Marina Piccinelli

An image-based modeling framework for patient-specific computational hemodynamics

We present a modeling framework designed for patient-specific computational hemodynamics to be performed in the context of large-scale studies. The framework takes advantage of the integration of image processing, geometric analysis and mesh generation techniques, with an accent on full automation and high-level interaction. Image segmentation is performed using implicit deformable models taking advantage of a novel approach for selective initialization of vascular branches, as well as of a strategy for the segmentation of small vessels. A robust definition of centerlines provides objective geometric criteria for the automation of surface editing and mesh generation. The framework is available as part of an open-source effort, the Vascular Modeling Toolkit, a first step towards the sharing of tools and data which will be necessary for computational hemodynamics to play a role in evidence-based medicine.

A Framework for Geometric Analysis of Vascular Structures: Application to Cerebral Aneurysms

There is well-documented evidence that vascular geometry has a major impact in blood flow dynamics and consequently in the development of vascular diseases, like atherosclerosis and cerebral aneurysmal disease. The study of vascular geometry and the identification of geometric features associated with a specific pathological condition can therefore shed light into the mechanisms involved in the pathogenesis and progression of the disease. Although the development of medical imaging technologies is providing increasing amounts of data on the three-dimensional morphology of the in vivo vasculature, robust and objective tools for quantitative analysis of vascular geometry are still lacking. In this paper, we present a framework for the geometric analysis of vascular structures, in particular for the quantification of the geometric relationships between the elements of a vascular network based on the definition of centerlines. The framework is founded upon solid computational geometry criteria, which confer robustness of the analysis with respect to the high variability of in vivo vascular geometry. The techniques presented are readily available as part of the VMTK, an open source framework for image segmentation, geometric characterization, mesh generation and computational hemodynamics specifically developed for the analysis of vascular structures. As part of the Aneurisk project, we present the application of the present framework to the characterization of the geometric relationships between cerebral aneurysms and their parent vasculature.

An objective approach to digital removal of saccular aneurysms: technique and applications.

Human studies of haemodynamic factors in the pathogenesis of cerebral aneurysms require knowledge of the pre-aneurysmal vasculature. This paper presents an objective and automated technique to digitally remove an aneurysm and reconstruct the parent artery, based on lumen geometries segmented from angiographic images. Relying on robust computational geometry concepts, notably Voronoi diagrams of the digitised lumen surface, the aneurysm attachment region is first defined objectively using lumen centrelines. Centrelines within this region are replaced by smooth interpolations, which then guide the interpolation of Voronoi points within the attachment region. Combined with Voronoi points from outside the attachment region, the parent artery lumen, without the aneurysm, can be reconstructed. Plausible reconstructions were obtained, automatically, for a set of 10 side-wall or terminal aneurysms, of various sizes and shapes, from the ANEURISK project data set. Application of image-based computational fluid dynamics analysis to a five side-wall aneurysm cases data set revealed an association between the recently proposed gradient oscillatory number (GON) and the site of aneurysm formation in four of five cases; however, elevated GON was also evident at non-aneurysmal sites. A potential application to the automated delineation of aneurysms for morphological characterisations is also suggested. The proposed approach may serve as a broad platform for investigating haemodynamic and morphological factors in aneurysm initiation, rupture and therapy in a way amenable to large-scale clinical studies or routine clinical use. Nevertheless, while the parent artery reconstructions are plausible, it remains to be proven that they are faithful representations of the pre-aneurysmal artery.

