Colocalization of thin-walled dome regions with low hemodynamic wall shear stress in unruptured cerebral aneurysms

Clinical article

Laith M. Kadasi Cerebrovascular and Endovascular Division, Department of Neurosurgery, Tufts Medical Center; and
Tufts University School of Medicine, Boston, Massachusetts

Search for other papers by Laith M. Kadasi in
Current site
Google Scholar
PubMed
Close
 B.Sc.
,
Walter C. Dent Cerebrovascular and Endovascular Division, Department of Neurosurgery, Tufts Medical Center; and

Search for other papers by Walter C. Dent in
Current site
Google Scholar
PubMed
Close
 M.S.
, and
Adel M. Malek Cerebrovascular and Endovascular Division, Department of Neurosurgery, Tufts Medical Center; and
Tufts University School of Medicine, Boston, Massachusetts

Search for other papers by Adel M. Malek in
Current site
Google Scholar
PubMed
Close
 M.D., Ph.D.
Restricted access

Purchase Now

USD  $45.00

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $525.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $624.00
USD  $45.00
USD  $525.00
USD  $624.00
Print or Print + Online Sign in

Object

Wall shear stress (WSS) plays a role in regulating endothelial function and has been suspected in cerebral aneurysm rupture. The aim of this study was to evaluate the spatial relationship between localized thinning of the aneurysm dome and estimated hemodynamic factors, hypothesizing that a low WSS would correlate with aneurysm wall degeneration.

Methods

Steady-state computational fluid dynamics analysis was performed on 16 aneurysms in 14 patients based on rotational angiographic volumes to derive maps of WSS, its spatial gradient (WSSG), and pressure. Local dome thickness was estimated categorically based on tissue translucency from high-resolution intraoperative microscopy findings. Each computational model was oriented to match the corresponding intraoperative view and numerically sampled in thin and normal adjacent dome regions, with controls at the neck and parent vessel. The pressure differential was computed as the difference between aneurysm dome points and the mean neck pressure. Pulsatile time-dependent confirmatory analysis was carried out in 7 patients.

Results

Matched-pair analysis revealed significantly lower levels of WSS (0.381 Pa vs 0.816 Pa; p < 0.0001) in thin-walled dome areas than in adjacent baseline thickness regions. Similarly, log WSSG and log WSS × WSSG were both lower in thin regions (both p < 0.0001); multivariate logistic regression analysis identified lower WSS and higher pressure differential as independent correlates of lower wall thickness with an area under the curve of 0.80. This relationship was observed in both steady-state and time-dependent pulsatile analyses.

Conclusions

Thin-walled regions of unruptured cerebral aneurysms colocalize with low WSS, suggesting a cellular mechanotransduction link between areas of flow stasis and aneurysm wall thinning.

Abbreviations used in this paper:

ACoA = anterior communicating artery; CFD = computational fluid dynamics; MCA = middle cerebral artery; PD = pressure differential; SAH = subarachnoid hemorrhage; WSS = wall shear stress; WSSG = WSS gradient.
  • Collapse
  • Expand
  • 1

    Abruzzo T, , Shengelaia GG, , Dawson RC III, , Owens DS, , Cawley CM, & Gravanis MB: Histologic and morphologic comparison of experimental aneurysms with human intracranial aneurysms. AJNR Am J Neuroradiol 19:13091314, 1998

    • Search Google Scholar
    • Export Citation
  • 2

    Asari S, & Ohmoto T: Growth and rupture of unruptured cerebral aneurysms based on the intraoperative appearance. Acta Med Okayama 48:257262, 1994

    • Search Google Scholar
    • Export Citation
  • 3

    Baharoglu MI, , Schirmer CM, , Hoit DA, , Gao BL, & Malek AM: Aneurysm inflow-angle as a discriminant for rupture in sidewall cerebral aneurysms: morphometric and computational fluid dynamic analysis. Stroke 41:14231430, 2010

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4

    Boussel L, , Rayz V, , McCulloch C, , Martin A, , Acevedo-Bolton G, & Lawton M, et al.: Aneurysm growth occurs at region of low wall shear stress: patient-specific correlation of hemodynamics and growth in a longitudinal study. Stroke 39:29973002, 2008

