815
Ko eJ, e al. J Neu oIn e en Su g 2024;16:815–823. doi:10.1136/jnis-2023-020403
O iginal esea ch
In i o and in silico assessmen o low modula ion
a e deploying he Con ou Neu o ascula Sys em in
in ac anial aneu ysmmodels
Jana Ko e ,1,2 F anziska Gaidzik ,1,2 Naomi La sen ,3 E ik Schü z,2
Timo Damm,4 F i z Woda g ,3 Jan- Be nd Hö ene ,4 Ola Jansen,3
Gábo Janiga ,1,2 Philipp Be g ,2,5 Ma iya S P a di se a 4
Basic science
To ci e: Ko eJ, GaidzikF,
La senN, e al.
J Neu oIn e en Su g
2024;16:815–823.
►Addi ional supplemen al
ma e ial is published online
only. To iew, please isi
he jou nal online (h p:// dx.
doi. o g/ 10. 1136/ jnis- 2023-
020403).
1Labo a o y o Fluid Dynamics
and Technical Flows, Uni e si y
o Magdebu g, Magdebu g,
Ge many
2Resea ch campus STIMULATE,
Uni e si y o Magdebu g,
Magdebu g, Ge many
3Depa men o Radiology and
Neu o adiology, Uni e si y
Medical Cen e Schleswig-
Hols ein (UKSH), Kiel, Ge many
4Sec ion Biomedical Imaging,
Molecula Imaging No h
Compe ence Cen e (MOIN
CC), Depa men o Radiology
and Neu o adiology, Uni e si y
Medical Cen e Schleswig-
Hols ein (UKSH), Kiel Uni e si y,
Kiel, Ge many
5Depa men o Heal hca e
Telema ics and Medical
Enginee ing, Uni e si y o
Magdebu g, Magdebu g,
Ge many
Co espondence o
Jana Ko e; ko e. j@ ou look. com
JK and FG con ibu ed equally.
PB and MSP con ibu ed
equally.
Recei ed 6 Ap il 2023
Accep ed 15 July 2023
Published Online Fi s
18Oc obe 2023
© Au ho (s) (o hei
employe (s)) 2024. Re- use
pe mi ed unde CC BY- NC. No
comme cial e- use. See igh s
and pe missions. Published
by BMJ.
ABSTRACT
Backg ound The no el Con ou Neu o ascula Sys em
(Con ou ) has been epo ed o be e icien and sa e o
he ea men o in ac anial, wide- necked bi u ca ion
aneu ysms. Flow in he aneu ysm and pos e io ce eb al
a e ies (PCAs) a e Con ou deploymen has no been
analyzed in de ail ye . Howe e , his in o ma ion is c ucial
o p edic ing aneu ysm ea men ou comes.
Me hods Time- esol ed h ee- dimensional eloci y
maps in 14 combina ions o pa ien - based basila ip
aneu ysm models wi h and wi hou Con ou de ices
(sizes be ween 5 and 14 mm) we e analyzed using ou -
dimensionsal (4D) low MRI and nume ical/image- based
low simula ions. A complex i ual p ocessing pipeline
was de eloped o mimic he expe imen al shape and
posi ion o he Con ou oge he wi h he simula ions.
Resul s On a e age, he Con ou signi ican ly educed
in a- aneu ysmal low eloci y by 67% (mean w/ =
0.03m/s; mean w/o = 0.12m/s; p- alue=0.002), and
he ime- a e aged wall shea s ess by mo e han
87% (mean w/ = 0.17Pa; mean w/o = 1.35Pa; p-
alue=0.002), as obse ed by nume ical simula ions.
Fu he mo e, a signi ican educ ion in low (P<0.01) was
con i med by he neck in low a e, kine ic ene gy, and
in low concen a ion index a e Con ou deploymen .
No ably, de ice size has a s onge e ec on educing
low han de ice posi ioning. Howe e , posi ioning
a ec ed low in he PCAs, while being obus in
e ec i ely educing low.
Conclusions This s udy showed he high e icacy o
he Con ou de ice in educing low wi hin aneu ysms
ega dless o he exac posi ion. Howe e , we obse ed
an e ec on he low in PCAs, which needs o be
in es iga ed u he .
INTRODUCTION
In ac anial aneu ysms (IAs) ca y he isk o
up u e and need o be iden i ied and ea ed i his
isk is high.1–3 Neu o ascula hemodynamics play
a i al ole in IA o ma ion and up u e.4 Indeed,
coil emboliza ion has become an es ablished ech-
nique o endo ascula ea men o IA.5 Howe e ,
emboliza ion o wide- necked bi u ca ion aneu-
ysms (WNBAs) wi h coils is mo e challenging as i
equi es assis ing de ices such as s en s o balloons
and esul s in ela i ely low occlusion (40%) and
high complica ion (21%) a es.6 In asaccula low
dis up o s such as he Wo en EndoB idge (WEB;
Mic o en ion/Te umo, Aliso Viejo, CA) we e
designed as single implan s o simpli y endo ascula
WNBA ea men .
Recen ly, a new in asaccula de ice, called
Con ou Neu o ascula Sys em (Con ou , Ce us
Endo ascula , F emon , CA), was de eloped.
Ini ial s udies showed he e icacy and sa e y
o ea ing un up u ed IAs wi h his de ice,
including WNBAs.7–11 Mo eo e , Con ou has
been used o ea acu ely up u ed aneu ysms
bo h as a s and- alone de ice and in combina ion
wi h coils.12–15 A sys ema ic e iew based on
WHAT IS ALREADY KNOWN ON THIS TOPIC
⇒Flow modula ion is an e ec i e ea men
o wide- necked aneu ysms. The Con ou
Neu o ascula Sys em (Con ou ) is a no el, hal -
sphe e- shaped, low- modula ing de ice ha
is placed in he aneu ysm neck and comes in
di e en sizes.
