Modeling and Computational Comparison of the Displacement Forces Exerted between the AFX Unibody Aortic Stent Graft and its Hybrid Combination with a Nitinol-based Proximal Aortic Cuff.

BACKGROUND: The bifurcated AFX (Endologix, Inc, Irvine, CA, USA) aortic stent-graft is the sole unibody endograft for the management of Abdominal Aortic Aneurysms (AAA). In order to improve the AFX central sealing and clinical efficacy in challenging cases, a replacement of the central chromium-cobaltium AFX extension with a Nitinol-based proximal aortic cuff has been suggested. Yet, comparative data regarding the hemodynamic performance of this design is missing. Aim of this study was to compare the displacement forces (DF) acting on the hybrid AFX-Endurant design, with the classic AFX and Endurant endografts, in angulated and non-angulated cases based on patient-specific Computational Fluid Dynamics (CFD) simulations. METHODS: 3D endograft models of 11 treated AAA cases were reconstructed from Computed Tomography Angiography (CTA) imaging data: 5 cases of AFX, 3 cases of the combination AFX-Endurant and 3 cases of the classic Endurant design. The DF on the main-body, the iliac limbs, and the entire stent-graft was calculated by processing the velocity and pressure fields generated by pulsatile CFD simulations. RESULTS: The range of total DF (acting on the whole endograft structure) in the AFX, hybrid AFX-Endurant and Endurant group was 2.5-5.2N, 2.0-5.9N and 1.9-2.9N respectively, with the maximum total DF being lower for Endurant. The DF on the main-body of the classic and hybrid AFX cases were higher than the right and left iliac limbs (2.5-4.9N vs. 0.6-5.3N and 0.7-3.6N respectively). Conversely, the DF on the main-body of the Endurant cases was comparable to the force exerted on the right and left limbs. When separating the cases with respect to their neck angulation, the DF on all endograft parts (main-body, limbs) and on the endograft as a whole were lower for the hybrid AFX-Endurant group compared to the classic AFX and Endurant groups, for cases with almost straight neck. CONCLUSION: The off-label use of the hybrid AFX-Endurant stent-graft does not seem superior to the conventional AFX or Endurant endografts in angulated cases but was associated with lower DF than AFX or Endurant in non-angulated cases. The clinical value and utility of these findings remain to be elucidated.

Endograft Specific Haemodynamics After Endovascular Aneurysm Repair: Flow Characteristics of Four Stent Graft Systems.

OBJECTIVES: The implication of haemodynamics in the occurrence of complications after endovascular aneurysm repair (EVAR) has been raised in the literature. Different aortic stent graft configurations may lead to different haemodynamic properties. The current study deals with the post-operative haemodynamic variability between four stent graft systems with different structure, material, and type of fixation. METHODS: Computed tomography data of 32 patients were used, equally distributed among the four endograft groups, namely the AFX, Endurant, Excluder, and Nellix. Velocity, wall shear stress (WSS), and helicity statistics were calculated, in regions around the flow division where disturbances are expected. The haemodynamic data were compared between and within the groups. RESULTS: The morphology of AAAs pre-operatively did not vary significantly among the four groups. Before the flow division, lowest velocity was observed in Endurant cases and highest in Nellix cases. Endurant induced the lowest peak WSS and Nellix the highest (p = .03). The helicity levels were low in AFX and Nellix cases and high in Endurant and Excluder cases. After the flow division, the trend in the results was preserved. Nellix induced the highest velocity and WSS, followed closely by Excluder and AFX. There was a significant increase of helicity before and after flow division in AFX (p <0.001, R2 = 0.09) and Nellix (p <0.001) cases. CONCLUSIONS: It has been shown that different types of endografts induce variable haemodynamic conditions around the flow division. The parallel limb structure, featured by Nellix, seems to induce favourable flow conditions in terms of velocity and WSS, while helical flow before the flow division is suppressed. High WSS is generally considered to be a desirable flow characteristic in endovascular devices, whereas helicity extremes (very low or high) are potentially a negative sign. Endurant, with the stiffer material and the short neck structure, was associated with the lowest blood velocity and WSS values but preserved high helicity levels. The AFX and Excluder, which include the same material, induced similar haemodynamic conditions.

