Automated generation of 0D and 1D reduced-order models of patient-specific blood flow.

Three-dimensional (3D) cardiovascular fluid dynamics simulations typically require hours to days of computing time on a high-performance computing cluster. One-dimensional (1D) and lumped-parameter zero-dimensional (0D) models show great promise for accurately predicting blood bulk flow and pressure waveforms with only a fraction of the cost. They can also accelerate uncertainty quantification, optimization, and design parameterization studies. Despite several prior studies generating 1D and 0D models and comparing them to 3D solutions, these were typically limited to either 1D or 0D and a singular category of vascular anatomies. This work proposes a fully automated and openly available framework to generate and simulate 1D and 0D models from 3D patient-specific geometries, automatically detecting vessel junctions and stenosis segments. Our only input is the 3D geometry; we do not use any prior knowledge from 3D simulations. All computational tools presented in this work are implemented in the open-source software platform SimVascular. We demonstrate the reduced-order approximation quality against rigid-wall 3D solutions in a comprehensive comparison with N = 72 publicly available models from various anatomies, vessel types, and disease conditions. Relative average approximation errors of flows and pressures typically ranged from 1% to 10% for both 1D and 0D models, measured at the outlets of terminal vessel branches. In general, 0D model errors were only slightly higher than 1D model errors despite requiring only a third of the 1D runtime. Automatically generated ROMs can significantly speed up model development and shift the computational load from high-performance machines to personal computers.

On the Periodicity of Cardiovascular Fluid Dynamics Simulations.

Three-dimensional cardiovascular fluid dynamics simulations typically require computation of several cardiac cycles before they reach a periodic solution, rendering them computationally expensive. Furthermore, there is currently no standardized method to determine whether a simulation has yet reached that periodic state. In this work, we propose the use of an asymptotic error measurement to quantify the difference between simulation results and their ideal periodic state using open-loop lumped-parameter modeling. We further show that initial conditions are crucial in reducing computational time and develop an automated framework to generate appropriate initial conditions from a one-dimensional model of blood flow. We demonstrate the performance of our initialization method using six patient-specific models from the Vascular Model Repository. In our examples, our initialization protocol achieves periodic convergence within one or two cardiac cycles, leading to a significant reduction in computational cost compared to standard methods. All computational tools used in this work are implemented in the open-source software platform SimVascular. Automatically generated initial conditions have the potential to significantly reduce computation time in cardiovascular fluid dynamics simulations.

Integrated Image-Based Computational Fluid Dynamics Modeling Software as an Instructional Tool.

Computational modeling of cardiovascular flows is becoming increasingly important in a range of biomedical applications, and understanding the fundamentals of computational modeling is important for engineering students. In addition to their purpose as research tools, integrated image-based computational fluid dynamics (CFD) platforms can be used to teach the fundamental principles involved in computational modeling and generate interest in studying cardiovascular disease. We report the results of a study performed at five institutions designed to investigate the effectiveness of an integrated modeling platform as an instructional tool and describe "best practices" for using an integrated modeling platform in the classroom. Use of an integrated modeling platform as an instructional tool in nontraditional educational settings (workshops, study abroad programs, in outreach) is also discussed. Results of the study show statistically significant improvements in understanding after using the integrated modeling platform, suggesting such platforms can be effective tools for teaching fundamental cardiovascular computational modeling principles.

A community effort to create standards for evaluating tumor subclonal reconstruction.

Tumor DNA sequencing data can be interpreted by computational methods that analyze genomic heterogeneity to infer evolutionary dynamics. A growing number of studies have used these approaches to link cancer evolution with clinical progression and response to therapy. Although the inference of tumor phylogenies is rapidly becoming standard practice in cancer genome analyses, standards for evaluating them are lacking. To address this need, we systematically assess methods for reconstructing tumor subclonality. First, we elucidate the main algorithmic problems in subclonal reconstruction and develop quantitative metrics for evaluating them. Then we simulate realistic tumor genomes that harbor all known clonal and subclonal mutation types and processes. Finally, we benchmark 580 tumor reconstructions, varying tumor read depth, tumor type and somatic variant detection. Our analysis provides a baseline for the establishment of gold-standard methods to analyze tumor heterogeneity.

Construction of Analysis-Suitable Vascular Models Using Axis-Aligned Polycubes.

Image-based modeling is an active and growing area of biomedical research that utilizes medical imaging to create patient-specific simulations of physiological function. Under this paradigm, anatomical structures are segmented from a volumetric image, creating a geometric model that serves as a computational domain for physics-based modeling. A common application is the segmentation of cardiovascular structures to numerically model blood flow or tissue mechanics. The segmentation of medical image data typically results in a discrete boundary representation (surface mesh) of the segmented structure. However, it is often desirable to have an analytic representation of the model, which facilitates systematic manipulation. For example, the model then becomes easier to union with a medical device, or the geometry can be virtually altered to test or optimize a surgery. Furthermore, to employ increasingly popular isogeometric analysis (IGA) methods, the parameterization must be analysis suitable. Converting a discrete surface model to an analysis-suitable model remains a challenge, especially for complex branched structures commonly encountered in cardiovascular modeling. To address this challenge, we present a framework to convert discrete surface models of vascular geometries derived from medical image data into analysis-suitable nonuniform rational B-splines (NURBS) representation. This is achieved by decomposing the vascular geometry into a polycube structure that can be used to form a globally valid parameterization. We provide several practical examples and demonstrate the accuracy of the methods by quantifying the fidelity of the parameterization with respect to the input geometry.

