Development of fibrinous thrombus analogue for in-vitro abdominal aortic aneurysm studies.
ABSTRACT To develop different thrombus analogues, with mechanical properties similar to those of human fibrinous thrombus, for in-vitro aneurysm sac pressure studies.
Using dynamic mechanical analysis we determined the E-modulus (/E(*)/) at 0.8, 1.0, 1.5 and 3.9 Hz of ten different human fibrinous thrombus samples. We also determined loss and storage modulus to quantify the visco-elastic properties. For comparison, we measured the E-modulus (|E(*)|), loss and storage modulus of gelatin, Novalyse ST8, ST14 and ST20 with and without contrast agent.
Mean E-modulus of the thrombus samples (SD) at 0.8, 1.0, 1.5 and 3.9 Hz was 39 (16), 37 (15), 37 (15) and 38 (14)kPa, respectively. Median (SD) storage and loss modulus were 35 (12) and 8 (4)kPa, respectively. Median (SD) tandelta was 0.25 (0.06). The E-modulus of gelatin, Novalyse ST8, ST14 and ST20 was 4, 27, 48 and 60 kPa, respectively. The E-modulus of Novalyse ST8, ST14 and ST20 mixed with contrast agent was 18, 23 and 33 kPa, respectively. Median (SD) storage, loss modulus and tan delta of the six Novalyse samples were 30 (15), 3 (1) and 0.087 (0.04), respectively.
All the thrombus analogues, except gelatin, had an E-modulus in the range of human fibrinous thrombi. Novalyse samples are validated thrombus analogues for in-vitro aneurysm sac pressure studies. Gelatin is not appropriate to simulate fibrinous thrombus.
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ABSTRACT: The pulsatile wall motion (PWM) of AAA is reduced after endovascular stent-graft placement. The purpose of this study was to identify whether PWM after endografting was useful in the classification of endoleak. 162 patients treated with EVAR underwent pre- and post-operative PWM assessment with ultrasonography. Follow-up was 1-9 years. 111 patients had well-excluded aneurysms, three patients had enlarging aneurysms without any recognizable endoleak (endotension), 16 had type I, 31 had type II and 1 had type III endoleak. The PWM was reduced from about 1mm pre-operatively to 0.24 mm post-operatively in well-excluded aneurysms. PWM remained stable during follow-up. Type I endoleak was associated with moderately reduced PWM (proximal endoleak 0.79 mm and distal 0.32 mm). PWM in patients with type II endoleak was higher (0.32 mm) post-operatively (p=0.002) compared to well-excluded aneurysms. PWM is permanently reduced after endografting. The smallest reduction in PWM was in patients with type II endoleaks. However, the overlap between the groups does not allow reliable identification of patients having endoleak with PWM-measurements.European Journal of Vascular and Endovascular Surgery 01/2005; 28(6):623-8. · 2.82 Impact Factor
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ABSTRACT: To ascertain the nature of the pressure wave transmitted through aneurysm thrombus and the changes produced after endovascular repair and the development of type I and II endoleaks. A 25 mm Talent endovascular graft was deployed in a latex model of an abdominal aortic aneurysm, which was incorporated in a pulsatile flow unit. The graft was surrounded by thrombus analogue to simulate conditions in vivo. Pressure waveforms in the sac were captured over 5s at 1000 Hz in these settings: (i) no endoleaks (baseline), after introduction of (ii) type I (iii) type II and (iv) combined type I and II endoleaks. The arterial blood pressure settings used were 140/100 and 130/90 mmHg, denoted the high and low settings, respectively. ANOVA in Minitab 13 was applied for statistical analysis. Pulsatile waveforms were transmitted through the thrombus. Intrasac pressure after stent-grafting reduced to 110/107, 99/96 mmHg (p<0.001) (high, low settings, respectively). Introduction of a type I endoleak caused this to rise to 120/112, 115/107 mmHg (p<0.001, vs. baseline); after producing a type II endoleak these were 101/98, 91/88 mmHg (p<0.001, vs. baseline). A combined type I and II endoleak produced intrasac pressures identical to that of a type I endoleak. Intrasac pressure waveforms following EVAR are easily defined following a type I endoleak. Waveforms obtained following type II endoleak simulation resemble the baseline waveform in an attenuated form. Intrasac pressures are, therefore, a reliable marker for type I, but not a type II endoleak. In the case of a combined endoleak, the type I endoleak waveform effectively masks that of the type II. Intrasac thrombus faithfully transmits intrasac pressures.European Journal of Vascular and Endovascular Surgery 10/2004; 28(4):373-8. · 2.82 Impact Factor