Computed Tomography Evaluation of Autosomal Dominant Polycystic Kidney Disease Progression: A Progress Report

At the moment, there are no effective therapies to prevent or slow the progression of autosomal dominant polycystic kidney disease (ADPKD). Radiologic evaluations are used to monitor volume of renal cysts and parenchyma during disease evolution. Volumetric quantifications based on computed tomography were used to investigate the relation between structural and functional changes in patients with advanced-stage ADPKD. By use of image-processing techniques, volume of kidneys, renal cysts, fully enhanced parenchyma, and faintly contrast-enhanced parenchyma, referred to as intermediate, was estimated. GFR measurements and computed tomography evaluations were repeated 6 mo later. No statistically significant correlations were found between volumes of cysts and parenchyma and intermediate volume and GFR. However, the ratio of intermediate over parenchymal volume strongly correlated with GFR (r = -0.81, P < 0.001). In addition, there were significant correlations between percentage changes in intermediate volume (absolute or relative to parenchyma) and GFR changes during the observation period (r = -0.70 and r = -0.75, P < 0.01). These data support the hypothesis of a significant relation between radiologic appearance of renal structure and functional changes and suggest new ways that renal dysfunction in ADPKD may be predicted. Further work is necessary to determine the nature of faintly contrast-enhanced parenchyma and its role in renal functional loss.

High-resolution computational fluid dynamics detects flow instabilities in the carotid siphon: Implications for aneurysm initiation and rupture?

The carotid siphon is by nature a tortuous vessel segment with sharp bends and large area variations, and of relevance to the study of intracranial aneurysm initiation and rupture. The aim of this paper was to determine whether the siphon might harbor flow instabilities, if care is taken to resolve them. This study focused on five consecutive internal carotid artery (ICA) aneurysm cases from the open-source Aneurisk dataset. The aneurysm, always downstream of the siphon, was digitally removed using previously developed and verified tools. Computational fluid dynamic (CFD) models included long cervical segments upstream, and middle and anterior cerebral arteries downstream. High-resolution pulsatile simulations were performed using the equivalent of ~24 million linear tetrahedra on average (range 16-32 M) and 30,000 time-steps/cycle. Two of the five cases were laminar with mild flow instabilities right after peak systole. One of the cases experienced strong periodic vortex shedding at a frequency of around 100 Hz. The remaining two cases harbored higher frequency flow instabilities and complex 3D vortical structures, extending to the cerebral arteries downstream. Our findings suggest that the carotid siphon, a conduit to the majority of anterior intracranial aneurysms, may experience flow instabilities, consistent with in vitro reports, but seemingly at odds with the majority of CFD studies, which have been done at lower resolutions. This has obvious implications for elucidating the forces involved in aneurysm initiation; and propagation of flow instabilities into ICA or downstream aneurysms could also impact understanding of the forces involved in aneurysm rupture.

Geometry of the internal carotid artery and recurrent patterns in location, orientation, and rupture status of lateral aneurysms: an image-based computational study

BACKGROUND:Intracranial aneurysm development and rupture may be associated to the morphology of the parent vessel. OBJECTIVE:To quantitatively characterize the geometry of the internal carotid artery (ICA) in relation to the location and orientation of lateral aneurysms and to identify recurrent patterns associated with their rupture status. METHODS:The geometry of 54 ICAs hosting lateral aneurysms was analyzed by means of computational geometry techniques. The ICA was split into individual bends, and the bend hosting the aneurysm was described in terms of curvature, torsion, length, and radius. Aneurysm position and orientation with respect to the parent vessel and specifically the hosting bend were characterized, as well as angles between the portions of the parent artery immediately upstream of and downstream from the aneurysm and the aneurysm ostium. Differences in geometric parameters with respect to rupture status and their performance as classifiers were evaluated. RESULTS:ICA bends hosting ruptured aneurysms were shorter with a smaller radius, lower maximum curvature, and lower proximal torsion compared with those hosting unruptured lesions. Ruptured aneurysms occurred in more distal portions of the ICA, along the outer wall of the vessel, and closer to the curvature peak within the hosting bend than unruptured ones. The proximal portions of ICAs hosting ruptured aneurysms approached the ostium region at a smaller angle. CONCLUSION:Geometric factors relative to the ICA were associated with the distribution of aneurysms and their rupture status. The present work has potential implications in the quest for hemodynamic factors contributing to the development, progression, and rupture of intracranial aneurysms.

