Atheroma

An atheroma is an accumulation of degenerative material in the tunica intima (inner layer) of artery walls.
The material consists of (mostly) macrophage cells, or
debris, containing lipids (cholesterol and fatty acids), calcium and a variable amount of brous connective tissue.
The accumulated material forms a swelling in the artery
wall, which may intrude into the channel of the artery,
narrowing it and restricting blood ow. Atheroma occurs
in atherosclerosis, which is one of the three subtypes of
arteriosclerosis (which are atherosclerosis, Monckebergs
arteriosclerosis and arteriolosclerosis).[1]

cedure. Therefore, existing diagnostic strategies for detecting atheroma and tracking response to treatment have
been extremely limited. The methods most commonly
relied upon, patient symptoms and cardiac stress testing,
do not detect any symptoms of the problem until atheromatous disease is very advanced.

2 History of research

In developed countries, with improved public health, inIn the context of heart or artery matters, atheromata are
fection control and increasing life spans, atheroma procommonly referred to as atheromatous plaques. It is an
cesses have become an increasingly important problem
unhealthy condition, but is found in most humans.[2]
and burden for society. Atheromata continue to be the
Veins do not develop atheromata, unless surgically moved primary underlying basis for disability and death, despite
to function as an artery, as in bypass surgery. The ac- a trend for gradual improvement since the early 1960s
cumulation (swelling) is always in the tunica intima, be- (adjusted for patient age). Thus, increasing eorts totween the endothelium lining and the smooth muscle wards better understanding, treating and preventing the
tunica media (middle layer) of the artery wall. While the problem are continuing to evolve.
early stages, based on gross appearance, have traditionAccording to United States data, 2004, for about 65% of
ally been termed fatty streaks by pathologists, they are not
men and 47% of women, the rst symptom of cardiocomposed of fat cells, i.e. adipose cells, but of accumuvascular disease is myocardial infarction (heart attack) or
lations of white blood cells, especially macrophages, that
sudden death (death within one hour of symptom onset.)
have taken up oxidized low-density lipoprotein (LDL).
After they accumulate large amounts of cytoplasmic Most artery ow-disrupting events occur at locations with
membranes (with associated high cholesterol content) less than 50% lumen narrowing. From clinical studthey are called foam cells. When foam cells die, their ies published in the late 1990s to IVUS (in-the-arterycontents are released, which attracts more macrophages ultrasound) to visualize disease status, the typical heart atand creates an extracellular lipid core near the center to tack occurs at locations with about 20% stenosis (narrowinner surface of each atherosclerotic plaque. Conversely, ing), prior to sudden lumen closure and resulting myocarthe outer, older portions of the plaque become more cal- dial infarction. Cardiac stress testing, traditionally the
cied, less metabolically active and more physically sti most commonly performed noninvasive testing method
for blood ow limitations, generally only detects lumen
over time.
narrowing of ~75% or greater, although some physicians
advocate nuclear stress methods that can sometimes detect as little as 50%.

Diculty of tracking and researching atheroma

3 Artery and atheroma behavior

For most people, the rst clinical symptoms result from

atheroma progression within the heart arteries, most commonly resulting in a heart attack and ensuing debility.
However, the heart arteries, because (a) they are small
(from about 5 mm down to microscopic), (b) they are hidden deep within the chest and (c) they never stop moving,
have been a dicult target organ to track, especially clinically in individuals who are still asymptomatic. Additionally, all mass-applied clinical strategies focus on both
(a) minimal cost and (b) the overall safety of the pro-

The healthy epicardial coronary artery consists of three

layers, the intima, media, and adventitia.[3][4] Atheroma
and changes in the artery wall usually result in small
aneurysms (enlargements) just large enough to compensate for the extra wall thickness with no change in the
lumen diameter. However, eventually, typically as a result of rupture of vulnerable plaques and clots within the
lumen over the plaque, stenosis (narrowing) of the vessel
develops in some areas. Less frequently, the artery en1

