AJR 2001; 176:235-239
© American Roentgen Ray Society
Endovascular Treatment of Cerebral Aneurysms
An In Vitro Study with Detachable Platinum Coils and Tricellulose Acetate Polymer
Michel Piotin1,2,
Shinya Mandai1,
Kenji Sugiu1,
Philippe Gailloud1 and
Daniel A. Rüfenacht1
1
Department of Radiology, Section of Neuroradiology, Geneva University
Hospital, Switzerland.
2
Present address: 29 Ave. Laumière, 75019
Paris, France.
Received April 14, 2000;
accepted after revision June 15, 2000.
Supported by grants from Fonds National Suisse de la Recherche Scientifique
project 32-42529.94 and from William Cook Europe A/S (Bjaeverskov,
Denmark).
Address correspondence to M. Piotin.
Abstract
OBJECTIVE. The purpose of our experimental study was to determine
the effectiveness of filling the cavity of in vitro aneurysms with detachable
platinum coils and the combination of detachable platinum coils and liquid
embolic agent.
MATERIALS AND METHODS. Silicone aneurysm models were connected to a
circulatory system to simulate arterial flow. A microcatheter was used to
introduce detachable coils into the aneurysm cavities. First, platinum coils
were introduced until the point of minimal dense packing, indicated by
aneurysmal circulatory exclusion. Packing was continued up to maximal dense
packing, indicated by protrusion of the coil into the parent artery.
Volumetric ratios (coil volume-aneurysm volume) were calculated for minimal
and maximal dense packing. Then, after purposeful undercoiling of aneurysm
models, a micropump system was used to fill the aneurysm by stepwise injection
of tricellulose acetate polymer through the coil mesh until angiographic
aneurysm exclusion was completed. The volumetric ratios of maximal packing
with coils and tricellulose acetate polymer in relation to the aneurysm volume
were calculated.
RESULTS. Maximal dense packing ratios with coils (mean, 32.5%;
standard deviation [SD], 3%) were slightly higher than those with the minimal
dense packing (mean, 28.2%; SD, 3%) but were always less than 37%. The ratios
of packing with the combined use of coils and tricellulose acetate polymer
were greater than 100% (mean, 124.4%; SD, 15%).
CONCLUSION. Knowledge of the volumetric ratio of maximal dense
packing was useful for effective filling with coils and tricellulose acetate
polymer. The combined use of coils and liquid polymer appeared more effective
than the use of coils alone for the complete occlusion of the aneurysm
lumen.
Introduction
Detachable coils are now widely used for the treatment of cerebral
aneurysms. When the aneurysm is not tightly occluded, however, the coils have
a propensity to gather together from being pushed and displaced toward the
dome by arterial pulsatile flow. In clinical practice, this situation is seen
more often in large aneurysms with wide necks than in aneurysms with narrow
necks. Dense packing has been proposed to avoid this problem. There is no
definition of "dense packing," and no one knows exactly to what
extent coils or other embolic agents can be placed in an aneurysm cavity. The
aim of this experiment was to perform precise in vitro volumetric measurements
to define dense packing of small aneurysms with platinum coils and with
detachable platinum coils and a liquid polymer.
Materials and Methods
Two different kinds of in vitro silicone side-wall aneurysm models were
made according to the method of Gailloud et al.
[1]. The aneurysm models had a
parent vessel with an internal lumen of 5 mm and a lateral spheric aneurysm
cavity with an internal diameter of either 10 mm for the small type (neck, 3
mm) or 12 mm for the large one (neck, 5 mm). Four small aneurysms (models 1-4)
and four large ones (models 5-8) were made using the same technique. To
measure the volume of each aneurysm precisely, we developed a special
micropump capable of injecting liquid in small amounts with an accuracy to 1.0
nmL. Aneurysm volume measurements were performed with the parent artery
horizontal and the dome of the aneurysm vertical so that the plane of the
orifice of the aneurysm was horizontal. A microcatheter (Tracker-18; Target
Therapeutics, Fremont, CA) was placed into each model so that its tip was at
the level of the orifice of the aneurysm. Then stepwise filling of the sac
with contrast medium was achieved under fluoroscopic control (Integris V 3000
BN; Philips, Best, The Netherlands) until the surface of the fluid was level
with the orifice. This infusion was repeated five times in each aneurysm
model, and we regarded the average of the five measurements as the definitive
aneurysm volume.
