Search

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.

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.

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.sup.2], P < 0.01), and a scaling exponent of -0.38 ([R.sup.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. allometric scaling; cardiovascular disease; magnetic resonance imaging

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 anglograms 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 [+ or -] 0.6 to 31.6 [+ or -] 5.7 dyn/[cm.sup.2] and OSI decreased from 0.22 [+ or -] 0.03 to 0.03 [+ or -] 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. atherosclerosis; shear stress; magnetic resonance imaging; finite element analysis doi:10.1152/ajpheart.01301.2005