Abstract
Hemodynamic forces play critical roles in vascular pathologies such as atherosclerosis, aneurysms, and stenosis. However, detailed relationships between the specific in vivo hemodynamic microenvironment and vascular responses leading to the triggering or exacerbation of pathological remodeling of the vessel remain elusive. We have developed a hemodynamics-biology co-mapping technique that enables in situ correlation between the in vivo blood flow field and vascular changes secondary to hemodynamic insult. The hemodynamics profile is obtained from computational fluid dynamics simulation within the vascular geometry reconstructed from three-dimensional in vivo images, whereas the vascular response is obtained from histology or immunohistochemistry on harvested vascular tissue. The hemodynamics field is virtually sectioned in the histological slicing planes and digitally co-mapped with the histological images, thereby enabling correlation of the specific local vascular responses with the inciting hemodynamic stresses. We demonstrate application of this technique to rabbit basilar terminus subjected to elevated flow. Morphological changes at the basilar terminus 5 days after the flow increase were co-mapped with the initial wall shear stress and wall shear stress gradient distributions, from which localization of destructive remodeling in a specific hemodynamic zone was noticed. This method paves the way for further investigations to determine the connection between in vivo mechanical stimuli and biological responses, such as initiation of aneurysmal remodeling.
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Abbreviations
- 2D:
-
Two-dimensional
- 3D:
-
Three-dimensional
- BA:
-
Basilar artery
- BT:
-
Basilar terminus
- CCA:
-
Common carotid artery
- CFD:
-
Computational fluid dynamics
- CT:
-
Computed tomographic
- CTA:
-
Computed tomographic angiography
- DSA:
-
Digital subtraction angiography
- IEL:
-
Internal elastic lamina
- MR:
-
Magnetic resonance
- MRI:
-
Magnetic resonance imaging
- Pa:
-
Pascal
- PET:
-
Positron emission tomography
- ROI:
-
Region of interest
- s:
-
Seconds
- TCD:
-
Transcranial Doppler
- WSS:
-
Wall shear stress
- WSSG:
-
Wall shear stress gradient
References
Alnaes MS, Isaksen J et al (2007) Computation of hemodynamics in the circle of Willis. Stroke 38(9): 2500–2505
Bassiouny HS, White S et al (1992) Anastomotic intimal hyperplasia: mechanical injury or flow induced. J Vasc Surg 15(4):708–716; discussion 716–717
Castro MA, Putman CM et al (2006) Computational fluid dynamics modeling of intracranial aneurysms: effects of parent artery segmentation on intra-aneurysmal hemodynamics. AJNR Am J Neuroradiol 27(8): 1703–1709
Cebral JR, Castro MA et al (2005) Efficient pipeline for image-based patient-specific analysis of cerebral aneurysm hemodynamics: technique and sensitivity. IEEE Trans Med Imaging 24(4): 457–467
Cebral JR, Castro MA et al (2005) Characterization of cerebral aneurysms for assessing risk of rupture by using patient-specific computational hemodynamics models. AJNR Am J Neuroradiol 26(10): 2550–2559
Cummins PM, von Offenberg Sweeney N et al (2007) Cyclic strain-mediated matrix metalloproteinase regulation within the vascular endothelium: a force to be reckoned with. Am J Physiol Heart Circ Physiol 292(1): H28–H42
Czosnyka M, Richards H et al (1994) Frequency-dependent properties of cerebral blood transport—an experimental study in anaesthetized rabbits. Ultrasound Med Biol 20(4): 391–399
Davies PF (1995) Flow-mediated endothelial mechanotransduction. Physiol Rev 75(3): 519–560
Davies PF (2000) Spatial hemodynamics, the endothelium, and focal atherogenesis: a cell cycle link?. Circ Res 86(2): 114–116
DePaola N, Gimbrone MA Jr et al (1992) Vascular endothelium responds to fluid shear stress gradients. Arterioscler Thromb 12(11): 1254–1257
Friedman MH, Giddens DP (2005) Blood flow in major blood vessels-modeling and experiments. Ann Biomed Eng 33(12): 1710– 1713
Friedman MH, Himburg HA et al (2006) Statistical hemodynamics: a tool for evaluating the effect of fluid dynamic forces on vascular biology in vivo. J Biomech Eng 128(6): 965–968
