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Intracranial Aneurysms: Midterm
Outcome of Pipeline Embolization
Device—A Prospective Study in
143 Patients with 178 Aneurysms1
Simon Chun-Ho Yu, MD
Ching-Kwong Kwok, FRCS
Pui-Wai Cheng, FRCR
Kwong-Yau Chan, FRCS
Samuel Shun Lau, FRCR
Wai-Man Lui, FRCS
Ka-Ming Leung, FRCS
Raymand Lee, FRCR
Harold Kin-Ming Cheng, FRCS
Yuk-Ling Cheung, FRCR
Chi-Ming Chan, FRCR
George Kwok-Chu Wong, FRCS
Joyce Wai-Yi Hui, FRCR
Yiu-Chung Wong, FRCR
Chong-Boon Tan, FRCR
Wai-Lun Poon, FRCR
Kai-Yuen Pang, FRCS
Alain Kai-Sing Wong, FRCS
Kai-Hung Fung, FRCR
1
 From the Department of Imaging and Interventional
Radiology (S.C.H.Y., J.W.Y.H.) and Division of Neurosurgery,
Department of Surgery (G.K.C.W.), the Chinese University
of Hong Kong, Prince of Wales Hospital, 30-32 Ngan Shing
Street, Room 2A061, 2/F, New Extension Block, Shatin,
New Territories, Hong Kong; Departments of Neurosurgery
(C.K.K., K.Y.C.) and Radiology (S.S.L.), Kwong Wah Hospital,
Hong Kong; Scanning Department, St. Teresa Hospital,
Hong Kong (P.W.C.); Division of Neurosurgery, Department
of Surgery (W.M.L., K.M.L.) and Department of Radiology
(R.L.), Queen Mary Hospital, Hong Kong; Department of
Neurosurgery (H.K.M.C.) and Department of Radiology
and Imaging (Y.L.C., C.M.C.), Queen Elizabeth Hospital,
Hong Kong; Department of Radiology, Tuen Mun Hospital,
Hong Kong (Y.C.W., C.B.T., W.L.P.); and Neurosurgical Unit,
Department of Surgery (K.Y.P., A.K.S.W.) and Department
of Radiology (K.H.F.), Pamela Youde Nethersole Eastern
Hospital, Hong Kong. From the 2011 RSNA Annual Meeting.
Received February 22, 2012; revision requested March 26;
revision received April 20; accepted August 2; final version
accepted August 2. Supported by the Vascular and Inter-
ventional Radiology Foundation. Address correspondence
to S.C.H.Y. (e-mail: simonyu@cuhk.edu.hk).
q
 RSNA, 2012
Radiology: Volume 265: Number 3—December 2012  n  radiology.rsna.org
Original Research  n  Neuroradiology
Purpose: To evaluate the midterm clinical and angiographic outcomes
after pipeline embolization device (PED) placement for
treatment of intracranial aneurysms.
Materials and This prospective nonrandomized multicenter study was
Methods: approved by the review boards of all involved centers; in-
formed consent was obtained. Patients (143 patients, 178
aneurysms) with unruptured saccular or fusiform aneu-
rysms or recurrent aneurysms after previous treatment
were included and observed angiographically for up to 18
months and clinically for up to 3 years. Study endpoints
included complete aneurysm occlusion; neurologic compli-
cations within 30 days and up to 3 years; clinical outcome of
cranial nerve palsy after PED placement; angiographic evi-
dence of occlusion or stenosis of parent artery and that of
occlusion of covered side branches at 6, 12, and 18 months;
and clinical and computed tomographic evidence of perfo-
rator infarction.
Results: There were five (3.5%) cases of periprocedural death or
major stroke (modified Rankin Scale [mRS] . 3) (95% con-
fidence interval [CI]: 1.3%, 8.4%), including two posttreat-
ment delayed ruptures, two intracerebral hemorrhages, and
one thromboembolism. Five (3.5%) patients had minor neu-
rologic complications within 30 days (mRS = 1) (95% CI:
1.3%, 8.4%), including transient ischemic attack (n = 2),
small cerebral infarction (n = 2), and cranial nerve palsy
(n = 1). Beyond 30 days, there was one fatal intracerebral
hemorrhage and one transient ischemic attack. Ten of 13
patients (95% CI: 46%, 93.8%) completely recovered from
symptoms of cranial nerve palsy within a median of 3.5
months. Angiographic results at 18 months revealed a com-
plete aneurysm occlusion rate of 84% (49 of 58; 95% CI:
72.1%, 92.2%), with no cases of parent artery occlusion,
parent artery stenosis (,50%) in three patients, and occlu-
sion of a covered side branch in two cases (posterior com-
municating arteries). Perforator infarction did not occur.
Conclusion: PED placement is a reasonably safe and effective treatment
for intracranial aneurysms. The treatment is promising for
aneurysms of unfavorable morphologic features, such as
wide neck, large size, fusiform morphology, incorporation of
side branches, and posttreatment recanalization, and should
be considered a first choice for treating unruptured aneu-
rysms and recurrent aneurysms after previous treatments.
q
 RSNA, 2012
Supplemental material: http://radiology.rsna.org/lookup
/suppl/doi:10.1148/radiol.12120422/-/DC1
893
NEURORADIOLOGY: Pipeline Embolization Device for Intracranial Aneurysms Yu et al
A
lthough coil placement has been
accepted as a treatment for in-
tracranial aneurysms, unfavor-
able aneurysm features, such as wide
neck, large size, fusiform morphol-
ogy, and posttreatment recanalization,
remain important challenges (1–6).
Stent-assisted coil placement has been
developed to address these challenges
but has been associated with relatively
high rates of aneurysm recurrence and
procedure-induced mortality (4). Such
limitations of coil placement have fu-
eled the continual search for better
endovascular options for treatment of
intracranial aneurysms. Endovascular
placement of flow diversion devices
such as the pipeline embolization de-
vice (PED) (ev3 Neurovascular, Irvine,
Calif) for endoluminal circumferential
reconstruction of segmental vascular
defects as a treatment for intracranial
aneurysms is gaining widespread accep-
tance (7–10). The purpose of this study
was to evaluate the midterm clinical
