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

Clinical article

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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.

Article Information

Address correspondence to: Adel M. Malek, M.D., Ph.D., Department of Neurosurgery, Tufts Medical Center, 800 Washington Street, Boston, Massachusetts 02111. email: amalek@tuftsmedicalcenter.org.

Please include this information when citing this paper: published online March 29, 2013; DOI: 10.3171/2013.2.JNS12968.

© AANS, except where prohibited by US copyright law.

Headings

Figures

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    A: Intraoperative high-resolution microscopic image of an unruptured anterior communicating artery (ACOM) aneurysm from a right frontotemporal approach. B: Schematic showing patches of thin, translucent portions of the dome and the aneurysm neck (dashed line).

  • View in gallery

    Case 2. A: Volume rendering of a high-resolution 3D rotational angiogram obtained in a patient with an ACoA aneurysm (arrow) who underwent a left-sided craniotomy for simultaneous clipping of an MCA aneurysm. B: Computational fluid dynamic model of the ACoA aneurysm showing cross-sectional velocity map and vectors.

  • View in gallery

    Illustration of the analysis method. A: Intraoperative microscopic image of the aneurysm dome at the time of surgical clipping (left) with corresponding sampled regions (center and right) performed on a constant-color surface representation on the model corresponding to the thin-walled portion of the dome (yellow arrow) and adjacent baseline thickness region (black arrow), as well as sampled regions of the parent vessel (green dots) and aneurysm neck (black dots). Red dots represent manually selected samples corresponding with the thin-walled portion of the aneurysm dome. Yellow dots represent manually selected points sampled from the adjacent baseline thickness region of the aneurysm dome. B–D: Corresponding computed 3D maps of the WSS (B), pressure (C), and WSSG (D) at which selected sample points from panel A were obtained. Note the expected artifactual microscope light reflection just to the right of the head of the yellow arrow.

  • View in gallery

    Upper: Graph comparing on a per-aneurysm basis the WSS in thin- and thick-walled regions of the aneurysm dome. Lower: Bar graph showing the mean WSS and mean WSS normalized with respect to the mean parent vessel WSS in all regions based on regional type. *p < 0.0001.

  • View in gallery

    Upper: Pressure differential between the dome region and mean pressure at the aneurysm neck. Lower: Logarithmic transformations of WSSG and WSS × WSSG product reveal lower values in thin-walled regions consistent with flow stasis. *p < 0.0001.

  • View in gallery

    Case 14. A: Volume rendering of a high-resolution 3D rotational angiogram illustrating the location of an MCA aneurysm assessed via confirmatory pulsatile analysis. B: Intraoperative microscopic image of the aneurysm dome at the time of surgical clipping indicating foci of thin tissue (black arrow) and normal baseline tissue (white arrow). C: Corresponding 3D map of computed WSS with the distribution of selected points that were recorded throughout the cardiac cycle. D: Mean WSS values of each sample group throughout the cardiac cycle. ACA = anterior cerebral artery; ICA = internal carotid artery.

References

  • 1

    Abruzzo TShengelaia GGDawson RC IIIOwens DSCawley CMGravanis MB: Histologic and morphologic comparison of experimental aneurysms with human intracranial aneurysms. AJNR Am J Neuroradiol 19:130913141998

    • Search Google Scholar
    • Export Citation
  • 2

    Asari SOhmoto T: Growth and rupture of unruptured cerebral aneurysms based on the intraoperative appearance. Acta Med Okayama 48:2572621994

    • Search Google Scholar
    • Export Citation
  • 3

    Baharoglu MISchirmer CMHoit DAGao BLMalek AM: Aneurysm inflow-angle as a discriminant for rupture in sidewall cerebral aneurysms: morphometric and computational fluid dynamic analysis. Stroke 41:142314302010

    • Search Google Scholar
    • Export Citation
  • 4

    Boussel LRayz VMcCulloch CMartin AAcevedo-Bolton GLawton M: Aneurysm growth occurs at region of low wall shear stress: patient-specific correlation of hemodynamics and growth in a longitudinal study. Stroke 39:299730022008

