Automated Parameterization and Patching of Bifurcating Vessels

Recent developments in computational modeling of human arteries have opened the possibility of performing subject-specific analyses on increasingly larger numbers of subjects. This achievement will eventually lead to a better understanding of the role of geometry and hemodynamics in the initiation and development of vascular disease. The availability of data from population or longitudinal studies raises the problem of quantitatively comparing distributions of geometric and hemodynamic quantities among different models. This task is made difficult by the fact that modeled arterial segments typically comprise bifurcations and regions of high curvature. A technique for comparing surface distributions among realistic models of the carotid bifurcation has been recently proposed in [1]. In that work, surface mesh nodes were classified as belonging to semi-automatically defined quadrilateral patches, and nodal quantities of interest averaged over each patch. This avoided node-to-node comparison and the need for registration. However, patch definition required user interaction and was thus subject to operator-variability. In this work we present a fully automated technique for parameterization and patching of the surface of bifurcating vessels. The method is based on robust and objective schemes aimed at preserving the consistency of the parameterization over a wide range of bifurcating geometries, allowing quantitative comparison of surface distributions in presence of high anatomic variability

Geometry of the carotid bifurcation predicts its exposure to disturbed flow

BACKGROUND AND PURPOSE: That certain vessels might be at so-called geometric risk of atherosclerosis rests on assumptions of wide interindividual variations in disturbed flow and of a direct relationship between disturbed flow and lumen geometry. In testing these often-implicit assumptions, the present study aimed to determine whether investigations of local risk factors in atherosclerosis can indeed rely on surrogate geometric markers of disturbed flow. METHODS: Computational fluid dynamics simulations were performed on carotid bifurcation geometries derived from MRI of 25 young adults. Disturbed flow was quantified as the surface area exposed to low and oscillatory shear beyond objectively-defined thresholds. Interindividual variations in disturbed flow were contextualized with respect to effects of uncertainties in imaging and geometric reconstruction. Relationships between disturbed flow and various geometric factors were tested via multiple regression. RESULTS: Relatively wide variations in disturbed flow were observed among the 50 vessels. Multiple regression revealed a significant (P\u3c0.002) relationship between disturbed flow and both proximal area ratio (β≈0.5) and bifurcation tortuosity (β≈-0.4), but not bifurcation angle, planarity, or distal area ratio. These findings were shown to be insensitive to assumptions about the flow conditions and to the choice of disturbed flow indicator and threshold. CONCLUSIONS: Certain geometric features of the young adult carotid bifurcation are robust surrogate markers of its exposure to disturbed flow. It may therefore be reasonable to consider large-scale retrospective or prospective imaging studies of local risk factors for atherosclerosis without the need for time-consuming and expensive flow imaging or CFD studies. © 2008 American Heart Association, Inc

Haemodynamics in the retinal vasculature during the progression of diabetic retinopathy

Introduction: Diabetic Retinopathy (DR) remains a major ocular disease, which can potentially lead to blindness if left untreated. The human retina is a very dynamic tissue, making it difficult to associate any changes with a disease and not with normal variability among people. 96 images from twenty-four subjects were used in this study, including the period of the three years before DR and the first year of DR (4 images per patient, one per year). Methods: The images were firstly segmented to obtain the vascular trees, selecting the same segments in the entire four-year period, to make a meaningful comparison. The trees, which included a parent vessel and two children branches, were connected using an implemented semi-automated tool. Some hemodynamic features were calculated, using the geometric measurements from the segmentation. At the branching points, the fluid dynamics conditions were estimated under the assumptions of Pouiseuille flow: stiff, straight and uniform tube. Blood fl ow velocity (v), blood fl ow rate (Q), Reynolds number (Re), pressure (P) and wall sheer stress (WSS) were calculated, both for arteries and veins. Blood viscosity (mu=0.04 P), tube ́s length (L) and diameter (D), were used to compute fl uid resistance to fl ow (R=128 mu L / pi D^4) through each vessel. Based on previous studies, the boundary conditions adopted to solve the problem were P_CRA = P_CRV = 45mmHg. Q_CRA and Q_CRV were derived from v_CRA, d_CRA, v_CRV, d_CRV by using the formula Q=VA. WSS was computed as WSS=32muQ/d^3. Re was calculated as Re=v d rho/mu, where rho=1.0515 g/mL is the blood density. Each feature (response variable) was analysed by using a linear mixed model, with the levels of the disease being the fixed effects explanatory variable, and the patients being the random effect with a random intercept. Results: Our study showed that veins were mostly affected during the last stages of the diabetic eye. Furthermore, the blood fl ow of both children and the Re in the small child branch were mostly affected in the arteries. Table 1 includes only the signifi cant features, with the relevant p-values (a=0.05) and Akaike Information Criterion (AIC). Conclusion: Alongside the already established importance of the retinal geometry, this study showed that the hemodynamic features can also be used as biomarkers of progression to DR. During this four-year period of the disease‘s progression, retina is adapting to the new underlying conditions