and angiographic outcomes after PED
placement for intracranial aneurysms.
Materials and Methods
Study Design
This was a prospective multicenter
study conducted in accordance to the
Declaration of Helsinki and Declaration
Advances in Knowledge
nn Neurologic complications were
rare beyond 30 days and did not
occur beyond the 1st year.
nn Approximately three-quarters of
patients with cranial nerve palsy
became asymptomatic after pipe-
line embolization device (PED)
treatment.
nn Delayed rupture after PED treat-
ment did not occur in aneurysms
smaller than 20 mm in size or in
aneurysms treated with coil
placement and 20 mm or larger
in size.
nn The occlusion rate of side
branches covered by using PED
was approximately 1%.
894 radiology.rsna.org  n Radiology: Volume 265: Number 3—December 2012
of Good Clinical Practice and approved
by the review boards of all involved
centers. Signed informed consent was
obtained. Inclusion criteria were as
follows: (a) saccular or fusiform in-
tracranial aneurysms; (b) untreated
unruptured aneurysms or recurrent
aneurysms after previous treatment;
(c) aneurysms of a diameter of 10 mm
or larger, dome-to-neck ratio of 1 or
smaller, neck diameter of 4 mm or
larger, or multiple aneurysms located
within a 1-cm distance; and (d) parent
vessel of a diameter of 2.5–5.0 mm dis-
tal or proximal to the target aneurysm.
Exclusion criteria were as follows: (a)
dissecting aneurysm (n = 14), (b) his-
tory of subarachnoid or intracerebral
hemorrhage within the past 50 days
(n = 13), (c) intracranial arteriovenous
malformation (n = 1), or (d) parent
artery stenosis of 50% or greater at the
site of PED placement (n = 2). Between
September 2008 and September 2011,
178 unruptured or previously treated
aneurysms in 143 patients were treat-
ed in seven hospitals. There were 36
male patients (25.2%) and 107 female
patients (74.8%), with a mean age of
54.9 years 6 11.4 (standard deviation)
(median age, 55 years; age range, 27–
82 years). At the time of data analysis
Implications for Patient Care
nn The use of concomitant endosac-
cular coil treatment at the time
of flow diverter placement to
build up a stable organized
thrombus involving fibrin forma-
tion may be a reasonable treat-
ment strategy to prevent post-
treatment rupture.
nn PED is a reasonably safe and ef-
fective treatment for intracranial
aneurysms; the treatment is
promising for aneurysms of unfa-
vorable morphologic features,
such as wide neck, large size,
fusiform morphology, incorpora-
tion of side branches, and post-
treatment recanalization.
nn PED should be considered a first
choice for treating unruptured
aneurysms and recurrent aneu-
rysms after previous treatments.
in January 2012, the patients had been
observed for an average of 17.6 months
6 10.8 (median, 18.2 months; range,
3–39.2 months).
Study Endpoints
The primary effectiveness endpoint
was angiographic evidence of complete
aneurysm occlusion at 6, 12, and 18
months and recanalization of the aneu-
rysm. Complete occlusion was defined
as complete aneurysm obliteration in-
cluding the neck or class 1 by using
the Montreal scale (6). Recanalization
of aneurysm was defined as imaging
evidence of incomplete aneurysm oblit-
eration after an initial finding of com-
plete obliteration. The primary safety
endpoint was periprocedural death or
major stroke within 30 days. A major
stroke was defined as any stroke that
resulted in severe disability, with mod-
ified Rankin Scale (mRS) score of 4 or
5. The secondary endpoints were as fol-
lows: (a) other complications within 30
days; (b) all neurologic complications
as evaluated with mRS score during a
follow-up period up to 3 years; (c) clini-
cal outcome of cranial nerve palsy after
PED placement up to 3 years; (d) an-
giographic evidence of occlusion or ste-
nosis of a parent artery at 6, 12, and 18
Published online before print
10.1148/radiol.12120422  Content code:
Radiology 2013; 265:893–901
Abbreviations:
CI = confidence interval
DSA = digital subtraction angiography
mRS = modified Rankin Scale
PED = pipeline embolization device
Author contributions:
Guarantors of integrity of entire study, S.C.H.Y., Y.L.C.,
J.W.Y.H., Y.C.W.; study concepts/study design or data
acquisition or data analysis/interpretation, all authors;
manuscript drafting or manuscript revision for important
intellectual content, all authors; manuscript final version
approval, all authors; literature research, S.C.H.Y., S.S.L.,
R.L., H.K.M.C., G.K.C.W., Y.C.W., K.Y.P.; clinical studies,
S.C.H.Y., C.K.K., P.W.C., K.Y.C., S.S.L., W.M.L., K.M.L., R.L.,
H.K.M.C., Y.L.C., C.M.C., G.K.C.W., J.W.Y.H., Y.C.W., C.B.T.,
W.L.P., K.Y.P., K.H.F.; statistical analysis, S.C.H.Y., R.L.,
Y.C.W., C.B.T., K.H.F.; and manuscript editing, S.C.H.Y.,
C.K.K., P.W.C., K.Y.C., W.M.L., Y.L.C., G.K.C.W., Y.C.W., K.Y.P.,
A.K.S.W., K.H.F.
Conflicts of interest are listed at the end of this article.
NEURORADIOLOGY: Pipeline Embolization Device for Intracranial Aneurysms Yu et al
months; (e) angiographic evidence of
occlusion of covered arterial branches
at 6, 12, and 18 months; and (f) clinical
and computed tomographic (CT) evi-
dence of infarction due to occlusion of
perforating arteries covered by the PED
up to 3 years. CT angiography or mag-
netic resonance (MR) angiography was
used alternatively if digital subtraction
angiography (DSA) was refused by the
patient. Angiographic findings were re-
viewed independently and anonymously
by two reviewers. Discrepancy was set-
tled by using consensus.
PED placement was the sole inter-