WHAT THIS STUDY ADDS
⇒In a- aneu ysmal low modula ion and he
e ec o di e en de ice sizes and posi ions
we e quan i ied o he i s ime.
⇒Fou - dimensional low MRI and compu a ional
luid dynamics we e used o ob ain ime-
esol ed, h ee- dimensional maps o he low
inside pa ien - de i ed aneu ysm models wi h
and wi hou he Con ou de ice.
⇒The Con ou de ice induced conside able low
educ ion o all sizes and deploymen s.
HOW THIS STUDY MIGHT AFFECT RESEARCH,
PRACTICE OR POLICY
⇒The low educ ion caused by he Con ou
de ice was cons an and abo e 60%, ega dless
o he exac posi ioning o he de ice wi hin
a 5° angle, possibly a e ing he need o
epea ed de ice eposi ioning. Howe e , he
Con ou posi ioning in luences he low di ision
in o he pos e io ce eb al a e ies (PCAs),
which equi es u he in es iga ion. Mo eo e ,
he e ec o s onge Con ou disposi ioning
(highe ha 5°) on aneu ysm and PCA low is
unknown.
Zei sch i enab eilung. P o ec ed by copy igh . on Sep embe 9, 2024 a Uni e si a sbiblio hekh p://jnis.bmj.com/J Neu oIn e en Su g: i s published as 10.1136/jnis-2023-020403 on 18 Oc obe 2023. Downloaded om
816 Ko eJ, e al. J Neu oIn e en Su g 2024;16:815–823. doi:10.1136/jnis-2023-020403
Basic science
six s udies,7–9 11 14 15 including 131 IAs ea ed wi h ei he
Con ou o Con ou and coils, showed a pooled adequa e
occlusion a e o 84%.16
Expe ience wi h he Con ou de ice is limi ed. Mos o he
a o emen ioned s udies had a e ospec i e design, including
angiog aphic (X- ay- based) and clinical neu ological ollow- up.
Only one s udy discussed MRI ollow- ups, epo ing s ong
me al a i ac s o igina ing om he implan .8
The p ima y pu pose o he Con ou is o dis up and di e
he low om an IA. Howe e , o he bes o he au ho s’
knowledge, he di ec low changes caused by he Con ou ha e
no been e alua ed ye . In a p e ious expe imen al s udy, he
washou ime o an angiog aphic con as agen obse ed wi h
digi al sub ac ion angiog aphy (DSA) was used as a su oga e
ma ke o he e ec i eness o he de ice.17 Howe e , he anal-
ysis was limi ed o a wo- dimensional (2D) e alua ion o he
low and migh be ope a o dependen .
The e o e, his s udy aimed o quan i y he in a- aneu ysmal
changes in low, induced by placing he Con ou in IA models, which
we e based on pa ien da a, using ime- dependen , high- dimensional
compu a ional luid dynamic (CFD) simula ions. Fu he mo e, ou -
dimensional (4D) low MRI expe imen s we e conduc ed o assess
he easibili y o e alua ing IA hemodynamics wi h in i o modali y
in he p esence o he Con ou de ice.
MATERIALS AND METHODS
In his s udy, a complex p ocessing pipeline was de eloped, s a ing
wi h ou pa ien - based basila ip aneu ysm models. The p ocessing
pipeline, comp ising he expe imen al me hod and he in- silico low
assessmen , is shown in igu e 1. De ails will be explained wi hin he
ollowing subsec ions.
Pa ien -based aneu ysm models
The ou pa ien - based basila ip aneu ysm models A1–4
( igu e 1A), we e designed and h ee- dimensionally (3D)
p in ed in- house17 18 ( o de ails see online supplemen al ile
S1 and able S1). The diame e s (heigh , neck, dome) o he
IA sac we e 3.5×2.7×3.2 mm (A1), 6.9×2.8×3.3 mm (A2),
8.4×6.7×8.4 mm (A3), and 16.4×9.2×10.2 mm (A4), espec-
i ely ( igu e 1A). IA models we e designed as WNBAs wi h a
compa able dome- o- neck a io (1.2±0.1). All models sha ed
he same pa en essel and pos e io ce eb al a e ies. The
models eady o 3D p in ing a e eely a ailable a Zenodo.19
The i ual model used o CFD simula ions is sligh ly
di e en om he one used o 4D low MRI measu emen s.
Namely, supe io ce eb al a e ies (SCA) we e ini ially modelled
o expe imen s, bu due o hei small size hey we e pa ially
occluded du ing he 3D p in ing p ocess. Thus, o p ese e he
compa abili y be ween 4D low MRI and CFD he SCAs we e
emo ed om he i ual models used o CFD analysis. The
exclusion o he b anches does no a ec he change o he
hemodynamics in he IAs by placemen o he Con ou sys em
analyzed in his s udy (see online supplemen al able S2, online
supplemen al igu e S1).
Expe imen al me hods
Flow se up and in i o de ice deploymen
IA models we e in eg a ed in o a closed cycle low se up and
supplied wi h saline solu ion a a mean low a e o 150 mL/min
o mimic low in he basila a e y obse ed in i o (Isma ec
MCP S anda d, Cole Pa me , IL).20 Time- dependen low and
p essu e wa e o ms we e measu ed a he inle and ou le s (see
online supplemen al igu es S2/S3) and only p essu e a he ip
o he IA sac using low and p essu e senso s (ME8PXL- M12,
T ansonic Sys em Inc, NY; PRESS- N- 000; PendoTech, NJ),
espec i ely ( igu e 2B).
Ten Con ou s (C1–10) o h ee sizes—5 mm (C1–5), 11 mm
(C6–9), and 14 mm (C10)—we e deployed in o IAs (A1–4)
unde luo oscopy (Allu a Xpe FD, Philips, The Ne he lands)
by an expe ienced neu o adiologis (>10 yea s o expe ience,
FW) (deploymen : A1: C1–2; A2: C3–5; A3: C6–9; A4: C10;
o de ails see online supplemen al ile S2).