A Re-Engineered Software Interface and Workflow for the Open-Source SimVascular Cardiovascular Modeling Package.

Patient-specific simulation plays an important role in cardiovascular disease research, diagnosis, surgical planning and medical device design, as well as education in cardiovascular biomechanics. simvascular is an open-source software package encompassing an entire cardiovascular modeling and simulation pipeline from image segmentation, three-dimensional (3D) solid modeling, and mesh generation, to patient-specific simulation and analysis. SimVascular is widely used for cardiovascular basic science and clinical research as well as education, following increased adoption by users and development of a GATEWAY web portal to facilitate educational access. Initial efforts of the project focused on replacing commercial packages with open-source alternatives and adding increased functionality for multiscale modeling, fluid-structure interaction (FSI), and solid modeling operations. In this paper, we introduce a major SimVascular (SV) release that includes a new graphical user interface (GUI) designed to improve user experience. Additional improvements include enhanced data/project management, interactive tools to facilitate user interaction, new boundary condition (BC) functionality, plug-in mechanism to increase modularity, a new 3D segmentation tool, and new computer-aided design (CAD)-based solid modeling capabilities. Here, we focus on major changes to the software platform and outline features added in this new release. We also briefly describe our recent experiences using SimVascular in the classroom for bioengineering education.

SimVascular: An Open Source Pipeline for Cardiovascular Simulation.

Patient-specific cardiovascular simulation has become a paradigm in cardiovascular research and is emerging as a powerful tool in basic, translational and clinical research. In this paper we discuss the recent development of a fully open-source SimVascular software package, which provides a complete pipeline from medical image data segmentation to patient-specific blood flow simulation and analysis. This package serves as a research tool for cardiovascular modeling and simulation, and has contributed to numerous advances in personalized medicine, surgical planning and medical device design. The SimVascular software has recently been refactored and expanded to enhance functionality, usability, efficiency and accuracy of image-based patient-specific modeling tools. Moreover, SimVascular previously required several licensed components that hindered new user adoption and code management and our recent developments have replaced these commercial components to create a fully open source pipeline. These developments foster advances in cardiovascular modeling research, increased collaboration, standardization of methods, and a growing developer community.

The Vascular Model Repository: A Public Resource of Medical Imaging Data and Blood Flow Simulation Results.

Patient-specific blood flow simulations may provide insight into disease progression, treatment options, and medical device design that would be difficult or impossible to obtain experimentally. However, publicly available image data and computer models for researchers and device designers are extremely limited. The National Heart, Lung, and Blood Institute sponsored Open Source Medical Software Corporation (contract nos. HHSN268200800008C and HHSN268201100035C) and its university collaborators to build a repository (www.vascularmodel.org) including realistic, image-based anatomic models and related hemodynamic simulation results to address this unmet need.

Methods for quantifying three-dimensional deformation of arteries due to pulsatile and nonpulsatile forces: implications for the design of stents and stent grafts.

The knowledge of dynamic changes in the vascular system has become increasingly important in ensuring the safety and efficacy of endovascular devices. We developed new methods for quantifying in vivo three-dimensional (3D) arterial deformation due to pulsatile and nonpulsatile forces. A two-dimensional threshold segmentation technique combined with a level set method enabled calculation of the consistent centroid of the cross-sectional vessel lumen, whereas an optimal Fourier smoothing technique was developed to eliminate spurious irregularities of the centerline connecting the centroids. Longitudinal strain and novel metrics for axial twist and curvature change were utilized to characterize 3D deformations of the abdominal aorta, common iliac artery, and superficial femoral artery (SFA) due to musculoskeletal motion and deformations of the coronary artery due to cardiac pulsatile motion. These illustrative applications show the significance of each deformation metric, revealing significant longitudinal strain and axial twist in the SFA and coronary artery, and pronounced changes in vessel curvature in the coronary artery and in the inferior region of the SFA. The proposed methods may aid in designing preclinical tests aimed at replicating dynamic in vivo conditions in the arterial tree for the purpose of developing more durable endovascular devices including stents and stent grafts.

In vivo MR angiographic quantification of axial and twisting deformations of the superficial femoral artery resulting from maximum hip and knee flexion.