Each aneurysm model was then connected to a circulatory system and to a
pump (Drapier type; Collin, Cachan, France), which provided pulsatile flow.
Pressure values delivered by the pump were set to match physiologic
conditions. The circulating fluid, normal saline solution, was kept at
37°C. The Tracker-18 microcatheter was navigated, under fluoroscopic
guidance, to the aneurysm orifice. Dense packing of the aneurysm was then
attempted with mechanically detachable spiral platinum coils (DCS-18; William
Cook Europe, Bjaeverskov, Denmark). Digital subtraction angiography was
performed after each coil had been introduced. We defined minimal dense
packing as the point at which circulation in the aneurysm appeared to have
ceased angiographically. Maximal dense packing was defined as the point at
which the introduction of an additional coil caused a slight protrusion of the
coil into the parent artery. We performed dense packing in four aneurysms, two
small and two large (Fig. 1).
The calculation of the total volume of the coils introduced into each aneurysm
was based on the 0.015-inch diameter of the coil, which corresponds to 1.140
mm3/cm. Then the volumetric ratios of minimal dense packing and
maximal dense packing regarding the actual aneurysm volume were
calculated.
Dense packing of the aneurysms was then attempted with mechanically
detachable spiral platinum coils and tricellulose acetate polymer. Coils were
deposed into the aneurysm to create a mesh but without stopping circulation in
the sac. We purposefully undercoiled the aneurysms so that we could see the
aneurysms fill with contrast material before we instilled the liquid polymer
(Fig. 2A). The occlusion of the
aneurysm was then terminated by filling the aneurysm cavity with tricellulose
acetate polymer (Fig. 2B). The
coil mesh served as a scaffold for liquid polymer deposition. The catheter tip
was positioned in the coil mesh, and a solution of tricellulose acetate
polymer and dimethyl sulfoxide, containing bismuth trioxide powder to gain
radiopacity, was slowly injected by stepwise filling with the micropump
system. Because tricellulose acetate polymer is heavier than saline and blood,
the dome of the aneurysm was orientated downward during injection. The
tricellulose acetate polymer injection was performed over a period of 5-10 min
under fluoroscopic control until total filling of the aneurysm had been
achieved. Then the volumetric ratio of maximal dense packing regarding the
actual aneurysm volume was calculated.
Results
The average volume for the small aneurysms (10-mm diameter), models 1-4,
was 478 mm3 (standard deviation [SD], 24 mm3). The
average volume for the large aneurysms (12-mm diameter), models 5-8, was 854
mm3 (SD, 40 mm3). The volumetric ratio for minimal dense
packing was 28.2% (SD, 3%). The volumetric ratio for maximal dense packing was
32.5% (SD, 3%). Concerning aneurysm packing with coils and tricellulose
acetate polymer (models 3, 4, 7, and 8), the total volume of embolic agent
placed with regard to the total volume of the internal lumen of the aneurysm
was always greater than 100% (mean, 124.4%; SD, 15%) either because of the
protrusion of embolic agent into the vessel lumen (Fig.
3A,3B)
or because of the contraction of the liquid polymer during retraction and
precipitation (Table 1).
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Fig. 3A. —Aneurysm (model 4). Photograph obtained after embolization
with coils and polymer shows coil mesh and polymer cast that fills sac.
Despite high filling ratio of 140.2%, polymer protrusion is minor, consistent
with polymer retraction during precipitation.
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Discussion
Tricellulose acetate polymer solution, a liquid polymer for occlusion of
aneurysms, was developed and has been used in experimental studies and
clinical cases by colleagues in Japan
[2,3,4,5,6].
During embolization, tricellulose acetate polymer matches the lumen of
irregularly shaped aneurysms without increasing intraaneurysmal pressure. The
organic solvent that is used for tricellulose acetate polymer manipulation is
dimethyl sulfoxide. Although the potential angiotoxicity of dimethyl sulfoxide
is still controversial, no toxic effect has been found if used in the minimal
amount that is necessary to keep tricellulose acetate polymer in solution and
to wash the microcatheter hub and lumen before tricellulose acetate polymer
delivery [3,
4,
7]. Bismuth trioxide is a
nontoxic nonsoluble agent that has been used by Debrun et al.