Figu e 1 P ocessing pipeline used o mimic he expe imen s by nume ical CFD simula ions. On he expe imen al side, pa ien - based IA models
(A)and he co esponding low se up (B)we e used o acqui e µCT and 4D low MRI da a (C).Flow and p essu e senso s p o ided he bounda y
condi ions o CFD. Fo placing he Con ou in he i ual aneu ysm model, i s , he CAD- model o he Con ou was de o med acco ding o µCT
images (D).Nex , he posi ion o he Con ou inside he model was de e mined om µCT da a and he de o med Con ou acco dingly placed
(E).Finally, CFD simula ions we e ca ied ou and compa ed wi h 4D low MRI indings (F). CAD, Compu e Aided Design; CFD, compu a ional luid
dynamic; 4D, ou - dimensional; IA, in ac anial aneu ysm; μCT, mic o- CT; w/o, wi hou .
Zei sch i enab eilung. P o ec ed by copy igh . on Sep embe 9, 2024 a Uni e si a sbiblio hekh p://jnis.bmj.com/J Neu oIn e en Su g: i s published as 10.1136/jnis-2023-020403 on 18 Oc obe 2023. Downloaded om
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Basic science
Figu e 2 Quali a i e and quan i a i e compa ison o 4D low MRI and CFD eloci y ields. Fo each aneu ysm size, one ep esen a i e case is
shown. (A)Veloci y s eamlines be o e Con ou deploymen o A1–A4. (B)His og am plo s be o e Con ou deploymen o he 4D low MRI and CFD
eloci y alues a e in e pola ing hem on he same g id. Median alues a e displayed wi h a dashed e ical line. (C)The eloci y magni ude in
he co onal plane is displayed on he le ( op ow: wi hou Con ou , bo om ow: wi h Con ou ) o bo h modali ies. Resul s wi hou Con ou show
high co espondence be ween 4D low MRI and CFD. Me al a i ac s caused signal oids in he model wi h Con ou and pa ly no eloci ies could be
ob ained in 4D low MRI o hese cases (black a ows), despi e o IA sac o A4 C10 (g een dashed ci cle). The highly- esol ed CFD da a can p o ide
a de ailed iew o he low in he aneu ysm wi h Con ou . P essu e alues a he aneu ysm ip (senso da a and CFD) a e displayed on he igh . CFD,
compu a ional luid dynamic; 4D, ou - dimensional.
Zei sch i enab eilung. P o ec ed by copy igh . on Sep embe 9, 2024 a Uni e si a sbiblio hekh p://jnis.bmj.com/J Neu oIn e en Su g: i s published as 10.1136/jnis-2023-020403 on 18 Oc obe 2023. Downloaded om
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4D low MRI
4D low MRI da a we e acqui ed by using a 3T whole- body
MR sys em equipped wi h a 32- channel head coil (Ingenia CX,
R5 V6.1, Philips Heal hca e, Bes , The Ne he lands). Veloci-
ies we e quan i ied wi h a ime- esol ed phase- con as MR
sequence wi h 3D co e age (4D low MRI, igu e 1C). Tempo al
and spa ial esolu ion was 63 ms and (0.75 mm)3, espec i ely.
The eloci y- encoding pa ame e was se o 75 cm/s o all IA
models, abou 10% highe han he maximum eloci y obse ed
a he inle essel wi hou Con ou . Linea o se phase co ec-
ion, eloci y aliasing, and essel masking we e pe o med using
GT low (V3.1.12, Gy o ools, Swi ze land) ( o de ails see online
supplemen al ile S3).
In silico low assessmen
To accu a ely mimic he exac shape and posi ion o he Con ou
by using CFD, he Con ou was digi alized and i ually deployed
( igu e 1) as desc ibed in de ail below.
Con ou digi aliza ion
To de elop a digi al Con ou eady- o- be- placed in he IA
model ( igu e 1D), i s , mic o- CT (μCT) was acqui ed om all
Con ou s inside he IA models (a i aCT 80; Scanco Medical AG,
B ü isellen, Swi ze land; 45 keV, 80 mm ield o iew, econ-
s uc ed o 26 µm iso opic oxel size). He e, a scala mask based
on signal in ensi y was c ea ed using a h eshold- based, seeded,
egion- g owing algo i hm.21 Nex , he mesh was gene a ed
based on he scala mask using a ma ching cubes algo i hm.22
Second, a 3D compu e - aided Con ou design (CAD- Con ou )
was c ea ed based on 2D ep esen a ions o he uncons ained
de ice p o ided by he manu ac u e (Fusion 360 2.0, Au odesk
Inc, USA). Speci ically, he CAD- Con ou consis ed o 72 ci cles
equally spaced om each o he connec ed a he base o he
de ice, adjacen o he adiopaque ma ke . In his way, an uncon-
s ained model o he Con ou was ob ained, which changed
a e deploymen (see igu e 1D).
Thus, and hi d, o accu a ely ob ain he shape o he μCT-
Con ou , he CAD- Con ou was non- igidly ans o med o
he μCT da a, by alignmen o he adiopaque ma ke s. Then,
he CAD- Con ou was adap ed o he shape o he μCT-
Con ou using a la ice modi ie (Blende , Blende Founda ion,
3.1., Ams e dam, The Ne he lands). The modi ie smoo hly
de o med he CAD- Con ou acco ding o he shape o he
μCT- Con ou . Hence, a cons ained con igu a ion o he CAD-
Con ou was achie ed, which was used o he highly esol ed
CFD simula ions.