4 INTIMA-MEDIA THICKNESS MEASUREMENTS IN THE CAROTID ARTERY

larges so much that a gross aneurysmal enlargement of den hemorrhage (bleeding), major symptoms and debilthe artery results. All three results are often observed, at ity; often rapid death. The main stimulus for aneurysm
dierent locations, within the same individual.
formation is pressure atrophy of the structural support
of the muscle layers. The main structural proteins are
collagen and elastin. This causes thinning and the wall
3.1 Stenosis and closure
balloons allowing gross enlargement to occur, as is common in the abdominal region of the aorta.
Over time, atheromata usually progress in size and thickness and induce the surrounding muscular central region
(the media) of the artery to stretch out, termed remodeling, typically just enough to compensate for their size 4 Intima-media thickness measuch that the caliber of the artery opening (lumen) resurements in the carotid artery
mains unchanged until typically over 50% of the artery
wall cross-sectional area consists of atheromatous tissue
Since the 1990s, both small clinical and several larger(see: Glagov, below).
scale pharmaceutical trials have used carotid intimaIf the muscular wall enlargement eventually fails to keep
media thickness (IMT) as a surrogate endpoint for evaluup with the enlargement of the atheroma volume, or a
ating the regression and/or progression of atherosclerotic
clot forms and organizes over the plaque, then the lumen
cardiovascular disease. Many studies have documented
of the artery begins to narrow, commonly as a result of
the relationship between the carotid intima-media thickrepeated ruptures of the covering tissues separating the
ness and the presence and severity of atherosclerosis. In
atheroma from the blood stream. This becomes a more
2003, the European Society of Hypertension-European
common event after decades of living, increasingly more
Society of Cardiology recommended the use of IMT
common after people are in their 30s to 40s.
measurements in high-risk patients to help identify tarThe endothelium (the cell monolayer on the inside of the get organ damage not revealed by other exams such as
vessel) and covering tissue, termed brous cap, separate the electrocardiogram.
atheroma from the blood in the lumen. If a rupture ocThough carotid intima-media thickness seems to be
curs of the endothelium and brous cap, then a platelet
strongly associated with atherosclerosis, not all of the
and clotting response over the rupture rapidly develops.
processes of thickening of the intima-media are due to
Additionally, the rupture may result in a shower of deatherosclerosis. Intimal thickening is in fact a complex
bris. Platelet and clot accumulation over the rupture may
process, depending on a variety of factors, not necessarproduce narrowing/closure of the lumen, and tissue damily related to atherosclerosis. Local hemodynamics play
age may occur due to either closure of the lumen resultan important role, higher blood pressure and changes in
ing in loss of blood ow beyond the ruptured atheroma
shear stress being potential causes of intimal thickening.
and/or by occlusion of smaller downstream vessels by deChanges in shear stress and blood pressure may cause a
bris. See vulnerable plaque. This is the principal mechlocal delay in lumen transportation of potentially atheroanism of myocardial infarction, stroke or other related
genic particles, which favors the penetration of particles
cardiovascular disease problems. As research has shown,
into the arterial wall and consequent plaque formation.
this process is not a result of stenosis. Prior to the rupture,
However non-atherosclerotic reactions may also exist, as
there may have been no lumen narrowing, even aneurysin intimal hyperplasia and intimal brocellular hypertromal enlargement, at the atheroma. On average, by clinphy, two dierent compensatory reactions of the arterial
ical research using IVUS, a minor stenosis, about 20%,
wall to changes in shear stress, which also consist in thickis present over those unstable atheroma which rupture
ening of the arterial wall. In some cases, more than one
and result in major disability or death. Comparatively,
of these reactions may be present, and indeed as all of
stenoses of about 75% are required to produce detectable
these are associated to particular ow conditions, they
abnormalities during cardiac stress tests.
are often found in common areas, such as the inow side
of branches, the inner curvature at bends and opposite
the ow divider at bifurcations. However, changes in the
3.2 Artery enlargement
IMT above thresholds of around 900 m almost certainly
If the muscular wall enlargement is overdone over time, are indicative of an atherosclerotic pathology.
then a gross enlargement of the artery results, usually
over decades of living. This is a less common outcome. Atheroma within aneurysmal enlargement (vessel
bulging) can also rupture and shower debris of atheroma
and clot downstream. If the arterial enlargement continues to 2 to 3 times the usual diameter, the walls often become weak enough that with just the stress of the
pulse, a loss of wall integrity may occur leading to sud-