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ABSTRACT: To evaluate stent-graft and aneurysm wall motions during the cardiac cycle using cine magnetic resonance imaging (MRI) to identify mechanisms of long-term failure of endovascular aneurysm repair (EVAR). Prior to and after EVAR in 7 patients with abdominal aortic aneurysms (AAA), 12 MRI images per cardiac cycle were acquired in transverse, sagittal, and coronal planes of the aneurysm. Two independent observers blinded to the aim of the study manually traced stent-graft and aneurysm wall contours. Translation was defined as the maximal displacement of the contours in the peak-systolic image compared to the end-diastolic image. Aneurysm wall motions before and after repair were compared. Stent-graft and aneurysm configuration changes during the cardiac cycle were evaluated. The relation between translation and the degree of angulation of the stent-graft was calculated. The anteroposterior translation of the aneurysm decreased from a median 1.05 mm (range <0.5-1.29) before EVAR to within pixel size (<0.5 mm) after EVAR (p=0.04). The cranial-caudal translation of the aneurysm increased from a median 1.01 mm (range <0.5-1.51) before to 1.69 mm (range 1.1-1.99) after EVAR (p=0.02). In 4 stent-grafts, bending during cardiac systole was observed at the site of maximal angulation of the device. In transverse sections, 2-dimensional pulsatile wall motion of the aneurysm was 0.25 cm(2) (range 0.07-0.29) before and 0.17 cm(2) (range 0.07-0.42) after EVAR (p=0.79). No pulsatility of the stent-graft itself was observed. The correlation coefficient between angulation of the stent-graft and the increase in cranial-caudal translation after EVAR was 0.67 (p>0.05). After EVAR, increased longitudinal translation of both the aneurysm and stent-graft was observed, indicating downward pulling forces at the proximal fixation site. Secondly, increased bending was seen at the site of maximal angulation, which implies a risk of metal fatigue and fabric damage at sites of stent-graft angulation.Journal of Endovascular Therapy 06/2003; 10(3):433-9. · 2.70 Impact Factor
Development of fibrinous
thrombus analogue for in-vitro
J. Biomech. 2007; 40(2): 289-296
J.H. van Bockel
Objective: To develop different thrombus analogues, with mechan-
ical properties similar to those of human fibrinous thrombus, for
in-vitro aneurysm sac pressure studies.
the E-modulus (|E∗|) at 0.8Hz, 1.0Hz, 1.5Hz and 3.9Hz of 10
different human fibrinous thrombus samples. We also determined
loss and storage modulus to quantify the visco-elastic properties. For
comparison, we measured the E-modulus (|E∗|), loss and storage
modulus of gelatin, Novalyse ST8, ST14 and ST20 with and without
Using Dynamic Mechanical Analysis we determined
Results: Mean E-modulus of the thrombus samples (SD) at 0.8Hz,
1.0Hz, 1.5Hz and 3.9Hz was 39 (16)kPa, 37 (15)kPa, 37 (15)kPa and
38 (14)kPa, respectively. Median (SD) storage and loss modulus were
35 (12)kPa and 8 (4)kPa, respectively. Median (SD) tanδ was 0,25
(0,06). The E-modulus of gelatin, Novalyse ST8, ST14 and ST20
was 4kPa, 27kPa, 48kPa and 60kPa, respectively. The E-modulus of
Novalyse ST8, ST14 and ST20 mixed with contrast agent was 18kPa,
23kPa and 33kPa, respectively. Median (SD) storage, loss modulus
and tanδ of the 6 Novalyse samples were 30 (15)kPa, 3 (1)kPa and
0.087 (0.04), respectively.
Conclusion: All the thrombus analogues, except gelatin, had an E-
modulus in the range of human fibrinous thrombi. Novalyse samples
are validated thrombus analogues for in-vitro aneurysm sac pressure
studies. Gelatin is not appropriate to simulate fibrinous thrombus.
An abdominal aortic aneurysm (AAA) is a localized widening of the main artery
in the abdomen (aorta). AAAs are found in 4% to 8% of elderly men and 0.5
to 1.5% of elderly women . Abdominal aortic aneurysms are an increasing
healthcare problem considering that the average life time increases. AAAs are
usually asymptomatic, but rupture can occur, which leads to death in more than
80%. Conventionally, AAAs are repaired by interposition of a tube or bifurcated
graft through large abdominal operation with cross clamping of the aorta. Elective
operation carries an operative mortality of 5% .
Endovascular aneurysm repair (EVAR) was introduced as a less invasive alter-
native to conventional aneurysm surgery, since it avoids the surgical exploration of
the abdomen and aortic cross-clamping . During EVAR a stentgraft is placed
inside the AAA through the groin. The aneurysm sac is isolated by the stentgraft
from systemic pressure and blood flow. This method reduces operative mortality
to less than 2% and carries a lower rate of short-term systemic complications and
a shorter hospitalization [2, 4].
The Achilles heel of Endovascular Aneurysm Repair (EVAR) is the occur-
rence of an incomplete seal of the endovascular graft (endoleak) and a persistent
pressurization of the aneurysm sac without blood flow in the sac (endotension)
[5, 6]. Endoleak and endotension can still cause AAA rupture because of increased
aneurysm sac pressure.
