Aneurysmal Remodeling in the Circle of Willis after Carotid Occlusion in an Experimental Model

Tutino, Vincent M.; Mandelbaum, Max; Choi, Hoon; Pope, L; Siddiqui, Adnan H.; Kolega, John

doi:10.1038/jcbfm.2013.209

Cited by 28 publications

(32 citation statements)

References 39 publications

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“…In particular, the curvature of the parent vessel has been shown to play a role in aneurysm formation, as well as aneurysm growth and possible progression to rupture. Experiments on animal models showed that increased vessel tortuosity preceded aneurysm formation following bilateral carotid ligation in rabbit models (Tutino et al, 2014). Following analysis on 3D synthetic models of curved arteries, Foutrakis et al (1999) and Hoi et al (2004) theorized that high hemodynamic stress is responsible for the formation of aneurysms on the lateral outer wall of the curved bends.…”

Section: Discussionmentioning

confidence: 99%

Curvature effect on hemodynamic conditions at the inner bend of the carotid siphon and its relation to aneurysm formation

Lauric

Hippelheuser

Safain

et al. 2014

Journal of Biomechanics

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Although high-impact hemodynamic forces are thought to lead to cerebral aneurysmal change, little is known about the aneurysm formation on the inner aspect of vascular bends such as the internal carotid artery (ICA) siphon where wall shear stress (WSS) is expected to be low. This study evaluates the effect of vessel curvature and hemodynamics on aneurysm formation along the inner carotid siphon. Catheter 3D-rotational angiographic volumes of 35 ICA (10 aneurysms, 25 controls) were evaluated in 3D for radius of curvature and peak curvature of the siphon bend, followed by univariate statistical analysis. Computational fluid dynamic (CFD) simulations were performed on patient-derived models after aneurysm removal and on synthetic variants of increasing curvature. Peak focal siphon curvature was significantly higher in aneurysm bearing ICAs (0.36±0.045 vs. 0.30±0.048 mm−1, p=0.003), with no difference in global radius of curvature (p=0.36). In CFD simulations, increasing parametric curvature tightness (from 5 to 3 mm radius) resulted in dramatic increase of WSS and WSS gradient magnitude (WSSG) on the inner wall of the bend. In patient-derived data, the location of aneurysms coincided with regions of low WSS (<4 Pa) flanked by high WSS and WSSG peaks. WSS peaks correlated with the aneurysm neck. In contrast, control siphon bends displayed low, almost constant, WSS and WSSG profiles with little spatial variation. High bend curvature induces dynamically fluctuating high proximal WSS and WSSG followed by regions of flow stasis and recirculation, leading to local conditions known to induce destructive vessel wall remodeling and aneurysmal initiation.

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Section: Discussionmentioning

confidence: 99%

Curvature effect on hemodynamic conditions at the inner bend of the carotid siphon and its relation to aneurysm formation

Lauric

Hippelheuser

Safain

et al. 2014

Journal of Biomechanics

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“…A similar change was reported in a model of cerebral aneurysm in rabbits. 13 The MRA technique tested in this study appears to be sufficiently accurate and reproducible for future preclinical studies in mice. Representative serial magnetic resonance images of a mouse with aneurysmal subarachnoid hemorrhage.…”

Section: Discussionmentioning

confidence: 99%

Successful Serial Imaging of the Mouse Cerebral Arteries Using Conventional 3-T Magnetic Resonance Imaging