Gao L, Hoi Y et al (2008) Nascent aneurysm formation at the basilar terminus induced by hemodynamics. Stroke 39(7): 2085–2090
Gijsen FJ, Oortman RM et al (2003) Usefulness of shear stress pattern in predicting neointima distribution in sirolimus-eluting stents in coronary arteries. Am J Cardiol 92(11): 1325–1328
Glagov S, Zarins C et al (1988) Hemodynamics and atherosclerosis. Insights and perspectives gained from studies of human arteries. Arch Pathol Lab Med 112(10): 1018–1031
Goessling W, North TE et al (2007) Ultrasound biomicroscopy permits in vivo characterization of zebrafish liver tumors. Nat Methods 4(7): 551–553
Gonzalez CF, Cho YI et al (1992) Intracranial aneurysms: flow analysis of their origin and progression. AJNR Am J Neuroradiol 13(1): 181–188
Graham KC, Wirtzfeld LA et al (2005) Three-dimensional high-frequency ultrasound imaging for longitudinal evaluation of liver metastases in preclinical models. Cancer Res 65(12): 5231–5237
Greve JM, Les AS et al (2006) Allometric scaling of wall shear stress from mice to humans: quantification using cine phase-contrast MRI and computational fluid dynamics. Am J Physiol Heart Circ Physiol 291(4): H1700–H1708
Groen H, Van Walsum T et al (2009) Fusion of histology and shear stress based on in vivo images. In: Proceedings of the ASME 2009 summer bioengineering conference (SBC2009-206727), Lake Tahoe, CA, June 17–21
Hashimoto T, Meng H et al (2006) Intracranial aneurysms: links among inflammation, hemodynamics and vascular remodeling. Neurol Res 28(4): 372–380
Hoi Y, Gao L et al (2008) In vivo assessment of rapid cerebrovascular morphological adaptation following acute blood flow increase. J Neurosurg 109(6): 1141–1147
Hoi Y, Meng H et al (2004) Effects of arterial geometry on aneurysm growth: three-dimensional computational fluid dynamics study. J Neurosurg 101(4): 676–681
Holden M (2008) A review of geometric transformations for nonrigid body registration. IEEE Trans Med Imaging 27(1): 111–128
Jeppsson PG, Olin T (1960) Cerebral Angiography in the Rabbit: An Investigation of Vascular Anatomy and Variation in Circulatory Pattern with Conditions of Injection. Lunds Universitets Arsskrift. N. F. Avd. 2 56(14): 1–55
Jou LD, Wong G et al (2005) Correlation between lumenal geometry changes and hemodynamics in fusiform intracranial aneurysms. AJNR Am J Neuroradiol 26(9): 2357–2363
Judenhofer MS, Wehrl HF et al (2008) Simultaneous PET-MRI: a new approach for functional and morphological imaging. Nat Med 14(4): 459–465
LaDisa JF Jr, Olson LE et al (2005) Alterations in wall shear stress predict sites of neointimal hyperplasia after stent implantation in rabbit iliac arteries. Am J Physiol Heart Circ Physiol 288(5): H2465–H2475
Li D, Robertson AM (2009) A structural multi-mechanism damage model for cerebral arterial tissue. J Biomech Eng (in press)
Malek AM, Alper SL et al (1999) Hemodynamic shear stress and its role in atherosclerosis. JAMA 282(21): 2035–2042
Meng H, Swartz DD et al (2006) A model system for mapping vascular responses to complex hemodynamics at arterial bifurcations in vivo. Neurosurgery 59(5): 1094–1101
Meng H, Wang Z et al (2007) Complex hemodynamics at the apex of an arterial bifurcation induces vascular remodeling resembling cerebral aneurysm initiation. Stroke 38(6): 1924–1931
Metaxa E, Meng H et al (2008) Nitric oxide-dependent stimulation of endothelial cell proliferation by sustained high flow. Am J Physiol Heart Circ Physiol 295(2): H736–H742
Moore JA, Steinman DA et al (1998) Computational blood flow modelling: errors associated with reconstructing finite element models from magnetic resonance images. J Biomech 31(2): 179–184
Moore JA, Steinman DA et al (1999) Accuracy of computational hemodynamics in complex arterial geometries reconstructed from magnetic resonance imaging. Ann Biomed Eng 27(1): 32–41
Nakahashi TK, Hoshina K et al (2002) Flow loading induces macrophage antioxidative gene expression in experimental aneurysms. Arterioscler Thromb Vasc Biol 22(12): 2017–2022
Nelson RJ, Perry S et al (1990) Transcranial Doppler ultrasound studies of cerebral autoregulation and subarachnoid hemorrhage in the rabbit. J Neurosurg 73(4): 601–610
