Accurately assessing the complex tissue mechanics of cerebral aneurysms (CAs) is critical for elucidating how CAs grow and whether that growth will lead to rupture. The factors that have been implicated in CA progression – blood flow dynamics, immune infiltration, and extracellular matrix remodeling – all occur heterogeneously throughout the CA. Thus, it stands to reason that the mechanical properties of CAs are also spatially heterogeneous. Here, we present a new method for characterizing the mechanical heterogeneity of human CAs using generalized anisotropic inverse mechanics, which uses biaxial stretching experiments and inverse analyses to determine the local Kelvin moduli and principal alignments within the tissue. Using this approach, we find that there is significant mechanical heterogeneity within a single acquired human CA. These results were confirmed using second harmonic generation imaging of the CA’s fiber architecture and a correlation was observed. This approach provides a single-step method for determining the complex heterogeneous mechanics of CAs, which has important implications for future identification of metrics that can improve accuracy in prediction risk of rupture.

1.
Etminan
N
,
Buchholz
BA
,
Dreier
R
,
Bruckner
P
,
Torner
JC
,
Steiger
HJ
,
Cerebral aneurysms: formation, progression, and developmental chronology
.
Transl Stroke Res
.
2014
;
5
(
2
):
167
. .
2.
Caranci
F
,
Briganti
F
,
Cirillo
L
,
Leonardi
M
,
Muto
M
.
Epidemiology and genetics of intracranial aneurysms
.
Eur J Radiol
.
2013
;
82
(
10
):
1598
. .
3.
Zhao
J
,
Lin
H
,
Summers
R
,
Yang
M
,
Cousins
BG
,
Tsui
J
.
Current treatment strategies for intracranial aneurysms: an overview
.
Angiology
.
2018
;
69
(
1
):
17
. .
4.
Williams
LN
,
Brown
RD
.
Management of unruptured intracranial aneurysms
.
Neurol Clin Pract
.
2013
;
3
(
2
):
99
. .
5.
Cebral
JR
,
Castro
MA
,
Burgess
JE
,
Pergolizzi
RS
,
Sheridan
MJ
,
Putman
CM
.
Characterization of cerebral aneurysms for assessing risk of rupture by using patient-specific computational hemodynamics models
.
AJNR Am J Neuroradiol
.
2005
;
26
(
10
):
2550
9
.
6.
Boscolo
E
,
Pavesi
G
,
Zampieri
P
,
Conconi
M
,
Calore
C
,
Scienza
R
,
Endothelial cells from human cerebral aneurysm and arteriovenous malformation release ET-1 in response to vessel rupture
.
Int J Mol Med
.
2006
;
18
(
5
):
813
9
.
7.
Malek
AM
,
Izumo
S
.
Mechanism of endothelial cell shape change and cytoskeletal remodeling in response to fluid shear stress
.
J Cell Sci
.
1995
;
109
(
Pt 4
):
713
26
.
8.
Tóth
BK
,
Raffai
G
,
Bojtàr
I
.
Analysis of the mechanical parameters of human brain aneurysm
.
Acta Bioeng Biomech
.
2005
;
7
(
1
).
9.
Valencia
A
,
Contente
A
,
Ignat
M
,
Mura
J
,
Bravo
E
,
Rivera
R
,
Mechanical test of human cerebral aneurysm specimens obtained from surgical clipping
.
J Mech Med Biol
.
2015
;
15
(
05
):
1550075
.
10.
Cebral
JR
,
Duan
X
,
Chung
BJ
,
Putman
C
,
Aziz
K
,
Robertson
AM
.
Wall mechanical properties and hemodynamics of unruptured intracranial aneurysms
.
AJNR Am J Neuroradiol
.
2015
;
36
(
9
):
1695
. .
11.
Seshaiyer
P
,
Hsu
FPK
,
Shah
AD
,
Kyriacou
SK
,
Humphrey
JD
.
Multiaxial mechanical behavior of human saccular aneurysms
.
Comput Methods Biomech Biomed Eng
.
2001
;
4
(
3
):
281
9
.
12.
Martufi
G
,
Forneris
A
,
Nobakht
S
,
Rinker
KD
,
Moore
RD
,
di Martino
ES
.
Case Study: intra-patient heterogeneity of aneurysmal tissue properties
.
Front Cardiovasc Med
.
2018
;
5
:
82
. .
13.
Raghupathy
R
,
Barocas
VH
.
Generalized anisotropic inverse mechanics for soft tissues
.
J Biomech Eng
.
2010
;
132
(
8
):
081006
. .
14.