Abdominal Aortic Aneurysm Endovascular Repair: Profiling Postimplantation Morphometry and Hemodynamics With Image-Based Computational Fluid Dynamics.

Endovascular aneurysm repair (EVAR) has disseminated rapidly as an alternative to open surgical repair for the treatment of abdominal aortic aneurysms (AAAs), because of its reduced invasiveness, low mortality, and morbidity rate. The effectiveness of the endovascular devices used in EVAR is always at question as postoperative adverse events can lead to re-intervention or to a possible fatal scenario for the circulatory system. Motivated by the assessment of the risks related to thrombus formation, here the impact of two different commercial endovascular grafts on local hemodynamics is explored through 20 image-based computational hemodynamic models of EVAR-treated patients (N = 10 per each endograft model). Hemodynamic features, susceptible to promote thrombus formation, such as flow separation and recirculation, are quantitatively assessed and compared with the local hemodynamics established in image-based infrarenal abdominal aortic models of healthy subjects (N = 10). Moreover, the durability of endovascular devices is investigated analyzing the displacement forces (DFs) acting on them. The hemodynamic analysis is complemented by a geometrical characterization of the EVAR-induced reshaping of the infrarenal abdominal aortic vascular region. The findings of this study indicate that (1) the clinically observed propensity to thrombus formation in devices used in EVAR strategies can be explained in terms of local hemodynamics by means of image-based computational hemodynamics approach; (2) reportedly prothrombotic hemodynamic structures are strongly associated with the geometry of the aortoiliac tract postoperatively; and (3) DFs are associated with cross-sectional area of the aortoiliac tract postoperatively. In perspective, our study suggests that future clinical followup studies could include a geometric analysis of the region of the implant, monitoring shape variations that can lead to hemodynamic disturbances of clinical significance.

Studying the interaction of stent-grafts and treated abdominal aortic aneurysms: time to move caudally!

Since the advent of endovascular repair of aortic aneurysms (EVAR), clinical focus has been on preventing loss of sealing at the level of the infrarenal neck, which leads to type I endoleak and repressurization of the aneurysm sac. Enhanced mechanisms for central fixation and seal have consequently lowered the incidence of migration and endoleaks. However, endograft limb thrombosis and its causal mechanisms have not been addressed adequately in the literature. This article reviews the pathophysiological mechanisms associated with limb thrombosis in order to facilitate better clinical judgment to prevent iliac adverse effects.

Thromboresistance comparison of the HeartMate II ventricular assist device with the device thrombogenicity emulation- optimized HeartAssist 5 VAD.

Approximately 7.5 × 106 patients in the US currently suffer from end-stage heart failure. The FDA has recently approved the designations of the Thoratec HeartMate II ventricular assist device (VAD) for both bridge-to-transplant and destination therapy (DT) due to its mechanical durability and improved hemodynamics. However, incidence of pump thrombosis and thromboembolic events remains high, and the life-long complex pharmacological regimens are mandatory in its VAD recipients. We have previously successfully applied our device thrombogenicity emulation (DTE) methodology for optimizing device thromboresistance to the Micromed Debakey VAD, and demonstrated that optimizing device features implicated in exposing blood to elevated shear stresses and exposure times significantly reduces shear-induced platelet activation and significantly improves the device thromboresistance. In the present study, we compared the thrombogenicity of the FDA-approved HeartMate II VAD with the DTE-optimized Debakey VAD (now labeled HeartAssist 5). With quantitative probability density functions of the stress accumulation along large number of platelet trajectories within each device which were extracted from numerical flow simulations in each device, and through measurements of platelet activation rates in recirculation flow loops, we specifically show that: (a) Platelets flowing through the HeartAssist 5 are exposed to significantly lower stress accumulation that lead to platelet activation than the HeartMate II, especially at the impeller-shroud gap regions (b) Thrombus formation patterns observed in the HeartMate II are absent in the HeartAssist 5 (c) Platelet activation rates (PAR) measured in vitro with the VADs mounted in recirculation flow-loops show a 2.5-fold significantly higher PAR value for the HeartMate II. This head to head thrombogenic performance comparative study of the two VADs, one optimized with the DTE methodology and one FDA-approved, demonstrates the efficacy of the DTE methodology for drastically reducing the device thrombogenic potential, validating the need for a robust in silico/in vitro optimization methodology for improving cardiovascular devices thromboresistance.