The di ec use o Con ou segmen ed om µCT images was
no easible due o he limi ed spa ial esolu ion o he μCT
which esul ed in segmen a ion a e ac s such as subs an ially
inc eased wi e hickness o he Con ou and he p esence o ully
occluded Con ou segmen s (see online supplemen al ile S4,
online supplemen al able S3, online supplemen al igu e S4).
Vi ual de ice deploymen
The i ual IA models and he cons ained CAD- Con ou s we e
loca ed in di e en coo dina e sys ems. To ensu e ha he CAD-
Con ou s we e co ec ly posi ioned wi hin he IA sac, i s , he
3D- p in ed wall o he aneu ysm model was segmen ed om he
same μCT images as he μCT- Con ou ( igu e 1E). The μCT- wall
was aligned wi h he CAD- wall using an i e a i e, closes - poin
algo i hm (MeshLab 2022.02, ISTI - CNR, Pisa, I aly). Second,
he esul ing ans o ma ion ma ix was applied o he CAD-
Con ou . As CAD- wall and CAD- aneu ysm lie in an iden ical
coo dina e sys em, his single ans o ma ion ensu ed ha he
Con ou was co ec ly placed wi hin he CAD- aneu ysm.
CFD simula ions
Nume ical CFD simula ions we e ca ied ou using a ini e olume
sol e (S a CCM+2021.3 16.6, Siemens, E langen, Ge many).
Bounda y condi ions ob ained in he expe imen s ( igu e 1C) we e
applied a he ex uded inle and ou le s (measu ed mass low and
p essu e wa e o ms) o he IA models. Fu he mo e, igid essel
walls and he mimicking luid p ope ies we e used (wa e : densi y
= 998 kg/m³, dynamic iscosi y = 0.001 Pa·s).
Spa ial disc e iza ion o he IA and CAD- Con ou models was
pe o med wi h a base cell size o 0.1 mm a he aneu ysm sac
and pa en essel, while 0.02 mm was chosen a he Con ou
s u s and 0.3 mm a he essel ex usions. The o al cell coun
wi hin he IA models wi h Con ou anged om 8.8 million (A1)
o 11.6 million cells (A4). The models wi hou Con ou ea u ed
a o al cell coun o 2.4 o 4 million cells.
In o al, 14 ime- dependen CFD simula ions we e ca ied ou
( ou wi hou : A1–4; 10 wi h Con ou : A1 C1–2, A2 C3–5, A3
C6–9, A4 C10). Tempo al esolu ion was 1 ms o e h ee ca diac
cycles, whe eas only he las cycle was analyzed. Cycle leng h o
1.26 s was de e mined om he expe imen .
Da a analysis
The expe imen al 4D low MRI esul s we e compa ed wi h
he calcula ed CFD eloci y by in e pola ing he eloci y ields
om 4D low MRI and CFD inside he un ea ed IA sac on o
a g id wi h he base size o 0.3 mm. Nex , he changes in he
in a- aneu ysmal low a e placing he Con ou we e e alua ed.
Namely, oscilla o y shea index (OSI), oscilla o y eloci y index
(OVI), neck in low a e (NIR), ime- a e aged wall shea s ess
(TAWSS), eloci y (V), kine ic ene gy (KE), in low concen a ion
index (ICI), and aneu ysm u no e ime (TOT), which is he
aneu ysm sac olume di ided by he NIR, we e e alua ed (see
online supplemen al ile S5). Fo each pa ame e (P) wi h (w/)
and wi hou (w/o) Con ou , he ea men e ec (TE) was calcu-
la ed o C1–10, espec i ely.
TE
p=
Mean P
w/
−Mean P
w/o
Mean Pw/o
(1)
The ou le low o le and igh pos e io ce eb al a e ies
(PCAs) was no malized by he o al ou low. S a is ical analysis
was pe o med in MATLAB (MATLAB R2022a, The Ma h-
Wo ks, Na ick, MA), using he pai ed Wilcoxon es . Wi h he
Bon e oni co ec ion he P alue was se o 0.007. The chosen
in low plane o calcula ing NIR is shown in igu e 1F.
RESULTS
Flow compa ison be ween 4D low MRI and CFD
Wi hou Con ou
The eloci y ields calcula ed in he IA geome ies wi hou
Con ou we e simila o hose measu ed wi h 4D low MRI
( igu e 2A, s eamline and eloci y magni ude images). Fo A4,
he low je en e ing he aneu ysm sac was obse ed in bo h
modali ies. In CFD, he je appea s o be b oade and sligh ly
shi ed o he igh side o he IA’s wall. In A3, he simula ed low
je was clea ly isible and he 4D low MRI did no dis inc ly
show he low a ached o he wall. Howe e , he o e all low
ield emained simila be ween 4D low MRI and CFD. Fo he
smalle models (A1 and A2), he highly esol ed CFD simula-
ions showed ine eloci y s uc u es, which we e no isible
on he 4D low MRI eloci y maps. Gene ally, 4D low MRI
esul s su e ed om limi ed spa ial esolu ion, especially o
Zei sch i enab eilung. P o ec ed by copy igh . on Sep embe 9, 2024 a Uni e si a sbiblio hekh p://jnis.bmj.com/J Neu oIn e en Su g: i s published as 10.1136/jnis-2023-020403 on 18 Oc obe 2023. Downloaded om
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small aneu ysms (A1 and A2), and a eloci y noise ha is compa-
able o he eloci ies obse ed a he cen e o he aneu ysm
and along he walls. Quan i a i ely, as shown in he his og am
plo s in igu e 2B, wo smalle sized IAs (A1 and A2) had a
highe ela i e equency o low eloci y alues measu ed wi h
4D low MRI (median 0.056 m/s o A1 and 0.023 m/s o A2)
when compa ed wi h CFD (median 0.11 m/s o A1 and 0.047
m/s o A2). Fo A3 he median alues o bo h modali ies we e
simila (median 0.179 m/s o 4D low MRI and 0.163 m/s o
CFD), whe eas o A4, he measu ed alues we e sligh ly highe
(median 0.115 m/s o 4D low MRI and 0.09 m/s o CFD).