Mechanisms such as these may explain, at least in part,

why the carotid artery seems to be a preferential site
for analyzing the relation between wall thickness and
atherosclerosis. In general, wall thickening may be in
the intimal layer or in the muscular medial layer. As the
carotid artery is an elastic artery, the muscular media is
relatively small. Hence, thickening of the carotid arterial
wall is due essentially to intimal thickening. In muscu-

3
lar arteries wall thickening may imply instead (or also) a
thickening of the medial wall. Whether or not wall thickening in the carotid artery and the femoral artery (or other
muscular arteries) have the same meaning is as yet uncertain. Several studies seem to suggest that the mechanisms
underlying their evolution may at least in part dier, with
consequently possibly dierent clinical implications.

clear that both angioplasty and bypass interventions do

not prevent future heart attack.

Another issue to consider, once the choice to examine the

carotid artery has been dened, is on which segment of
the carotid artery to perform the measurement. Often,
the measurement of the IMT is measured in three tracts:
in the common carotid, at one or two cm from the ow divider, at the bifurcation and in the internal carotid artery.

One way to see atheroma is the very invasive and costly

IVUS ultrasound technology; it gives us the precise volume of the inside intima plus the central media layers of
about 2.5 cm (1 in) of artery length. Unfortunately, it
gives no information about the structural strength of the
artery. Angiography does not visualize atheroma; it only
makes the blood ow within blood vessels visible. Alternative methods that are non or less physically invasive and
less expensive per individual test have been used and are
continuing to be developed, such as those using computed
tomography (CT; led by the electron beam tomography
form, given its greater speed) and magnetic resonance
imaging (MRI). The most promising since the early 1990s
has been EBT, detecting calcication within the atheroma
before most individuals start having clinically recognized
symptoms and debility. Interestingly, statin therapy (to
lower cholesterol) does not slow the speed of calcication as determined by CT scan. MRI coronary vessel
wall imaging, although currently limited to research studies, has demonstrated the ability to detect vessel wall
thickening in asymptomatic high risk individuals.[5] As
a non-invasive, ionising radiation free technique, MRI
based techniques could have future uses in monitoring
disease progression and regression. Most visualization
techniques are used in research, they are not widely available to most patients, have signicant technical limitations, have not been widely accepted and generally are
not covered by medical insurance carriers.

From an academic standpoint, the region to select for

IMT measurement is still an object of study. IMT measurements of the deep wall by ultrasound are generally
more reliable than measurements performed on the outer
wall. This dierence in the accuracy of near and far wall
measurements may be a problem, as some studies have
used both measurements to quantify the IMT.
A practical approach to tracking disease presence and
progression on any given individual is to select and track
those regions with the greatest thickness, i.e. greatest disease burden, as opposed to arbitrarily selecting a particular segment in which the individual may not have much
pathology.

Evolution of strategies
changing focus

and

The sudden nature of the complications of pre-existing

atheroma, vulnerable plaque (non-occlusive or soft
plaque), have led, since the 1950s, to the development of
intensive care units and complex medical and surgical interventions. Angiography and later cardiac stress testing
was begun to either visualize or indirectly detect stenosis.
Next came bypass surgery, to plumb transplanted veins,
sometimes arteries, around the stenoses and more recently angioplasty, now including stents, most recently
drug coated stents, to stretch the stenoses more open.
Yet despite these medical advances, with success in reducing the symptoms of angina and reduced blood ow,
atheroma rupture events remain the major problem and
still sometimes result in sudden disability and death despite even the most rapid, massive and skilled medical and
surgical intervention available anywhere today. According to some clinical trials, bypass surgery and angioplasty
procedures have had at best a minimal eect, if any, on
improving overall survival. Typically mortality of bypass
operations is between 1 and 4%, of angioplasty between
1 and 1.5%.
Additionally, these vascular interventions are often done
only after an individual is symptomatic, often already
partially disabled, as a result of the disease. It is also

The older methods for understanding atheroma, dating

to before World War II, relied on autopsy data. Autopsy data has long shown initiation of fatty streaks in
later childhood with slow asymptomatic progression over
decades.