PURPOSE: The goal of this study was to quantify in vivo deformations of the superficial femoral artery (SFA) during maximum knee and hip flexion with use of magnetic resonance (MR) angiography to improve description of the complex, dynamic SFA environment. MATERIALS AND METHODS: Contrast medium-enhanced MR angiography was performed on the leg vasculature of eight healthy adults in the supine and fetal positions. The SFA was defined as the centerline path of the iliofemoral segment from the profunda femoris to the descending genicular artery. Deformations that resulted from flexion from the supine position to the fetal position were quantified with the SFA path and its branches. RESULTS: Fourteen SFAs shortened from the supine position to fetal position, whereas two lengthened. Six of eight left SFAs twisted counterclockwise, and seven of eight right SFAs twisted clockwise. Straightness percentages for supine and fetal SFAs were 99.1%+/-0.4% and 98.7%+/-0.6%, respectively. From the supine position to the fetal position, the SFA shortened 13%+/-11% (P<.001) and twisted 60 degrees+/-34 degrees (P<.001). SFA arc length and percent shortening were strongly correlated (r>.8) between left and right limbs; however, no significant correlation existed for SFA twist angle. CONCLUSIONS: Complex and varying vascular and muscular anatomy among study participants made SFA lengths and deformations from the supine position to the fetal position unpredictable a priori; however, there were strong symmetries between left and right SFAs in terms of arc length, length change, and direction of twist. The data show that, from the supine position to the fetal position, the SFA tended to shorten and twist substantially, suggesting these as possible fracture mechanisms and also providing important parameters for stent design.

Allometric scaling of wall shear stress from mice to humans: quantification using cine phase-contrast MRI and computational fluid dynamics.

Allometric scaling laws relate structure or function between species of vastly different sizes. They have rarely been derived for hemodynamic parameters known to affect the cardiovascular system, e.g., wall shear stress (WSS). This work describes noninvasive methods to quantify and determine a scaling law for WSS. Geometry and blood flow velocities in the infrarenal aorta of mice and rats under isoflurane anesthesia were quantified using two-dimensional magnetic resonance angiography and phase-contrast magnetic resonance imaging at 4.7 tesla. Three-dimensional models constructed from anatomic data were discretized and used for computational fluid dynamic simulations using phase-contrast velocity imaging data as inlet boundary conditions. WSS was calculated along the infrarenal aorta and compared between species to formulate an allometric equation for WSS. Mean WSS along the infrarenal aorta was significantly greater in mice and rats compared with humans (87.6, 70.5, and 4.8 dyn/cm(2), P < 0.01), and a scaling exponent of -0.38 (R(2) = 0.92) was determined. Manipulation of the murine genome has made small animal models standard surrogates for better understanding the healthy and diseased human cardiovascular system. It has therefore become increasingly important to understand how results scale from mouse to human. This noninvasive methodology provides the opportunity to serially quantify changes in WSS during disease progression and/or therapeutic intervention.

Abdominal aortic hemodynamics in young healthy adults at rest and during lower limb exercise: quantification using image-based computer modeling.

Localization of atherosclerotic lesions in the abdominal aorta has been previously correlated to areas of adverse hemodynamic conditions, such as flow recirculation, low mean wall shear stress, and high temporal oscillations in shear. Along with its many systemic benefits, exercise is also proposed to have local benefits in the vasculature via the alteration of these regional flow patterns. In this work, subject-specific models of the human abdominal aorta were constructed from magnetic resonance angiograms of five young, healthy subjects, and computer simulations were performed under resting and exercise (50% increase in resting heart rate) pulsatile flow conditions. Velocity fields and spatial variations in mean wall shear stress (WSS) and oscillatory shear index (OSI) are presented. When averaged over all subjects, WSS increased from 4.8 +/- 0.6 to 31.6 +/- 5.7 dyn/cm2 and OSI decreased from 0.22 +/- 0.03 to 0.03 +/- 0.02 in the infrarenal aorta between rest and exercise. WSS significantly increased, whereas OSI decreased between rest and exercise at the supraceliac, infrarenal, and suprabifurcation levels, and significant differences in WSS were found between anterior and posterior sections. These results support the hypothesis that exercise provides localized benefits to the cardiovascular system through acute mechanical stimuli that trigger longer-term biological processes leading to protection against the development or progression of atherosclerosis.

Predicting changes in blood flow in patient-specific operative plans for treating aortoiliac occlusive disease.

Traditionally, a surgeon will select a procedure for a particular patient on the basis of past experience with patients with a similar state of disease. The experience gained from this patient will be selectively used when treating the next patient with similar symptoms. This article describes a surgical planning system that was developed to enable a vascular surgeon to create and test alternative operative plans prior to surgery for a given patient. One-dimensional and three-dimensional hemodynamic (i.e., blood flow) simulations were performed for rest and exercise for operative plans for two aorto-femoral bypass patients and compared with actual postoperative data. The information obtained from one-dimensional (volume flow distribution and pressure losses) and three-dimensional (flow, pressure, and wall shear stress) hemodynamic simulations may be clinically relevant to vascular surgeons planning interventions.