Towards optimal flow diverter porosity for the treatment of intracranial aneurysm.

PURPOSE: Low-porosity endovascular stents, known as flow diverters (FDs), have been proposed as an effective and minimally invasive treatment for sidewall intracranial aneurysms (IAs). Although it has been reported that the efficacy of a FD is substantially influenced by its porosity, clinical doctors would clearly prefer to do their interventions optimally based on refined quantitative data. This study focuses on the association between the porosity configurations and the FD efficacy, in order to provide practical data to help the clinical doctors optimize the interventions. METHOD: Numerical simulations in fluid dynamics were performed using four patient-specific IA geometries, pulsatile velocity profiles and braided fully resolved FDs. The variation of velocity and wall shear stress within the IAs, were investigated in this study. Lattice Boltzmann method (LBM) was used to solve the main challenge centered on the diversity of spatial scales since the typical diameter of struts of FDs is only 25µm while the artery normally can be larger by a hundred times. RESULTS: Numerical simulations revealed that the blood flow within IA sac was substantially reduced when the porosity is less than 86%. In particular, the flow condition within each IA sac is favorite to initialize thrombus formation when porosity is less than 70%. CONCLUSION: Our study suggests the existence of a porosity threshold below which the efficacy of a FD will be sufficient for the patients to initialize the thrombus formation. Therefore, by estimating the porosity of FD on patient-specific information, it may be potentially to predict whether or the blood flow condition will successfully become prothrombotic after the FD intervention.

A physical description of the adhesion and aggregation of platelets.

The early stages of clot formation in blood vessels involve platelet adhesion-aggregation. Although these mechanisms have been extensively studied, gaps in their understanding still persist. We have performed detailed in vitro experiments, using the well-known Impact-R device, and developed a numerical model to better describe and understand this phenomenon. Unlike previous studies, we took into account the differential role of pre-activated and non-activated platelets, as well as the three-dimensional nature of the aggregation process. Our investigation reveals that blood albumin is a major parameter limiting platelet aggregate formation in our experiment. Simulations are in very good agreement with observations and provide quantitative estimates of the adhesion and aggregation rates that are hard to measure experimentally. They also provide a value of the effective diffusion of platelets in blood subject to the shear rate produced by the Impact-R.

Does the gravity orientation of saccular aneurysms influence hemodynamics? An experimental study with and without flow diverter stent.

Most intracranial aneurysms morphologic studies focused on characterization of size, location, aspect ratio, relationship to the surrounding vasculature and hemodynamics. However, the spatial orientation with respect to the gravity direction has not been taken into account although it could trigger various hemodynamic conditions. The present work addresses this possibility. It was divided in two parts: 1) the orientations of 18, 3D time-of-flight MRI (3D TOF MRI), scans of saccular aneurysms were analyzed. This investigation suggested that there was no privileged orientation for cerebral aneurysms. The aneurysms were oriented in the brain as follows: 9 - down, 9 - up; 11 - right, 7 - left; 6 - front, 12 - back. 2) Based on these results, subsidiary in vitro experiments were performed, analyzing the behavior of red blood cells (RBCs) within a silicone model of aneurysm before and after flow diverter stent (FDS) deployment in the parent vessel. These experiments used a test bench that reproduces physiological pulsatile flow conditions for two orientations: an aneurysm sack pointing either up (opposite to gravitational force) and down (along the gravitational force). The results showed that the orientation of an aneurysm significantly affects the intra-aneurysmal RBCs behavior after stenting, and therefore that gravity can affect the intra-aneurysm behavior of RBCs. This suggests that the patient׳s aneurysm orientation could impact the outcome of the FDS treatment. The implementation of this effect in patient-specific numerical and preoperative decision support techniques could contribute to better understand the intrasaccular biological and hemodynamic events induced by FDS.

Multilevel segmentation of intracranial aneurysms in CT angiography images.