[8]. Although aneurysms might
become totally occluded with tricellulose acetate polymer solution alone, the
purpose of this study was to evaluate in vitro the possibility of the combined
use of platinum coils and liquid polymer (tricellulose acetate polymer) to
occlude saccular aneurysms.
Coil Embolization
The goal of endovascular treatment of cerebral aneurysms is to completely
and permanently exclude the sac from arterial circulation while preserving the
parent vessel. Aneurysm thrombosis followed by endothelialization across the
aneurysm orifice must be achieved. Coils, either tungsten or platinum, have
been used extensively to treat ruptured aneurysms during the acute stage
[9,
10]. Vinuela et al.
[11] reported a 2.2% risk of
rebleeding in 6-36 months in 403 patients with ruptured aneurysms; aneurysms
had been incompletely occluded with Guglielmi detachable coils in these
patients. Although few clinical series concerning early and late
histopathologic findings after endovascular therapy with coils have been
performed in humans
[12,13,14],
animal studies have yielded contradictory results concerning thrombus
formation, presence or lack of persistent thrombus, and healing of the
arterial wall with endothelialization at the site of the neck
[15,16,17].
Thus, aneurysms incompletely occluded with coils have a potential risk to
rebleed after treatment [18].
Coil thrombogenicity has been considered a favorable characteristic for
aneurysm exclusion
[18,19,20];
however, coil thrombogenicity is also a significant risk to endovascular
therapy because it exposes the distal vascular bed to a temporary risk of
thromboembolism [21]. An
aneurysm that has been filled may appear radiographically dense, but we know
from experimental studies that a significant part of the sac becomes occluded
by induced thrombus formation
[22]. The clot has no
permanency in many cases and exposes the initially excluded sac to the
possibility of recanalization and coil compaction
[12]. Graves et al.
[23] reported the results of
coil compaction after aneurysm thrombosis with platinum coils. The coil
compaction caused incomplete aneurysm exclusion even, in some aneurysms, when
initial occlusion had been achieved.
Cellulose Acetate Polymer Embolization
The problem with the use of liquid material for aneurysmal exclusion is
thought to be the leakage of the material into the parent artery during
injection [24,
25]. Cellulose acetate polymer
solution has moderate viscosity and passes through a Tracker-18 microcatheter.
The tricellulose acetate polymer solidifies centripetally in one mass in
approximately 5 min as far as the blood flows in contact with the polymer
[2]. In clinical cases, flow is
controlled by manual compression of the carotid artery for anterior
circulation aneurysms or by occlusion of the proximal parent artery with a
balloon catheter for basilar aneurysms
[3,
4]. The injection speed
influences the pattern in which the tricellulose acetate polymer cast forms.
For instance, if 0.5 mL of tricellulose acetate polymer is injected into
saline over 10 sec, the polymer precipitates and forms a long string pattern.
When the same amount is injected more slowly over a period of 2 min,
tricellulose acetate polymer solidifies immediately after emerging from the
catheter tip and forms a mass without adhering to the catheter.
In their experiments on surgically created lateral wall aneurysms of the
carotid arteries in dogs, Sugiu et al.
[5] found a slow progressive
organization of thrombus around the polymer mass and endothelialization that
bridged the aneurysmal neck. The intraaneurysmal free space around the implant
was filled with fibrous tissue 3-4 weeks after treatment. Although
crescent-shaped aneurysm remnants indicating compaction, regrowth, or both
have often been observed in aneurysms treated with balloons or coils
[23,
26,
27], they were rarely noted in
aneurysms treated with cellulose acetate polymer, and a layer of new
endothelial cells had formed over the orifice and continued smoothly to the
parent arterial wall [5].