Loss of dopamine D2 receptors induces atrophy in the temporal and parietal cortices and the caudal thalamus of ethanol-consuming mice.

BACKGROUND: The need of an animal model of alcoholism becomes apparent when we consider the genetic diversity of the human populations, an example being dopamine D2 receptor (DRD2) expression levels. Research suggests that low DRD2 availability is associated with alcohol abuse, while higher DRD2 levels may be protective against alcoholism. This study aims to establish whether (i) the ethanol-consuming mouse is a suitable model of alcohol-induced brain atrophy and (ii) DRD2 protect the brain against alcohol toxicity. METHODS: Adult Drd2+/+ and Drd2-/- mice drank either water or 20% ethanol solution for 6 months. At the end of the treatment period, the mice underwent magnetic resonance (MR) imaging under anesthesia. MR images were registered to a common space, and regions of interest were manually segmented. RESULTS: We found that chronic ethanol intake induced a decrease in the volume of the temporal and parietal cortices as well as the caudal thalamus in Drd2-/- mice. CONCLUSIONS: The result suggests that (i) normal DRD2 expression has a protective role against alcohol-induced brain atrophy and (ii) in the absence of Drd2 expression, prolonged ethanol intake reproduces a distinct feature of human brain pathology in alcoholism, the atrophy of the temporal and parietal cortices.

Fluid structure interaction with contact surface methodology for evaluation of endovascular carotid implants for drug-resistant hypertension treatment.

Drug-resistant hypertensive patients may be treated by mechanical stimulation of stretch-sensitive baroreceptors located in the sinus of carotid arteries. To evaluate the efficacy of endovascular devices to stretch the carotid sinus such that the induced strain might trigger baroreceptors to increase action potential firing rate and thereby reduce systemic blood pressure, numerical simulations were conducted of devices deployed in subject-specific carotid models. Two models were chosen--a typical physiologic carotid and a diminutive atypical physiologic model representing a clinically worst case scenario--to evaluate the effects of device deployment in normal and extreme cases, respectively. Based on the anatomical dimensions of the carotids, two different device sizes were chosen out of five total device sizes available. A fluid structure interaction (FSI) simulation methodology with contact surface between the device and the arterial wall was implemented for resolving the stresses and strains induced by device deployment. Results indicate that device deployment in the carotid sinus of the physiologic model induces an increase of 2.5% and 7.5% in circumferential and longitudinal wall stretch, respectively, and a maximum of 54% increase in von Mises arterial stress at the sinus wall baroreceptor region. The second device, deployed in the diminutive carotid model, induces an increase of 6% in both circumferential and longitudinal stretch and a 50% maximum increase in von Mises stress at the sinus wall baroreceptor region. Device deployment has a minimal effect on blood-flow patterns, indicating that it does not adversely affect carotid bifurcation hemodynamics in the physiologic model. In the smaller carotid model, deployment of the device lowers wall shear stress at sinus by 16% while accelerating flow entering the external carotid artery branch. Our FSI simulations of carotid arteries with deployed device show that the device induces localized increase in wall stretch at the sinus, suggesting that this will activate baroreceptors and subsequently may control hypertension in drug-resistant hypertensive patients, with no consequential deleterious effects on the carotid sinus hemodynamics.

Relationship of Effective Circulating Volume with Sublingual Red Blood Cell Velocity and Microvessel Pressure Difference: A Clinical Investigation and Computational Fluid Dynamics Modeling.

The characteristics of physiologic hemodynamic coherence are not well-investigated. We examined the physiological relationship between circulating blood volume, sublingual microcirculatory perfusion, and tissue oxygenation in anesthetized individuals with steady-state physiology. We assessed the correlation of mean circulatory filling pressure analogue (Pmca) with sublingual microcirculatory perfusion and red blood cell (RBC) velocity using SDF+ imaging and a modified optical flow-based algorithm. We also reconstructed the 2D microvessels and applied computational fluid dynamics (CFD) to evaluate the correlation of Pmca and RBC velocity with the obtained pressure and velocity fields in microvessels from CFD (pressure difference, (Δp)). Twenty adults with a median age of 39.5 years (IQR 35.5−44.5) were included in the study. Sublingual velocity distributions were similar and followed a log-normal distribution. A constant Pmca value of 14 mmHg was observed in all individuals with sublingual RBC velocity 6−24 µm s−1, while a Pmca < 14 mmHg was observed in those with RBC velocity > 24 µm s−1. When Pmca ranged between 11 mmHg and 15 mmHg, Δp fluctuated between 0.02 Pa and 0.1 Pa. In conclusion, the intact regulatory mechanisms maintain a physiological coupling between systemic hemodynamics, sublingual microcirculatory perfusion, and tissue oxygenation when Pmca is 14 mmHg.