Hemodynamics in the retinal vasculature during the progression of diabetic retinopathy

Purpose: Several studies have established, using various measurement modalities, that progression from diabetes to diabetic retinopathy is associated with changes in haemodynamics or measurable vascular geometry. In this study we take vessel measurements from standard fundus images, and estimate haemodynamic parameters (which are not directly observable) using a simple haemodynamic model. We show that there are statistically significant changes in some estimated haemodynamic parameters associated with the development of DR. Methods: A longitudinal study of twenty-four subjects was conducted. For each subject four fundus images were used, taken annually during the three years before the appearance of DR and in the first year of DR. A venous and arterial vascular bifurcation, each of which consisted of a parent vessel and two child branches was extracted, and at the branching nodes a zero dimensional model estimated the fluid dynamic conditions in terms of volumetric blood flow, blood flow velocity, nodal pressure, wall shear stress and Reynolds number. These features were statistically analyzed using linear mixed models. Results: A number of parameters, primarily venous, showed significant change with the development of DR, including early change two years before the onset of DR. A large proportion of overall variance is accounted for by individual patient differences, making progressive study essential. Conclusion: This is the first paper to demonstrate that haemodynamic feature estimates extracted from standard fundus images are sensitive to progression from diabetes to DR. In our future work, we aim to test whether the variations in haemodynamic conditions are predictive of progression prior to the appearance of retinal lesions

A fluid-dynamic based approach to reconnect the retinal vessels in fundus photography

This paper introduces the use of fluid-dynamic modeling to determine the connectivity of overlapping venous and arterial vessels in fundus images. Analysis of the retinal vascular network may provide information related to systemic and local disorders. However, the automated identification of the vascular trees in retinal images is a challenging task due to the low signal-to-noise ratio, nonuniform illumination and the fact that fundus photography is a projection on to the imaging plane of three-dimensional retinal tissue. A zero-dimensional model was created to estimate the hemodynamic status of candidate tree configurations. Simulated annealing was used to search for an optimal configuration. Experimental results indicate that simulated annealing was very efficient on test cases that range from small to medium size networks, while ineffective on large networks. Although for large networks the nonconvexity of the cost function and the large solution space made searching for the optimal solution difficult, the accuracy (average success rate = 98.35%), and simplicity of our novel approach demonstrate its potential effectiveness in segmenting retinal vascular trees

Shear stress reverses dome formation in confluent renal tubular cells.

It has been shown that MDCK cells, a cell line derived from canine renal tubules, develop cell domes due to fluid pumped under cell monolayer and focal detachment from the adhesion surface. In vitro studies have shown that primary cilia of kidney tubular epithelial cells act as mechanosensors, increasing intracellular calcium within seconds upon changes in fluid shear stress (SS) on cell membrane. We then studied the effect of prolonged SS exposure on cell dome formation in confluent MDCK cell monolayers.A parallel plate flow chamber was used to apply laminar SS at 2 dynes/cm(2) to confluent cell monolayers for 6 hours. Control MDCK cell monolayers were maintained in static condition. The effects of Ca(2+) blockade and cell deciliation on SS exposure were also investigated.Seven days after reaching confluence, static cultures developed liquid filled domes, elevating from culture plate. Exposure to SS induced almost complete disappearance of cell domes (0.4±0.8 vs. 11.4±2.8 domes/mm(2), p0.01, n=14). SS induced dome disappearance took place within minutes to hours, as shown by time-lapse videomicroscopy. Exposure to SS importantly affected cell cytoskeleton altering actin stress fibers expression and organization, and the distribution of tight junction protein ZO-1. Dome disappearance induced by flow was completely prevented in the presence of EGTA or after cell deciliation.These data indicate that kidney tubular cells are sensitive to apical flow and that these effects are mediated by primary cilia by regulation of Ca(2+) entry in to the cell. SS induced Ca(2+) entry provokes contraction of cortical actin ring that tenses cell-cell borders and decreases basal stress fibers. These processes may increase paracellular permeability and decrease basal adhesion making dome disappear. Elucidation of the effects of apical fluid flow on tubular cell function may open new insights on the pathophysiology of kidney diseases associated with cilia dysfunction