Raghupathy
R
,
Witzenburg
C
,
Lake
SP
,
Sander
EA
,
Barocas
VH
.
Identification of regional mechanical anisotropy in soft tissue analogs
.
J Biomech Eng
.
2011
;
133
(
9
):
091011
. .
15.
Witzenburg
C
,
Raghupathy
R
,
Kren
SM
,
Taylor
DA
,
Barocas
VH
.
Mechanical changes in the rat right ventricle with decellularization
.
J Biomech
.
2012
;
45
(
5
):
842
. .
16.
Raghupathy
R
,
Barocas
VH
.
Form from function: generalized anisotropic inverse mechanics for soft tissues
.
J Biomech Eng
.
2011
;
8
.
17.
Newman
ME
.
Analysis of weighted networks
.
Phys Rev E Stat Nonlin Soft Matter Phys
.
2004
;
70
(
5
):
056131
. .
18.
Witzenburg
CM
,
Dhume
RY
,
Lake
SP
,
Barocas
VH
.
Automatic segmentation of mechanically inhomogeneous tissues based on deformation gradient jump
.
IEEE Trans Med Imaging
.
2016
;
35
(
1
):
29
. .
19.
Feinberg
AW
,
Alford
PW
,
Jin
H
,
Ripplinger
CM
,
Werdich
AA
,
Sheehy
SP
,
Controlling the contractile strength of engineered cardiac muscle by hierarchal tissue architecture
.
Biomaterials
.
2012
;
33
(
23
):
5732
. .
20.
Hasan
D
,
Chalouhi
N
,
Jabbour
P
,
Hashimoto
T
.
Macrophage imbalance (M1 vs. M2) and upregulation of mast cells in wall of ruptured human cerebral aneurysms: preliminary results
.
J Neuroinflammation
.
2012
;
9
(
1
):
222
. .
21.
Qiu
H
,
Zhu
Y
,
Sun
Z
,
Trzeciakowski
JP
,
Gansner
M
,
Depre
C
,
Short communication: vascular smooth muscle cell stiffness as a mechanism for increased aortic stiffness with aging
.
Circ Res
.
2010
;
107
(
5
):
615
. .
22.
Humphrey
JD
,
Rajagopal
KR
.
A constrained mixture model for growth and remodelling of soft tissues
.
Math Models Methods Appl Sci
.
2002
;
12
(
03
):
407
30
.
23.
Steucke
KE
,
Win
Z
,
Stemler
TR
,
Walsh
EE
,
Hall
JL
,
Alford
PW
.
Empirically determined vascular smooth muscle cell mechano-adaptation law
.
J Biomech Eng
.
2017
;
139
(
7
). .
24.
Humphrey
JD
,
Rajagopal
KR
.
A constrained mixture model for growth and remodelling of soft tissues
.
Math Models Methods Appl Sci
.
2002
;
12
(
03
).
25.
Kubo
Y
,
Koji
T
,
Kashimura
H
,
Otawara
Y
,
Ogawa
A
,
Ogasawara
K
.
Female sex as a risk factor for the growth of asymptomatic unruptured cerebral saccular aneurysms in elderly patients: clinical article
.
J Neurosurgery
.
2014
;
121
(
3
):
599
604
.
26.
Brinjikji
W
,
Zhu
YQ
,
Lanzino
G
,
Cloft
HJ
,
Murad
MH
,
Wang
Z
,
Risk factors for growth of intracranial aneurysms: a systematic review and meta-analysis
.
AJNR Am J Neuroradiol
.
2016
;
37
(
4
):
615
20
. .
27.
Ghods
AJ
,
Lopes
D
,
Chen
M
.
Gender differences in cerebral aneurysm location
.
Front Neurol
.
2012
;
3
:
78
.
28.
Welleweerd
JC
,
Nelissen
BG
,
Koole
D
,
de Vries
JP
,
Moll
FL
,
Pasterkamp
G
,
Histological analysis of extracranial carotid artery aneurysms
.
PLoS One
.
2015
;
10
(
1
):
e0117915
. .
29.
Witzenburg
CM
,
Barocas
VH
.
A nonlinear anisotropic inverse method for computational dissection of inhomogeneous planar tissues
.
Comput Methods Biomech Biomed Eng
.
2016
;
19
(
15
):
1630
. .
30.
Genovese
K
,
Casaletto
L
,
Humphrey
JD
,
Lu
J
.
Digital image correlation-based point-wise inverse characterization of heterogeneous material properties of gallbladder in vitro
.
Proc R Soc A
.
2014
;
470
(
2167
).
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.