From human clinical trials, it has become increasingly

evident that a more eective focus of treatment is slowing, stopping and even partially reversing the atheroma
growth process. There are several prospective epidemiologic studies including the Atherosclerosis Risk in Communities (ARIC) Study and the Cardiovascular Health
Study (CHS), which have supported a direct correlation
of CIMT with myocardial infarction and stroke risk in patients without cardiovascular disease history. The ARIC
Study was conducted in 15,792 individuals between 5
and 65 years of age in 4 dierent regions of the USA
between 1987 and 1989. The baseline CIMT was measured and measurements were repeated at 47 year intervals by carotid B mode ultrasonography in this study.
An increase in CIMT was correlated with an increased
risk for CAD. The CHS was initiated in 1988, and the
relationship of CIMT with risk of myocardial infarction
and stroke was investigated in 4,476 subjects 65 years
of age. At the end of approximately 6 years of follow-up,
CIMT measurements were correlated with cardiovascular
events.

4
Paroi artrielle et Risque Cardiovasculaire in Asia
Africa/Middle East and Latin America (PARC-AALA)
is another important large-scale study, in which 79 centers from countries in Asia, Africa, the Middle East, and
Latin America participated, and the distribution of CIMT
according to dierent ethnic groups and its association
with the Framingham cardiovascular score was investigated. Multi-linear regression analysis revealed that an
increased Framingham cardiovascular score was associated with CIMT, and carotid plaque independent of geographic dierences.

6 DIAGNOSIS
els and hypertension are best known and researched.
More recently, some of the complex immune system patterns that promote, or inhibit, the inherent inammatory
macrophage triggering processes involved in atheroma
progression are slowly being better elucidated in animal
models of atherosclerosis.

A 4-minute animation of the atherosclerosis process,

entitled Pathogenesis of Acute MI, commissioned by
Paul M. Ridker at the Harvard Medical School, can
be viewed at pri-med.com . While the animation contains a few technical errors, partly due to the great diCahn et al. prospectively followed-up 152 patients with culty/complexity of making a truly accurate presentation,
coronary artery disease for 611 months by carotid artery it correctly illustrates the principal issues.
ultrasonography and noted 22 vascular events (myocardial infarction, transient ischemic attack, stroke, and
coronary angioplasty) within this time period. They 6 Diagnosis
concluded that carotid atherosclerosis measured by this
non-interventional method has prognostic signicance in
Arterial wall xation, staining and thin section: historcoronary artery patients.
ically this has been the gold standard for detection and
In the Rotterdam Study, Bots et al. followed 7,983 pa- description of atheroma, though only done after autopsy.
tients >55 years of age for a mean period of 4.6 years, and With special stains and examination, micro calcications
reported 194 incident myocardial infarctions within this can be detected, typically with smooth muscle cells of the
period. CIMT was signicantly higher in the myocardial arterial media near the fatty streaks within a year or two
infarction group compared to the other group. Demircan of fatty streaks forming.
et al. found that the CIMT of patients with acute coroCIMT (carotid IMT) as mentioned in the Evolution of
nary syndrome were signicantly increased compared to
Strategies and Changing Focus section, Interventional
patients with stable angina pectoris.
and non-interventional methods to detect atheroscleroIt has been reported in another study that a maximal sis, specically vulnerable plaque (non-occlusive or soft
CIMT value of 0.956 mm had 85.7% sensitivity and plaque), are widely used in research and clinical practice
85.1% specicity to predict angiographic CAD. The today; Carotid Intima-media thickness Scan (CIMT can
study group consisted of patients admitted to the cardi- be measured by B-mode ultrasonography) measurement
ology outpatient clinic with symptoms of stable angina has been recommended by the American Heart Associapectoris. The study showed CIMT was higher in patients tion as the most useful method to identify atherosclerosis
with signicant CAD than in patients with non-critical and may now very well be the gold standard for detection.
coronary lesions. Regression analysis revealed that thickIVUS is the current most sensitive method detecting and
ening of the mean intima-media complex more than 1.0
measuring more advanced atheroma within living indiwas predictive of signicant CAD our patients. There
viduals, though it is typically not used until decades after
was incremental signicant increase in CIMT with the
atheroma begin forming due to cost and body invasivenumber coronary vessel involved. In accordance with
ness.
the literature, it was found that CIMT was signicantly
higher in the presence of CAD. Furthermore, CIMT was CT scans using state of the art higher resolution spiincreased as the number of involved vessels increased and ral, or the higher speed EBT, machines have been the
the highest CIMT values were noted in patients with left most eective method for detecting calcication present
main coronary involvement. However, human clinical tri- in plaque. However, the atheroma have to be adals have been slow to provide clinical & medical evidence, vanced enough to have relatively large areas of calcipartly because the asymptomatic nature of atheromata cation within them to create large enough regions of
make them especially dicult to study. Promising results ~130 Hounseld units which a CT scanners software can
are found using carotid intima-media thickness scanning recognize as distinct from the other surrounding tissues.
(CIMT can be measured by B-mode ultrasonography), B- Typically, such regions start occurring within the heart arvitamins that reduce a protein corrosive, homocysteine teries about 23 decades after atheroma start developing.
and that reduce neck carotid artery plaque volume and Hence the detection of much smaller plaques than previously possible is being developed by some companies,
thickness, and stroke, even in late-stage disease.
such as Image Analysis. The presence of smaller, spotty
Additionally, understanding what drives atheroma deplaques may actually be more dangerous for progressing
velopment is complex with multiple factors involved,
to acute myocardial infarction.[6]
only some of which, such as lipoproteins, more importantly lipoprotein subclass analysis, blood sugar lev- Arterial ultrasound, especially of the carotid arteries, with
measurement of the thickness of the artery wall, oers a

