Assess the total set of mechanical loads and mechanical properties of vessel wall and plaque constituents involved in plaque rupture

Cardiovascular disease (CVD) is the leading cause of death of the aging
population worldwide. Annually 17,5 million people decease because of CVD. CVD
is the term used for high blood pressure, coronary heart disease, heart
failure, stroke and congenital heart diseases. CVD affects all socio-economic
classes and both men and women. The number of deaths due to CVD is expected to
rise in the coming years, notably as more and more children are threatened by
the combined impacts of tobacco, alcohol, obesity and physical inactivity
(World heart federation, 2007). In Europe CVD causes over 1 million deaths each
year, which is nearly half of all deaths in Europe (48%).

Atherosclerosis is a vascular disease, where the arterial wall thickens as the
result of a build up of fatty material, such as cholesterol. The fatty deposits
are called plaques, and if they become too big, the flow of blood is
restricted. A vulnerable plaque is considered to have a large necrotic core, a
thin fibrous cap, the presence of inflammatory cells, intraplaque hemorrhage
and/or neovascularisation (vaso vasorum). It is hypothesized that, when the
stress in the fibrous cap exceeds the strength of the cap, rupture of the cap
can occur (thus likely in vulnerable plaques). If rupture occurs a thrombus
will be formed which for example can travel to the brain and cause a stroke.

The possibility to identify the risk of rupture of a carotid plaque will have
tremendous impact in clinical decision making. Selection of candidates from
surgery is based mainly on duplex ultrasonography, where now only the size of
the stenosis is considered. Symptomatic patients with a 30-69% stenosis, are
currently not operated upon according to the guidelines. Identification of the
risk of plaque rupture could identify patients who have a high risk of
recurrent stroke, and would therefore benefit of carotid intervention, such as
endarterectomy or stent placement. This could potentially prevent a substantial
number of strokes. Furthermore, in all symptomatic patients with a 70-99%
stenosis carotid intervention should be considered, according to the
guidelines. However, only one out of six patients with a 70-99% stenosis
benefits from a carotid intervention . Summarizing, the size of stenosis alone
is not a reliable predictor for plaque rupture. Plaque composition and activity
are thought to be useful predictors of future thromboembolic events as well.

A vulnerable plaque is considered to have a large necrotic core, a thin fibrous
cap, the presence of inflammatory cells, intraplaque hemorrhage and/or
neovascularisation (vasa vasorum). The micro vascular networks are thought to
play a central role in the early process of plaque progression and
vulnerability. Another important hypothesis is that, when the stress in the
fibrous cap exceeds the strength of the cap, rupture of the cap will occur.
Therefore, identification of patients at high risk of stroke (i.e. with
unstable/vulnerable plaques) in an early stage would permit timely intervention
while substantially reducing unnecessary overtreatment of stable plaques.

In order to identify those patients, new methods for plaque rupture prediction
are explored. These new methods use finite element analysis (FEA) of imaged
intact plaques to calculate wall stresses and relate these results with
prediction of rupture in patient-specific geometries. These models seem to
better estimate the risk of rupture than stenosis size alone. Wall stress and
strain calculations with FEA incorporate blood pressure data, stenosis
geometry, wall and plaque composition and thickness.

In this study pre-operative 3D ultrasound will be performed to obtain
patient-specific geometry and deformation. During endarterectomy the plaque
will be dissected very carefully, to obtain an intact plaque (tube like
structure) in order to apply sufficient loads in the ex-vivo experimental set
up. By making use of ultrasound, a pressure radius relation can be obtained
from this experiment, moreover the wall strains can be determined with
dedicated software. After the loading experiment the plaque will be tested
locally by indentation experiments, to determine the material stiffness of the
different plaque components. Finally histology will be performed to determine
the exact components. Data from all these experiments will be used as input for
the plaque rupture prediction model.

The main goal of this study is to assess the total set of mechanical loads and
mechanical properties of the vessel wall and plaque constituents involved in
plaque rupture.

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