vention without coils in most cases.
A standard procedure for PED place-
ment was adopted (9). Concomitant
coil treatment of aneurysms at the time
of PED placement was performed for
previously untreated aneurysms 20 mm
or larger in size, after the occurrence
of delayed rupture of aneurysms after
PED placement in two aneurysms 20
mm or larger in diameter early in the
study. Coil treatment was performed
to induce a stable organized thrombus
involving fibrin formation, not for com-
plete coil occlusion of the aneurysm;
therefore, dense packing was not per-
formed. Coil treatment for smaller an-
eurysms (,20 mm) was optional. All
procedures were performed with the
use of general anesthesia through the
right common femoral artery by using a
6-F guiding catheter (Neuron Delivery
Catheter, 6F 053; Penumbra, Alameda,
Calif) and microcatheters (Renegade
HI-Flo, Boston Scientific, Natick, Mass;
Marksman, eV3 Neurovascular). The
operating team in each center consist-
ed of at least one operator with more
than 10 years of experience in endovas-
cular treatment of cerebral aneurysms
(S.C.H.Y., C.K.K., P.W.C., W.M.L.,
H.K.M.C., Y.L.C., C.B.T., K.Y.P., and
K.H.F.). Device diameter was at least
equivalent to that of the proximal par-
ent artery. The target was to place one
device for each patient, unless an ad-
ditional device was necessary for stent
placement across the aneurysmal seg-
ment from normal artery to normal
artery. PED apposition to vessel wall
was assessed with DSA and nonsub-
tracted angiographic images. Good
Radiology: Volume 265: Number 3—December 2012  n  radiology.rsna.org 895
wall apposition was defined as perfect
conformity of PED to vessel wall. The
procedure was considered successful
if the PED was placed at the vascular
segment to completely cover the aneu-
rysm. Patients were treated with daily
oral clopidogrel (75 mg) and aspirin (80
mg) for 3 days before PED treatment
and for 3 months afterward. At least
100 mg of daily oral aspirin was then
given for another 3 months. A screening
test for clopidogrel resistance was not
performed. Heparin was administered
intravenously during the procedure to
maintain an activated clotting time be-
tween 250 and 300 seconds and was
not reversed at the end of procedure.
Statistical Analysis
Subgroup analysis of correlation be-
tween the occurrence of complete oc-
clusion of aneurysm within 6 months
and six potential predictors was per-
formed by using the Pearson x2 test and
the Fisher exact test. The potential pre-
dictors were as follows: (a) previously
treated aneurysm versus untreated an-
eurysm; (b) aneurysm size smaller than
10 mm versus 10 mm or larger; (c)
aneurysm neck less than 4 mm versus
4 mm or greater; (d) aneurysm dome-
to-neck ratio greater than 1 versus 1 or
smaller; (e) location of aneurysm not in
the ophthalmic segment or supraclinoid
segment; and (f) use of more than one
PED versus one PED. Subgroup univar-
iate and multivariate analysis of the six
potential predictors for occurrence of
complete occlusion of aneurysm within
6 months were performed with a bi-
nary logistic regression model. Because
some patients had multiple aneurysms,
the observation of angiographic study
endpoints on individual aneurysms
was not independent in all cases; the
difference in endpoints between single
aneurysms and multiple aneurysms was
analyzed by using the Pearson x2 test,
the Fisher exact test, and univariate
and multivariate analysis by using a bi-
nary logistic regression model. Because
this study involved seven different cen-
ters, the center effect was studied by
analyzing correlation of periprocedural
death and major stroke with particular
centers by using the Fisher exact test.
Software (SPSS, version 20; SPSS, Chi-
cago, Ill) was used. A P value less than
.05 was considered to indicate a signifi-
cant difference.
Results
Patient Characteristics
Among all 143 patients, 116 were
asymptomatic (81.1%; 95% confi-
dence interval [CI]: 73.5%, 87%), 14
had cranial nerve palsy (9.8%; 95%
CI: 5.7%, 16.2%), and 13 presented
with headache (9.1%; 95% CI: 5.1%,
15.4%). Thirty-four of 178 aneurysms
(19.1%; 95% CI: 13.8%, 25.8%) had
been treated previously, with clipping
procedure (n = 1), wrapping procedure
(n = 1), clipping procedure and coil
treatment (n = 2), stent-assisted coil
treatment (n = 7), and coil treatment
(n = 23). The previous treatment was
given for ruptured aneurysm in 26 of 34
cases (76%; 95% CI: 58.4%, 88.6%),
at a median of 1.5 days (range, 0–13
days) after rupture and at a median of
16.1 months (range, 1.7–290 months)
before PED placement. The mRS score
was 0 in 127 patients before PED treat-
ment. In the 14 patients with cranial
nerve palsy, mRS score was 1 (n = 10)
or 2 (n = 4). In the two patients with
residual symptoms due to previous sub-
arachnoid hemorrhage, mRS was 1 (n =
1) or 3 (n = 1).
Aneurysm Characteristics
There were 173 saccular aneurysms
(97.2%; 95% CI: 93.2%, 99%) and five
fusiform aneurysms (2.8%; 95% CI:
1%, 6.8%). Other aneurysm charac-
teristics are shown in Table 1. Average
diameters of the proximal and distal
parent artery measured 3.7 mm 6 0.6
(range, 2.5–5.3 mm) and 3.4 mm 6 0.6
(range, 2.5–4.9 mm), respectively.
Treatment Characteristics
The procedure was successfully accom-
plished in all aneurysms. One PED was
placed in 145 aneurysms (81.5%; 145
of 178; 95% CI: 74.8%, 86.7%), two in
32 aneurysms (18%; 32 of 178; 95% CI:
12.8%, 24.6%), and four in one aneu-
rysm (0.5%; one of 178; 95% CI: 0%,
NEURORADIOLOGY: Pipeline Embolization Device for Intracranial Aneurysms Yu et al