Computational Fluid Dynamic Analysis Supports the Hemodynamic Stability of Hybrid Combinations With the AFX Bifurcate and Nitinol-Based Proximal Segments in Solutions of Failed Endovascular Aneurysm Repair.

Hybrid endograft combinations of two or more different types of covered stents are rarely reported to treat complex abdominal aortic aneurysm cases or primary and secondary endoleaks. Clinical and laboratory data regarding the clinical efficacy and mechanical stability of such combinations are lacking. Based on a recently published case report, we describe and comment on the hemodynamic profile of a representative simulated hybrid case of AFX and Nitinol-based proximal cuff and support the stability of this combination in non-angulated cases.

Remodeling effects of carotid artery stenting versus endarterectomy with patch angioplasty in terms of morphology and hemodynamics.

BACKGROUND: Carotid endarterectomy (CEA) remains the first-line treatment option of symptomatic and asymptomatic carotid stenosis, while stenting (CAS) is reserved for selected patients at high surgical risk. Here, we compare the vascular remodeling process in CEA- and CAS-treated patients with respect to morphological and hemodynamic features, because of their possible engagement in carotid atherosclerosis. METHODS: Twelve (12) patients were included, half with patched CEA and half with CAS. Pre- and post-operative 3D image-based models of the carotid bifurcation were anatomically characterized in terms of flare, tortuosity, and curvature. Individual computational fluid dynamics simulations allowed to quantify the postoperative hemodynamic milieu in terms of (1) wall shear stress and (2) helical flow. RESULTS: Carotid flare increased in all cases, but a more marked increase emerged after CEA compared to CAS. Tortuosity and curvature increased after CEA but decreased after CAS. CEA patients presented with significantly higher postoperative tortuosity than CAS patients. CEA was associated with a worse (non-statistically significant) score in all flow disturbance indicators vs. CAS. CONCLUSION: The increased flare and tortuosity of the carotid bifurcation after CEA vs. CAS is a marked difference in the vascular remodeling process between the two modalities. CAS seems to induce a less pro-restenosis hemodynamic environment compared to CEA. The emerged differences stimulate further analysis on a larger cohort with long-term outcomes, to shed light on the clinical impact of the observations.

A mathematical model of blood, cerebrospinal fluid and brain dynamics.

Using first principles of fluid and solid mechanics a comprehensive model of human intracranial dynamics is proposed. Blood, cerebrospinal fluid (CSF) and brain parenchyma as well as the spinal canal are included. The compartmental model predicts intracranial pressure gradients, blood and CSF flows and displacements in normal and pathological conditions like communicating hydrocephalus. The system of differential equations of first principles conservation balances is discretized and solved numerically. Fluid-solid interactions of the brain parenchyma with cerebral blood and CSF are calculated. The model provides the transitions from normal dynamics to the diseased state during the onset of communicating hydrocephalus. Predicted results were compared with physiological data from Cine phase-contrast magnetic resonance imaging to verify the dynamic model. Bolus injections into the CSF are simulated in the model and found to agree with clinical measurements.

In-stent graft helical flow intensity reduces the risk of migration after endovascular aortic repair.

