Vascular dysfunction in the pathogenesis of Alzheimer's disease--A review of endothelium-mediated mechanisms and ensuing vicious circles.

Late-onset dementia is a major health concern in the ageing population. Alzheimer's disease (AD) accounts for the largest proportion (65-70%) of dementia cases in the older population. Despite considerable research effort, the pathogenesis of late-onset AD remains unclear. Substantial evidence suggests that the neurodegenerative process is initiated by chronic cerebral hypoperfusion (CCH) caused by ageing and cardiovascular conditions. CCH causes reduced oxygen, glucose and other nutrient supply to the brain, with direct damage not only to the parenchymal cells, but also to the blood-brain barrier (BBB), a key mediator of cerebral homeostasis. BBB dysfunction mediates the indirect neurotoxic effects of CCH by promoting oxidative stress, inflammation, paracellular permeability, and dysregulation of nitric oxide, a key regulator of regional blood flow. As such, BBB dysfunction mediates a vicious circle in which cerebral perfusion is reduced further and the neurodegenerative process is accelerated. Endothelial interaction with pericytes and astrocytes could also play a role in the process. Reciprocal interactions between vascular dysfunction and neurodegeneration could further contribute to the development of the disease. A comprehensive overview of the complex scenario of interacting endothelium-mediated processes is currently lacking, and could prospectively contribute to the identification of adequate therapeutic interventions. This study reviews the current literature of in vitro and ex vivo studies on endothelium-mediated mechanisms underlying vascular dysfunction in AD pathogenesis, with the aim of presenting a comprehensive overview of the complex network of causative relationships. Particular emphasis is given to vicious circles which can accelerate the process of neurovascular degeneration.

Development of two electronic bladder diaries: a patient and healthcare professionals pilot study.

AIMS: Assess patients' preferences in a pilot crossover study of two different electronic voiding diaries against a standard paper diary. Assess urological health professional (HP) opinions on the electronic bladder diary reporting system. METHODS: Two different electronic diaries were developed: (1) electronically read diary-a card with predefined slots read by a card reader and (2) e-diary-a handheld touch screen device. Data uploaded from either electronic diary produced an electronic report. We recruited 22 patients split into two cohorts for each electronic diary, 11 completed each type of electronic diary for 3 days either preceded or followed by a standard paper diary for 3 days. Both diaries were completed on the 7th day. Patients' perceptions of both diaries were recorded using a standardized questionnaire. A HP study recruited 22 urologists who were given the paper diary and the electronic reports. Time taken for analysis was recorded along with accuracy and HP preferences. RESULTS: The majority of patients (82%) preferred the e-diary and only 1/11 found it difficult to use. Patients had the same preference for the electronically read diary as the paper diary. The paper diary took 66% longer to analyze than the electronic report (P < 0.001) and was analyzed with an accuracy of 58% compared to 100%. Slightly more HP (9%) preferred the electronic report to the paper diary. CONCLUSIONS: This proposed e-diary with its intuitive interface has overcome previous deficiencies in electronic diaries with most patients finding the format user-friendly. Electronic reports make analysis and interpretation by HP quicker and more accurate.

An In Silico Modelling Approach to Predict Hemodynamic Outcomes in Diabetic and Hypertensive Kidney Disease.

Early diagnosis of kidney disease remains an unmet clinical challenge, preventing timely and effective intervention. Diabetes and hypertension are two main causes of kidney disease, can often appear together, and can only be distinguished by invasive biopsy. In this study, we developed a modelling approach to simulate blood velocity, volumetric flow rate, and pressure wave propagation in arterial networks of ageing, diabetic, and hypertensive virtual populations. The model was validated by comparing our predictions for pressure, volumetric flow rate and waveform-derived indexes with in vivo data on ageing populations from the literature. The model simulated the effects of kidney disease, and was calibrated to align quantitatively with in vivo data on diabetic and hypertensive nephropathy from the literature. Our study identified some potential biomarkers extracted from renal blood flow rate and flow pulsatility. For typical patient age groups, resistive index values were 0.69 (SD 0.05) and 0.74 (SD 0.02) in the early and severe stages of diabetic nephropathy, respectively. Similar trends were observed in the same stages of hypertensive nephropathy, with a range from 0.65 (SD 0.07) to 0.73 (SD 0.05), respectively. Mean renal blood flow rate through a single diseased kidney ranged from 329 (SD 40, early) to 317 (SD 38, severe) ml/min in diabetic nephropathy and 443 (SD 54, early) to 388 (SD 47, severe) ml/min in hypertensive nephropathy, showing potential as a biomarker for early diagnosis of kidney disease. This modelling approach demonstrated its potential application in informing biomarker identification and facilitating the setup of clinical trials.