3.6%). Suboptimal vessel wall apposition Table 1

of PED occurred in two cases, one at the
curvature of the carotid siphon, and the Aneurysm Characteristics
other at a preexisting stent (Neuroform; Characteristic No. of Occurrences (n = 178) Percentage*
Boston Scientific) placed for stent-as-
sisted coil treatment. Good wall appo- Aneurysm diameter (mean, 7.0 mm 6 5.5;
sition was achieved in both cases after   median, 5.0 mm; range, 1.9–30 mm)
  ,10 mm 145 81.5 (74.8, 86.7)†
balloon remodeling (Gateway; Boston
  10–25 mm 29 16.3 (11.4, 22.7)†
Scientific). Acute thrombosis of the par-
  .25 mm 4 2.2 (0.7, 6)‡
ent artery occurred in the case of poor
Neck size (mean, 5.3 mm 6 4.0; median, 4.0 mm;
wall apposition at the carotid siphon 15
  range, 1.1–28 mm)
minutes after PED placement. The ves-
  ,4 mm 82 46.1 (38.6, 53.7)
sel was completely recanalized after ab-   4 mm 96 53.9 (46.3, 61.4)
ciximab administration without ischemic Dome-to-neck ratio (mean, 1.4 6 0.9; median, 1.0;
consequence, before the suboptimal wall   range, 0.6–6.7)
apposition was corrected with a balloon.   1 95 53.4 (45.8, 60.8)
Concomitant coil placement at the time   .1 83 46.6 (39.2, 54.2)
of PED placement was performed in nine Aneurysm location
aneurysms that had not been treated   Ophthalmic segment ICA 55 30.9 (24.3, 38.3)
previously, including four aneurysms 20   Supraclinoid ICA 50 28.1 (21.8, 35.4)
mm or larger in size and five aneurysms   Siphon ICA 32 18 (12.8, 24.6)
from 10 mm up to 20 mm (Table 2).   PCA segment of ICA 28 15.7 (10.9, 22.1)
Other treatment characteristics are   Distal ICA 4 2.2 (0.7, 6)
shown in Table 2. Daily oral clopidogrel   Vertebral artery 4 2.2 (0.7, 6)
(75 mg) was given for 3 days before PED   M1 segment of MCA 3 1.7 (0.4 5.3)
treatment and for 3 months afterward   A1 segment of ACA 2 1.1 (0.2, 4.4)
for each patient. The median dose of as- Angiographic evidence of intrasaccular thrombus 7 3.9 (1.7, 8.3)
pirin was 100 mg (range, 80–300 mg).   before treatment
Stenosis of parent artery at the site of aneurysm
The median dose of heparin was 3000
  before treatment
IU (range, 1000–8000 IU). The average
  25% 2 1.1 (0.2, 4.4)
duration of hospital stay for PED place-
  .25% to  50 11 6.2 (3.3, 11.1)
ment was 3.8 days 6 3.2 (median, 3
Previous treatment
days; range, 1–21 days).  Yes 34 19.1 (13.8, 25.8)
 No 144 80.9 (74.2, 86.2)
Primary Endpoints
Among 210 follow-up angiographic ex- Note.—ACA = anterior cerebral artery, ICA = internal carotid artery, MCA = middle cerebral artery, PCA = posterior
communicating artery.
aminations, there were 103 DSA exami-
* Data in parentheses are 95% CIs.
nations (49%; 95% CI: 42.1%, 56%), 64
†
Pretreatment intrasaccular thrombus in three cases.
MR angiographic examinations (30.5%; ‡
Pretreatment intrasaccular thrombus in one case.
95% CI: 24.4%, 37.3%), and 43 CT
angiographic examinations (20.5%;
95% CI: 15.4%, 26.7%). Complete oc-
clusion was found in 78 of 140 aneu- from an aneurysm occurred in cases of The periprocedural death or major
rysms (55.7%; 95% CI: 47.1%, 64%) incomplete aneurysm occlusion, apart stroke rate was 3.5% (five of 143; 95%
at 6 months, 61 of 75 aneurysms (81%; from two cases of delayed rupture after CI: 1.3%, 8.4%) (Table 4). There was
95% CI: 70.3%, 89.1%) at 12 months, PED placement that occurred within one case of ipsilateral ischemic stroke
and 49 of 58 aneurysms (84%; 95% CI: 30 days in large-size aneurysms (20 due to a small left capsular infarct im-
72.1%, 92.2%) at 18 months (Table 3). mm). These two aneurysms were not mediately after PED placement (mRS
In 66 aneurysms with complete occlu- occluded immediately after PED. Sub- = 4). There were two cases of major
sion at 6 months, 33 were followed to group analysis did not identify any fac- hemorrhagic stroke due to a large left
12 months and 28 to 18 months; late tors correlated with early occurrence of parieto-occipital intracerebral hem-
recanalization of an aneurysm did not complete occlusion of aneurysm within orrhage (mRS = 5) and a large cere-
occur in this group. For the five cases of 6 months. No difference in 6-month an- bellar hemorrhage (mRS = 6), which
fusiform aneurysm, complete occlusion eurysm occlusion rate between single occurred in vascular territories inde-
occurred in three cases (60%; 95% CI: aneurysms and multiple aneurysms was pendent from locations of instrumenta-
17%, 92.7%) at 6 months. No bleeding observed (Table E1 [online]). tion or PED placement for aneurysms