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5

    Castro MA, , Putman CM, , Sheridan MJ, & Cebral JR: Hemodynamic patterns of anterior communicating artery aneurysms: a possible association with rupture. AJNR Am J Neuroradiol 30:297302, 2009

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6

    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 26:25502559, 2005

    • Search Google Scholar
    • Export Citation
  • 7

    Cebral JR, , Mut F, , Weir J, & Putman CM: Association of hemodynamic characteristics and cerebral aneurysm rupture. AJNR Am J Neuroradiol 32:264270, 2011

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8

    Chappell DC, , Varner SE, , Nerem RM, , Medford RM, & Alexander RW: Oscillatory shear stress stimulates adhesion molecule expression in cultured human endothelium. Circ Res 82:532539, 1998

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9

    Chien S: Mechanotransduction and endothelial cell homeostasis: the wisdom of the cell. Am J Physiol Heart Circ Physiol 292:H1209H1224, 2007

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10

    Cho A, , Mitchell L, , Koopmans D, & Langille BL: Effects of changes in blood flow rate on cell death and cell proliferation in carotid arteries of immature rabbits. Circ Res 81:328337, 1997

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11

    Dai G, , Kaazempur-Mofrad MR, , Natarajan S, , Zhang Y, , Vaughn S, & Blackman BR, et al.: Distinct endothelial phenotypes evoked by arterial waveforms derived from atherosclerosis-susceptible and -resistant regions of human vasculature. Proc Natl Acad Sci U S A 101:1487114876, 2004

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12

    De Keulenaer GW, , Chappell DC, , Ishizaka N, , Nerem RM, , Alexander RW, & Griendling KK: Oscillatory and steady laminar shear stress differentially affect human endothelial redox state: role of a superoxide-producing NADH oxidase. Circ Res 82:10941101, 1998

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13

    Frösen J, , Piippo A, , Paetau A, , Kangasniemi M, , Niemelä M, & Hernesniemi J, et al.: Remodeling of saccular cerebral artery aneurysm wall is associated with rupture: histological analysis of 24 unruptured and 42 ruptured cases. Stroke 35:22872293, 2004

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14

    Hassan T, , Timofeev EV, , Saito T, , Shimizu H, , Ezura M, & Matsumoto Y, et al.: A proposed parent vessel geometry-based categorization of saccular intracranial aneurysms: computational flow dynamics analysis of the risk factors for lesion rupture. J Neurosurg 103:662680, 2005

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15

    Hayakawa M, , Katada K, , Anno H, , Imizu S, , Hayashi J, & Irie K, et al.: CT angiography with electrocardiographically gated reconstruction for visualizing pulsation of intracranial aneurysms: identification of aneurysmal protuberance presumably associated with wall thinning. AJNR Am J Neuroradiol 26:13661369, 2005

    • Search Google Scholar
    • Export Citation
  • 16

    Hop JW, , Rinkel GJE, , Algra A, & van Gijn J: Case-fatality rates and functional outcome after subarachnoid hemorrhage: a systematic review. Stroke 28:660664, 1997

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17

    Jou LD, , Lee DH, , Morsi H, & Mawad ME: Wall shear stress on ruptured and unruptured intracranial aneurysms at the internal carotid artery. AJNR Am J Neuroradiol 29:17611767, 2008

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18

    Kadasi LM, , Dent WC, & Malek AM: Cerebral aneurysm wall thickness analysis using intraoperative microscopy: effect of size and gender on thin translucent regions. J Neurointervent Surg [epub ahead of print], 2012

    • Search Google Scholar
    • Export Citation
  • 19

    Kolega J, , Gao L, , Mandelbaum M, , Mocco J, , Siddiqui AH, & Natarajan SK, et al.: Cellular and molecular responses of the basilar terminus to hemodynamics during intracranial aneurysm initiation in a rabbit model. J Vasc Res 48:429442, 2011

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20

    Kondo S, , Hashimoto N, , Kikuchi H, , Hazama F, , Nagata I, & Kataoka H: Apoptosis of medial smooth muscle cells in the development of saccular cerebral aneurysms in rats. Stroke 29:181189, 1998