A multiscale computational framework to evaluate flow alterations during mechanical thrombectomy for treatment of ischaemic stroke.

The treatment of ischaemic stroke increasingly relies upon endovascular procedures known as mechanical thrombectomy (MT), which consists in capturing and removing the clot with a catheter-guided stent while at the same time applying external aspiration with the aim of reducing haemodynamic loads during retrieval. However, uniform consensus on procedural parameters such as the use of balloon guide catheters (BGC) to provide proximal flow control, or the position of the aspiration catheter is still lacking. Ultimately the decision is left to the clinician performing the operation, and it is difficult to predict how these treatment options might influence clinical outcome. In this study we present a multiscale computational framework to simulate MT procedures. The developed framework can provide quantitative assessment of clinically relevant quantities such as flow in the retrieval path and can be used to find the optimal procedural parameters that are most likely to result in a favorable clinical outcome. The results show the advantage of using BGC during MT and indicate small differences between positioning the aspiration catheter in proximal or distal locations. The framework has significant potential for future expansions and applications to other surgical treatments.

Determining Clinically-Viable Biomarkers for Ischaemic Stroke Through a Mechanistic and Machine Learning Approach.

Assessment of distal cerebral perfusion after ischaemic stroke is currently only possible through expensive and time-consuming imaging procedures which require the injection of a contrast medium. Alternative approaches that could indicate earlier the impact of blood flow occlusion on distal cerebral perfusion are currently lacking. The aim of this study was to identify novel biomarkers suitable for clinical implementation using less invasive diagnostic techniques such as Transcranial Doppler (TCD). We used 1D modelling to simulate pre- and post-stroke velocity and flow wave propagation in a typical arterial network, and Sobol's sensitivity analysis, supported by the use of Gaussian process emulators, to identify biomarkers linked to cerebral perfusion. We showed that values of pulsatility index of the right anterior cerebral artery > 1.6 are associated with poor perfusion and may require immediate intervention. Three additional biomarkers with similar behaviour, all related to pulsatility indices, were identified. These results suggest that flow pulsatility measured at specific locations could be used to effectively estimate distal cerebral perfusion rates, and ultimately improve clinical diagnosis and management of ischaemic stroke.

Integrating particle tracking with computational fluid dynamics to assess haemodynamic perturbation by coronary artery stents.

AIMS: Coronary artery stents have profound effects on arterial function by altering fluid flow mass transport and wall shear stress. We developed a new integrated methodology to analyse the effects of stents on mass transport and shear stress to inform the design of haemodynamically-favourable stents. METHODS AND RESULTS: Stents were deployed in model vessels followed by tracking of fluorescent particles under flow. Parallel analyses involved high-resolution micro-computed tomography scanning followed by computational fluid dynamics simulations to assess wall shear stress distribution. Several stent designs were analysed to assess whether the workflow was robust for diverse strut geometries. Stents had striking effects on fluid flow streamlines, flow separation or funnelling, and the accumulation of particles at areas of complex geometry that were tightly coupled to stent shape. CFD analysis revealed that stents had a major influence on wall shear stress magnitude, direction and distribution and this was highly sensitive to geometry. CONCLUSIONS: Integration of particle tracking with CFD allows assessment of fluid flow and shear stress in stented arteries in unprecedented detail. Deleterious flow perturbations, such as accumulation of particles at struts and non-physiological shear stress, were highly sensitive to individual stent geometry. Novel designs for stents should be tested for mass transport and shear stress which are important effectors of vascular health and repair.

Three-dimensional morphological analysis of intracranial aneurysms: a fully automated method for aneurysm sac isolation and quantification.