896 radiology.rsna.org  n Radiology: Volume 265: Number 3—December 2012

NEURORADIOLOGY: Pipeline Embolization Device for Intracranial Aneurysms Yu et al

in the right carotid siphon and left in- Table 2

ternal carotid artery, respectively. The
former occurred 27 days after PED Treatment Characteristics
placement. The latter occurred on the Treatment Characteristic Datum
day of PED placement after abciximab
administration for acute parent artery Concomitant coil treatment for previously untreated aneurysms
thrombosis. There were two cases of   (median, five coils; range, four to eight coils)
  Aneurysm size 10 mm to , 20 mm 5 of 14 aneurysms
major hemorrhagic stroke (mRS = 5, 6)
  Aneurysm size 20 mm to 25 mm 2 of 7 aneurysms
due to posttreatment delayed rupture
  Aneurysm size . 25 mm 2 of 2 aneurysms
of large aneurysms that were untreated
Aneurysms previously treated with coil placement
previously (22 mm, 25 mm). Delayed
 (,10 mm, n = 21; 10 mm, n = 10)
rupture occurred in two of five (40%;
  Aneurysm size 10 mm to , 20 mm 8 aneurysms
95% CI: 7.3%, 83%) uncoiled aneu-   Aneurysm size 20 mm to 25 mm 0 aneurysms
rysms 20 mm or larger in size and in   Aneurysm size . 25 mm 2 aneurysms
none of six (0%) coiled aneurysms 20 No. of arterial side branches covered by PED per case
mm or larger. These six coiled aneu-   (total 174 branches covered)
rysms included four with concomitant   No branch 22 cases
coil placement performed at the time   One branch 104 cases
of PED placement (Fig 1) and two   Two branches 36 cases
treated previously with coil placement.   Three branches 10 cases
No other aneurysm ruptures occurred.   Four branches 1 case
Periprocedural death or major stroke No. of PEDs covering each arterial side branch (total 174 branches)
occurred in three centers, at a rate of   One PED 148 branches
9% (three of 33), 7% (one of 15), and   (two became occluded)
3% (one of 32), respectively. No corre-   Two PEDs 25 branches
lation with a particular center was ob-   Four PEDs 1 branch
served (P = .64). Arterial side branch covered by PED (total 174 branches)
  Ophthalmic artery 107 cases
Secondary Endpoints   Posterior communicating artery 37 cases
  (two became occluded)
Apart from major stroke or death,
  Anterior choroidal artery 22 cases
there were six other cases of peripro-
  Middle cerebral artery (with perforating arteries) 3 cases
cedural complications occurring in five
  Posterior inferior cerebellar artery 3 cases
patients (3.5%; five of 143; 95% CI:   Anterior cerebral artery 2 cases
1.3%, 8.4%). All were minor, including
two transient ischemic attacks within 1
day after PED placement (mRS = 1), Table 3
one small ipsilateral occipital infarction
immediately after PED placement (mRS Angiographic Outcome
= 1), one small contralateral thalamic Parameter 6 Months 12 Months 18 Months
and corona radiata infarct 1 week after
No. of aneurysm or parent 140 75 58
self-withdrawal from aspirin (mRS = 1),
  artery examined
one cranial nerve palsy that occurred
Incidence (rate) of complete occlusion 78 (55.7) [47.1, 64] 61 (81) [70.3, 89.1] 49 (84) [72.1, 92.2]
after the procedure and subsided after
  of aneurysm*
1 week (mRS = 1), and one retroper-
Recanalization of aneurysm … 0 0
itoneal hematoma related to femoral Incidence of parent artery occlusion 0 0 0
arterial puncture (mRS = 0). Incidence of parent artery stenosis
Beyond 30 days, there were two   50% 2 3 3
neurologic complications (1.4%; two of   .50% 0 0 0
134; 95% CI: 0.2%, 5.5%). One patient No. of arterial side branches examined 140 70 58
died of a recurrent intracerebral hemor- Incidence of side branch occlusion 2 2 2
rhage at the left parieto-occipital lobe 11
months after PED placement. The site of * Data in parentheses are percentages, and data in brackets are 95% CIs.

hemorrhage was unrelated to the treat-

ed aneurysm or PED in the right carotid patient who often stopped taking aspirin neurologic complications occurred in 12