PURPOSE: Segmentation of aneurysms plays an important role in interventional planning. Yet, the segmentation of both the lumen and the thrombus of an intracranial aneurysm in computed tomography angiography (CTA) remains a challenge. This paper proposes a multilevel segmentation methodology for efficiently segmenting intracranial aneurysms in CTA images. METHODS: The proposed methodology first uses the lattice Boltzmann method (LBM) to extract the lumen part directly from the original image. Then, the LBM is applied again on an intermediate image whose lumen part is filled by the mean gray-level value outside the lumen, to yield an image region containing part of the aneurysm boundary. After that, an expanding disk is introduced to estimate the complete contour of the aneurysm. Finally, the contour detected is used as the initial contour of the level set with ellipse to refine the aneurysm. RESULTS: The results obtained on 11 patients from different hospitals showed that the proposed segmentation was comparable with manual segmentation, and that quantitatively, the average segmentation matching factor (SMF) reached 86.99%, demonstrating good segmentation accuracy. Chan-Vese method, Sen's model, and Luca's model were used to compare the proposed method and their average SMF values were 39.98%, 40.76%, and 77.11%, respectively. CONCLUSIONS: The authors have presented a multilevel segmentation method based on the LBM and level set with ellipse for accurate segmentation of intracranial aneurysms. Compared to three existing methods, for all eleven patients, the proposed method can successfully segment the lumen with the highest SMF values for nine patients and second highest SMF values for the two. It also segments the entire aneurysm with the highest SMF values for ten patients and second highest SMF value for the one. This makes it potential for clinical assessment of the volume and aspect ratio of the intracranial aneurysms.

Determination of a shear rate threshold for thrombus formation in intracranial aneurysms.

BACKGROUND: Particular intra-aneurysmal blood flow conditions, created naturally by the growth of an aneurysm or induced artificially by implantation of a flow diverter stent (FDS), can potentiate intra-aneurysmal thrombosis. The aim of this study was to identify hemodynamic indicators, relevant to this process, which could be used as a prediction of the success of a preventive endovascular treatment. METHOD: A cross sectional study on 21 patients was carried out to investigate the possible association between intra-aneurysmal spontaneous thrombus volume and the dome to neck aspect ratio (AR) of the aneurysm. The mechanistic link between these two parameters was further investigated through a Fourier analysis of the intra-aneurysmal shear rate (SR) obtained by computational fluid dynamics (CFD). This analysis was first applied to 10 additional patients (4 with and 6 without spontaneous thrombosis) and later to 3 patients whose intracranial aneurysms only thrombosed after FDS implantation. RESULTS: The cross sectional study revealed an association between intra-aneurysmal spontaneous thrombus volume and the AR of the aneurysm (R(2)=0.67, p<0.001). Fourier analysis revealed that in cases where thrombosis occurred, the SR harmonics 0, 1, and 2 were always less than 25/s, 10/s, and 5/s, respectively, and always greater than these values where spontaneous thrombosis was not observed. CONCLUSIONS: Our study suggests the existence of an SR threshold below which thrombosis will occur. Therefore, by analyzing the SR on patient specific data with CFD techniques, it may be potentially possible to predict whether or the intra-aneurysmal flow conditions, after FDS implantation, will become prothrombotic.

Quantitative analysis of platelets aggregates in 3D by digital holographic microscopy.

Platelet spreading and retraction play a pivotal role in the platelet plugging and the thrombus formation. In routine laboratory, platelet function tests include exhaustive information about the role of the different receptors present at the platelet surface without information on the 3D structure of platelet aggregates. In this work, we develop, a method in Digital Holographic Microscopy (DHM) to characterize the platelet and aggregate 3D shapes using the quantitative phase contrast imaging. This novel method is suited to the study of platelets physiology in clinical practice as well as the development of new drugs.

MR derived volumetric flow rate waveforms of internal carotid artery in patients treated for unruptured intracranial aneurysms by flow diversion technique.