PURPOSE: Morphological descriptors are practical and essential biomarkers for diagnosis and treatment selection for intracranial aneurysm management according to the current guidelines in use. Nevertheless, relatively little work has been dedicated to improve the three-dimensional quantification of aneurysmal morphology, to automate the analysis, and hence to reduce the inherent intra and interobserver variability of manual analysis. In this paper we propose a methodology for the automated isolation and morphological quantification of saccular intracranial aneurysms based on a 3D representation of the vascular anatomy. METHOD: This methodology is based on the analysis of the vasculature skeleton's topology and the subsequent application of concepts from deformable cylinders. These are expanded inside the parent vessel to identify different regions and discriminate the aneurysm sac from the parent vessel wall. The method renders as output the surface representation of the isolated aneurysm sac, which can then be quantified automatically. The proposed method provides the means for identifying the aneurysm neck in a deterministic way. The results obtained by the method were assessed in two ways: they were compared to manual measurements obtained by three independent clinicians as normally done during diagnosis and to automated measurements from manually isolated aneurysms by three independent operators, nonclinicians, experts in vascular image analysis. All the measurements were obtained using in-house tools. The results were qualitatively and quantitatively compared for a set of the saccular intracranial aneurysms (n = 26). RESULTS: Measurements performed on a synthetic phantom showed that the automated measurements obtained from manually isolated aneurysms where the most accurate. The differences between the measurements obtained by the clinicians and the manually isolated sacs were statistically significant (neck width: p <0.001, sac height: p = 0.002). When comparing clinicians' measurements to automatically isolated sacs, only the differences for the neck width were significant (neck width: p <0.001, sac height: p = 0.95). However, the correlation and agreement between the measurements obtained from manually and automatically isolated aneurysms for the neck width: p = 0.43 and sac height: p = 0.95 where found. CONCLUSIONS: The proposed method allows the automated isolation of intracranial aneurysms, eliminating the interobserver variability. In average, the computational cost of the automated method (2 min 36 s) was similar to the time required by a manual operator (measurement by clinicians: 2 min 51 s, manual isolation: 2 min 21 s) but eliminating human interaction. The automated measurements are irrespective of the viewing angle, eliminating any bias or difference between the observer criteria. Finally, the qualitative assessment of the results showed acceptable agreement between manually and automatically isolated aneurysms.

Role of distal cerebral vasculature in vessel constriction after aneurysm treatment with flow diverter stents.

BACKGROUND: Treatment of intracranial aneurysms with flow diverter stent (FDS) procedures can lead to caliber changes of jailed vessels. The reason some branches remain unchanged and others are affected by narrowing remains unknown. OBJECTIVE: To investigate the influence of resistance to flow from distal vasculature on stent-induced hemodynamic modifications affecting bifurcating vessels. MATERIALS AND METHODS: Radiological images and demographic data were acquired for 142 aneurysms treated with a FDS. Vascular resistance was estimated from patient-specific anatomic data. Correlation analysis was used to identify correspondence between anatomic data and clinical outcome. Computational Fluid Dynamics was performed on a typical patient-specific model to evaluate the influence of FDS on flow. Relevant hemodynamic variables along the bifurcating vessels were quantitatively analyzed and validated with in vitro data obtained using power Doppler ultrasound. RESULTS: Statistical analysis showed a correlation between clinical outcome and FDS resistance to flow considering overall jailed vessel vascular resistance (r=0.5, P<0.001). Computational predictions of blood flow showed that hemodynamics is minimally affected by FDS treatment in the ophthalmic artery. CONCLUSIONS: Jailed vessels are affected by narrowing when resistance to flow from the FDS constitutes a larger proportion of the overall vessel resistance to flow. This knowledge may contribute to better understanding of intracranial hemodynamics after a FDS procedure and reinforce indications for flow diversion in the treatment of intracranial aneurysms.

An engineering approach towards a more discrete and efficient urinary drainage system.