5
way to partially track the disease progression. As of 2006,
the thickness, commonly referred to as IMT for intimalmedial thickness, is not measured clinically though it
has been used by some researchers since the mid-1990s
to track changes in arterial walls. Traditionally, clinical carotid ultrasounds have only estimated the degree
of blood lumen restriction, stenosis, a result of very advanced disease. The National Institute of Health did a
veyear $5 million study, headed by medical researcher
Kenneth Ouriel, to study intravascular ultrasound techniques regarding atherosclerotic plaque.[7] More progressive clinicians have begun using IMT measurement as a
way to quantify and track disease progression or stability
within individual patients.
Angiography, since the 1960s, has been the traditional
way of evaluating for atheroma. However, angiography is
only motion or still images of dye mixed with the blood
with the arterial lumen and never show atheroma; the wall
of arteries, including atheroma with the arterial wall remain invisible. The limited exception to this rule is that
with very advanced atheroma, with extensive calcication within the wall, a halo-like ring of radiodensity can
be seen in most older humans, especially when arterial
lumens are visualized end-on. On cine-oro, cardiologists and radiologists typically look for these calcication shadows to recognize arteries before they inject any
contrast agent during angiograms.

consuming foods containing omega-3 fatty acids

such as sh, sh-derived supplements, as well as
ax seed oil, borage oil, and other non-animal-based
oils;
abdominal fat reduction;
aerobic exercise;
inhibitors of cholesterol synthesis (known as statins);
low normal blood glucose levels (glycosylated
hemoglobin, also called HbA1c);
micronutrient
(vitamins,
magnesium) consumption;

potassium,

and

maintaining normal, or healthy, blood pressure levels;

aspirin supplement

9 Additional images
Illustration comparing a normal blood vessel and
partially blocked vessel due to atherosclerotic plaque
build-up

10 See also

Classication of lesions

Angiogram
Type I: Isolated macrophage foam cells[3][8]
Type II: Multiple foam cell layers

[3][8]

Atherosclerosis

Type III: Preatheroma, intermediate lesion

[3][8]

Type IV: Atheroma

[3][8]

Type V: Fibroatheroma

[3][8]

Atherothrombosis
Coronary circulation
Coronary catheterization

Type VI: Fissured, ulcerated, hemorrhagic, thrombotic lesion[3][8]

EBT

Type VII: Calcic lesion[3][8]