Little is known about the hemodynamic disturbances induced by the cerebral aneurysms in the parent artery and the effect of flow diverter stents (FDS) on these latter. A better understanding of the aneurysm-parent vessel complex relationship may aid our understanding of this disease and to optimize its treatment. The ability of volumetric flow rate (VFR) waveform to reflect the arterial compliance modifications is well known. By analyzing the VFR waveform and the pulsatility in the parent vessel, this study aimed to test the hypotheses that (1) intracranial aneurysms might disrupt the blood flow of the parent vessel and (2) the treatment by FDS might have measurable corrective effect on these changes. Ten patients followed for unruptured intracranial aneurysms treated by FDS and ten healthy volunteers as control group were included in this study. Two-dimensional quantitative phase-contrast magnetic resonance imaging (MRI) was performed on each patient on the ICA artery upstream and downstream to the aneurysm, and on each volunteer at similar locations. The aneurysms altered significantly the parent vessel pulsatility and this effect was correlated to their volume. The aneurysms treatment by FDS allowed for the restoration of a normally modulated flow and pulsatility correction in the parent vessel.

An in vitro test bench reproducing coronary blood flow signals.

BACKGROUND: It is a known fact that blood flow pattern and more specifically the pulsatile time variation of shear stress on the vascular wall play a key role in atherogenesis. The paper presents the conception, the building and the control of a new in vitro test bench that mimics the pulsatile flows behavior based on in vivo measurements. METHODS: An in vitro cardiovascular simulator is alimented with in vivo constraints upstream and provided with further post-processing analysis downstream in order to mimic the pulsatile in vivo blood flow quantities. This real-time controlled system is designed to perform real pulsatile in vivo blood flow signals to study endothelial cells' behavior under near physiological environment. The system is based on an internal model controller and a proportional-integral controller that controls a linear motor with customized piston pump, two proportional-integral controllers that control the mean flow rate and temperature of the medium. This configuration enables to mimic any resulting blood flow rate patterns between 40 and 700 ml/min. In order to feed the system with reliable periodic flow quantities in vivo measurements were performed. Data from five patients (1 female, 4 males; ages 44-63) were filtered and post-processed using the Newtonian Womersley's solution. These resulting flow signals were compared with 2D axisymmetric, numerical simulation using a Carreau non-Newtonian model to validate the approximation of a Newtonian behavior. RESULTS: This in vitro test bench reproduces the measured flow rate time evolution and the complexity of in vivo hemodynamic signals within the accuracy of the relative error below 5%. CONCLUSIONS: This post-processing method is compatible with any real complex in vivo signal and demonstrates the heterogeneity of pulsatile patterns in coronary arteries among of different patients. The comparison between analytical and numerical solution demonstrate the fair quality of the Newtonian Womersley's approximation. Therefore, Womersley's solution was used to calculate input flow rate for the in vitro test bench.

High-resolution MRI visualization of aneurysmal thrombosis after flow diverter stent placement.

Flow-diverter stents are the new promising tools in the treatment of intracranial aneurysms allowing progressive aneurysm occlusion. Here, we report a case where high-resolution magnetic resonance imaging showed thrombus at fundus of the aneurysm sac, indicating a progressive intraaneurysmal thrombosis after flow-diverter placement.

Myeloperoxidase oxidized LDL interferes with endothelial cell motility through miR-22 and heme oxygenase 1 induction: possible involvement in reendothelialization of vascular injuries.