Modern urinary catheter-to-leg-bag systems suffer from a number of shortcomings. Drainage tubing of current urinary leg bags is perceived as unnecessarily bulky compared to the indwelling catheters to which it is connected, and catheter designs are prone to the formation of biofilms, leading ultimately to encrustation and blocking. We used analytical and experimental engineering methodologies, aligned with current international (International Standards Organisation) and European standards, to optimise drainage tube size and flow efficiency and characterise tube kinking behaviour. Using computational fluid dynamics, we studied the influence of modern Foley catheter design on urodynamics and explored its potential influence on biofilm formation and encrustation. Results indicate that tubing diameters could be reduced by 40%-50% and still satisfy current International Standards Organisation flow rate standards for leg bags; this might also reduce the likelihood of tube kinking. The computational study showed how current catheter design may promote the development of lower velocity recirculating flows and high shear in proximity of regions known to be affected by bacterial adhesion and biofilm formation. If confirmed, these findings will give manufacturers greater flexibility to develop less obtrusive and more encrustation-resistant products for end users.

Reversible Brain Edema Associated with Flow Diverter Stent Procedures: A Retrospective Single- Center Study to Evaluate Frequency, Clinical Evolution, and Possible Mechanism.

BACKGROUND: Hemorrhage and ischemia after flow diverter stent (FDS) procedures for intracranial aneurysms are the most common complications and have been extensively described. Temporary brain edema (TBE) is an unknown complication that could be associated with particular FDS procedures. OBJECTIVE: To estimate the frequency, clinical presentation, imaging findings, and possible mechanisms associating TBE with FDS. METHODS: Unruptured aneurysms treated with FDS implantation performed in our service from June 2015 to March 2018 were reviewed. Medical antecedents, endovascular procedure, clinical assessments before and after treatment, aneurysm characteristics, and image records were collected. Artery diameters of patients in whom TEB developed were also calculated to investigate any correlation between TBE and anatomic descriptors. RESULTS: A total of 179 FDS procedures in 176 patients were reviewed. Six patients (3.4%) presented with symptomatic TBE, and all TBE patients had undergone FDS implantation from the middle cerebral artery (MCA) to the internal carotid artery (ICA). A Pearson product-moment correlation coefficient (PPCC) found smaller MCA diameters and MCA/ICA ratios in these 6 patients (respectively PPCC = -0.619, P < 0.04; PPCC = -0.647, P < 0.03). Hemorrhagic and ischemic complications were less frequent than TBE (2.3% and 1.1% vs. 3.4%). CONCLUSIONS: TBE was more frequent than ischemic or hemorrhagic complications after FDS in this study. TBE seemed to be associated with a particular FDS positioning in small arteries, inducing flow changes and disruption of the blood-brain barrier.

Non-invasive Stenotic Renal Artery Haemodynamics by in silico Medicine.

Background: Measuring the extent to which renal artery stenosis (RAS) alters renal haemodynamics may permit precision medicine by physiologically guided revascularization. This currently requires invasive intra-arterial pressure measurement with associated risks and is rarely performed. The present proof-of-concept study investigates an in silico approach that uses computational fluid dynamic (CFD) modeling to non-invasively estimate renal artery haemodynamics from routine anatomical computed tomography (CT) imaging of RAS. Methods: We evaluated 10 patients with RAS by CT angiography. Intra-arterial renal haemodynamics were invasively measured by a transducing catheter under resting and hyperaemic conditions, calculating the translesional ratio of distal to proximal pressure (Pd/Pa). The diagnostic and quantitative accuracy of the CFD-derived virtual Pd/Pa ratio (vPd/Pa) was evaluated against the invasively measured Pd/Pa ratio (mPd/Pa). Results: Hyperaemic haemodynamics was infeasible and CT angiography in 4 patients had insufficient image resolution. Resting flow data is thus reported for 7 stenosed arteries from 6 patients (one patient had bilateral RAS). The comparison showed a mean difference of 0.015 (95% confidence intervals of ± 0.08), mean absolute error of 0.064, and a Pearson correlation coefficient of 0.6, with diagnostic accuracy for a physiologically significant Pd/Pa of ≤ 0.9 at 86%. Conclusion: We describe the first in silico estimation of renal artery haemodynamics from CT angiography in patients with RAS, showing it is feasible and diagnostically accurate. This provides a methodological framework for larger prospective studies to ultimately develop non-invasive precision medicine approaches for studies and interventions of RAS and resistant hypertension.

Bayesian sensitivity analysis of a 1D vascular model with Gaussian process emulators.