Wi h Con ou
S ong MRI a i ac s o igina ing om he adiopaque ma ke o he
Con ou ( igu e 2C, black a ows) we e obse ed on 4D low MRI
images. All 4D low MRI da a ob ained in he icini y o s ong a i-
ac s mus be analyzed ca e ully, as he a i ac s a ec he phase- based
low encoding. Fu he mo e, he s ong low educ ion inside he IA
leads o nea - ze o eloci ies in he IA sac, which a e close o he 4D
low MRI eloci y noise limi . All o his p e en s he use o 4D low
MRI o assess pos - ea men IA hemodynamics, especially o small
IAs. As a esul , he analysis o eloci y ields measu ed wi h MRI close
o he Con ou is impossible and limi ed only o he a i ac - ee a ea.
Figu e 3 Vi ual ascula model wi h and wi hou Con ou (A, D),oscilla o y shea index (B, E, OSI), and oscilla o y eloci y index (C, F, OVI). No e
he a ia ion in posi ion and o ien a ion o he de ice. G een a ows highligh he highe OSI in he egions close o he Con ou loca ions.
Zei sch i enab eilung. P o ec ed by copy igh . on Sep embe 9, 2024 a Uni e si a sbiblio hekh p://jnis.bmj.com/J Neu oIn e en Su g: i s published as 10.1136/jnis-2023-020403 on 18 Oc obe 2023. Downloaded om

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Fo case A4 C10, low di ision on he le and igh PCAs e ealed
highe low h ough he le PCA wi h bo h modali ies ( igu e 2C,
co onal plane, g een ci cle). This is o e ing he pe spec i e
ha measu ing low by 4D low MRI close o he implan is no
comple ely impossible. O e all, he s ong low educ ion induced
by he Con ou was de ec ed by CFD and 4D low MRI.
Rema kably, he p essu e cu es acqui ed om CFD and
senso measu emen s showed excellen ag eemen h oughou
he whole ca diac cycle o all cases (mean de ia ion o 6%
wi hou and 8% wi h Con ou ).
In a-aneu ysmal de ice e icacy
The majo i y o he de ices we e loca ed cen ally in he pa en
essel ( igu e 3A/D). A2 C5 and A4 C10 we e sligh ly shi ed
owa ds he igh and A3 C7 o he le PCA bi u ca ion.
Compa ed wi h a e ical middle line h ough he aneu ysm
model, he implan ed de ices we e shi ed by an angle be ween
1° and 5°. Conce ning he low pa ame e s OSI ( igu e 3B and E)
and OVI ( igu e 3C and F), he in a- aneu ysmal educ ion a e
deploymen was isible o C1–4 and o C6–9. Conce ning
C5 and C10, OSI and OVI we e inc eased, espec i ely. Fo all
cases wi h Con ou s, excep C5 and C10, OSI and OVI we e
highe , especially a ound he loca ion o he Con ou (see g een
a ows), and lowe wi hin he aneu ysm dome compa ed wi h
hose wi hou Con ou .
E ec o de ice size
A g ea e educ ion in NIR, TAWSS, V, KE, and ICI was ound
a e deploying a smalle - sized (83–99%, de ice size 5 mm, A1/
A2 C1–5) han a la ge - sized Con ou (48–95%, de ice size
11 mm, A3 C6–9), as ep esen ed in igu e 4A. Fo A3 (C6–9)
a high educ ion o 86–95% is isible only o KE, and o C10
one o 87–100% o TAWSS, V, and KE. S ill, an o e all educ-
ion o mo e han 40% is isible o C1–10 o hese pa ame-
e s, excep o ICI wi hin C10. The educ ion in OSI and OVI
was s able a mo e han 58% o A3 (C6–9). In con as , his
Figu e 4 Quan i ica ion o low educ ion o he Con ou . (A) T ea men e ec o chosen hemodynamic pa ame e s in %. (B)No malized mean
ou le low di ision wi h low da a de i ed om senso measu emen s in % and he ea men e ec on o he ou le low di ision o he le and
igh PCAs. ICI, in low concen a ion index; IR, neck in low a e (mL/s); KE, kine ic ene gy (Pa); OSI, oscilla o y shea index; OVI, oscilla o y eloci y
index; PCA, pos e io ce eb al a e y; TAWSS, ime- a e aged wall shea s ess (Pa); V, eloci y (m/s); w/, wi h Con ou ; w/o, wi hou Con ou .
Zei sch i enab eilung. P o ec ed by copy igh . on Sep embe 9, 2024 a Uni e si a sbiblio hekh p://jnis.bmj.com/J Neu oIn e en Su g: i s published as 10.1136/jnis-2023-020403 on 18 Oc obe 2023. Downloaded om
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educ ion was lowe in A1/A2/A4 han in all cases o A3 excep
C9 o OVI/OSI e en inc eased.
E ec o he aneu ysm heigh
The heigh o he aneu ysm sac A2 was almos wo imes la ge
han A1 (6.9 mm s 3.5 mm), while he size o he neck and
dome was compa able. The e o e, he same Con ou size was
implan ed. Rema kably, no speci ic di e ence in he ea men
e ec a ibu ed o he di e en aneu ysm heigh s was ound.
E ec o he de ice posi ioning
Fou de ices (C6–9) we e placed in A3. He e, low educ ion
anged wi hin a di e ence o Δ 8.63% (KE) and Δ 13.53% (NIR)
o Δ 20.06% (OVI). De ailed TE alues can be ound in online
supplemen al able S4.