Cardiovascular disease linked to atherosclerosis is the leading cause of death worldwide. Atherosclerosis is mainly linked to dysfunction in vascular endothelial cells and subendothelial accumulation of oxidized forms of LDL. In the present study, we investigated the role of myeloperoxidase oxidized LDL (Mox-LDL) in endothelial cell dysfunction. We studied the effect of proinflammatory Mox-LDL treatment on endothelial cell motility, a parameter essential for normal vascular processes such as angiogenesis and blood vessel repair. This is particularly important in the context of an atheroma plaque, where vascular wall integrity is affected and interference with its repair could contribute to progression of the disease. We investigated in vitro the effect of Mox-LDL on endothelial cells angiogenic properties and we also studied the signalling pathways that could be affected by analysing Mox-LDL effect on the expression of angiogenesis-related genes. We report that Mox-LDL inhibits endothelial cell motility and tubulogenesis through an increase in miR-22 and heme oxygenase 1 expression. Our in vitro data indicate that Mox-LDL interferes with parameters associated with angiogenesis. They suggest that high LDL levels in patients would impair their endothelial cell capacity to cope with a damaged endothelium contributing negatively to the progression of the atheroma plaque.

Segmentation of the thrombus of giant intracranial aneurysms from CT angiography scans with lattice Boltzmann method.

Computed Tomography Angiography (CTA) plays an essential role in the diagnosis, treatment evaluation, and monitoring of cerebral aneurysms. Segmentation of CTA medical images of giant intracranial aneurysms (GIA) provides quantitative measurements of thrombus and aneurysms geometrical characteristics allowing 3D reconstruction. In fact, GIA demonstrated neuroradiological features and propensity of partial or total spontaneous intra-aneurysmal thrombosis generating a thrombus. Despite intensive researches on medical image segmentation, aneurysm (Lumen, Thrombus, and Parent Blood Vessels) segmentation remains as a difficult problem that has not been yet resolved. In this paper, we proposed a Lattice Boltzmann Geodesic Active Contour Method (LBGM) for aneurysm segmentation in CTA images in order to estimate both the volumes of the thrombus and the aneurysm. Although the noise in the CTA images is very strong and the edges of the thrombus are not so different than the surrounding tissues, the aneurysms are segmented effectively. Based on these results, a method using a dome-neck aspect ratio (AR) parameter for the evaluation of the Spontaneous Thrombosis (ST) phenomena demonstrates the promising potentiality of this LBGM for clinical applications.

Estimation of the viscoelastic properties of vessel walls using a computational model and Doppler ultrasound.

Human arteries affected by atherosclerosis are characterized by altered wall viscoelastic properties. The possibility of noninvasively assessing arterial viscoelasticity in vivo would significantly contribute to the early diagnosis and prevention of this disease. This paper presents a noniterative technique to estimate the viscoelastic parameters of a vascular wall Zener model. The approach requires the simultaneous measurement of flow variations and wall displacements, which can be provided by suitable ultrasound Doppler instruments. Viscoelastic parameters are estimated by fitting the theoretical constitutive equations to the experimental measurements using an ARMA parameter approach. The accuracy and sensitivity of the proposed method are tested using reference data generated by numerical simulations of arterial pulsation in which the physiological conditions and the viscoelastic parameters of the model can be suitably varied. The estimated values quantitatively agree with the reference values, showing that the only parameter affected by changing the physiological conditions is viscosity, whose relative error was about 27% even when a poor signal-to-noise ratio is simulated. Finally, the feasibility of the method is illustrated through three measurements made at different flow regimes on a cylindrical vessel phantom, yielding a parameter mean estimation error of 25%.

Noninvasive Young's modulus evaluation of tissues surrounding pulsatile vessels using ultrasound Doppler measurement.

This paper presents an indirect approach to estimating the mechanical properties of tissues surrounding the arterial vessels using ultrasound (US) Doppler measurements combined with an inverse problem-solving method. The geometry of the structure and the dynamic behavior of the inner fluid are first evaluated using a novel dual-beam US system. A numerical phantom associated with a parametric finite element simulator that calculates the hydrodynamic pressure and the displacement on the walls' boundaries is then built. The simulation results are iteratively compared to the US measurement results to deduce the value of the unknown parameters, i.e., the Young's modulus and the pressure resulting from the downstream load. The feasibility of the proposed approach was experimentally tested in vitro using a phantom composed of a latex tube surrounded by a cryogel tissue-mimicking material.