One-dimensional models of the cardiovascular system can capture the physics of pulse waves but involve many parameters. Since these may vary among individuals, patient-specific models are difficult to construct. Sensitivity analysis can be used to rank model parameters by their effect on outputs and to quantify how uncertainty in parameters influences output uncertainty. This type of analysis is often conducted with a Monte Carlo method, where large numbers of model runs are used to assess input-output relations. The aim of this study was to demonstrate the computational efficiency of variance-based sensitivity analysis of 1D vascular models using Gaussian process emulators, compared to a standard Monte Carlo approach. The methodology was tested on four vascular networks of increasing complexity to analyse its scalability. The computational time needed to perform the sensitivity analysis with an emulator was reduced by the 99.96% compared to a Monte Carlo approach. Despite the reduced computational time, sensitivity indices obtained using the two approaches were comparable. The scalability study showed that the number of mechanistic simulations needed to train a Gaussian process for sensitivity analysis was of the order O(d), rather than O(d×103) needed for Monte Carlo analysis (where d is the number of parameters in the model). The efficiency of this approach, combined with capacity to estimate the impact of uncertain parameters on model outputs, will enable development of patient-specific models of the vascular system, and has the potential to produce results with clinical relevance.

Modeling of the acute effects of primary hypertension and hypotension on the hemodynamics of intracranial aneurysms.

Hemodynamics is a risk factor in intracranial aneurysms (IA). Hypertension and pharmacologically induced hypotension are common in IA patients. This study investigates how hypertension and hypotension may influence aneurysmal hemodynamics. Images of 23 IAs at typical locations were used to build patient-specific Computational Fluid Dynamics models. The effects of hypotension and hypertension were simulated through boundary conditions by modulating the normotensive flow and pressure waveforms, in turn produced by a 1D systemic vascular model. Aneurysm location and flow pattern types were used to categorize the influence of hypotension and hypertension on relevant flow variables (velocity, pressure and wall shear stress). Results indicate that, compared to other locations, vertebrobasilar aneurysms (VBA) are more sensitive to flow changes. In VBAs, space-averaged velocity at peak systole increased by 30% in hypertension (16-21% in other locations). Flow in VBAs in hypotension decreased by 20% (10-13% in other locations). Momentum-driven hemodynamic types were also more affected by hypotension and hypertension, than shear-driven types. This study shows how patient-specific modeling can be effectively used to identify location-specific flow patterns in a clinically-relevant study, thus reinforcing the role played by modeling technologies in furthering our understanding of cardiovascular disease, and their potential in future healthcare.

Modifiable lifestyle factors in dementia: a systematic review of longitudinal observational cohort studies.

BACKGROUND: Numerous population-based longitudinal studies suggest an association between modifiable lifestyle factors and late-life dementia. A comprehensive description of these factors and their quantification criteria is an important preliminary step toward the elucidation of causes and mechanisms underlying the onset and progression of dementia. OBJECTIVE: To present a systematic review of modifiable lifestyle factors associated with dementia risk in longitudinal observational cohort-studies. METHODS: A systematic review of original articles, published in English until December 2013, listed in four electronic databases (including PubMed, MEDLINE, PsycINFO) was conducted. RESULTS: 75 papers from 33 epidemiologic studies met the inclusion criteria. Included papers focused on dietary habits (n = 26), leisure activities (social, physical, mental) (n = 23), beverages (juice, tea, coffee, alcohol) (n = 15), smoking (n = 13), social network (n = 6), and combined lifestyle factors (n = 2). CONCLUSIONS: Broad consensus emerged on the protective role against dementia of leisure activities. Conflicting results were found for the association between dementia and putative risk factors (smoking) and protective factors (mild-to-moderate alcohol consumption, dietary antioxidants, Mediterranean diet, and living with others). However, studies varied largely in the quantification of lifestyle factors in terms of intensity, frequency and duration of exposure, and in the choice of confounders in statistical analyses. The need for standardized quantification criteria emerges, together with the current limitation in reliably tracking the past history of each patient, from childhood and young adulthood to midlife.

Accuracy vs. computational time: translating aortic simulations to the clinic.