siphon. Repeated transient ischemic (mRS = 1). Neurologic complication did patients after PED treatment (8.4%; 12
attacks within 6 months occurred in a not occur beyond the 1st year. In total, of 143; 95% CI: 4.6%, 14.5%).

Radiology: Volume 265: Number 3—December 2012  n  radiology.rsna.org 897

NEURORADIOLOGY: Pipeline Embolization Device for Intracranial Aneurysms Yu et al

In the 12 patients with neurologic Figure 1

complications (mRS  1) occurring
within 30 days or beyond 30 days af-
ter PED placement, 11 of them had an
mRS score of 0 before PED placement
and one of them had an mRS score of 1
before PED placement because of cra-
nial nerve palsy. One hundred sixteen
patients with an mRS score of 0 before
PED placement had a postprocedural
mRS score that remained 0 throughout
follow-up period. The mRS score had
gradually improved in 10 of 13 patients
with cranial nerve palsy and in two pa-
tients with residual disability due to
previous subarachnoid hemorrhage.
Cranial nerve palsy involving the
third, fourth, or sixth nerve occurred
in 14 patients before the PED proce-
dure. One of them died of a peripro-
cedural complication, 13 patients were
left for follow-up. Aneurysm size was
smaller than 10 mm (n = 6), 10–25 mm
(n = 4), or greater than 25 mm (n =
3). The mRS score before the PED pro-
cedure was 1 (n = 9) and 2 (n = 4).
During the follow-up period, 10 of 13
patients (77%; 95% CI: 46%, 93.8%)
completely recovered from symptoms
of cranial nerve palsy within a median
of 3.5 months (range, 1–8.9 months). Figure 1:  Cranial nerve palsy in a 55-year-old woman. (a) Lateral DSA image shows a large intracranial aneu-
The symptoms remained unchanged in rysm (24-mm diameter) at supraclinoid internal carotid artery. (b) Frontal radiograph shows PED (between arrows)
the other three patients. Among the after placement across the neck of aneurysm after concomitant coil placement at same session. Dense packing
10 patients with cranial nerve function was not performed because the purpose was not to achieve complete coil occlusion of the aneurysm. (c) Lateral
who recovered after PED placement, DSA image subsequently shows partial stasis of contrast media at the dependent part of the aneurysm. (d) Frontal
five had their aneurysms completely oc- DSA image shows complete obliteration of the aneurysm (arrow) 6 months after treatment.
cluded at the time of recovery. Among
the three patients with symptoms of Table 4
cranial nerve palsy that remained un-
Death or Major Stroke Up to 3 Years
changed after PED placement, two of
them had their aneurysms completely .30 Days to
occluded at the time of assessment. Parameter 30 Days 12 Months 13–24 Months 25–36 Months
All parent arteries remained pat- No. of patients observed 143 132 96 45
ent in all 178 aneurysms during the within period
follow-up period. Parent artery ste- No. of deaths 2 (1.4) [0.2, 5.5]* 1 (0.7) [0, 4.8] 0 1†
nosis occurred in two of 140 cases No. of ipsilateral ischemic stroke 1 (0.7) [0, 4.4] 0 0 0
at 6 months (1.4%; 95% CI: 0.3%, No. of ipsilateral subarachnoid 2 (1.4) [0.2, 5.5] 0 0 0
5.6%), to a degree of 20% and 30%, hemorrhage
without clinical consequence. Angio- No. of contralateral 2 (1.4) [0.2, 5.5] 1 (0.7) [0, 4.8] 0 0
graphic follow-up at 12 and 18 months intracerebral hemorrhage
revealed one further case of 40% ste- All stroke 5 (3.5) [1.3, 8.4] 1 (0.7) [0, 4.8] 0 0
nosis. All the stenoses were located Death or stroke 5 (3.5) [1.3, 8.4] 1 (0.7) [0, 4.8] 0 1
at the internal carotid artery, involv- Note.—Data in parentheses are percentages, and data in brackets are 95% CIs.
ing the ophthalmic segment (n = 2) * Due to ipsilateral subarachnoid hemorrhage and contralateral intracerebral hemorrhage.
and the supraclinoid segment (n = 1). †
Due to pulmonary tuberculosis at 27th month.
Occlusion rate of covered arterial side