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21

    Kraiss LW, , Geary RL, , Mattsson EJR, , Vergel S, , Au YPT, & Clowes AW: Acute reductions in blood flow and shear stress induce platelet-derived growth factor-A expression in baboon prosthetic grafts. Circ Res 79:4553, 1996

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22

    Lindekleiv HM, , Valen-Sendstad K, , Morgan MK, , Mardal KA, , Faulder K, & Magnus JH, et al.: Sex differences in intracranial arterial bifurcations. Gend Med 7:149155, 2010

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23

    Malek AM, , Alper SL, & Izumo S: Hemodynamic shear stress and its role in atherosclerosis. JAMA 282:20352042, 1999

  • 24

    Meng H, , Wang Z, , Hoi Y, , Gao L, , Metaxa E, & Swartz DD, et al.: Complex hemodynamics at the apex of an arterial bifurcation induces vascular remodeling resembling cerebral aneurysm initiation. Stroke 38:19241931, 2007

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25

    Mizoi K, , Yoshimoto T, & Nagamine Y: Types of unruptured cerebral aneurysms reviewed from operation video-recordings. Acta Neurochir (Wien) 138:965969, 1996

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26

    Molyneux AJ, , Kerr RSC, , Yu LM, , Clarke M, , Sneade M, & Yarnold JA, et al.: International subarachnoid aneurysm trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised comparison of effects on survival, dependency, seizures, rebleeding, subgroups, and aneurysm occlusion. Lancet 366:809817, 2005

    • Search Google Scholar
    • Export Citation
  • 27

    Nixon AM, , Gunel M, & Sumpio BE: The critical role of hemodynamics in the development of cerebral vascular disease. A review. J Neurosurg 112:12401253, 2010

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 28

    Raaymakers TWM, , Rinkel GJE, , Limburg M, & Algra A: Mortality and morbidity of surgery for unruptured intracranial aneurysms: a meta-analysis. Stroke 29:15311538, 1998

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29

    Schirmer CM, & Malek AM: Prediction of complex flow patterns in intracranial atherosclerotic disease using computational fluid dynamics. Neurosurgery 61:842852, 2007

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 30

    Shojima M, , Oshima M, , Takagi K, , Torii R, , Hayakawa M, & Katada K, et al.: Magnitude and role of wall shear stress on cerebral aneurysm: computational fluid dynamic study of 20 middle cerebral artery aneurysms. Stroke 35:25002505, 2004

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 31

    Tardy Y, , Resnick N, , Nagel T, , Gimbrone MA Jr, & Dewey CF Jr: Shear stress gradients remodel endothelial monolayers in vitro via a cell proliferation-migration-loss cycle. Arterioscler Thromb Vasc Biol 17:31023106, 1997

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 32

    Tuttle JL, , Nachreiner RD, , Bhuller AS, , Condict KW, , Connors BA, & Herring BP, et al.: Shear level influences resistance artery remodeling: wall dimensions, cell density, and eNOS expression. Am J Physiol Heart Circ Physiol 281:H1380H1389, 2001

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 33

    van Gijn J, & Rinkel GJE: Subarachnoid haemorrhage: diagnosis, causes and management. Brain 124:249278, 2001

  • 34

    Wang Z, , Kolega J, , Hoi Y, , Gao L, , Swartz DD, & Levy EI, et al.: Molecular alterations associated with aneurysmal remodeling are localized in the high hemodynamic stress region of a created carotid bifurcation. Neurosurgery 65:169178, 2009

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 35

    Wiebers DO, , Whisnant JP, , Huston J III, , Meissner I, , Brown RD Jr, & Piepgras DG, et al.: Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment. Lancet 362:103110, 2003

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 36

    Xiang J, , Natarajan SK, , Tremmel M, , Ma D, , Mocco J, & Hopkins LN, et al.: Hemodynamic-morphologic discriminants for intracranial aneurysm rupture. Stroke 42:144152, 2011

    • Crossref
    • Search Google Scholar
    • Export Citation

Metrics

All Time Past Year Past 30 Days
Abstract Views 1181 258 16
Full Text Views 341 24 2
PDF Downloads 255 25 4
EPUB Downloads 0 0 0