Rationale for Embolization with Coils and Tricellulose Acetate
Polymer
Tricellulose acetate polymer can fill a greater volume of the aneurysm than
coils. Although the problem with the use of cellulose acetate polymer for
aneurysm exclusion is the potential hazardous leakage of the material into the
parent artery during injection, the measurement of leakage into the parent
artery was not the primary goal of our study. Because there is always space
between the wall of the parent artery and the microcatheter that is used for
the infusion of polymer, the performance of the balloon-assisted technique
might help prevent this problem, especially in wide-necked aneurysms
[28]. This space is necessary
so that the dimethyl sulfoxide diffuses and the tricellulose acetate polymer
mass forms without increasing intraaneurysmal pressure. Platinum coils do not
occupy the entire volume of an aneurysm sac, and subsequent coil compaction is
the main factor that can hinder complete aneurysm occlusion. Tricellulose
acetate polymer solidifies, matching the lumen of the aneurysm, but there is
still a small amount of space between the tricellulose acetate polymer mass
and the aneurysmal wall. Thus, the goal of the present study was to address
the possible use of the combination of platinum coils and tricellulose acetate
polymer to ensure complete occlusion of the aneurysm sac. Because detachable
coils form a mass that is essentially round, it is easy to create a basketlike
coil mesh in which polymer deposition becomes safer. In the present study, the
total volume of embolic agent placed with regard to the total volume of the
internal lumen of the aneurysm was greater than 100%. Protrusion of the
embolic agent into the vessel lumen of the parent artery was obvious in model
4, which explains why the calculated volumetric ratio was so high. For the
three remaining aneurysms (1 small, 2 large aneurysms), neither protrusion nor
distal migration was noted. The high ratios were consistent with the way
tricellulose acetate polymer solidifies, which results from the contraction of
the liquid polymer during retraction and precipitation after progressive
diffusion of dimethyl sulfoxide into the blood stream. The major advantage of
tricellulose acetate polymer over other liquid embolic agents is that the
catheter does not adhere to the polymer.
Limitations of the Experiment
Although most aneurysms are located at arterial bifurcations and our model
aneurysms were side-wall aneurysms, we believe these aneurysms were
satisfactory for the basic purpose of the experiment; however, these models
did not reflect the conditions that are present in clinical situations. For
instance, the circulating saline fluid was not as viscous as blood and did not
clot like blood. In vivo the endosaccular thrombosis occurs with detachable
coils; therefore, fewer coils are required to achieve minimal dense packing.
Volumetric ratios of in vivo aneurysm packing would therefore be expected to
be lower. In addition, several attempts to position the last coils were used
in some patients to achieve maximal dense packing in this study. More
tentative packing is usually used in clinical settings to avoid aneurysm
perforation, especially in patients with ruptured aneurysms. The volumetric
ratios with maximal dense packing here were, perhaps, not entirely
realistic.
Aneurysm volumes can also be assessed accurately in vitro with different
imaging modalities, including CT and rotational angiography
[29]. Conversely, it is
impossible to measure in vivo the volume of aneurysms precisely, partially
because human aneurysms are irregular and not spheric in shape. The platinum
coil size (0.015-inch; diameter of the spiral, 3-10 mm; length, 6-20 cm) and
type (mechanically detachable) do not correspond to those currently used at
many centers (a 0.010-inch standard or a 0.0085-inch soft Guglielmi detachable
coil [GDC-10]). The use of smaller (2 mm) and softer coils would certainly
have resulted in a better filling of the aneurysm sac, and the subsequent
volumetric ratios would have been higher.
The use of a balloon microcatheter to bridge the aneurysmal neck during
polymer injection would have allowed safer embolization by avoiding
tricellulose acetate polymer protrusion into the parent artery, although this
technique would have permitted flow control into the vessel during polymer
deposition.
Even though the experimental conditions did not exactly reproduce the
clinical setting, our results confirmed the impression that space is left in
the aneurysm sac after placement of a coil in a side-wall aneurysm as
completely as possible. There is very little difference between the volume of
coils required for minimal dense packing as compared with that required for
maximal dense packing. Aneurysm embolization with the use of platinum coils
and tricellulose acetate polymer could be an option in the endovascular
treatment of cerebral aneurysms, but further animal studies to evaluate the
histopathologic response and to assess long-term aneurysm exclusion are
mandatory.
Acknowledgments
We are grateful to A. Jacottet (Ecole Polytechnique
Fédérale de
Lausanne, Switzerland) who was instrumental in the conception and the
construction of the micropump system.
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Abstract
Introduction