During the last years endovascular aneurysm repair (EVAR) became the elective treatment for abdominal aortic aneurysms (AAAs) thanks to lower mortality and morbidity rates than open surgery. In face of these advantages, stent-graft performances are still clinically suboptimal. In particular, post-surgical complications derive from device migration as a consequence of the hemodynamic forces acting on the endograft. In this regard, while the importance of hemodynamic surface forces is well recognized, the role of the in-stent flow is still unclear. Here we hypothesize that in-stent helical blood flow patterns might influence the distribution of the displacement forces (DFs) acting on the stent-graft and, ultimately, the risk of stent migration. To test this hypothesis, the hemodynamics of 20 post-EVAR models of patients treated with two different commercial endografts was analyzed using computational hemodynamics. The main findings of the study indicate that: (1) helical flow intensity decreases the risk of endograft migration, as given by an inverse correlation between helicity intensity (h2) and time-averaged displacement forces (TADFs) (p < 0.05); (2) unbalanced counter-rotating helical structures in the legs of the device contribute, in particular along the systole, to significantly suppress TADFs (p < 0.01); (3) as expected, helical flow intensity is positively correlated with pressure drop and resistance to flow (p < 0.001). The findings of this study suggest that a design strategy promoting in-stent helical flow structures could contribute to minimize the risk of migration of implanted EVAR devices.

Haemodynamic performance of AFX and Nellix endografts: a computational fluid dynamics study.

OBJECTIVES: The objective of this study is to analyse the flow conditions in the AFX and Nellix endografts (EGs) accounting for their postimplantation configuration in patients with an endovascular aneurysm repair-treated abdominal aortic aneurysm. METHODS: We reconstructed post-endovascular aneurysm repair computed tomography scans of patients treated with an AFX or Nellix EG creating post-implantation EG models. We examined 16 patients, 8 in each group. The blood flow properties were obtained by computational fluid dynamics simulations and were subsequently compared with physiological infrarenal blood flow properties measured in 5 healthy subjects. Specifically, pressure drop, maximum velocity and wall shear stress were measured at peak systole and mean helicity at mid-diastole. RESULTS: Our statistical analyses showed that the haemodynamic properties in both control regions did not vary statistically after the implantation of either the AFX or the Nellix EG, except for helicity that was significantly lower in the abdominal part of the Nellix EG compared with the expected physiological measurement. Regardless of the overall blood flow restoration, it is important to note that low pressure drop was detected along the limbs of the AFX and suppressed blood helical motion was detected at the entrance of the Nellix device. CONCLUSIONS: It is observed from the results that the AFX EG has achieved absolute restoration of blood flow after endovascular aneurysm repair, although the development of secondary flow in the upper part of the EG and the low pressure drop in its limbs should be acknowledged. The Nellix EG also seems to be haemodynamically efficient. However, the suppression of helical flow before blood enters the device might raise concerns about its clinical application.

Cerebrospinal fluid flow in the normal and hydrocephalic human brain.

Advances in magnetic resonance (MR) imaging techniques enable the accurate measurements of cerebrospinal fluid (CSF) flow in the human brain. In addition, image reconstruction tools facilitate the collection of patient-specific brain geometry data such as the exact dimensions of the ventricular and subarachnoidal spaces (SAS) as well as the computer-aided reconstruction of the CSF-filled spaces. The solution of the conservation of CSF mass and momentum balances over a finite computational mesh obtained from the MR images predict the patients' CSF flow and pressure field. Advanced image reconstruction tools used in conjunction with first principles of fluid mechanics allow an accurate verification of the CSF flow patters for individual patients. This paper presents a detailed analysis of pulsatile CSF flow and pressure dynamics in a normal and hydrocephalic patient. Experimental CSF flow measurements and computational results of flow and pressure fields in the ventricular system, the SAS and brain parenchyma are presented. The pulsating CSF motion is explored in normal and pathological conditions of communicating hydrocephalus. This paper predicts small transmantle pressure differences between lateral ventricles and SASs (approximately 10 Pa). The transmantle pressure between ventricles and SAS remains small even in the hydrocephalic patient (approximately 30 Pa), but the ICP pulsatility increases by a factor of four. The computational fluid dynamics (CFD) results of the predicted CSF flow velocities are in good agreement with Cine MRI measurements. Differences between the predicted and observed CSF flow velocities in the prepontine area point towards complex brain-CSF interactions. The paper presents the complete computational model to predict the pulsatile CSF flow in the cranial cavity.

Comparison of physiological and post-endovascular aneurysm repair infrarenal blood flow.