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NEURORADIOLOGY: Pipeline Embolization Device for Intracranial Aneurysms Yu et al

Figure 2

Figure 2:  Fusiform aneurysm of M1 segment of right middle cerebral artery that was incidentally discovered at CT angiogra-
phy in a 32-year-old woman. (a) Oblique DSA image obtained just before PED placement shows the fusiform aneurysm (arrow),
a small saccular aneurysm next to it, and adjacent perforating arteries. (b, c) After placement of two PEDs (size, 2.5 3 20 mm
and 2.75 3 20 mm), oblique angiograms (b) without subtraction and (c) with subtraction show coverage of the two aneurysms
and perforating arteries by PED (between arrows). (d) Oblique DSA image shows complete obliteration of the two aneurysms
and preservation of the perforating arteries 3 months after treatment.

branches at 6 months was 1.4% (two Discussion placement. Neurologic complications

of 140; 95% CI: 0.3%, 5.6%). Both
occluded branches were posterior
communicating arteries, covered by
one PED. There was no clinical conse-
quence (Table 3). Because of the low
incidence of these angiographic end-
points, difference between single an-
eurysms and multiple aneurysms was
unlikely and not analyzed. In three
patients with perforating arteries
covered by PED at the M1 segment,
which involved two PEDs (n = 1) and
one PED (n = 2), clinical or CT evi-
dence of perforator infarction did not
occur (Fig 2).
In our series of PED treatment for
unruptured intracranial aneurysms or
recurrent aneurysms after a previous
treatment, high rates of complete aneu-
rysm occlusion and preservation of the
parent artery were achieved. Although
complete aneurysm occlusion rate was
high, occlusion occurred at a slow pace,
and the reason for this delayed occlu-
sion rate remains unclear. Periproce-
dural death or major stroke rate was
low and appeared to be further im-
proved with concomitant coil treatment
to prevent delayed rupture after PED
were rare beyond 30 days and did not
occur beyond the 1st year. The major-
ity of patients with cranial nerve palsy
became asymptomatic after PED treat-
ment. Arterial complications such as
parent artery occlusion, parent artery
stenosis, or side branch occlusion were
nonexistent or rare. Perforator infarc-
tion did not occur. These findings sug-
gest that PED therapy represents a via-
ble treatment option for these patients.
For intracranial aneurysms with un-
favorable morphology for coil treatment
and aneurysms with recurrence after
coil treatment, the availability of an