Automatic Neck Plane Detection and 3D Geometric Characterization of Aneurysmal Sacs

Geometric indices defined on intracranial aneurysms have been widely used in rupture risk assessment and surgical planning. However, most indices employed in clinical settings are currently evaluated based on two-dimensional images that inevitably fail to capture the three-dimensional nature of complex aneurysmal shapes. In addition, since measurements are performed manually, they can suffer from poor inter and intra operator repeatability. The purpose of the current work is to introduce objective and robust techniques for the 3D characterization of intracranial aneurysms, while preserving a close connection to the way aneurysms are currently characterized in clinical settings. Techniques for automatically identifying the neck plane, key aneurysm dimensions, shape factors, and orientations relative to the parent vessel are demonstrated in a population of 15 sidewall and 15 terminal aneurysms whose surface has been obtained by two trained operators using both level-set segmentation and thresholding, the latter reflecting typical clinical practice. Automatically-identified neck planes are shown to be in concordance with those manually positioned by an expert neurosurgeon, and automatically-derived geometric indices are shown to be largely insensitive to segmentation method or operator. By capturing the 3D nature of aneurysmal sacs and by minimizing observer variability, our approach allows large retrospective and prospective studies on aneurysm geometric risk factors to be performed using routinely acquired clinical images.

Applications of variational data assimilation in computational hemodynamics

The development of new technologies for acquiring measures and images in order to investigate cardiovascular diseases raises new challenges in scientific computing. These data can be in fact merged with the numerical simulations for improving the accuracy and reliability of the computational tools. Assimilation of measured data and numerical models is well established in meteorology, whilst it is relatively new in computational hemodynamics. Different approaches are possible for the mathematical setting of this problem. Among them, we follow here a variational formulation, based on the minimization of the mismatch between data and numerical results by acting on a suitable set of control variables. Several modeling and methodological problems related to this strategy are open, such as the analysis of the impact of the noise affecting the data, and the design of effective numerical solvers. In this chapter we present three examples where a mathematically sound (variational) assimilation of data can significantly improve the reliability of the numerical models. Accuracy and reliability of computational models are increasingly important features in view of the progressive adoption of numerical tools in the design of new therapies and, more in general, in the decision making process of medical doctors.

Numerical treatment of boundary conditions to replace lateral branches in hemodynamics

In this paper, we discuss a technique for weakly enforcing flow rate conditions in computational hemodynamics. In particular, we study the effectiveness of cutting lateral branches from the computational domain and replacing them with non-perturbing boundary conditions to simplify the geometrical reconstruction and the numerical simulation. All these features are investigated both in the case of rigid and compliant walls. Several numerical results are presented to discuss the reliability of the proposed method.

Impact of hemodynamics on lumen boundary displacements in abdominal aortic aneurysms by means of dynamic computed tomography and computational fluid dynamics

The aim of the present work is to quantitatively assess the three-dimensional distributions of the displacements experienced during the cardiac cycle by the luminal boundary of abdominal aortic aneurysm (AAA) and to correlate them with the local bulk hemodynamics. Ten patients were acquired by means of time resolved computed tomography, and each patient-specific vascular morphology was reconstructed for all available time frames. The AAA lumen boundary motion was tracked, and the lumen boundary displacements (LBD) computed for each time frame. The intra-aneurysm hemodynamic quantities, specifically wall shear stress (WSS), were evaluated with computational fluid dynamics simulations. Co-localization of LBD and WSS distributions was evaluated by means of Pearson correlation coefficient. A clear anisotropic distribution of LBD was evidenced in both space and time; a combination of AAA lumen boundary inward- and outward-directed motions was assessed. A co-localization between largest outward LBD and high WSS was demonstrated supporting the hypothesis of a mechanistic relationship between anisotropic displacement and hemodynamic forces related to the impingement of the blood on the lumen boundary. The presence of anisotropic displacement of the AAA lumen boundary and their link to hemodynamic forces have been assessed, highlighting a new possible role for hemodynamics in the study of AAA progression.