Alberto Marzo

Reproducibility of haemodynamical simulations in a subject-specific stented aneurysm model - A report on the Virtual Intracranial Stenting Challenge 2007

This paper presents the results of the Virtual Intracranial Stenting Challenge (VISC) 2007, an international initiative whose aim was to establish the reproducibility of state-of-the-art haemodynamical simulation techniques in subject-specific stented models of intracranial aneurysms (IAs). IAs are pathological dilatations of the cerebral artery walls, which are associated with high mortality and morbidity rates due to subarachnoid haemorrhage following rupture. The deployment of a stent as flow diverter has recently been indicated as a promising treatment option, which has the potential to protect the aneurysm by reducing the action of haemodynamical forces and facilitating aneurysm thrombosis. The direct assessment of changes in aneurysm haemodynamics after stent deployment is hampered by limitations in existing imaging techniques and currently requires resorting to numerical simulations. Numerical simulations also have the potential to assist in the personalized selection of an optimal stent design prior to intervention. However, from the current literature it is difficult to assess the level of technological advancement and the reproducibility of haemodynamical predictions in stented patient-specific models. The VISC 2007 initiative engaged in the development of a multicentre-controlled benchmark to analyse differences induced by diverse grid generation and computational fluid dynamics (CFD) technologies. The challenge also represented an opportunity to provide a survey of available technologies currently adopted by international teams from both academic and industrial institutions for constructing computational models of stented aneurysms. The results demonstrate the ability of current strategies in consistently quantifying the performance of three commercial intracranial stents, and contribute to reinforce the confidence in haemodynamical simulation, thus taking a step forward towards the introduction of simulation tools to support diagnostics and interventional planning.

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. Alzheimers 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.

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.

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.

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 Womersleys 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).

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.

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.

neurIST complex information processing toolchain for the integrated management of cerebral aneurysms

Cerebral aneurysms are a multi-factorial disease with severe consequences. A core part of the European project @neurIST was the physical characterization of aneurysms to find candidate risk factors associated with aneurysm rupture. The project investigated measures based on morphological, haemodynamic and aneurysm wall structure analyses for more than 300 cases of ruptured and unruptured aneurysms, extracting descriptors suitable for statistical studies. This paper deals with the unique challenges associated with this task, and the implemented solutions. The consistency of results required by the subsequent statistical analyses, given the heterogeneous image data sources and multiple human operators, was met by a highly automated toolchain combined with training. A testimonial of the successful automation is the positive evaluation of the toolchain by over 260 clinicians during various hands-on workshops. The specification of the analyses required thorough investigations of modelling and processing choices, discussed in a detailed analysis protocol. Finally, an abstract data model governing the management of the simulation-related data provides a framework for data provenance and supports future use of data and toolchain. This is achieved by enabling the easy modification of the modelling approaches and solution details through abstract problem descriptions, removing the need of repetition of manual processing work.

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 individuals VFR waveform at a location within the carotid tree can be estimated by taking the groups archetypal waveform for that location, and scaling by the individuals average flow rate.

Predicting hemodynamics in native and residual coarctation: preliminary results of a Rigid-Wall Computational-Fluid-Dynamics model (RW-CFD) validated against clinically invasive pressure measures at rest and during pharmacological stress

Current clinical assessment of borderline aortic coarctation may involve cardiovascular magnetic resonance(CMR) but if inconclusive, invasive catheterization pressure measurements are required to evaluate the pressure gradient at rest and during pharmacological stress(isoprenaline).