    • Search Google Scholar
    • Export Citation
  • 5

    Castro MAPutman CMSheridan MJCebral JR: Hemodynamic patterns of anterior communicating artery aneurysms: a possible association with rupture. AJNR Am J Neuroradiol 30:2973022009

    • Search Google Scholar
    • Export Citation
  • 6

    Cebral JRCastro MABurgess JEPergolizzi RSSheridan MJPutman CM: Characterization of cerebral aneurysms for assessing risk of rupture by using patient-specific computational hemodynamics models. AJNR Am J Neuroradiol 26:255025592005

    • Search Google Scholar
    • Export Citation
  • 7

    Cebral JRMut FWeir JPutman CM: Association of hemodynamic characteristics and cerebral aneurysm rupture. AJNR Am J Neuroradiol 32:2642702011

    • Search Google Scholar
    • Export Citation
  • 8

    Chappell DCVarner SENerem RMMedford RMAlexander RW: Oscillatory shear stress stimulates adhesion molecule expression in cultured human endothelium. Circ Res 82:5325391998

    • 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:H1209H12242007

    • Search Google Scholar
    • Export Citation
  • 10

    Cho AMitchell LKoopmans DLangille BL: Effects of changes in blood flow rate on cell death and cell proliferation in carotid arteries of immature rabbits. Circ Res 81:3283371997

    • Search Google Scholar
    • Export Citation
  • 11

    Dai GKaazempur-Mofrad MRNatarajan SZhang YVaughn SBlackman BR: Distinct endothelial phenotypes evoked by arterial waveforms derived from atherosclerosis-susceptible and -resistant regions of human vasculature. Proc Natl Acad Sci U S A 101:14871148762004

    • Search Google Scholar
    • Export Citation
  • 12

    De Keulenaer GWChappell DCIshizaka NNerem RMAlexander RWGriendling KK: Oscillatory and steady laminar shear stress differentially affect human endothelial redox state: role of a superoxide-producing NADH oxidase. Circ Res 82:109411011998

    • Search Google Scholar
    • Export Citation
  • 13

    Frösen JPiippo APaetau AKangasniemi MNiemelä MHernesniemi J: Remodeling of saccular cerebral artery aneurysm wall is associated with rupture: histological analysis of 24 unruptured and 42 ruptured cases. Stroke 35:228722932004

    • Search Google Scholar
    • Export Citation
  • 14

    Hassan TTimofeev EVSaito TShimizu HEzura MMatsumoto Y: A proposed parent vessel geometry-based categorization of saccular intracranial aneurysms: computational flow dynamics analysis of the risk factors for lesion rupture. J Neurosurg 103:6626802005

    • Search Google Scholar
    • Export Citation
  • 15

    Hayakawa MKatada KAnno HImizu SHayashi JIrie K: 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 26:136613692005

    • Search Google Scholar
    • Export Citation
  • 16

    Hop JWRinkel GJEAlgra Avan Gijn J: Case-fatality rates and functional outcome after subarachnoid hemorrhage: a systematic review. Stroke 28:6606641997

    • Search Google Scholar
    • Export Citation
  • 17

    Jou LDLee DHMorsi HMawad ME: Wall shear stress on ruptured and unruptured intracranial aneurysms at the internal carotid artery. AJNR Am J Neuroradiol 29:176117672008

    • Search Google Scholar
    • Export Citation
  • 18

    Kadasi LMDent WCMalek 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 JGao LMandelbaum MMocco JSiddiqui AHNatarajan SK: Cellular and molecular responses of the basilar terminus to hemodynamics during intracranial aneurysm initiation in a rabbit model. J Vasc Res 48:4294422011

    • Search Google Scholar
    • Export Citation
  • 20

    Kondo SHashimoto NKikuchi HHazama FNagata IKataoka H: Apoptosis of medial smooth muscle cells in the development of saccular cerebral aneurysms in rats. Stroke 29:1811891998