State of the art simulations of aortic haemodynamics feature full fluid-structure interaction (FSI) and coupled 0D boundary conditions. Such analyses require not only significant computational resource but also weeks to months of run time, which compromises the effectiveness of their translation to a clinical workflow. This article employs three computational fluid methodologies, of varying levels of complexity with coupled 0D boundary conditions, to simulate the haemodynamics within a patient-specific aorta. The most comprehensive model is a full FSI simulation. The simplest is a rigid walled incompressible fluid simulation while an alternative middle-ground approach employs a compressible fluid, tuned to elicit a response analogous to the compliance of the aortic wall. The results demonstrate that, in the context of certain clinical questions, the simpler analysis methods may capture the important characteristics of the flow field.

Computational hemodynamics in cerebral aneurysms: the effects of modeled versus measured boundary conditions.

Modeling of flow in intracranial aneurysms (IAs) requires flow information at the model boundaries. In absence of patient-specific measurements, typical or modeled boundary conditions (BCs) are often used. This study investigates the effects of modeled versus patient-specific BCs on modeled hemodynamics within IAs. Computational fluid dynamics (CFD) models of five IAs were reconstructed from three-dimensional rotational angiography (3DRA). BCs were applied using in turn patient-specific phase-contrast-MR (pc-MR) measurements, a 1D-circulation model, and a physiologically coherent method based on local WSS at inlets. The Navier-Stokes equations were solved using the Ansys®-CFX™ software. Wall shear stress (WSS), oscillatory shear index (OSI), and other hemodynamic indices were computed. Differences in the values obtained with the three methods were analyzed using boxplot diagrams. Qualitative similarities were observed in the flow fields obtained with the three approaches. The quantitative comparison showed smaller discrepancies between pc-MR and 1D-model data, than those observed between pc-MR and WSS-scaled data. Discrepancies were reduced when indices were normalized to mean hemodynamic aneurysmal data. The strong similarities observed for the three BCs models suggest that vessel and aneurysm geometry have the strongest influence on aneurysmal hemodynamics. In absence of patient-specific BCs, a distributed circulation model may represent the best option when CFD is used for large cohort studies.

The effects of aortic coarctation on cerebral hemodynamics and its importance in the etiopathogenesis of intracranial aneurysms.

OBJECTIVES: Hemodynamic changes in the cerebral circulation in presence of coarctation of aorta (CoA) and their significance in the increased intracranial aneurysms (IAs) formation in these patients remain unclear. In the present study, we measured the flow-rate waveforms in the cerebral arteries of a patient with CoA, followed by an analysis of different hemodynamic indices in a coexisting IA. MATERIALS AND METHODS: Phase-contrast Magnetic Resonance (pc-MR) volumetric flow-rate (VFR) measurements were performed in cerebral arteries of a 51 years old woman with coexisting CoA, and five healthy volunteers. Numerical predictions of a number of relevant hemodynamic indices were performed in an IA located in sub-clinoid part of left internal carotid artery (ICA) of the patient. Computations were performed using Ansys(®)-CFX(™) solver using the VFR values measured in the patient as boundary conditions (BCs). A second analysis was performed using the average VFR values measured in healthy volunteers. The VFR waveforms measured in the patient and healthy volunteers were compared followed by a comparison of the hemodynamic indices obtained using both approaches. The results are discussed in the background of relevant literature. RESULTS: Mean flow-rates were increased by 27.1% to 54.9% (2.66-5.44 ml/sec) in the cerebral circulation of patients with CoA as compared to healthy volunteers (1.2-3.95 ml/sec). Velocities were increased inside the IA by 35-45%. An exponential rise of 650% was observed in the area affected by high wall shear stress (WSS>15Pa) when flow-rates specific to CoA were used as compared to population average flow-rates. Absolute values of space and time averaged WSS were increased by 65%. Whereas values of maximum pressure on the IA wall were increased by 15% the area of elevated pressure was actually decreased by 50%, reflecting a more focalized jet impingement within the IA of the CoA patient. CONCLUSIONS: IAs can develop in patients with CoA several years after the surgical repair. Cerebral flow-rates in CoA patients are significantly higher as compared to average flow-rates in healthy population. The increased supra-physiological WSS (>15Pa), OSI (>0.2) and focalized pressure may play an important role in the etiopathogenesis of IAs in patients with CoA.