Signi icance
Mean NIR, TAWSS, V, KE, ICI, and TOT we e signi ican ly
highe (P<0.01) o cases wi hou Con ou , while OVI (P=0.16)
and OSI (P=0.11) did no di e signi ican ly be ween g oups
(see able 1 and online supplemen al igu e S5).
Flow changes in he pos e io ce eb al a e ies
The le ou low a ied be ween 44% and 52% and he igh
be ween 47% and 56% ( igu e 4B). The TE on he ou low was
low a 0.1–5.7%; only in C5 was he e ec s onge (TE=10%).
C5 was also mos shi ed o he le PCA (see igu e 3). C6/C7 as
compa ed wi h C8/C9 had a smalle e ec on he low al e a ion
and he Con ou was placed highe inside he aneu ysm so ha
he PCAs we e less a ec ed.
DISCUSSION
Endo ascula ea men o WNBAs wi h Con ou is a no el
echnique ha has no been s udied well ye , bu he ea men
esul s in high IA occlusion a es and sa e y.11 14 16 In his s udy,
he in a- aneu ysmal low educ ion as well as low al e a ions
in he PCAs, ha we e a ec ed by he Con ou , we e analyzed.
Aneu ysm models ep esen ing di e en shapes and sizes,
oge he wi h he e ec o di e en Con ou deploymen s in he
same geome y, we e in es iga ed. In con as o exis ing mini-
mally in asi e echniques, Con ou can ea IAs wi h complex
shapes ega dless o aneu ysm heigh and does no equi e pos -
in e en ional an ipla ele he apy.7 8
Compa ison o 4D low MRI and CFD
Due o s ong me al a i ac s wi hin 4D low MRI da a caused
by Con ou , i is ad an ageous o use CFD o analyzing he
e ec o Con ou deploymen ( igu es 2 and 3). Being he i s -
e e nume ical s udy analyzing low al e a ions by Con ou , i
was necessa y o compa e he CFD esul s quali a i ely wi h
measu ed 4D low MRI eloci y ields in he me al a i ac s- ee
egions and quan i a i ely wi h measu ed p essu e senso da a
and 4D low MRI da a be o e Con ou deploymen ( igu e 2).
Veloci y- encoded s eamlines and his og am plo s showed he
highes di e ences be ween bo h modali ies in he smalle IAs
(A1 and A2). This is a ibu ed o he ela i ely highe in luence
o measu emen noise, 3D- p in ing inhomogenei ies o egis a-
ion e o s ha in luence he acqui ed alues. Fu he mo e, he
SCAs, which we e pa ly p esen in he 3D p in ed models bu
emo ed om he i ual CFD model, migh cause a de ia ion.
Howe e , o he la ge IA models (A3 and A4) he eloci y ields
a e mo e simila and he main cha ac e is ics ( low je o median
alues) a e nea ly in acco dance. The indings a e in ag eemen
wi h Sindee e al, who showed he compa ibili y o MRI and
CFD wi hin IAs.23
In a-aneu ysmal low
The subsequen in- dep h analysis e ealed a s ong low
educ ion in all cases o NIR, ICI, and TAWSS and he in a-
aneu ysmal low (KE and V). Acco ding o Oua ed e al,24 o
low di e e s en (FDS) deploymen , a educ ion in eloci y
g ea e han 35% can be conside ed as a success ul occlusion o
an aneu ysm. In he p esen s udy, eloci y educ ion was highe
han 60% o all cases and hus indica es a po en ially e ec i e
occlusion, con i ming he indings o ecen in i o s udies.11 14 16
Aneu ysm occlusion is also ensu ed by he use o a WEB.25 26
Howe e , he sizing o he de ice depends on he aneu ysm
wid h and heigh , whe e heigh is usually limi ed o 10 mm. The
Con ou is cha ac e ized by i s heigh - independen implemen a-
ion as i is placed di ec ly a he neck,15 and aneu ysm heigh did
no a ec he e icacy o he Con ou .
Compa ing he TE be ween Con ou and FDS, he la e shows
a lowe educ ion in NIR (ΔNIR >29%), TAWSS (ΔTAWSS
>23%), and V (ΔV >20%) wi hin he aneu ysm.27 Kulcsá e al
epo ed ha TAWSS and V educ ion cause IA occlusion, bu
hey could no de e mine a p edic i e h eshold alue.28 FDS
deploymen ca ies he isk o occluding small la e al b anches
and FDS a e di icul o use in bi u ca ion aneu ysms,29 which
does no apply o he Con ou .11 Ne e heless, he Coun ou is
no well sui ed o small- neck aneu ysms in con as o in- essel
de ices such as FDS.8
Compa ed wi h in asaccula coiling, he Con ou showed
a simila ly e ec i e low educ ion. S ill, his educ ion a e
coiling is no signi ican ly ela ed o aneu ysm occlusion.30
Coiling ca ies he ad an age o conse ing pa en essel low,
bu implemen a ion is mo e complex and no sui able o
WNBAs wi hou he use o addi ional s en s o balloons.10
In con as o he NIR, TAWSS, and V educ ions, Con ou
deploymen en iches he oscilla o y e ec s inside he aneu ysm
in some cases ( igu e 4A and able 1). This inding is in line
wi h a p e ious s udy in which OVI inc eased inside he IA a e
implan ing an FDS.31 Rolo e al31 ound ha FDS malposi-
ioning inc eases OSI, bu has no majo e ec on low educ ion.