Endovascular aneurysm repair (EVAR) of abdominal aortic aneurysms results in redirection of blood through the deployed endograft (EG). Even though EVAR is clinically effective, the absolute flow restoration is not warranted. Our purpose was to compare the physiological with the post-EVAR infrarenal flow conditions. We developed patient-specific models based on computed tomography data of five healthy volunteers and ten patients treated with the Endurant® stent-graft system. Wall shear stress (WSS), helicity, pressure and velocity fields were calculated using computational fluid dynamics. The results showed a decrease of peak WSS on the part of the EG that resides in the iliac arteries, compared to the physiological value (p = 0.01). At the abdominal part, the average helicity seems to increase after EVAR, while at the iliac arteries part, the intensity of helical flow seems physiological. Pressure drop and peak velocity in the iliac arteries part are lower than the physiological values (p = 0.04). The comparison revealed that most hemodynamic properties converge to normal levels at the abdominal part whereas statistically significant variations were observed in the iliac arteries part. The delineation of the differences between physiological and postoperative flow data could pave the way for the improvement of EG designs.

HRI usability evaluation of interaction modes for a teleoperated agricultural robotic sprayer.

Teleoperation of an agricultural robotic system requires effective and efficient human-robot interaction. This paper investigates the usability of different interaction modes for agricultural robot teleoperation. Specifically, we examined the overall influence of two types of output devices (PC screen, head mounted display), two types of peripheral vision support mechanisms (single view, multiple views), and two types of control input devices (PC keyboard, PS3 gamepad) on observed and perceived usability of a teleoperated agricultural sprayer. A modular user interface for teleoperating an agricultural robot sprayer was constructed and field-tested. Evaluation included eight interaction modes: the different combinations of the 3 factors. Thirty representative participants used each interaction mode to navigate the robot along a vineyard and spray grape clusters based on a 2 × 2 × 2 repeated measures experimental design. Objective metrics of the effectiveness and efficiency of the human-robot collaboration were collected. Participants also completed questionnaires related to their user experience with the system in each interaction mode. Results show that the most important factor for human-robot interface usability is the number and placement of views. The type of robot control input device was also a significant factor in certain dependents, whereas the effect of the screen output type was only significant on the participants' perceived workload index. Specific recommendations for mobile field robot teleoperation to improve HRI awareness for the agricultural spraying task are presented.

Effect of macroscale formation of intraluminal thrombus on blood flow in abdominal aortic aneurysms.

A mathematical approach of blood flow within an abdominal aortic aneurysm (AAA) with intraluminal thrombus (ILT) is presented. The macroscale formation of ILT is modeled as a growing porous medium with variable porosity and permeability according to values proposed in the literature. The model outlines the effect of a porous ILT on blood flow in AAAs. The numerical solution is obtained by employing a structured computational mesh of an idealized fusiform AAA geometry and applying the Galerkin weighted residual method in generalized curvilinear coordinates. Results on velocity and pressure fields of independent cases with and without ILT are presented and discussed. The vortices that develop within the aneurysmal cavity are studied and visualized as ILT becomes more condensed. From a mechanistic point of view, the reduction of bulge pressure, as ILT is thickening, supports the observation that ILT could protect the AAA from a possible rupture. The model also predicts a relocation of the maximum pressure region toward the zone proximal to the neck of the aneurysm. However, other mechanisms, such as the gradual wall weakening that usually accompany AAA and ILT formation, which are not included in this study, may offset this effect.

Pulsatile cerebrospinal fluid dynamics in the human brain.

Disturbances of the cerebrospinal fluid (CSF) flow in the brain can lead to hydrocephalus, a condition affecting thousands of people annually in the US. Considerable controversy exists about fluid and pressure dynamics, and about how the brain responds to changes in flow patterns and compression in hydrocephalus. This paper presents a new model based on the first principles of fluid mechanics. This model of fluid-structure interactions predicts flows and pressures throughout the brain's ventricular pathways consistent with both animal intracranial pressure (ICP) measurements and human CINE phase-contrast magnetic resonance imaging data. The computations provide approximations of the tissue deformations of the brain parenchyma. The model also quantifies the pulsatile CSF motion including flow reversal in the aqueduct as well as the changes in ICPs due to brain tissue compression. It does not require the existence of large transmural pressure differences as the force for ventricular expansion. Finally, the new model gives an explanation of communicating hydrocephalus and the phenomenon of asymmetric hydrocephalus.