Little is known about the biomechanical environment in the aneurysm sac after
EVAR. Aneurysm and stent-graft motions have been visualized to understand the
complex patterns of forces in the aneurysm. Cine MRI after EVAR demonstrated
increased pulsatile cranial-caudal translation of the aneurysm during the heart cy-
cle. Anteroposterior translation of the aneurysm and pulsatile wall motion of the
stent-graft were beneath the detection of cine MRI (<0.5mm) .
Many studies, in-vivo as well as in-vitro, have been undertaken to investigate
aneurysm sac pressure in the presence of endoleaks and endotension. In-vitro
studies give the opportunity to investigate endoleak and endotension in acontrolled
way. Furthermore circulation models are preferable, because these studies are less
expensive, less time-consuming and, unlike for animal and clinical trials, ethical
issues are avoided.
Manufacturing of life-like fusiform non-axisymmetrical AAAmodels has been
published . Validation of biomechanical properties of these aneurysm models
is essential. Computer simulation demonstrated that elevated sac pressure can be
caused by the complex fluid-structure interactions between luminal blood flow,
endovascular graft wall, stagnant sac blood, intraluminal thrombus and aneurysm
The human aortic thrombus can reduce the pressure on the aortic wall . So
thrombus should be incorporated in the aneurysm model to simulate the in-vivo
situation if pressure measurement studies are carried out. The human thrombus,
which is obtained during open aneurysm surgery, can not be fitted exactly into
latex aneurysm models. A thrombus analogue is needed, which is easy to mould
into the aneurysm model and has the same mechanical properties after hardening.
As underlying idea for the present work, we assume that for understanding
the pressure build-up on the aneurysm wall, the thrombus can be considered as
behaving as a solid media as was done in several earlier publications [11, 12]. Fur-
thermore, we will assume that the mechanical properties of thrombus is isotropic
since from scanning electron microscopy (SEM) images it can be observed that no
clear privileged direction exist in the material texture .
The pulsatile wall motion of aneurysms of 6cm is less than 0.5mm after EVAR
[7, 14]. Hence, the deformation of the thrombus remains small so we expect that
its material behavior can be assumed linear. This assumption will be investigated
in the present study.
The Young’s modulus (E-modulus), describing the elastic stiffness and the
damping of the material, is the most important characteristic of the mechanical
property of human fibrinous thrombus because the motion of aneurysm sac throm-
bus is quasi-static (heart rate: 1-2Hz) and therefore the inertia effects are assumed
non-significant. Only the stiffness and maybe the viscosity are relevant in this
circumstance. The aim of this study is (1) to measure the E-modulus, of human
fibrinous thrombus and (2) to develop a thrombus analogue with same E-modulus
4.2.1Theory of experiments
Dynamic Mechanical Analysis is a high precision technique for determination of
mechanical and viscoelastic properties of materials. A Dynamic Mechanical An-
alyzer (DMA) runs automatically dynamic mechanical analysis, by deforming a
sample under action of a pair of equal and opposite forces (F). These forces do
not act along the same line of action (Figure 4.1). Points A and B move to a and
b and points E and F move to e and f, respectively. The shear stress, the ratio
between the external force (F) and the area of the sample (τ = F/A), results in a
change of sample shape. The thickness of the sample (t) is constant, so the shear
stress induces a shear strain. Engineering shear strain, for small deformations, is
defined as the ratio of amplitude (∆x) and thickness (t) of the sample (υ = x/t)
and thus corresponds to the small deformation angle of the sample (Figure 4.1).
The shear elastic modulus, also called the G-modulus is the ratio of shear
stress to shear strain. It expresses the resistance of a material to shearing. The
Figure 4.1: Schematic of a sample under action of a pair of equal and opposite
forces (F). These forces do not act along the same line of action. Points A and B
move to a en b and points E and F move to e and f. ∆x is the amplitude of the
sinusoidal strain (=30 µm). t is the thickness of the sample.
G-modulus is given by:
∆x/t= (F/∆x) · (t/A)
The amplitude (∆x) and frequency are defined by the operator of the DMA. Am-
plitude and frequency are kept constant by the DMA during sample testing. The
dimensions of the samples, the thickness and area, are known. The DMA calcu-
lates the stiffness of the sample (F/∆x) after measuring the external force (F).
The G-modulus of the sample is calculated by multiplying the stiffness with the
ratio between thickness and area (see equation (4.1)).
The E-modulus (|E∗|) is a measure of stiffness of a material that yields infor-
mation about the deformability of the material. Although the E-modulus as well
as the G-modulus is the ratio between stress to strain, the E-modulus is associ-
ated with uniaxial stress and the G-modulus with shear stress. The unit of the