This leads o he assump ion ha adequa e posi ioning o he
Con ou could ensu e a dec ease in OSI/OVI ( igu es 3 and 4,
able 1). Mo eo e , high OSI co ela ed wi h ecanaliza ion a e
coil emboliza ion.32
Table 1 Compa ison o hemodynamic mean esul s be ween wi h
(w/) and wi hou (w/o) Con ou including SD and P alue
Mean w/ ±SD w/ Mean w/o ±SD w/ P alue
NIR* (mL/s) 0.53 ±0.62 1.46 ±1.28 0.002
TAWSS* (Pa) 0.17 ±0.17 1.35 ±0.73 0.002
V* (m/s) 0.03 ±0.03 0.12 ±0.05 0.002
KE* (J) 1.06 ±1.29 16.03 ±11.9 0.002
ICI* 0.64 ±0.84 1.43 ±1.23 0.002
OVI 0.04 ±0.04 0.06 ±0.01 0.16
OSI 0.05 ±0.04 0.08 ±0.02 0.105
TOT* (s) 3.46 ±3.9 0.28 ±0.15 0.002
Signi ican di e ences a e ma ked wi h an as e isk*.
ICI, in low concen a ion index; KE, kine ic ene gy; NIR, neck in low a e; OSI,
oscilla o y shea index; OVI, oscilla o y eloci y index; TAWSS, ime- a e aged wall
shea s ess; TOT, aneu ysm u no e ime ; V, eloci y.
Zei sch i enab eilung. P o ec ed by copy igh . on Sep embe 9, 2024 a Uni e si a sbiblio hekh p://jnis.bmj.com/J Neu oIn e en Su g: i s published as 10.1136/jnis-2023-020403 on 18 Oc obe 2023. Downloaded om
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The calcula ed aneu ysm TOT ( able 1) is a measu e o low
s asis and has been s udied as a po en ial ma ke o h ombus
o ma ion, and subsequen ly IA occlusion.33–36 The mean TOT in
all models we e signi ican ly highe a e Con ou deploymen ,
hus con i ming he posi i e ea men e ec o he Con ou and
inc easing he chance o h ombus o ma ion. These esul s a e
in acco dance wi h he washou ime calcula ions obse ed wi h
DSA in he same aneu ysm models.17
Ou le low al e a ion
Fu he mo e, due o i s shape, acco ding o ou indings, he
Con ou dis u bs ou le essel low by al e ing low di ision in o
he PCAs, depending on he posi ioning ( igu e 4B). S ill, he
in a- aneu ysmal low educ ion emained independen om he
de ice posi ioning. Thus, an angula shi o 5° a ec s low al e -
a ion h ough he PCAs bu no in a- aneu ysmal low educ ion.
Howe e , i emains unce ain i his esul can be eplica ed in
i o. Likely, he deploymen o he Con ou would no al e
he low demand in he dis al ascula beds, esul ing in simila
ou low bounda y condi ions. As a esul , minimal changes
in low di ision among he PCAs can be expec ed ollowing
Con ou deploymen . The e o e, hese indings equi e u he
in es iga ion. In compa ison, pa en essel low is conse ed by
deploying WEB and coiling as no pa o he de ice is placed
ou side he IA.25 37
Limi a ions
This s udy has se e al limi a ions. Fi s , 4D low MRI migh be
a ec ed by insu icien spa ial esolu ion,38 especially wi hin
small IAs. Mo eo e , MR images we e impai ed by me al a i-
ac s, mos ly due o he adiopaque ma ke . The me al a i ac s
caused by Con ou seem o be d as ically s onge han o
FDS.39 Thus, compa ison o he CFD simula ions o 4D low was
mainly limi ed o he cases wi hou Con ou and o he p essu e
senso measu emen s.
Second, while e o s we e made o ealis ically mimic he
Con ou placemen , mino misalignmen s we e obse ed.
S ill, i was he bes app oach a ailable since di ec use o µCT
segmen ed Con ou s was no possible due o segmen a ion a i-
ac s (online supplemen al ile S4). Ne e heless, his is he i s
s udy o i ually mimic Con ou placemen ealis ically, enabling
nume ical analysis o ele an hemodynamic pa ame e s.
Thi d, he inpu low wa e o ms o CFD we e no pa ien -
speci ic bu mimicked he shape o a ca diac cycle and mean low
a e epo ed in a basila a e y in i o (see online supplemen al
igu es S2 and S3).
Fou h, o compa e hemodynamic pa ame e s be ween he
cu en nume ical s udy and a p e ious expe imen al s udy17
(speci ically TOT s washou ime (WOT)), a saline solu-
ion was u ilized o bo h expe imen s and CFD simula ions.
The iscosi y o saline di e s om ha o blood, po en ially
hinde ing a di ec compa ison o he esul s in his s udy o in
i o IA hemodynamics. Howe e , addi ional simula ions did no
e eal a subs an ial impac o iscosi y on he ea men e ec o
he Con ou analyzed in his s udy (online supplemen al igu e
S6).
Fi h, only IAs o he basila a e y we e conside ed in his
s udy, and all models had iden ical pa en essel and pos e io
ce eb al a e ies. This limi s he gene alizabili y o he ob ained
esul s. In addi ion, SCAs we e emo ed om he i ual IA
model due o small essel diame e s and essel occlusion a e
3D p in ing. This p e en ed he analysis o low h ough SCAs.
Ne e heless, he exclusion o he b anches did no a ec he
ea men e ec o he Con ou in he IA (see online supple-
men al able S2, online supplemen al igu e S1).
Six h, due o he complex wo k low and esou ce- in ensi e
na u e o he s udy, only 10 cases we e ini ially conside ed.
To enhance he obus ness o he indings, a la ge sample size
should be included in u u e in es iga ions.
Las , his s udy aises impo an clinical ques ions ha canno
be ully add essed wi hin he scope o a single s udy. These
include he impac o Con ou placemen on low in he PCA,
he obus ness o he Con ou e iciency om de ice posi-
ioning, namely he e ec o mo e p onounced (>5°) de ice
angula ion, and he p edic ion o IA occlusion s a us based on
he low educ ion. Add essing hese ques ions will be he ocus
o u u e esea ch.