Makino

Hokamura²,

Natsume

et al. 2015

J Cereb Blood Flow Metab

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Serial imaging studies can be useful in characterizing the pathologic and physiologic remodeling of cerebral arteries in various mouse models. We tested the feasibility of using a readily available, conventional 3-T magnetic resonance imaging (MRI) to serially image cerebrovascular remodeling in mice. We utilized a mouse model of intracranial aneurysm as a mouse model of the dynamic, pathologic remodeling of cerebral arteries. Aneurysms were induced by hypertension and a single elastase injection into the cerebrospinal fluid. For the mouse cerebrovascular imaging, we used a conventional 3-T MRI system and a 40-mm saddle coil. We used non-enhanced magnetic resonance angiography (MRA) to detect intracranial aneurysm formation and T2-weighted imaging to detect aneurysmal subarachnoid hemorrhage. A serial MRI was conducted every 2 to 3 days. MRI detection of aneurysm formation and subarachnoid hemorrhage was compared against the postmortem inspection of the brain that was perfused with dye. The imaging times for the MRA and T2-weighted imaging were 3.7 ± 0.5 minutes and 4.8 ± 0.0 minutes, respectively. All aneurysms and subarachnoid hemorrhages were correctly identified by two masked observers on MRI. This MRI-based serial imaging technique was useful in detecting intracranial aneurysm formation and subarachnoid hemorrhage in mice. 1 There are a number of mouse models of the physiologic or pathologic remodeling of cerebral arteries. Journal of Cerebral Blood2-5 To study the remodeling of cerebral arteries, a noninvasive, serial imaging technique that can visualize the cerebral arteries is an extremely useful tool.We report on the feasibility of using a readily available, conventional 3-T clinical magnetic resonance imaging (MRI) system to serially image cerebral arteries in mice. As a test case, we utilized a mouse model of an intracranial aneurysm that shows dynamic changes in the cerebral arteries. 2,6,7 In this model, intracranial aneurysms were induced by a combination of systemic hypertension and a single injection of elastase into the cerebrospinal fluid.

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“…These images were compared to electron micrographs of rabbit casts prepared in the same manner in a previous study. (5)…”

Section: Introductionmentioning

confidence: 99%

Assessment of Vascular Geometry for Bilateral Carotid Artery Ligation to Induce Early Basilar Terminus Aneurysmal Remodeling in Rats

Tutino¹,

Liaw²,

Spernyak³

et al. 2016

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Bilateral common carotid artery (CCA) ligation in rabbits is a model for basilar terminus (BT) aneurysm formation. We asked if this model could be replicated in rats. Fourteen female Sprague Dawley rats underwent bilateral CCA ligation (n=8) or sham surgery (n=6). After 7 days, 5 ligated and 3 sham rats were euthanized for histological evaluation of BT aneurysm formation, while the remaining rats were imaged with magnetic resonance angiography, euthanized, and subjected to corrosion casting of the Circle of Willis (CoW). 3D micro computed tomography images of CoW casts were used for flow simulations at the rat BT, and electron micrographs of the casts were analyzed for aneurysmal and morphological changes. Results from these analyses were compared to rabbit model data (n=10 ligated and n=6 sham). Bilateral CCA ligation did not produce aneurysmal damage at the rat BT. While the surgical manipulation increased rat basilar artery flow, fluid dynamics simulations showed that the initial hemodynamic stress at the rat BT was significantly less than in rabbits. Rats also exhibited fewer morphological and pathological changes (minor changes only occurred in the posterior CoW) than rabbits, which had drastic changes throughout the CoW. A comparison of CoW anatomies demonstrated a greater number of branching arteries at the BT, larger CoW arteries in relation to basilar artery, and a steeper BT bifurcation angle in the rat. These differences could account for the lower hemodynamic stress at the BT and in the cerebrovasculature of the rat. In conclusion, bilateral CCA ligation in rats does not recapitulate the rabbit model of early flow-induced BT aneurysm. We suspect that the different CoW morphology of the rat lessens hemodynamic insults, thereby diminishing flow-induced aneurysmal remodeling.

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Aneurysmal Remodeling in the Circle of Willis after Carotid Occlusion in an Experimental Model

Cited by 28 publications

References 39 publications

Curvature effect on hemodynamic conditions at the inner bend of the carotid siphon and its relation to aneurysm formation

Curvature effect on hemodynamic conditions at the inner bend of the carotid siphon and its relation to aneurysm formation

Successful Serial Imaging of the Mouse Cerebral Arteries Using Conventional 3-T Magnetic Resonance Imaging

Assessment of Vascular Geometry for Bilateral Carotid Artery Ligation to Induce Early Basilar Terminus Aneurysmal Remodeling in Rats

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