Effects of smoking and hypertension on wall shear stress and oscillatory shear index at the site of intracranial aneurysm formation.

OBJECTIVE: The mechanisms by which smoking and hypertension lead to increased incidence of intracranial aneurysm (IA) formation remain poorly understood. The current study investigates the effects of these risk factors on wall shear stress (WSS) and oscillatory shear index (OSI) at the site of IA initiation. METHODS: Two (n=2) IAs from two patients with history of smoking and hypertension were artificially removed with the help of software @neuFuse (Supercomputing Solutions, Bologna, Italy) and the vessel geometry reconstructed to mimic the condition prior to IA formation. Two computational fluid dynamics (CFD) analyses were performed on each data-set by using in turn the normal physiological values of blood viscosity (BV), and high BV values specific to smoking and hypertension, obtained from literature. RESULTS: At normal BV, high WSS (>15 Pa) was observed at the site of IA initiation in both patients. When BV values specific to smoking and hypertension were used, both the areas affected by high WSS (>15 Pa) and the maximum WSS were increased whilst the magnitude and distribution of OSI showed no significant change. CONCLUSIONS: Long-term exposure to high WSS may result in an increased risk of IA development. An incremental increase in areas of high WSS observed secondary to smoking and hypertension may indicate a further increase in the risk of IA initiation. Interestingly, the relationship between BV and the area of increased WSS was not linear, reflecting the need for patient-specific CFD analysis.

Influence of inlet boundary conditions on the local haemodynamics of intracranial aneurysms.

Haemodynamics is believed to play an important role in the initiation, growth and rupture of intracranial aneurysms. In this context, computational haemodynamics has been extensively used in an effort to establish correlations between flow variables and clinical outcome. It is common practice in the application of Dirichlet boundary conditions at domain inlets to specify transient velocities as either a flat (plug) profile or a spatially developed profile based on Womersley's analytical solution. This paper provides comparative haemodynamics measures for three typical cerebral aneurysms. Three dimentional rotational angiography images of aneurysms at three common locations, viz. basilar artery tip, internal carotid artery and middle cerebral artery were obtained. The computational tools being developed in the European project @neurIST were used to reconstruct the fluid domains and solve the unsteady Navier-Stokes equations, using in turn Womersley and plug-flow inlet velocity profiles. The effects of these assumptions were analysed and compared in terms of relevant haemodynamic variables within the aneurismal sac. For the aneurysm at the basilar tip geometries with different extensions of the afferent vasculature were considered to study the plausibility of a fully-developed axial flow at the inlet boundaries. The study shows that assumptions made on the velocity profile while specifying inlet boundary conditions have little influence on the local haemodynamics in the aneurysm, provided that a sufficient extension of the afferent vasculature is considered and that geometry is the primary determinant of the flow field within the aneurismal sac. For real geometries the Womersley profile is at best an unnecessary over-complication, and may even be worse than the plug profile in some anatomical locations (e.g. basilar confluence).

MR derived volumetric flow rate waveforms at locations within the common carotid, internal carotid, and basilar arteries.

The volumetric flow rate (VFR) waveform over the cardiac cycle in the cerebral vasculature is a significant factor in many studies, which involve cerebrovascular function. Perhaps contrary to expectation, the literature in this area is sparse and the characteristics of blood flow waveforms are ill defined. A better understanding of the variation of blood flow rate and pulsatility may aid our knowledge of risk factors involved in diseases and conditions, such as stroke, arteriovenous malformation, or aneurysm rupture. This study sought to characterise the blood flow waveform over the cardiac cycle at levels within the carotid artery and basilar artery (BA) in a normal cohort. The study cohort consisted of 22 subjects (recruitment age: 20 to 40 years) with no history of vascular disease (median age=26 years, interquartile range=25 to 32 years). Two-dimensional quantitative phase-contrast magnetic resonance imaging was performed on each subject at nine anatomic locations within the carotid artery and BA. Significant differences in pulsatility were present within the carotid tree. Archetypal VFR waveforms were established for this group at the nine locations. A normal individual's VFR waveform at a location within the carotid tree can be estimated by taking the group's archetypal waveform for that location, and scaling by the individual's average flow rate.