Ourselin S, Roche A et al (2001) Reconstructing a 3d structure from serial histological sections. Image Vis Comput 19: 25–31
Perktold K, Kenner T et al (1988) Numerical blood flow analysis: arterial bifurcation with a saccular aneurysm. Basic Res Cardiol 83(1): 24–31
Perktold K, Peter R et al (1989) Pulsatile non-Newtonian blood flow simulation through a bifurcation with an aneurysm. Biorheology 26(6): 1011–1030
Podoleanu AG (2005) Optical coherence tomography. Br J Radiol 78(935): 976–988
Sho E, Sho M et al (2004) Hemodynamic forces regulate mural macrophage infiltration in experimental aortic aneurysms. Exp Mol Pathol 76(2): 108–116
Shojima M, Oshima M et al (2005) Role of the bloodstream impacting force and the local pressure elevation in the rupture of cerebral aneurysms. Stroke
Slager CJ, Wentzel JJ et al (2005) The role of shear stress in the destabilization of vulnerable plaques and related therapeutic implications. Nat Clin Pract Cardiovasc Med 2(9): 456–464
Steinman DA (2002) Image-based computational fluid dynamics modeling in realistic arterial geometries. Ann Biomed Eng 30(4): 483–497
Steinman DA, Taylor CA (2005) Flow imaging and computing: large artery hemodynamics. Ann Biomed Eng 33(12): 1704–1709
Szymanski MP, Metaxa E et al (2008) Endothelial cell layer subjected to impinging flow mimicking the apex of an arterial bifurcation. Ann Biomed Eng 36(10): 1681–1689
Thomas JB, Milner JS et al (2003) Reproducibility of image-based computational fluid dynamics models of the human carotid bifurcation. Ann Biomed Eng 31(2): 132–141
Townsend DW, Carney JP et al (2004) PET/CT today and tomorrow. J Nucl Med 45(1): 4s–14s
Ujiie H, Tamano Y et al (2001) Is the aspect ratio a reliable index for predicting the rupture of a saccular aneurysm? Neurosurgery 48(3):495–502; discussion 502–503
Ungersböck K, Tenckhoff D et al (1995) Transcranial Doppler and cortical microcirculation at increased intracranial pressure and during the cushing response: an experimental study on rabbits. Neurosurgery 36(1): 147–157
Valencia A (2005) Simulation of unsteady laminar flow in models of terminal aneurysm of the basilar artery. Int J Comput Fluid Dyn 19: 337–345
Vanninen R, Manninen H et al (2003) Broad-based intracranial aneurysms: thrombosis induced by stent placement. AJNR Am J Neuroradiol 24(2): 263–266
Walpola PL, Gotlieb AI et al (1995) Expression of ICAM-1 and VCAM-1 and monocyte adherence in arteries exposed to altered shear stress. Arterioscler Thromb Vasc Biol 15(1): 2–10
Wang Z, Kolega J et al (2009) Molecular alterations associated with aneurysmal remodeling are localized in the high hemodynamic stress region of a created carotid bifurcation. Neurosurgery 65(1):169–177; discussion 177–178
Watton PN, Raberger NB et al (2009) Coupling the hemodynamic environment to the evolution of cerebral aneurysms: computational framework and numerical examples. J Biomech Eng 131(10): 101003
Wentzel JJ, Krams R et al (2001) Relationship between neointimal thickness and shear stress after Wallstent implantation in human coronary arteries. Circulation 103(13): 1740–1745
Windberger U, Bartholovitsch A et al (2003) Whole blood viscosity, plasma viscosity and erythrocyte aggregation in nine mammalian species: reference values and comparison of data. Exp Physiol 88(3): 431–440
Wirtzfeld LA, Wu G et al (2005) A new three-dimensional ultrasound microimaging technology for preclinical studies using a transgenic prostate cancer mouse model. Cancer Res 65(14): 6337–6345
Zarins CK, Giddens DP et al (1983) Carotid bifurcation atherosclerosis. Quantitative correlation of plaque localization with flow velocity profiles and wall shear stress. Circ Res 53(4): 502–514
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Tremmel, M., Xiang, J., Hoi, Y. et al. Mapping vascular response to in vivo Hemodynamics: application to increased flow at the basilar terminus. Biomech Model Mechanobiol 9, 421–434 (2010). https://doi.org/10.1007/s10237-009-0185-y
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DOI: https://doi.org/10.1007/s10237-009-0185-y