Hemorheologic-Hemodynamic
Atherosclerosis

Type VIII: Fibrotic lesion[3][8]

ApoA-1 Milano

Treatment

Many approaches have been promoted as methods to reduce atheroma progression:

Theory

of

Lipoprotein
LDL, HDL, IDL and VLDL

11 References
[1] http://www.mercksource.com[]

reducing or eliminating consumption of foods that

contain saturated fat and cholesterol;
eating a diet of raw fruits, vegetables, nuts, beans,
berries, and grains;

[2] Lusis AJ (September 2000). Atherosclerosis. Nature

407 (6801): 23341. doi:10.1038/35025203. PMC
2826222. PMID 11001066.
[3] Coronary Artery Atherosclerosis at eMedicine

12 FURTHER READING

[4] Waller BF, Orr CM, Slack JD, Pinkerton CA, Van Tassel J, Peters T (June 1992). Anatomy, histology, and
pathology of coronary arteries: a review relevant to new
interventional and imaging techniquesPart I. Clin Cardiol 15 (6): 4517. doi:10.1002/clc.4960150613. PMID
1617826.
[5] Kim 2002, Circulation
[6] Ehara S, Kobayashi Y, Yoshiyama M, et al. (November 2004). Spotty calcication typies the culprit plaque
in patients with acute myocardial infarction: an intravascular ultrasound study. Circulation 110 (22): 3424
9. doi:10.1161/01.CIR.0000148131.41425.E9. PMID
15557374.
[7] Dr.
Kenneth Ouriel (biography)".
New YorkPresbyterian Hospital. 2009-09-22. Retrieved 2009-0922.
[8] Stary, Herbert C. (2003). Atlas of atherosclerosis: progression and regression. Parthenon Pub. p. 16. ISBN
978-1-84214-153-3.

12

Further reading

Ornish D, Brown SE, Scherwitz LW, et al. (July

1990).
Can lifestyle changes reverse coronary heart disease? The Lifestyle Heart Trial.
Lancet 336 (8708): 12933. doi:10.1016/01406736(90)91656-U. PMID 1973470.
Gould KL, Ornish D, Scherwitz L, et al.
(September 1995).
Changes in myocardial
perfusion abnormalities by positron emission
tomography after long-term, intense risk factor modication. JAMA 274 (11): 894901.
doi:10.1001/jama.1995.03530110056036. PMID
7674504.
Ornish D, Scherwitz LW, Billings JH, et al. (December 1998). Intensive lifestyle changes for reversal of coronary heart disease. JAMA 280 (23):
20017. doi:10.1001/jama.280.23.2001. PMID
9863851.
Ornish D (November 1998). Avoiding revascularization with lifestyle changes: The Multicenter Lifestyle Demonstration Project.
The
American Journal of Cardiology 82 (10B): 72T
76T. doi:10.1016/s0002-9149(98)00744-9. PMID
9860380.
Dod HS, Bhardwaj R, Sajja V, et al. (February
2010).
Eect of intensive lifestyle changes
on endothelial function and on inammatory
markers of atherosclerosis.
The American Journal of Cardiology 105 (3): 3627.
doi:10.1016/j.amjcard.2009.09.038.
PMID
20102949.

Silberman A, Banthia R, Estay IS, et al. (2010).

The eectiveness and ecacy of an intensive cardiac rehabilitation program in 24 sites. American Journal of Health Promotion 24 (4): 2606.
doi:10.4278/ajhp.24.4.arb. PMID 20232608.
Glagov S, Weisenberg E, Zarins CK, Stankunavicius R, Kolettis GJ (May 1987). Compensatory enlargement of human atherosclerotic coronary arteries.
The New England
Journal of Medicine 316 (22):
13715.
doi:10.1056/NEJM198705283162204.
PMID
3574413.
Sparks RA (July 1976). Letter: Fomites in vaginitis. Canadian Medical Association Journal 115 (1):
19. doi:10.1503/cmaj.1050120. PMC 1878585.
PMID 1277053.

13
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Atheroma Source: http://en.wikipedia.org/wiki/Atheroma?oldid=642538150 Contributors: William Avery, Rsabbatini, Finlay McWalter,

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