Bayes pulmonary embolism assisted-diagnosis: a new expert system for clinical use

Background: The diagnosis of pulmonary embolism demands flexible decision models, both for the presence of clinical confounders and for the variability of local diagnostic resources. As Bayesian networks fully meet this requirement, Bayes Pulmonary embolism Assisted Diagnosis (BayPAD), a probabilistic expert systems focused on pulmonary embolism, was developed. Methods: To quantitatively validate and improve BayPAD, the system was applied to 750 patients from a prospective study done in an Italian tertiary hospital where the true pulmonary embolism status was confirmed using pulmonary angiography or ruled out with a lung scan. The proportion of correct diagnoses made by BayPAD (accuracy) and the correctness of the pulmonary embolism probabilities predicted by the model (calibration) were calculated. The calibration was evaluated according to the Cox regression-calibration model. Results: Before refining the model, accuracy was 88.6%. Once refined, accuracy was 97.2% and 98%, respectively, in the training and validation samples. According to Cox analysis, calibration was satisfactory, despite a tendency to exaggerate the effect of the findings on the probability of pulmonary embolism. The lack of some investigations (like Spiral computed tomographic scan and Lower limbs doppler ultrasounds) in the pool of available data often prevents BayPAD from reaching the diagnosis without invasive procedures. Conclusions: BayPAD offers clinicians a flexible and accurate strategy to diagnose pulmonary embolism. Simple to use, the system performs case-based reasoning to optimise the use of resources available within a particular hospital. Bayesian networks are expected to have a prominent role in the clinical management of complex diagnostic problems in the near future

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

Variation in the carotid bifurcation geometry of young versus older adults: Implications for geometric risk of atherosclerosis

Background and Purpose - Retrospective analysis of clinical data has demonstrated major variations in carotid bifurcation geometry, in support of the notion that an individual\u27s vascular anatomy or local hemodynamics may influence the development of atherosclerosis. On the other hand, anecdotal evidence suggests that vessel geometry is more homogenous in youth, which would tend to undermine this geometric risk hypothesis. The purpose of our study was to test whether the latter is indeed the case. Methods - Cross-sectional images of the carotid bifurcations of 25 young adults (24±4 years) and a control group of 25 older subjects (63±10 years) were acquired via MRI. Robust and objective techniques were developed to automatically characterize the 3D geometry of the bifurcation and the relative dimensions of the internal, external, and common carotid arteries (ICA, ECA, and CCA, respectively). Results - Young vessels exhibited significantly less interindividual variation in the following geometric parameters: bifurcation angle (48.5±6.3° versus 63.6±15.4°); ICA angle (21.6±6.7° versus 29.2±11.3°); CCA tortuosity (0.010±0.003 versus 0.014±0.011); ICA tortuosity (0.025±0.013 versus 0.086±0.105); ECA/CCA diameter ratio (0.81±0.06 versus 0.75±0.13), ICA/CCA (0.81 ±0.06 versus 0.77±0.12) diameter ratio, and bifurcation area ratio (1.32±0.15 versus 1.19±0.35). Conclusions - The finding of more modest interindividual variations in young adults suggests that, if there is a geometric risk for atherosclerosis, its early detection may prove challenging. Taken together with the major interindividual variations seen in older vessels, it suggests a more complex interrelationship between vascular geometry, local hemodynamics, vascular aging, and atherosclerosis, the elucidation of which now calls for prospective studies. © 2005 American Heart Association, Inc