    • Search Google Scholar
    • Export Citation
  • 21

    Kraiss LWGeary RLMattsson EJRVergel SAu YPTClowes AW: Acute reductions in blood flow and shear stress induce platelet-derived growth factor-A expression in baboon prosthetic grafts. Circ Res 79:45531996

    • Search Google Scholar
    • Export Citation
  • 22

    Lindekleiv HMValen-Sendstad KMorgan MKMardal KAFaulder KMagnus JH: Sex differences in intracranial arterial bifurcations. Gend Med 7:1491552010

    • Search Google Scholar
    • Export Citation
  • 23

    Malek AMAlper SLIzumo S: Hemodynamic shear stress and its role in atherosclerosis. JAMA 282:203520421999

  • 24

    Meng HWang ZHoi YGao LMetaxa ESwartz DD: Complex hemodynamics at the apex of an arterial bifurcation induces vascular remodeling resembling cerebral aneurysm initiation. Stroke 38:192419312007

    • Search Google Scholar
    • Export Citation
  • 25

    Mizoi KYoshimoto TNagamine Y: Types of unruptured cerebral aneurysms reviewed from operation video-recordings. Acta Neurochir (Wien) 138:9659691996

    • Search Google Scholar
    • Export Citation
  • 26

    Molyneux AJKerr RSCYu LMClarke MSneade MYarnold JA: 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 366:8098172005

    • Search Google Scholar
    • Export Citation
  • 27

    Nixon AMGunel MSumpio BE: The critical role of hemodynamics in the development of cerebral vascular disease. A review. J Neurosurg 112:124012532010

    • Search Google Scholar
    • Export Citation
  • 28

    Raaymakers TWMRinkel GJELimburg MAlgra A: Mortality and morbidity of surgery for unruptured intracranial aneurysms: a meta-analysis. Stroke 29:153115381998

    • Search Google Scholar
    • Export Citation
  • 29

    Schirmer CMMalek AM: Prediction of complex flow patterns in intracranial atherosclerotic disease using computational fluid dynamics. Neurosurgery 61:8428522007

    • Search Google Scholar
    • Export Citation
  • 30

    Shojima MOshima MTakagi KTorii RHayakawa MKatada K: Magnitude and role of wall shear stress on cerebral aneurysm: computational fluid dynamic study of 20 middle cerebral artery aneurysms. Stroke 35:250025052004

    • Search Google Scholar
    • Export Citation
  • 31

    Tardy YResnick NNagel TGimbrone MA JrDewey CF Jr: Shear stress gradients remodel endothelial monolayers in vitro via a cell proliferation-migration-loss cycle. Arterioscler Thromb Vasc Biol 17:310231061997

    • Search Google Scholar
    • Export Citation
  • 32

    Tuttle JLNachreiner RDBhuller ASCondict KWConnors BAHerring BP: Shear level influences resistance artery remodeling: wall dimensions, cell density, and eNOS expression. Am J Physiol Heart Circ Physiol 281:H1380H13892001

    • Search Google Scholar
    • Export Citation
  • 33

    van Gijn JRinkel GJE: Subarachnoid haemorrhage: diagnosis, causes and management. Brain 124:2492782001

  • 34

    Wang ZKolega JHoi YGao LSwartz DDLevy EI: Molecular alterations associated with aneurysmal remodeling are localized in the high hemodynamic stress region of a created carotid bifurcation. Neurosurgery 65:1691782009

    • Search Google Scholar
    • Export Citation
  • 35

    Wiebers DOWhisnant JPHuston J IIIMeissner IBrown RD JrPiepgras DG: Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment. Lancet 362:1031102003

    • Search Google Scholar
    • Export Citation
  • 36

    Xiang JNatarajan SKTremmel MMa DMocco JHopkins LN: Hemodynamic-morphologic discriminants for intracranial aneurysm rupture. Stroke 42:1441522011

    • Search Google Scholar
    • Export Citation

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