Patient-specific blood flow modeling combining imaging data and computational fluid dynamics can aid in the assessment of coronary artery disease. Accurate coronary segmentation and realistic physiologic modeling of boundary conditions are important steps to ensure a high diagnostic performance. Segmentation of the coronary arteries can be constructed by a combination of automated algorithms with human review and editing. However, blood pressure and flow are not impacted equally by different local sections of the coronary artery tree. Focusing human review and editing towards regions that will most affect the subsequent simulations can significantly accelerate the review process. We define geometric sensitivity as the standard deviation in hemodynamics-derived metrics due to uncertainty in lumen segmentation. We develop a machine learning framework for estimating the geometric sensitivity in real time. Features used include geometric and clinical variables, and reduced-order models. We develop an anisotropic kernel regression method for assessment of lumen narrowing score, which is used as a feature in the machine learning algorithm. A multi-resolution sensitivity algorithm is introduced to hierarchically refine regions of high sensitivity so that we can quantify sensitivities to a desired spatial resolution. We show that the mean absolute error of the machine learning algorithm compared to 3D simulations is less than 0.01. We further demonstrate that sensitivity is not predicted simply by anatomic reduction but also encodes information about hemodynamics which in turn depends on downstream boundary conditions. This sensitivity approach can be extended to other systems such as cerebral flow, electro-mechanical simulations, etc.

Physics-based simulation is needed to understand the function of biological structures and can be applied across a wide range of scales, from molecules to organisms. Simbios (the National Center for Physics-Based Simulation of Biological Structures, http://www.simbios.stanford.edu/) is one of seven NIH-supported National Centers for Biomedical Computation. This article provides an overview of the mission and achievements of Simbios, and describes its place within systems biology. Understanding the interactions between various parts of a biological system and integrating this information to understand how biological systems function is the goal of systems biology. Many important biological systems comprise complex structural systems whose components interact through the exchange of physical forces, and whose movement and function is dictated by those forces. In particular, systems that are made of multiple identifiable components that move relative to one another in a constrained manner are multibody systems. Simbios' focus is creating methods for their simulation. Simbios is also investigating the biomechanical forces that govern fluid flow through deformable vessels, a central problem in cardiovascular dynamics. In this application, the system is governed by the interplay of classical forces, but the motion is distributed smoothly through the materials and fluids, requiring the use of continuum methods. In addition to the research aims, Simbios is working to disseminate information, software and other resources relevant to biological systems in motion.

Computational fluid dynamics (CFD) modeling of blood flow from image-based patient specific models can provide useful physiologic information for guiding clinical decision making. A novel method for the generation of image-based, 3-D, multiscale vascular surface models for CFD is presented. The method generates multiscale surfaces based on either a linear triangulated or a globally smooth nonuniform rational B-spline (NURB) representation. A robust local curvature analysis is combined with a novel global feature analysis to set mesh element size. The method is particularly useful for CFD modeling of complex vascular geometries that have a wide range of vasculature size scales, in conditions where 1) initial surface mesh density is an important consideration for balancing surface accuracy with manageable size volumetric meshes, 2) adaptive mesh refinement based on flow features makes an underlying explicit smooth surface representation desirable, and 3) semi-automated detection and trimming of a large number of inlet and outlet vessels expedites model construction.

Current practice in vascular surgery utilizes only diagnostic and empirical data to plan treatments, which does not enable quantitative a priori prediction of the outcomes of interventions. We have previously described simulation-based medical planning methods to model blood flow in arteries and plan medical treatments based on physiologic models. An important consideration for the design of these patient-specific modeling systems is the accessibility to physicians with modest computational resources. We describe a simulation-based medical planning environment developed for the World Wide Web (WWW) using the Virtual Reality Modeling Language (VRML) and the Java programming language.