, Helft G, Smith D, et al. Lipid lower-
sound measurement of change in carotid plaque volume: a tool for rapid
ing by simvastatin induces regression of human atherosclerotic lesions: two
evaluation of new therapies. Stroke 2005;36:1904–9.
years’ follow-up by high-resolution noninvasive magnetic resonance imaging.
 Schminke U, Motsch L, Hilker L, Kessler C. Three-dimensional ultra-
sound observation of carotid artery plaque ulceration. Stroke 2000;31:
 Di Carli MF, Dorbala S. Cardiac PET-CT. J Thorac Imaging 2007;22:101–6.
 Tawakol A, Migrino RQ, Hoffmann U, Abbara S, Houser S, Gewirtz H,
 Golemati S, Stoitsis JS, Perakis D, Varela E, Alexandridi A, Davos C, et al. Carotid
et al. Noninvasive in vivo measurement of vascular inﬂammation with
artery motion estimation from sequences of B-mode ultrasound images:
F-18 ﬂuorodeoxyglucose positron emission tomography. J Nucl Cardiol
effect of scanner settings and image normalization. IEEE Trans Instrum Meas
 Tahara N, Kai H, Ishibashi M, Nakaura H, Kaida H, Baba K, et al. Simvastatin
 Golemati S, Stoitsis JS, Sifakis E, Balkizas T, Nikita KS. Using the Hough Trans-
attenuates plaque inﬂammation evaluation by ﬂuorodeoxyglucose positron
form to segment ultrasound images of longitudinal and transverse sections of
emission tomography. J Am Coll Cardiol 2006;48:1825–31.
the carotid artery. Ultrasound Med Biol 2007;33(12):1918–32.
 Tardif JC, Gregoire J, L’Allier PL, Anderson TJ, Bertrand O, Reeves F, et al. Effects of
 Gastounioti A, Golemati S, Stoitsis JS, Nikita KS. Comparison of Kalman-ﬁlter-
the acyl coenzyme A: cholesterol acyltransferase inhibitor avasimibe on human
based approaches for block matching in arterial wall motion analysis from B-
atherosclerotic lesions. Circulation 2004;110:3372–7.
mode ultrasound. IOP Meas Sci Technol 2011;22(11):114008 (9 pp.).
 de Groot E, van Leuven SI, Duivenvoorden R, Meuwese MC, Akdim F, Bots
 Tsiaparas NN, Golemati S, Andreadis I, Stoitsis JS, Valavanis I, Nikita KS.
ML, et al. Measurement of carotid intima-media thickness to assess pro-
Assessment of carotid atherosclerosis from B-mode ultrasound images using
gression and regression of atherosclerosis. Nat Clin Practice Cardiovasc Med
directional multiscale texture features. IOP Meas Sci Technol 2012;23:114004
 Smith Jr SC, Greenland P, Grundy SM. AHA Conference Proceedings. Prevention
 Stoitsis J, Golemati S, Nikita KS. A modular software system to assist interpreta-
conference V: beyond secondary prevention: identifying the high-risk patient
tion of medical images—application to vascular ultrasound images. IEEE Trans
for primary prevention: executive summary. American Heart Association. Cir-
 Kyrgiazos G, Gerostathopoulos I, Kolias V, Stoitsis JS, Nikita KS. A semantically-
 Taylor AJ, Villines TC, Stanek EJ, Devine PJ, Griffen L, Miller M, et al. Extended-
aided approach for online annotation and retrieval of medical images. In:
release niacin or ezetimibe and carotid intima-media thickness. N Engl J Med
Proceedings of the 33rd Annual International Conference of the IEEE Engineer-
ing in Medicine and Biology Society. 2011. p. 2372–5.
 Tegos TJ, Sohail M, Sabetai MM, Robless P, Akbar N, Pare G, et al. Echomor-
 Zhang YT, Poon C, MacPherson E. Editorial note on health informatics. IEEE
phologic and histopathologic characteristics of unstable carotid plaques. Am J
Trans Inf Technol Biomed 2009;13(3):281–3.
Alzheimer’s and Related Diseases Research Award Fund 2010 – 2011 FINAL PROJECT REPORT SUMMARIES The Alzheimer's and Related Diseases Research Award Fund (ARDRAF) was established by the Virginia General Assembly in 1982 and is administered by the Virginia Center on Aging at Virginia Commonwealth University. Summaries of the final project reports submitted by investigators funded during
Ergebnisübersicht: Euskirchen-Dom-Esch,PLS 2011 [ 471126021 ] 23.06.2011 - 25.06.2011 Reiter-WB 1. P Veronique Klaßen (RFV Jan von Werth Jülich)3. P Sabrina Adamek (RSZ Euskirchen-Dom-Esch)5. P Anne-Selina Adamek (RSZ Euskirchen-Dom-Esch)5. P Hanna-Jörne Hamacher (Meckenheimer RC e.V.)7. P Yakira Heitzer (RG Zülpich-Merzenich)8. P Janina Müsch (RFV St.Hubertus e.V.) Reiter-WB