CONCLUSIONS
In his s udy, he e ec i eness o Con ou was shown and, o he
i s ime, low was analyzed in de ail, quan i a i ely add essing
IA low educ ion. Con ou educed in a- aneu ysmal eloci y
and TAWSS o all cases. O e all compa ison be ween wi h and
wi hou Con ou showed a signi ican educ ion in he chosen
hemodynamic pa ame e s. De ice size has a g ea e e ec on
educing low han does posi ioning. Howe e , posi ioning in lu-
ences he low di ision in o he PCAs, which equi es u he
in es iga ion.
Co ec ion no ice Since his pape i s published, he symbol * has been added
o he ca ego y TOT in able 1.
X Naomi La sen @naomila sen6 and Ma iya S P a di se a @MP a di se a
Acknowledgemen s We acknowledge Philips Heal hca e o suppo in 4D
low MRI expe imen s. We hank Ce us Endo ascula o p o iding he Con ou
Neu o ascula Sys em o in i o es ing. We acknowledge suppo by Kiel Uni e si y
and he Medical Facul y o suppo ing he Molecula Imaging No h Compe ence
Cen e (MOIN CC) as co e acili y o imaging in i o.
Con ibu o s Concep ualiza ion and design: JK, FG, MSP, NL, PB. Implan a ion
o he Con ou s and choice o he aneu ysm models: MSP and FW. Acquisi ion o
MRI da a and cons uc ion o he 3D p in ed models: MSP. Acquisi ion o mCT da a:
TD. De elopmen o he i ual p e- p ocessing pipeline: JK, FG, ES. Conduc ion o
CFD simula ions: JK, FG. Da a analysis and in e p e a ion: NL, JK, FG, MP, PB. Da a
isualiza ion: JK, FG. S a is ical analysis: JK. Supe ision and unding acquisi ion: PB,
NL, FW, JBH, OJ. W i ing – o iginal d a p epa a ion: JK, FG, MSP. W i ing – e iew
and edi ing: JK, FG, MSP, NL, TD, FW, JSH, OJ, PB, GJ. Gua an o : JK. All au ho s ha e
ead and ag eed o he published e sion o he manusc ip . JK and FG con ibu ed
equally o his pape and sha e i s au ho ship. MP and PB con ibu ed equally o
his pape and sha e las au ho ship.
Funding This wo k was suppo ed by he Ge man Resea ch Founda ion (GRK2154:
P2b, SPP2311: p ojec no. 465189657), he Ge man Fede al Minis y o Educa ion
and Resea ch wi hin he Resea ch Campus STIMULATE (g an no. 13GW0473A),
and he B uhn Founda ion. MOIN CC was ounded by a g an om he Eu opean
Regional De elopmen Fund (ERDF) and he Zukun sp og amm Wi scha o
Schleswig- Hols ein (p ojec no. 122- 09- 053).
Compe ing in e es s The au ho (s) decla ed he ollowing po en ial con lic s o
in e es wi h espec o he esea ch, o his a icle: MSP has ecei ed a esea ch
g an om Ce us endo ascula ; FW has ecei ed ees o consul ing and speaking
om Bal In e na ional SAS and Ce us Endo ascula .
Pa ien consen o publica ion No applicable.
E hics app o al No applicable.
P o enance and pee e iew No commissioned; ex e nally pee e iewed.
Da a a ailabili y s a emen MRI, CFD, low and p essu e senso da a a e
a ailable upon easonable eques . Digi al aneu ysm models eady o 3D p in ing
a e a ailable o download a he Zenodo esea ch eposi o y [doi: 10.5281/
zenodo.4723100].
Supplemen al ma e ial This con en has been supplied by he au ho (s). I
has no been e ed by BMJ Publishing G oup Limi ed (BMJ) and may no ha e
been pee - e iewed. Any opinions o ecommenda ions discussed a e solely hose
o he au ho (s) and a e no endo sed by BMJ. BMJ disclaims all liabili y and
esponsibili y a ising om any eliance placed on he con en . Whe e he con en
Zei sch i enab eilung. P o ec ed by copy igh . on Sep embe 9, 2024 a Uni e si a sbiblio hekh p://jnis.bmj.com/J Neu oIn e en Su g: i s published as 10.1136/jnis-2023-020403 on 18 Oc obe 2023. Downloaded om
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Basic science
includes any ansla ed ma e ial, BMJ does no wa an he accu acy and eliabili y
o he ansla ions (including bu no limi ed o local egula ions, clinical guidelines,
e minology, d ug names and d ug dosages), and is no esponsible o any e o
and/o omissions a ising om ansla ion and adap a ion o o he wise.
Open access This is an open access a icle dis ibu ed in acco dance wi h he
C ea i e Commons A ibu ion Non Comme cial (CC BY- NC 4.0) license, which
pe mi s o he s o dis ibu e, emix, adap , build upon his wo k non- comme cially,
and license hei de i a i e wo ks on di e en e ms, p o ided he o iginal wo k is
p ope ly ci ed, app op ia e c edi is gi en, any changes made indica ed, and he use
is non- comme cial. See:h p://c ea i ecommons.o g/licenses/by-nc/4.0/.
ORCID iDs
JanaKo e h p://o cid.o g/0000-0002-0434-712X
F anziskaGaidzik h p://o cid.o g/0000-0003-1924-821X
NaomiLa sen h p://o cid.o g/0000-0002-8782-8278
F i zWoda g h p://o cid.o g/0000-0003-1413-2699
Gábo Janiga h p://o cid.o g/0000-0002-4560-9640
PhilippBe g h p://o cid.o g/0000-0003-4140-6771
Ma iya SP a di se a h p://o cid.o g/0000-0001-9442-088X
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Zei sch i enab eilung. P o ec ed by copy igh . on Sep embe 9, 2024 a Uni e si a sbiblio hekh p://jnis.bmj.com/J Neu oIn e en Su g: i s published as 10.1136/jnis-2023-020403 on 18 Oc obe 2023. Downloaded om