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NEURORADIOLOGY: Pipeline Embolization Device for Intracranial Aneurysms Yu et al
alternative treatment option of reason-
able safety and effectiveness is of sub-
stantial clinical importance. Knowledge
of the complication risks of coil place-
ment with or without balloon or stent
assistance in treatment of unruptured
intracranial aneurysms may provide a
reference on the safety of PED treat-
ment for unruptured aneurysms. In the
Analysis of Treatment by Endovascular
Approach of Nonruptured Aneurysms,
or ATENA, study of 649 patients with
unruptured intracranial aneurysms,
thromboembolic complications and
intraprocedural aneurysm rupture oc-
curred in 9.7% of procedures, and neu-
rologic complications including death
occurred in 5.4% of patients (11). With
the relatively high aneurysm recurrence
rate of 14.9% with endovascular coil
treatment (4), PED is a reasonably
promising alternative treatment.
A review of six prior studies on flow
diverters for unruptured intracranial
aneurysms, including the PED and SILK
flow diverter (Balt Extrusion, Montmo-
rency, France) (7–10,12,13) showed
that procedure success rates in terms of
device placement were high for the two
devices and had always been 100% suc-
cessful for the PED (7,8,10). Complete
aneurysm occlusion rates at 6 months
had been high. Suboptimal apposition
of device to vessel wall and acute or
delayed thrombosis of parent artery
were extremely uncommon or rare.
Stenosis of parent artery at 6 months
and delayed posttreatment aneurysm
were also extremely rare. The results of
these previous studies have suggested
that the safety and treatment effective-
ness of flow diverters are promising.
These findings have been confirmed in
our study. There are certain study pa-
rameters that have been evaluated in
our study but not covered in the pre-
vious studies, including the evaluation
of longer-term clinical outcome up to
3 years and longer-term angiographic
outcome up to 6 months, evaluation of
the effect of PED treatment on aneu-
rysm-related cranial nerve palsy, and
evaluation of the risk of side branch
occlusion due to PED placement. The
results of our study on these study pa-
rameters were all favorable. Our study
900 radiology.rsna.org  n Radiology: Volume 265: Number 3—December 2012
showed a finding different from what
was reported previously. Perforator in-
farction due to compromise of perfora-
tor perfusion had been reported in two
patients within 2 days after double PED
placement at M1 and A1 segments, re-
spectively (9,14), and in three patients
at 4 weeks to 7 months after SILK flow
diverter placement at the basilar artery
(15). Perforator infarction was not ob-
served in our study, and the reason
is unclear; perhaps further studies in
larger scales are required to clarify this
point.
A major concern with flow diverters
is their inability to immediately occlude
the aneurysm with the risk of aneurysm
rupture during the “latency” period
(16). Delayed rupture of large-size an-
eurysms (17–35 mm) after treatment
with flow diverters did occur with un-
known incidence (12,13,17,18). Rup-
ture may occur as early as 2–48 days or
as late as 5 months (13,17). Reported
cases so far involved the use of a SILK
flow diverter (12,13,17,18), but not a
PED (7–10); the current study showed
that aneurysms treated with the PED
are not exempted. Hypotheses for
the mechanisms of rupture included
proximal migration of the flow divert-
er with redirection of the jet inside
the aneurysm sac (12) and aneurysm
wall weakening due to a high content
of proteolytic enzymes formed within
nonorganized red thrombus as a result
of flow stagnation developed within a
short period (18). For large-size aneu-
rysms harboring partial thrombosis,
the approach of endoluminal coil place-
ment had been challenged, and surgical
excision or parent artery occlusion had
been advocated, because these aneu-
rysms are likely extraluminal disorders
involving subacute or chronic dissec-
tions, repeated intramural hematomas,
proliferating vasa vasorum, and trig-
gering of inflammatory mechanisms,
such that subarachnoid hemorrhage
from the aneurysms originates from
the periphery of their walls instead of
the lumen of their sacs or necks (19).
Whether treatment with flow diverters
is reliable for this vasculopathy remains
unknown at the moment. However,
the use of concomitant endosaccular
coil placement at the time of flow di-
verter placement to build up a stable
organized thrombus involving fibrin
formation may be a reasonable treat-
ment strategy to prevent posttreatment
rupture. Adoption of such preventive
measures in the current study had re-
sulted in no further incidence of aneu-
rysm rupture; further observation in a
larger study is warranted to verify such
a proposal.
The study was limited by imperfect
follow-up. Furthermore, the majority
of the aneurysms were located at the
internal carotid artery and were small.
Evolution of aneurysm volume was not
studied. We cannot confidently identify
specific risk factors for given complica-
tions, given the small sample size and
rare nature of these events. Further
studies on the effect of PED treatment
for fusiform aneurysms and the risk of
delayed rupture of large-size aneurysms
after PED treatment are necessary.
In conclusion, our findings suggest-
ed that PED placement is a reasonably
safe and effective treatment for intra-
cranial aneurysms; the treatment is
promising for aneurysms of unfavorable
morphologic features, such as wide
neck, large size, fusiform morphol-
ogy, incorporation of side branches,
and posttreatment recanalization, and
should be considered a first choice for
treating unruptured aneurysms and
recurrent aneurysms after previous
treatments.

Disclosures of Conflicts of Interest: S.C.H.Y.
No relevant conflicts of interest to disclose.
C.K.K. No relevant conflicts of interest to dis-
close. P.W.C. No relevant conflicts of interest
to disclose. K.Y.C. No relevant conflicts of in-
terest to disclose. S.S.L. No relevant conflicts
of interest to disclose. W.M.L. No relevant con-
flicts of interest to disclose. K.M.L. No relevant
conflicts of interest to disclose. R.L. No rele-
vant conflicts of interest to disclose. H.K.M.C.
No relevant conflicts of interest to disclose.
Y.L.C. No relevant conflicts of interest to dis-
close. C.M.C. No relevant conflicts of interest
to disclose. G.K.C.W. No relevant conflicts of
interest to disclose. J.W.Y.H. No relevant con-
flicts of interest to disclose. Y.C.W. No relevant
conflicts of interest to disclose. C.B.T. No rele-
vant conflicts of interest to disclose. W.L.P. No
relevant conflicts of interest to disclose. K.Y.P.
No relevant conflicts of interest to disclose.
A.K.S.W. No relevant conflicts of interest to
disclose. K.H.F. No relevant conflicts of interest
to disclose.
NEURORADIOLOGY: Pipeline Embolization Device for Intracranial Aneurysms Yu et al

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